Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms

In the paper

“Several population-based and prospective epidemiological studies have shown that adherence to the Mediterranean diet might have a protective effect against cardiovascular disease, stroke, obesity, diabetes, hypertension, several type of cancers, allergic diseases and, most recently, Alzheimer and Parkinson’s disease (7–18).”

What the sources say

• Partly supported

  The Discussion (page not specified) reports lower risks of coronary heart disease, stroke, and cardiovascular mortality with greater Mediterranean-diet adherence. It also discusses weight loss and lower blood pressure, but the supplied passages do not support the attributed protective effects against diabetes, cancers, allergic diseases, or Alzheimer’s and Parkinson’s disease. (LLM, conf=0.88)

  cites [7] Fung, 2009, Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women, Circulation sourceExperimental — accuracy not yet measured
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [8] Lopez-Garcia, 2014, The Mediterranean-style dietary pattern and mortality among men and women with cardiovascular disease, Am J Clin Nutr sourceExperimental — accuracy not yet measured
• Not checked yetcites [9] Tektonidis, 2015, A Mediterranean diet and risk of myocardial infarction, heart failure and stroke: a population-based cohort study, Atherosclerosis source
• Partly supported

  The Discussion (page unavailable) reports protective associations for cardiovascular disease, cancer, and obesity; the Abstract reports lower BMI and obesity risk with greater Mediterranean-diet adherence in a cross-sectional Spanish population. Our copy does not report a protective effect of Mediterranean-diet adherence against stroke, diabetes, hypertension, allergic diseases, or Alzheimer’s or Parkinson’s disease. Its mention of diabetes and hypertension concerns risks associated with obesity, not effects of the diet. (LLM, conf=0.88)

  cites [10] Schröder, 2004, Adherence to the traditional Mediterranean diet is inversely associated with body mass index and obesity in a Spanish population, J Nutr sourceExperimental — accuracy not yet measured
• Supported

  The Discussion (page not available in our copy) describes this as a large prospective study and reports that adherence to a Mediterranean diet was associated with a significantly lower risk of developing type 2 diabetes. In the sentence’s group of citations, this paper supports the diabetes component of the hedged claim. (LLM, conf=0.92)

  cites [11] Martínez-González, 2008, Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study, BMJ source
• Not checked yetcites [12] Núñez-Córdoba, 2009, The Mediterranean diet and incidence of hypertension: the Seguimiento Universidad de Navarra (SUN) Study, Am J Epidemiol source
• Not checked yetcites [13] Panagiotakos, 2007, Long-term adoption of a Mediterranean diet is associated with a better health status in elderly people; a cross-sectional survey in Cyprus, Asia Pac J Clin Nutr
• Not checked yetcites [14] La Vecchia, 2009, Association between Mediterranean dietary patterns and cancer risk, Nutr Rev source
• Partly supported

  The study summary (p. 2) reports a modest association between Mediterranean-diet adherence and lower breast-cancer risk, particularly in postmenopausal women. It does not establish protection against several types of cancer or the other listed conditions, including cardiovascular and neurological diseases. (LLM, conf=0.88)

  cites [15] Buckland, 2013, Adherence to the Mediterranean diet and risk of breast cancer in the European prospective investigation into cancer and nutrition cohort study, Int J Cancer sourceExperimental — accuracy not yet measured
• Not checked yetcites [16] Buckland, 2010, Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study, Am J Clin Nutr source

In the paper

“However, accumulating data from a combination of epidemiological, human clinical trials, animal and molecular studies indicate that diet remains a key factor in the prevention of cardiovascular disease, obesity, type 2 diabetes and some of the most common types of cancer (6).”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [6] Fontana, 2015, Promoting health and longevity through diet: from model organisms to humans, Cell source

In the paper

“In contrast, a poor adherence to the Mediterranean diet was associated with increased l-Ruminococcus and Streptococcus bacteria, and higher urinary TMAO concentration (96).”

What the sources say

• Partly supported

  The Discussion reports that lower Mediterranean-diet adherence is linked to higher urinary TMAO. The section ‘Microbial genera linked to specific intake of nutrients and dietary patterns’ associates L-Ruminococcus and Streptococcus with animal-derived nutrients and negatively with vegetable-based diets, but does not directly establish that both increase with lower Mediterranean-diet adherence. Page numbers are not available in our copy. (LLM, conf=0.86)

  cites [96] De Filippis, 2016, High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome, Gut sourceExperimental — accuracy not yet measured

In the paper

“Consuming a Mediterranean diet rich in minimally processed plant foods has been associated with a reduced risk of developing multiple chronic diseases and increased life expectancy.”

In the paper

“The exact mechanism by which an increased adherence to the traditional Mediterranean diet exerts its favorable effects is not known.”

In the paper

“Data from several randomized clinic trials have demonstrated a beneficial effect in the primary and secondary prevention of cardiovascular disease, type 2 diabetes, atrial fibrillation, and breast cancer.”

In the paper

“For example, in Southern Italy in the 1950s, very little meat was eaten, typically only once every week or two, and milk was never used except in coffee (caffé macchiato) or for infants.”

What the sources say

• Not checked yetcites [1] Keys, 1983, From Naples to seven countries–a sentimental journey, Prog Biochem Pharmacol
• Not checked yetcites [2] Keys, 1954, Studies on serum cholesterol and other characteristics of clinically healthy men in Naples, AMA Arch Intern Med source

In the paper

“After a 27-month average follow-up, the trial was stopped early because the Mediterranean diet group had a significant 70% reduction in all-cause mortality due to a 73% reduction in coronary heart disease mortality and analogous major reductions in nonfatal complications (21).”

What the sources say

• Not checked yetcites [21] de Lorgeril, 1994, Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease, Lancet source

In the paper

“Several randomized controlled clinical trials have confirmed that replacing dietary saturated fat intake with vegetable polyunsaturated fats reduce cardiovascular disease incidence by approximately 30%, which is similar to the decrease induced by statin’s therapy (35).”

What the sources say

• Not checked yetcites [35] Cholesterol Treatment Trialists’ (CTT) Collaborators, 2012, The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials, Lancet source

In the paper

“However, we need the bear in mind that epidemiological studies are by nature observational rather than experimental, and the observed associations do not imply a cause–effect relationship.”

In the paper

“Substituting calories from mono- or poly-unsaturated fat with trans fatty acids increases LDL cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a), and lowers plasma high-density lipoprotein cholesterol and apolipoprotein A1 levels (44).”

What the sources say

• Not checked yetcites [44] Mozaffarian, 2009, Quantitative effects on cardiovascular risk factors and coronary heart disease risk of replacing partially hydrogenated vegetable oils with other fats and oils, Eur J Clin Nutr source

In the paper

“In a large epidemiological study, involving 22,043 men and women, higher adherence to a traditional Mediterranean diet was associated with a significant lower total, cardiac, and cancer mortality, independently of the individual dietary components (19).”

What the sources say

• Not checked yetcites [19] Trichopoulou, 2003, Adherence to a Mediterranean diet and survival in a Greek population, N Engl J Med source

In the paper

“The absolute risk reduction was of about three major cardiovascular events per 1,000 person-years, for a relative risk reduction of approximately 30%.”

What the sources say

• Not checked yetcites [24] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source

In the paper

“Consistently the incidence of coronary heart disease and certain cancers, which was very low in those countries, has increased substantially (1,2,4).”

What the sources say

• Not checked yetcites [1] Keys, 1983, From Naples to seven countries–a sentimental journey, Prog Biochem Pharmacol
• Not checked yetcites [2] Keys, 1954, Studies on serum cholesterol and other characteristics of clinically healthy men in Naples, AMA Arch Intern Med source
• Not checked yetcites [4] Menotti, 2007, Forty-year coronary mortality trends and changes in major risk factors in the first 10 years of follow-up in the seven countries study, Eur J Epidemiol source

In the paper

“Population-based and prospective epidemiological studies have shown that reduced intake of saturated fat is associated with lower plasma cholesterol levels and reduced incidence of coronary heart disease, especially when saturated fat is substituted with polyunsaturated and monounsaturated fat (33).”

What the sources say

• Not checked yetcites [33] Sacks, 2017, Dietary fats and cardiovascular disease: a presidential advisory from the American Heart Association, Circulation source

In the paper

“Plasma low-density lipoprotein (LDL) cholesterol concentration in monkeys and newborn humans are typically lower than 60 mg/dL, and LDL-cholesterol levels higher than 100 mg/dL are common only in people consuming Western diets rich in saturated fat from animal origin (32).”

What the sources say

• Not checked yetcites [32] Kwiterovich, 1973, Neonatal diagnosis of familial type-II hyperlipoproteinaemia, Lancet source

In the paper

“The problem is that since 1950s, the composition of the Mediterranean diet has changed dramatically, and the quality and quantity of food people eat nowadays, for example in Italy, Greece and Spain, has little to do with the Traditional Mediterranean diet (3).”

What the sources say

• Not checked yetcites [3] Turrini, 2001, Food consumption patterns in Italy: the INN-CA Study 1994-1996, Eur J Clin Nutr source

In the paper

“Other intervention trials using the Mediterranean diet have also shown some beneficial effects in the treatment of obesity, the metabolic syndrome, and arthritis (28–30).”

What the sources say

• Not checked yetcites [28] Shai, 2008, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet, N Engl J Med source
• Not checked yetcites [29] Salas-Salvadó, 2008, Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED randomized trial, Arch Intern Med source
• Not checked yetcites [30] Sköldstam, 2003, An experimental study of a Mediterranean diet intervention for patients with rheumatoid arthritis, Ann Rheum Dis source

In the paper

“In addition, low-glycemic foods rich in dietary fiber have been shown to lower insulin production and increase the levels of short-chain fatty acids produced by fiber fermentation, which have both been demonstrated to inhibit cholesterol synthesis (42).”

What the sources say

• Not checked yetcites [42] Theuwissen, 2008, Water-soluble dietary fibers and cardiovascular disease, Physiol Behav source

In the paper

“The incidence of type 2 diabetes, peripheral artery disease, atrial fibrillation, breast cancer, but not the incidence of heart failure, was significantly reduced in individuals randomized to the Mediterranean diet (25–27).”

What the sources say

• Not checked yetcites [25] Salas-Salvadó, 2011, Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial, Diabetes Care source
• Not checked yetcites [26] Toledo, 2015, Mediterranean diet and invasive breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial, JAMA Intern Med source
• Not checked yetcites [27] Papadaki, 2017, Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial, Eur J Heart Fail source

In the paper

“It has been estimated that substituting 5% of energy intake from saturated fats with an equal amount of energy from polyunsaturated fats, monounsaturated fats, or carbohydrates from whole grains is associated with a 25%, 15%, and 9% lower risk of coronary heart disease, respectively.”

What the sources say

• Not checked yetcites [34] Li, 2015, Saturated fats compared with unsaturated fats and sources of carbohydrates in relation to risk of coronary heart disease: a prospective cohort study, J Am Coll Cardiol source

In the paper

“Hypercholesterolemia is one of the key risk factors in promoting atherosclerosis, which is the underlying cause of approximately 90% of cases of myocardial infarction, 60% of strokes, most cases of chronic heart failure, peripheral arterial disease, and vascular dementia (31).”

What the sources say

• Not checked yetcites [31] Goldstein, 2015, A century of cholesterol and coronaries: from plaques to genes to statins, Cell source

In the paper

“Indeed, individuals heterozygous for mutations that inactivate one copy of the PCSK9 gene have plasma LDL-cholesterol levels that are approximately 30% lower (which are similar to those induced by treatment with statins), and experience a 90% reduction in heart attacks, independently of smoking, hypertension, and diabetes (36).”

What the sources say

• Not checked yetcites [36] Kathiresan, 2008, A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction, N Engl J Med source

In the paper

“Because of the very low consumption of meat, milk, and butter, the intake of saturated fat in the traditional Mediterranean diet is low (approximately 8% of energy), despite a relative high intake of total fat (25% to 35% of calorie) coming predominantly from extra-virgin olive oil, a wide variety of nuts, seeds, and the germ of whole grains.”

In the paper

“Compared with patients randomized to a step I National Cholesterol Education Program prudent diet, those following the Indo-Mediterranean diet rich in α-linolenic acid experienced an approximate 50% reduction in the rate of nonfatal myocardial infarction and an approximate 60% reduction in the rate of sudden cardiac death (23).”

What the sources say

• Not checked yetcites [23] Singh, 2002, Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial, Lancet source

In the paper

“there were 16 cardiac deaths in the control and 3 in the experimental “Mediterranean α-linolenic acid–rich diet” group; 17 nonfatal myocardial infarction in the control and 5 in the experimental groups; overall, mortality was 20 in the control, 8 in the intervention group (21).”

What the sources say

• Not checked yetcites [21] de Lorgeril, 1994, Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease, Lancet source

In the paper

“The PRIDIMED study was a primary prevention randomized trial on the effects of a Mediterranean diet, supplemented with approximately 1 liter per week of extra-virgin olive oil or 30 g of mixed nuts per day, conducted in 7,447 men and women at high cardiometabolic risk, but with no evident cardiovascular disease at baseline.”

What the sources say

• Not checked yetcites [24] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source

In the paper

“However, among the components of the combined primary end point, only the comparisons of stroke risk reached statistical significance, but not myocardial infarction alone.”

What the sources say

• Not checked yetcites [24] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N Engl J Med source

In the paper

“Probably, other lifestyle factors, such as a dramatic increase in sedentary lifestyle, excessive calorie intake, psychological stress and pollution might have contributed to the increased incidence of these and other chronic diseases in all these Mediterranean countries (5).”

What the sources say

• Not checked yetcites [5] Bertozzi, 2017, Beyond calories: an integrated approach to promote health, longevity, and well-being, Gerontology source

In the paper

“In particular, data from randomized controlled studies indicate that high consumption of water-soluble fibers (which are found in high concentrations in beans and fruits) has a significant cholesterol-lowering effect; each additional gram of water-soluble fiber in the diet lowers plasma LDL cholesterol concentrations by approximately 1.12 mg/L (41,42).”

What the sources say

• Not checked yetcites [41] Salas-Salvadó, 2008, Effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: a randomised trial, Br J Nutr source
• Not checked yetcites [42] Theuwissen, 2008, Water-soluble dietary fibers and cardiovascular disease, Physiol Behav source

In the paper

“It has been hypothesized that water-soluble fiber reduces the (re)absorption of cholesterol and bile acids in the small intestine, thus resulting in an augmented LDL uptake by the liver (42).”

What the sources say

• Not checked yetcites [42] Theuwissen, 2008, Water-soluble dietary fibers and cardiovascular disease, Physiol Behav source

In the paper

“In contrast, in another randomized clinical trial, feeding customized, isocaloric, moderately protein-restricted diets for 4–6 weeks to middle-aged overweight and mildly obese men resulted in a significant decrease in body weight, fat mass, and fasting blood glucose levels, and a major increase in circulating FGF21 concentration (79).”

What the sources say

• Not checked yetcites [79] Fontana, 2016, Decreased consumption of branched-chain amino acids improves metabolic health, Cell Rep source

In the paper

“Total protein intake in the traditional Mediterranean diet is on average 20% lower than in typical Western diet (e.g., 90 vs 70 g/day), with animal protein consumption being 50 to 60% lower (e.g., 30 vs 70 g/day).”

In the paper

“In rodents, methionine restriction improves glucose metabolism, protects against obesity and hepatic steatosis, and reduces oxidative stress.”

What the sources say

• Not checked yetcites [80] Brown-Borg, 2017, Cutting back on the essentials: can manipulating intake of specific amino acids modulate health and lifespan, Ageing Res Rev source

In the paper

“The intake of ibuprofen and aspirin has also been associated with a reduction in the risk of developing cancer, in particular colon cancer, and possibly Alzheimer’s disease because of preferentially reduced secretion of the highly amyloidogenic, Abeta42 peptide (62,63).”

What the sources say

• Not checked yetcites [62] Harris, 2012, Reduction in cancer risk by selective and nonselective cyclooxygenase-2 (COX-2) inhibitors, J Exp Pharmacol source
• Not checked yetcites [63] Zhou, 2003, Nonsteroidal anti-inflammatory drugs can lower amyloidogenic Abeta42 by inhibiting Rho, Science source

In the paper

“Moreover, it has been shown that the high-fiber content of the traditional Mediterranean diet can enhance fecal mass and the excretion of estrogens, resulting in reduced plasma concentrations of estrone and estradiol (71).”

What the sources say

• Not checked yetcites [71] Goldin, 1982, Estrogen excretion patterns and plasma levels in vegetarian and omnivorous women, N Engl J Med source

In the paper

“For example, trans fatty acid intake has been associated with elevated inflammatory markers and an increased risk of developing type 2 diabetes (51,52).”

What the sources say

• Not checked yetcites [51] Lopez-Garcia, 2005, Consumption of trans fatty acids is related to plasma biomarkers of inflammation and endothelial dysfunction, J Nutr source
• Not checked yetcites [52] Salmerón, 2001, Dietary fat intake and risk of type 2 diabetes in women, Am J Clin Nutr source

In the paper

“Additionally, a high-fiber diet may directly protect against colon cancer, the second most frequent tumor in Western countries, by accelerating colonic transit and by sequestering and therefore limiting the absorption of carcinogenic substances.”

In the paper

“Importantly, the individuals randomized to the ad libitum modified Mediterranean diet not only lost a significant amount of body weight, but experienced a substantial reduction in fasting glucose and C-peptide, in the area under the curve for insulin, and in total and free testosterone (66).”

What the sources say

• Not checked yetcites [66] Kaaks, 2003, Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial, Eur J Clin Nutr source

In the paper

“It has been hypothesized that the short-chain fatty acids produced by the gut microbiota metabolism of the great bulk of resistant starch and oligosaccharides present in the Mediterranean diet can induce satiety by inhibiting gastric emptying through the increased production of gut hormones, such as glucagon like peptide-1 (GLP-1) and peptide-YY (PYY) (67).”

What the sources say

• Not checked yetcites [67] Cani, 2009, The role of the gut microbiota in energy metabolism and metabolic disease, Curr Pharm Des source

In the paper

“Moreover, the women on the Mediterranean diet had a significant elevation of the plasma concentration of several binding proteins, such as IGFBP-1, IGFBP-2, and SHBG, resulting in a reduction of the biological activity of insulin-like growth factor 1 (IGF-1), testosterone, and estradiol (66).”

What the sources say

• Not checked yetcites [66] Kaaks, 2003, Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial, Eur J Clin Nutr source

In the paper

“This dose is not sufficient to exert, by itself, a powerful anti-inflammatory effect, but it might be high enough to produce a protection against platelet aggregation and coronary thrombosis.”

In the paper

“However, it is possible that the low-glycemic index, the high intake of monounsaturated and n-3 fatty acids, and the lower intake of branch-chain amino acids may exert some additional beneficial effects in reducing insulin resistance and compensatory hyperinsulinemia (69,70).”

What the sources say

• Not checked yetcites [69] Ludwig, 2002, The glycemic index: physiological mechanisms relating to obesity, diabetes, and cardiovascular disease, JAMA source
• Not checked yetcites [70] Lovejoy, 1999, Dietary fatty acids and insulin resistance, Curr Atheroscler Rep source

In the paper

“The aleuron layer of wheat bran contains a number of phytoprotectants (i.e., ferulic acid, alkylresorcinols, apigenin, lignans, and phytic acid), which have antioxidative and anti-inflammatory potential, and anticarcinogenic activities in rodent animal models of colon and skin cancer (56–59).”

What the sources say

• Not checked yetcites [56] Ogiwara, 2002, Radical scavenging activity and cytotoxicity of ferulic acid, Anticancer Res
• Not checked yetcites [57] Ozaki, 1992, Antiinflammatory effect of tetramethylpyrazine and ferulic acid, Chem Pharm Bull (Tokyo) source
• Not checked yetcites [58] Yang, 2001, Inhibition of carcinogenesis by dietary polyphenolic compounds, Annu Rev Nutr source
• Not checked yetcites [59] Reddy, 2000, Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention, Cancer Res

In the paper

“In contrast, data from a recent rodent study show that selectively reducing the dietary intake of branched-chain amino acids significantly improves glucose tolerance, β cell metabolic stress, and body composition (79).”

What the sources say

• Not checked yetcites [79] Fontana, 2016, Decreased consumption of branched-chain amino acids improves metabolic health, Cell Rep source

In the paper

“Moreover, data from several epidemiological studies suggest that high protein intake is associated with an increased risk of obesity, cardiovascular disease, and type 2 diabetes (76).”

What the sources say

• Not checked yetcites [76] Tinker, 2011, Biomarker-calibrated dietary energy and protein intake associations with diabetes risk among postmenopausal women from the Women’s Health Initiative, Am J Clin Nutr source

In the paper

“Most likely, the reduction in body fat induced by this low-energy density high-fiber Mediterranean diet explains most of the improvement in insulin sensitivity, because the beneficial effects on insulin were no longer statistically significant after adjustment for changes in weight and/or waist circumference (66).”

What the sources say

• Not checked yetcites [66] Kaaks, 2003, Effects of dietary intervention on IGF-I and IGF-binding proteins, and related alterations in sex steroid metabolism: the Diet and Androgens (DIANA) Randomised Trial, Eur J Clin Nutr source

In the paper

“Plasma levels of oxidized LDL predict acute coronary heart disease in relatively healthy individuals and in patients with coronary heart disease, and is a prognostic marker for subclinical atherosclerosis (47).”

What the sources say

• Not checked yetcites [47] Meisinger, 2005, Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population, Circulation source

In the paper

“This is important because in multiple model organisms, including rats and mice, dietary methionine restriction has consistently been shown to extend average and maximal life span, and protect against multiple chronic disease, in particular cancer (80).”

What the sources say

• Not checked yetcites [80] Brown-Borg, 2017, Cutting back on the essentials: can manipulating intake of specific amino acids modulate health and lifespan, Ageing Res Rev source

In the paper

“Calorie restriction without malnutrition has been shown to be extremely effective in cancer prevention in rodents and monkeys, and in humans results in major reductions of several metabolic and hormonal factors implicated in the pathogenesis of numerous common cancers and in the biology of aging itself (65).”

What the sources say

• Not checked yetcites [65] Most, 2017, Calorie restriction in humans: an update, Ageing Res Rev source

In the paper

“In addition, methionine restriction induces plasma elevations of adiponectin and FGF21, and reduces serum IGF-1, T4, and leptin concentration, which are all hormonal adaptations induced in long-lived rodents by calorie restriction as well (80).”

What the sources say

• Not checked yetcites [80] Brown-Borg, 2017, Cutting back on the essentials: can manipulating intake of specific amino acids modulate health and lifespan, Ageing Res Rev source

In the paper

“In particular, formononetin, biochanin A, coumestans, genistein, and daidzein (found in beans and in particular fava beans and lupin), which are low-potency estrogenic molecules (i.e., phytoestrogens), can compete with endogenous estrogens in binding to the estrogen receptors, and thus blocking its mitogenic effects (72).”

What the sources say

• Not checked yetcites [72] Surh, 2003, Cancer chemoprevention with dietary phytochemicals, Nat Rev Cancer source

In the paper

“Moreover, it has been shown that isocaloric restriction of protein or substitution of plant for animal proteins markedly inhibits prostate and breast cancer growth in human xenograft animal models of cancer, with reduced serum IGF-1 levels and downregulation of the mechanistic target of rapamycin (mTOR) activity in the tumor and normal tissue as well (74).”

What the sources say

• Not checked yetcites [74] Lamming, 2015, Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model, Oncotarget source

In the paper

“In a recent epidemiological study, individuals aged 50–65 years with the highest protein intake (more than 20% of calories from protein) had a 75% increase in total mortality and a fourfold increase in cancer mortality.”

What the sources say

• Not checked yetcites [75] Levine, 2014, 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 source

In the paper

“Spermidine is known to inhibit histone acetyltransferases, which results in higher resistance to oxidative stress, to increase autophagy as well as to markedly reduce subclinical inflammation and the rates of cell necrosis during aging (60).”

What the sources say

• Not checked yetcites [60] Eisenberg, 2016, Cardioprotection and lifespan extension by the natural polyamine spermidine, Nat Med source

In the paper

“Insulin, estrogens, androgens, and IGF-1 are powerful mitogens for cells, and stimulate the development and growth of several common tumors, including breast, colon, prostate, pancreatic, and endometrial cancer (68).”

What the sources say

• Not checked yetcites [68] Longo, 2010, Calorie restriction and cancer prevention: metabolic and molecular mechanisms, Trends Pharmacol Sci source

In the paper

“Dietary, genetic, and pharmacological (rapamycin) inhibition of mTOR extends life span in multiple model organisms (83).”

What the sources say

• Not checked yetcites [83] Fontana, 2010, Extending healthy life span–from yeast to humans, Science source

In the paper

“Consistently, in a recent randomized clinical trial, obese individuals randomized to a Mediterranean diet for 2 years experienced a reshaping of the gut microbiota, with an increase in Bacteroides, Prevotella, and Faecalibacterium genera, and most importantly of the Roseburia and Ruminococcus genera and Parabacteroides distasonis and Faecalibacterium prausnitzii bacterial species, which are known”

What the sources say

• Not checked yetcites [93] Haro, 2017 ;61(12), Consumption of Two Healthy Dietary Patterns Restored Microbiota Dysbiosis in Obese Patients With Metabolic Dysfunction, Mol Nutr Food Res source

In the paper

“Both the quantity and quality of what we eat is essential to promote metabolic and molecular health (6).”

What the sources say

• Not checked yetcites [6] Fontana, 2015, Promoting health and longevity through diet: from model organisms to humans, Cell source

In the paper

“In contrast, the restriction of individual amino acids upregulates the GCN2 pathway, which stabilizes ATF4, a transcription factor indispensable for the Integrated Stress Response (84).”

What the sources say

• Not checked yetcites [84] Hine, 2015, Endogenous hydrogen sulfide production is essential for dietary restriction benefits, Cell source

In the paper

“Elevated level of TMAO induces vascular inflammation and a direct prothrombotic effect by increasing platelet hyper-responsiveness to multiple agonists in both rodents and humans, and might be involved in the pathogenesis of obesity and type 2 diabetes (90,91).”

What the sources say

• Not checked yetcites [90] Zhu, 2016, Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk, Cell source
• Not checked yetcites [91] Schugar, 2017, The TMAO-producing enzyme flavin-containing monooxygenase 3 regulates obesity and the beiging of white adipose tissue, Cell Rep source

In the paper

“The activation of the pro-aging and pro-cancer mTOR pathways is modulated by energy intake but also by a cocktail of different essential amino acids, with the branched-chain amino acids leucine and isoleucine playing a fundamental role (82).”

What the sources say

• Not checked yetcites [82] Efeyan, 2012, Amino acids and mTORC1: from lysosomes to disease, Trends Mol Med source