In 2017, the total cost of diagnosed diabetes on the American healthcare system was $327 billion, and is expected to grow to $490 billion by 2030.

[1] Ping Zhang et al., “Global Healthcare Expenditure on Diabetes for 2010 and 2030.” Diabetes Research and Clinical Practice 87, no. 3 (March 2010): 293–301. https://doi.org/10.1016/j.diabres.2010.01.026.

Diagnosis of diabetes dramatically increases your risk for the development of many chronic diseases.

[2] American Diabetes Association, “Economic Costs of Diabetes in the U.S. in 2012.” Diabetes Care, March 6, 2013, DC_122625. https://doi.org/10.2337/dc12-2625.

The average adult with type 1 diabetes injects approximately 0.5 to 1.0 units of insulin per kilogram of body weight per day.

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Insulin resistance is a major condition that underlies many chronic metabolic diseases, including (but not limited to) type 1 diabetes, type 1.5 diabetes, type 2 diabetes, prediabetes, gestational diabetes, coronary artery disease, atherosclerosis, cancer, high cholesterol, high blood pressure, obesity, polycystic ovary syndrome (PCOS), peripheral neuropathy, retinopathy, Alzheimer’s disease, chronic kidney disease, and fatty liver disease.

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[8] Biagio Arcidiacono et al., “Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms.” Experimental Diabetes Research 2012 (2012). https://doi.org/10.1155/2012/789174.

[9] Kevin M. Korenblat et al., “Liver, Muscle, and Adipose Tissue Insulin Action Is Directly Related to Intrahepatic Triglyceride Content in Obese Subjects.” Gastroenterology 134, no. 5 (May 2008): 1369–75. https://doi.org/10.1053/j.gastro.2008.01.075.

[10] Krupa Shah et al., “Diet and Exercise Interventions Reduce Intrahepatic Fat Content and Improve Insulin Sensitivity in Obese Older Adults.” Obesity 17, no. 12 (December 2009): 2162–68. https://doi.org/10.1038/oby.2009.126.

[11] Shira Zelber-Sagi, Vlad Ratziu, and Ran Oren, “Nutrition and Physical Activity in NAFLD: An Overview of the Epidemiological Evidence.” World Journal of Gastroenterology : WJG 17, no. 29 (August 7, 2011): 3377–89. https://doi.org/10.3748/wjg.v17.i29.3377.

[12] Wenjie Dai et al., “Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus.” Medicine 96, no. 39 (September 29, 2017). https://doi.org/10.1097/MD.0000000000008179.

[13] Petter Bjornstad and Robert H. Eckel, “Pathogenesis of Lipid Disorders in Insulin Resistance: A Brief Review.” Current Diabetes Reports 18, no. 12 (October 17, 2018): 127. https://doi.org/10.1007/s11892-018-1101-6.

[14] Wenguang Chang et al., “The Relationship Between Phospholipids and Insulin Resistance: From Clinical to Experimental Studies.” Journal of Cellular and Molecular Medicine, November 6, 2018. https://doi.org/10.1111/jcmm.13984.

[15] Giovanni Targher and Christopher D. Byrne, “Non-Alcoholic Fatty Liver Disease: An Emerging Driving Force in Chronic Kidney Disease.” Nature Reviews. Nephrology 13, no. 5 (2017): 297–310. https://doi.org/10.1038/nrneph.2017.16.

[16] S. S. Lim et al. “Metabolic Syndrome in Polycystic Ovary Syndrome: A Systematic Review, Meta-Analysis and Meta-Regression.” Obesity Reviews, October 19, 2018. https://doi.org/10.1111/obr.12762.

[17] V. De Leo et al., “Genetic, Hormonal and Metabolic Aspects of PCOS: An Update.” Reproductive Biology and Endocrinology: RB&E 14, no. 1 (July 16, 2016): 38. https://doi.org/10.1186/s12958-016-0173-x.

[18] Ling Han et al., “Peripheral Neuropathy Is Associated with Insulin Resistance Independent of Metabolic Syndrome.” Diabetology & Metabolic Syndrome 7 (2015): 14. https://doi.org/10.1186/s13098-015-0010-y.

[19] Yu Na Cho et al., “The Role of Insulin Resistance in Diabetic Neuropathy in Koreans with Type 2 Diabetes Mellitus: A 6-Year Follow-up Study.” Yonsei Medical Journal 55, no. 3 (May 2014): 700–708. https://doi.org/10.3349/ymj.2014.55.3.700.

[20] G. Stennis Watson and Suzanne Craft, “The Role of Insulin Resistance in the Pathogenesis of Alzheimer’s Disease: Implications for Treatment.” CNS Drugs 17, no. 1 (2003): 27–45. https://doi:10.2165/00023210-200317010-00003.

[21] Dean Sherzai et al., “The Association Between Diabetes and Dementia Among Elderly Individuals: A Nationwide Inpatient Sample Analysis.” Journal of Geriatric Psychiatry and Neurology 29, no. 3 (May 2016): 120–25. https://doi.org/10.1177/0891988715627016.

[22] Ayesha Z. Sherzai et al., “Insulin Resistance and Cognitive Test Performance in Elderly Adults: National Health and Nutrition Examination Survey (NHANES).” Journal of the Neurological Sciences 388 (May 15, 2018): 97–102. https://doi.org/10.1016/j.jns.2017.11.031.

Recent research suggests that 65 percent of all people living with type 1 diabetes for more than 20 years will die of cardiovascular disease and that more than 50 percent of people living with type 1 diabetes for more than 30 years will die of kidney failure.

[23] Secrest, Aaron, and Raynard E. Washington. “Chapter 35: Mortality in Type 1 Diabetes.” Diabetes in America 3rd Edition, MORTALITY IN TYPE 1 DIABETES, Chapter 35 (n.d.): 16. https://www.niddk.nih.gov/about-niddk/strategic-plans-reports/diabetes-in-america-3rd-edition.

Controlling and reversing insulin resistance today can prevent the onset of many chronic metabolic diseases in the future.

[24] Robert J. Tanenberg, “Transitioning Pharmacologic Therapy from Oral Agents to Insulin for Type 2 Diabetes.” Current Medical Research and Opinion 20, no. 4 (April 2004): 541–53. https://doi.org/10.1185/030079903125003134.

Even though type 1 diabetes is one of the most common autoimmune diseases in children, affecting approximately 100,000 people in the United States every year, this diagnosis seemed very atypical.

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Less than 30 percent of the schools met the minimum requirement of 25 hours of nutrition education, a standard set by the National Academy of Sciences.

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The prevailing wisdom in the world of diabetes nutrition is that a low-carbohydrate diet is the safest and most effective way to control your blood glucose and will help you lose weight, reduce your fasting blood glucose, drop your A1c, lower your cholesterol, and reduce your blood pressure.

[5] Timothy David Noakes and Johann Windt, “Evidence That Supports the Prescription of Low-Carbohydrate High-Fat Diets: A Narrative Review.” British Journal of Sports Medicine 51, no. 2 (January 2017): 133–39. https://doi.org/10.1136/bjsports-2016-096491.

[6] Amy L. McKenzie et al., “A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes.” JMIR Diabetes 2, no. 1 (2017): e5. https://doi.org/10.2196/diabetes.6981.

[7] Sarah J. Hallberg et al., “Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.” Diabetes Therapy 9, no. 2 (April 1, 2018): 583–612. https://doi.org/10.1007/s13300-018-0373-9.

That all foods containing carbohydrates act the same way in your body, causing uncontrollable blood glucose fluctuations that then lead to increased appetite, weight gain, and obesity.

[8] H. Guldbrand et al., “In Type 2 Diabetes, Randomisation to Advice to Follow a Low-Carbohydrate Diet Transiently Improves Glycaemic Control Compared with Advice to Follow a Low-Fat Diet Producing a Similar Weight Loss.” Diabetologia 55, no. 8 (August 1, 2012): 2118–27. https://doi.org/10.1007/s00125-012-2567-4.

[9] Jeff S. Volek et al., “Carbohydrate Restriction Has a More Favorable Impact on the Metabolic Syndrome Than a Low Fat Diet | SpringerLink.” Lipids 44, no. 4 (April 2009): 297–309. https://link.springer.com/article/10.1007%2Fs11745-008-3274-2.

[10] P. A. Dyson, S. Beatty, and D. R. Matthews, “A Low-Carbohydrate Diet Is More Effective in Reducing Body Weight Than Healthy Eating in Both Diabetic and Non-Diabetic Subjects.” Diabetic Medicine 24, no. 12 (December 2007): 1430–35. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1464-5491.2007.02290.x.

[11] Y. Wady Aude et al., “The National Cholesterol Education Program Diet vs. a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat: A Randomized Trial.” Archives of Internal Medicine 164, no. 19 (October 25, 2004): 2141–46. https://doi.org/10.1001/archinte.164.19.2141.

They compare very low-carbohydrate diets against diets containing 25 to 35 percent fat (and containing significant amounts of animal foods), and erroneously conclude that eating carbohydrates worsens your long-term health.

[12] Bonnie J. Brehm et al., “A Randomized Trial Comparing a Very Low Carbohydrate Diet and a Calorie-Restricted Low Fat Diet on Body Weight and Cardiovascular Risk Factors in Healthy Women.” The Journal of Clinical Endocrinology and Metabolism 88, no. 4 (April 2003): 1617–23. https://doi.org/10.1210/jc.2002-021480.

[13] Grant D. Brinkworth et al., “Long term Effects of a Very-Low-Carbohydrate Weight Loss Diet Compared with an Isocaloric Low-Fat Diet after 12 Mo.” The American Journal of Clinical Nutrition 90, no. 1 (July 2009): 23–32. https://doi.org/10.3945/ajcn.2008.27326.

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[20] H. Guldbrand et al., “In Type 2 Diabetes, Randomisation to Advice to Follow a Low-Carbohydrate Diet Transiently Improves Glycaemic Control Compared with Advice to Follow a Low-Fat Diet Producing a Similar Weight Loss.” Diabetologia 55, no. 8 (August 1, 2012): 2118–27. https://doi.org/10.1007/s00125-012-2567-4.

[21] Angela K. Halyburton et al., “Low- and High-Carbohydrate Weight-Loss Diets Have Similar Effects on Mood but Not Cognitive Performance.” The American Journal of Clinical Nutrition 86, no. 3 (September 2007): 580–87. https://doi.org/10.1093/ajcn/86.3.580.

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Beta cells release small amounts of first-phase insulin to help your liver take up glucose from the portal vein, then later release second-phase insulin once larger amounts of glucose get into general circulation.

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Your coworker would, yes, die.

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These studies clearly demonstrate that increasing your fat intake has an immediate negative impact on the ability of insulin to communicate with tissues, which can then develop into a chronic state of insulin resistance and diabetes if your fat intake remains high.

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[49] M. E. Griffin et al., “Free Fatty Acid-Induced Insulin Resistance Is Associated with Activation of Protein Kinase C Theta and Alterations in the Insulin Signaling Cascade.” Diabetes 48, no. 6 (June 1999): 1270–74. https://doi.org/10.2337/diabetes.48.6.1270. 

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More than fifty years later, this research is still considered one of the most profound observations in carbohydrate biology; however, the modern scientific world is quick to misinterpret this simple and very powerful insight.

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If you’ve ever noticed that a high-fat meal takes longer for your stomach to process than a lower fat meal, this is exactly why — because the presence of dietary fat slows the digestion of all food material, causing a temporary traffic jam in your stomach.

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This is one reason why diets high in fat are effective at curbing your appetite and making you feel full for long periods of time.

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The reason most people and health professionals consider adipose tissue dangerous is that, much like insulin, excess fat increases your risk for many chronic diseases— especially the deep abdominal fat that surrounds your in ternal organs—because the more fat you store in your abdomen, the higher your risk for obesity, cardiovascular disease, hypertension, diabetes, and insulin resistance.

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The problem is that these signals don’t just recruit more hungry macrophages; they also trigger chronic inflammation, and in the process create a state of adipose tissue insulin resistance.

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Within hours of a single high- fat meal, insulin receptors become less numerous and less functional, perform less work, and have a very difficult time recognizing insulin in your blood.

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These dysfunctional insulin receptors keep glucose outside of cells, leaving glucose trapped in your blood for long periods of time.

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However, the first method is the only one that minimizes your risk for long- term chronic disease, while the second method significantly increases your risk for cardiovascular mortality.

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Fatty liver disease occurs when the amount of fat in your liver is more than 5 percent by weight, resulting in liver enlargement, which can then lead to liver fibrosis, a condition marked by the formation of scar tissue.

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While it’s certainly true that eating or drinking refined sugars like sucrose and high-fructose corn syrup (HFCS) can contribute to fatty liver disease, a growing body of research shows that a high- fat diet results in a progressive decline in liver function over time.

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The accumulation of excess fat in your beta cells leads to severe dysfunction known as lipotoxicity.

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Autopsies have revealed that in the majority of patients with type 2 diabetes, more than half of the beta cell population has died.

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After the age of 20, your body stops making new beta cells; therefore beta cell death is considered irreversible.

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Given what scientists understand about autoimmunity, they be lieve that certain individuals have a genetic predisposition to type 1 and type 1.5 diabetes at birth, but develop autoimmunity only when exposed to one or more environmental “triggers,” including a viral infection, a bacterial infection, or exposure to cow’s milk protein at a very young age.

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A growing body of scientific evidence demonstrates that insulin resistance is a growing concern in autoimmune diabetes owing to less- than- ideal lifestyle choices, and eating a diet that consists of low- carbohydrate foods like meat, fish, dairy, eggs, and oils, or a diet containing significant quantities of refined sugar and processed foods.

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However, the overwhelming majority of trans fats in most people’s diets originate from a process known as hydrogenation, a chemical manufacturing process that food manufacturers use to convert unsaturated fatty acids into saturated fatty acids.

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[2] Joyce A. Nettleton et al., “Fats in Foods: Current Evidence for Dietary Advice.” Annals of Nutrition & Metabolism 72, no. 3 (April 2018): 248–54. https://doi.org/10.1159/000488006.

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Studies show that industrial trans fats can significantly increase your risk for congestive heart disease, and that even small amounts of trans fats can directly elevate your LDL cholesterol, reduce your HDL cholesterol, cause vascular inflammation, and accelerate the development of atherosclerotic plaques, both in your heart and in peripheral blood vessels.

[4] Ronald P. Mensink et al., “Effects of Dietary Fatty Acids and Carbohydrates on the Ratio of Serum Total to HDL Cholesterol and on Serum Lipids and Apolipoproteins: A Meta-Analysis of 60 Controlled Trials.” The American Journal of Clinical Nutrition 77, no. 5 (May 2003): 1146–55. https://doi.org/10.1093/ajcn/77.5.1146.

[5] Paul Nestel, “Trans Fatty Acids: Are Its Cardiovascular Risks Fully Appreciated?” Clinical Therapeutics 36, no. 3 (March 1, 2014): 315–21. https://doi.org/10.1016/j.clinthera.2014.01.020.

[6] Russell J. de Souza et al., “Intake of Saturated and Trans Unsaturated Fatty Acids and Risk of All Cause Mortality, Cardiovascular Disease, and Type 2 Diabetes: Systematic Review and Meta-Analysis of Observational Studies.” BMJ 351 (2015): PMC4532752. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532752/.

[7] Riya Ganguly and Grant N. Pierce, “The Toxicity of Dietary Trans Fats.” Food and Chemical Toxicology 78 (2015): 170–76. https://www.sciencedirect.com/science/article/pii/S0278691515000435.

Studies have shown that those who eat more industrial trans fats have a greater risk for Alzheimer’s disease than those who eat the fewest, either due to direct damage to neurons in your brain or indirectly by increasing your cholesterol levels, which are known to be associated with Alzheimer’s disease.

[8] Martha Clare Morris et al., “Dietary Fats and the Risk of Incident Alzheimer Disease.” Archives of Neurology 60, no. 2 (February 1, 2003): 194–200. https://doi.org/10.1001/archneur.60.2.194.

[9] Shui-Lin Niu, Drake C. Mitchell, and Burton J. Litman, “Trans Fatty Acid Derived Phospholipids Show Increased Membrane Cholesterol and Reduced Receptor Activation as Compared to Their Cis Analogs.” Biochemistry 44, no. 11 (March 22, 2005): 4458–65. https://doi.org/10.1021/bi048319+.

[10] Alina Solomon et al., “Midlife Serum Cholesterol and Increased Risk of Alzheimer’s and Vascular Dementia Three Decades Later.” Dementia and Geriatric Cognitive Disorders 28, no. 1 (2009): 75–80. https://doi.org/10.1159/000231980.

When it comes to the connection between trans fats and insulin resistance, ample evidence has shown that trans fats directly impair the ability of beta cells to respond to glucose in both animals and cell culture.

[11] A. K. Thompson, A.-M. Minihane, and C. M. Williams, “Trans Fatty Acids, Insulin Resistance and Diabetes.” European Journal of Clinical Nutrition 65, no. 5 (May 2011): 553–64. https://doi.org/10.1038/ejcn.2010.240.

The Nurses’ Health Study, in which researchers from the Harvard T. H. Chan School of Public Health performed an analysis on data from more than 200,000 individuals taken over the course of nineteen years, showed that a higher intake of trans fatty acids was associated with a higher risk of type 2 diabetes over the course of fourteen years.

[12] J. Salmerón et al., “Dietary Fat Intake and Risk of Type 2 Diabetes in Women.” The American Journal of Clinical Nutrition 73, no. 6 (June 2001): 1019–26. https://doi.org/10.1093/ajcn/73.6.1019.

In fact, the scientific world is so knowledgeable about the detrimental effects of saturated fat that scientists actually induce obesity and insulin resistance in animals and humans using diets high in saturated fat.

[13] Muhammad-Quaid Zaman et al., “Lipid Profile and Insulin Sensitivity in Rats Fed with High-Fat or High-Fructose Diets.” British Journal of Nutrition 106, Suppl S1 (October 2011): S206–S210. https://doi.org/10.1017/S0007114511004454.

[14] M. G. Sridhar et al., “Bitter Gourd (Momordica charantia) Improves Insulin Sensitivity by Increasing Skeletal Muscle Insulin-Stimulated IRS-1 Tyrosine Phosphorylation in High-Fat-Fed Rats.” The British Journal of Nutrition 99, no. 4 (April 2008): 806–12. https://doi.org/10.1017/S000711450783176X.

[15] Natalia Sinitskaya et al., “Increasing the Fat-to-Carbohydrate Ratio in a High-Fat Diet Prevents the Development of Obesity but Not a Prediabetic State in Rats.” Clinical Science 113, no. 10 (November 1, 2007): 417–25. https://doi.org/10.1042/CS20070182.

[16] Sneha Sundaram and Lin Yan, “Time-Restricted Feeding Reduces Adiposity in Mice Fed a High-Fat Diet.” Nutrition Research 36, no. 6 (June 1, 2016): 603–11. https://doi.org/10.1016/j.nutres.2016.02.005.

[17] Michael Roden, “How Free Fatty Acids Inhibit Glucose Utilization in Human Skeletal Muscle.” News in Physiological Sciences 19 (June 2004): 92–96. https://doi.org/10.1152/nips.01459.2003.

[18] Girish Kewalramani, Philip J. Bilan, and Amira Klip, “Muscle Insulin Resistance: Assault by Lipids, Cytokines and Local Macrophages.” Current Opinion in Clinical Nutrition and Metabolic Care 13, no. 4 (July 2010): 382–90. https://doi.org/10.1097/MCO.0b013e32833aabd9.

Saturated fatty acids directly interfere with insulin signaling within hours of entering muscle and liver cells, inhibiting the ability of your muscle and liver to uptake glucose from your blood.

[19] Howard A. Wolpert et al., “Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients with Type 1 Diabetes Implications for Carbohydrate-Based Bolus Dose Calculation and Intensive Diabetes Management.” Diabetes Care 36, no. 4 (April 1, 2013): 810–16. https://doi.org/10.2337/dc12-0092.

[20] Carmel E. M. Smart et al., “Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children with Type 1 Diabetes, and the Effect Is Additive.” Diabetes Care 36, no. 12 (December 2013): 3897–3902. https://doi.org/10.2337/dc13-1195.

[21] Megan Paterson et al., “The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management.” Current Diabetes Reports 15, no. 9 (July 23, 2015): 1–9. https://doi.org/10.1007/s11892-015-0630-5.

These inflammatory signals create chronic low- grade inflammation and directly inhibit the action of insulin.

[22] Girish Kewalramani, Philip J. Bilan, and Amira Klip, “Muscle Insulin Resistance: Assault by Lipids, Cytokines and Local Macrophages.” Current Opinion in Clinical Nutrition and Metabolic Care 13, no. 4 (July 2010): 382–90. https://doi.org/10.1097/MCO.0b013e32833aabd9.

Diets high in saturated fat are also especially dangerous for your liver, as they are extremely effective at promoting fatty liver disease, which can eventually lead to liver cirrhosis and induce an advanced state of liver insulin resistance and liver inflammation.

[23] Panu K. Luukkonen et al., “Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.” Diabetes Care, May 25, 2018, dc180071. https://doi.org/10.2337/dc18-0071.

The connection is so strong that researchers have developed a mathematical model (called the Hegsted equation) that specifically predicts how the saturated fat in your diet impacts the cholesterol level in your blood.

[24] D. M. Hegsted et al., “Quantitative Effects of Dietary Fat on Serum Cholesterol in Man.” The American Journal of Clinical Nutrition 17, no. 5 (November 1965): 281–95. https://doi.org/10.1093/ajcn/17.5.281.

Although the specifics of the equation are beyond the scope of this book, the most important thing to understand is that saturated fat in your diet increases your LDL cholesterol (more than dietary cholesterol itself )!

[25] Brittanie M. Volk et al., “Application of the Hegsted Equation to Low Carbohydrate-Low Fat Diet Comparisons.” The FASEB Journal 22, no. 1 Suppl (March 1, 2008): 1092.17-1092.17. https://www.fasebj.org/doi/abs/10.1096/fasebj.22.1_supplement.1092.17.

Data from more than one million participants enrolled in more than a hundred studies have demonstrated a strong positive relationship between your total LDL cholesterol level and your risk for coronary artery disease.

[26] Brian A. Ference and Nitin Mahajan, “The Role of Early LDL Lowering to Prevent the Onset of Atherosclerotic Disease.” Current Atherosclerosis Reports 15, no. 4 (April 1, 2013): 312. https://doi.org/10.1007/s11883-013-0312-1.

[27] Prospective Studies Collaboration, “Blood Cholesterol and Vascular Mortality by Age, Sex, and Blood Pressure: A Meta-Analysis of Individual Data from 61 Prospective Studies with 55,000 Vascular Deaths.” The Lancet 370, no. 9602 (December 1, 2007): 1829–39. https://doi.org/10.1016/S0140-6736(07)61778-4.

[28] The Emerging Risk Factors Collaboration, “Major Lipids, Apolipoproteins, and Risk of Vascular Disease.” JAMA 302, no. 18 (November 11, 2009): 1993–2000. https://doi.org/10.1001/jama.2009.1619.

Here are a few things that are extremely important to understand. 1. All LDL particles increase your risk for heart disease, regardless of whether they are small or large. 2. Large, buoyant LDL particles increase your risk for heart disease by approximately 31 percent. 3. Small, dense LDL particles increase your risk for heart disease by approximately 44 percent. 4. The most effective way to reduce your LDL cholesterol is by reducing your saturated fat intake, reducing or eliminating your cholesterol intake, and increasing your intake of carbohydrate- rich whole foods.

[29] Jennifer G. Robinson, “What Is the Role of Advanced Lipoprotein Analysis in Practice?” Journal of the American College of Cardiology 60, no. 25 (December 2012): 2607–15. https://doi.org/10.1016/j.jacc.2012.04.067.

[30] James D. Otvos et al., “Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial.” Circulation 113, no. 12 (March 28, 2006): 1556–63. https://doi.org/10.1161/CIRCULATIONAHA.105.565135.

Suggests that substituting higher quality unsaturated fatty acids for lower quality saturated fatty acids and trans fatty acids dramatically improves your insulin sensitivity within weeks, in addition to reduced LDL cholesterol and reduced body fat.

[31] Ulf Risérus, Walter C. Willett, and Frank B. Hu, “Dietary Fats and Prevention of Type 2 Diabetes.” Progress in Lipid Research 48, no. 1 (January 2009): 44–51. https://doi.org/10.1016/j.plipres.2008.10.002.

Higher PUFA intake correlated with less type 2 diabetes risk, but that higher MUFA intake did not.

[32] J. Salmerón et al., “Dietary Fat Intake and Risk of Type 2 Diabetes in Women.” The American Journal of Clinical Nutrition 73, no. 6 (June 2001): 1019–26. https://doi.org/10.1093/ajcn/73.6.1019.

Substituting PUFAs for saturated fatty acids significantly decreased type 2 diabetes risk.

[33] Katie A. Meyer et al., “Dietary Fat and Incidence of Type 2 Diabetes in Older Iowa Women.” Diabetes Care 24, no. 9 (September 1, 2001): 1528–35. https://doi.org/10.2337/diacare.24.9.1528.

Substituting foods rich in PUFAs for foods rich in saturated fatty acids improves your insulin sensitivity within as little as four to five weeks, without changing any other aspect of your diet.

[34] F. Pérez-Jiménez et al. “A Mediterranean and a High-Carbohydrate Diet Improve Glucose Metabolism in Healthy Young Persons.” Diabetologia 44, no. 11 (November 2001): 2038–43. https://doi.org/10.1007/s001250100009.

[35] L. K. Summers et al., “Substituting Dietary Saturated Fat with Polyunsaturated Fat Changes Abdominal Fat Distribution and Improves Insulin Sensitivity.” Diabetologia 45, no. 3 (March 2002): 369–77. https://doi.org/10.1007/s00125-001-0768-3.

[36] F. B. Hu, R. M. van Dam, and S. Liu, “Diet and Risk of Type II Diabetes: The Role of Types of Fat and Carbohydrate.” Diabetologia 44, no. 7 (July 2001): 805–17. https://doi.org/10.1007/s001250100547.

Studies also consistently show that replacing foods rich in saturated fats with those high in unsaturated fats is a simple and powerful way to lower your LDL cholesterol, raise your HDL cholesterol, and protect against sudden cardiac death.

[37] Benoît Lamarche et al. “Combined Effects of a Dietary Portfolio of Plant Sterols, Vegetable Protein, Viscous Fibre and Almonds on LDL Particle Size.” British Journal of Nutrition 92, no. 4 (October 2004): 657–63. https://doi.org/10.1079/BJN20041241.

[38] F. B. Hu and M. J. Stampfer, “Nut Consumption and Risk of Coronary Heart Disease: A Review of Epidemiologic Evidence.” Current Atherosclerosis Reports 1, no. 3 (November 1999): 204–9. https://www.ncbi.nlm.nih.gov/pubmed/11122711.

Replacing 10 percent of your calories from saturated fat with carbohydrate- rich whole foods can reduce your total cholesterol by about 20 mg/ dL and your LDL cholesterol by about 14 mg/ dL.

[39] R. Clarke et al., “Dietary Lipids and Blood Cholesterol: Quantitative Meta-Analysis of Metabolic Ward Studies.” BMJ: British Medical Journal 314, no. 7074 (January 11, 1997): 112–17. 10.1136/bmj.314.7074.112.

They have a high nutrient density and are rich in protective phytochemical compounds, including lignans, sterols, antioxidants, fiber, polyphenols, minerals, and bioflavonoids.

[40] Emilio Ros, “Eat Nuts, Live Longer.” Journal of the American College of Cardiology 70, no. 20 (November 14, 2017): 2533–35. https://dx.doi.org/10.1016/j.jacc.2017.09.1082.

[38 again] F. B. Hu and M. J. Stampfer, “Nut Consumption and Risk of Coronary Heart Disease: A Review of Epidemiologic Evidence.” Current Atherosclerosis Reports 1, no. 3 (November 1999): 204–209. https://www.ncbi.nlm.nih.gov/pubmed/11122711.

In fact, there is a large body of compelling research that demonstrates how eating meat and dairy not only increases your risk for high blood glucose, insulin resistance, weight gain, increased fasting glucose, and increased fasting insulin concentrations, but also causes inflammation and promotes heart disease and hypertension over the course of time.

[1] D. Aune, G. Ursin, and M. B. Veierød, “Meat Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis of Cohort Studies.” Diabetologia 52, no. 11 (November 1, 2009): 2277–87. https://doi.org/10.1007/s00125-009-1481-x.

[2] Rob M. van Dam et al., “Dietary Fat and Meat Intake in Relation to Risk of Type 2 Diabetes in Men.” Diabetes Care 25, no. 3 (March 1, 2002): 417–24. https://doi.org/10.2337/diacare.25.3.417.

[3] Teresa T. Fung et al., “Dietary Patterns, Meat Intake, and the Risk of Type 2 Diabetes in Women.” Archives of Internal Medicine 164, no. 20 (November 8, 2004): 2235–240. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/217599.

[4] Edith J. M. Feskens, Diewertje Sluik, and Geertruida J. van Woudenbergh, “Meat Consumption, Diabetes, and Its Complications.” Current Diabetes Reports 13, no. 2 (April 1, 2013): 298–306. https://doi.org/10.1007/s11892-013-0365-0.

[5] Martin Lajous et al., “Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women.” Diabetes Care 35, no. 1 (January 2012): 128–30. https://doi.org/10.2337/dc11-1518.

[6] Renata Micha, Sarah K. Wallace, and Dariush Mozaffarian, “Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes: A Systematic Review and Meta-Analysis.” Circulation 121, no. 21 (June 1, 2010): 2271–83. https://doi.org/10.1161/CIRCULATIONAHA.109.924977.

[7] An Pan et al., “Red Meat Consumption and Risk of Type 2 Diabetes: 3 Cohorts of US Adults and an Updated Meta-Analysis123.” The American Journal of Clinical Nutrition 94, no. 4 (October 2011): 1088–96. https://doi.org/10.3945/ajcn.111.018978.

[8] M. B. Schulze et al., “Processed Meat Intake and Incidence of Type 2 Diabetes in Younger and Middle-Aged Women.” Diabetologia 46, no. 11 (November 2003): 1465–73. https://doi.org/10.1007/s00125-003-1220-7.

[9] Yiqing Song et al., “A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women: The Women’s Health Study.” Diabetes Care 27, no. 9 (September 1, 2004): 2108–15. https://doi.org/10.2337/diacare.27.9.2108.

[10] A. Steinbrecher et al., “Meat Consumption and Risk of Type 2 Diabetes: The Multiethnic Cohort.” Public Health Nutrition 14, no. 4 (April 2011): 568–74. https://doi.org/10.1017/S1368980010002004.

[11] Geertruida J. van Woudenbergh et al., “Meat Consumption and Its Association with C-Reactive Protein and Incident Type 2 Diabetes.” Diabetes Care 35, no. 7 (July 2012): 1499–505. https://doi.org/10.2337/dc11-1899.

[12] The InterAct Consortium, “Association Between Dietary Meat Consumption and Incident Type 2 Diabetes: The EPIC-InterAct Study.” Diabetologia 56, no. 1 (January 1, 2013): 47–59. https://doi.org/10.1007/s00125-012-2718-7.

[13] Xia Wang et al., “Red and Processed Meat Consumption and Mortality: Dose-Response Meta-Analysis of Prospective Cohort Studies.” Public Health Nutrition 19, no. 5 (April 2016): 893–905. https://doi.org/10.1017/S1368980015002062.

[14] H. A. Kahn et al., “Association Between Reported Diet and All-Cause Mortality. Twenty-One-Year Follow-up on 27,530 Adult Seventh-Day Adventists.” American Journal of Epidemiology 119, no. 5 (May 1984): 775–87. 10.1093/oxfordjournals.aje.a113798.

[15] Michael J. Orlich et al., “Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2.” JAMA Internal Medicine 173, no. 13 (July 8, 2013): 1230–38. https://doi.org/10.1001/jamainternmed.2013.6473.

[16] Mingyang Song et al., “Association of Animal and Plant Protein Intake with All-Cause and Cause-Specific Mortality.” JAMA Internal Medicine, August 1, 2016. https://doi.org/10.1001/jamainternmed.2016.4182.

[17] Sabine Rohrmann et al., “Meat Consumption and Mortality—Results from the European Prospective Investigation into Cancer and Nutrition.” BMC Medicine 11 (2013): 63. https://doi.org/10.1186/1741-7015-11-63.

[18] Hiroshi Noto et al., “Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies.” PLOS ONE 8, no. 1 (2013): e55030. https://doi.org/10.1371/journal.pone.0055030.

[19] Teresa T. Fung et al., “Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality: Two Cohort Studies.” Annals of Internal Medicine 153, no. 5 (September 7, 2010): 289–98. 10.7326/0003-4819-153-5-201009070-00003.

The EPIC study also revealed that replacing 5 percent of saturated fat with fructose (from fruits or refined sources) reduces your diabetes risk by 30 percent, and that replacing 5 percent of protein with fructose reduces your diabetes risk by 28 percent.

[20] InterAct Consortium, “Association Between Dietary Meat Consumption and Incident Type 2 Diabetes: The EPIC-InterAct Study.” Diabetologia 56, no. 1 (January 2013): 47–59. https://doi.org/10.1007/s00125-012-2718-7.

[21] Nita G. Forouhi and Nicholas J. Wareham, “The EPIC-InterAct Study: A Study of the Interplay Between Genetic and Lifestyle Behavioral Factors on the Risk of Type 2 Diabetes in European Populations.” Current Nutrition Reports 3, no. 4 (2014): 355–63. https://doi.org/10.1007/s13668-014-0098-y.

[22] Monique van Nielen et al., “Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study.” Diabetes Care 37, no. 7 (July 1, 2014): 1854–62. https://doi.org/10.2337/dc13-2627.

[23] Matthias B. Schulze et al., “Carbohydrate Intake and Incidence of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.” British Journal of Nutrition 99, no. 5 (May 2008): 1107–16. https://doi.org/10.1017/S0007114507853360.

[24] Ivonne Sluijs et al., “Carbohydrate Quantity and Quality and Risk of Type 2 Diabetes in the European Prospective Investigation into Cancer and Nutrition—Netherlands (EPIC-NL) Study.” The American Journal of Clinical Nutrition 92, no. 4 (October 1, 2010): 905–11. https://doi.org/10.3945/ajcn.2010.29620.

[25] InterAct Consortium, “Adherence to Predefined Dietary Patterns and Incident Type 2 Diabetes in European Populations: EPIC-InterAct Study.” Diabetologia 57, no. 2 (2014): 321–33. https://doi.org/10.1007/s00125-013-3092-9.

[26] Sara Ahmadi-Abhari et al., “Dietary Intake of Carbohydrates and Risk of Type 2 Diabetes: The European Prospective Investigation into Cancer-Norfolk Study.” British Journal of Nutrition 111, no. 2 (January 2014): 342–52. https://doi.org/10.1017/S0007114513002298.

Most importantly, those who ate a vegetarian diet in the long term were 74 percent less likely to develop diabetes, even when compared with those who ate meat only once per week.

[27] Arnold Vang et al., “Meats, Processed Meats, Obesity, Weight Gain and Occurrence of Diabetes Among Adults: Findings from Adventist Health Studies.” Annals of Nutrition and Metabolism 52, no. 2 (2008): 96–104. https://doi.org/10.1159/000121365.

[28] S. Tonstad et al., “Vegetarian Diets and Incidence of Diabetes in the Adventist Health Study-2.” Nutrition, Metabolism, and Cardiovascular Diseases 23, no. 4 (April 2013): 292–99. https://doi.org/10.1016/j.numecd.2011.07.004.

[29] Michael J. Orlich et al., “Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2.” JAMA Internal Medicine 173, no. 13 (July 8, 2013): 1230–38. https://doi.org/10.1001/jamainternmed.2013.6473.

[30] Lap Tai Le and Joan Sabaté, “Beyond Meatless, the Health Effects of Vegan Diets: Findings from the Adventist Cohorts.” Nutrients 6, no. 6 (May 27, 2014): 2131–47. https://doi.org/10.3390/nu6062131.

They found that men who ate processed meats (bacon, hot dogs, hamburgers, sausage, salami, and bologna) at least 5 times per week were 46 percent more likely to develop type 2 diabetes than those who ate meat once a month.

[31] Rob M. van Dam et al., “Dietary Fat and Meat Intake in Relation to Risk of Type 2 Diabetes in Men.” Diabetes Care 25, no. 3 (March 1, 2002): 417–24. https://doi.org/10.2337/diacare.25.3.417.

Eating just one serving per day of unprocessed red meat increased diabetes risk by 12 percent and eating one serving per day of processed red meat increased diabetes risk by 32 percent.

[32] An Pan et al., “Changes in Red Meat Consumption and Subsequent Risk of Type 2 Diabetes Mellitus: Three Cohorts of US Men and Women.” JAMA Internal Medicine 173, no. 14 (July 22, 2013): 1328–35. https://doi.org/10.1001/jamainternmed.2013.6633.

The Women’s Health Study followed more than 37,000 women over 45 years old for 8.8 years and found that those who ate the most red meat were 28 percent more likely to develop diabetes, and those who ate the most total processed meat were at a 43 percent increased risk for diabetes.

[33] Yiqing Song et al., “A Prospective Study of Red Meat Consumption and Type 2 Diabetes in Middle-Aged and Elderly Women: The Women’s Health Study.” Diabetes Care 27, no. 9 (September 1, 2004): 2108–15. https://doi.org/10.2337/diacare.27.9.2108.

Recent data from Spanish researchers observed in more than 18,000 people over the course of fourteen years shows that eating three or more servings of either processed or unprocessed meat (including chicken) was associated with a significantly higher risk for the development of type 2 diabetes, and that switching from processed meat to unprocessed meat did not reduce diabetes risk.

[34] A. Mari-Sanchis et al., “Meat Consumption and Risk of Developing Type 2 Diabetes in the SUN Project: A Highly Educated Middle-Class Population.” PLOS ONE 11, no. 7 (July 20, 2016). https://doi.org/10.1371/journal.pone.0157990.

A meta-analysis published in 2013 provides a comprehensive summary of large-scale studies on the risk of developing type 2 diabetes from various types of meat, and the results are summarized in the table below.

[35] Edith J. M. Feskens, Diewertje Sluik, and Geertruida J. van Woudenbergh, “Meat Consumption, Diabetes, and Its Complications.” Current Diabetes Reports 13, no. 2 (April 1, 2013): 298–306. https://doi.org/10.1007/s11892-013-0365-0.

The Physicians’ Health Study found that people with diabetes significantly elevate their risk for all- cause mortality after eating about five eggs per week, and two other studies involving more than 80,000 people found that eating more than six eggs per week significantly increases the risk of cardiovascular disease in people with diabetes.

[36] Luc Djoussé and J. Michael Gaziano, “Egg Consumption in Relation to Cardiovascular Disease and Mortality: The Physicians’ Health Study.” The American Journal of Clinical Nutrition 87, no. 4 (April 2008): 964–69. 10.1093/ajcn/87.4.964.

[37] Adnan I. Qureshi et al., “Regular Egg Consumption Does Not Increase the Risk of Stroke and Cardiovascular Diseases.” Medical Science Monitor 13, no. 1 (January 2007): CR1-8. https://www.ncbi.nlm.nih.gov/pubmed/17179903.

[38] F. B. Hu et al., “A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women.” JAMA 281, no. 15 (April 21, 1999): 1387–94. 10.1001/jama.281.15.1387.

Researchers found that three eggs per week significantly increased arterial plaque formation in carotid arteries, significantly elevating the risk for hypertension, stroke, and heart attack.

[39] J. David Spence, David J. A. Jenkins, and Jean Davignon, “Egg Yolk Consumption and Carotid Plaque.” Atherosclerosis 224, no. 2 (October 2012): 469–73. https://doi.org/10.1016/j.atherosclerosis.2012.07.032.

Studies have also shown that eating more than two and a half eggs per week increases the risk for the development of prostate cancer by more than 81 percent.

[40] Erin L. Richman et al., “Egg, Red Meat, and Poultry Intake and Risk of Lethal Prostate Cancer in the Prostate-Specific Antigen-Era: Incidence and Survival.” Cancer Prevention Research 4, no. 12 (December 2011): 2110–21. https://doi.org/10.1158/1940-6207.CAPR-11-0354.

The authors found that the strongest correlation was between egg consumption and colon cancer, and that eating more than five eggs per week increased colon cancer risk by 42 percent.

[41] Genevieve Tse and Guy D. Eslick, “Egg Consumption and Risk of GI Neoplasms: Dose-Response Meta-Analysis and Systematic Review.” European Journal of Nutrition 53, no. 7 (October 2014): 1581–90. https://doi.org/10.1007/s00394-014-0664-5.

Studies have also shown that eating more than two and a half eggs per week increases the risk for the development of prostate cancer by more than 81 percent.

[42] Mattias Johansson et al., “One-Carbon Metabolism and Prostate Cancer Risk: Prospective Investigation of Seven Circulating B Vitamins and Metabolites.” Cancer Epidemiology, Biomarkers & Prevention 18, no. 5 (May 2009): 1538–43. https://doi.org/10.1158/1055-9965.EPI-08-1193.

[43] Elizabeth A. Platz, Steven K. Clinton, and Edward Giovannucci, “Association Between Plasma Cholesterol and Prostate Cancer in the PSA Era.” International Journal of Cancer 123, no. 7 (October 1, 2008): 1693–98. https://doi.org/10.1002/ijc.23715.

[44] Kristine Pelton, Michael R. Freeman, and Keith R. Solomon, “Cholesterol and Prostate Cancer.” Current Opinion in Pharmacology 12, no. 6 (December 2012): 751–59. https://doi.org/10.1016/j.coph.2012.07.006.

Cholesterol is elevated in tumor cells in all tissues, and increasing blood cholesterol has been shown to promote tumor growth and metastases.

[45] Pedro M. R. Cruz et al., “The Role of Cholesterol Metabolism and Cholesterol Transport in Carcinogenesis: A Review of Scientific Findings, Relevant to Future Cancer Therapeutics.” Frontiers in Pharmacology 4 (2013): 119. https://doi.org/10.3389/fphar.2013.00119.

[46] K. A. Steinmetz and J. D. Potter, “Egg Consumption and Cancer of the Colon and Rectum.” European Journal of Cancer Prevention 3, no. 3 (May 1994): 237–45. https://www.ncbi.nlm.nih.gov/pubmed/8061589.

[47] P. Cruse, M. Lewin, and C. G. Clark, “Dietary Cholesterol Is Co-Carcinogenic for Human Colon Cancer.” The Lancet 1, no. 8119 (April 7, 1979): 752–55. 10.1016/s0140-6736(79)91209-1.

Choline is also elevated in tumor cells and is metabolized in the large intestine into pro-inflammatory compounds that may promote cancer development.

[48] W. H. Wilson Tang et al., “Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk.” The New England Journal of Medicine 368, no. 17 (April 25, 2013): 1575–84. https://doi.org/10.1056/NEJMoa1109400.

[49] Zeneng Wang et al., “Gut Flora Metabolism of Phosphatidylcholine Promotes Cardiovascular Disease.” Nature 472, no. 7341 (April 7, 2011): 57–63. https://doi.org/10.1038/nature09922.

[50] Erin L. Richman et al., “Choline Intake and Risk of Lethal Prostate Cancer: Incidence and Survival.” The American Journal of Clinical Nutrition 96, no. 4 (October 2012): 855–63. https://doi.org/10.3945/ajcn.112.039784.

Data from the Nurses’ Health Study indicates that eating more than seven eggs per week doubled the risk of all-cause mortality in male subjects, and that eating more than seven eggs per week increased the risk for heart disease in males living with diabetes.

[51] Luc Djoussé and J. Michael Gaziano, “Egg Consumption in Relation to Cardiovascular Disease and Mortality: The Physicians’ Health Study.” The American Journal of Clinical Nutrition 87, no. 4 (April 2008): 964–69. 10.1093/ajcn/87.4.964.

This includes (a) fatty acid accumulation in muscle and liver, (b) chronic liver glucose export, (c) increased insulin secretion, (d) increased beta cell reproduction, and (e) eventual beta cell suicide.

[52] Bodo C. Melnik, “Leucine Signaling in the Pathogenesis of Type 2 Diabetes and Obesity.” World Journal of Diabetes 3, no. 3 (March 15, 2012): 38–53. https://doi.org/10.4239/wjd.v3.i3.38.

[53] Roberto Zoncu, Alejo Efeyan, and David M. Sabatini, “mTOR: From Growth Signal Integration to Cancer, Diabetes and Ageing.” Nature Reviews: Molecular Cell Biology 12, no. 1 (January 2011): 21–35. 10.1038/nrm3025.

Leucine promotes more insulin production than any other amino acid, and some scientists believe that increased leucine intake from both meat and dairy products stimulates beta cells to chronically overproduce insulin.

[54] Mikael Nilsson, Jens J. Holst, and Inger M. E. Björk, “Metabolic Effects of Amino Acid Mixtures and Whey Protein in Healthy Subjects: Studies Using Glucose-Equivalent Drinks.” The American Journal of Clinical Nutrition 85, no. 4 (April 2007): 996–1004. https://academic.oup.com/ajcn/article/85/4/996/4648854.

Iron is an essential mineral that plays key roles in critical biochemical pathways, including mitochondrial energy metabolism, oxygen transport, and the production and release of neurotransmitters, as well as the synthesis of DNA, collagen, and steroid hormones.

[55] I. V. Milto et al., “Molecular and Cellular Bases of Iron Metabolism in Humans.” Biochemistry 81, no. 6 (June 2016): 549–64. https://doi.org/10.1134/S0006297916060018.

The metabolic effects of iron in many tissues is very clear – iron itself is not dangerous; it’s the intake and storage of excess iron that leads to biochemical complications that significantly increase your risk for type 2 diabetes.

[56] Michelle McMacken and Sapana Shah, “A Plant-Based Diet for the Prevention and Treatment of Type 2 Diabetes.” Journal of Geriatric Cardiology 14, no. 5 (May 2017): 342–54. https://doi.org/10.11909/j.issn.1671-5411.2017.05.009.

[57] Zhuoxian Zhao et al., “Body Iron Stores and Heme-Iron Intake in Relation to Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis.” PLOS ONE 7, no. 7 (July 26, 2012): e41641. https://doi.org/10.1371/journal.pone.0041641.

[58] Frédéric Fumeron et al. and Insulin Resistance Syndrome (DESIR) Study Group, “Ferritin and Transferrin Are Both Predictive of the Onset of Hyperglycemia in Men and Women over 3 Years: The Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) Study.” Diabetes Care 29, no. 9 (September 2006): 2090–94. https://doi.org/10.2337/dc06-0093.

[59] E. Ferrannini, “Insulin Resistance, Iron, and the Liver.” The Lancet 355, no. 9222 (June 24, 2000): 2181–82. https://doi.org/10.1016/S0140-6736(00)02397-7.

[60] Wei Bao et al., “Dietary Iron Intake, Body Iron Stores, and the Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis.” BMC Medicine 10 (October 10, 2012): 119. https://doi.org/10.1186/1741-7015-10-119.

Studies involving more than 185,000 people showed that as little as 5 milligrams per day of dietary heme iron from animal foods can elevate type 2 diabetes risk by as much as 224 percent, suggesting that even small amounts of animal products can significantly increase your risk for elevated blood glucose and whole-body inflammation.

[61] Setor K. Kunutsor et al., “Ferritin Levels and Risk of Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-Analysis of Prospective Evidence.” Diabetes/Metabolism Research and Reviews 29, no. 4 (May 2013): 308–18. https://doi.org/10.1002/dmrr.2394.

Nitrosamine compounds are known to be beta cell toxins that can directly trigger oxidative stress and beta cell death. Research has shown that consumption of foods with a high nitrite and nitrosamine content have been associated with the development of type 1 diabetes.

[62] S. M. Virtanen et al., “Nitrate and Nitrite Intake and the Risk for Type 1 Diabetes in Finnish Children.” Diabetic Medicine 11, no. 7 (August 9, 1994): 656–62. https://doi.org/10.1111/j.1464-5491.1994.tb00328.x.

[63] Raquel Villegas et al., “The Association of Meat Intake and the Risk of Type 2 Diabetes May Be Modified by Body Weight.” International Journal of Medical Sciences 3, no. 4 (October 27, 2006): 152–59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633824/.

[64] G. G. Dahlquist et al., “Dietary Factors and the Risk of Developing Insulin Dependent Diabetes in Childhood.” BMJ: British Medical Journal 300, no. 6735 (May 19, 1990): 1302–6. 10.1136/bmj.300.6735.1302.

[65] T. Helgason and M. R. Jonasson, “Evidence for a Food Additive as a Cause of Ketosis-Prone Diabetes.” The Lancet 2, no. 8249 (October 3, 1981): 716–20. 10.1016/s0140-6736(81)91048-5.

The strongest associations were death from diabetes, respiratory diseases, and kidney disease.

[66] Arash Etemadi et al., “Mortality from Different Causes Associated with Meat, Heme Iron, Nitrates, and Nitrites in the NIH-AARP Diet and Health Study: Population Based Cohort Study.” BMJ 357 (May 9, 2017): j1957. https://doi.org/10.1136/bmj.j1957.

A randomized control trial from 2003 revealed that heme iron found only in meat may actually accelerate the conversion of nitrate into nitrosamine compounds, but that non- heme iron found in plants did not.

[67] Amanda Jane Cross, Jim R. A. Pollock, and Sheila Anne Bingham, “Haem, Not Protein or Inorganic Iron, Is Responsible for Endogenous Intestinal N-Nitrosation Arising from Red Meat.” Cancer Research 63, no. 10 (May 15, 2003): 2358–60. https://www.ncbi.nlm.nih.gov/pubmed/12750250.

Processed meat contains on average four times the amount of sodium as unprocessed meat, and researchers have calculated that eating just one 50-gram serving of processed meat per day could increase your risk for cardiovascular disease by as much as 27 percent.

[68] Renata Micha, Sarah K. Wallace, and Dariush Mozaffarian, “Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes: A Systematic Review and Meta-Analysis.” Circulation 121, no. 21 (June 1, 2010): 2271–83. https://doi.org/10.1161/CIRCULATIONAHA.109.924977.

[69] Edith J. M. Feskens, Diewertje Sluik, and Geertruida J. van Woudenbergh, “Meat Consumption, Diabetes, and Its Complications.” Current Diabetes Reports 13, no. 2 (April 1, 2013): 298–306. https://doi.org/10.1007/s11892-013-0365-0.

Researchers from Finland analyzed the data of more than 24,000 people over the course of twelve years to determine which compounds were the most predictive of type 2 diabetes, and found that sodium was the strongest predictor of type 2 diabetes risk.

[70] Satu Männistö et al., “High Processed Meat Consumption Is a Risk Factor of Type 2 Diabetes in the ATBC Study.” The British Journal of Nutrition 103, no. 12 (June 2010): 1817–22. https://doi.org/10.1017/S0007114510000073.

They found that the foods with the highest AGE content were beef, cheese, poultry, pork, fish, and eggs, whereas the foods with the lowest AGE content were those that were highest in carbohydrate content, including grains, legumes, breads, vegetables, and fruits.

[71 Jaime Uribarri et al., “Advanced Glycation End Products in Foods and a Practical Guide to Their Reduction in the Diet.” Journal of the American Dietetic Association 110, no. 6 (June 2010): 911-16.e12. https://doi.org/10.1016/j.jada.2010.03.018.

Studies have shown that this can be 20 to 30 percent higher in those with both type 1 diabetes and type 2 diabetes, and 40 to 100 percent higher in those who have both diabetes and coronary artery disease.

[72] T. J. Berg et al., “The Advanced Glycation End Product Nepsilon-(Carboxymethyl)Lysine Is Increased in Serum from Children and Adolescents with Type 1 Diabetes.” Diabetes Care 21, no. 11 (November 1998): 1997–2002. 10.2337/diacare.21.11.1997.

[73] B. K. Kilhovd et al., “Serum Levels of Advanced Glycation End Products Are Increased in Patients with Type 2 Diabetes and Coronary Heart Disease.” Diabetes Care 22, no. 9 (September 1999): 1543–48. 10.2337/diacare.22.9.1543.

[74] P. S. Sharp, S. Rainbow, and S. Mukherjee, “Serum Levels of Low Molecular Weight Advanced Glycation End Products in Diabetic Subjects.” Diabetic Medicine 20, no. 7 (July 2003): 575–79. 10.1046/j.1464-5491.2003.00973.x.

[75] Kathryn C. B. Tan et al., “Association Between Acute-Phase Reactants and Advanced Glycation End Products in Type 2 Diabetes.” Diabetes Care 27, no. 1 (January 2004): 223–28. 10.2337/diacare.27.1.223.

Therefore, limiting your exposure to dietary AGEs and controlling your blood glucose with precision are two extremely important things that you can do to help prevent diabetes complications.

[76] Amy G. Huebschmann et al., “Diabetes and Advanced Glycoxidation End Products.” Diabetes Care 29, no. 6 (June 2006): 1420–32. https://doi.org/10.2337/dc05-2096.

[77] Melpomeni Peppa et al., “Glycotoxins: A Missing Link in the ‘Relationship of Dietary Fat and Meat Intake in Relation to Risk of Type 2 Diabetes in Men.’” Diabetes Care 25, no. 10 (October 1, 2002): 1898–99. https://doi.org/10.2337/diacare.25.10.1898.

Given that type 1 diabetes has doubled in prevalence over the past twenty- five years, scientists are constantly on the lookout for environmental and genetic triggers that might help explain why the rate of type 1 diabetes diagnosis is higher today than it has been at any point in human history and why the prevalence of type 1 diabetes is increasing by about 3 percent per year.

[78] Francesco Maria Egro, “Why Is Type 1 Diabetes Increasing?” Journal of Molecular Endocrinology 51, no. 1 (August 1, 2013): R1–13. https://doi.org/10.1530/JME-13-0067.

[79] P. Onkamo et al., “Worldwide Increase in Incidence of Type I Diabetes—the Analysis of the Data on Published Incidence Trends.” Diabetologia 42, no. 12 (December 1999): 1395–403. https://doi.org/10.1007/s001250051309.

[80] Edwin A. M. Gale, “The Rise of Childhood Type 1 Diabetes in the 20th Century.” Diabetes 51, no. 12 (December 1, 2002): 3353–61. https://doi.org/10.2337/diabetes.51.12.3353.

[81] Mark A. Atkinson, “The Pathogenesis and Natural History of Type 1 Diabetes.” Cold Spring Harbor Perspectives in Medicine 2, no. 11 (November 2012). https://doi.org/10.1101/cshperspect.a007641.

[82] E. A. M. Gale, “Type 1 Diabetes in the Young: The Harvest of Sorrow Goes On.” Diabetologia 48, no. 8 (August 2005): 1435–38. https://doi.org/10.1007/s00125-005-1833-0.

[83] M. Karvonen et al., “Incidence of Childhood Type 1 Diabetes Worldwide. Diabetes Mondiale (DiaMond) Project Group.” Diabetes Care 23, no. 10 (October 2000): 1516–26. 10.2337/diacare.23.10.1516.

[84] Elizabeth J. Mayer-Davis et al., “Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012.” New England Journal of Medicine 376 (2017): 1419–29. https://doi.org/10.1056/NEJMoa1610187.

MAP is a mycobacterium, or a bacteria that grows like a fungus, and has been shown to influence susceptibility to autoimmune type 1 diabetes.

[85] Valentina Rosu et al., “Mycobacterium Avium Subspecies Paratuberculosis Is Not Associated with Type-2 Diabetes Mellitus.” Annals of Clinical Microbiology and Antimicrobials 7 (April 22, 2008): 9. https://doi.org/10.1186/1476-0711-7-9.

[86] L. A. Waddell et al., “The Zoonotic Potential of Mycobacterium Avium Ssp. Paratuberculosis: A Systematic Review and Meta-Analyses of the Evidence.” Epidemiology and Infection 143, no. 15 (November 2015): 3135–57. https://doi.org/10.1017/S095026881500076X.

This means that MAP is present in milk and dairy products that you purchase at the grocery store, including raw milk, bulk milk, pasteurized milk, infant food formula, cheese, ice cream, and flavored milk drinks.

[87] Raja Atreya et al., “Facts, Myths and Hypotheses on the Zoonotic Nature of Mycobacterium Avium Subspecies Paratuberculosis.” International Journal of Medical Microbiology 304, no. 7 (October 2014): 858–67. https://doi.org/10.1016/j.ijmm.2014.07.006.

A study published in 2007 revealed that more than 68 percent of all US dairy operations housed cows infected with MAP, and that more than 95 percent of farms containing more than 500 cows housed animals infected with MAP.

[88] US Department of Agriculture. “Johne’s Disease on U.S. Dairies, 1991–2007.” Veterinary Services Centers for Epidemiology and Animal Health, April 2008. https://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_is_Johnes.pdf.

Approximately 3 out of every 100 milk products purchased in the United States contain living MAP bacteria, meaning that milk and milk products are a vehicle that transports infectious bacteria directly from cows to humans, increasing your risk for developing various autoimmune diseases, including type 1 diabetes.

[89] Jay L. E. Ellingson et al., “Detection of Viable Mycobacterium Avium Subsp. Paratuberculosis in Retail Pasteurized Whole Milk by Two Culture Methods and PCR.” Journal of Food Protection 68, no. 5 (May 1, 2005): 966–72. https://doi.org/10.4315/0362-028X-68.5.966.

Studies have shown that between 15 and 20 percent of commonly eaten meat products test positive for MAP DNA, and that ground beef presents the greatest risk for transporting MAP into the human food chain.

[90] B. Klanicova et al., “Real-Time Quantitative PCR Detection of Mycobacterium Avium Subspecies in Meat Products.” Journal of Food Protection 74, no. 4 (April 1, 2011): 636–40. https://doi.org/10.4315/0362-028X.JFP-10-332.

A recent investigation in 298 children in Sardinia, Italy, found that those who ate more meat before the age of 2 years old developed significantly more cases of type 1 diabetes and that “high meat consumption tends to be an important early life cofactor for type 1 diabetes development.”

[91] Sandro Muntoni et al., “High Meat Consumption Is Associated with Type 1 Diabetes Mellitus in a Sardinian Case-Control Study.” Acta Diabetologica 50, no. 5 (October 2013): 713–19. https://doi.org/10.1007/s00592-012-0385-2.

This same research team also showed that both milk consumption and meat intake are significantly correlated with the incidence of type 1 diabetes in children younger than 15 years old in forty countries around the world.

[92] S. Muntoni et al., “Nutritional Factors and Worldwide Incidence of Childhood Type 1 Diabetes.” The American Journal of Clinical Nutrition 71, no. 6 (June 2000): 1525–29. https://doi.org/10.1093/ajcn/71.6.1525.

The process is known as molecular mimicry, a sneaky tactic used by various bacteria and viruses in which pathogenic proteins attempt to evade detection by the human immune system by “disguising” themselves as mammalian proteins.

[93] Daniela Paccagnini et al., “Linking Chronic Infection and Autoimmune Diseases: Mycobacterium Avium Subspecies Paratuberculosis, SLC11A1 Polymorphisms and Type-1 Diabetes Mellitus.” PLOS ONE 4, no. 9 (September 21, 2009): e7109. https://doi.org/10.1371/journal.pone.0007109.

This fascinating research clearly illustrates that foods high in animal protein pose significantly more metabolic risk than foods high in plant protein, increasing your risk for chronic disease and early death.

[94] Luc Djoussé and J. Michael Gaziano, “Egg Consumption in Relation to Cardiovascular Disease and Mortality: The Physicians’ Health Study.” The American Journal of Clinical Nutrition 87, no. 4 (April 2008): 964–69. 10.1093/ajcn/87.4.964.

[95] Teresa T. Fung et al., “Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality: Two Cohort Studies.” Annals of Internal Medicine 153, no. 5 (September 7, 2010): 289–98. 10.7326/0003-4819-153-5-201009070-00003

[96] H. A. Kahn et al., “Association Between Reported Diet and All-Cause Mortality. Twenty-One-Year Follow-up on 27,530 Adult Seventh-Day Adventists.” American Journal of Epidemiology 119, no. 5 (May 1984): 775–87. 10.1093/oxfordjournals.aje.a113798.

[97] P. Lagiou et al., “Low Carbohydrate-High Protein Diet and Mortality in a Cohort of Swedish Women.” Journal of Internal Medicine 261, no. 4 (April 2007): 366–74. https://doi.org/10.1111/j.1365-2796.2007.01774.x.

[98] Hiroshi Noto et al., “Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies.” PLOS ONE 8, no. 1 (January 25, 2013). https://doi.org/10.1371/journal.pone.0055030.

[99] Michael J. Orlich et al., “Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2.” JAMA Internal Medicine 173, no. 13 (July 8, 2013): 1230–38. https://doi.org/10.1001/jamainternmed.2013.6473.

[100] Sabine Rohrmann et al., “Meat Consumption and Mortality—Results from the European Prospective Investigation into Cancer and Nutrition.” BMC Medicine 11 (2013): 63. https://doi.org/10.1186/1741-7015-11-63.

[101] Sara B. Seidelmann et al., “Dietary Carbohydrate Intake and Mortality: A Prospective Cohort Study and Meta-Analysis.” The Lancet: Public Health 3, no. 9 (September 2018): e419–28. https://doi.org/10.1016/S2468-2667(18)30135-X.

[102] Mingyang Song et al., “Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality.” JAMA Internal Medicine 176, no. 10 (August 1, 2016): 1453–63. https://doi.org/10.1001/jamainternmed.2016.4182.

[103] A. Trichopoulou et al., “Low-Carbohydrate-High-Protein Diet and Long-Term Survival in a General Population Cohort.” European Journal of Clinical Nutrition 61, no. 5 (May 2007): 575–81. https://doi.org/10.1038/sj.ejcn.1602557.

[104] Xia Wang et al., “Red and Processed Meat Consumption and Mortality: Dose-Response Meta-Analysis of Prospective Cohort Studies.” Public Health Nutrition 19, no. 5 (April 2016): 893–905. https://doi.org/10.1017/S1368980015002062.

One of the most impressive studies to demonstrate the detrimental effects of animal protein consumption was performed in 2014 at the Longevity Institute at the University of Southern California.

[105] Morgan E. Levine et al., “Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population.” Cell Metabolism 19, no. 3 (March 4, 2014): 407–17. https://doi.org/10.1016/j.cmet.2014.02.006.

Research involving more than 4,000 Dutch participants showed that eating more than 28 grams of fish per day significantly increased diabetes risk by 32 percent, with lean fish being more problematic than fatty fish, which admittedly seems counterintuitive.

[106] Geertruida J. van Woudenbergh et al., “Eating Fish and Risk of Type 2 Diabetes.” Diabetes Care 32, no. 11 (November 2009): 2021–26. https://doi.org/10.2337/dc09-1042.

A few meta- analyses published in 2012 and 2013 found no significant association between fish intake and type 2 diabetes risk— researchers found neither a positive nor negative correlation.

[107] Pengcheng Xun and Ka He, “Fish Consumption and Incidence of Diabetes: Meta-Analysis of Data from 438,000 Individuals in 12 Independent Prospective Cohorts with an Average 11-Year Follow-Up.” Diabetes Care 35, no. 4 (April 1, 2012): 930–38. https://doi.org/10.2337/dc11-1869.

[108] Ming Zhang, Eliane Picard-Deland, and André Marette, “Fish and Marine Omega-3 Polyunsatured Fatty Acid Consumption and Incidence of Type 2 Diabetes: A Systematic Review and Meta-Analysis.” International Journal of Endocrinology 2013 (2013): 501015. https://doi.org/10.1155/2013/501015.

[109] Alice Wallin et al., “Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes: Systematic Review and Meta-Analysis of Prospective Studies.” Diabetes Care 35, no. 4 (April 2012): 918–29. https://doi.org/10.2337/dc11-1631.

Another meta- analysis, published in 2018, that investigated how fish consumption influences type 2 diabetes risk in more than 250,000 people found that fish consumption was weakly correlated with type 2 diabetes risk, much less than has been observed with white meat, red meat, unprocessed meat, and processed meat.

[110] Yunping Zhou, Changwei Tian, and Chongqi Jia, “Association of Fish and N-3 Fatty Acid Intake with the Risk of Type 2 Diabetes: A Meta-Analysis of Prospective Studies.” The British Journal of Nutrition 108, no. 3 (August 2012): 408–17. https://doi.org/10.1017/S0007114512002036.

Elevated mercury levels are associated with a host of metabolic and neurologic conditions, including hypertension, cardiovascular disease, coronary artery dysfunction, and atherosclerosis, and studies in mice show that elevated blood mercury levels can directly interfere with beta cell function, contributing to beta cell death.

[111] Bruna Fernandes Azevedo et al., “Toxic Effects of Mercury on the Cardiovascular and Central Nervous Systems.” Journal of Biomedicine and Biotechnology 2012 (2012): article ID 949048. https://doi.org/10.1155/2012/949048.

[112] Ya Wen Chen et al., “The Role of Phosphoinositide 3-Kinase/Akt Signaling in Low-Dose Mercury-Induced Mouse Pancreatic Beta-Cell Dysfunction in Vitro and in Vivo.” Diabetes 55, no. 6 (June 2006): 1614–24. https://doi.org/10.2337/db06-0029.

Dioxins are carcinogenic compounds that cause reproductive and developmental problems, damage your immune system, and interfere with hormonal signaling.

[113] R. D. Kimbrough, “Polychlorinated Biphenyls (PCBs) and Human Health: An Update.” Critical Reviews in Toxicology 25, no. 2 (1995): 133–63. https://doi.org/10.3109/10408449509021611.

[114] Dariush Mozaffarian and Eric B. Rimm, “Fish Intake, Contaminants, and Human Health: Evaluating the Risks and the Benefits.” JAMA 296, no. 15 (October 18, 2006): 1885–99. https://doi.org/10.1001/jama.296.15.1885.

They are associated with thyroid hormone disruption, neurodevelopmental deficits, and cancer.

[115] Thomas A. McDonald, “A Perspective on the Potential Health Risks of PBDEs.” Chemosphere 46, no. 5 (February 2002): 745–55. 10.1016/s0045-6535(01)00239-9.

Persistent ingestion of pesticide residue in humans leads to nervous system disorders, disrupted hormones and endocrine system functioning, and cancer.

[116] Arnold Schecter et al., “Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA.” Environmental Health Perspectives 118, no. 6 (June 2010): 796–802. https://doi.org/10.1289/ehp.0901347.

A study published in 2005 in the journal Science analyzed over two metric tons of farmed and wild salmon from around the world and found that concentrations of DDT (a banned pesticide), PCBs, and dioxins in farmed salmon were significantly higher than their wild- caught counterparts.

[117] Ronald A. Hites et al., “Global Assessment of Organic Contaminants in Farmed Salmon.” Science 303, no. 5655 (January 9, 2004): 226–29. https://doi.org/10.1126/science.1091447.

This has been the subject of many books, scientific articles, conferences, YouTube videos, and podcasts, and the message is very clear: refined sugars accelerate weight gain, obesity, heart disease, atherosclerosis, high cholesterol, diabetes, and cancer.

[1] Isabelle Aeberli et al., “Low to Moderate Sugar-Sweetened Beverage Consumption Impairs Glucose and Lipid Metabolism and Promotes Inflammation in Healthy Young Men: A Randomized Controlled Trial.” The American Journal of Clinical Nutrition 94, no. 2 (August 2011): 479–85. https://doi.org/10.3945/ajcn.111.013540.

[2] Michael I. Goran et al., “The Obesogenic Effect of High Fructose Exposure During Early Development.” Nature Reviews: Endocrinology 9, no. 8 (August 2013): 494–500. https://doi.org/10.1038/nrendo.2013.108.

[3] Simin Liu, “Intake of Refined Carbohydrates and Whole Grain Foods in Relation to Risk of Type 2 Diabetes Mellitus and Coronary Heart Disease.” Journal of the American College of Nutrition 21, no. 4 (August 1, 2002): 298–306. https://doi.org/10.1080/07315724.2002.10719227.

[4] Kimber L. Stanhope et al., “Consumption of Fructose and High Fructose Corn Syrup Increase Postprandial Triglycerides, LDL-Cholesterol, and Apolipoprotein-B in Young Men and Women.” Journal of Clinical Endocrinology & Metabolism 96, no. 10 (October 1, 2011): E1596–E1605. https://doi.org/10.1210/jc.2011-1251.

[5] Kimber L. Stanhope et al., “Consuming Fructose-Sweetened, Not Glucose-Sweetened, Beverages Increases Visceral Adiposity and Lipids and Decreases Insulin Sensitivity in Overweight/Obese Humans.” The Journal of Clinical Investigation 119, no. 5 (May 2009): 1322–34. https://doi.org/10.1172/JCI37385.

[6] Kimber L. Stanhope, Jean-Marc Schwarz, and Peter J. Havel, “Adverse Metabolic Effects of Dietary Fructose: Results from the Recent Epidemiological, Clinical, and Mechanistic Studies.” Current Opinion in Lipidology 24, no. 3 (June 2013): 198–206. https://doi.org/10.1097/MOL.0b013e3283613bca.

The combination of these factors creates insulin resistance mainly in your liver but also in your muscle, and significantly increases your risk for heart disease.

[7] David S. Ludwig et al., “Dietary Carbohydrates: Role of Quality and Quantity in Chronic Disease.” BMJ 361 (June 13, 2018): k2340. https://doi.org/10.1136/bmj.k2340.

[8] Dagfinn Aune et al., “Whole Grain and Refined Grain Consumption and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-Analysis of Cohort Studies.” European Journal of Epidemiology 28, no. 11 (November 2013): 845–58. https://doi.org/10.1007/s10654-013-9852-5.

[9] Emily A. Hu et al., “White Rice Consumption and Risk of Type 2 Diabetes: Meta-Analysis and Systematic Review.” BMJ 344 (March 15, 2012): e1454. https://doi.org/10.1136/bmj.e1454.

[10] Sylvia H. Ley et al., “Prevention and Management of Type 2 Diabetes: Dietary Components and Nutritional Strategies.” The Lancet 383, no. 9933 (June 7, 2014): 1999–2007. https://doi.org/10.1016/S0140-6736(14)60613-9.

Given that the majority of your stool is composed of pure bacteria, the more food you eat in its whole state, the happier your bacteria become, the more immune-boosting short-chain fatty acids they produce, the more they multiply and colonize your gut, and the more regularly they are replaced by new bacteria.

[11] Jian Tan et al., “The Role of Short-Chain Fatty Acids in Health and Disease.” Advances in Immunology 121 (2014): 91–119. https://doi.org/10.1016/B978-0-12-800100-4.00003-9.

Vitamins are required for thousands of metabolic reactions, including (but not limited to) DNA synthesis and repair, protein synthesis and repair, RNA synthesis and repair, glycogen synthesis, fatty acid synthesis, hormone synthesis, and neurotransmitter synthesis.

[12] Mario C. De Tullio, “Beyond the Antioxidant: The Double Life of Vitamin C.” Sub-Cellular Biochemistry 56 (2012): 49–65. https://doi.org/10.1007/978-94-007-2199-9_4.

[13] J. M. Sacheck and J. B. Blumberg, “Role of Vitamin E and Oxidative Stress in Exercise.” Nutrition 17, no. 10 (October 2001): 809–14. 10.1016/s0899-9007(01)00639-6.

[14] Chih-Chien Sung et al., “Role of Vitamin D in Insulin Resistance.” Journal of Biomedicine & Biotechnology 2012 (2012): 634195. https://doi.org/10.1155/2012/634195.

[15] P. J. McLaughlin and J. L. Weihrauch, “Vitamin E Content of Foods.” Journal of the American Dietetic Association 75, no. 6 (December 1979): 647–65. https://www.ncbi.nlm.nih.gov/pubmed/389993.

[16] Karin Dina and Rick Dina, The Raw Food Nutrition Handbook: An Essential Guide to Understanding Raw Food Diets. Summertown, TN: Healthy Living Publications, 2015.

The most recent estimates suggest that your body is comprised of about 45 percent human cells and 55 percent bacterial cells, and these bacteria exist in a friendly symbiotic relationship with human cells.

[17] Ron Sender, Shai Fuchs, and Ron Milo, “Revised Estimates for the Number of Human and Bacteria Cells in the Body.” PLOS Biology 14, no. 8 (August 19, 2016). https://doi.org/10.1371/journal.pbio.1002533.

Maintaining excellent gut health is critical for maintaining total body metabolic health, and a dysregulated gut microflora has been linked with many chronic diseases, including autism, depression, Hashimoto’s thyroiditis, inflammatory bowel disease, and type 1 diabetes.

[18] H. S. Gill and F. Guarner, “Probiotics and Human Health: A Clinical Perspective.” Postgraduate Medical Journal 80, no. 947 (September 1, 2004): 516–26. https://doi.org/10.1136/pgmj.2003.008664.

[19] Alessio Fasano and Terez Shea-Donohue, “Mechanisms of Disease: The Role of Intestinal Barrier Function in the Pathogenesis of Gastrointestinal Autoimmune Diseases.” Nature Clinical Practice. Gastroenterology & Hepatology 2, no. 9 (September 2005): 416–22. https://doi.org/10.1038/ncpgasthep0259.

[20] Einar Husebye, “The Pathogenesis of Gastrointestinal Bacterial Overgrowth.” Chemotherapy 51 Suppl 1 (2005): 1–22. https://doi.org/10.1159/000081988.

[21] Jeroen Visser et al., “Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms.” Annals of the New York Academy of Sciences 1165 (May 2009): 195–205. https://doi.org/10.1111/j.1749-6632.2009.04037.x.

[22] Chris Kresser, Your Personal Paleo Code: The 3-Step Plan to Lose Weight, Reverse Disease, and Stay Fit and Healthy for Life. Boston: Little, Brown Spark, 2013.

[23] Alda J. Leonel and Jacqueline I. Alvarez-Leite, “Butyrate: Implications for Intestinal Function.” Current Opinion in Clinical Nutrition and Metabolic Care 15, no. 5 (September 2012): 474–79. https://doi.org/10.1097/MCO.0b013e32835665fa.

Some research shows that short- chain fatty acids can even prevent macrophages from entering your adipose tissue and creating an insulin- resistant state, as we discussed in chapter 3.

[24] Kees Meijer, Paul de Vos, and Marion G. Priebe, “Butyrate and Other Short-Chain Fatty Acids as Modulators of Immunity: What Relevance for Health?” Current Opinion in Clinical Nutrition and Metabolic Care 13, no. 6 (November 2010): 715–21. https://doi.org/10.1097/MCO.0b013e32833eebe5.

Studies have shown that the addition of fiber powder (like Metamucil or psyllium husk) to a poor diet does not protect against colon cancer, but that diets high in fiber- rich foods do.

[25] C. Hillemeier, “An Overview of the Effects of Dietary Fiber on Gastrointestinal Transit.” Pediatrics 96, no. 5 Pt 2 (November 1995): 997–99. https://www.ncbi.nlm.nih.gov/pubmed/7494680.

[26] Wendy R. Russell et al., “High-Protein, Reduced-Carbohydrate Weight-Loss Diets Promote Metabolite Profiles Likely to Be Detrimental to Colonic Health.” The American Journal of Clinical Nutrition 93, no. 5 (May 1, 2011): 1062–72. https://doi.org/10.3945/ajcn.110.002188.

[27] Wendy R. Russell et al., “Colonic Bacterial Metabolites and Human Health.” Current Opinion in Microbiology 16, no. 3 (June 2013): 246–54. https://doi.org/10.1016/j.mib.2013.07.002.

[28] D. J. Jenkins et al., “Fiber and Starchy Foods: Gut Function and Implications in Disease.” The American Journal of Gastroenterology 81, no. 10 (October 1986): 920–30. https://www.ncbi.nlm.nih.gov/pubmed/3020970.

Antioxidants are electron donors that hand out electrons to “quench” dangerous free radicals that are in search of electrons.

[29] P. M. Clarkson, “Antioxidants and Physical Performance.” Critical Reviews in Food Science and Nutrition 35, no. 1–2 (January 1995): 131–41. https://doi.org/10.1080/10408399509527692.

[30] P. M. Clarkson and H. S. Thompson, “Antioxidants: What Role Do They Play in Physical Activity and Health?” The American Journal of Clinical Nutrition 72, no. 2 Suppl (August 2000): 637S–646S. 10.1093/ajcn/72.2.637S.

[31] C. K. Sen, “Antioxidants in Exercise Nutrition.” Sports Medicine 31, no. 13 (2001): 891–908. https://www.ncbi.nlm.nih.gov/pubmed/11708399.

[32] M. Edeas et al., “Maillard Reaction, Mitochondria and Oxidative Stress: Potential Role of Antioxidants.” Pathologie-Biologie 58, no. 3 (June 2010): 220–25. https://doi.org/10.1016/j.patbio.2009.09.011.

[33] Maria L. Urso and Priscilla M. Clarkson, “Oxidative Stress, Exercise, and Antioxidant Supplementation.” Toxicology 189, no. 1–2 (July 15, 2003): 41–54. 10.1016/s0300-483x(03)00151-3.

Plant foods contain on average 64 times more antioxidant content than animal foods.

[34] Monica H. Carlsen et al., “The Total Antioxidant Content of More than 3100 Foods, Beverages, Spices, Herbs and Supplements Used Worldwide.” Nutrition Journal 9 (January 22, 2010): 3. https://doi.org/10.1186/1475-2891-9-3.

In fact, ample research shows that diets rich in phytochemicals reduce the risk of premature death.

[35] A. Heather Eliassen et al., “Plasma Carotenoids and Risk of Breast Cancer over 20 y of Follow-Up.” The American Journal of Clinical Nutrition 101, no. 6 (June 2015): 1197–1205. https://doi.org/10.3945/ajcn.114.105080.

[36] Kerry L. Ivey et al., “Flavonoid Intake and All-Cause Mortality.” The American Journal of Clinical Nutrition 101, no. 5 (May 2015): 1012–20. https://doi.org/10.3945/ajcn.113.073106.

[37] Wenlong Jiang, Huabing Wei, and Ben He, “Dietary Flavonoids Intake and the Risk of Coronary Heart Disease: A Dose-Response Meta-Analysis of 15 Prospective Studies.” Thrombosis Research 135, no. 3 (March 1, 2015): 459–63. https://doi.org/10.1016/j.thromres.2014.12.016.

[38] Emanuele Leoncini et al., “Carotenoid Intake from Natural Sources and Head and Neck Cancer: A Systematic Review and Meta-Analysis of Epidemiological Studies.” Cancer Epidemiology, Biomarkers & Prevention 24, no. 7 (July 2015): 1003–11. https://doi.org/10.1158/1055-9965.EPI-15-0053.

[39] Yu-Jian Liu et al., “Dietary Flavonoids Intake and Risk of Type 2 Diabetes: A Meta-Analysis of Prospective Cohort Studies.” Clinical Nutrition 33, no. 1 (February 2014): 59–63. https://doi.org/10.1016/j.clnu.2013.03.011.

[40] Mira Soni et al., “Phytoestrogens and Cognitive Function: A Review.” Maturitas 77, no. 3 (March 2014): 209–20. https://doi.org/10.1016/j.maturitas.2013.12.010.

[41] Xia Wang et al., “Flavonoid Intake and Risk of CVD: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.” The British Journal of Nutrition 111, no. 1 (January 14, 2014): 1–11. https://doi.org/10.1017/S000711451300278X.

[42] Ze-Mu Wang et al., “Flavonol Intake and Stroke Risk: A Meta-Analysis of Cohort Studies.” Nutrition 30, no. 5 (May 2014): 518–23. https://doi.org/10.1016/j.nut.2013.10.009.

[43] Pan Wei et al., “Systematic Review of Soy Isoflavone Supplements on Osteoporosis in Women.” Asian Pacific Journal of Tropical Medicine 5, no. 3 (March 2012): 243–48. https://doi.org/10.1016/S1995-7645(12)60033-9.

Ample large-scale research studies show that simply increasing your intake of intact fiber from whole foods can dramatically reduce the frequency and magnitude of high blood glucose following a meal and reduces your risk for insulin resistance, type 2 diabetes, and cardiovascular disease.

[44] Supriya Krishnan et al., “Glycemic Index, Glycemic Load, and Cereal Fiber Intake and Risk of Type 2 Diabetes in US Black Women.” Archives of Internal Medicine 167, no. 21 (November 26, 2007): 2304–9. https://doi.org/10.1001/archinte.167.21.2304.

[45] Matthias B. Schulze et al., “Glycemic Index, Glycemic Load, and Dietary Fiber Intake and Incidence of Type 2 Diabetes in Younger and Middle-Aged Women.” The American Journal of Clinical Nutrition 80, no. 2 (August 2004): 348–56. 10.1093/ajcn/80.2.348.

[46] Teresa T. Fung et al., “Whole-Grain Intake and the Risk of Type 2 Diabetes: A Prospective Study in Men.” The American Journal of Clinical Nutrition 76, no. 3 (September 2002): 535–40. 10.1093/ajcn/76.3.535.

When your liver is exposed to large concentrations of glucose in a short period of time, your brain responds by increasing your total energy expenditure to “waste” excess calories.

[47] M. Dirlewanger et al., “Effects of Short-Term Carbohydrate or Fat Overfeeding on Energy Expenditure and Plasma Leptin Concentrations in Healthy Female Subjects.” International Journal of Obesity 24, no. 11 (November 2000): 1413–18. https://doi.org/10.1038/sj.ijo.0801395.

De novo lipogenesis is a very well studied (and unnecessarily controversial) phenomenon in animals and humans and occurs to a small extent either when you increase your intake of refined carbohydrate foods and when you massively overeat calories.

[48] M. K. Hellerstein, “De Novo Lipogenesis in Humans: Metabolic and Regulatory Aspects.” European Journal of Clinical Nutrition 53, Suppl 1 (April 1999): S53-65. https://www.ncbi.nlm.nih.gov/pubmed/10365981.

[49] M. K. Hellerstein, J. M. Schwarz, and R. A. Neese, “Regulation of Hepatic de Novo Lipogenesis in Humans.” Annual Review of Nutrition 16 (1996): 523–57. https://doi.org/10.1146/annurev.nu.16.070196.002515.

[50] P. Pasquet et al., “Massive Overfeeding and Energy Balance in Men: The Guru Walla Model.” The American Journal of Clinical Nutrition 56, no. 3 (1992): 483–90. https://www.ncbi.nlm.nih.gov/pubmed/1503058.

A thought- provoking paper by one of the world’s experts on DNL explains that the process of converting carbohydrate to fat in humans is an extremely inefficient process and generally occurs only on 1 to 2 percent of all the carbohydrate energy you eat.

[51] Marc K. Hellerstein, “No Common Energy Currency: De Novo Lipogenesis as the Road Less Traveled.” The American Journal of Clinical Nutrition 74, no. 6 (December 1, 2001): 707–708. 10.1093/ajcn/74.6.707.

Even though this may sound plausible, the truth is that DNL is an active pathway in pigs, rats, mice, cows, dogs, cats, and birds, and a largely inactive pathway in humans.

[52] Allred, J.B., and D.F. Bowers. “Regulation of Acetyl CoA Carboxylase and Gene Expression.” In Nutrition and Gene Expression, 269–95, 2018. https://doi.org/10.1201/9781351075114.

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[55] Mersmann HJ, Koong LJ. “Effect of Plane of Nutrition on Adipose Tissue Metabolism in Genetically Obese and Lean Pigs.” J. Nutr. 114 (1984): 862–68. 10.1093/jn/114.5.862.

[56] Tepperman, H. M., and J. Tepperman. “ADAPTIVE HYPERLIPOGENESIS.” Federation Proceedings 23 (February 1964): 73–75. https://www.ncbi.nlm.nih.gov/pubmed/14114698.

High- Fat Diet: In people who eat a high- fat, low- carbohydrate diet containing between 100– 200 grams of fat per day, less than 1 gram of newly synthesized fatty acids is made from DNL per day.

[57] Faix, D., R. Neese, C. Kletke, S. Wolden, D. Cesar, M. Coutlangus, C. H. Shackleton, and M. K. Hellerstein. “Quantification of Menstrual and Diurnal Periodicities in Rates of Cholesterol and Fat Synthesis in Humans.” Journal of Lipid Research 34, no. 12 (December 1993): 2063–75. https://www.ncbi.nlm.nih.gov/pubmed/8301227.

[58] Hellerstein, M. K., M. Christiansen, S. Kaempfer, C. Kletke, K. Wu, J. S. Reid, K. Mulligan, N. S. Hellerstein, and C. H. Shackleton. “Measurement of de Novo Hepatic Lipogenesis in Humans Using Stable Isotopes.” The Journal of Clinical Investigation 87, no. 5 (May 1991): 1841–52. https://doi.org/10.1172/JCI115206.

[59] Hellerstein, M. K., C. Grunfeld, K. Wu, M. Christiansen, S. Kaempfer, C. Kletke, and C. H. Shackleton. “Increased de Novo Hepatic Lipogenesis in Human Immunodeficiency Virus Infection.” The Journal of Clinical Endocrinology and Metabolism 76, no. 3 (March 1993): 559–65. https://doi.org/10.1210/jcem.76.3.8445011.

[60] Hellerstein, M. K., and R. A. Neese. “Mass Isotopomer Distribution Analysis: A Technique for Measuring Biosynthesis and Turnover of Polymers.” The American Journal of Physiology 263, no. 5 Pt 1 (November 1992): E988-1001. https://doi.org/10.1152/ajpendo.1992.263.5.E988.

[61] Lee, W. N., E. A. Bergner, and Z. K. Guo. “Mass Isotopomer Pattern and Precursor-Product Relationship.” Biological Mass Spectrometry 21, no. 2 (February 1992): 114–22. https://doi.org/10.1002/bms.1200210210.

Low- Fat Diet: In people who eat a high- carbohydrate diet containing between 65–75 percent carbohydrate and 10–20 percent fat, DNL accounted for less than 10 grams of newly synthesized fatty acids per day.

[62] Hirsch, Jules. “Fatty Acid Patterns in Human Adipose Tissue.” In Comprehensive Physiology, 181–89. American Cancer Society, 2011. https://doi.org/10.1002/cphy.cp050117.

[63] Hudgins, L. C., M. Hellerstein, C. Seidman, R. Neese, J. Diakun, and J. Hirsch. “Human Fatty Acid Synthesis Is Stimulated by a Eucaloric Low Fat, High Carbohydrate Diet.” The Journal of Clinical Investigation 97, no. 9 (May 1, 1996): 2081–91. https://doi.org/10.1172/JCI118645.

Experiments show that people who eat approximately 2,000 grams of carbohydrate energy per day (4,500 calories of excess energy) for 7–10 days at a time manufacture about 150 grams of newly synthesized fatty acids from DNL per day.

[64] Acheson, K. J., J. P. Flatt, and E. Jéquier. “Glycogen Synthesis versus Lipogenesis after a 500 Gram Carbohydrate Meal in Man.” Metabolism: Clinical and Experimental 31, no. 12 (December 1982): 1234–40. 10.1016/0026-0495(82)90010-5.

[65] Acheson, K. J., Y. Schutz, T. Bessard, K. Anantharaman, J. P. Flatt, and E. Jéquier. “Glycogen Storage Capacity and de Novo Lipogenesis during Massive Carbohydrate Overfeeding in Man.” The American Journal of Clinical Nutrition 48, no. 2 (August 1, 1988): 240–47. https://doi.org/10.1093/ajcn/48.2.240.

[66] Clore, J. N., S. T. Helm, and W. G. Blackard. “Loss of Hepatic Autoregulation after Carbohydrate Overfeeding in Normal Man.” The Journal of Clinical Investigation 96, no. 4 (October 1995): 1967–72. https://doi.org/10.1172/JCI118243.

[67] Schwarz, J. M., R. A. Neese, S. Turner, D. Dare, and M. K. Hellerstein. “Short-Term Alterations in Carbohydrate Energy Intake in Humans. Striking Effects on Hepatic Glucose Production, de Novo Lipogenesis, Lipolysis, and Whole-Body Fuel Selection.” The Journal of Clinical Investigation 96, no. 6 (December 1995): 2735–43. https://doi.org/10.1172/JCI118342.

[68] Horton, T. J., H. Drougas, A. Brachey, G. W. Reed, J. C. Peters, and J. O. Hill. “Fat and Carbohydrate Overfeeding in Humans: Different Effects on Energy Storage.” The American Journal of Clinical Nutrition 62, no. 1 (July 1995): 19–29. https://doi.org/10.1093/ajcn/62.1.19.

While it is true that excess insulin can certainly stimulate DNL, a study performed in insulin- resistant obese men demonstrated that the amount of newly synthesized fatty acids is so small that it does not account for even a minor part of excess body fat present in obesity.

[69] Schwarz, Jean-Marc, R NEESE, C SHACKLETON, and MK HELLERSTEIN. “DENOVO LIPOGENESIS (DNL) DURING FASTING AND ORAL FRUCTOSE IN LEAN AND OBESE HYPERINSULINEMIC SUBJECTS.” Diabetes 42 (May 1, 1993): A39–A39. https://www.researchgate.net/publication/298239400_DENOVO_LIPOGENESIS_DNL_DURING_FASTING_AND_ORAL_FRUCTOSE_IN_LEAN_AND_OBESE_HYPERINSULINEMIC_SUBJECTS

People who eat diets containing more carbohydrate energy increase the size of their liver and muscle glycogen stores over time, whereas people who eat diets low in carbohydrate energy have limited glycogen stores in both their liver and muscle.

[70] Jonas Bergström et al., “Diet, Muscle Glycogen and Physical Performance.” Acta Physiologica Scandinavica 71, no. 2–3 (October 1, 1967): 140–50. https://doi.org/10.1111/j.1748-1716.1967.tb03720.x.

In a given day, your brain will burn up to 60 percent of all the glucose in circulation because it is the largest consumer of glucose in your body and does not possess the ability to burn amino acids from protein or fatty acids from lipids.

[71] David H. Wasserman, “Four Grams of Glucose.” American Journal of Physiology: Endocrinology and Metabolism 296, no. 1 (January 2009): E11–E21. https://doi.org/10.1152/ajpendo.90563.2008.

While the ketogenic diet may seem like a logical approach to reducing blood glucose fluctuations, it is based on the outdated and incorrect carbohydrate- centric model of diabetes that we covered in chapter 3, which points a finger at carbohydrates as the cause of insulin resistance and type 2 diabetes, even though overwhelming evidence shows that low- carbohydrate, high- fat diets are actually the cause of insulin resistance and type 2 diabetes.

[1] Guenther Boden, “Fatty Acid-Induced Inflammation and Insulin Resistance in Skeletal Muscle and Liver.” Current Diabetes Reports 6, no. 3 (June 2006): 177–81. https://www.ncbi.nlm.nih.gov/pubmed/16898568.

[2] Guenther Boden, “Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM.” Diabetes 46, no. 1 (January 1, 1997): 3–10. https://doi.org/10.2337/diab.46.1.3.

[3] G. Boden and G. I. Shulman. “Free Fatty Acids in Obesity and Type 2 Diabetes: Defining Their Role in the Development of Insulin Resistance and β-Cell Dysfunction.” European Journal of Clinical Investigation 32 (June 1, 2002): 14–23. https://doi.org/10.1046/j.1365-2362.32.s3.3.x.

[4] Samar I. Itani et al., “Lipid-Induced Insulin Resistance in Human Muscle Is Associated with Changes in Diacylglycerol, Protein Kinase C, and IκB-α.” Diabetes 51, no. 7 (July 1, 2002): 2005–11. https://doi.org/10.2337/diabetes.51.7.2005.

[5] David B. Savage, Kitt Falk Petersen, and Gerald I. Shulman, “Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance.” Physiological Reviews 87, no. 2 (April 1, 2007): 507–20. https://doi.org/10.1152/physrev.00024.2006.

[6] C. Xiao et al., “Differential Effects of Monounsaturated, Polyunsaturated and Saturated Fat Ingestion on Glucose-Stimulated Insulin Secretion, Sensitivity and Clearance in Overweight and Obese, Non-Diabetic Humans.” Diabetologia 49, no. 6 (April 5, 2006): 1371–79. https://doi.org/10.1007/s00125-006-0211-x.

[7] Jacques Delarue and Christophe Magnan, “Free Fatty Acids and Insulin Resistance.” Current Opinion in Clinical Nutrition and Metabolic Care 10, no. 2 (March 2007): 142–48. https://doi.org/10.1097/MCO.0b013e328042ba90.

[8] Jose E. Galgani, Cedric Moro, and Eric Ravussin, “Metabolic Flexibility and Insulin Resistance.” American Journal of Physiology: Endocrinology and Metabolism 295, no. 5 (November 2008): E1009-1017. https://doi.org/10.1152/ajpendo.90558.2008.

[9] M. E. Griffin et al., “Free Fatty Acid-Induced Insulin Resistance Is Associated with Activation of Protein Kinase C Theta and Alterations in the Insulin Signaling Cascade.” Diabetes 48, no. 6 (June 1999): 1270–74. 10.2337/diabetes.48.6.1270.

[10] Sandro M. Hirabara, Rui Curi, and Pierre Maechler, “Saturated Fatty Acid-Induced Insulin Resistance Is Associated with Mitochondrial Dysfunction in Skeletal Muscle Cells.” Journal of Cellular Physiology 222, no. 1 (January 2010): 187–94. https://doi.org/10.1002/jcp.21936.

[11] Amanda R. Martins et al., “Mechanisms Underlying Skeletal Muscle Insulin Resistance Induced by Fatty Acids: Importance of the Mitochondrial Function.” Lipids in Health and Disease 11 (2012): 30. https://doi.org/10.1186/1476-511X-11-30.

[12] M. Roden et al., “Mechanism of Free Fatty Acid-Induced Insulin Resistance in Humans.” The Journal of Clinical Investigation 97, no. 12 (June 15, 1996): 2859–65. https://doi.org/10.1172/JCI118742.

[13] Michael Roden, “How Free Fatty Acids Inhibit Glucose Utilization in Human Skeletal Muscle.” News in Physiological Sciences 19 (June 2004): 92–96. https://www.ncbi.nlm.nih.gov/pubmed/15143200.

[14] G. I. Shulman, “Cellular Mechanisms of Insulin Resistance.” The Journal of Clinical Investigation 106, no. 2 (July 2000): 171–76. https://doi.org/10.1172/JCI10583.

[15] Leonardo Silveira et al., “Updating the Effects of Fatty Acids on Skeletal Muscle.” Journal of Cellular Physiology 217, no. 1 (October 2008): 1–12. https://doi.org/10.1002/jcp.21514.

[16] Maho Sumiyoshi, Masahiro Sakanaka, and Yoshiyuki Kimura, “Chronic Intake of High-Fat and High-Sucrose Diets Differentially Affects Glucose Intolerance in Mice.” The Journal of Nutrition 136, no. 3 (March 1, 2006): 582–87. 10.1093/jn/136.3.582.

[17] R. Taylor, “Banting Memorial Lecture 2012: Reversing the Twin Cycles of Type 2 Diabetes.” Diabetic Medicine 30, no. 3 (March 2013): 267–75. https://doi.org/10.1111/dme.12039.

[18] Pey-Yu Wang et al., “Impairment of Glucose Tolerance in Normal Adults Following a Lowered Carbohydrate Intake.” The Tohoku Journal of Experimental Medicine 189, no. 1 (1999): 59–70. 10.1620/tjem.189.59.

[19] Yamamoto Noguchi et al., “Mixed Model of Dietary Fat Effect on Postprandial Glucose-Insulin Metabolism from Carbohydrates in Type 1 Diabetes.” Conference Proceedings: . . . Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference 2015 (August 2015): 8058–61. https://doi.org/10.1109/EMBC.2015.7320263.

[20] Chunli Yu et al., “Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-Associated Phosphatidylinositol 3-Kinase Activity in Muscle.” The Journal of Biological Chemistry 277, no. 52 (December 27, 2002): 50230–36. https://doi.org/10.1074/jbc.M200958200.

[21] Ewa Pańkowska, Marlena Błazik, and Lidia Groele, “Does the Fat-Protein Meal Increase Postprandial Glucose Level in Type 1 Diabetes Patients on Insulin Pump: The Conclusion of a Randomized Study.” Diabetes Technology & Therapeutics 14, no. 1 (January 2012): 16–22. https://doi.org/10.1089/dia.2011.0083.

[22] Carmel E. M. Smart et al., “Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children with Type 1 Diabetes, and the Effect Is Additive.” Diabetes Care 36, no. 12 (December 2013): 3897–3902. https://doi.org/10.2337/dc13-1195.

[23] Megan Paterson et al., “The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management.” Current Diabetes Reports 15, no. 9 (July 23, 2015): 1–9. https://doi.org/10.1007/s11892-015-0630-5.

[24] Andreas Neu et al., “Higher Glucose Concentrations Following Protein- and Fat-Rich Meals—the Tuebingen Grill Study: A Pilot Study in Adolescents with Type 1 Diabetes.” Pediatric Diabetes 16, no. 8 (December 1, 2015): 587–91. https://doi.org/10.1111/pedi.12224.

At the time, researchers thought that they could induce ketosis as well as a condition known as metabolic acidosis, both of which were known to have anticonvulsant effects.

[25] David Chesney et al., “Biochemical Abnormalities of the Ketogenic Diet in Children.” Clinical Pediatrics 38, no. 2 (March 1, 1999): 107–9. https://doi.org/10.1177/000992289903800207.

The researchers reported a complete list of early-and late- onset side effects that also included acid reflux, hair loss, kidney stones, muscle cramps or weakness, hypoglycemia, low platelet count, impaired cognition, an inability to concentrate, impaired mood, renal tubular acidosis, disordered mineral metabolism, stunted growth, increased risk for one fractures, osteopenia and osteoporosis, increased bruising, sepsis, pneumonia, acute pancreatitis, hyperlipidemia, high cholesterol, insulin resistance, elevated cortisol, increased risk for cardiovascular disease, increased risk for atherosclerosis, cardiomyopathy, heart arrhythmia, myocardial infarction, menstrual irregularities, amenorrhea (loss of period), and an increased risk for all- cause mortality.

[26] Hoon Chul Kang et al., “Early- and Late-Onset Complications of the Ketogenic Diet for Intractable Epilepsy.” Epilepsia 45, no. 9 (September 1, 2004): 1116–23. https://doi.org/10.1111/j.0013-9580.2004.10004.x.

In 2005, scientists from Temple University followed 10 obese patients living with type 2 diabetes for two weeks and observed that in this condensed time period, patients reduced their A1c by 0.5 percent and increased their insulin sensitivity by 75 percent.

[27] Guenther Boden et al., “Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes,” Annals of Internal Medicine 142, no. 6 (March 5, 2005): 403–11. 10.7326/0003-4819-142-6-200503150-00006.

That same year, another team of researchers from Duke University found that sixteen weeks of a ketogenic diet in 28 different overweight patients led to dramatic reductions in A1c, diabetes medication needs, body weight, and triglyceride levels.

[28] William S. Yancy Jr. et al., “A Low-Carbohydrate, Ketogenic Diet to Treat Type 2 Diabetes,” Nutrition & Metabolism 2 (2005): 34. doi: 10.1186/1743-7075-2-34.10.1186/1743-7075-2-34.

Researchers at the University of Kuwait studied the effect of a ketogenic diet on 66 obese subjects and observed significant weight loss, reduced total cholesterol, reduced LDL cholesterol, reduced triglycerides, and reduced blood glucose.

[29] Hussein M. Dashti et al., “Long Term Effects of Ketogenic Diet in Obese Subjects with High Cholesterol Level.” Molecular and Cellular Biochemistry 286, no. 1–2 (June 2006): 1–9. https://doi.org/10.1007/s11010-005-9001-x.

In this time frame, the participants on average lost 50 to 66 pounds on average and significantly dropped their total cholesterol, LDL cholesterol, triglycerides, and blood glucose, while increasing their HDL.

[30] Hussein M. Dashti et al., “Beneficial Effects of Ketogenic Diet in Obese Diabetic Subjects.” Molecular and Cellular Biochemistry 302, no. 1–2 (July 23, 2007): 249–56. https://doi.org/10.1007/s11010-007-9448-z.

The researchers found that a ketogenic diet dropped the participants’ A1c by 1.0 percent while reducing or eliminating common oral diabetes medications, along with significant reductions in fasting glucose, body weight, BMI, and triglycerides.

[31] Amy L. McKenzie et al., “A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes.” JMIR Diabetes 2, no. 1 (2017): e5. https://doi.org/10.2196/diabetes.6981.

The same researchers extended their findings to 349 people living with type 2 diabetes over the course of a year and found that a ketogenic diet dramatically reduced insulin and oral medication needs, as well as body weight, and led to a 1.3 percent reduction in A1c.

[32]  Sarah J. Hallberg et al., “Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study.” Diabetes Therapy, February 7, 2018. https://doi.org/10.1007/s13300-018-0373-9.

Their total insulin use dropped from 47 units per day to 30 units per day, resulting in a 24-- hour carbohydrate- to- insulin ratio of 1:1 (30 grams of daily carbohydrate to 30 units of daily insulin).

[33] Daniel F. O’ Neill, Eric C. Westman, and Richard K. Bernstein, “The Effects of a Low-Carbohydrate Regimen on Glycemic Control and Serum Lipids in Diabetes Mellitus.” Metabolic Syndrome and Related Disorders 1, no. 4 (December 2003): 291–98. https://doi.org/10.1089/1540419031361345.

A study published in 2005 found that a ketogenic diet significantly reduced the number of hypoglycemic episodes, insulin requirements, and A1c values in 22 individuals living with type 1 diabetes over a twelve- month period.

[34] Jørgen Vesti Nielsen, Eva Jönsson, and Anette Ivarsson, “A Low Carbohydrate Diet in Type 1 Diabetes: Clinical Experience—a Brief Report.” Upsala Journal of Medical Sciences 110, no. 3 (2005): 267–73. 10.3109/2000-1967-074.

Over the course of those four years, all participants lost an average of 2 pounds, but only 48 percent of them adhered to the low- carbohydrate diet.

[35] Jørgen Vesti Nielsenet al., “Low Carbohydrate Diet in Type 1 Diabetes, Long-Term Improvement and Adherence: A Clinical Audit.” Diabetology & Metabolic Syndrome 4, no. 1 (May 31, 2012): 23. https://doi.org/10.1186/1758-5996-4-23.

One notable exception to the list of short- term improvements mentioned above is that a ketogenic diet almost always raises LDL cholesterol levels.

[36] Nassib Bezerra Bueno et al., “Very-Low-Carbohydrate Ketogenic Diet v. Low-Fat Diet for Long-Term Weight Loss: A Meta-Analysis of Randomised Controlled Trials.” The British Journal of Nutrition 110, no. 7 (October 2013): 1178–87. https://doi.org/10.1017/S0007114513000548.

[37 Priya Sumithran and Joseph Proietto, “Ketogenic Diets for Weight Loss: A Review of Their Principles, Safety and Efficacy.” Obesity Research & Clinical Practice 2, no. 1 (March 2008): I—II. https://doi.org/10.1016/j.orcp.2007.11.003.

LDL particles are the lipid particle known to have the highest correlation with cardiovascular disease, which means that irrespective of other health benefits, a ketogenic diet is likely to raise your cardiovascular mortality risk.

[38] R. Clarke et al., “Dietary Lipids and Blood Cholesterol: Quantitative Meta-Analysis of Metabolic Ward Studies.” BMJ: British Medical Journal 314, no. 7074 (January 11, 1997): 112–17. 10.1136/bmj.314.7074.112.

[39] The Emerging Risk Factors Collaboration, “Major Lipids, Apolipoproteins, and Risk of Vascular Disease.” JAMA 302, no. 18 (November 11, 2009): 1993–2000. https://doi.org/10.1001/jama.2009.1619.

[40] Brian A. Ference et al., “Low-Density Lipoproteins Cause Atherosclerotic Cardiovascular Disease. 1. Evidence from Genetic, Epidemiologic, and Clinical Studies. A Consensus Statement from the European Atherosclerosis Society Consensus Panel.” European Heart Journal 38, no. 32 (August 21, 2017): 2459–72. https://doi.org/10.1093/eurheartj/ehx144.

[41] Brian A. Ference and Nitin Mahajan, “The Role of Early LDL Lowering to Prevent the Onset of Atherosclerotic Disease.” Current Atherosclerosis Reports 15, no. 4 (April 1, 2013): 312. https://doi.org/10.1007/s11883-013-0312-1.

[42] D. M. Hegsted et al., “Quantitative Effects of Dietary Fat on Serum Cholesterol in Man.” The American Journal of Clinical Nutrition 17, no. 5 (November 1965): 281–95. 10.1093/ajcn/17.5.281.

[43] P. N. Hopkins, “Effects of Dietary Cholesterol on Serum Cholesterol: A Meta-Analysis and Review.” The American Journal of Clinical Nutrition 55, no. 6 (June 1, 1992): 1060–70. https://doi.org/10.1093/ajcn/55.6.1060.

[44] Samia Mora et al., “Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared with Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women.” Circulation 119, no. 7 (February 24, 2009): 931–39. https://doi.org/10.1161/CIRCULATIONAHA.108.816181.

[45] Prospective Studies Collaboration, “Blood Cholesterol and Vascular Mortality by Age, Sex, and Blood Pressure: A Meta-Analysis of Individual Data from 61 Prospective Studies with 55,000 Vascular Deaths.” The Lancet 370, no. 9602 (December 1, 2007): 1829–39. https://doi.org/10.1016/S0140-6736(07)61778-4.

[46] Brittanie M. Volk et al., “Application of the Hegsted Equation to Low Carbohydrate-Low Fat Diet Comparisons.” The FASEB Journal 22, no. 1_Suppl (March 1, 2008): 1092.17-1092.17. https://www.fasebj.org/doi/abs/10.1096/fasebj.22.1_supplement.1092.17.

Many ketogenic professionals aren’t concerned by the total LDL concentration and focus instead on the types of LDL particles, but as we covered in chapter 4, all LDL particle sizes increase your risk for atherosclerosis and coronary artery disease, regardless of particle size.

[47] Jennifer G. Robinson, “What Is the Role of Advanced Lipoprotein Analysis in Practice?” Journal of the American College of Cardiology 60, no. 25 (December 2012): 2607–15. https://doi.org/10.1016/j.jacc.2012.04.067.

[48] James D. Otvos et al., “Low-Density Lipoprotein and High-Density Lipoprotein Particle Subclasses Predict Coronary Events and Are Favorably Changed by Gemfibrozil Therapy in the Veterans Affairs High-Density Lipoprotein Intervention Trial.” Circulation 113, no. 12 (March 28, 2006): 1556–63. https://doi.org/10.1161/CIRCULATIONAHA.105.565135.

Researchers at the Harvard T. H. Chan School of Public Health analyzed the data of more than 129,000 people over more than twenty years and found that a low- carbohydrate diet based on animal foods was associated with higher all- cause mortality and higher cancer mortality, and that simply substituting plant foods for animal foods (while still eating a low- carbohydrate diet) dropped total and cardiovascular mortality.

[49] Teresa T. Fung et al., “Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality: Two Cohort Studies.” Annals of Internal Medicine 153, no. 5 (September 7, 2010): 289–98. 10.7326/0003-4819-153-5-201009070-00003.

They concluded that vegetarian and vegan diets offer significant protection against death from cancer, heart disease, and diabetes, and that those who chose to eat more meat and dairy products in the long term significantly increased their risk for death.

[50] Lap Tai Le  and Joan Sabaté, “Beyond Meatless, the Health Effects of Vegan Diets: Findings from the Adventist Cohorts.” Nutrients 6, no. 6 (May 27, 2014): 2131–47. https://doi.org/10.3390/nu6062131.

They found that women who ate the highest amount of protein were 60 percent more likely to die of cardiovascular disease than those who ate the lowest amount of protein.

[51] P. Lagiou et al., “Low Carbohydrate-High Protein Diet and Mortality in a Cohort of Swedish Women.” Journal of Internal Medicine 261, no. 4 (April 2007): 366–74. https://doi.org/10.1111/j.1365-2796.2007.01774.x.

Ketogenic dieters eat between 1.0 and 1.5 grams of protein per kilogram of their “ideal” body weight, which translates to approximately 60 to 88 grams of protein per day for a 130- pound woman.

[52] Amy L. McKenzie et al., “A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes.” JMIR Diabetes 2, no. 1 (2017): e5. https://doi.org/10.2196/diabetes.6981.

They calculated that replacing 50 grams of carbohydrate with 15 grams of animal protein per day (replacing 2 medium apples with 2 ounces of chicken breast) was associated with a 22 percent increased risk of premature death from any cause.

[53] A. Trichopoulou et al., “Low-Carbohydrate-High-Protein Diet and Long-Term Survival in a General Population Cohort.” European Journal of Clinical Nutrition 61, no. 5 (May 2007): 575–81. https://doi.org/10.1038/sj.ejcn.1602557.

The authors further stated that “these findings support the hypothesis that the short-term benefits of low- carbohydrate diets for weight loss are potentially irrelevant.”

[54] Hiroshi Noto et al., “Low-Carbohydrate Diets and All-Cause Mortality: A Systematic Review and Meta-Analysis of Observational Studies.” PLOS ONE 8, no. 1 (January 25, 2013). https://doi.org/10.1371/journal.pone.0055030.

This is exactly the crux of the argument— most mainstream diabetes recommendations encourage eating more animal protein as a means of losing weight and “stabilizing blood glucose,” but large- scale research shows exactly the opposite.

[55] Song, Mingyang, Teresa T. Fung, Frank B. Hu, Walter C. Willett, Valter D. Longo, Andrew T. Chan, and Edward L. Giovannucci. “Association of Animal and Plant Protein Intake With All-Cause and Cause-Specific Mortality.” JAMA Internal Medicine, August 1, 2016. https://doi.org/10.1001/jamainternmed.2016.4182.

They found that animal foods high in protein and fat such as lamb, beef, pork, and chicken were associated with a higher risk for premature death, and that plant foods high in protein and in fat such as vegetables, nuts, peanut butter, and whole- grain breads were associated with a lower risk for premature death, suggesting that the type of food you eat may be as important as the percentage of carbohydrate, fat, and protein in your overall diet.

[56] Sara B. Seidelmann et al., “Dietary Carbohydrate Intake and Mortality: A Prospective Cohort Study and Meta-Analysis.” The Lancet: Public Health 3, no. 9 (September 2018): e419–e428. https://doi.org/10.1016/S2468-2667(18)30135-X.

A study performed by researchers in Toronto of 47 men and women with high cholesterol for four weeks showed that a plant- based low- carbohydrate diet (also called the Eco- Atkins diet) produced greater reductions in total cholesterol and LDL cholesterol than did a high- carbohydrate lacto- ovo- vegetarian diet containing low- fat dairy products.

[57] David J. A. Jenkins et al. “The Effect of a Plant-Based Low-Carbohydrate (‘Eco-Atkins’) Diet on Body Weight and Blood Lipid Concentrations in Hyperlipidemic Subjects.” Archives of Internal Medicine 169, no. 11 (June 8, 2009): 1046–54. https://doi.org/10.1001/archinternmed.2009.115.

The same research group then studied what happened over the course of six months in the same two groups and found that Eco- Atkins dieters lost more weight and reduced their total cholesterol, LDL cholesterol, and triglycerides more than the lacto-ovo-vegetarian group.

[58] David J. A. Jenkins et al., “Effect of a 6-Month Vegan Low-Carbohydrate (‘Eco-Atkins’) Diet on Cardiovascular Risk Factors and Body Weight in Hyperlipidaemic Adults: A Randomised Controlled Trial.” BMJ Open 4, no. 2 (February 1, 2014): e003505. https://doi.org/10.1136/bmjopen-2013-003505.

Instead, his patients resumed their normal state of physical and mental activity, their cardiovascular health improved, and their food cravings subsided.

[59] W. D. Sansum, N. R. Blatherwick, and Ruth Bowden, “The Use of High Carbohydrate Diets in the Treatment of Diabetes Mellitus.” Journal of the American Medical Association 86, no. 3 (January 16, 1926): 178–81. https://doi.org/10.1001/jama.1926.02670290018006.

Even though the sample size was small, these results were part of a collection of early, detailed investigations that demonstrated the power of a low- fat, high- carbohydrate diet on increasing carbohydrate tolerance and insulin sensitivity, contrary to what many researchers hypothesized to be true.

[60] J. Shirley Sweeney, “Dietary Factors That Influence the Dextrose Tolerance Test: A Preliminary Study.” Archives of Internal Medicine 40, no. 6 (December 1, 1927): 818–30. https://doi.org/10.1001/archinte.1927.00130120077005.

Israel Rabinowitch, MD, and his colleagues at the Montreal General Hospital discovered that plant- based diets low in fat improve insulin sensitivity.

[61] I. M. Rabinowitch, “Experiences with a High Carbohydrate-Low Calorie Diet for the Treatment of Diabetes Mellitus.” Canadian Medical Association Journal 23, no. 4 (October 1930): 489–98. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC382094/.

[62] I. M. Rabinowitch, “The Present Status of the High Carbohydrate-Low Calorie Diets for the Treatment of Diabetes.” Canadian Medical Association Journal 26, no. 2 (February 1932): 141–48. https://www.ncbi.nlm.nih.gov/pubmed/20318598.

[63] I. M. Rabinowitch, “Observations on the Significance of the Cholesterol Content of the Blood Plasma in Diabetes Mellitus.” Canadian Medical Association Journal 28, no. 2 (February 1933): 162–68. https://www.ncbi.nlm.nih.gov/pubmed/20319008.

“Suffice it to say that it now appears to be fairly well established that carbohydrates improve whereas fats impair, carbohydrate tolerance; and that carbohydrates increase whereas fats decrease the sensitivity of the individual, animal and man, to insulin.”

[64] I. M. Rabinowitch, “Effects of the High Carbohydrate-Low Calorie Diet Upon Carbohydrate Tolerance in Diabetes Mellitus.” Canadian Medical Association Journal 33, no. 2 (August 1935): 136–44. https://www.ncbi.nlm.nih.gov/pubmed/20319961.

Those who ate a high-carbohydrate diet experienced a peak blood glucose value of 120 mg/ dL, and their final blood glucose at the three- hour mark was slightly over 100 mg/ dL.

[65] H. P. Himsworth, “High Carbohydrate Diets and Insulin Efficiency.” British Medical Journal 2, no. 3836 (July 14, 1934): 57–60. 10.1136/bmj.2.3836.57.

Using this experimental setup, he observed that subjects became more insulin sensitive as the fat content of their diet dropped, and that those in the group eating 13 percent of their calories from fat experienced the highest level of insulin sensitivity.

[66] H. P. Himsworth, “The dietetic factor determining the glucose tolerance and sensitivity to insulin in healthy men.” Clinical Science 2 (1935): 67–94.

“There is no indication that healthy people taking a diet high in carbohydrates are especially liable to diabetes; in fact, numerous observations show improvement of carbohydrate tolerance following its greater intake.”

[67] I. Singh, “Low-Fat Diet and Therapeutic Doses of Insulin in Diabetes Mellitus.” The Lancet 268, no. 6861 (February 26, 1955): 422–25. 10.1016/s0140-6736(55)90211-7.

Walter Kempner, MD, at Duke University demonstrated that high- fat diets not only caused insulin resistance and type 2 diabetes, but that patients could begin reversing long- standing diabetic retinopathy in a matter of days by eating a highly processed diet that included fruit and fruit juice.

[68]  W. Kempner, R. L. Peschel, and C. Schlayer, “Effect of Rice Diet on Diabetes Mellitus Associated with Vascular Disease.” Postgraduate Medicine 24, no. 4 (October 1958): 359–71.10.1080/00325481.1958.11692236.

To uncouple weight loss from a low- fat diet, James W. Anderson, MD, and Kyleen Ward, RD, conducted a study in 1979 in which they enrolled twenty subjects who had been living with type 2 diabetes for up to twenty years.

[69] J. W. Anderson and K. Ward, “High-Carbohydrate, High-Fiber Diets for Insulin-Treated Men with Diabetes Mellitus.” The American Journal of Clinical Nutrition 32, no. 11 (November 1979): 2312–21. https://doi.org/10.1093/ajcn/32.11.2312.

In just over three weeks, 39 percent of the participants using insulin to manage their blood glucose were able to discontinue insulin altogether, and 71 percent of those using oral medications discontinued their use.

[70] R. J. Barnard, T. Jung, and S. B. Inkeles, “Diet and Exercise in the Treatment of NIDDM. The Need for Early Emphasis.” Diabetes Care 17, no. 12 (December 1994): 1469–72. 10.2337/diacare.17.12.1469.

Researchers followed participants for 22 weeks and observed larger reductions in A1c, body weight, and LDL cholesterol.

[71] Neal D. Barnard et al., “A Low-Fat Vegan Diet Improves Glycemic Control and Cardiovascular Risk Factors in a Randomized Clinical Trial in Individuals with Type 2 Diabetes.” Diabetes Care 29, no. 8 (August 1, 2006): 1777–83. https://doi.org/10.2337/dc06-0606.

When they followed these individuals for a total of 74 weeks, those in the plant-based group reduced their A1c more than those in the conventional diet group despite equivalent weight loss.

[72] Neal D. Barnard et al., “A Low-Fat Vegan Diet and a Conventional Diabetes Diet in the Treatment of Type 2 Diabetes: A Randomized, Controlled, 74-Wk Clinical Trial.” The American Journal of Clinical Nutrition 89, no. 5 (May 2009): 1588S-1596S. https://doi.org/10.3945/ajcn.2009.26736H.

They demonstrate how a whole- food plant- based diet can reduce the incidence of diabetes complications including coronary artery disease, high cholesterol, high blood pressure, chronic inflammation, chronic kidney disease, and peripheral neuropathy, and review potential mechanisms by which diets rich in whole plant foods and low or absent in animal foods reduce diabetes risk and insulin resistance.

[73] Michelle McMacken and Sapana Shah, “A Plant-Based Diet for the Prevention and Treatment of Type 2 Diabetes.” Journal of Geriatric Cardiology : JGC 14, no. 5 (May 2017): 342–54. https://doi.org/10.11909/j.issn.1671-5411.2017.05.009.

Researchers uncovered that those who ate fresh fruit three days per week were 13 to 28 percent less likely to experience macrovascular complications (heart disease and stroke) and microvascular damage (kidney disease, retinopathy, and neuropathy) than those who ate zero fruit.

[74] Huaidong Du et al., “Fresh Fruit Consumption in Relation to Incident Diabetes and Diabetic Vascular Complications: A 7-y Prospective Study of 0.5 Million Chinese Adults.” PLOS Medicine 14, no. 4 (April 11, 2017): e1002279. https://doi.org/10.1371/journal.pmed.1002279.

They concluded that replacing 5 percent of a diet containing saturated fatty acids with fructose (from either fruit or refined sources) is associated with a 30 percent decreased risk of diabetes, and that replacing 5 percent of protein with fructose is associated with a 28 percent reduction in diabetes risk.

[75] Sara Ahmadi-Abhari et al., “Dietary Intake of Carbohydrates and Risk of Type 2 Diabetes: The European Prospective Investigation into Cancer-Norfolk Study.” British Journal of Nutrition 111, no. 2 (January 2014): 342–52. https://doi.org/10.1017/S0007114513002298.

A diet high in saturated fat is the worst offender because saturated fat not only accelerates the development of insulin resistance but increases your total cholesterol, LDL cholesterol, and speeds up the rate at which atherosclerotic plaque accumulates inside blood vessels in all tissues.

[76] R. Clarke et al., “Dietary Lipids and Blood Cholesterol: Quantitative Meta-Analysis of Metabolic Ward Studies.” BMJ : British Medical Journal 314, no. 7074 (January 11, 1997): 112–17. 10.1136/bmj.314.7074.112.

Even under these moderate dietary restrictions, patients in the low- fat, low- cholesterol group reduced their recurrence of a heart attack by 71 percent.

[77] Thomas P. Lyon et al., “Lipoproteins and Diet in Coronary Heart Disease—A Five-Year Study.” California Medicine 84, no. 5 (May 1956): 325–28. https://www.ncbi.nlm.nih.gov/pubmed/13316532.

The authors conclude that “in the African population of Uganda coronary heart disease is almost non- existent,” and have strong evidence that a low- fat plant- based whole- food diet is the main reason why.

[78] A. G. Shaper and K. W. Jones, “Serum-Cholesterol, Diet, and Coronary Heart-Disease in Africans and Asians in Uganda: 1959.” International Journal of Epidemiology 41, no. 5 (October 2012): 1221–25. https://doi.org/10.1093/ije/dys137.

Those taught to eat a low- fat diet high in carbohydrate- rich foods such as fruits, starchy vegetables, legumes, and whole grains experienced a regression in coronary artery disease and experienced fewer cardiac events.

[79] Dean Ornish et al., “Intensive Lifestyle Changes for Reversal of Coronary Heart Disease.” JAMA 280, no. 23 (December 16, 1998): 2001–7. https://doi.org/10.1001/jama.280.23.2001.

Five patients who dropped out of the study went on to experience a total of ten more cardiac events!

[80] C. B. Esselstyn et al., “A Strategy to Arrest and Reverse Coronary Artery Disease: A 5-Year Longitudinal Study of a Single Physician’s Practice.” The Journal of Family Practice 41, no. 6 (December 1995): 560–68. https://www.ncbi.nlm.nih.gov/pubmed/7500065.

More important, of the 21 patients who did not comply, 13 participants experienced adverse cardiac events, resulting in a 62 percent recurrence rate.

[81] Caldwell B. Esselstyn et al., “A Way to Reverse CAD?” The Journal of Family Practice 63, no. 7 (July 2014): 356–364b. https://www.ncbi.nlm.nih.gov/pubmed/25198208.

Most important, those who were the most compliant dropped their risk for a cardiac event more than fourfold.

[82] Satish K. Gupta et al., “Regression of Coronary Atherosclerosis through Healthy Lifestyle in Coronary Artery Disease Patients—Mount Abu Open Heart Trial.” Indian Heart Journal 63, no. 5 (October 2011): 461–69. https://www.ncbi.nlm.nih.gov/pubmed/23550427.

While this study does not prove that their diet is responsible for low rates of cardiovascular disease, given that the Tsimane “have the lowest reported levels of coronary artery disease of any population recorded to date,” it’s certainly worth paying attention to their lifelong dietary habits.

[83] Hillard Kaplan et al., “Coronary Atherosclerosis in Indigenous South American Tsimane: A Cross-Sectional Cohort Study.” The Lancet 389, no. 10080 (29 2017): 1730–39. https://doi.org/10.1016/S0140-6736(17)30752-3.

The truth is that there are many populations around the world who eat plant- rich diets that have extremely low rates of heart disease, including the Bantu peoples of Central and Southern Africa, natives of New Guinea, certain Ecuadorian villages and Native Americans in Mexico, as well as the five Blue Zones as originally documented by Dan Buettner, including Ikaria (Greece), Okinawa (Japan), Sardinia (Italy), Loma Linda (California), and the Nicoya Peninsula (Costa Rica).

[84] Dan Buettner, The Blue Zones: 9 Lessons for Living Longer from the People Who’ve Lived the Longest, 2nd ed. New York: National Geographic, 2012.

[85] Nathan Pritikin, A Review of Medical Literature on Relationships of Various Degenerative Diseases to Diet and Activity. The Nathan and Ilene Pritikin Family Trust, 1988.

It turns out that many evidence- based investigations have not only found soy to be safe, it’s actually protective against a host of chronic diseases, including breast cancer, prostate cancer, and cardiovascular disease.

[1] Song-Yi Park et al., “Legume and Isoflavone Intake and Prostate Cancer Risk: The Multiethnic Cohort Study.” International Journal of Cancer 123, no. 4 (August 15, 2008): 927–32. https://doi.org/10.1002/ijc.23594.

[2] Mary S. Anthony, “Phytoestrogens and Cardiovascular Disease.” Arteriosclerosis, Thrombosis, and Vascular Biology 22, no. 8 (August 1, 2002): 1245–47. https://doi.org/10.1161/01.ATV.0000027188.24963.EA.

[3] H. Adlercreutz et al., “Phytoestrogens and Prostate Disease.” The Journal of Nutrition 130, no. 3 (March 1, 2000): 658S-659S. https://doi.org/10.1093/jn/130.3.658S.

[4] H. Adlercreutz, “Phytoestrogens: Epidemiology and a Possible Role in Cancer Protection.” Environmental Health Perspectives 103 Suppl 7 (October 1995): 103–12. https://doi.org/10.1289/ehp.95103s7103.

[5] T. Ranich, S. J. Bhathena, and M. T. Velasquez, “Protective Effects of Dietary Phytoestrogens in Chronic Renal Disease.” Journal of Renal Nutrition 11, no. 4 (October 2001): 183–93. https://www.ncbi.nlm.nih.gov/pubmed/11679998.

[6] H. P. Lee et al., “Risk Factors for Breast Cancer by Age and Menopausal Status: A Case-Control Study in Singapore.” Cancer Causes & Control: CCC 3, no. 4 (July 1992): 313–22. https://link.springer.com/article/10.1007/BF00146884.

[7] X. O. Shu et al., “Soyfood Intake During Adolescence and Subsequent Risk of Breast Cancer Among Chinese Women.” Cancer Epidemiology, Biomarkers & Prevention 10, no. 5 (May 2001): 483–88. https://www.ncbi.nlm.nih.gov/pubmed/11352858.

Studies comparing adults who ate the most soy compared with the least showed a 59 percent risk reduction in breast cancer and 31 percent risk reduction in prostate cancer.

[8] Ye Won Hwang et al., “Soy Food Consumption and Risk of Prostate Cancer: A Meta-Analysis of Observational Studies.” Nutrition and Cancer 61, no. 5 (2009): 598–606. https://doi.org/10.1080/01635580902825639.

[9] Sang-Ah Lee et al., “Adolescent and Adult Soy Food Intake and Breast Cancer Risk: Results from the Shanghai Women’s Health Study.” The American Journal of Clinical Nutrition 89, no. 6 (June 2009): 1920–26. https://doi.org/10.3945/ajcn.2008.27361.

A meta- analysis published in The New England Journal of Medicine found that the consumption of soy protein versus animal protein significantly decreases total cholesterol, LDL cholesterol, and triglycerides.

[10] J. W. Anderson, B. M. Johnstone, and M. E. Cook-Newell, “Meta-Analysis of the Effects of Soy Protein Intake on Serum Lipids.” The New England Journal of Medicine 333, no. 5 (August 3, 1995): 276–82. https://doi.org/10.1056/NEJM199508033330502.

There is almost no credible evidence to suggest traditional soyfoods exert clinically relevant adverse effects in healthy individuals when consumed in amounts consistent with Asian intake.

[11] Mark Messina, “Insights Gained from 20 Years of Soy Research.” The Journal of Nutrition 140, no. 12 (December 2010): 2289S-2295S. https://doi.org/10.3945/jn.110.124107.

And most recently, a 2018 meta- analysis of thirty studies published in the journal Nutrients found a statistically significant association between soy consumption and decreased prostate cancer risk.

[12] Catherine C. Applegate et al., “Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis.” Nutrients 10, no. 1 (January 4, 2018). https://doi.org/10.3390/nu10010040.

Fiber is considered a prebiotic— food that your gut bacteria metabolize— and this prebiotic is vitally important in helping these bacteria manufacture short- chain fatty acids that boost immune function, fight infections, improve insulin signaling, and promote insulin sensitivity.

[13] Kees Meijer, Paul de Vos, and Marion G. Priebe. “Butyrate and Other Short-Chain Fatty Acids as Modulators of Immunity: What Relevance for Health?” Current Opinion in Clinical Nutrition and Metabolic Care 13, no. 6 (November 2010): 715–21. https://doi.org/10.1097/MCO.0b013e32833eebe5.

[14] Othman A. Baothman et al., “The Role of Gut Microbiota in the Development of Obesity and Diabetes.” Lipids in Health and Disease 15 (June 18, 2016). https://doi.org/10.1186/s12944-016-0278-4.

[15] Bach Knudsen and Knud Erik, “Microbial Degradation of Whole-Grain Complex Carbohydrates and Impact on Short-Chain Fatty Acids and Health.” Advances in Nutrition 6, no. 2 (March 1, 2015): 206–13. https://doi.org/10.3945/an.114.007450.

[16] James M. Lattimer and Mark D. Haub, “Effects of Dietary Fiber and Its Components on Metabolic Health.” Nutrients 2, no. 12 (December 15, 2010): 1266–89. https://doi.org/10.3390/nu2121266.

[17] Daniel Li, Jennifer Kirsop, and W. H. Wilson Tang. “Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis.” Current Diabetes Reports 15, no. 9 (September 2015): 63. https://doi.org/10.1007/s11892-015-0634-1.

Saturated fat— the primary component of coconut oil and most vegetable oils— is the most common trigger for insulin resistance because even small amounts can impair the function of insulin receptors in your muscle and liver within hours of a single high- fat meal.

[18] José Manuel García-López et al., “Should the Amounts of Fat and Protein Be Taken into Consideration to Calculate the Lunch Prandial Insulin Bolus? Results from a Randomized Crossover Trial.” Diabetes Technology & Therapeutics 15, no. 2 (February 2013): 166–71. https://doi.org/10.1089/dia.2012.0149.

[19] l L. C. Gormsen et al., “Time-Course Effects of Physiological Free Fatty Acid Surges on Insulin Sensitivity in Humans.” Acta Physiologica 201, no. 3 (March 2011): 349–56. https://doi.org/10.1111/j.1748-1716.2010.02181.x.

[20] Sandro M. Hirabara et al., “Time-Dependent Effects of Fatty Acids on Skeletal Muscle Metabolism.” Journal of Cellular Physiology 210, no. 1 (January 2007): 7–15. https://doi.org/10.1002/jcp.20811.

[21] Andreas Neu et al., “Higher Glucose Concentrations Following Protein- and Fat-Rich Meals—the Tuebingen Grill Study: A Pilot Study in Adolescents with Type 1 Diabetes.” Pediatric Diabetes 16, no. 8 (December 1, 2015): 587–91. https://doi.org/10.1111/pedi.12224.

[22] Ewa Pańkowska, Marlena Błazik, and Lidia Groele, “Does the Fat-Protein Meal Increase Postprandial Glucose Level in Type 1 Diabetes Patients on Insulin Pump: The Conclusion of a Randomized Study.” Diabetes Technology & Therapeutics 14, no. 1 (January 2012): 16–22. https://doi.org/10.1089/dia.2011.0083.

[23] Carmel E. M. Smart et al., “Both Dietary Protein and Fat Increase Postprandial Glucose Excursions in Children with Type 1 Diabetes, and the Effect Is Additive.” Diabetes Care 36, no. 12 (December 2013): 3897–3902. https://doi.org/10.2337/dc13-1195.

[24] Howard A. Wolpert et al., “Dietary Fat Acutely Increases Glucose Concentrations and Insulin Requirements in Patients With Type 1 Diabetes Implications for Carbohydrate-Based Bolus Dose Calculation and Intensive Diabetes Management.” Diabetes Care 36, no. 4 (April 1, 2013): 810–16. https://doi.org/10.2337/dc12-0092.

Staying well hydrated is very important for physical and cognitive performance; gastrointestinal, kidney, and heart function; skin health, and the prevention of headaches.

[25] Barry M. Popkin, Kristen E. D’Anci, and Irwin H. Rosenberg, “Water, Hydration, and Health.” Nutrition Reviews 68, no. 8 (August 1, 2010): 439–58. https://doi.org/10.1111/j.1753-4887.2010.00304.x.

Evidence-based research has consistently demonstrated that green tea helps reduce your risk for cancer, improves artery function, and protects against cardiovascular disease.

[26] Nikolaos Alexopoulos et al., “The Acute Effect of Green Tea Consumption on Endothelial Function in Healthy Individuals.” European Journal of Cardiovascular Prevention and Rehabilitation 15, no. 3 (June 2008): 300–305. https://doi.org/10.1097/HJR.0b013e3282f4832f.

[27] Nicoline Jochmann et al., “The Efficacy of Black Tea in Ameliorating Endothelial Function Is Equivalent to That of Green Tea.” The British Journal of Nutrition 99, no. 4 (April 2008): 863–68. https://doi.org/10.1017/S0007114507838992.

[28] Ze-Mu Wang et al., “Black and Green Tea Consumption and the Risk of Coronary Artery Disease: A Meta-Analysis.” The American Journal of Clinical Nutrition 93, no. 3 (March 2011): 506–15. https://doi.org/10.3945/ajcn.110.005363.

[29] K. S. Woo et al., “Chinese Adults Are Less Susceptible Than Whites to Age-Related Endothelial Dysfunction.” Journal of the American College of Cardiology 30, no. 1 (July 1997): 113–18. 10.1016/s0735-1097(97)00111-3.

Fresh coconut water provides important nutrients such as B vitamins, vitamin C, and sodium, and the cytokinins found in coconut water may contain potent anti- cancer properties.

[30] Jean W. H. Yong et al., “The Chemical Composition and Biological Properties of Coconut (Cocos nucifera L.) Water.” Molecules 14, no. 12 (December 9, 2009): 5144–64. https://doi.org/10.3390/molecules14125144.

Kombucha has been shown to improve resistance against cancer, prevent cardiovascular diseases, promote digestive functions, stimulate the immune system, reduce inflammation, and aid in liver detoxification.

[31] C. Dufresne and E. Farnworth, “Tea, Kombucha, and Health: A Review.” Food Research International 33, no. 6 (July 1, 2000): 409–21. https://doi.org/10.1016/S0963-9969(00)00067-3.

[32] G. Sreeramulu, Y. Zhu, and W. Knol, “Kombucha Fermentation and Its Antimicrobial Activity.” Journal of Agricultural and Food Chemistry 48, no. 6 (June 2000): 2589–94. 10.1021/jf991333m.

[33] Jessica Martínez Leal et al., “A Review on Health Benefits of Kombucha Nutritional Compounds and Metabolites.” CyTA—Journal of Food 16, no. 1 (January 1, 2018): 390–99. https://doi.org/10.1080/19476337.2017.1410499.

While there are several meta- analyses that suggest low to moderate levels of alcohol consumption can be beneficial for cardiovascular health and reduced mortality, compelling research has shown that drinking even small amounts of alcohol is harmful.

[34] E. B. Rimm et al., “Review of Moderate Alcohol Consumption and Reduced Risk of Coronary Heart Disease: Is the Effect Due to Beer, Wine, or Spirits.” BMJ (Clinical Research Ed.) 312, no. 7033 (March 23, 1996): 731–36. 10.1136/bmj.312.7033.731.

[35] Augusto Di Castelnuovo et al., “Meta-Analysis of Wine and Beer Consumption in Relation to Vascular Risk.” Circulation 105, no. 24 (June 18, 2002): 2836–44. https://doi.org/10.1161/01.CIR.0000018653.19696.01.

[36] Augusto Di Castelnuovo et al., “Alcohol Dosing and Total Mortality in Men and Women: An Updated Meta-Analysis of 34 Prospective Studies.” Archives of Internal Medicine 166, no. 22 (December 11, 2006): 2437–45. https://doi.org/10.1001/archinte.166.22.2437.

[37] Kristi Reynolds et al., “Alcohol Consumption and Risk of Stroke: A Meta-Analysis.” JAMA 289, no. 5 (February 5, 2003): 579–88. 10.1001/jama.289.5.579.

The authors concluded that the safest level of alcohol consumption is none.

[38] GBD 2016 Alcohol Collaborators, “Alcohol Use and Burden for 195 Countries and Territories, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016.” The Lancet 392, no. 10152 (22 2018): P1015–P1035. https://doi.org/10.1016/S0140-6736(18)31310-2.

Alcohol carries a risk of liver disease, and the most powerful ways to improve your metabolic health include quitting smoking, exercising regularly, and eating a healthy diet.

[39] Alice Park, “Alcohol Really Is Good for Your Heart—Most of the Time.” Time, March 22, 2017. https://time.com/4709302/alcohol-heart-disease-risk/.

That’s partially because we think that counting calories is a huge pain and a waste of time, but it’s mostly because research has shown that eating fiber- rich foods is a great way to feel full without having to worry about how many calories you are eating.

[40] N. Wright et al., “The BROAD Study: A Randomised Controlled Trial Using a Whole Food Plant-Based Diet in the Community for Obesity, Ischaemic Heart Disease or Diabetes.” Nutrition & Diabetes 7, no. 3 (March 2017): e256. https://doi.org/10.1038/nutd.2017.3.

[41] J. W. Anderson and K. Ward, “High-Carbohydrate, High-Fiber Diets for Insulin-Treated Men with Diabetes Mellitus.” The American Journal of Clinical Nutrition 32, no. 11 (November 1979): 2312–21. https://doi.org/10.1093/ajcn/32.11.2312.

Even though fruits have been relentlessly marketed as simple sugars, they are in fact complex nutritional packets containing an exceptionally high density of micronutrients, including vitamins, minerals, fiber, water, antioxidants, and phytochemicals.

[42] Ramachandran Vinayagam and Baojun Xu, “Antidiabetic Properties of Dietary Flavonoids: A Cellular Mechanism Review.” Nutrition & Metabolism 12, no. 1 (December 2015). https://doi.org/10.1186/s12986-015-0057-7.

[43] Rui Hai Liu, “Health Benefits of Fruit and Vegetables Are from Additive and Synergistic Combinations of Phytochemicals.” The American Journal of Clinical Nutrition 78, no. 3 (September 1, 2003): 517S-520S. https://doi.org/10.1093/ajcn/78.3.517S.

[44] Monica H. Carlsen et al., “The Total Antioxidant Content of More than 3100 Foods, Beverages, Spices, Herbs and Supplements Used Worldwide.” Nutrition Journal 9 (January 22, 2010): 3. https://doi.org/10.1186/1475-2891-9-3.

For reference, the standard American diet (SAD) has an omega-- 6 to omega- 3 ratio of approximately 20:1. A better ratio for optimal metabolic health is between 4:1 and 1:1.

[45] A. P. Simopoulos, “The Importance of the Ratio of Omega-6/Omega-3 Essential Fatty Acids.” Biomedicine & Pharmacotherapy 56, no. 8 (October 1, 2002): 365–79. https://doi.org/10.1016/S0753-3322(02)00253-6.

The first, as we’ve pointed out, is that your body converts LA into a collection of omega-- 6 EFAs that are pro- inflammatory, and research shows that excessive omega-- 6 intake is associated with chronic inflammatory diseases, including fatty liver disease, cardiovascular disease, obesity, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer’s disease.

[46] Artemis P. Simopoulos, “An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.” Nutrients 8, no. 3 (March 2, 2016). https://doi.org/10.3390/nu8030128.

[47] E. Patterson et al., “Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids.” Journal of Nutrition and Metabolism 2012 (2012). https://doi.org/10.1155/2012/539426.

Together, both EPA and DHA promote the formation of new neurons in your brain, improve memory, and may help prevent against dementia and Alzheimer’s disease.

[48] Simon C. Dyall, “Long-Chain Omega-3 Fatty Acids and the Brain: A Review of the Independent and Shared Effects of EPA, DPA and DHA.” Frontiers in Aging Neuroscience 7 (April 21, 2015). https://doi.org/10.3389/fnagi.2015.00052.

[49] Tommy Cederholm, Norman Salem, and Jan Palmblad, “ω-3 Fatty Acids in the Prevention of Cognitive Decline in Humans.” Advances in Nutrition 4, no. 6 (November 1, 2013): 672–76. https://doi.org/10.3945/an.113.004556.

[50] R. J. T. Mocking et al., “Meta-Analysis and Meta-Regression of Omega-3 Polyunsaturated Fatty Acid Supplementation for Major Depressive Disorder.” Translational Psychiatry 6, no. 3 (March 2016): e756–e756. https://doi.org/10.1038/tp.2016.29.

Do your best to grind them up immediately prior to eating them so that the EFAs are easy to absorb and have the highest chance of increasing your omega-- 3 status.

[51] J. Alejandro Austria et al., “Bioavailability of Alpha-Linolenic Acid in Subjects after Ingestion of Three Different Forms of Flaxseed.” Journal of the American College of Nutrition 27, no. 2 (April 2008): 214–21. 10.1080/07315724.2008.10719693.

[52] David C. Nieman et al., “Chia Seed Supplementation and Disease Risk Factors in Overweight Women: A Metabolomics Investigation.” Journal of Alternative and Complementary Medicine 18, no. 7 (July 2012): 700–708. https://doi.org/10.1089/acm.2011.0443.

EPA and DHA supplementation has been shown to be beneficial for reducing Alzheimer’s disease risk; improving language skills, concentration, and motor skills; reducing depressive symptoms; reducing suicidal thoughts and behaviors; reducing schizophrenic symptoms; reducing aggressive impulse behavior; and reducing anxiety.

[53] Rhonda P. Patrick, “Role of Phosphatidylcholine-DHA in Preventing APOE4-Associated Alzheimer’s Disease.” FASEB Journal 33, no. 2 (February 2019): 1554–64. https://doi.org/10.1096/fj.201801412R.

[54] Rhonda P. Patrick and Bruce N. Ames, “Vitamin D and the Omega-3 Fatty Acids Control Serotonin Synthesis and Action, Part 2: Relevance for ADHD, Bipolar Disorder, Schizophrenia, and Impulsive Behavior.” FASEB Journal 29, no. 6 (June 2015): 2207–22. https://doi.org/10.1096/fj.14-268342.

[55] Joseph R. Hibbeln et al., “Vegetarian Diets and Depressive Symptoms among Men.” Journal of Affective Disorders 225 (January 1, 2018): 13–17. https://doi.org/10.1016/j.jad.2017.07.051.

As you can see in the table above, our omega-- 3 indices were both greater than the 4 percent threshold for excellent health, and our omega-- 6 to omega- 3 ratios were both between the 1:1 and 4:1 ratio as described earlier.

[56] Barbara Sarter et al., “Blood Docosahexaenoic Acid and Eicosapentaenoic Acid in Vegans: Associations with Age and Gender and Effects of an Algal-Derived Omega-3 Fatty Acid Supplement.” Clinical Nutrition 34, no. 2 (April 2015): 212–18. https://doi.org/10.1016/j.clnu.2014.03.003.

Eating green light foods can ensure that your intake of all fat- soluble vitamins meets or exceeds nutritional requirements.

[57] Institute of Medicine, Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: The National Academies Press, 2000. https://doi.org/10.17226/9810.

Vitamin A plays important roles in cell differentiation, eye health, skin integrity, mucous membranes, bone growth, teeth health, reproduction, and hormone synthesis.

[58] Institute of Medicine, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: The National Academies Press, 2001. https://doi.org/10.17226/10026.

Deficiency symptoms such as nighttime blindness are virtually nonexistent in our world today.

[59] Institute of Medicine, Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: The National Academies Press, 2001. https://doi.org/10.17226/10026.

Research has demonstrated the importance of vitamin D for fighting infections and building a strong immune system.

[60] John S. Adams and Martin Hewison, “Unexpected Actions of Vitamin D: New Perspectives on the Regulation of Innate and Adaptive Immunity.” Nature Clinical Practice. Endocrinology & Metabolism 4, no. 2 (February 2008): 80–90. https://doi.org/10.1038/ncpendmet0716.

Vitamin D deficiency has been linked to impaired glucose metabolism, insulin resistance, an increased risk of developing type 1 diabetes, and an increased risk for developing type 2 diabetes.

[61] E. Hyppönen et al., “Intake of Vitamin D and Risk of Type 1 Diabetes: A Birth-Cohort Study.” The Lancet 358, no. 9292 (November 3, 2001): 1500–503. https://doi.org/10.1016/S0140-6736(01)06580-1.

[62] Paul Knekt et al., “Serum Vitamin D and Subsequent Occurrence of Type 2 Diabetes.” Epidemiology 19, no. 5 (September 2008): 666–71. https://doi.org/10.1097/EDE.0b013e318176b8ad.

[63] Anastassios G. Pittas et al., “Vitamin D and Calcium Intake in Relation to Type 2 Diabetes in Women.” Diabetes Care 29, no. 3 (March 2006): 650–56. 10.2337/diacare.29.03.06.dc05-1961.

[64] Christine Dalgård et al., “Vitamin D Status in Relation to Glucose Metabolism and Type 2 Diabetes in Septuagenarians.” Diabetes Care 34, no. 6 (June 2011): 1284–88. https://doi.org/10.2337/dc10-2084.

[65] Mohammed E Al-Sofiani et al., “Effect of Vitamin D Supplementation on Glucose Control and Inflammatory Response in Type II Diabetes: A Double Blind, Randomized Clinical Trial.” International Journal of Endocrinology and Metabolism 13, no. 1 (January 2015): e22604. https://doi.org/10.5812/ijem.22604.

[66] Catherine A. Peterson, Aneesh K. Tosh, and Anthony M. Belenchia, “Vitamin D Insufficiency and Insulin Resistance in Obese Adolescents.” Therapeutic Advances in Endocrinology and Metabolism 5, no. 6 (December 2014): 166–89. https://doi.org/10.1177/2042018814547205.

[67] T. Mezza et al., “Vitamin D Deficiency: A New Risk Factor for Type 2 Diabetes?” Annals of Nutrition & Metabolism 61, no. 4 (2012): 337–48. https://doi.org/10.1159/000342771.

[68] Ki-Chul Sung et al., “High Levels of Serum Vitamin D Are Associated with a Decreased Risk of Metabolic Diseases in Both Men and Women, but an Increased Risk for Coronary Artery Calcification in Korean Men.” Cardiovascular Diabetology 15, no. 1 (August 12, 2016): 112. https://doi.org/10.1186/s12933-016-0432-3.

This report has been extensively debated, with many studies and experts suggesting that the optimal vitamin D level is 2.5 to 5 times as high, between 50 ng/ ml and 100 ng/ ml.

[69] Dr. Wes Youngberg, Goodbye Diabetes. Hart Books, 2013.

While it has been recognized that obtaining vitamin D from sun exposure is optimal— and studies have shown it’s best to expose as much of your body to the sun as possible between the hours of ten a.m. and three p.m., at least three times per week, for fifteen to thirty minutes per session— this often isn’t possible or even sufficient for people who live in places that don’t get as much sunlight, such as the northern latitudes.

[70] Fahad M. Alshahrani et al., “Vitamin D: Light Side and Best Time of Sunshine in Riyadh, Saudi Arabia.” Dermato-Endocrinology 5, no. 1 (January 1, 2013): 177–80. https://doi.org/10.4161/derm.23351.

[71] Chittari V. Harinarayan et al., “Vitamin D Status and Sun Exposure in India.” Dermato-Endocrinology 5, no. 1 (January 1, 2013): 130–41. https://doi.org/10.4161/derm.23873.

[72] Emanuela Cicarma et al., “Sun and Sun Beds: Inducers of Vitamin D and Skin Cancer.” Anticancer Research 29, no. 9 (September 2009): 3495–3500. https://www.ncbi.nlm.nih.gov/pubmed/19667143.

Vitamin E refers to a group of compounds with potent antioxidant activity that fight free radicals, boost your immune system, and prevent blood clots.

[73] National Institutes of Health, Office of Dietary Supplements, “Vitamin E: Fact Sheet for Health Professionals.” https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/.

When patients took the same beta- carotene supplement with two- thirds of a pint of almond ice cream containing 200 grams of fat, the amount of beta- carotene in their blood increased 2.5- fold.

[74] M. R. Prince and J. K. Frisoli, “Beta-Carotene Accumulation in Serum and Skin.” The American Journal of Clinical Nutrition 57, no. 2 (February 1993): 175–81. https://doi.org/10.1093/ajcn/57.2.175.

This type of research is designed to get a specific result to benefit industry and is not applicable to those who maximize their nutrient density with every bite.

[75] Nuray Z. Unlu et al., “Carotenoid Absorption from Salad and Salsa by Humans Is Enhanced by the Addition of Avocado or Avocado Oil.” The Journal of Nutrition 135, no. 3 (March 2005): 431–36. https://doi.org/10.1093/jn/135.3.431.

Some research suggests that optimal beta- carotene absorption occurs with as little as 5 grams of fat per day in children.

[76] J. J. Castenmiller and C. E. West, “Bioavailability and Bioconversion of Carotenoids.” Annual Review of Nutrition 18 (1998): 19–38. https://doi.org/10.1146/annurev.nutr.18.1.19.

Another study in children found that either 2.4 grams of fat per meal or 21 grams of fat per day is sufficient for optimal utilization of vitamin A.

[77] Judy D. Ribaya-Mercado et al., “Carotene-Rich Plant Foods Ingested with Minimal Dietary Fat Enhance the Total-Body Vitamin A Pool Size in Filipino Schoolchildren as Assessed by Stable-Isotope-Dilution Methodology.” The American Journal of Clinical Nutrition 85, no. 4 (April 2007): 1041–49. https://doi.org/10.1093/ajcn/85.4.1041.

Research conducted in adults suggests that eating as little as 3 to 5 grams of fat per meal in adults results in optimal absorption of alpha- carotene, beta- carotene, and vitamin E, and that higher- fat meals improve only lutein absorption.

[78] A. J. Roodenburg et al., “Amount of Fat in the Diet Affects Bioavailability of Lutein Esters but Not of Alpha-Carotene, Beta-Carotene, and Vitamin E in Humans.” The American Journal of Clinical Nutrition 71, no. 5 (May 2000): 1187–93. https://doi.org/10.1093/ajcn/71.5.1187.

[79] P. Jayarajan, V. Reddy, and M. Mohanram, “Effect of Dietary Fat on Absorption of Beta Carotene from Green Leafy Vegetables in Children.” The Indian Journal of Medical Research 71 (January 1980): 53–56. https://www.ncbi.nlm.nih.gov/pubmed/7380511.

Besides the fact that the naturally occurring fat content in whole plants is more than enough to absorb carotenoids, it’s also important to understand that if a particular meal or snack does not have sufficient quantities of fat to absorb carotenoids into chylomicron particles, carotenoids can be temporarily stored in epithelial cells until an adequate amount of fat present in a subsequent meal becomes available.

[80] P. Borel et al., “Chylomicron Beta-Carotene and Retinyl Palmitate Responses Are Dramatically Diminished When Men Ingest Beta-Carotene with Medium-Chain Rather than Long-Chain Triglycerides.” The Journal of Nutrition 128, no. 8 (August 1998): 1361–67. https://doi.org/10.1093/jn/128.8.1361.

[81] Shellen R. Goltz et al., “Meal Triacylglycerol Profile Modulates Postprandial Absorption of Carotenoids in Humans.” Molecular Nutrition & Food Research 56, no. 6 (June 2012): 866–77. https://doi.org/10.1002/mnfr.201100687.

The mnemonic SLAMENGHI describes these factors: species of carotenoids, linkages at molecular level, amount of carotenoid, matrix, effectors, nutrient status, genetics, host- related factors, and interactions among these variables.

[82] Karin H. van het Hof et al., “Dietary Factors That Affect the Bioavailability of Carotenoids.” The Journal of Nutrition 130, no. 3 (March 1, 2000): 503–6. https://doi.org/10.1093/jn/130.3.503.

Symptoms of B12 deficiency include anemia, peripheral neuropathy, concentration loss, memory loss, insomnia, impaired bowel and bladder control, appetite loss, flatulence, and constipation.

[83] Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and Its Panel on Folate, Other B Vitamins, and Choline. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press, 1998. https://www.ncbi.nlm.nih.gov/books/NBK114310/.

[84] Marilyn H. Hill et al., “A Vitamin B-12 Supplement of 500 Μg/d for Eight Weeks Does Not Normalize Urinary Methylmalonic Acid or Other Biomarkers of Vitamin B-12 Status in Elderly People with Moderately Poor Vitamin B-12 Status.” The Journal of Nutrition 143, no. 2 (February 2013): 142–47. https://doi.org/10.3945/jn.112.169193.

It is possible to have a normal vitamin B12 level but still have elevated MMA and HC, but this condition is quite rare.

[85] Pankaj Vashi et al., “Methylmalonic Acid and Homocysteine as Indicators of Vitamin B-12 Deficiency in Cancer.” PLOS ONE 11, no. 1 (January 25, 2016). https://doi.org/10.1371/journal.pone.0147843.

Just about any oral supplement will work because all forms are broken down into cobalamin, which your body then converts into active forms in tissues.

[86] Cristiana Paul and David M. Brady, “Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements with Potential to Mitigate B12-Related Genetic Polymorphisms.” Integrative Medicine 16, no. 1 (February 2017): 42–49. PMC5312744.

The good news is that about 1 percent of vitamin B12 is passively absorbed into your blood, which means that you can easily meet your vitamin B12 requirement by supplementing with a single 2,500- microgram dose once per week.

[87] Mustafa Vakur Bor et al., “Daily Intake of 4 to 7 Microg Dietary Vitamin B-12 Is Associated with Steady Concentrations of Vitamin B-12-Related Biomarkers in a Healthy Young Population.” The American Journal of Clinical Nutrition 91, no. 3 (March 2010): 571–77. https://doi.org/10.3945/ajcn.2009.28082.

[88] J. M. Scott, “Bioavailability of Vitamin B12.” European Journal of Clinical Nutrition 51 Suppl 1 (January 1997): S49–S53. https://www.ncbi.nlm.nih.gov/pubmed/9023481.

Researchers believe it to be the most suitable measurement for assessing your endogenous insulin secretion.

[1] Jerry P. Palmer et al., “C-peptide Is the Appropriate Outcome Measure for Type 1 Diabetes Clinical Trials to Preserve β-Cell Function: Report of an ADA Workshop, 21–22 October 2001.” Diabetes 53, no. 1 (January 1, 2004): 250–64. https://doi.org/10.2337/diabetes.53.1.250.

A fasting C-- peptide value of between 3.0 and 4.0 ng/ mL indicates that your beta cells are capable of manufacturing sufficient insulin, and that it’s possible to completely reverse insulin resistance and eliminate your need for diabetes medications by maximizing your insulin sensitivity.

[2] J. W. Anderson, “High Carbohydrate, High Fiber Diets for Patients with Diabetes.” Advances in Experimental Medicine and Biology 119 (1979): 263–73. 10.1007/978-1-4615-9110-8_38.

[3] J. W. Anderson et al., “Metabolic Effects of High-Carbohydrate, High-Fiber Diets for Insulin-Dependent Diabetic Individuals.” The American Journal of Clinical Nutrition 54, no. 5 (November 1991): 936–43. https://doi.org/10.1093/ajcn/54.5.936.

[4] J. W. Anderson and K. Ward, “Long-Term Effects of High-Carbohydrate, High-Fiber Diets on Glucose and Lipid Metabolism: A Preliminary Report on Patients with Diabetes.” Diabetes Care 1, no. 2 (April 1978): 77–82. 10.2337/diacare.1.2.77.

[5] T. G. Kiehm, J. W. Anderson, and K. Ward, “Beneficial Effects of a High Carbohydrate, High Fiber Diet on Hyperglycemic Diabetic Men.” The American Journal of Clinical Nutrition 29, no. 8 (August 1976): 895–99. https://doi.org/10.1093/ajcn/29.8.895.

Although optimal beta cell function may never be completely restored, adopting the Mastering Diabetes Method is one of the most powerful things you can do to prevent further damage and even restore beta cell function.

[6] Hana Kahleova et al., “A Plant-Based Dietary Intervention Improves Beta-Cell Function and Insulin Resistance in Overweight Adults: A 16-Week Randomized Clinical Trial.” Nutrients 10, no. 2 (February 9, 2018). https://doi.org/10.3390/nu10020189.

[7] A. M. Rosenfalck et al., “A Low-Fat Diet Improves Peripheral Insulin Sensitivity in Patients with Type 1 Diabetes.” Diabetic Medicine 23, no. 4 (April 2006): 384–92. https://doi.org/10.1111/j.1464-5491.2005.01810.x.

There are five antibodies that are mainly responsible for the destruction of beta cells and insulin, listed in the table below.

[8] W. E. Winter and D. A. Schatz, “Autoimmune Markers in Diabetes.” Clinical Chemistry 57, no. 2 (February 1, 2011): 168–75. https://doi.org/10.1373/clinchem.2010.148205.

One notable exception is the GAD antibody— some people test positive but do not display any symptoms of blood glucose instability or autoimmune diabetes.

[9] Elin Pettersen Sørgjerd et al., “Presence of Anti-GAD in a Non-Diabetic Population of Adults; Time Dynamics and Clinical Influence: Results from the HUNT Study.” BMJ Open Diabetes Research and Care 3, no. 1 (June 1, 2015): e000076. https://doi.org/10.1136/bmjdrc-2014-000076.

Type 1 diabetes generally occurs in individuals younger than 30 years of age who test positive for one or more antibodies and have a fasting C-- peptide of 0.2 nmol/ L or less.

[10] Emma Leighton, Christopher A.R. Sainsbury, and Gregory C. Jones, “A Practical Review of C-Peptide Testing in Diabetes.” Diabetes Therapy 8, no. 3 (June 2017): 475–87. https://doi.org/10.1007/s13300-017-0265-4.

[11] Jerry P. Palmer et al., “C-peptide Is the Appropriate Outcome Measure for Type 1 Diabetes Clinical Trials to Preserve β-Cell Function: Report of an ADA Workshop, 21–22 October 2001.” Diabetes 53, no. 1 (January 1, 2004): 250–64. https://doi.org/10.2337/diabetes.53.1.250.

The majority of people diagnosed with type 1 diabetes experience a state called diabetic ketoacidosis (DKA), characterized by extremely high blood glucose values (greater than 300 mg/ dL), excessive thirst, unexplained weight loss, frequent urination, muscle cramping, and low energy.

[12] Juliet A. Usher-Smith et al., “Factors Associated with the Presence of Diabetic Ketoacidosis at Diagnosis of Diabetes in Children and Young Adults: A Systematic Review.” BMJ 343 (July 7, 2011). https://doi.org/10.1136/bmj.d4092.

Even though this classification is less known, researchers believe that type 1.5 diabetes affects more people than type 1 diabetes around the world.

[13] E. Laugesen, J. A. Østergaard, and R. D. G. Leslie, “Latent Autoimmune Diabetes of the Adult: Current Knowledge and Uncertainty.” Diabetic Medicine 32, no. 7 (July 2015): 843–52. https://doi.org/10.1111/dme.12700.

Type 1.5 diabetes is also common in patients diagnosed with type 2 diabetes who are lean and do not have the metabolic syndrome (high blood pressure, high cholesterol or triglycerides, and excess fat around their waist), especially if they eat well and are physically active.

[14] Kyriazoula Chatzianagnostou, Giorgio Iervasi, and Cristina Vassalle, “Challenges of LADA Diagnosis and Treatment: Lessons from 2 Case Reports.” American Journal of Therapeutics 23, no. 5 (October 2016): e1270-4. https://doi.org/10.1097/MJT.0000000000000349.

A though scientists do not know the exact mechanism of action, sulfonylureas are known to stimulate beta cells in the manufacture and secretion of insulin, to increase liver glucose output, and to moderately increase insulin sensitivity.

[15] Daniele Sola et al., “Sulfonylureas and Their Use in Clinical Practice.” Archives of Medical Science 11, no. 4 (August 12, 2015): 840–48. https://doi.org/10.5114/aoms.2015.53304.

What this means is very important— sulfonylureas may stimulate your beta cells to make more insulin today, but over the course of time they cause beta cell damage, eventually resulting in impaired insulin production.

[16] Robert C. Turner, “The U.K. Prospective Diabetes Study: A Review.” Diabetes Care 21, no. Suppl 3 (December 1, 1998): C35–C38. https://doi.org/10.2337/diacare.21.3.C35.

Worst of all, a study involving more than 5,000 participants showed that use of sulfonylureas for an average of 4.8 years led to a 70 percent increase in the risk of death as compared with metformin.

[17] Scot H. Simpson et al., “Dose-Response Relation Between Sulfonylurea Drugs and Mortality in Type 2 Diabetes Mellitus: A Population-Based Cohort Study.” CMAJ: Canadian Medical Association Journal 174, no. 2 (January 17, 2006): 169–74. https://doi.org/10.1503/cmaj.050748.

Given that meglitinides directly stimulate insulin production by the beta cells in your pancreas, the most notable side effects include hypoglycemia and weight gain, followed by gastrointestinal inflammation.

[18] Beatriz Luna and Mark N. Feinglos, “Oral Agents in the Management of Type 2 Diabetes Mellitus.” American Family Physician 63, no. 9 (May 1, 2001): 1747. https://www.ncbi.nlm.nih.gov/pubmed/11352285.

When you eat food, your small intestine and colon release GLP-- 1, a powerful hormone with many actions, which include activating smooth muscles to assist in moving food through your intestines, inhibiting the secretion of glucagon to prevent your liver from dumping glucose into your blood, communicating with your brain to turn off hunger signals, and stimulating your beta cells to make more beta cells and secrete more insulin.

[19] Patrick E. MacDonald et al., “The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion.” Diabetes 51, no. suppl 3 (December 1, 2002): S434–S442. https://doi.org/10.2337/diabetes.51.2007.S434.

GLP-- 1 agonists are known to cause gastrointestinal problems including gas, bloating, diarrhea, and flatulence, and have been shown to also increase your risk for pancreatitis and gallbladder disease.

[20] Amy G. Egan et al., “Pancreatic Safety of Incretin-Based Drugs—FDA and EMA Assessment.” The New England Journal of Medicine 370, no. 9 (February 27, 2014): 794–97. https://doi.org/10.1056/NEJMp1314078.

[21] American Diabetes Association, “Standards of Medical Care in Diabetes—2017 Abridged for Primary Care Providers.” Clinical Diabetes 35, no. 1 (January 1, 2017): 5–26. https://doi.org/10.2337/cd16-0067.

[22] Steven P. Marso et al., “Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.” The New England Journal of Medicine 375, no. 4 (July 28, 2016): 311–22. https://doi.org/10.1056/NEJMoa1603827.

[23] Jean-Luc Faillie et al., “Association of Bile Duct and Gallbladder Diseases with the Use of Incretin-Based Drugs in Patients with Type 2 Diabetes Mellitus.” JAMA Internal Medicine 176, no. 10 (October 1, 2016): 1474–81. https://doi.org/10.1001/jamainternmed.2016.1531.

There are numerous ugly side effects of DPP-- 4 inhibitors, including increased risk for pancreatitis and severe joint pain.

[24] Amy G. Egan et al., “Pancreatic Safety of Incretin-Based Drugs—FDA and EMA Assessment.” The New England Journal of Medicine 370, no. 9 (February 27, 2014): 794–97. https://doi.org/10.1056/NEJMp1314078.

[25] Center for Drug Evaluation and Research, “Drug Safety and Availability—FDA Drug Safety Communication: FDA Warns That DPP-4 Inhibitors for Type 2 Diabetes May Cause Severe Joint Pain.” https://www.fda.gov/Drugs/DrugSafety/ucm459579.htm.

DPP-- 4 inhibitors have also been linked with a significantly increased risk of heart failure.

[26] Benjamin M. Scirica et al., “Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus.” The New England Journal of Medicine 369, no. 14 (October 3, 2013): 1317–26. https://doi.org/10.1056/NEJMoa1307684.

[27] Faiez Zannad et al., “Heart Failure and Mortality Outcomes in Patients with Type 2 Diabetes Taking Alogliptin versus Placebo in EXAMINE: A Multicentre, Randomised, Double-Blind Trial.” The Lancet 385, no. 9982 (May 23, 2015): 2067–76. https://doi.org/10.1016/S0140-6736(14)62225-X.

[28] Jacob A. Udell et al., “Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Moderate or Severe Renal Impairment: Observations from the SAVOR-TIMI 53 Trial.” Diabetes Care 38, no. 4 (April 1, 2015): 696–705. https://doi.org/10.2337/dc14-1850.

SGLT-- 2 inhibitors do just that— they alter the way your kidney functions so that it becomes very good at “wasting” glucose into the toilet, allowing theamount of glucose in your blood to drop 24 hours a day.

[29] Sanjay Kalra, “Sodium Glucose Co-Transporter-2 (SGLT2) Inhibitors: A Review of Their Basic and Clinical Pharmacology.” Diabetes Therapy 5, no. 2 (December 2014): 355–66. https://doi.org/10.1007/s13300-014-0089-4.

They may also increase your risk for limb amputation.

[30] S. Halimi and B. Vergès, “Adverse Effects and Safety of SGLT-2 Inhibitors.” Diabetes & Metabolism 40, no. 6 Suppl 1 (December 2014): S28–S34. https://doi.org/10.1016/S1262-3636(14)72693-X.

[31] Center for Drug Evaluation and Research, “Drug Safety and Availability—FDA Drug Safety Communication: FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings about Too Much Acid in the Blood and Serious Urinary Tract Infections.” https://www.fda.gov/Drugs/DrugSafety/ucm475463.htm.

[32] American Diabetes Association, “Standards of Medical Care in Diabetes—2017 Abridged for Primary Care Providers.” Clinical Diabetes 35, no. 1 (January 1, 2017): 5–26. https://doi.org/10.2337/cd16-0067.

[33] Center for Drug Evaluation and Research, “Drug Safety and Availability—FDA Drug Safety Communication: FDA Revises Label of Diabetes Drug Canagliflozin (Invokana, Invokamet) to Include Updates on Bone Fracture Risk and New Information on Decreased Bone Mineral Density.” https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-revises-label-diabetes-drug-canagliflozin-invokana-invokamet.

[34] Center for Drug Evaluation and Research, “Drug Safety and Availability—FDA Drug Safety Communication: FDA Confirms Increased Risk of Leg and Foot Amputations with the Diabetes Medicine Canagliflozin (Invokana, Invokamet, Invokamet XR).” https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm.

[35] Bruce Neal et al., “Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.” New England Journal of Medicine 377, no. 7 (August 17, 2017): 644–57. https://doi.org/10.1056/NEJMoa1611925.

Because SGLT-- 2 inhibitors target your kidney, SGLT- 2 inhibitors are known to cause acute kidney injury, which can be treated only with dialysis.

[36] Auryan Szalat et al., “Can SGLT2 Inhibitors Cause Acute Renal Failure? Plausible Role for Altered Glomerular Hemodynamics and Medullary Hypoxia.” Drug Safety 41, no. 3 (March 2018): 239–52. https://doi.org/10.1007/s40264-017-0602-6.

[37] Kai Hahn et al., “Acute Kidney Injury from SGLT2 Inhibitors: Potential Mechanisms.” Comments and Opinion. Nature Reviews Nephrology 12, no. 12 (November 16, 2016): 711–12 https://doi.org/10.1038/nrneph.2016.159.

In more than 50 percent of the cases reported to the FDA, “the events of acute kidney injury occurred within 1 month of starting the medication, and most patients improved after stopping it.”

[38] Center for Drug Evaluation and Research, “Drug Safety and Availability—FDA Drug Safety Communication: FDA Strengthens Kidney Warnings for Diabetes Medicines Canagliflozin (Invokana, Invokamet) and Dapagliflozin (Farxiga, Xigduo XR).” https://www.fda.gov/Drugs/DrugSafety/ucm505860.htm.

Thiazolidinediones (TZDs) are a commonly prescribed class of diabetes medication that increase the storage of fatty acids in adipose tissue as well as increase adipose tissue mass, and spare your muscles, liver, and beta cells from the harmful metabolic effects of excess fatty acids.

[39] Jerry R. Greenfield, Donald J. Chisholm, and Department of Endocrinology, “Thiazolidinediones—Mechanisms of Action.” Australian Prescriber 27, no. 3 (June 1, 2004): 67–70. https://doi.org/10.18773/austprescr.2004.059.

[40] Hans Hauner, “The Mode of Action of Thiazolidinediones.” Diabetes/Metabolism Research and Reviews 18 Suppl 2 (April 2002): S10-15. https://doi.org/10.1002/dmrr.249.

Think of TZDs as medications that “keeps fat where it belongs.”

[41] Hannele Yki-Järvinen, “Thiazolidinediones.” New England Journal of Medicine 351, no. 11 (September 9, 2004): 1106–18. https://doi.org/10.1056/NEJMra041001.

TZDs are also known to increase your appetite, by acting directly on receptors in your brain that make you hungry.

[42] Min Lu et al., “Brain PPARγ Promotes Obesity and Is Required for the Insulin-Sensitizing Effect of Thiazolidinediones.” Nature Medicine 17, no. 5 (May 2011): 618–22. https://doi.org/10.1038/nm.2332.

The United States and United Kingdom soon followed by banning sales of troglitazone because it caused liver dysfunction and liver failure in some patients.

[43] Sonal Singh, Yoon K. Loke, and Curt D. Furberg, “Thiazolidinediones and Heart Failure: A Teleo-Analysis.” Diabetes Care 30, no. 8 (August 1, 2007): 2148–53. https://doi.org/10.2337/dc07-0141.

[44] Richard W. Nesto et al., “Thiazolidinedione Use, Fluid Retention, and Congestive Heart Failure: A Consensus Statement from the American Heart Association and American Diabetes Association.” Diabetes Care 27, no. 1 (January 1, 2004): 256–63. https://doi.org/10.2337/diacare.27.1.256.

Amylin analogues are designed to mimic the action of amylin.

[45] Ole Schmitz, Birgitte Brock, and Jorgen Rungby, “Amylin Agonists: A Novel Approach in the Treatment of Diabetes.” Diabetes 53, Suppl 3 (December 1, 2004): S233–S238. https://doi.org/10.2337/diabetes.53.suppl_3.S233.

In your liver, metformin reduces liver glucose export; in your intestine, metformin reduces glucose absorption; and in your muscle, metformin increases glucose uptake.

[46] Graham Rena, D. Grahame Hardie, and Ewan R. Pearson, “The Mechanisms of Action of Metformin.” Diabetologia 60, no. 9 (2017): 1577–85. https://doi.org/10.1007/s00125-017-4342-z.

[47] Amira Klip and Lawrence A. Leiter, “Cellular Mechanism of Action of Metformin.” Diabetes Care 13, no. 6 (June 1, 1990): 696–704. https://doi.org/10.2337/diacare.13.6.696.

One of the most interesting aspects of metformin use is that research indicates that it may actually reduce your risk for cardiovascular disease, especially in obese patients.

[48] Elizabeth Selvin et al., “Cardiovascular Outcomes in Trials of Oral Diabetes Medications: A Systematic Review.” Archives of Internal Medicine 168, no. 19 (October 27, 2008): 2070–80. https://doi.org/10.1001/archinte.168.19.2070.

[49] UK Prospective Diabetes Study (UKPDS) Group, “Effect of Intensive Blood-Glucose Control with Metformin on Complications in Overweight Patients with Type 2 Diabetes (UKPDS 34).” The Lancet 352, no. 9131 (September 12, 1998): 854–65. https://doi.org/10.1016/S0140-6736(98)07037-8.

Pharmaceutical medications may help to control your blood glucose, improve insulin secretion, reduce your blood pressure, reduce your cholesterol, and reduce pain, but intensive treatment of blood glucose with medications can increase your risk for heart failure, liver failure, kidney failure, stroke, and even death, and that’s certainly nothing to take lightly.

[50] Partha Sardar et al., “Effect of Intensive Versus Standard Blood Glucose Control in Patients with Type 2 Diabetes Mellitus in Different Regions of the World: Systematic Review and Meta-Analysis of Randomized Controlled Trials.” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 4, no. 5 (May 14, 2015). https://doi.org/10.1161/JAHA.114.001577.

[51] Edoardo Mannucci et al., “Is Glucose Control Important for Prevention of Cardiovascular Disease in Diabetes?” Diabetes Care 36, Suppl 2 (August 1, 2013): S259–S263. https://doi.org/10.2337/dcS13-2018.

[52] Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study Group et al., “Effects of Intensive Glucose Lowering in Type 2 Diabetes.” The New England Journal of Medicine 358, no. 24 (June 12, 2008): 2545–59. https://doi.org/10.1056/NEJMoa0802743.

[53] ACCORD Study Group et al., “Long-Term Effects of Intensive Glucose Lowering on Cardiovascular Outcomes.” The New England Journal of Medicine 364, no. 9 (March 3, 2011): 818–28. https://doi.org/10.1056/NEJMoa1006524.

[54] “The University Group Diabetes Program. A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients with Adult-Onset Diabetes. V. Evaluation of Pheniformin Therapy.” Diabetes 24, Suppl 1 (1975): 65–184. https://www.ncbi.nlm.nih.gov/pubmed/1090475.

Including legumes in your breakfast meal is a great way to control your blood glucose for many hours in the beginning of the day.

[1] Furio Brighenti et al., “Colonic Fermentation of Indigestible Carbohydrates Contributes to the Second-Meal Effect.” The American Journal of Clinical Nutrition 83, no. 4 (April 2006): 817–22. https://doi.org/10.1093/ajcn/83.4.817.

[2] D. J. Jenkins et al., “Exceptionally Low Blood Glucose Response to Dried Beans: Comparison with Other Carbohydrate Foods.” British Medical Journal 281, no. 6240 (August 30, 1980): 578–80. 10.1136/bmj.281.6240.578.

[3] D. J. Jenkins et al., “Slow Release Dietary Carbohydrate Improves Second Meal Tolerance.” The American Journal of Clinical Nutrition 35, no. 6 (June 1982): 1339–46. https://doi.org/10.1093/ajcn/35.6.1339.

[4] Rebecca C. Mollard et al., “First and Second Meal Effects of Pulses on Blood Glucose, Appetite, and Food Intake at a Later Meal.” Applied Physiology, Nutrition, and Metabolism 36, no. 5 (October 2011): 634–42. https://doi.org/10.1139/h11-071.

[5] T. M. Wolever et al., “Second-Meal Effect: Low-Glycemic-Index Foods Eaten at Dinner Improve Subsequent Breakfast Glycemic Response.” The American Journal of Clinical Nutrition 48, no. 4 (October 1988): 1041–47. https://doi.org/10.1093/ajcn/48.4.1041.

Including these plants in your daily regimen can make a big difference in your blood glucose control; they also possess potent antioxidant, cholesterol-and lipid-lowering activity.

[6] D. K. Patel et al., “An Overview on Antidiabetic Medicinal Plants Having Insulin Mimetic Property.” Asian Pacific Journal of Tropical Biomedicine 2, no. 4 (April 2012): 320–30. https://doi.org/10.1016/S2221-1691(12)60032-X.

[7] Jun Yin, Huili Xing, and Jianping Ye, “Efficacy of Berberine in Patients with Type 2 Diabetes Mellitus.” Metabolism: Clinical and Experimental 57, no. 5 (May 2008): 712–17. https://doi.org/10.1016/j.metabol.2008.01.013.

[8] J. K. Grover, S. Yadav, and V. Vats, “Medicinal Plants of India with Anti-Diabetic Potential.” Journal of Ethnopharmacology 81, no. 1 (June 1, 2002): 81–100. https://doi.org/10.1016/S0378-8741(02)00059-4.

[9] E. Nemes-Nagy et al., “Effect of a Dietary Supplement Containing Blueberry and Sea Buckthorn Concentrate on Antioxidant Capacity in Type 1 Diabetic Children.” Acta Physiologica Hungarica 95, no. 4 (December 2008): 383–93. https://doi.org/10.1556/APhysiol.95.2008.4.5.

[10] Syed Ibrahim Rizvi and Neetu Mishra, “Traditional Indian Medicines Used for the Management of Diabetes Mellitus.” Journal of Diabetes Research 2013 (2013): Art. ID 712092. https://doi.org/10.1155/2013/712092.

Amla has been shown to be more effective than some pharmaceutical medications in reducing blood glucose, cholesterol, and blood pressure, and is considered to be the most powerful cholesterol-reducing food on the planet and one of the most powerful antidiabetic foods on the planet.

[11] V. Khan et al., “A Pharmacological Appraisal of Medicinal Plants with Antidiabetic Potential.” Journal of Pharmacy and Bioallied Sciences 4, no. 1 (January 2012): 27–42. https://www.ncbi.nlm.nih.gov/pubmed/22368396.

[12] Muhammad Shoaib Akhtar et al., “Effect of Amla Fruit (Emblica Officinalis Gaertn.) on Blood Glucose and Lipid Profile of Normal Subjects and Type 2 Diabetic Patients.” International Journal of Food Sciences and Nutrition 62, no. 6 (September 2011): 609–16. https://doi.org/10.3109/09637486.2011.560565.

[13] Prasan R. Bhandari and Mohammad Ameeruddin Kamdod, “Emblica Officinalis (Amla): A Review of Potential Therapeutic Applications.” International Journal of Green Pharmacy 6, no. 4 (2012). https://greenpharmacy.info/index.php/ijgp/article/view/272.

[14] Monica H. Carlsen et al., “The Total Antioxidant Content of More than 3100 Foods, Beverages, Spices, Herbs and Supplements Used Worldwide.” Nutrition Journal 9 (January 22, 2010): 3. https://doi.org/10.1186/1475-2891-9-3.

[15] Jason Jerome D’souza et al., “Anti-Diabetic Effects of the Indian Indigenous Fruit Emblica officinalis Gaertn: Active Constituents and Modes of Action.” Food & Function 5, no. 4 (April 2014): 635–44. https://doi.org/10.1039/c3fo60366k.

[16] Nishat Fatima, Usharani Pingali, and N. Muralidhar, “Study of Pharmacodynamic Interaction of Phyllanthus Emblica Extract with Clopidogrel and Ecosprin in Patients with Type II Diabetes Mellitus.” Phytomedicine 21, no. 5 (April 15, 2014): 579–85. https://doi.org/10.1016/j.phymed.2013.10.024.

[17] Nishat Fatima, Usharani Pingali, and Raveendranadh Pilli, “Evaluation of Phyllanthus Emblica Extract on Cold Pressor Induced Cardiovascular Changes in Healthy Human Subjects.” Pharmacognosy Research 6, no. 1 (2014): 29–35. https://doi.org/10.4103/0974-8490.122914.

[18] Biswas Gopa, Jagatkumar Bhatt, and Kovur G. Hemavathi, “A Comparative Clinical Study of Hypolipidemic Efficacy of Amla (Emblica officinalis) with 3-Hydroxy-3-Methylglutaryl-Coenzyme-A Reductase Inhibitor Simvastatin.” Indian Journal of Pharmacology 44, no. 2 (March 2012): 238–42. https://doi.org/10.4103/0253-7613.93857.

[19] Shirin Hasani-Ranjbar et al., “The Efficacy and Safety of Herbal Medicines Used in the Treatment of Hyperlipidemia: A Systematic Review.” Current Pharmaceutical Design 16, no. 26 (2010): 2935–47. 10.2174/138161210793176464.

[20] A. Jacob et al., “Effect of the Indian Gooseberry (Amla) on Serum Cholesterol Levels in Men Aged 35–55 Years.” European Journal of Clinical Nutrition 42, no. 11 (November 1988): 939–44. https://www.ncbi.nlm.nih.gov/pubmed/3250870.

[21] Savita Khanna et al., “Supplementation of a Standardized Extract from Phyllanthus Emblica Improves Cardiovascular Risk Factors and Platelet Aggregation in Overweight/Class-1 Obese Adults.” Journal of Medicinal Food 18, no. 4 (April 2015): 415–20. https://doi.org/10.1089/jmf.2014.0178.

[22] Mani Krishnaveni and Sankaran Mirunalini, “Therapeutic Potential of Phyllanthus Emblica (Amla): The Ayurvedic Wonder.” Journal of Basic and Clinical Physiology and Pharmacology 21, no. 1 (2010): 93–105. https://www.ncbi.nlm.nih.gov/pubmed/20506691.

[23] AbulKalam Najmi et al., “A Pharmacological Appraisal of Medicinal Plants with Antidiabetic Potential.” Journal of Pharmacy and Bioallied Sciences 4, no. 1 (2012): 27. https://doi.org/10.4103/0975-7406.92727.

[24] Snehal S. Patel et al., “Experimental Study on Effect of Hydroalcoholic Extract of Emblica Officinalis Fruits on Glucose Homeostasis and Metabolic Parameters.” Ayu 34, no. 4 (October 2013): 440–44. https://doi.org/10.4103/0974-8520.127731.

[25] Pingali Usharani, Nishat Fatima, and Nizampatnam Muralidhar, “Effects of Phyllanthus Emblica Extract on Endothelial Dysfunction and Biomarkers of Oxidative Stress in Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind, Controlled Study.” Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 6 (July 26, 2013): 275–84. https://doi.org/10.2147/DMSO.S46341.

LDL cholesterol was reduced by more than 40 percent in 3 weeks, triglycerides were reduced by more than 45 percent, and HDL cholesterol increased by more than 25 percent.

[26] Muhammad Shoaib Akhtar et al., “Effect of Amla Fruit (Emblica officinalis Gaertn.) on Blood Glucose and Lipid Profile of Normal Subjects and Type 2 Diabetic Patients.”

Simvastatin treatment was found to be more effective than amla at reducing VLDL cholesterol and triglycerides.

[27] Gopa, Bhatt, and Hemavathi, “A Comparative Clinical Study of Hypolipidemic Efficacy of Amla (Emblica Officinalis) with 3-Hydroxy-3-Methylglutaryl-Coenzyme-A Reductase Inhibitor Simvastatin.”

The Journal of the American Medical Association in 2011 including more than 32,000 people found that statin medication increased the risk of developing type 2 diabetes by approximately 12 percent.

[28] Naveed Sattar et al., “Statins and Risk of Incident Diabetes: A Collaborative Meta-Analysis of Randomised Statin Trials.” The Lancet 375, no. 9716 (February 27, 2010): 735–42. https://doi.org/10.1016/S0140-6736(09)61965-6.

[29] David Preiss et al., “Risk of Incident Diabetes with Intensive-Dose Compared with Moderate-Dose Statin Therapy: A Meta-Analysis.” JAMA 305, no. 24 (June 22, 2011): 2556–64. https://doi.org/10.1001/jama.2011.860.

Celiac disease affects roughly one in a hundred people (1 percent), and roughly one in a thousand (0.1 percent) may suffer from a condition known as non-celia gluten sensitivity (NCGS), a mild intolerance to gluten that is not autoimmune by nature.

[30] Pasquale Mansueto et al., “Non-Celiac Gluten Sensitivity: Literature Review.” Journal of the American College of Nutrition 33, no. 1 (2014): 39–54. https://doi.org/10.1080/07315724.2014.869996.

[31] Daniel F. McCarter, “Non-Celiac Gluten Sensitivity: Important Diagnosis or Dietary Fad?” n.d., 2. https://www.aafp.org/afp/2014/0115/p82.html.

In some individuals, the gliadin fraction of gluten triggers an autoimmune reaction that can result in the destruction of insulin-producing beta cells in your pancreas.

[32] Jeroen Visser et al., “Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms.” Annals of the New York Academy of Sciences 1165 (May 2009): 195–205. https://doi.org/10.1111/j.1749-6632.2009.04037.x.

[33] A. Fasano et al., “Zonulin, a Newly Discovered Modulator of Intestinal Permeability, and Its Expression in Coeliac Disease.” The Lancet 355, no. 9214 (April 29, 2000): 1518–19. https://doi.org/10.1016/S0140-6736(00)02169-3.

If you have a compromised intestinal barrier, then every time you eat food, partially digested proteins leak into circulation, resulting in a chronic state of inflammation that either raises your risk for autoimmune disease or exacerbates your preexisting autoimmune disease.

[34] Alessio Fasano, “Zonulin, Regulation of Tight Junctions, and Autoimmune Diseases.” Annals of the New York Academy of Sciences 1258, no. 1 (July 2012): 25–33. https://doi.org/10.1111/j.1749-6632.2012.06538.x.

Researchers have discovered that a large proportion of people with type 1 diabetes also have impaired gut function, suggesting that an impaired intestinal barrier may actually be a prerequisite for the development of type 1 diabetes.

[35] Anna Sapone et al., “Zonulin Upregulation Is Associated with Increased Gut Permeability in Subjects with Type 1 Diabetes and Their Relatives.” Diabetes 55, no. 5 (May 2006): 1443–49. 10.2337/db05-1593.

[36] Alessio Fasano, “Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer.” Physiological Reviews 91, no. 1 (January 2011): 151–75. https://doi.org/10.1152/physrev.00003.2008.

Data from more than 300,000 participants shows that people who consume the most soda are 26 percent more likely to develop type 2 diabetes than those who drink the least.

[37] Vasanti S. Malik et al., “Sugar-Sweetened Beverages and Risk of Metabolic Syndrome and Type 2 Diabetes: A Meta-Analysis.” Diabetes Care 33, no. 11 (November 2010): 2477–83. https://doi.org/10.2337/dc10-1079.

Data from the Nurses’ Health Study and Health Professionals Follow-Up Study demonstrate that regular consumption of sugar-sweetened sodas increased the risk of cancers such as non-Hodgkin’s lymphoma and multiple myeloma.

[38] Dagfinn Aune, “Soft Drinks, Aspartame, and the Risk of Cancer and Cardiovascular Disease.” The American Journal of Clinical Nutrition 96, no. 6 (December 1, 2012): 1249–51. https://doi.org/10.3945/ajcn.112.051417.

A single cup of coffee containing 80 mg of caffeine has been shown to dramatically reduce the ability of blood vessels to dilate by as much as 72 percent, depending on how many cups you drink.

[39] Chris M. Papamichael et al., “Effect of Coffee on Endothelial Function in Healthy Subjects: The Role of Caffeine.” Clinical Science 109, no. 1 (July 1, 2005): 55–60. https://doi.org/10.1042/CS20040358.

Both of these findings suggest that caffeinated coffee can impair both cardiovascular health and glucose metabolism.

[40] S. Buscemi et al., “Dose-Dependent Effects of Decaffeinated Coffee on Endothelial Function in Healthy Subjects.” European Journal of Clinical Nutrition 63, no. 10 (October 2009): 1200–1205. https://doi.org/10.1038/ejcn.2009.51.

[41] S. Buscemi et al., “Acute Effects of Coffee on Endothelial Function in Healthy Subjects.” European Journal of Clinical Nutrition 64, no. 5 (May 2010): 483–89. https://doi.org/10.1038/ejcn.2010.9.

Researchers have found that drinking caffeinated coffee improves fasting blood glucose and blood glucose control and reduces hyperinsulinemia in both men and women.

[42] S. Bidel et al., “Effects of Coffee Consumption on Glucose Tolerance, Serum Glucose and Insulin Levels—a Cross-Sectional Analysis.” Hormone and Metabolic Research 38, no. 1 (January 2006): 38–43. https://doi.org/10.1055/s-2006-924982.

Another research group found that those who drank 5 cups of caffeinated coffee or more per day experienced 1.5 percent lower fasting blood glucose and 4.3 percent lower post-meal blood glucose in comparison with those who did not drink coffee on a daily basis.

[43] T. Yamaji et al., “Coffee Consumption and Glucose Tolerance Status in Middle-Aged Japanese Men.” Diabetologia 47, no. 12 (December 2004): 2145–51. https://doi.org/10.1007/s00125-004-1590-5.

In addition, subjects who drank more caffeinated coffee were more insulin sensitive.

[44] E. E. Agardh et al., “Coffee Consumption, Type 2 Diabetes and Impaired Glucose Tolerance in Swedish Men and Women.” Journal of Internal Medicine 255, no. 6 (June 2004): 645–52. https://doi.org/10.1111/j.1365-2796.2004.01331.x.

A study on Dutch men and women found that those who drank 7 or more cups of caffeinated coffee per day had a 31 percent reduced risk of developing type 2 diabetes compared to those who drank 2 or less cups per day.

[45] R. M. van Dam et al., “Coffee Consumption and Incidence of Impaired Fasting Glucose, Impaired Glucose Tolerance, and Type 2 Diabetes: The Hoorn Study.” Diabetologia 47, no. 12 (December 2004): 2152–59. https://doi.org/10.1007/s00125-004-1573-6.

Adding green tea to your diet is a simple and excellent way to increase your intake of antioxidants, keep your blood vessels flexible, and prevent the development of atherosclerosis.

[46] Draženka Komes et al., “Green Tea Preparation and Its Influence on the Content of Bioactive Compounds.” Food Research International 43, no. 1 (January 2010): 167–76. https://doi.org/10.1016/j.foodres.2009.09.022.

Research has shown that most people eat approximately the same weight of food on a daily basis, with very small day-to-day variations.

[1] K. H. Duncan, J. A. Bacon, and R. L. Weinsier, “The Effects of High and Low Energy Density Diets on Satiety, Energy Intake, and Eating Time of Obese and Nonobese Subjects.” The American Journal of Clinical Nutrition 37, no. 5 (May 1983): 763–67. https://doi.org/10.1093/ajcn/37.5.763.

Studies have shown that people eat about 3 to 5 pounds of food per day, regardless of whether it contains foods with a low, medium, or high calorie density.

[2] E. A. Bell et al., “Energy Density of Foods Affects Energy Intake in Normal-Weight Women.” The American Journal of Clinical Nutrition 67, no. 3 (March 1998): 412–20. https://doi.org/10.1093/ajcn/67.3.412.

Therefore, if you strategically eat green light foods with a low calorie density, by the time you’re full you will have eaten substantially fewer total calories than if you ate foods in the yellow or red light categories.

[3] John M. de Castro, “Macronutrient and Dietary Energy Density Influences on the Intake of Free-Living Humans.” Appetite 46, no. 1 (January 2006): 1–5. https://doi.org/10.1016/j.appet.2005.05.005.

This research shows that you can cut out as many as 2,000 calories per day by eating foods low in calorie density, and you’re likely to feel just as satisfied as if you were eating foods with a high calorie density.

[4] B. J. Rolls et al., “Energy Density but Not Fat Content of Foods Affected Energy Intake in Lean and Obese Women.” The American Journal of Clinical Nutrition 69, no. 5 (May 1999): 863–71. https://doi.org/10.1093/ajcn/69.5.863.

When you eat food, these neurons are in constant communication with your brain to make minute-by-minute decisions about when to start eating, when to slow down, and when to stop eating altogether.

[5] Erika K. Williams et al., “Sensory Neurons That Detect Stretch and Nutrients in the Digestive System.” Cell 166, no. 1 (June 30, 2016): 209–21. https://doi.org/10.1016/j.cell.2016.05.011.

Nerves in your stomach and small intestine secrete serotonin, which not only makes you feel happy but also propels partially digested food through your small intestine and tells your stomach to wait before releasing more food downstream.

[6] Paul P. Bertrand and Rebecca L. Bertrand, “Serotonin Release and Uptake in the Gastrointestinal Tract.” Autonomic Neuroscience: Basic & Clinical 153, no. 1–2 (September 2, 2009): 47–57. https://doi.org/10.1016/j.autneu.2009.08.002.

Scientists believe that because bulk is the most effective satiety signal, the amount of bulk in our food is the most important determinant of how satisfied you feel after a meal.

[7] B. J. Rolls et al., “Volume of Food Consumed Affects Satiety in Men.” The American Journal of Clinical Nutrition 67, no. 6 (June 1998): 1170–77. https://doi.org/10.1093/ajcn/67.6.1170.

Not only do these short-chain fatty acids boost immune function, fight infections, improve insulin signaling, and promote insulin sensitivity, they also communicate with your brain to control how much food you eat.

[8] Karen K. Ryan and Randy J. Seeley, “Food as a Hormone.” Science 339, no. 6122 (February 22, 2013): 918–19. https://doi.org/10.1126/science.1234062.

[9] Trond Ulven, “Short-Chain Free Fatty Acid Receptors FFA2/GPR43 and FFA3/GPR41 as New Potential Therapeutic Targets.” Frontiers in Endocrinology 3 (2012): 111. https://doi.org/10.3389/fendo.2012.00111.

Researchers have found that adding fiber-rich foods to your meals and significantly increasing your total fiber intake can make a dramatic difference in how full you (and your gut bacteria) feel at all times.

[10] Michelle L. Sleeth et al., “Free Fatty Acid Receptor 2 and Nutrient Sensing: A Proposed Role for Fibre, Fermentable Carbohydrates and Short-Chain Fatty Acids in Appetite Regulation.” Nutrition Research Reviews 23, no. 1 (June 2010): 135–45. https://doi.org/10.1017/S0954422410000089.

Many people who adopt a low-carbohydrate or ketogenic diet find that they are less hungry than before, and as a result, they eat fewer total calories, which can promote rapid weight loss.

[11] Guenther Boden et al., “Effect of a Low-Carbohydrate Diet on Appetite, Blood Glucose Levels, and Insulin Resistance in Obese Patients with Type 2 Diabetes,” Annals of Internal Medicine 142, no. 6 (March 15, 2005): 403–11.10.7326/0003-4819-142-6-200503150-00006.

[12] Alexandra M. Johnstone et al., “Effects of a High-Protein Ketogenic Diet on Hunger, Appetite, and Weight Loss in Obese Men Feeding Ad Libitum.” The American Journal of Clinical Nutrition 87, no. 1 (January 1, 2008): 44–55. https://doi.org/10.1093/ajcn/87.1.44.

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Drinking water before a meal does not have the same effect on satiety as eating foods with a high water content.

[14] B. J. Rolls, E. A. Bell, and M. L. Thorwart, “Water Incorporated into a Food but Not Served with a Food Decreases Energy Intake in Lean Women.” The American Journal of Clinical Nutrition 70, no. 4 (October 1999): 448–55. https://doi.org/10.1093/ajcn/70.4.448.

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[1] Guenther Boden, “Fatty Acid-Induced Inflammation and Insulin Resistance in Skeletal Muscle and Liver.” Current Diabetes Reports 6, no. 3 (June 2006): 177–81. https://www.ncbi.nlm.nih.gov/pubmed/16898568.

In order to survive long periods of limited food availability, our human ancestors often fasted for extended periods of time, sometimes up to ten days in a row.

[1] Leo Pruimboom et al., “Influence of a 10-Day Mimic of Our Ancient Lifestyle on Anthropometrics and Parameters of Metabolism and Inflammation: The ‘Study of Origin.’” BioMed Research International 2016 (2016): 6935123. https://doi.org/10.1155/2016/6935123.

[2] Jake Jacobson, “Increase Your Healthspan by Mimicking Hunter Gathers’ Meal Frequency.” Journal of Evolution and Health 2, no. 1 (March 14, 2017). https://doi.org/10.15310/2334-3591.1063.

[3] Elizabeth Marshall Thomas, The Old Way: A Story of the First People. New York: Picador, 2007.

Hard at work in a science lab at Cornell University, Clive McCay and his colleagues were the first to observe that restricting the calorie intake of laboratory rats allowed them to live longer than their ad libitum counterparts, who were given access to food twenty-four hours a day.

[4] C. M. McCay et al., “Retarded Growth, Life Span, Ultimate Body Size and Age Changes in the Albino Rat After Feeding Diets Restricted in Calories.” The Journal of Nutrition 18, no. 1 (July 1, 1939): 1–13. https://doi.org/10.1111/j.1753-4887.1975.tb05227.x.

McCay and his colleagues didn’t realize it at the time, but what seemed like a simple observation would unlock an explosion of scientific research that would begin to explain biological mechanisms responsible for reducing the rate of aging, increasing longevity, improving memory, and stimulating weight loss, while simultaneously reducing the risk for chronic metabolic conditions such as heart disease, cancer, and type 2 diabetes.

[5] Roger B. McCay McDonald and Jon J. Ramsey, “Honoring Clive McCay and 75 Years of Calorie Restriction Research.” The Journal of Nutrition 140, no. 7 (July 2010): 1205–10. https://doi.org/10.3945/jn.110.122804.

Even though their initial observations came from experiments with laboratory rodents, in almost every organism studied to date (including yeast, worms, flies, mice, rats, and most recently, monkeys), calorie restriction has been shown to increase longevity and prolong or delay the onset of many age-related diseases.

[6] Robin J. Mockett et al., “Effects of Caloric Restriction Are Species-Specific.” Biogerontology 7, no. 3 (June 2006): 157–60. https://doi.org/10.1007/s10522-006-9004-3.

They discovered that calorie restriction dramatically increases fat oxidation and slows the rate at which mitochondrial proteins are synthesized and degraded.

[7] Matthew D. Bruss et al., “Calorie Restriction Increases Fatty Acid Synthesis and Whole Body Fat Oxidation Rates.” American Journal of Physiology: Endocrinology and Metabolism 298, no. 1 (January 2010): E108-116. https://doi.org/10.1152/ajpendo.00524.2009.

[8] John C. Price et al., “The Effect of Long Term Calorie Restriction on in Vivo Hepatic Proteostatis: A Novel Combination of Dynamic and Quantitative Proteomics.” Molecular & Cellular Proteomics 11, no. 12 (December 2012): 1801–14. https://doi.org/10.1074/mcp.M112.021204.

[9] Donald J. Roohk et al., “Dexamethasone-Mediated Changes in Adipose Triacylglycerol Metabolism Are Exaggerated, Not Diminished, in the Absence of a Functional GR Dimerization Domain.” Endocrinology 154, no. 4 (April 2013): 1528–39. https://doi.org/10.1210/en.2011-1047

That calorie restriction is one of the most powerful methods of improving all aspects of glucose metabolism, including weight loss, reduced fasting blood glucose, reduced post-meal blood glucose, reduced insulin requirements, increased mitochondrial function, reduced oxidative stress, and dramatically increased insulin sensitivity.

[10] Piero Ruggenenti et al., “Renal and Systemic Effects of Calorie Restriction in Patients With Type 2 Diabetes with Abdominal Obesity: A Randomized Controlled Trial.” Diabetes 66, no. 1 (January 2017): 75–86. https://doi.org/10.2337/db16-0607.

[11] Yukiko Minamiyama et al., “Calorie Restriction Improves Cardiovascular Risk Factors via Reduction of Mitochondrial Reactive Oxygen Species in Type II Diabetic Rats.” The Journal of Pharmacology and Experimental Therapeutics 320, no. 2 (February 2007): 535–43. https://doi.org/10.1124/jpet.106.110460.

[12] Carrie E. McCurdy and Gregory D. Cartee, “Akt2 Is Essential for the Full Effect of Calorie Restriction on Insulin-Stimulated Glucose Uptake in Skeletal Muscle.” Diabetes 54, no. 5 (May 1, 2005): 1349–56. https://doi.org/10.2337/diabetes.54.5.1349.

[13] David J. Dean et al., “Calorie Restriction Increases Cell Surface GLUT-4 in Insulin-Stimulated Skeletal Muscle.” American Journal of Physiology: Endocrinology and Metabolism 275, no. 6 (December 1, 1998): E957–64. 10.1152/ajpendo.1998.275.6.E957.

[14] Robert T. Davidson, Edward B. Arias, and Gregory D. Cartee, “Calorie Restriction Increases Muscle Insulin Action but Not IRS-1-, IRS-2-, or Phosphotyrosine-PI 3-Kinase.” American Journal of Physiology: Endocrinology and Metabolism 282, no. 2 (February 1, 2002): E270–76. https://doi.org/10.1152/ajpendo.00232.2001.

[15] G. D. Cartee, E. W. Kietzke, and C. Briggs-Tung, “Adaptation of Muscle Glucose Transport with Caloric Restriction in Adult, Middle-Aged, and Old Rats.” American Journal of Physiology: Regulatory, Integrative and Comparative Physiology 266, no. 5 (May 1, 1994): R1443–47.10.1152/ajpregu.1994.266.5.R1443.

[16] Rocco Barazzoni et al., “Moderate Caloric Restriction, but Not Physiological Hyperleptinemia Per Se, Enhances Mitochondrial Oxidative Capacity in Rat Liver and Skeletal Muscle—Tissue-Specific Impact on Tissue Triglyceride Content and AKT Activation.” Endocrinology 146, no. 4 (April 2005): 2098–2106. https://doi.org/10.1210/en.2004-1396.

A 20 to 50 percent reduction in calorie intake has been shown to increase lifespan by up to 50 percent and prevent or delay the onset of many chronic diseases including obesity, type 2 diabetes, cancer, nephropathy, cardiomyopathy, neurodegeneration, and multiple autoimmune diseases.

[17] Jasper Most et al., “Calorie Restriction in Humans: An Update.” Ageing Research Reviews 39 (October 2017): 36–45. https://doi.org/10.1016/j.arr.2016.08.005.

[18] Leonie K. Heilbronn and Eric Ravussin, “Calorie Restriction and Aging: Review of the Literature and Implications for Studies in Humans.” The American Journal of Clinical Nutrition 78, no. 3 (September 2003): 361–69. https://doi.org/10.1093/ajcn/78.3.361.

[19] Julie A. Mattison et al., “Impact of Caloric Restriction on Health and Survival in Rhesus Monkeys: The NIA Study.” Nature 489, no. 7415 (September 13, 2012). https://doi.org/10.1038/nature11432.

[20] Ricki J. Colman et al., “Caloric Restriction Reduces Age-Related and All-Cause Mortality in Rhesus Monkeys.” Nature Communications 5 (April 1, 2014): 3557. https://doi.org/10.1038/ncomms4557.

It may seem illogical, but scientists have uncovered that reducing food intake for extended periods of time allows blood vessels everywhere to relax, which in turn reduces blood pressure.

[21] C. F. García-Prieto et al., “Mild Caloric Restriction Reduces Blood Pressure and Activates Endothelial AMPK-PI3K-Akt-ENOS Pathway in Obese Zucker Rats.” Vascular Pharmacology 65–66 (February 1, 2015): 3–12. https://doi.org/10.1016/j.vph.2014.12.001.

Studies have shown that calorie restriction improves the function of the endothelial cells that line the inside of blood vessels, improving their ability to manufacture nitric oxide (NO), a gas that allows blood vessels to dilate.

[22] K. Korybalska et al., “Weight Loss-Dependent and -Independent Effects of Moderate Calorie Restriction on Endothelial Cell Markers in Obesity.” Journal of Physiology and Pharmacology 68, no. 4 (August 2017): 597–608. https://www.jpp.krakow.pl/journal/archive/08_17/pdf/597_08_17_article.pdf

[23] Catarina Rippe et al., “Short-Term Calorie Restriction Reverses Vascular Endothelial Dysfunction in Old Mice by Increasing Nitric Oxide and Reducing Oxidative Stress.” Aging Cell 9, no. 3 (June 2010): 304–12. https://doi.org/10.1111/j.1474-9726.2010.00557.x.

[24] Anthony J. Donato et al., “Life-Long Caloric Restriction Reduces Oxidative Stress and Preserves Nitric Oxide Bioavailability and Function in Arteries of Old Mice.” Aging Cell 12, no. 5 (October 2013): 772–83. https://doi.org/10.1111/acel.12103.

[25] Michela Zanetti et al., “Caloric Restriction Improves Endothelial Dysfunction During Vascular Aging: Effects on Nitric Oxide Synthase Isoforms and Oxidative Stress in Rat Aorta.” Experimental Gerontology 45, no. 11 (November 2010): 848–55. https://doi.org/10.1016/j.exger.2010.07.002.

[26] Juha Ketonen, Taru Pilvi, and Eero Mervaala, “Caloric Restriction Reverses High-Fat Diet-Induced Endothelial Dysfunction and Vascular Superoxide Production in C57Bl/6 Mice.” Heart and Vessels 25, no. 3 (May 2010): 254–62. https://doi.org/10.1007/s00380-009-1182-x.

And in addition to increased NO synthesis, negative calorie balance reduces cardiovascular inflammation, which increases blood flow to tissues.

[27] Yue Liu, HouZao Chen, and DePei Liu, “Mechanistic Perspectives of Calorie Restriction on Vascular Homeostasis.” Science China. Life Sciences 57, no. 8 (August 2014): 742–54. https://doi.org/10.1007/s11427-014-4709-z.

[28] Laura Castello et al., “Calorie Restriction Protects Against Age-Related Rat Aorta Sclerosis.” The FASEB Journal 19, no. 13 (November 2005): 1863–65. https://doi.org/10.1096/fj.04-2864fje.

When it comes to the direct benefits of negative calorie balance on your risk for heart disease, studies show that calorie restriction substantially reduces LDL cholesterol and triglycerides and directly improves the function of your heart muscle.

[29] Luigi Fontana et al. and Washington University School of Medicine CALERIE Group, “Calorie Restriction or Exercise: Effects on Coronary Heart Disease Risk Factors. A Randomized, Controlled Trial.” American Journal of Physiology: Endocrinology and Metabolism 293, no. 1 (July 2007): E197-202. https://doi.org/10.1152/ajpendo.00102.2007.

[30] Cynthia M. Kroeger et al., “Improvement in Coronary Heart Disease Risk Factors during an Intermittent Fasting/Calorie Restriction Regimen: Relationship to Adipokine Modulations.” Nutrition & Metabolism 9, no. 1 (October 31, 2012): 98. https://doi.org/10.1186/1743-7075-9-98.

[31] Wei Yu et al., “Moderate Calorie Restriction Attenuates Age-Associated Alterations and Improves Cardiac Function by Increasing SIRT1 and SIRT3 Expression.” Molecular Medicine Reports 18, no. 4 (October 2018): 4087–94. https://doi.org/10.3892/mmr.2018.9390.

[32] Yuji Hirowatari et al., “Effect of Dietary Modification by Calorie Restriction on Cholesterol Levels in Lipoprotein(a) and Other Lipoprotein Classes.” Annals of Clinical Biochemistry 54, no. 5 (September 2017): 567–76. https://doi.org/10.1177/0004563216672247.

In laboratory animals, negative calorie balance has been demonstrated to be a very effective strategy to prevent and reverse cancer.

[33] Valter D. Longo and Luigi Fontana, “Calorie Restriction and Cancer Prevention: Metabolic and Molecular Mechanisms.” Trends in Pharmacological Sciences 31, no. 2 (February 2010): 89–98. https://doi.org/10.1016/j.tips.2009.11.004.

In monkeys, restricting calorie intake by 50 percent significantly reduces the incidence of cancer.

[34] Ricki J. Colman et al., “Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys.” Science 325, no. 5937 (July 10, 2009): 201–204. https://doi.org/10.1126/science.1173635.

A large body of evidence suggests that negative calorie balance in humans shares many of the same molecular mechanisms found in other mammals, and researchers are very excited to learn more because calorie restrictions widely known to be the most reproducible way to increase lifespan and protect against cancer in mammals.

[35] Luigi Fontana and Samuel Klein, “Aging, Adiposity, and Calorie Restriction.” JAMA 297, no. 9 (March 7, 2007): 986–94. https://doi.org/10.1001/jama.297.9.986.

[36] Stephen D. Hursting et al., “Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans.” Annual Review of Medicine 54 (2003): 131–52. https://doi.org/10.1146/annurev.med.54.101601.152156.

Testing how calorie restriction affects cancer incidence in humans is significantly more challenging than it is in other mammals because it is difficult to conduct long-term survival studies due to compliance, cost, and ethical considerations.

[37] K. A. Al-Regaiey, “The Effects of Calorie Restriction on Aging: A Brief Review.” European Review for Medical and Pharmacological Sciences 20, no. 11 (2016): 2468–73. https://www.ncbi.nlm.nih.gov/pubmed/27338076.

Despite this, data from studies of long-term calorie restriction in humans suggest that the molecular mechanisms are very similar to those found in rodents and monkeys.

[38] Luigi Fontana et al., “Long-Term Calorie Restriction Is Highly Effective in Reducing the Risk for Atherosclerosis in Humans.” Proceedings of the National Academy of Sciences of the United States of America 101, no. 17 (April 27, 2004): 6659–63. https://doi.org/10.1073/pnas.0308291101.

[39] Timothy E. Meyer et al., “Long-Term Caloric Restriction Ameliorates the Decline in Diastolic Function in Humans.” Journal of the American College of Cardiology 47, no. 2 (January 17, 2006): 398–402. https://doi.org/10.1016/j.jacc.2005.08.069.

[40] Luigi Fontana et al., “Effect of Long-Term Calorie Restriction with Adequate Protein and Micronutrients on Thyroid Hormones.” The Journal of Clinical Endocrinology and Metabolism 91, no. 8 (August 2006): 3232–35. https://doi.org/10.1210/jc.2006-0328.

[41] Luigi Fontana, Samuel Klein, and John O. Holloszy, “Effects of Long-Term Calorie Restriction and Endurance Exercise on Glucose Tolerance, Insulin Action, and Adipokine Production.” Age 32, no. 1 (March 2010): 97–108. https://doi.org/10.1007/s11357-009-9118-z.

There are many reasons that calorie restriction is very powerful at reducing cancer incidence, resulting from reduced body weight, reduced inflammatory cytokines, reduced growth factors, reduced oxidative stress, improved DNA repair processes, and reduced cell replication rates.

[42] F. X. Pi-Sunyer, “A Review of Long-Term Studies Evaluating the Efficacy of Weight Loss in Ameliorating Disorders Associated with Obesity.” Clinical Therapeutics 18, no. 6 (December 1996): 1006–35; discussion 1005. 10.1016/s0149-2918(96)80057-9.

[43] Nathan J. O’Callaghan et al., “Weight Loss in Obese Men Is Associated with Increased Telomere Length and Decreased Abasic Sites in Rectal Mucosa.” Rejuvenation Research 12, no. 3 (June 2009): 169–76. https://doi.org/10.1089/rej.2008.0819.

[44] K. L. Rudolph et al., “Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice.” Cell 96, no. 5 (March 5, 1999): 701–12. 10.1016/s0092-8674(00)80580-2.

[45] N. Weraarchakul et al., “The Effect of Aging and Dietary Restriction on DNA Repair.” Experimental Cell Research 181, no. 1 (March 1989): 197–204.

[46] J. T. Wachsman, “The Beneficial Effects of Dietary Restriction: Reduced Oxidative Damage and Enhanced Apoptosis.” Mutation Research 350, no. 1 (February 19, 1996): 25–34. 10.1016/0027-5107(95)00087-9.

[47] C. Leeuwenburgh et al., “Caloric Restriction Attenuates Dityrosine Cross-Linking of Cardiac and Skeletal Muscle Proteins in Aging Mice.” Archives of Biochemistry and Biophysics 346, no. 1 (October 1, 1997): 74–80. https://doi.org/10.1006/abbi.1997.0297.

[48] Ana Maria Cuervo et al., “Autophagy and Aging: The Importance of Maintaining ‘Clean’ Cells.” Autophagy 1, no. 3 (December 2005): 131–40. 10.4161/auto.1.3.2017.

As early as the 1940s, researchers identified that inducing negative energy balance has a very powerful effect in reducing tumor number and size, and since that time the evidence has grown substantially.

[49] Albert Tannenbaum, “The Genesis and Growth of Tumors. II. Effects of Caloric Restriction per Se.” Cancer Research 2, no. 7 (July 1, 1942): 460–67. https://cancerres.aacrjournals.org/content/2/7/460.

Research from Cyrus’ laboratory at UC Berkeley showed that negative calorie balance reduces the global cell proliferation rate, which means that cells in all tissues reduce the speed at which they replicate, which in turn reduces the rate of formation of cancerous cells.

[50] Airlia C. S. Thompson et al., “Reduced in Vivo Hepatic Proteome Replacement Rates but Not Cell Proliferation Rates Predict Maximum Lifespan Extension in Mice.” Aging Cell 15, no. 1 (February 2016): 118–27. https://doi.org/10.1111/acel.12414.

[51] Matthew D. Bruss et al., “The Effects of Physiological Adaptations to Calorie Restriction on Global Cell Proliferation Rates.” American Journal of Physiology: Endocrinology and Metabolism 300, no. 4 (April 2011): E735-745. https://doi.org/10.1152/ajpendo.00661.2010.

Because daily movement is such a powerful insulin sensitizer, we can all but guarantee that following these recommendations will further reduce your need for oral medication and insulin, reduce your fasting and post-meal blood glucose, reduce your total cholesterol, reduce your LDL cholesterol, increase your HDL cholesterol, and improve the condition of blood vessels in tissues all over your body.

[1] J. A. Hawley and S. J. Lessard, “Exercise Training-Induced Improvements in Insulin Action.” Acta Physiologica 192, no. 1 (January 2008): 127–35. https://doi.org/10.1111/j.1748-1716.2007.01783.x.

[2] John A. Hawley and John O. Holloszy, “Exercise: It’s the Real Thing!” Nutrition Reviews 67, no. 3 (March 2009): 172–78. https://doi.org/10.1111/j.1753-4887.2009.00185.x.

[3] John A. Hawley, “Exercise as a Therapeutic Intervention for the Prevention and Treatment of Insulin Resistance.” Diabetes/Metabolism Research and Reviews 20, no. 5 (October 2004): 383–93. https://doi.org/10.1002/dmrr.505.

[4] Brian D. Tran et al., “Altered Insulin Response to an Acute Bout of Exercise in Pediatric Obesity.” Pediatric Exercise Science, April 10, 2014. https://www.ncbi.nlm.nih.gov/pubmed/24723046.

[5] John P. Kirwan et al., “Effects of 7 Days of Exercise Training on Insulin Sensitivity and Responsiveness in Type 2 Diabetes Mellitus.” American Journal of Physiology: Endocrinology and Metabolism 297, no. 1 (July 1, 2009): E151–56. https://doi.org/10.1152/ajpendo.00210.2009.

[6] Gabriele Fuchsjäger-Mayrl et al., “Exercise Training Improves Vascular Endothelial Function in Patients with Type 1 Diabetes.” Diabetes Care 25, no. 10 (October 1, 2002): 1795–1801. https://doi.org/10.2337/diacare.25.10.1795.

Each cell can contain as few as 100 and as many as 5,000 copies of mitochondria.

[7] Francis J. Miller et al., “Precise Determination of Mitochondrial DNA Copy Number in Human Skeletal and Cardiac Muscle by a PCR-Based Assay: Lack of Change of Copy Number with Age.” Nucleic Acids Research 31, no. 11 (June 1, 2003): e61. 10.1093/nar/gng060.

[8] Logan W. Cole, “The Evolution of Per-Cell Organelle Number.” Frontiers in Cell and Developmental Biology 4 (August 18, 2016). https://doi.org/10.3389/fcell.2016.00085.

Inside each mitochondria, glucose, fatty acids, and amino acids are stripped of their energy-containing parts to produce a high-energy compound known as ATP, which is then used to power thousands of reactions inside the cell, including complex processes like protein synthesis, nutrient absorption, cell replication, and cell death.

[9] Donald D. Newmeyer and Shelagh Ferguson-Miller, “Mitochondria: Releasing Power for Life and Unleashing the Machineries of Death.” Cell 112, no. 4 (February 21, 2003): 481–90. https://doi.org/10.1016/S0092-8674(03)00116-8.

[10] Yorka Muñoz et al., “Parkinson’s Disease: The Mitochondria-Iron Link.” Parkinson’s Disease 2016 (2016). https://doi.org/10.1155/2016/7049108.

Specifically, the 1,000 to 2,000 mitochondria densely packed into each liver cell generate the large amounts of ATP required for deciding which glucose to keep, which glucose to export, which hormones to make, which fuels to break down, which fuels to store, which DNA to copy, which cells to destroy, which vitamins to store, which fatty acids to package, which protein to degrade, which amino acids to convert, and which triglycerides to package into lipoprotein particles.

[11] Bruce Alberts et al., Molecular Biology of the Cell, 3rd ed. Garland Science, 1994.

Muscle mitochondria are mainly responsible for generating ATP to control how nutrients get in and out of the cells and to contract and elongate muscle fiber when you exercise.

[12] Vladimir B. Ritov et al., “Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes.” Diabetes 54, no. 1 (January 2005): 8–14. 10.2337/diabetes.54.1.8.

[13] A. M Cogswell, R. J. Stevens, and D. A. Hood, “Properties of Skeletal Muscle Mitochondria Isolated from Subsarcolemmal and Intermyofibrillar Regions.” American Journal of Physiology: Cell Physiology 264, no. 2 (February 1, 1993): C383–89. 10.1152/ajpcell.1993.264.2.C383.

When you engage in physical activity, mitochondria can increase the rate of ATP production by as much as 100 times.

[14] Barbara E. Ainsworth et al., “2011 Compendium of Physical Activities: A Second Update of Codes and Met Values.” Medicine & Science in Sports & Exercise 43, no. 8 (August 1, 2011): 1575–81. https://doi.org/10.1249/MSS.0b013e31821ece12.

[15] Craig Porter and Benjamin T. Wall, “Skeletal Muscle Mitochondrial Function: Is It Quality or Quantity That Makes the Difference in Insulin Resistance?” The Journal of Physiology 590, no. 23 (December 1, 2012): 5935–36. https://doi.org/10.1113/jphysiol.2012.241083.

Releasing too much can result in life-threatening hypoglycemia, and releasing too little results in high blood glucose. So when this mitochondrial population is compromised, your chronic disease risk increases dramatically.

[16] Jeong-a Kim, Yongzhong Wei, and James R. Sowers, “Role of Mitochondrial Dysfunction in Insulin Resistance.” Circulation Research 102, no. 4 (February 29, 2008): 401–14. https://doi.org/10.1161/CIRCRESAHA.107.165472.

The beauty of this relationship is that regardless of which is the chicken and which is the egg, improving one improves the other.

[17] Raghavakaimal Sreekumar and K. Sreekumaran Nair, “Skeletal Muscle Mitochondrial Dysfunction & Diabetes.” The Indian Journal of Medical Research 125, no. 3 (March 2007): 399–410. https://www.ncbi.nlm.nih.gov/pubmed/17496364.

[18] Zi Long et al., “Evolution of Metabolic Disorder in Rats Fed High Sucrose or High Fat Diet: Focus on Redox State and Mitochondrial Function.” General and Comparative Endocrinology 242 (October 20, 2015): 92–100. https://doi.org/10.1016/j.ygcen.2015.10.012.

[19] Elizabeth V. Menshikova et al., “Effects of Exercise on Mitochondrial Content and Function in Aging Human Skeletal Muscle.” The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 61, no. 6 (June 2006): 534–40. 10.1093/gerona/61.6.534.

This presents a huge problem, because not only are there fewer mitochondria to begin with, the existing mitochondria don’t burn fuel efficiently.

[20] Vladimir B. Ritov et al., “Deficiency of Subsarcolemmal Mitochondria in Obesity and Type 2 Diabetes.” Diabetes 54, no. 1 (January 2005): 8–14. 10.2337/diabetes.54.1.8.

[21] Porter and Wall, “Skeletal Muscle Mitochondrial Function: Is It Quality or Quantity That Makes the Difference in Insulin Resistance?” 10.1113/jphysiol.2012.241083.

[22] Vladimir B. Ritov et al., “Deficiency of Electron Transport Chain in Human Skeletal Muscle Mitochondria in Type 2 Diabetes Mellitus and Obesity.” American Journal of Physiology: Endocrinology and Metabolism 298, no. 1 (January 2010): E49-58. https://doi.org/10.1152/ajpendo.00317.2009.

[23] David Kelley et al., “Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes.” Diabetes 51, no. 10 (October 2002): 2944–50. 10.2337/diabetes.51.10.2944.

[24] Frederico G. S. Toledo et al., “Mitochondrial Capacity in Skeletal Muscle Is Not Stimulated by Weight Loss Despite Increases in Insulin Action and Decreases in Intramyocellular Lipid Content.” Diabetes 57, no. 4 (April 1, 2008): 987–94. https://doi.org/10.2337/db07-1429.

[25] David E. Kelley, “Skeletal Muscle Fat Oxidation: Timing and Flexibility Are Everything.” Journal of Clinical Investigation 115, no. 7 (July 1, 2005): 1699–1702. https://doi.org/10.1172/JCI25758.

[26] B. H. Goodpaster et al., “Skeletal Muscle Lipid Content and Insulin Resistance: Evidence for a Paradox in Endurance-Trained Athletes.” The Journal of Clinical Endocrinology and Metabolism 86, no. 12 (December 2001): 5755–61.10.1210/jcem.86.12.8075.

This results in improved endurance, increased strength, and an increased ability to perform work.

[27] Hans Hoppeler and Martin Fluck, “Plasticity of Skeletal Muscle Mitochondria: Structure and Function.” Medicine and Science in Sports and Exercise 35, no. 1 (January 2003): 95–104. https://www.ncbi.nlm.nih.gov/pubmed/12544642.

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Exercise physiologists have known for decades that a sedentary lifestyle can reduce the number of muscle mitochondria, leading to a decrease in muscular endurance, strength, and work output.

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Large amounts of free radicals are formed in the mitochondria, and they damage cell membranes, protein, and DNA.

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While this sounds great, a closer look at rigorous science shows that even minor elevations in plasma lipids not only induce muscle insulin resistance but also alter the gene expression of key mitochondrial proteins, resulting in reduced mitochondrial function and a decreased rate of ATP synthesis.

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Increasing dietary fat content from 35 to 50 percent (as is easily achieved on a low-carbohydrate diet) results in a reduced expression of all genes involved in mitochondrial respiration—the very genes necessary for mitochondria to extract ATP from various intracellular fuels.

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This means that people who eat high-fat, low-carbohydrate diets often make more free radicals in their liver and muscle, dramatically increasing their level of cellular inflammation and silently crippling the function of trillions of muscle mitochondria.

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Glucose is preferentially burned for energy during short-duration, higher-intensity bursts of energy, whereas fatty acids are preferentially burned for energy during longer- duration, lower-intensity exercise.

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Not only does eating frequent meals high in whole carbohydrate energy increase the size of your glycogen stores, frequent meals low in carbohydrate energy also shrink your glycogen stores over time and cause your muscles to break down more protein during exercise.

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Recent compelling scientific research has shown that eating 1 to 2 servings of nitrate-rich vegetables 1 to 2 hours before your workout has a profound impact on blood vessels all over your body.

[58] Tennille D. Presley et al., “Acute Effect of a High Nitrate Diet on Brain Perfusion in Older Adults.” Nitric Oxide: Biology and Chemistry 24, no. 1 (January 1, 2011): 34–42. https://doi.org/10.1016/j.niox.2010.10.002.

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[61] Andrew J. Webb et al., “Acute Blood Pressure Lowering, Vasoprotective, and Antiplatelet Properties of Dietary Nitrate via Bioconversion to Nitrite.” Hypertension 51, no. 3 (March 1, 2008): 784–90. https://doi.org/10.1161/HYPERTENSIONAHA.107.103523.

This in turn allows you to perform more work with less perceived effort.

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The intensity of your exercise session is another large factor in determining whether you require basal insulin during exercise.

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In the Phase 2 Afterburn, your insulin sensitivity is higher than before you exercised, albeit slowly decreasing toward your pre-exercise level.

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The plant-based eaters were not exercising regularly, but they had measurably better cardiometabolic health than the endurance runners, despite the fact that the runners were 5 percent leaner.

[71] Luigi Fontana et al., “Long-Term Low-Calorie Low-Protein Vegan Diet and Endurance Exercise Are Associated with Low Cardiometabolic Risk.” Rejuvenation Research 10, no. 2 (June 2007): 225–34. https://doi.org/10.1089/rej.2006.0529.