Life Extension Magazine®
A good diet is essential for anyone wishing to achieve healthy longevity.
With conflicting stories appearing in the mass media, ascertaining what the best food choices are can be a daunting task.
There is disagreement among nutrition scientists, and there are often new studies or opinions that substantially alter dietary recommendations.
For example, saturated fats have been claimed to cause cardiovascular disease,1 but this claim is debatable among nutrition scientists.2-5 Interestingly, on a low-carbohydrate diet, high dietary saturated fats do not increase saturated fats in the bloodstream.6
Discussion of the effects of dietary saturated fat rarely acknowledge the fact that there are about a dozen different saturated fats, each of which has unique properties.7,8 Palmitate is the most abundant saturated fat found in foods.9,10 Palmitate constitutes nearly a third of butterfat and beef fat. Palmitate is more likely to cause inflammation than the other saturated fats11 (particularly in obese people).9,12 But palmitate is not inflammatory if consumed with olive oil or fish oil.13-15 A saturated fat called myristate strongly raises blood cholesterol,16 but the saturated fat stearate does not.17 The saturated fat butyrate improves insulin sensitivity.18
The human body derives energy either from glucose (from carbohydrate) or from fat (or from ketones from fat).19 Carbohydrates only became a primary source of energy with the advent of agriculture. As a source of energy, glucose is much more damaging to blood vessels than fat (saturated fat usually can’t be oxidized). Glucose is the preferred energy source for cancer cells.20 With the exception of dietary fiber, the fewer carbohydrates in the diet the better, unless there are compensating benefits, such as eating them with blueberries.
Protein is much more complicated. Protein contains essential amino acids, which are important for growth, maintenance, and metabolism of the human body. These functions are especially important for growing children, but are also important for the elderly and to prevent muscle loss in those who exercise. Adequate protein is also important for good immune system function.21
Population studies indicate that consumption of red meat and processed meat increases cancer and cardiovascular disease.22 Subjects randomly assigned to a vegetarian diet or an omnivorous diet had lower blood pressure when on the vegetarian diet.23 Moderately low protein intake seems advisable for most adults (plant protein preferred), although the amount is hard to specify and is dependent on circumstances.
In seeking a healthy diet, I frequently make substantial changes to my eating patterns. In my search for greater clarity, I attended the American Society for Nutrition conference in Boston, March 28 to April 1, 2015.
My reports of scientific conferences normally only describe the presentations made by the scientists. But because everyone eats, because diet and dieting have such substantial influence on health, and because the discoveries of nutrition scientists so often seem contradictory or confusing, for this report I am following each presentation description with my interpretations and recommendations. These comments will be my opinions, which are not necessarily those of the Life Extension® Foundation.
My dietary opinions have been substantially influenced by scientists advocating a ketogenic diet, that is, a diet low in carbohydrates, and moderately low in protein. I have been on a vegetarian ketogenic diet for over a year. Insofar as food can only consist of carbohydrate, protein, and fat, my diet is high in fat and fiber. When dietary carbohydrate is low, the liver converts fat into ketones to provide energy for the brain. Although fiber is classified as a carbohydrate, when digested, fiber is converted to beneficial fats in the large intestine.
What do I eat? My “main course” is a vegetable salad (broccoli, green leafy vegetables, shredded cabbage) laden with healthy oil (like olive oil), to which I add walnuts, shredded coconut, and a scoop of whey protein. Among other things I eat are cream cheese with cauliflower, as well as avocado mixed with healthful flavorings such as cocoa powder and wheat grass powder.
Although this is a report on a scientific conference, because diet is such a personal matter, and because I am making recommendations, I need to disclose the basis for my opinions. I believe there is good science behind these opinions, and for that reason I am beginning by reporting the views of Dr. Eric Westman, one of the leading scientific advocates of a ketogenic diet.
Health Benefits Of A Ketogenic Diet
Eric Westman, MD, (Duke University Outpatient Clinic, Durham, North Carolina) is one of the pioneers in challenging the benefits of low-fat diets. He has conducted a number of studies showing that low-carbohydrate, high-fat diets (ketogenic diets) result in less hunger, better compliance, and greater weight loss than low-fat diets.24-26
Dr. Westman conducted a clinical trial in which type II diabetics were randomized to low-calorie diets or to ketogenic diets that did not restrict calories. The diabetics on the ketogenic diet showed greater weight loss, greater reduction in glycated hemoglobin (HbA1C), and greater reduction or elimination of required diabetic medications (95.2 versus 62%).27 Subsequent studies by others have confirmed the benefit of a ketogenic diet for treatment of type II diabetes.28,29 Dr. Westman is opening a clinic entirely devoted to weight loss and diabetes treatment using a ketogenic diet (For more information, go to www.healclinics.com).
When carbohydrates are low, the liver converts fats into ketones, which can serve as a fuel source for many tissues, including the brain.30 Dietary ketosis should not be confused with the ketoacidosis of diabetes, which involves acidity as well as much higher blood ketone concentrations.31,32 Unlike sugar, which stimulates appetite,33 ketones reduce appetite.34,35 As a source of energy for the brain, ketones make mitochondria more efficient, reduce free radical production, and protect against a variety of brain diseases, including epilepsy, stroke, and Alzheimer’s disease.36,37
A ketogenic diet has been shown to increase cognitive performance in aged rats.38 Cancer cells thrive on the glucose resulting from dietary carbohydrates, but are generally unable to use ketones as an energy source.39 Ketones have been shown to suppress tumors and prolong survival in mice that have metastatic cancer.40,41
Saturated fats have been claimed to cause cardiovascular disease,1 but this claim is debatable among nutrition scientists.2-5 A lot probably depends on the type of saturated fat and what other foods it is consumed with.
Insulin resistance results when excess fat accumulates in muscle, liver, and pancreas rather than in fat cells.42 But on a carbohydrate-restricted diet, fats are used for energy rather than stored.6 On a low-carbohydrate diet, high dietary saturated fats do not increase saturated fats in the bloodstream.6 Cardiovascular risk factors may be reduced on a high-fat, low-carbohydrate (ketogenic) diet,43,44 and a low-carbohydrate diet has been shown to increase insulin sensitivity.45,46
My interpretation/recommendation: A diet low in carbohydrates, moderately low in protein, and high in proper fats is recommended for persons trying to lose weight as well as for prevention and treatment of diabetes (and other age-related afflictions, notably cancer and cardiovascular disease).
Dietary Sugar
Deborah Sloboda, PhD, (Associate Professor, Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada) does research on the damaging effects of dietary sugar, particularly fructose.
Simple sugar constituted only about 2% of the prehistoric Paleolithic diet, but currently accounts for about 18 to 25% of total calories of the average modern Western diet.47 Modern man is thus consuming about 10 times more simple sugar than our early ancestors.
High fructose corn syrup, introduced in 1967, accounted for 42% of caloric sweeteners being used by the year 2000.48 Fructose consumption increases visceral (abdominal) fat while reducing insulin sensitivity.49 Dr. Sloboda is particularly concerned with fructose consumption during pregnancy, which can lead to gestational diabetes (temporary diabetes due to pregnancy), causing inflammatory metabolic disturbance for both the mother and the fetus.50,51 The amino acid taurine can partially reduce the damaging effects of fructose.51,52
My interpretation/recommendation: Fructose consumption should be limited because fructose can elevate blood triglycerides while causing insulin resistance and the diseases of inflammation and diabetes. The soft drinks accounting for about 90% of the soda market (Coca-Cola®, Pepsi®, Dr. Pepper®, Mountain Dew®, and Sprite®) all contain 60 to 65% fructose.53 Apple juice has more than twice the fructose as orange juice, yet apple juice is the most common sweetener in fruit drinks. Dried apples, dates, apricots, figs, and raisins are one-quarter to one-third fructose by weight, and should be eaten sparingly. Fructose can cause harm to both the mother and fetus during pregnancy and pregnant women should limit consumption of fructose-containing beverages, and perhaps even supplement with taurine.
Dietary Starch
Diane Birt, PhD, (Distinguished Professor Emeritus, Iowa State University) is interested in using digestion-resistant starch to improve human health. Starch, like sugar, is a form of carbohydrate, but starches that resist digestion in the stomach and small intestine, yet are digested in the large intestine, are called resistant starch or fiber.
Dr. Birt has described most foods in the typical Western diet as being highly digestible starches having a high glycemic index (which raise blood glucose).54 Such foods result in cycles of high and low blood glucose and blood insulin, often causing insulin resistance and type II diabetes.54 All starchy foods are composed of chains of sugar molecules, but not all starchy foods are as easily digested. Digestion-resistant starch eaten for breakfast reduces the surges of glucose and insulin at lunch.55
Legumes (beans) contain more resistant starch than potatoes, rice, pasta, bread, or breakfast cereals. But Dr. Birt wishes to develop foods with higher resistant starch content than legumes.54 Resistant starches have been shown to reduce obesity.56 Starches (dietary fibers) that are more viscous reduce appetite more than those that are less viscous,57 so the starches she is developing would be more viscous. Starches made of long unbranched chains of sugars are more digestion-resistant than starches having branched chains, a fact Dr. Birt also exploits when designing improved foods for health.54
My interpretation/recommendation: Rapidly digested carbohydrate starches such as potatoes, pastry, white bread, and breakfast cereals should be avoided, but beans and waxy corn starch are good sources of dietary fiber that can satisfy appetite while reducing insulin surges after eating.54,58
Dietary Fat
David Mutch, PhD, (Associate Professor, University of Guelph, Canada) is interested in how fats and inflammatory substances in the bloodstream relate to obesity. Although obesity is often associated with insulin resistance and metabolic syndrome, he estimates that 13 to 29% of obese persons (BMI greater than 30) are metabolically healthy, whereas 10 to 37% of lean persons (BMI less than 25) are metabolically unhealthy, having insulin resistance.59
Metabolically healthy obese people are less likely to have fat in heart cells or in the insulin-producing cells of the pancreas.59 Metabolically unhealthy people have higher blood levels of the saturated fat palmitate.60,61 Foods high in palminate include cocoa butter oil, palm oil, shortening, butter, lard, milk chocolate, fatty meats, pork and beef products, game meats, cashews, and eggs.61
Palmitate can induce inflammation and insulin resistance.62-64 Elevated blood palmitate and glucose cause insulin-producing cells in the pancreas to die, but the monounsaturated fat oleic acid (high in olive oil and avocado) protects cells against glucose and palmitate toxicity.13,14 Omega-3 fatty acid supplementation of a mouse diet high in saturated fat also prevents inflammation from palmitate.15
My interpretation/recommendation: Olive oil, fish oil, and avocado can protect against inflammation due to the saturated fat palmitate.
Kevin Fritsche, PhD, (Professor of Nutritional Immunology, University of Missouri) studies the effects of dietary fats on inflammation and the risk of cardiovascular disease. He believes that the inflammatory blood component C-reactive protein is more strongly associated with cardiovascular disease than LDL cholesterol.65 Release of the inflammatory protein IL-18 from fat cells of obese people is triple of that seen in those who are not obese.66 Although he affirms that trans-fatty acids promote inflammation and reduce function of the endothelial cells lining blood vessels,67 he finds not much support for the claim that omega-6 fatty acids are pro-inflammatory.68,69
The gut microbe Bifidobacteria has been shown to prevent the highly pro-inflammatory endotoxin lipopolysaccharide (or LPS, which constitutes 80% of the cell wall of gram-negative bacteria) from leaking into the bloodstream from the intestine.70-74 A high-fat, high-carbohydrate diet promotes inflammation by reducing the quantity of Bifidobacteria,73-75 although some foods (including walnuts, olive oil, and wheat bran) can lessen this effect.76
The magnitude of inflammation resulting from a high-fat, high-carbohydrate meal is markedly greater in obese than in non-obese subjects.77,78 Inflammation from a high-fat, high-carbohydrate meal may be independent of LPS concentration in the bloodstream.79
My interpretation/recommendation: LDL cholesterol is less of a cardiovascular disease concern than inflammation and insulin resistance. A high-fat diet should be avoided only if it is combined with a diet high in carbohydrates. Dietary carbohydrates cause insulin secretion, and insulin prevents fat from being used as an energy source, resulting in fat being stored in places other than fat cells, namely in muscle and pancreas, resulting in insulin resistance. Because this effect is largest in obesity, obese people should make a particular effort to reduce carbohydrates.
Weight-Loss Strategies
Catherine Hankey, PhD (Senior Lecturer in Human Nutrition, University of Glasgow, United Kingdom) reviewed studies on intermittent fasting as a weight-loss strategy. At any given time, about 40% of women and 20% of men will be fasting for weight loss.80
Dr. Hankey began by acknowledging the bestselling book The Fast Diet by Dr. Michael Mosley and Mimi Spencer, which advocates reducing calories to 25% the usual daily intake on two days each week (Monday and Thursday being the best choice for most people).
A high-protein diet can assist fasting because protein has been shown to reduce appetite.81 High-protein diets (25% or more of calories) are associated with the greatest weight loss (and not much hunger) for a few months. By two years, however, there is little lasting weight loss.81 A three-month comparison of subjects restricting calories 25% either on a daily basis with high protein, or only on two days per week with carbohydrate restriction, showed greater body fat reduction along with improved insulin sensitivity for the intermittent-fasting, carbohydrate-restricting group.82
My interpretation/recommendation: Complete fasting for more than a day is intolerable for most people, but Dr. Mosley’s book became a bestseller because so many people have succeeded in losing weight by eating only 25% of their usual calories twice weekly. I recommend this book to readers who have not succeeded with other weight-loss methods. The book contains recipes and strategies. Despite initial weight loss and reduction of hunger on a high-protein diet, high-protein diets are not recommended. Weight loss with a high-protein diet is only a temporary effect. Moreover, high dietary protein can result in chronic inflammation with subsequent increase in cancer and cardiovascular disease.83,84
Cynthia Kroeger and John Trepanowski, (PhD students, Department of Kinesiology and Nutrition, University of Illinois, Chicago) have conducted a number of studies together on the effects of alternate-day fasting (with 25% of usual calories consumed on the fast day).85-87 In one such study, the weight loss from endurance exercise and fasting in combination was compared with exercise and fasting alone. The combination resulted in a 13.2 pound weight loss, fasting alone resulted in a 6.6 pound weight loss, and exercise alone resulted in a 2.2 pound weight loss.88
Exercise alone is usually not very effective for weight loss,89,90 at least partially because of increased appetite. The most important role of exercise in dieting is to prevent loss of lean mass (and to boost AMPK enzyme activity).91 In another study, Kroeger and Trepanowski found that adding liquid meal replacement to intermittent fasting and calorie restriction resulted in an even greater reduction in weight, visceral fat, and LDL cholesterol. The liquid meals ensured greater portion control. Only the subjects receiving the liquid meal replacement showed a reduction in blood glucose, insulin, and homocysteine, as well as reduced LDL particle size.86
My interpretation/recommendation: Although exercise alone is not very effective for weight loss, exercise doubles the weight loss associated with a reduced-calorie diet, while preventing loss of muscle tissue. Combining exercise with calorie restriction is highly recommended for dieters.
Diana Thomas, PhD, (Professor of Mathematical Sciences, Montclair State University, Montclair, New Jersey) has created mathematical models to explain weight-loss effects associated with dieting.92,93 Weight lost in the initial phases of dieting is typically the result of greater water loss associated with protein and carbohydrate loss.94 Unlike fat, proteins (like muscle) and carbohydrates (like glycogen) are stored with much water in the body, so loss of lean mass or carbohydrate results in loss of considerable amounts of water.95,96 Calories required for weight loss increases with the duration of dieting because as dieting proceeds, weight loss increasingly means fat loss. According to Dr. Thomas, after four weeks of dieting, a reduction of about 2,000 dietary calories results in a loss of one pound. But by 24 weeks of dieting, a reduction of about 3,000 dietary calories is required to lose one pound.94
For an average person, resting metabolic rate accounts for 70% of calories consumed, physical activity accounts for 20%, and energy required to digest and metabolize food (the thermic effect of food) accounts for 10%.97
The thermic effect of protein is more than double the thermic effect of fat or carbohydrate.98 The thermic effect of glucose is reduced with insulin resistance because insulin facilitates glucose storage (which consumes more energy than glucose used as an energy source).99
Resting metabolic rate typically declines 2 to 3% every decade after age 20, mostly due to loss of lean, fat-free mass.97 Physical activity also tends to decline with age. These factors make weight loss increasingly difficult with age. On average, body weight is highest for those in the 50-59 age group, but much of the reason for this may be due to higher death rates among the obese.97
My interpretation/recommendation: Weight loss becomes more difficult with age largely because of the muscle loss associated with reduced activity. The more muscle (lean body mass) that a person has, the higher their resting metabolic rate will be. Resistance exercise is particularly important for building and maintaining muscle, as well as preventing the frailty too often associated with aging. Exercise should become a lifetime practice, not simply something done while dieting.
Muscle Loss In The Elderly
Ronenn Roubenoff, MD, (Internist, Tufts Medical Center, Boston) studies muscle loss in the elderly. He cited a three-year study of over 3,000 people in their 70s, which showed that loss of muscle quality was even greater than loss of muscle mass.100 Deterioration of muscle in the elderly not only leads to functional impairment and falls, but to chronic heart failure and chronic obstructive pulmonary disease.101-103 Endurance as well as resistance exercise, along with increased protein intake is recommended to prevent muscular atrophy in the elderly,104 although those with kidney problems due to diabetes may need to limit their protein intake.105
My interpretation/recommendation: As stated above, endurance exercise, resistance exercise, and adequate protein can prevent muscle wasting and can reduce frailty in the elderly (for whom muscle-wasting can be life threatening).
Circadian Rhythm And Diet
Frank Scheer, PhD, (Assistant Professor of Sleep Medicine, Harvard Medical School) is an expert on the effects of circadian (day-night cycle) rhythm on dietary metabolism. The brain has a clock that normally causes melatonin secretion to increase in the evening (facilitating sleep), which causes secretion of growth hormone and prolactin at sleep onset, and which causes secretion of the stress hormone cortisol before awakening.106 The risk of a heart attack in the morning is elevated 40% above the 24-hour average,106 at least partially because cortisol raises blood pressure.107 Dr. Scheer’s research has established that disruption of the circadian rhythm by jet lag or shift work leads to insulin resistance.108 Melatonin supplementation can lessen these circadian stresses.109
Dr. Scheer has also established that for those with a normal circadian rhythm, hunger is lowest at 8 a.m. and highest at 8 p.m.110 There is also a circadian effect on appetite for certain foods. The 8 p.m. appetite for sweets, starches, and meat is increased, but there is no circadian effect for vegetables or dairy products.110
Dr. Scheer conducted two studies showing that breakfast skippers and late eaters gain more weight (and have more trouble losing weight) than early eaters, despite consuming the same total number of calories.111,112 But a randomized study focused only on those who skip breakfast showed no effect on weight gain or loss.113 A review by other authors, while acknowledging that late-night eating contributes to metabolic syndrome, denied a similar effect for breakfast skipping, suggesting that breakfast skipping might be more successful than other strategies for calorie restriction.114
My interpretation/recommendation: Eating in the evening before bedtime can lead to greater weight gain than calorie counting would predict. Skipping breakfast is probably not a health hazard. Melatonin should be used to reduce the effects of jet lag or shift work.
Conclusions
There may be a revolution happening in the perception of the effects of dietary fat, especially in the context of a ketogenic diet. It would be hard to prove that the US Department of Agriculture dietary recommendations of high grain (carbohydrate, the “food pyramid”) and low fat115,116 contributed significantly to the current obesity epidemic, but if true, the government will not readily admit blame.117
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
References
- Kris-Etherton PM, Innis S, American Dietetic Association, Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: dietary fatty acids. J Am Diet Assoc. 2007 Sep;107(9):1599-611.
- Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr. 2010 Mar;91(3):535-46.
- Scarborough P, Rayner M, van Dis I, Norum K. Meta-analysis of effect of saturated fat intake on cardiovascular disease: over adjustment obscures true associations. Am J Clin Nutr. 2010 Aug;92(2):458-9; author reply 459.
- Chowdhury R, Warnakula S, Kunutsor S, et al. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014 Mar 18;160(6):398-406.
- Hooper L, Martin N, Abdelhamid A, Davey Smith G. Reduction in saturated fat intake for cardiovascular disease. Cochrane Database Syst Rev. 2015 Jun10;6:CD011737.
- Forsythe CE, Phinney SD, Feinman RD, et al. Limited effect of dietary saturated fat on plasma saturated fat in the context of a low carbohydrate diet. Lipids. 2010 Oct;45(10):947-62.
- Mensink RP, Zock PL, Kester AD, Katan MB. 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. Am J Clin Nutr. 2003 May;77(5):1146-15.
- Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Saturated fatty acids and risk of coronary heart disease: modulation by replacement nutrients. Curr Atheroscler Rep. 2010 Nov;12(6):384-90.
- Vock C, Gleissner M, Klapper M, Doring F. Identification of palmitate-regulated genes in HepG2 cells by applying microarray analysis. Biochim Biophys Acta. 2007 Sep;1770(9):1283-88.
- French MA, Sundram K, Clandinin MT. Cholesterolaemic effect of palmitic acid in relation to other dietary fatty acids. Asia Pac J Clin Nutr. 2002;11Suppl7:S401-7
- 11.Tian H, Liu C, Zou X, Wu W, Zhang C, Yuan D. MiRNA-194 regulates palmitic acid-induced toll-like receptor 4 inflammatory responses in THP-1 cells. Nutrients. 2015 May 13;7(5):3483-96.
- Laugerette F, Furet JP, Debard C, et al. Oil composition of high-fat diet affects metabolic inflammation differently in connection with endotoxin receptors in mice. Am J Physiol Endocrinol Metab. 2012 Feb 1;302(3):E374-86.
- Listenberger LL, Han X, Lewis SE, Cases et al. Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3077-82.
- Maedler K, Oberholzer J, Bucher P, Spinas GA, Donath MY. Monounsaturated fatty acids prevent the deleterious effects of palmitate and high glucose on human pancreatic beta-cell turnover and function. Diabetes. 2003 Mar;52(3):726-33.
- Awada M, Meynier A, Soulage CO, et al. n-3 PUFA added to high-fat diets affect differently adiposity and inflammation when carried by phospholipids or triacylglycerols in mice. Nutr Metab (Lond). 2013 Feb 15;10(1):23.
- Temme EH, Mensink RP, Hornstra G. Effects of medium chain fatty acids(MCFA), myristic acid, and oleic acid on serum lipoproteins in healthy subjects. J Lipid Res. 1997 Sep;38(9):1746-54.
- Hunter JE, Zhang J, Kris-Etherton PM. Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am J Clin Nutr. 2010 Jan;91(1):46-63.
- Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009 Jul;58(7):1509-17.
- Askew EW. Role of fat metabolism in exercise. Clin Sports Med. 1984 Jul;3(3):605-21.
- Bozzetti F, Gavazzi C, Mariani L, Crippa F. Glucose-based total parenteral nutrition does not stimulate glucose uptake by humans tumours. Clin Nutr (Edinburgh). 2004 Jun ;23(3):417-21.
- Rusu D, Drouin R, Pouliot Y, Gauthier S, Poubelle PE. A bovine whey protein extract can enhance innate immunity by priming normal human blood neutrophils. J Nutr. 2009 Feb;139(2):386-93.
- Sinha R, Cross AJ, Graubard BI, Leitzmann MF, Schatzkin A. Meat intake and mortality: a prospective study of over half a million people. Arch Intern Med. 2009 Mar 23;169(6):562-71.
- Rouse IL, Beilin LJ, Armstrong BK, Vandongen R. Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects. Lancet. 1983 Jan 1;1(8314-5):5-10.
- Yancy WS Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med. 2004 May 18;140(10):769-77.
- Lecheminant JD, Gibson CA, Sullivan DK, et al. Comparison of a low carbohydrate and low fat diet for weight maintenance in overweight or obese adults enrolled in a clinical weight management program. Nutr J. 2007 Nov 1;6:36.
- McClernon FJ, Yancy WS Jr, Eberstein JA, Atkins RC, Westman EC. The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood, hunger, and other self-reported symptoms. Obesity (Silver Spring). 2007 Jan;15(1):182-7.
- Westman EC, Yancy WS Jr, Mavropoulos JC, Marquart M, McDuffie JR. The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus. Nutr Metab (Lond). 2008 Dec19;5:36.
- Hussain TA, Mathew TC, Dashti AA, Asfar S, Al-Zaid N, Dashti HM. Effect of low-calorie versus low-carbohydrate ketogenic diet in type 2 diabetes. Nutrition. 2012 Oct;28(10):1016-21.
- Mobbs CV, Mastaitis J, Isoda F, Poplawski M. Treatment of diabetes and diabetic complications with a ketogenic diet. J Child Neurol. 2013 Aug;28(8):1009-14.
- Greene AE, Todorova MT, Seyfried TN. Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies. J Neurochem. 2003 Aug;86(3):529-37.
- Manninen AH. Metabolic effects of the very-low-carbohydrate diets: misunderstood “villains” of human metabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):7-11.
- Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and foodintake control: a complex relationship. Front Psychol. 2015 Feb 2;6:27.
- Gaysinskaya VA, Karatayev O, Shuluk J, Leibowitz SF. Hyperphagia induced by sucrose: relation to circulating and CSF glucose and corticosterone and or exigenic peptides in the arcuate nucleus. Pharmacol Biochem Behav. 2011 Jan;97(3):521-30.
- Gibson AA, Seimon RV, Lee CM, Ayre J, Franklin J, Markovic TP, Sainsbury A. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev. 2015 Jan;16(1):64-76.
- Veldhorst MA, Westerterp KR, van Vught AJ, Westerterp-Plantenga MS. Presence or absence of carbohydrates and the proportion of fat in a high-protein diet affect appetite suppression but not energy expenditure in normal-weight human subjects fed in energy balance. Br J Nutr. 2010 Nov;104(9):1395-405.
- Maalouf M, Rho JM, Mattson MP. The neuro protective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res Rev. 2009 Mar;59(2):293-315.
- Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012 Apr 9;3:59.
- Xu K, Sun X, Eroku BO, Tsipis CP, Puchowicz MA, LaManna JC. Diet-induced ketosis improves cognitive performance in aged rats. Adv Exp Med Biol. 2010;662:71-5.
- Seyfried TN, Flores RE, Poff AM, D’Agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014 Mar;35(3):515-27.
- Siri-Tarino PW, Sun Q, Hu FB, Krauss RM. Saturated fat, carbohydrate, and cardiovascular disease. Am J Clin Nutr. 2010 Mar;91(3):502-9.
- Poff AM, Ari C, Arnold P, Seyfried TN, D’Agostino DP. Ketone supplementation decreases tumor cell viability and prolongs survival of mice with metastatic cancer. Int J Cancer. 2014 Oct 1;135(7):1711-20.
- Borén J, Taskinen MR, Olofsson SO, Levin M. Ectopic lipid storage and insulin resistance: a harmful relationship. J Intern Med. 2013 Jul;274(1):25-40.
- Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gómez AL, Scheett TP, Volek JS. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr. 2002 Jul;132(7):1879-85
- Wood RJ, Volek JS, Davis SR, Dell’Ova C, Fernandez ML. Effects of a carbohydrate-restricted diet on emerging plasma markers for cardio vascular disease. Nutr Metab (Lond). 2006 May 4;3:19.
- Gower BA, Goss AM. A lower-carbohydrate, higher-fat diet reduces abdominal and intermuscular fat and increases insulin sensitivity in adults at risk of type 2 diabetes. J Nutr. 2015 Jan;145(1):177s-183s.
- Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology. 2009 May;136(5):1552-60.
- Gray C, Long S, Green C, Gardiner SM, Craigon J, Gardner DS. Maternal fructose and/or salt intake and reproductive outcome in the rat: effects on growth, fertility, sex ratio, and birth order. Biol Reprod. 2013 Sep;89(3):51.
- Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004 Apr;79(4):537-43.
- Stanhope KL, Havel PJ. Fructose consumption: recent results and their potential implications. Ann N Y Acad Sci. 2010 Mar;1190:15-24.
- Regnault TR, Gentili S, Sarr O, Toop CR, Sloboda DM. Fructose, pregnancy and later life impacts. Clin Exp Pharmacol Physiol. 2013 Nov;40(11):824-37.
- Li M, Reynolds CM, Sloboda DM, Gray C, Vickers MH. Maternal taurine supplementation attenuates maternal fructose-induced metabolic and inflammatory dysregulation and partially reverses adverse metabolic programming in offspring. J Nutr Biochem. 2015 Mar;26(3):267-76.
- Sloboda DM, Li M, Patel R, Clayton ZE, Yap C, Vickers MH. Early life exposure to fructose and offspring phenotype: implications for long term metabolic homeostasis. J Obes. 2014;2014:203474.
- Walker RW, Dumke KA, Goran MI. Fructose content in popular beverages made with and without high-fructose corn syrup. Nutrition. 2014 Jul-Aug;30(7-8):928-35.
- Birt DF, Boylston T, Hendrich S, et al. Resistant starch: promise for improving human health. Adv Nutr. 2013 Nov 6;4(6):587-601.
- Brighenti F, Benini L, Del Rio D, et al. Colonic fermentation of indigestible carbohydrates contributes to the second-meal effect. Am J Clin Nutr. 2006 Apr;83(4):817-22.
- Belobrajdic DP, King RA, Christophersen CT, Bird AR. Dietary resistant starch dose-dependently reduces adiposity in obesity-prone and obesity-resistant male rats. Nutr Metab (Lond). 2012 Oct 25;9(1):93.
- Wanders AJ, van den Borne JJ, de Graaf C, Hulshof T, Jonathan MC, Kristensen M, Mars M, Schols HA, Feskens EJ. Effects of dietary fibre on subjective appetite, energy intake and body weight: a systematic review of randomized controlled trials. Obes Rev. 2011 Sep;12(9):724-39.
- Behall KM, Scholfield DJ, Yuhaniak I, Canary J. Diets containing high amylose vs amylopectin starch: effects on metabolic variables in human subjects. Am J Clin Nutr. 1989 Feb;49(2):337-44.
- Badoud F, Perreault M, Zulyniak MA, Mutch DM. Molecular insights into the role of white adipose tissue in metabolically unhealthy normal weight and metabolically healthy obese individuals. FASEB J. 2015 Mar;29(3):748-58.
- Perreault M, Zulyniak MA, Badoud F, Stephenson S, Badawi A, Buchholz A, Mutch DM. A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals. PLoS One. 2014 Feb 10;9(2):e88539.
- https://www.lifeextension.com/pdf/bloodtestsamples/omega_check_interpretation_guide.pdf. Accessed September 29, 2015.
- Nakamura S, Takamura T, Matsuzawa-Nagata N, et al. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biolog Chem. 2009 May 29;284(22):14809-18.
- Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS. TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 2006 Nov;11;6(11):3015-25.
- Shaw B, Lambert S, Wong MH, Ralston JC, Stryjecki C, Mutch DM. Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes. J Nutrigenet Nutrigenomics. 2013;6(1):1-15.
- Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010 Jan 9;375(9709):132-40.
- Packard RR, Libby P. Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem. 2008 Jan;54(1):24-38.
- Lopez-Garcia E, Schulze MB, Meigs JB, Manson JE, Rifai N, Stampfer MJ, Willett WC, Hu FB. Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction. J Nutr. 2005 Mar;135(3):562-6.
- Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. J Acad Nutr Diet. 2012 Jul;112(7):1029-41, 1041.e1-15.
- Khandelwal S, Kelly L, Malik R, Prabhakaran D, Reddy S. Impact of omega-6fatty acids on cardiovascular outcomes: A review. J Preventive Cardiol. 2013 Feb;2(3):325-336.
- Park MS, Kim MJ, Ji GE. Assessment of lipopolysaccharide-binding activity of Bifidobacterium and its relationship with cell surface hydrophobicity, autoaggregation, and inhibition of interleukin-8 production. J Microbiol Biotechnol. 2007 Jul;17(7):1120-1126.
- Silhavy TJ, Kahne D, Walker S. The bacterial cell envelope. Cold Spring Harb Perspect Biol. 2010 May;2(5):a000414.
- Van Amersfoort ES, Van Berkel TJ, Kuiper J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clinical microbiology reviews. 2003 Jul;16(3):379-414.
- Cani PD, Neyrinck AM, Fava F, et al. Selective increases of bifido bacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia. 2007 Nov;50(11):2374-83.
- Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008 Jun;57(6):1470-81.
- Kim KA, Gu W, Lee IA, Joh EH, Kim DH. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One. 2012;7(10):e47713.
- Kelly CJ, Colgan SP, Frank DN. Of microbes and meals: the health consequences of dietary endotoxemia. Nutr Clin Pract. 2012 Apr;27(2):215-25.
- Patel C, Ghanim H, Ravishankar S, et al. Prolonged reactive oxygen species generation and nuclear factor-kappa Bactivation after a high-fat, high-carbohydrate meal in the obese. J Clin Endocrinol Metab. 2007 Nov;92(11):4476-9.
- Ghanim H, Abuaysheh S, Sia CL, et al. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance. Diabetes Care. 2009 Dec;32(12):2281-7.
- Fogarty CL, Nieminen JK, Peräneva L, et al. High-fat meals induce systemic cytokine release without evidence of endotoxemia-mediated cytokine production from circulating monocytes or myeloid dendritic cells. Acta Diabetol. 2015 Apr;52(2):315-22.
- Johnstone A. Fasting for weight loss: an effective strategy or latest dieting trend? Int J Obes (Lond). 2015 May;39(5):727-33.
- Weigle DS, Breen PA, Matthys CC, et al. A high-protein diet induces sustained reductions in appetite, ad libitum caloric intake, and body weight despite compensatory changes in diurnal plasma leptin and ghrelin concentrations. Am J Clin Nutr. 2005 Jul;82(1):41-8.
- Harvie M, Wright C, Pegington M, et al. The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr. 2013 Oct;110(8):1534-47.
- Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell. 2008 Oct;7(5):681-7.
- Levine ME, Suarez JA, Brandhorst S, 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 Metab. 2014 Mar 4;19(3):407-17
- Hoddy KK, Kroeger CM, Trepanowski JF, Barnosky A, Bhutani S, Varady KA. Meal timing during alternate day fasting: Impact on body weight and cardiovascular disease risk in obese adults. Obesity (Silver Spring). 2014 Dec;22(12):2524-31.
- Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012 Nov 21;11:98.
- Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF, Tangney CC, Varady KA. Improvement in coronary heart disease risk factors during an intermittent fasting/calorie restriction regimen: Relationship to adipokine modulations. Nutr Metab (Lond). 2012 Oct 31;9(1):98.
- Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity (Silver Spring). 2013 Jul;21(7):1370-9.
- Thomas DM, Bouchard C, Church T, et al. Why do individuals not lose moreweight from an exercise intervention at a defined dose? An energy balance analysis. Obes Rev. 2012 Oct;13(10):835-47.
- Johns DJ, Hartmann-Boyce J, Jebb SA, Aveyard P, Behavioural Weight Management Review Group. Diet or exercise interventions vs combined behavioral weight management programs: a systematic review and meta-analysis of direct comparisons. J Acad Nutr Diet. 2014 Oct;114(10):1557-68.
- Stiegler P, Cunliffe A. The role of diet and exercise for the maintenance of fat-free mass and resting metabolic rate during weight loss. Sports Med. 2006;36(3):239-62.
- Thomas DM, Ciesla A, Levine JA, Stevens JG, Martin CK. A mathematical model of weight change with adaptation. Math Biosci Eng. 2009 Oct;6(4):873-87.
- Heymsfield SB, Gonzalez MC, Shen W, Redman L, Thomas D. Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev. 2014 Apr;15(4):310-21.
- Thomas DM, Gonzalez MC, Pereira AZ, Redman LM, Heymsfield SB. Time to correctly predict the amount of weight loss with dieting. J Acad Nutr Diet. 2014 Jun;114(6):857-61.
- Puolanne E, Halonen M. Theoretical aspects of water-holding in meat. Meat Sci. 2010 Sep;86(1):151-65.
- Kreitzman SN, Coxon AY, Szaz KF. Glycogen storage: illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition. Am J Clin Nutr. 1992 Jul;56(1 Suppl):292S-293S.
- Villareal DT, Apovian CM, Kushner RF, Klein S; American Society for Nutrition; NAASO, The Obesity Society. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am J Clin Nutr. 2005 Nov;82(5):923-34.
- Welle S, Lilavivat U, Campbell RG. Thermic effect of feeding in man: increased plasma norepinephrine levels following glucose but not protein or fat consumption. Metabolism. 1981 Oct;30(10):953-8.
- Segal KR, Albu J, Chun A, Edano A, Legaspi B, Pi-Sunyer FX. Independent effects of obesity and insulin resistance on postprandial thermogenesis in men. J Clin Invest. 1992 Mar;89(3):824-33.
- Goodpaster BH, Park SW, Harris TB, et al. The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci. 2006 Oct;61(10):1059-64.
- Ishigaki EY, Ramos LG, Carvalho ES, Lunardi AC. Effectiveness of muscle strengthening and description of protocols for preventing falls in the elderly: a systematic review. Braz J Phys Ther. 2014 Mar-Apr;18(2):111-8.
- Gosker HR, Wouters EF, van der Vusse GJ, Schols AM. Skeletal muscle dysfunction in chronic obstructive pulmonary disease and chronic heart failure: underlying mechanisms and therapy perspectives. Am J Clin Nutr. 2000 May;71(5):1033-47.
- Gouzi F, Maury J, Molinari N, et al. Reference values for vastuslateralis fiber size and type in healthy subjects over 40 years old: a systematic review and meta-analysis. J Appl Physiol (1985). 2013 Aug 1;115(3):346-54.
- Deutz NE, Bauer JM, Barazzoni R, et al. Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group. Clin Nutr. 2014 Dec;33(6):929-36.
- Bauer J, Biolo G, Cederholm T, et al. Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group. J Am Med Dir Assoc. 2013 Aug;14(8):542-59.
- Hastings MH, Reddy AB, Maywood ES. A clockwork web: circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci. 2003 Aug;4(8):649-61.
- Whitworth JA, Brown MA, Kelly JJ, Williamson PM. Mechanisms of cortisol-induced hypertension in humans. Steroids. 1995 Jan;60(1):76-80.
- Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A . 2009 Mar 17;106(11):4453-8.
- Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med Rev. 2005 Feb;9(1):25-39
- Scheer FA, Morris CJ, Shea SA. The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors. Obesity (Silver Spring). 2013 Mar;21(3):421-3.
- Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Apr;37(4):604-11.
- Jakubowicz D, Barnea M, Wainstein J, Froy O. High caloric intake at breakfast vs. dinner differentially influences weight loss of overweight and obese women. Obesity (Silver Spring). 2013 Dec;21(12):2504-12.
- Dhurandhar EJ, Dawson J, Alcorn A, et al. The effectiveness of breakfast recommendations on weight loss: a randomized controlled trial. Am J Clin Nutr. 2014 Aug;100(2):507-13.
- Zilberter T, Zilberter EY. Breakfast: to skip or not to skip? Front Public Health. 2014 Jun 3;2:59.
- Willett WC. The dietary pyramid: does the foundation need repair? Am J Clin Nutr. 1998 Aug;68(2):218-9.
- Nestle M. Toward more healthful dietary patterns--a matter of policy. Public Health Rep. 1998 Sep-Oct;113(5):420-3.
- Johnston CS. Uncle Sam’s diet sensation: MyPyramid--an overview and commentary. Med Gen Med. 2005 Aug 2;7(3):78.