References

Albert, B. B., et al. (2014). “Higher omega-3 index is associated with increased insulin sensitivity and more favourable metabolic profile in middle-aged overweight men.” Sci Rep 4: 6697.

We assessed whether omega-3 index (red blood cell concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) was associated with insulin sensitivity and other metabolic outcomes in 47 overweight men aged 46.5 ± 5.1 years. Participants were assessed twice, 16 weeks apart. Insulin sensitivity was assessed by the Matsuda method from an oral glucose tolerance test. Linear associations were examined; stratified analyses were carried out with participants separated according to the omega-3 index: lower tertiles (LOI; n = 31) and highest tertile (HOI; n = 16). Increasing omega-3 index was correlated with higher insulin sensitivity (r = 0.23; p = 0.025), higher disposition index (r = 0.20; p = 0.054), and lower CRP concentrations (r = -0.39; p < 0.0001). Insulin sensitivity was 43% higher in HOI than in LOI men (Matsuda index 6.83 vs 4.78; p = 0.009). Similarly, HOI men had disposition index that was 70% higher (p = 0.013) and fasting insulin concentrations 25% lower (p = 0.038). HOI men displayed lower nocturnal systolic blood pressure (-6.0 mmHg; p = 0.025) and greater systolic blood pressure dip (14.7 vs 10.8%; p = 0.039). Men in the HOI group also had lower concentrations of CRP (41% lower; p = 0.033) and free fatty acids (21% lower, p = 0.024). In conclusion, higher omega-3 index is associated with increased insulin sensitivity and a more favourable metabolic profile in middle-aged overweight men.

Astrup, A., et al. (2020). “Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review.” J Am Coll Cardiol 76(7): 844-857.

The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.

Barnidge, E. K., et al. (2020). “The Right to Food: Building Upon “Food Is Medicine”.” American journal of preventive medicine 59(4): 611-614

Barth, J., et al. (2004). “Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis.” Psychosom Med 66(6): 802-813.

BACKGROUND: Prospective studies on physically healthy subjects have shown an association between depression and the subsequent development of coronary heart disease (CHD). The relative risk in meta-analytic aggregation is 1.64 (confidence interval [CI], 1.29-2.08) for any CHD event. However, the adverse impact of depression on CHD patients has not yet been the subject of a meta-analysis. OBJECTIVE: To quantify the impact of depressive symptoms (eg, BDI, HADS) or depressive disorders (major depression) on cardiac or all-cause mortality. We analyzed the strength of the relationship, the time dependency, and the differences in studies using depressive symptoms or a clinical diagnosis as predictors of mortality. METHOD: English and German language databases (Medline, PsycInfo, PSYNDEX) from 1980 to 2003 were searched for prospective cohort studies. Sixty-two publications were identified. The inclusion criteria were met by 29 publications reporting on 20 studies. A random model was used to estimate the combined overall effect as crude odds ratios (OR) or adjusted hazard ratios (HR [adj]). RESULTS: Depressive symptoms increase the risk of mortality in CHD patients. The risk of depressed patients dying in the 2 years after the initial assessment is two times higher than that of nondepressed patients (OR, 2.24; 1.37-3.60). This negative prognostic effect also remains in the long-term (OR, 1.78; 1.12-2.83) and after adjustment for other risk factors (HR [adj], 1.76; 1.27-2.43). The unfavorable impact of depressive disorders was reported for the most part in the form of crude odds ratios. Within the first 6 months, depressive disorders were found to have no significant effect on mortality (OR, 2.07; CI, 0.82-5.26). However, after 2 years, the risk is more than two times higher for CHD patients with clinical depression (OR, 2.61; 1.53-4.47). Only three studies reported adjusted hazard ratios for clinical depression and supported the results of the bivariate models. CONCLUSIONS: Depressive symptoms and clinical depression have an unfavorable impact on mortality in CHD patients. The results are limited by heterogeneity of the results in the primary studies. There is no clear evidence whether self-report or clinical interview is the more precise predictor. Nevertheless, depression has to be considered a relevant risk factor in patients with CHD.

Benziger, C. P., et al. (2016). “The Global Burden of Disease Study and the Preventable Burden of NCD.” Glob Heart 11(4): 393-397.

Noncommunicable diseases (NCD) now account for more than one-half of the global burden of disease. Cardiovascular diseases account for about one-half of NCD deaths, and the majority of cardiovascular disease deaths occur in low- and middle-income countries. The GBD (Global Burden of Disease) study measures and benchmarks health loss from death or disability from more than 300 diseases in over 100 countries. According to GBD analyses, the rise of NCD is in part due to increased life expectancy due to reduced premature mortality from communicable, child, and maternal illnesses, but preventable risk factors also contribute and present targets for NCD control efforts. In addition to traditional NCD risk factors, like tobacco smoking, high blood pressure, and unhealthful diet, nontraditional risk factors like air pollution and unhealthful alcohol consumption also play a role. The GBD study continues to grow by gathering more data from country partners than ever before, and by measuring health at the national and subnational levels and in smaller time increments. The GBD study will continue to provide the data to set priorities for and measure progress in the global effort to control the rising burden of NCD.

Bertoncini-Silva, C., et al. (2022). “Bioactive dietary components-Anti-obesity effects related to energy metabolism and inflammation.” Biofactors.

Obesity is the result of the long-term energy imbalance between the excess calories consumed and the few calories expended. Reducing the intake of energy dense foods (fats, sugars), and strategies such as fasting and caloric restriction can promote body weight loss. Not only energy in terms of calories, but also the specific composition of the diet can affect the way the food is absorbed and how its energy is stored, used or dissipated. Recent research has shown that bioactive components of food, such as polyphenols and vitamins, can influence obesity and its pathologic complications such as insulin resistance, inflammation and metabolic syndrome. Individual micronutrients can influence lipid turnover but for long-term effects on weight stability, dietary patterns containing several micronutrients may be required. At the molecular level, these molecules modulate signaling and the expression of genes that are involved in the regulation of energy intake, lipid metabolism, adipogenesis into white, beige and brown adipose tissue, thermogenesis, lipotoxicity, adipo/cytokine synthesis, and inflammation. Higher concentrations of these molecules can be reached in the intestine, where they can modulate the composition and action of the microbiome. In this review, the molecular mechanisms by which bioactive compounds and vitamins modulate energy metabolism, inflammation and obesity are discussed.

Blasbalg, T. L., et al. (2011). “Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century.” Am J Clin Nutr 93(5): 950-962.

BACKGROUND: The consumption of omega-3 (n-3) and omega-6 (n-6) essential fatty acids in Western diets is thought to have changed markedly during the 20th century. OBJECTIVE: We sought to quantify changes in the apparent consumption of essential fatty acids in the United States from 1909 to 1999. DESIGN: We calculated the estimated per capita consumption of food commodities and availability of essential fatty acids from 373 food commodities by using economic disappearance data for each year from 1909 to 1999. Nutrient compositions for 1909 were modeled by using current foods (1909-C) and foods produced by traditional early 20th century practices (1909-T). RESULTS: The estimated per capita consumption of soybean oil increased >1000-fold from 1909 to 1999. The availability of linoleic acid (LA) increased from 2.79% to 7.21% of energy (P < 0.000001), whereas the availability of α-linolenic acid (ALA) increased from 0.39% to 0.72% of energy by using 1909-C modeling. By using 1909-T modeling, LA was 2.23% of energy, and ALA was 0.35% of energy. The ratio of LA to ALA increased from 6.4 in 1909 to 10.0 in 1999. The 1909-T but not the 1909-C data showed substantial declines in dietary availability (percentage of energy) of n-6 arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Predicted net effects of these dietary changes included declines in tissue n–3 highly unsaturated fatty acid status (36.81%, 1909-T; 31.28%, 1909-C; 22.95%, 1999) and declines in the estimated omega-3 index (8.28, 1909-T; 6.51, 1909-C; 3.84, 1999). CONCLUSION: The apparent increased consumption of LA, which was primarily from soybean oil, has likely decreased tissue concentrations of EPA and DHA during the 20th century.

Bong, H. Y., et al. (2010). “Effects of corn gluten hydrolyzates, branched chain amino acids, and leucine on body weight reduction in obese rats induced by a high fat diet.” Nutr Res Pract 4(2): 106-113.

In this study, we compared corn gluten hydrolyzates, BCAAs, and leucine for their effects on body weight reduction in high fat-induced obese rats in order to determine the major active components in the corn gluten hydrolyzates. After obesity was induced for 13 weeks with high fat diet, the overweight-induced SD rats (n = 64) were stratified according to body weight, randomly blocked into eight treatments, and raised for 8 weeks. Four groups were changed to a normal diet and the other groups remained on the high fat diet. Each of the groups within both diets was fed either casein, corn gluten hydrolyzates, leucine, or branched chain amino acids, respectively. Daily food intake, body weight gain, and food efficiency ratio were significantly lower in the corn gluten hydrolyzate groups compared to the other groups, regardless of the high fat diet or normal fat diet. The rats fed the corn gluten hydrolyzates diet had the lowest perirenal fat pad weights whereas muscle weight was significantly increased in the corn gluten hydrolyzates groups. Plasma triglyceride, hepatic total lipid, and total cholesterol contents were significantly reduced in the corn gluten hydrolyzates groups. Other lipid profile measurements were not significantly changed. Plasma triglyceride and hepatic total lipid were also significantly reduced in the BCAA and leucine groups. Leptin levels were significantly lower and adiponectin was significantly higher in the corn gluten hydrolyzates groups. Fasting blood glucose, insulin, C-peptide, and HOMA-IR levels were also significantly reduced in the corn gluten hydrozylates groups, regardless of fat level.

Bremer, A. A., et al. (2012). “Toward a unifying hypothesis of metabolic syndrome.” Pediatrics 129(3): 557-570.

Despite a lack of consistent diagnostic criteria, the metabolic syndrome (MetS) is increasingly evident in children and adolescents, portending a tsunami of chronic disease and mortality as this generation ages. The diagnostic criteria for MetS apply absolute cutoffs to continuous variables and fail to take into account aging, pubertal changes, and race/ethnicity. We attempt to define MetS mechanistically to determine its specific etiologies and to identify targets for therapy. Whereas the majority of studies document a relationship of visceral fat to insulin resistance, ectopic liver fat correlates better with dysfunctional insulin dynamics from which the rest of MetS derives. In contrast to the systemic metabolism of glucose, the liver is the primary metabolic clearinghouse for 4 specific foodstuffs that have been associated with the development of MetS: trans-fats, branched-chain amino acids, ethanol, and fructose. These 4 substrates (1) are not insulin regulated and (2) deliver metabolic intermediates to hepatic mitochondria without an appropriate “pop-off” mechanism for excess substrate, enhancing lipogenesis and ectopic adipose storage. Excessive fatty acid derivatives interfere with hepatic insulin signal transduction. Reactive oxygen species accumulate, which cannot be quenched by adjacent peroxisomes; these reactive oxygen species reach the endoplasmic reticulum, leading to a compensatory process termed the “unfolded protein response,” driving further insulin resistance and eventually insulin deficiency. No obvious drug target exists in this pathway; thus, the only rational therapeutic approaches remain (1) altering hepatic substrate availability (dietary modification), (2) reducing hepatic substrate flux (high fiber), or (3) increasing mitochondrial efficiency (exercise).

Brouwer-Brolsma, E. M., et al. (2018). “Dairy product consumption is associated with pre-diabetes and newly diagnosed type 2 diabetes in the Lifelines Cohort Study.” Br J Nutr 119(4): 442-455.

Previous studies show associations between dairy product consumption and type 2 diabetes, but only a few studies conducted detailed analyses for a variety of dairy subgroups. Therefore, we examined cross-sectional associations of a broad variety of dairy subgroups with pre-diabetes and newly diagnosed type 2 diabetes (ND-T2DM) among Dutch adults. In total, 112 086 adults without diabetes completed a semi-quantitative FFQ and donated blood. Pre-diabetes was defined as fasting plasma glucose (FPG) between 5·6 and 6·9 mmol/l or HbA1c% of 5·7-6·4 %. ND-T2DM was defined as FPG ≥7·0 mmol/l or HbA1c ≥6·5 %. Logistic regression analyses were conducted by 100 g or serving increase and dairy tertiles (T1ref), while adjusting for demographic, lifestyle and dietary covariates. Median dairy product intake was 324 (interquartile range 227) g/d; 25 549 (23 %) participants had pre-diabetes; and 1305 (1 %) had ND-T2DM. After full adjustment, inverse associations were observed of skimmed dairy (OR100 g 0·98; 95 % CI 0·97, 1·00), fermented dairy (OR100 g 0·98; 95 % CI 0·97, 0·99) and buttermilk (OR150 g 0·97; 95 % CI 0·94, 1·00) with pre-diabetes. Positive associations were observed for full-fat dairy (OR100 g 1·003; 95 % CI 1·01, 1·06), non-fermented dairy products (OR100 g 1·01; 95 % CI 1·00, 1·02) and custard (ORserving/150 g 1·13; 95 % CI 1·03, 1·24) with pre-diabetes. Moreover, full-fat dairy products (ORT3 1·16; 95 % CI 0·99, 1·35), non-fermented dairy products (OR100 g 1·05; 95 % CI 1·01, 1·09) and milk (ORserving/150 g 1·08; 95 % CI 1·02, 1·15) were positively associated with ND-T2DM. In conclusion, our data showed inverse associations of skimmed and fermented dairy products with pre-diabetes. Positive associations were observed for full-fat and non-fermented dairy products with pre-diabetes and ND-T2DM.

Brouwer-Brolsma, E. M., et al. (2016). “Intake of different types of dairy and its prospective association with risk of type 2 diabetes: The Rotterdam Study.” Nutr Metab Cardiovasc Dis 26(11): 987-995.

BACKGROUND AND AIMS: The prevalence of type 2 diabetes (T2DM) is increasing. Several studies have suggested a beneficial effect of several major dairy nutrients on insulin production and sensitivity. Conversely, harmful effects have been suggested as well. This study aimed to investigate the impact of the full-range of dairy products and its association with incidence T2DM in Dutch adults aged ≥55 years participating in the Rotterdam Study. METHODS AND RESULTS: Dairy intake was assessed with a validated FFQ, including total, skimmed, semi-skimmed, full-fat, fermented, and non-fermented dairy, and subclasses of these product groups. Verified prevalent and incident diabetes were documented. Cox proportional hazards regression and spline regression were used to analyse data, adjusting for age, sex, alcohol, smoking, education, physical activity, body mass index, intake of total energy, energy-adjusted meat, and energy-adjusted fish intake. Median total dairy intake was 398 g/day (IQR 259-559 g/day). Through 9.5 ± 4.1 years of follow-up, 393 cases of incident T2DM were reported. Cox and spline regression did not point towards associations of total dairy consumption, dairy consumption based on fat content, non-fermented or fermented dairy consumption, or individual dairy product consumption with incident T2DM. The HR for total dairy intake and T2DM was 0.93 (95% CI: 0.70-1.23) in the upper quartile (P-for trend 0.76). CONCLUSIONS: This prospective cohort study did not point towards an association between dairy consumption and T2DM.

Brüning, J. C., et al. (2000). “Role of brain insulin receptor in control of body weight and reproduction.” Science 289(5487): 2122-2125.

Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice). Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.

Bulló, M., et al. (2011). “Mediterranean diet and oxidation: nuts and olive oil as important sources of fat and antioxidants.” Curr Top Med Chem 11(14): 1797-1810.

Oxidative stress has been involved in the aetiology of hypertension, insulin resistance, the metabolic syndrome, cardiovascular disease and other chronic conditions. Several epidemiological studies suggest that a diet rich in natural antioxidants is associated with protective effects against major diseases, especially cardiovascular disease. The Mediterranean diet is rich in fat and foods with important antioxidant properties, such as fruits and vegetables, olive oil, and nuts. In this review we focus on epidemiological evidence and clinical trials that relate the Mediterranean diet with oxidative stress markers. We focus our review on two important Mediterranean vegetable sources of potentially oxidized fat-olive oil and nuts.

Bush, D. E., et al. (2005). “Post-myocardial infarction depression.” Evid Rep Technol Assess (Summ)(123): 1-8.

Chan, J. M., et al. (1994). “Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men.” Diabetes Care 17(9): 961-969.

OBJECTIVE: To investigate the relation between obesity, fat distribution, and weight gain through adulthood and the risk of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We analyzed data from a cohort of 51,529 U.S. male health professionals, 40-75 years of age in 1986, who completed biennial questionnaires sent out in 1986, 1988, 1990, and 1992. During 5 years of follow-up (1987-1992), 272 cases of NIDDM were diagnosed among men without a history of diabetes, heart disease, and cancer in 1986 and who provided complete health information. Relative risks (RRs) associated with different anthropometric measures were calculated controlling for age, and multivariate RRs were calculated controlling for smoking, family history of diabetes, and age. RESULTS: We found a strong positive association between overall obesity as measured by body mass index (BMI) and risk of diabetes. Men with a BMI of > or = 35 kg/m2 had a multivariate RR of 42.1 (95% confidence interval [CI] 22.0-80.6) compared with men with a BMI < 23.0 kg/m2. BMI at age 21 and absolute weight gain throughout adulthood were also significant independent risk factors for diabetes. Fat distribution, measured by waist-to-hip ratio (WHR), was a good predictor of diabetes only among the top 5%, while waist circumference was positively associated with the risk of diabetes among the top 20% of the cohort. CONCLUSIONS: These data suggest that waist circumference may be a better indicator than WHR of the relationship between abdominal adiposity and risk of diabetes. Although early obesity, absolute weight gain throughout adulthood, and waist circumference were good predictors of diabetes, attained BMI was the dominant risk factor for NIDDM; even men of average relative weight had significantly elevated RRs.

Chandalia, M., et al. (2000). “Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus.” N Engl J Med 342(19): 1392-1398.

BACKGROUND: The effect of increasing the intake of dietary fiber on glycemic control in patients with type 2 diabetes mellitus is controversial. METHODS: In a randomized, crossover study, we assigned 13 patients with type 2 diabetes mellitus to follow two diets, each for six weeks: a diet containing moderate amounts of fiber (total, 24 g; 8 g of soluble fiber and 16 g of insoluble fiber), as recommended by the American Diabetes Association (ADA), and a high-fiber diet (total, 50 g; 25 g of soluble fiber and 25 g of insoluble fiber), containing foods not fortified with fiber (unfortified foods). Both diets, prepared in a research kitchen, had the same macronutrient and energy content. We compared the effects of the two diets on glycemic control and plasma lipid concentrations. RESULTS: Compliance with the diets was excellent. During the sixth week, the high-fiber diet, as compared with the the sixth week of the ADA diet, mean daily preprandial plasma glucose concentrations were 13 mg per deciliter [0.7 mmol per liter] lower (95 percent confidence interval, 1 to 24 mg per deciliter [0.1 to 1.3 mmol per liter]; P=0.04) and mean median difference, daily urinary glucose excretion 1.3 g (0.23; 95 percent confidence interval, 0.03 to 1.83 g; P= 0.008). The high-fiber diet also lowered the area under the curve for 24-hour plasma glucose and insulin concentrations, which were measured every two hours, by 10 percent (P=0.02) and 12 percent (P=0.05), respectively. The high-fiber diet reduced plasma total cholesterol concentrations by 6.7 percent (P=0.02), triglyceride concentrations by 10.2 percent (P=0.02), and very-low-density lipoprotein cholesterol concentrations by 12.5 percent (P=0.01). CONCLUSIONS: A high intake of dietary fiber, particularly of the soluble type, above the level recommended by the ADA, improves glycemic control, decreases hyperinsulinemia, and lowers plasma lipid concentrations in patients with type 2 diabetes.

Chassaing, B., et al. (2022). “Randomized Controlled-Feeding Study of Dietary Emulsifier Carboxymethylcellulose Reveals Detrimental Impacts on the Gut Microbiota and Metabolome.” Gastroenterology 162(3): 743-756.

BACKGROUND & AIMS: Epidemiologic and murine studies suggest that dietary emulsifiers promote development of diseases associated with microbiota dysbiosis. Although the detrimental impact of these compounds on the intestinal microbiota and intestinal health have been demonstrated in animal and in vitro models, impact of these food additives in healthy humans remains poorly characterized. METHODS: To examine this notion in humans, we performed a double-blind controlled-feeding study of the ubiquitous synthetic emulsifier carboxymethylcellulose (CMC) in which healthy adults consumed only emulsifier-free diets (n = 9) or an identical diet enriched with 15 g per day of CMC (n = 7) for 11 days. RESULTS: Relative to control subjects, CMC consumption modestly increased postprandial abdominal discomfort and perturbed gut microbiota composition in a way that reduced its diversity. Moreover, CMC-fed subjects exhibited changes in the fecal metabolome, particularly reductions in short-chain fatty acids and free amino acids. Furthermore, we identified 2 subjects consuming CMC who exhibited increased microbiota encroachment into the normally sterile inner mucus layer, a central feature of gut inflammation, as well as stark alterations in microbiota composition. CONCLUSIONS: These results support the notion that the broad use of CMC in processed foods may be contributing to increased prevalence of an array of chronic inflammatory diseases by altering the gut microbiome and metabolome (ClinicalTrials.gov, number NCT03440229).

Chehab, F. F. (2008). “Obesity and lipodystrophy–where do the circles intersect?” Endocrinology 149(3): 925-934.

Adipose tissue is unique in that it can undergo significant hypertrophy and atrophy, resulting in wide ranges of obesities and lipodystrophies. At the base of this elasticity is the lipid-filled adipocyte, which can either overfill by storing large amounts of triglycerides or shrink to a tiny cell by depleting its lipids and as such is remarkable in sustaining insults. As a major energy reservoir, the adipocyte may hold considerable calories necessary for survival and reproduction, two functions that are essential for the survival of the species. This review will summarize some of the recent studies that have advanced our understanding of the central and peripheral mechanisms that are initiated by adipocyte-secreted factors such as leptin, adiponectin, resistin, and retinol-binding protein 4. The intersection of obesity and lipodystrophy results in insulin resistance, which may be unlocked by elucidating the roles of these factors in pathways that control insulin sensitivity and glucose uptake.

Davidson, S., et al. (2007). “Are babies getting bigger? Secular trends in fetal growth in Israel–a retrospective hospital-based cohort study.” Isr Med Assoc J 9(9): 649-651.

BACKGROUND: A paradoxical secular trend of an increase in preterm births and a decrease in low birth weights has been reported in many developed countries over the last 25 years. OBJECTIVE: To determine if this trend is true for Israeli neonates, and to add new information on secular trends in crown-heel length and head circumference. METHODS: A hospital-based historic cohort design was used. Anthropometric data for 32,062 infants born at Rabin Medical Center in 1986-1987, 1994-1996, and 2003-2004 were collected from the hospital’s computerized registry and compared over time for absolute values and proportional trends. RESULTS: For the whole sample (gestational age 24-44 weeks) there was a significant increase in mean birth weight (by 41 g), crown-heel length (by 1.3 cm), and head circumference (by 0.1 cm) from 1986 to 2004 (P < 0.001). A similar trend was found on separate analysis of the post-term babies. Term infants showed an increase in mean length and head circumference (P < 0.001), but not weight, and moderately preterm infants (33-36 weeks) showed an increase in mean weight (81 g, P < 0.001) and mean length (1.0 cm, P < 0.001), but not head circumference. The proportion of post-term (42-44 weeks), preterm (24-36 weeks), very preterm (29-32 weeks), extremely preterm (24-28 weeks), low birth weight (< 2500 g) and very low birth weight (< 1500 g) infants decreased steadily and significantly over time (P < 0.002). CONCLUSIONS: Babies born in our facility, term and preterm, are getting bigger and taller. This increase is apparently associated with a drop (not a rise) in the proportion of preterm infants. These results might reflect improvements in antenatal care and maternal determinants.

De Vogli, R., et al. (2014). “The influence of market deregulation on fast food consumption and body mass index: a cross-national time series analysis.” Bull World Health Organ 92(2): 99-107, 107a.

OBJECTIVE: To investigate the effect of fast food consumption on mean population body mass index (BMI) and explore the possible influence of market deregulation on fast food consumption and BMI. METHODS: The within-country association between fast food consumption and BMI in 25 high-income member countries of the Organisation for Economic Co-operation and Development between 1999 and 2008 was explored through multivariate panel regression models, after adjustment for per capita gross domestic product, urbanization, trade openness, lifestyle indicators and other covariates. The possible mediating effect of annual per capita intake of soft drinks, animal fats and total calories on the association between fast food consumption and BMI was also analysed. Two-stage least squares regression models were conducted, using economic freedom as an instrumental variable, to study the causal effect of fast food consumption on BMI. FINDINGS: After adjustment for covariates, each 1-unit increase in annual fast food transactions per capita was associated with an increase of 0.033 kg/m2 in age-standardized BMI (95% confidence interval, CI: 0.013-0.052). Only the intake of soft drinks–not animal fat or total calories–mediated the observed association (β: 0.030; 95% CI: 0.010-0.050). Economic freedom was an independent predictor of fast food consumption (β: 0.27; 95% CI: 0.16-0.37). When economic freedom was used as an instrumental variable, the association between fast food and BMI weakened but remained significant (β: 0.023; 95% CI: 0.001-0.045). CONCLUSION: Fast food consumption is an independent predictor of mean BMI in high-income countries. Market deregulation policies may contribute to the obesity epidemic by facilitating the spread of fast food.

DiNicolantonio, J. J. and J. H. O’Keefe (2018). “Omega-6 vegetable oils as a driver of coronary heart disease: the oxidized linoleic acid hypothesis.” Open Heart 5(2): e000898.

Drehmer, M., et al. (2016). “Total and Full-Fat, but Not Low-Fat, Dairy Product Intakes are Inversely Associated with Metabolic Syndrome in Adults.” J Nutr 146(1): 81-89.

BACKGROUND: Growing evidence suggests that dairy products may have beneficial cardiometabolic effects. The current guidelines, however, limit the intake of full-fat dairy products. OBJECTIVE: We investigated the association of dairy consumption, types of dairy products, and dairy fat content with metabolic syndrome (MetSyn). METHODS: We analyzed baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicenter cohort study of 15,105 adults aged 35-74 y. We excluded participants with known diabetes, cardiovascular diseases, or other chronic diseases, and those who had extreme values of energy intake, leaving 9835 for analysis. Dairy consumption was assessed by a food-frequency questionnaire. We computed servings per day for total and subgroups of dairy intake. We computed a metabolic risk score (MetScore) as the mean z score of waist circumference, systolic blood pressure, HDL cholesterol (negative z score), fasting triglycerides, and fasting glucose. We performed multivariable linear regression to test the association of servings per day of dairy products with MetScore. RESULTS: In analyses that adjusted for demographics, menopausal status, family history of diabetes, dietary intake, nondietary lifestyle factors, and body mass index, we observed a graded inverse association for MetScore with total dairy (-0.044 ± 0.01, P = 0.009 for each additional dairy servings per day) and full-fat dairy (-0.126 ± 0.03, P < 0.001) but not with low-fat dairy intake. Associations were no longer present after additional adjustments for dairy-derived saturated fatty acids. CONCLUSIONS: Total and especially full-fat dairy food intakes are inversely and independently associated with metabolic syndrome in middle-aged and older adults, associations that seem to be mediated by dairy saturated fatty acids. Dietary recommendations to avoid full-fat dairy intake are not supported by our findings.

DuBroff, R. and M. de Lorgeril (2021). “Fat or fiction: the diet-heart hypothesis.” BMJ Evid Based Med 26(1): 3-7.

Dyall, S. C. (2015). “Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA.” Front Aging Neurosci 7: 52.

Omega-3 polyunsaturated fatty acids (PUFAs) exhibit neuroprotective properties and represent a potential treatment for a variety of neurodegenerative and neurological disorders. However, traditionally there has been a lack of discrimination between the different omega-3 PUFAs and effects have been broadly accredited to the series as a whole. Evidence for unique effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and more recently docosapentaenoic acid (DPA) is growing. For example, beneficial effects in mood disorders have more consistently been reported in clinical trials using EPA; whereas, with neurodegenerative conditions such as Alzheimer’s disease, the focus has been on DHA. DHA is quantitatively the most important omega-3 PUFA in the brain, and consequently the most studied, whereas the availability of high purity DPA preparations has been extremely limited until recently, limiting research into its effects. However, there is now a growing body of evidence indicating both independent and shared effects of EPA, DPA and DHA. The purpose of this review is to highlight how a detailed understanding of these effects is essential to improving understanding of their therapeutic potential. The review begins with an overview of omega-3 PUFA biochemistry and metabolism, with particular focus on the central nervous system (CNS), where DHA has unique and indispensable roles in neuronal membranes with levels preserved by multiple mechanisms. This is followed by a review of the different enzyme-derived anti-inflammatory mediators produced from EPA, DPA and DHA. Lastly, the relative protective effects of EPA, DPA and DHA in normal brain aging and the most common neurodegenerative disorders are discussed. With a greater understanding of the individual roles of EPA, DPA and DHA in brain health and repair it is hoped that appropriate dietary recommendations can be established and therapeutic interventions can be more targeted and refined.

Fiolet, T., et al. (2018). “Consumption of ultra-processed foods and cancer risk: results from NutriNet-Santé prospective cohort.” Bmj 360: k322.

OBJECTIVE: To assess the prospective associations between consumption of ultra-processed food and risk of cancer. DESIGN: Population based cohort study. SETTING AND PARTICIPANTS: 104 980 participants aged at least 18 years (median age 42.8 years) from the French NutriNet-Santé cohort (2009-17). Dietary intakes were collected using repeated 24 hour dietary records, designed to register participants’ usual consumption for 3300 different food items. These were categorised according to their degree of processing by the NOVA classification. MAIN OUTCOME MEASURES: Associations between ultra-processed food intake and risk of overall, breast, prostate, and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS: Ultra-processed food intake was associated with higher overall cancer risk (n=2228 cases; hazard ratio for a 10% increment in the proportion of ultra-processed food in the diet 1.12 (95% confidence interval 1.06 to 1.18); P for trend<0.001) and breast cancer risk (n=739 cases; hazard ratio 1.11 (1.02 to 1.22); P for trend=0.02). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (lipid, sodium, and carbohydrate intakes and/or a Western pattern derived by principal component analysis). CONCLUSIONS: In this large prospective study, a 10% increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10% in risks of overall and breast cancer. Further studies are needed to better understand the relative effect of the various dimensions of processing (nutritional composition, food additives, contact materials, and neoformed contaminants) in these associations. STUDY REGISTRATION: Clinicaltrials.gov NCT03335644.

Gow, R. V. and J. R. Hibbeln (2014). “Omega-3 fatty acid and nutrient deficits in adverse neurodevelopment and childhood behaviors.” Child Adolesc Psychiatr Clin N Am 23(3): 555-590.

Nutritional insufficiencies of omega-3 highly unsaturated fatty acids (HUFAs) may have adverse effects on brain development and neurodevelopmental outcomes. A recent meta-analysis reported a small to modest effect size for the efficacy of omega-3 in youth. Several controlled trials of omega-3 HUFAs combined with micronutrients show sizable reductions in aggressive, antisocial, and violent behavior in youth and young adult prisoners. Studies of HUFAs in youth, however, remain lacking. As the evidence base for omega-3 HUFAs as potential psychiatric treatment develops, dietary adjustments to increase omega-3 and reduce omega-6 HUFA consumption are sensible recommendations based on general health considerations.

Gregori, D., et al. (2014). “Evaluating food front-of-pack labelling: a pan-European survey on consumers’ attitudes toward food labelling.” Int J Food Sci Nutr 65(2): 177-186.

Nutrition labels on pre-packaged foods have been widely used as a medium to foster healthier eating habits in the general population, to contribute to a reduction in the incidence and prevalence of diet-related conditions. Yet, there is no convincing evidence that food labels are an effective means to achieve the desired effect at population level. Several factors have been suggested to account for this decoupling of efficacy, e.g. difficulties in understanding the information on food-labels. The present article presents the results of a survey on Europeans’ understanding of nutritional labels and evaluation on the communication tools for their diffusion. A total of 7550 phone interviews were conducted in 16 European Countries: Austria, Belgium, Denmark, France, Germany, Greece, Italy, the Netherlands, Poland, Portugal, Czech Republic, Slovenia, Spain, Sweden, United Kingdom and Hungary. Consumers were asked about their opinion on nutritional information provided at different levels and their commitment to healthy behaviour.

Gustafson, D. I., et al. (2022). “Making Healthy, Sustainable Diets Accessible and Achievable: A New Framework for Assessing the Nutrition, Environmental, and Equity Impacts of Packaged Foods.” Curr Dev Nutr 6(10): nzac136.

There is a growing global consensus among food system experts that diets and how we source our foods must change. The sustainable nutrition community continues exploring the environmental impact and dietary value of foods. Packaged foods have been largely ignored within the dialogue, and if they are addressed, existing frameworks tend to label them all as “ultraprocessed” and uniformly discourage their consumption. This approach lacks the nuance needed to holistically evaluate packaged foods within recommended dietary patterns. Additionally, there is considerable diversity of opinion within the literature on these topics, especially on how best to improve nutrition security in populations most at risk of diet-related chronic disease. In support of addressing these challenges, 8 sustainability and nutrition experts were convened by Clif Bar & Company for a facilitated discussion on the urgent need to drive adoption of healthy, sustainable diets; the crucial role that certain packaged foods can play in helping make such diets achievable and accessible; and the need for actionable guidance around how to recommend and choose packaged foods that consider human, societal, and planetary health. This article summarizes the meeting discussion, which informed the development of a proposed framework based on guiding principles for defining sustainable, nutritious packaged foods across key nutrition, environmental, economic, and sociocultural well-being indicators. Although additional research is needed to substantiate specific metrics in order to operationalize the framework, it is intended to be a foundation from which to build and refine as science and measurement capabilities advance, and an important step toward broader adoption of healthy, sustainable diets.

Hakimian, J. K., et al. (2019). “Dietary Supplementation with Omega-3 Polyunsaturated Fatty Acids Reduces Opioid-Seeking Behaviors and Alters the Gut Microbiome.” Nutrients 11(8).

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms, and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance, and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 polyunsaturated fatty acids (n-3 PUFAs), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that an n-3-PUFA-enriched diet ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and n-3 PUFA supplementation. We demonstrate that the withdrawal of opioids led to a significant depletion in specific microbiota genera, whereas n-3 PUFA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that n-3 PUFA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in n-3 PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

Hales, C. M., et al. (2020). “Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018.” NCHS Data Brief(360): 1-8.

Obesity is associated with serious health risks (1). Severe obesity further increases the risk of obesity-related complications, such as coronary heart disease and end-stage renal disease (2,3). From 1999-2000 through 2015-2016, a significantly increasing trend in obesity was observed (4). This report provides the most recent national data for 2017-2018 on obesity and severe obesity prevalence among adults by sex, age, and race and Hispanic origin. Trends from 1999-2000 through 2017-2018 for adults aged 20 and over are also presented.

Hall, K. D., et al. (2019). “Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake.” Cell Metab 30(1): 67-77.e63.

We investigated whether ultra-processed foods affect energy intake in 20 weight-stable adults, aged (mean ± SE) 31.2 ± 1.6 years and BMI = 27 ± 1.5 kg/m(2). Subjects were admitted to the NIH Clinical Center and randomized to receive either ultra-processed or unprocessed diets for 2 weeks immediately followed by the alternate diet for 2 weeks. Meals were designed to be matched for presented calories, energy density, macronutrients, sugar, sodium, and fiber. Subjects were instructed to consume as much or as little as desired. Energy intake was greater during the ultra-processed diet (508 ± 106 kcal/day; p = 0.0001), with increased consumption of carbohydrate (280 ± 54 kcal/day; p < 0.0001) and fat (230 ± 53 kcal/day; p = 0.0004), but not protein (-2 ± 12 kcal/day; p = 0.85). Weight changes were highly correlated with energy intake (r = 0.8, p < 0.0001), with participants gaining 0.9 ± 0.3 kg (p = 0.009) during the ultra-processed diet and losing 0.9 ± 0.3 kg (p = 0.007) during the unprocessed diet. Limiting consumption of ultra-processed foods may be an effective strategy for obesity prevention and treatment.

Hallahan, B., et al. (2016). “Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression.” Br J Psychiatry 209(3): 192-201.

BACKGROUND: Trials evaluating efficacy of omega-3 highly unsaturated fatty acids (HUFAs) in major depressive disorder report discrepant findings. AIMS: To establish the reasons underlying inconsistent findings among randomised controlled trials (RCTs) of omega-3 HUFAs for depression and to assess implications for further trials. METHOD: A systematic bibliographic search of double-blind RCTs was conducted between January 1980 and July 2014 and an exploratory hypothesis-testing meta-analysis performed in 35 RCTs including 6665 participants receiving omega-3 HUFAs and 4373 participants receiving placebo. RESULTS: Among participants with diagnosed depression, eicosapentaenoic acid (EPA)-predominant formulations (>50% EPA) demonstrated clinical benefits compared with placebo (Hedge’s G = 0.61, P<0.001) whereas docosahexaenoic acid (DHA)-predominant formulations (>50% DHA) did not. EPA failed to prevent depressive symptoms among populations not diagnosed for depression. CONCLUSIONS: Further RCTs should be conducted on study populations with diagnosed or clinically significant depression of adequate duration using EPA-predominant omega-3 HUFA formulations.

He, F. J., et al. (2014). “Salt reduction in England from 2003 to 2011: its relationship to blood pressure, stroke and ischaemic heart disease mortality.” BMJ Open 4(4): e004549.

OBJECTIVES: To determine the relationship between the reduction in salt intake that occurred in England, and blood pressure (BP), as well as mortality from stroke and ischaemic heart disease (IHD). DESIGN: Analysis of the data from the Health Survey for England. SETTING AND PARTICIPANTS: England, 2003 N=9183, 2006 N=8762, 2008 N=8974 and 2011 N=4753, aged ≥16 years. OUTCOMES: BP, stroke and IHD mortality. RESULTS: From 2003 to 2011, there was a decrease in mortality from stroke by 42% (p<0.001) and IHD by 40% (p<0.001). In parallel, there was a fall in BP of 3.0±0.33/1.4±0.20 mm Hg (p<0.001/p<0.001), a decrease of 0.4±0.02 mmol/L (p<0.001) in cholesterol, a reduction in smoking prevalence from 19% to 14% (p<0.001), an increase in fruit and vegetable consumption (0.2±0.05 portion/day, p<0.001) and an increase in body mass index (BMI; 0.5±0.09 kg/m(2), p<0.001). Salt intake, as measured by 24 h urinary sodium, decreased by 1.4 g/day (p<0.01). It is likely that all of these factors (with the exception of BMI), along with improvements in the treatments of BP, cholesterol and cardiovascular disease, contributed to the falls in stroke and IHD mortality. In individuals who were not on antihypertensive medication, there was a fall in BP of 2.7±0.34/1.1±0.23 mm Hg (p<0.001/p<0.001) after adjusting for age, sex, ethnic group, education, household income, alcohol consumption, fruit and vegetable intake and BMI. Although salt intake was not measured in these participants, the fact that the average salt intake in a random sample of the population fell by 15% during the same period suggests that the falls in BP would be largely attributable to the reduction in salt intake rather than antihypertensive medications. CONCLUSIONS: The reduction in salt intake is likely to be an important contributor to the falls in BP from 2003 to 2011 in England. As a result, it would have contributed substantially to the decreases in stroke and IHD mortality.

Hecht, E. M., et al. (2022). “Cross-sectional examination of ultra-processed food consumption and adverse mental health symptoms.” Public Health Nutr 25(11): 3225-3234.

OBJECTIVE: To explore whether individuals who consume higher amounts of ultra-processed food (UPF) have more adverse mental health symptoms. DESIGN: Using a cross-sectional design, we measured the consumption of UPF as a percentage of total energy intake in kilo-calories using the NOVA food classification system. We explored whether individuals who consume higher amounts of UPF were more likely to report mild depression, more mentally unhealthy days and more anxious days per month using multivariable analyses adjusting for potential confounding variables. SETTING: Representative sample from the United States National Health and Nutrition Examination Survey between 2007 and 2012. PARTICIPANTS: 10 359 adults aged 18+ without a history of cocaine, methamphetamine or heroin use. RESULTS: After adjusting for covariates, individuals with the highest level of UPF consumption were significantly more likely to report at least mild depression (OR: 1·81; 95 % CI1·09, 3·02), more mentally unhealthy (risk ratio (RR): 1·22; 95 % CI 1·18, 1·25) and more anxious days per month (RR: 1·19; 95 % CI 1·16, 1·23). They were also significantly less likely to report zero mentally unhealthy (OR: 0·60; 95 % CI 0·41, 0·88) or anxious days (OR: 0·65; 95 % CI 0·47, 0·90). CONCLUSIONS: Individuals reporting higher intakes of UPF were significantly more likely to report mild depression, more mentally unhealthy and more anxious days and less likely to report zero mentally unhealthy or anxious days. These data add important information to a growing body of evidence concerning the potential adverse effects of UPF consumption on mental health.

Heindel, J. J., et al. (2022). “Obesity II: Establishing causal links between chemical exposures and obesity.” Biochem Pharmacol 199: 115015.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens. Obesogens are a subset of environmental chemicals that act as endocrine disruptors affecting metabolic endpoints. The obesogen hypothesis posits that exposure to endocrine disruptors and other chemicals can alter the development and function of the adipose tissue, liver, pancreas, gastrointestinal tract, and brain, thus changing the set point for control of metabolism. Obesogens can determine how much food is needed to maintain homeostasis and thereby increase the susceptibility to obesity. The most sensitive time for obesogen action is in utero and early childhood, in part via epigenetic programming that can be transmitted to future generations. This review explores the evidence supporting the obesogen hypothesis and highlights knowledge gaps that have prevented widespread acceptance as a contributor to the obesity pandemic. Critically, the obesogen hypothesis changes the narrative from curing obesity to preventing obesity.

Hercberg, S., et al. (2022). “The Nutri-Score nutrition label.” Int J Vitam Nutr Res 92(3-4): 147-157.

Nutri-Score is a front-of-pack nutrition label with summary graded colour-coding, which aims to inform consumers, in a simple and understandable way, of the overall nutritional value of foods, in order to help them to make healthier choices at the point of purchase and to encourage manufacturers to improve the nutritional quality of their products. It is based on a five-colour scale (from dark green to dark orange) associated with letters, from A to E, to optimize logo accessibility and understanding by the consumer. Nutri-Score does not merely characterize foods as “healthy” or “unhealthy”. Rather, the graded logo provides semi-quantitative information, depending on the colour/ letter, of the relative overall nutritional composition of a food product compared to other similar products as to whether it is more or less favourable to health. Nutri-Score is the only proposed labelling scheme that adheres entirely to the concepts and processes that were published by the World Health Organisation (WHO) Europe concerning the validation studies that are required to select and evaluate a front-of-pack nutrition label. The aim of the present paper is to present the scientific basis for the design of the Nutri-Score and to summarize the various studies to validate its calculation method and its graphic format. We explore its effectiveness and superiority compared to other labelling schemes that have been implemented in other countries or supported by pressure groups. The necessity for objective, impartial consideration of how best to use Nutri-Score and avoid misunderstandings is highlighted.

Hibbeln, J. R. and R. V. Gow (2014). “The potential for military diets to reduce depression, suicide, and impulsive aggression: a review of current evidence for omega-3 and omega-6 fatty acids.” Mil Med 179(11 Suppl): 117-128.

The current burden of psychological distress and illness poses as a significant barrier to optimal force efficacy. Here we assess nutrients in military diets, specifically highly unsaturated essential fatty acids, in the reduction of risk or treatment of psychiatric distress. Moderate to strong evidence from several meta-analyses of prospective cohort trials indicate that Mediterranean diet patterns reduce risk of clinical depressions. Specific nutrients and foods of biological interest in relation to mental health outcomes are then discussed and evaluated. Moderate evidence indicates that when fish consumption decreases and simultaneously omega-6 increases, the risk of clinical depressive symptoms are elevated. One meta-analysis examining tissue compositions provides moderate to strong evidence that higher levels of omega-3 highly unsaturated fatty acids (HUFAs) (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) are associated with decreased risk of clinical depressions. Other meta-analytic reviews of randomized placebo-controlled trials provide moderate to strong evidence of significantly improving clinically depressive symptoms when the formulation given was >50% in eicosapentaenoic acid. Finally, a meta-analysis of omega-3 HUFAs provides modest evidence of clinical efficacy for attention-deficit hyperactivity disorder. This article recommends that a rebalancing of the essential fatty acid composition of U.S. military diets, achieve tissue compositions of HUFAs consistent with traditional Mediterranean diets, may help reduce military psychiatric distress and simultaneously increase force efficacy substantially.

Hoepner, L. A. (2019). “Bisphenol a: A narrative review of prenatal exposure effects on adipogenesis and childhood obesity via peroxisome proliferator-activated receptor gamma.” Environ Res 173: 54-68.

There is significant evidence of globally ubiquitous prenatal exposures to bisphenol A (BPA). Childhood obesity as an epidemic has been a global concern for over a decade. Experimental models and epidemiological evidence suggest that BPA may act as an obesogen during adipogenesis. Results from stem cell models and birth cohort studies support the developmental origins of health and disease theory. While literature reviews have presented a variety of potential mechanisms of BPA action during adipogenesis, there remains no consensus. This review is the first to explore the proliferator-activated receptor gamma (PPARγ) mechanism in detail. This review will also examine the obesogenic effect of prenatal exposure to BPA during critical windows of vulnerability. Although vast experimental literature exists, there is limited epidemiological evidence to support the hypothesis for the obesogenic effect of BPA. The primary goal of this review is to provide researchers with a roadmap of existing research and suggestions for future directions for analyzing the relationship between prenatal BPA exposures and childhood obesity.

Holmes, Z. C., et al. (2022). “Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake.” Microbiome 10(1): 114.

BACKGROUND: Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. RESULTS: Here, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals’ gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. CONCLUSIONS: Our findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake. Video Abstract.

Hu, Y., et al. (2019). “Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants.” J Am Heart Assoc 8(19): e013543.

Background Whether marine omega-3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial. Methods and Results This meta-analysis included study-level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed-effect meta-analysis. A meta-regression was conducted to estimate the dose-response relationship between marine omega-3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), marine omega-3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE-IT while introducing statistically significant heterogeneity. Statistically significant linear dose-response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE-IT. Conclusions Marine omega-3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE-IT. Risk reductions appeared to be linearly related to marine omega-3 dose.

Iglesias Molli, A. E., et al. (2017). “Metabolically healthy obese women have longer telomere length than obese women with metabolic syndrome.” PLOS ONE 12(4): e0174945.

INTRODUCTION: Obesity is the principal component in the Metabolic Syndrome (MetS) that determines the progression of metabolic complications. Metabolically healthy obese (MHO) individuals seem to be protected against those complications. Telomere length (TL) as a novel marker of cellular aging had a complex relationship to the MetS. The principal aim of this study was to investigate the TL in MHO, and to study the association between TL and the worsening of the metabolic condition. MATERIAL AND METHODS: We have determined the absolute TL (aTL) in 400 women (mean age of 46.76 ± 15.47 years; range: 18-86 years), grouped according to the metabolic condition in three groups: metabolically healthy non-obese women (MHNO), MHO and obese women with MetS (MSO); and grouped according to the number of components of MetS. RESULTS: We found that MHO displays significantly higher aTL than MSO (p = 0.033; r = -4.63; 95% CI r = -8.89 / -0.37), but did not differ from MHNO. A decrease in aTL with the progressive increase in the number of MetS components was also observed (p < 0.001; r = -2.06; 95% CI r = -3.13 / -0.99). In this way, our results indicate that aTL is influenced by the presence of MetS, but it is not affected by the presence of obesity. DISCUSSION: We found that shorter aTL is not associated with MHO, but is related to MetS and with the increased number of metabolic abnormalities.

Imamura, F., et al. (2018). “Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.” PLoS Med 15(10): e1002670.

BACKGROUND: We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). METHODS AND FINDINGS: Sixteen prospective cohorts from 12 countries (7 from the United States, 7 from Europe, 1 from Australia, 1 from Taiwan) performed new harmonised individual-level analysis for the prospective associations according to a standardised plan. In total, 63,682 participants with a broad range of baseline ages and BMIs and 15,180 incident cases of T2D over the average of 9 years of follow-up were evaluated. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Prespecified interactions by age, sex, BMI, and race/ethnicity were explored in each cohort and were meta-analysed. Potential heterogeneity by cohort-specific characteristics (regions, lipid compartments used for fatty acid assays) was assessed with metaregression. After adjustment for potential confounders, including measures of adiposity (BMI, waist circumference) and lipogenesis (levels of palmitate, triglycerides), higher levels of 15:0, 17:0, and t16:1n-7 were associated with lower incidence of T2D. In the most adjusted model, the hazard ratio (95% CI) for incident T2D per cohort-specific 10th to 90th percentile range of 15:0 was 0.80 (0.73-0.87); of 17:0, 0.65 (0.59-0.72); of t16:1n7, 0.82 (0.70-0.96); and of their sum, 0.71 (0.63-0.79). In exploratory analyses, similar associations for 15:0, 17:0, and the sum of all three fatty acids were present in both genders but stronger in women than in men (pinteraction < 0.001). Whereas studying associations with biomarkers has several advantages, as limitations, the biomarkers do not distinguish between different food sources of dairy fat (e.g., cheese, yogurt, milk), and residual confounding by unmeasured or imprecisely measured confounders may exist. CONCLUSIONS: In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.

Innes, J. K. and P. C. Calder (2018). “Omega-6 fatty acids and inflammation.” Prostaglandins Leukot Essent Fatty Acids 132: 41-48.

Inflammation is a normal process that is part of host defence and tissue healing. However, excessive or unresolved inflammation can lead to uncontrolled tissue damage, pathology and disease. In humans on a Western diet, the omega-6 polyunsaturated fatty acid arachidonic acid (ARA) makes a significant contribution to the fatty acids present in the membrane phospholipids of cells involved in inflammation. ARA is a precursor to a number of potent pro-inflammatory mediators including well described prostaglandins and leukotrienes, which has led to the development of anti-inflammatory pharmaceuticals that target the ARA pathway to successfully control inflammation. Hence, it is commonly believed that increasing dietary intake of the omega-6 fatty acids ARA or its precursor linoleic acid (LA) will increase inflammation. However, studies in healthy human adults have found that increased intake of ARA or LA does not increase the concentrations of many inflammatory markers. Epidemiological studies have even suggested that ARA and LA may be linked to reduced inflammation. Contrastingly, there is also evidence that a high omega-6 fatty acid diet inhibits the anti-inflammatory and inflammation-resolving effect of the omega-3 fatty acids. Thus, the interaction of omega-3 and omega-6 fatty acids and their lipid mediators in the context of inflammation is complex and still not properly understood.

Jernerén, F., et al. (2015). “Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.” Am J Clin Nutr 102(1): 215-221.

BACKGROUND: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE: We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.

Jones, A., et al. (2019). “Front-of-pack nutrition labelling to promote healthier diets: current practice and opportunities to strengthen regulation worldwide.” BMJ Glob Health 4(6): e001882.

Unhealthy diets are a leading cause of death and disability globally. The WHO recommends Member States implement front-of-pack (FOP) nutrition labels to guide consumers towards healthier food choices, as part of comprehensive strategies to prevent diet-related non-communicable diseases. Interest in FOP nutrition labelling is increasing, but there is limited guidance for policymakers developing regulations necessary for effective implementation. A rapidly evolving evidence base, limited regulatory capacity and possibility of legal challenge by affected food industry stakeholders can create ‘regulatory chill’, whereby governments are dissuaded from progressive public health policymaking. We use a framework for analysing public health law and available best-practice guidance to evaluate key components of 31 FOP nutrition labelling regulations endorsed by governments up to June 2019. Analysis of regulatory form shows recent rapid uptake of label formats that are easier for consumers to understand and increasing use of mandatory legislation. However, policymakers must decide much more than whether to apply ‘stars’, ‘traffic lights’ or ‘stop signs’. The substance of effective regulation must contain strategic regulatory objectives, clear specifications for displaying the label on pack, a valid scoring mechanism and a justified scope for including foods. While there are limited data on current practice, good governance of FOP nutrition labelling regulation also requires transparency and accountability in processes of label development, implementation, evaluation and enforcement to promote continuous improvement and withstand undue commercial interference. Whether developing new FOP nutrition labels or reforming existing ones, our findings support policymakers to design and implement best-practice, evidence-informed regulation.

Katz, D. L., et al. (2010). “Performance characteristics of NuVal and the Overall Nutritional Quality Index (ONQI).” Am J Clin Nutr 91(4): 1102s-1108s.

BACKGROUND: Improving diets has considerable potential to improve health, but progress in this area has been limited, and advice to increase fruit and vegetable intake has largely gone unheeded. OBJECTIVES: Our objective was to test the performance characteristics of the Overall Nutritional Quality Index (ONQI), a tool designed to help improve dietary patterns one well-informed choice at a time. DESIGN: The ONQI was developed by a multidisciplinary group of nutrition and public health scientists independent of food industry interests and is the basis for the NuVal Nutritional Guidance System. Dietary guidelines, existing nutritional scoring systems, and other pertinent scientific literature were reviewed. An algorithm incorporating >30 entries that represent both micro- and macronutrient properties of foods, as well as weighting coefficients representing epidemiologic associations between nutrients and health outcomes, was developed and subjected to consumer research and testing of performance characteristics. RESULTS: ONQI and expert panel rankings correlated highly (R = 0.92, P < 0.001). In consumer testing, approximately 80% of >800 study participants indicated that the ONQI would influence their purchase intent. ONQI scoring distinguished the more-healthful DASH (Dietary Approaches to Stop Hypertension) diet (mean score: 46) from the typical American diet according to the National Health and Nutrition Examination Survey (NHANES) 2003-2006 (mean score: 26.5; P < 0.01). In linear regression analysis of the NHANES 2003-2006 populations (n = 15,900), the NuVal system was significantly associated with the Healthy Eating Index 2005 (P < 0.0001). Recently generated data from ongoing studies indicate favorable effects on purchase patterns and significant correlation with health outcomes in large cohorts of men and women followed for decades. CONCLUSION: NuVal offers universally applicable nutrition guidance that is independent of food industry interests and is supported by consumer research and scientific evaluation of its performance characteristics.

Kim, S. P., et al. (2003). “Primacy of hepatic insulin resistance in the development of the metabolic syndrome induced by an isocaloric moderate-fat diet in the dog.” Diabetes 52(10): 2453-2460.

Obesity is highly correlated with insulin resistance and the development of type 2 diabetes. Insulin resistance will result in a decrease in insulin’s ability to stimulate glucose uptake into peripheral tissue and will suppress glucose production by the liver. However, the development of peripheral and hepatic insulin resistance relative to one another in the context of obesity-associated insulin resistance is not well understood. To examine this phenomena, we used the moderate fat-fed dog model, which has been shown to develop both subcutaneous and visceral adiposity and severe insulin resistance. Six normal dogs were fed an isocaloric diet with a modest increase in fat content for 12 weeks, and they were assessed at weeks 0, 6, and 12 for changes in insulin sensitivity and glucose turnover. By week 12 of the diet, there was a more than twofold increase in trunk adiposity as assessed by magnetic resonance imaging because of an accumulation in both subcutaneous and visceral fat depots with very little change in body weight. Fasting plasma insulin had increased by week 6 (150% of week 0) and remained increased up to week 12 of the study (170% of week 0). Surprisingly, there appeared to be no change in the rates of insulin-stimulated glucose uptake as measured by euglycemic-hyperinsulinemic clamps throughout the course of fat feeding. However, there was an increase in steady-state plasma insulin levels at weeks 6 and 12, indicating a moderate degree of peripheral insulin resistance. In contrast to the moderate defect seen in the periphery, there was a marked impairment in insulin’s ability to suppress endogenous glucose production during the clamp such that by week 12 of the study, there was a complete inability of insulin to suppress glucose production. Our results indicate that a diet enriched with a moderate amount of fat results in the development of both subcutaneous and visceral adiposity, hyperinsulinemia, and a modest degree of peripheral insulin resistance. However, there is a complete inability of insulin to suppress hepatic glucose production during the clamp, suggesting that insulin resistance of the liver may be the primary defect in the development of insulin resistance associated with obesity.

Kirkpatrick, C. F., et al. (2019). “Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force.” J Clin Lipidol 13(5): 689-711.e681.

Historically, low-carbohydrate (CHO) and very-low-CHO diets have been used for weight loss. Recently, these diets have been promoted for type 2 diabetes (T2D) management. This scientific statement provides a comprehensive review of the current evidence base available from recent systematic reviews and meta-analyses on the effects of low-CHO and very-low-CHO diets on body weight, lipoprotein lipids, glycemic control, and other cardiometabolic risk factors. In addition, evidence on emerging risk factors and potential safety concerns of low-CHO and very-low-CHO diets, especially for high-risk individuals, such as those with genetic lipid disorders, was reviewed. Based on the evidence reviewed, low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss. These diets may have advantages related to appetite control, triglyceride reduction, and reduction in the use of medication in T2D management. The evidence reviewed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase. There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers. Minimal data are available regarding long-term (>2 years) efficacy and safety. Clinicians are encouraged to consider the evidence discussed in this scientific statement when counseling patients on the use of low-CHO and very-low-CHO diets.

Klimentidis, Y. C., et al. (2011). “Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics.” Proc Biol Sci 278(1712): 1626-1632.

A dramatic rise in obesity has occurred among humans within the last several decades. Little is known about whether similar increases in obesity have occurred in animals inhabiting human-influenced environments. We examined samples collectively consisting of over 20 000 animals from 24 populations (12 divided separately into males and females) of animals representing eight species living with or around humans in industrialized societies. In all populations, the estimated coefficient for the trend of body weight over time was positive (i.e. increasing). The probability of all trends being in the same direction by chance is 1.2 × 10(-7). Surprisingly, we find that over the past several decades, average mid-life body weights have risen among primates and rodents living in research colonies, as well as among feral rodents and domestic dogs and cats. The consistency of these findings among animals living in varying environments, suggests the intriguing possibility that the aetiology of increasing body weight may involve several as-of-yet unidentified and/or poorly understood factors (e.g. viral pathogens, epigenetic factors). This finding may eventually enhance the discovery and fuller elucidation of other factors that have contributed to the recent rise in obesity rates.

Lee, M., et al. (2018). “Dairy food consumption is associated with a lower risk of the metabolic syndrome and its components: a systematic review and meta-analysis.” Br J Nutr 120(4): 373-384.

A systematic review and a meta-analysis of observational studies were performed to assess the dose-response relationship between specific types of dairy foods and the risk of the metabolic syndrome (MetS) and its components. Studies of dairy foods and the risk of the MetS and its components published up to June 2016 were searched using PubMed, EMBASE and a reference search. Random-effects models were used to estimate the pooled relative risks (RR) with 95 % CI. Finally, ten cross-sectional studies, two nested case-control studies and twenty-nine cohort studies were included for the analysis. In a dose-response analysis of cohort studies and cross-sectional studies, the pooled RR of the MetS for a one-serving/d increment of total dairy food (nine studies) and milk (six studies) consumption (200 g/d) were 0·91 (95 % CI 0·85, 0·96) and 0·87 (95 % CI 0·79, 0·95), respectively. The pooled RR of the MetS for yogurt (three studies) consumption (100 g/d) was 0·82 (95 % CI 0·73, 0·91). Total dairy food consumption was associated with lower risk of MetS components, such as hyperglycaemia, elevated blood pressure, hypertriacylglycerolaemia and low HDL- cholesterol. A one-serving/d increment of milk was related to a 12 % lower risk of abdominal obesity, and a one-serving/d increment of yogurt was associated with a 16 % lower risk of hyperglycaemia. These associations were not significantly different by study design, study location or adjustment factors. This meta-analysis showed that specific types of dairy food consumption such as milk and yogurt as well as total dairy food consumption were inversely related to risk of the MetS and its components.

Leite, F. H. M., et al. (2022). “Ultra-processed foods should be central to global food systems dialogue and action on biodiversity.” BMJ Glob Health 7(3).

Li, H., et al. (2022). “Association of Ultraprocessed Food Consumption With Risk of Dementia: A Prospective Cohort.” Neurology.

BACKGROUND: There has been a growing body of evidence associating consumption of ultra-processed foods (UPF) with adverse health outcomes including depression, cardiovascular disease, all-cause mortality. However, whether UPF are associated with dementia is unknown. The authors investigated the associations between UPF and dementia incidence in UK biobank. METHODS: We included 72,083 participants (55 years or older) who were free from dementia at baseline and provided at least two times 24-h dietary assessments from the UK Biobank study. Follow-up occurred through March 2021. UPF were defined according to the NOVA classification. Incident all-cause dementia comprising Alzheimer’s disease and vascular dementia was ascertained through electronic linkages to hospital and mortality records. Cox proportional hazards were used to estimate the association between the proportion (%) of UPF in the diet and the subsequent risk of dementia. In addition, substitution analysis was used to estimate the risk of dementia when substituting UPF with an equivalent proportion of unprocessed or minimally processed foods. RESULTS: During a total of 717,333 person-years of follow-up (median 10.0 years), 518 participants developed dementia, of which 287 developed Alzheimer’s disease and 119 developed vascular dementia. In the fully adjusted model, consumption of UPF was associated with higher risk of dementia (hazard ratio (HR) for 10% increase in UPF: 1.25; 95% confidence interval (CI): 1.14, 1.37), Alzheimer’s disease (HR: 1.14; 95% CI: 1.00, 1.30) and vascular dementia (HR: 1.28; 95% CI: 1.06, 1.55), respectively. In addition, replacing 10% of UPF weight in diet with an equivalent proportion of unprocessed or minimally processed foods was estimated to be associated with a 19% lower risk of dementia (HR: 0.81; 95% CI: 0.74, 0.89). CONCLUSIONS: In this prospective cohort study, higher consumption of UPF was associated with higher risk of dementia, while substituting unpr2ocessed or minimally processed foods for UPF was associated lower risk of dementia.

Liese, A. D., et al. (2005). “Dietary glycemic index and glycemic load, carbohydrate and fiber intake, and measures of insulin sensitivity, secretion, and adiposity in the Insulin Resistance Atherosclerosis Study.” Diabetes Care 28(12): 2832-2838.

OBJECTIVE: We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S(I)), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. RESEARCH DESIGN AND METHODS: Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S(I) and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S(I) with AIR. Multiple linear regression modeling was employed. RESULTS: No association was observed between glycemic index and S(I), fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S(I), insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S(I) and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. CONCLUSION: Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.

Ludwig, D. S., et al. (2013). “Pregnancy weight gain and childhood body weight: a within-family comparison.” PLoS Med 10(10): e1001521.

BACKGROUND: Excessive pregnancy weight gain is associated with obesity in the offspring, but this relationship may be confounded by genetic and other shared influences. We aimed to examine the association of pregnancy weight gain with body mass index (BMI) in the offspring, using a within-family design to minimize confounding. METHODS AND FINDINGS: In this population-based cohort study, we matched records of all live births in Arkansas with state-mandated data on childhood BMI collected in public schools (from August 18, 2003 to June 2, 2011). The cohort included 42,133 women who had more than one singleton pregnancy and their 91,045 offspring. We examined how differences in weight gain that occurred during two or more pregnancies for each woman predicted her children’s BMI and odds ratio (OR) of being overweight or obese (BMI≥85th percentile) at a mean age of 11.9 years, using a within-family design. For every additional kg of pregnancy weight gain, childhood BMI increased by 0.0220 (95% CI 0.0134-0.0306, p<0.0001) and the OR of overweight/obesity increased by 1.007 (CI 1.003-1.012, p = 0.0008). Variations in pregnancy weight gain accounted for a 0.43 kg/m(2) difference in childhood BMI. After adjustment for birth weight, the association of pregnancy weight gain with childhood BMI was attenuated but remained statistically significant (0.0143 kg/m(2) per kg of pregnancy weight gain, CI 0.0057-0.0229, p = 0.0007). CONCLUSIONS: High pregnancy weight gain is associated with increased body weight of the offspring in childhood, and this effect is only partially mediated through higher birth weight. Translation of these findings to public health obesity prevention requires additional study. Please see later in the article for the Editors’ Summary.

Lustig, R. H. (2017). “Processed Food-An Experiment That Failed.” JAMA Pediatr 171(3): 212-214.

Lustig, R. H. (2020). “Ultraprocessed Food: Addictive, Toxic, and Ready for Regulation.” Nutrients 12(11).

Past public health crises (e.g., tobacco, alcohol, opioids, cholera, human immunodeficiency virus (HIV), lead, pollution, venereal disease, even coronavirus (COVID-19) have been met with interventions targeted both at the individual and all of society. While the healthcare community is very aware that the global pandemic of non-communicable diseases (NCDs) has its origins in our Western ultraprocessed food diet, society has been slow to initiate any interventions other than public education, which has been ineffective, in part due to food industry interference. This article provides the rationale for such public health interventions, by compiling the evidence that added sugar, and by proxy the ultraprocessed food category, meets the four criteria set by the public health community as necessary and sufficient for regulation-abuse, toxicity, ubiquity, and externalities (How does your consumption affect me?). To their credit, some countries have recently heeded this science and have instituted sugar taxation policies to help ameliorate NCDs within their borders. This article also supplies scientific counters to food industry talking points, and sample intervention strategies, in order to guide both scientists and policy makers in instituting further appropriate public health measures to quell this pandemic.

Lustig, R. H., et al. (2012). “Public health: The toxic truth about sugar.” Nature 482(7383): 27-29.

Machín, L., et al. (2018). “Traffic Light System Can Increase Healthfulness Perception: Implications for Policy Making.” J Nutr Educ Behav 50(7): 668-674.

OBJECTIVE: To evaluate how information about low nutrient content included in the traffic light labeling system influences consumers’ perception of the healthfulness of products with high content of 1 key nutrient, and to compare the traffic light system with warnings in terms of the perception of healthfulness. DESIGN: Images of front-of-pack (FOP) nutrition labels (the traffic light labeling system with different numbers of nutrients with low content, and warnings) were evaluated in study 1, whereas product labels featuring the different FOP nutrition labels were evaluated in study 2. SETTING: Online studies conducted in Montevideo, Uruguay. PARTICIPANTS: A total of 1,228 Uruguayan Facebook users. MAIN OUTCOME MEASURES: Perception of healthfulness. ANALYSIS: The researchers used ANOVA to evaluate the influence of FOP nutrition labels on perceived healthfulness. RESULTS: The inclusion of information about low nutrient content in the traffic light system statistically significantly increased the perception of the healthfulness of products with high nutrient content. Nutritional warnings showed healthfulness ratings similar to those of the simplified version of the traffic light system. CONCLUSIONS AND IMPLICATIONS: Information about low nutrient content in the traffic light system might be used to infer health, and thus could raise the perception of healthfulness and decrease the traffic light system’s efficacy in discouraging the consumption of unhealthful products. A simplified version of the traffic light highlighting only high-nutrient content or nutritional warnings seems to overcome this problem.

Makki, K., et al. (2018). “The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease.” Cell Host Microbe 23(6): 705-715.

Food is a primordial need for our survival and well-being. However, diet is not only essential to maintain human growth, reproduction, and health, but it also modulates and supports the symbiotic microbial communities that colonize the digestive tract-the gut microbiota. Type, quality, and origin of our food shape our gut microbes and affect their composition and function, impacting host-microbe interactions. In this review, we will focus on dietary fibers, which interact directly with gut microbes and lead to the production of key metabolites such as short-chain fatty acids, and discuss how dietary fiber impacts gut microbial ecology, host physiology, and health. Hippocrates’ notion “Let food be thy medicine and medicine be thy food” remains highly relevant millennia later, but requires consideration of how diet can be used for modulation of gut microbial ecology to promote health.

Mamudu, H. M., et al. (2011). “UN resolution on the prevention and control of non-communicable diseases: an opportunity for global action.” Glob Public Health 6(4): 347-353.

In May 2010, the United Nations (UN) General Assembly unanimously adopted a resolution on non-communicable diseases (NCDs) that called for high-level meetings to address the global burden of NCDs. This paper highlights the growing global burden of NCDs (cardiovascular diseases, cancer, chronic obstructive pulmonary diseases and diabetes), provides a brief historical background on the adoption of the UN NCDs resolution and argues that the resolution provides a remarkable new opportunity for improved international collaboration to address NCDs. Additionally, the paper argues that while the existing World Health Organisation programme on NCDs be continued and expanded, the UN can provide the expanded political leadership that is necessary for multi-sectoral collaboration and can serve as a respected forum for dealing with the issue across numerous key UN agencies.

Méndez-García, L. A., et al. (2022). “Ten-Week Sucralose Consumption Induces Gut Dysbiosis and Altered Glucose and Insulin Levels in Healthy Young Adults.” Microorganisms 10(2).

Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.

Menichetti, G., et al. (2022). “Machine Learning Prediction of Food Processing.” medRxiv: 2021.2005.2022.21257615.

Despite the accumulating evidence that increased consumption of ultra-processed food has adverse health implications, it remains difficult to decide what constitutes processed food. Indeed, the current processing-based classification of food has limited coverage and does not differentiate between degrees of processing, hindering consumer choices and slowing research on the health implications of processed food. Here we introduce a machine learning algorithm that accurately predicts the degree of processing for any food, indicating that over 73% of the U.S. food supply is ultra-processed. We show that the increased reliance of an individual’s diet on ultra-processed food correlates with higher risk of metabolic syndrome, diabetes, angina, elevated blood pressure and biological age, and reduces the bio-availability of vitamins. Finally, we find that replacing foods with less processed alternatives can significantly reduce the health implications of ultra-processed food, suggesting that access to information on the degree of processing, currently unavailable to consumers, could improve population health.Competing Interest StatementA.-L.B. is the founder of Scipher Medicine and Narig Health, companies that explore the use of network-based tools in health, and Datapolis, that focuses on urban data.Funding StatementThis work was conducted with support from Harvard Catalyst|The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL 1TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or the National Institutes of Health. A.-L.B is partially supported by NIH grant 1P01HL132825, American Heart Association grant 151708, and ERC grant 810115-DYNASET.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:We are using epidemiological data from NHANES (https://www.cdc.gov/nchs/nhanes/index.htm).I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll codes and data necessary to train and test the algorithm are available at https://github.com/menicgiulia/MLFoodProcessing. Additional codes are available upon request at giulia.menichetti{at}channing.harvard.edu. All datasets can be accessed through the cited references.

Monteiro, C. A., et al. (2018). “The UN Decade of Nutrition, the NOVA food classification and the trouble with ultra-processing.” Public Health Nutr 21(1): 5-17.

Given evident multiple threats to food systems and supplies, food security, human health and welfare, the living and physical world and the biosphere, the years 2016-2025 are now designated by the UN as the Decade of Nutrition, in support of the UN Sustainable Development Goals. For these initiatives to succeed, it is necessary to know which foods contribute to health and well-being, and which are unhealthy. The present commentary outlines the NOVA system of food classification based on the nature, extent and purpose of food processing. Evidence that NOVA effectively addresses the quality of diets and their impact on all forms of malnutrition, and also the sustainability of food systems, has now accumulated in a number of countries, as shown here. A singular feature of NOVA is its identification of ultra-processed food and drink products. These are not modified foods, but formulations mostly of cheap industrial sources of dietary energy and nutrients plus additives, using a series of processes (hence ‘ultra-processed’). All together, they are energy-dense, high in unhealthy types of fat, refined starches, free sugars and salt, and poor sources of protein, dietary fibre and micronutrients. Ultra-processed products are made to be hyper-palatable and attractive, with long shelf-life, and able to be consumed anywhere, any time. Their formulation, presentation and marketing often promote overconsumption. Studies based on NOVA show that ultra-processed products now dominate the food supplies of various high-income countries and are increasingly pervasive in lower-middle- and upper-middle-income countries. The evidence so far shows that displacement of minimally processed foods and freshly prepared dishes and meals by ultra-processed products is associated with unhealthy dietary nutrient profiles and several diet-related non-communicable diseases. Ultra-processed products are also troublesome from social, cultural, economic, political and environmental points of view. We conclude that the ever-increasing production and consumption of these products is a world crisis, to be confronted, checked and reversed as part of the work of the UN Sustainable Development Goals and its Decade of Nutrition.

Moubarac, J. C., et al. (2014). “Food Classification Systems Based on Food Processing: Significance and Implications for Policies and Actions: A Systematic Literature Review and Assessment.” Curr Obes Rep 3(2): 256-272.

This paper is the first to make a systematic review and assessment of the literature that attempts methodically to incorporate food processing into classification of diets. The review identified 1276 papers, of which 110 were screened and 21 studied, derived from five classification systems. This paper analyses and assesses the five systems, one of which has been devised and developed by a research team that includes co-authors of this paper. The quality of the five systems is assessed and scored according to how specific, coherent, clear, comprehensive and workable they are. Their relevance to food, nutrition and health, and their use in various settings, is described. The paper shows that the significance of industrial food processing in shaping global food systems and supplies and thus dietary patterns worldwide, and its role in the pandemic of overweight and obesity, remains overlooked and underestimated. Once food processing is systematically incorporated into food classifications, they will be more useful in assessing and monitoring dietary patterns. Food classification systems that emphasize industrial food processing, and that define and distinguish relevant different types of processing, will improve understanding of how to prevent and control overweight, obesity and related chronic non-communicable diseases, and also malnutrition. They will also be a firmer basis for rational policies and effective actions designed to protect and improve public health at all levels from global to local.

Mozaffarian, D., et al. (2021). “Food Compass is a nutrient profiling system using expanded characteristics for assessing healthfulness of foods.” Nature Food 2(10): 809-818.

Nutrient profiling systems (NPS) aim to discriminate the healthfulness of foods for front-of-package labelling, warning labels, taxation, company ratings and more. Existing NPS often assess relatively few nutrients and ingredients, use inconsistent criteria across food categories and have not incorporated the newest science. Here, we developed and validated an NPS, the Food Compass, to incorporate a broader range of food characteristics, attributes and uniform scoring principles. We scored 54 attributes across 9 health-relevant domains: nutrient ratios, vitamins, minerals, food ingredients, additives, processing, specific lipids, fibre and protein, and phytochemicals. The domain scores were summed into a final Food Compass Score (FCS) ranging from 1 (least healthy) to 100 (most healthy) for all foods and beverages. Content validity was confirmed by assessing nutrients, food ingredients and other characteristics of public health concern; face validity was confirmed by assessing the FCS for 8,032 foods and beverages reported in NHANES/FNDDS 2015–16; and convergent and discriminant validity was confirmed from comparisons with the NOVA food processing classification, the Health Star Rating and the Nutri-Score. The FCS differentiated food categories and food items well, with mean ± s.d. ranging from 17.1 ± 17.2 for savoury snacks and sweet desserts to 81.6 ± 16.0 for legumes, nuts and seeds. In many food categories, the FCS provided important discrimination of specific foods and beverages as compared with NOVA, the Health Star Rating or the Nutri-Score. On the basis of demonstrated content, convergent and discriminant validity, the Food Compass provides an NPS scoring a broader range of attributes and domains than previous systems with uniform and transparent principles. This publicly available tool will help guide consumer choice, research, food policy, industry reformulations and mission-focused investment decisions.

Nadal, A., et al. (2017). “Endocrine-disrupting chemicals and the regulation of energy balance.” Nat Rev Endocrinol 13(9): 536-546.

Energy balance involves the adjustment of food intake, energy expenditure and body fat reserves through homeostatic pathways. These pathways include a multitude of biochemical reactions, as well as hormonal cues. Dysfunction of this homeostatic control system results in common metabolism-related pathologies, which include obesity and type 2 diabetes mellitus. Metabolism-disrupting chemicals (MDCs) are a particular class of endocrine-disrupting chemicals that affect energy homeostasis. MDCs affect multiple endocrine mechanisms and thus different cell types that are implicated in metabolic control. MDCs affect gene expression and the biosynthesis of key enzymes, hormones and adipokines that are essential for controlling energy homeostasis. This multifaceted spectrum of actions precludes compensatory responses and favours metabolic disorders. Herein, we review the main mechanisms used by MDCs to alter energy balance. This work should help to identify new MDCs, as well as novel targets of their action.

Nemeroff, C. B. and D. L. Musselman (2000). “Are platelets the link between depression and ischemic heart disease?” Am Heart J 140(4 Suppl): 57-62.

The role of platelets as the link between ischemic heart disease and depression is reviewed. Platelet function abnormalities, including increased platelet reactivity, may predispose depressed patients to clotting diatheses and may explain their vulnerability to cardiovascular disease. Platelet physiologic characteristics, influences on platelet response, and indicators of platelet reactivity are discussed. Measurements of platelet activation, secretion, and aggregation have enabled the study of platelet responses in patients with major depression. The findings of clinical trials evaluating platelet responses to antidepressant treatment are described, and recommendations for future studies are proposed.

Niewoehner, C. B., et al. (1990). “Hepatic uptake and metabolism of oral galactose in adult fasted rats.” Am J Physiol 259(6 Pt 1): E804-813.

Galactose is incorporated into glycogen by a different metabolic route than glucose and fructose, the other major dietary monosaccharides. Oral galactose (4 g/kg) was given to 24-h-fasted adult rats to 1) compare quantitatively the disposition of galactose with that of glucose and fructose; 2) examine the effects of galactose on hepatic utilization of other metabolic fuels; and 3) examine circulating and liver galactose concentrations to determine whether net hepatic uptake of galactose, like glucose, occurs against a concentration gradient. Galactose absorption, hepatic blood flow, portal venous, arterial, hepatic venous, and liver concentrations of galactose, glucose, lactate, and alanine, and hepatic glycogen concentrations were measured at intervals up to 240 min. Concentrations entering and exiting the liver, hepatic intracellular concentrations, and net hepatic uptake/output were calculated. Galactose concentration entering the liver increased to a peak of 18.8 +/- 0.8 mumol/ml plasma water at 60 min and then decreased but remained above the control value. Liver galactose concentration increased dramatically from 0.28 +/- 0.04 to 21.2 +/- 1.1 mumol/ml liver water and exceeded plasma concentrations, even during the 1st 120 min when concentration gradients across the liver indicated net galactose extraction. Whole blood galactose concentrations initially were lower and then exceeded plasma concentrations, indicating that erythrocytes maintained galactose concentrations exceeding those in plasma. The data suggest that the hepatic and erythrocyte transport systems for galactose represent active mechanisms. Fifty-one percent of absorbed galactose was lost in urine; 18% of the remaining galactose load could be accounted for by net glycogen accumulation. Net increases in galactose, lactate, and alanine uptake could account for the glycogen synthesized but not for the net hepatic glucose output, which changed very little (6% increase).

Nogal, A., et al. (2021). “Circulating Levels of the Short-Chain Fatty Acid Acetate Mediate the Effect of the Gut Microbiome on Visceral Fat.” Front Microbiol 12: 711359.

BACKGROUND: Acetate is a short-chain fatty acid (SCFA) produced by gut bacteria, which has been implicated in cardio-metabolic health. Here we examine the relationships of circulating acetate levels with gut microbiome composition and diversity and with visceral fat in a large population-based cohort. RESULTS: Microbiome alpha-diversity was positively correlated with circulating acetate levels (Shannon, Beta [95%CI] = 0.12 [0.06, 0.18], P = 0.002) after adjustment for covariates. Six serum acetate-associated bacterial genera were also identified, including positive correlations with Coprococcus, Barnesiella, Ruminococcus, and Ruminococcaceae NK4A21 and negative correlations were observed with Lachnoclostridium and Bacteroides. We also identified a correlation between visceral fat and serum acetate levels (Beta [95%CI] = -0.07 [-0.11, -0.04], P = 2.8 × 10(-4)) and between visceral fat and Lachnoclostridium (Beta [95%CI] = 0.076 [0.042, 0.11], P = 1.44 × 10(-5)). Formal mediation analysis revealed that acetate mediates ∼10% of the total effect of Lachnoclostridium on visceral fat. The taxonomic diversity showed that Lachnoclostridium and Coprococcus comprise at least 18 and 9 species, respectively, including novel bacterial species. By predicting the functional capabilities, we found that Coprococcus spp. present pathways involved in acetate production and metabolism of vitamins B, whereas we identified pathways related to the biosynthesis of trimethylamine (TMA) and CDP-diacylglycerol in Lachnoclostridium spp. CONCLUSIONS: Our data indicates that gut microbiota composition and diversity may influence circulating acetate levels and that acetate might exert benefits on certain cardio-metabolic disease risk by decreasing visceral fat. Coprococcus may play an important role in host health by its production of vitamins B and SCFAs, whereas Lachnoclostridium might have an opposing effect by influencing negatively the circulating levels of acetate and being involved in the biosynthesis of detrimental lipid compounds.

O’Hearn, M., et al. (2022). “Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018.” J Am Coll Cardiol 80(2): 138-151.

BACKGROUND: Few studies have assessed U.S. cardiometabolic health trends-optimal levels of multiple risk factors and absence of clinical cardiovascular disease (CVD)-or its impact on health disparities. OBJECTIVES: The purpose of this study was to investigate U.S. trends in optimal cardiometabolic health from 1999 to 2018. METHODS: We assessed proportions of adults with optimal cardiometabolic health, based on adiposity, blood glucose, blood lipids, blood pressure, and clinical CVD; and optimal, intermediate, and poor levels of each component among 55,081 U.S. adults in the National Health and Nutrition Examination Survey. RESULTS: In 2017-2018, only 6.8% (95% CI: 5.4%-8.1%) of U.S. adults had optimal cardiometabolic health, declining from 1999-2000 (P trend = 0.02). Among components of cardiometabolic health, the largest declines were for adiposity (optimal levels: 33.8%-24.0%; poor levels: 47.7%-61.9%) and glucose (optimal levels: 59.4%-36.9%; poor levels: 8.6%-13.7%) (P trend <0.001 for each). Optimal levels of blood lipids increased from 29.9%-37.0%, whereas poor decreased from 28.3%-14.7% (P trend <0.001). Trends over time for blood pressure and CVD were smaller. Disparities by age, sex, education, and race/ethnicity were evident in all years, and generally worsened over time. By 2017-2018, prevalence of optimal cardiometabolic health was lower among Americans with lower (5.0% [95% CI: 2.8%-7.2%]) vs higher education (10.3% [95% CI: 7.6%-13.0%]); and among Mexican American (3.2% [95% CI: 1.4%-4.9%]) vs non-Hispanic White (8.4% [95% CI: 6.3%-10.4%]) adults. CONCLUSIONS: Between 1999 and 2000 and 2017 and 2018, U.S. cardiometabolic health has been poor and worsening, with only 6.8% of adults having optimal cardiometabolic health, and disparities by age, sex, education, and race/ethnicity. These novel findings inform the need for nationwide clinical and public health interventions to improve cardiometabolic health and health equity.

Qin, P., et al. (2020). “Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.” Eur J Epidemiol 35(7): 655-671.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I(2) = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I(2) = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I(2) = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I(2) = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I(2) = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I(2) = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I(2) = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I(2) = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (P(non-linearity) = 0.359), T2DM (P(non-linearity) = 0.706), hypertension (P(non-linearity) = 0.510) and all-cause mortality (P(non-linearity) = 0.259). For ASBs, we found linear associations with risk of obesity (P(non-linearity) = 0.299) and T2DM (P(non-linearity) = 0.847) and non-linear associations with hypertension (P(non-linearity) = 0.019) and all-cause mortality (P(non-linearity) = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Renoir, T., et al. (2013). “Mind and body: how the health of the body impacts on neuropsychiatry.” Front Pharmacol 4: 158.

It has long been established in traditional forms of medicine and in anecdotal knowledge that the health of the body and the mind are inextricably linked. Strong and continually developing evidence now suggests a link between disorders which involve Hypothalamic-Pituitary-Adrenal axis (HPA) dysregulation and the risk of developing psychiatric disease. For instance, adverse or excessive responses to stressful experiences are built into the diagnostic criteria for several psychiatric disorders, including depression and anxiety disorders. Interestingly, peripheral disorders such as metabolic disorders and cardiovascular diseases are also associated with HPA changes. Furthermore, many other systemic disorders associated with a higher incidence of psychiatric disease involve a significant inflammatory component. In fact, inflammatory and endocrine pathways seem to interact in both the periphery and the central nervous system (CNS) to potentiate states of psychiatric dysfunction. This review synthesizes clinical and animal data looking at interactions between peripheral and central factors, developing an understanding at the molecular and cellular level of how processes in the entire body can impact on mental state and psychiatric health.

Reynolds, A., et al. (2019). “Carbohydrate quality and human health: a series of systematic reviews and meta-analyses.” Lancet 393(10170): 434-445.

BACKGROUND: Previous systematic reviews and meta-analyses explaining the relationship between carbohydrate quality and health have usually examined a single marker and a limited number of clinical outcomes. We aimed to more precisely quantify the predictive potential of several markers, to determine which markers are most useful, and to establish an evidence base for quantitative recommendations for intakes of dietary fibre. METHODS: We did a series of systematic reviews and meta-analyses of prospective studies published from database inception to April 30, 2017, and randomised controlled trials published from database inception to Feb 28, 2018, which reported on indicators of carbohydrate quality and non-communicable disease incidence, mortality, and risk factors. Studies were identified by searches in PubMed, Ovid MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. We excluded prospective studies and trials reporting on participants with a chronic disease, and weight loss trials or trials involving supplements. Searches, data extraction, and bias assessment were duplicated independently. Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, dose-response testing, and subgroup analyses. The GRADE approach was used to assess quality of evidence. FINDINGS: Just under 135 million person-years of data from 185 prospective studies and 58 clinical trials with 4635 adult participants were included in the analyses. Observational data suggest a 15-30% decrease in all-cause and cardiovascular related mortality, and incidence of coronary heart disease, stroke incidence and mortality, type 2 diabetes, and colorectal cancer when comparing the highest dietary fibre consumers with the lowest consumers Clinical trials show significantly lower bodyweight, systolic blood pressure, and total cholesterol when comparing higher with lower intakes of dietary fibre. Risk reduction associated with a range of critical outcomes was greatest when daily intake of dietary fibre was between 25 g and 29 g. Dose-response curves suggested that higher intakes of dietary fibre could confer even greater benefit to protect against cardiovascular diseases, type 2 diabetes, and colorectal and breast cancer. Similar findings for whole grain intake were observed. Smaller or no risk reductions were found with the observational data when comparing the effects of diets characterised by low rather than higher glycaemic index or load. The certainty of evidence for relationships between carbohydrate quality and critical outcomes was graded as moderate for dietary fibre, low to moderate for whole grains, and low to very low for dietary glycaemic index and glycaemic load. Data relating to other dietary exposures are scarce. INTERPRETATION: Findings from prospective studies and clinical trials associated with relatively high intakes of dietary fibre and whole grains were complementary, and striking dose-response evidence indicates that the relationships to several non-communicable diseases could be causal. Implementation of recommendations to increase dietary fibre intake and to replace refined grains with whole grains is expected to benefit human health. A major strength of the study was the ability to examine key indicators of carbohydrate quality in relation to a range of non-communicable disease outcomes from cohort studies and randomised trials in a single study. Our findings are limited to risk reduction in the population at large rather than those with chronic disease. FUNDING: Health Research Council of New Zealand, WHO, Riddet Centre of Research Excellence, Healthier Lives National Science Challenge, University of Otago, and the Otago Southland Diabetes Research Trust.

Rosenbloom, A. L., et al. (1990). “The little women of Loja–growth hormone-receptor deficiency in an inbred population of southern Ecuador.” N Engl J Med 323(20): 1367-1374.

BACKGROUND AND METHODS: Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. RESULTS: Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients’ heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low–less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. CONCLUSIONS: We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males.

Russell, C., et al. (2021). “The drivers, trends and dietary impacts of non-nutritive sweeteners in the food supply: a narrative review.” Nutr Res Rev 34(2): 185-208.

Poor diets, including excess added sugar consumption, contribute to the global burden of disease. Subsequently, many nutrition policies have been implemented to reduce added sugar intake and improve population health, including taxes, education, labelling and environmental interventions. A potential consequence of these policy actions is the substitution of added sugars with non-nutritive sweeteners (NNS) in a variety of foods and beverages. NNS are used to reduce the energy and sugar content of foods and beverages while maintaining their palatability. Evidence of the toxicological risks of NNS is inconsistent, though concerns have been raised over the potential substitution effects of ultra-processed foods containing NNS for whole foods. This review aimed to provide an overview of current NNS food supply and consumption patterns, assess added sugar-reduction policies and their impact on NNS, and determine the impact of NNS on food choice, energy intake and diet quality. NNS are widely available in a variety of products, though most commonly in carbonated beverages, dairy products, confectionery, table-top sweeteners and fruit drinks. However, the longitudinal trends of different product categories, and differences between geographies and economy-income levels, require further study. Few studies have examined NNS consumption trends globally, though an increase in NNS consumption in beverages has been observed in some regions. Research examining how the increased availability of low-sugar, NNS-containing products affects global dietary patterns is limited, particularly in terms of their potential substitution effects.

Sagaceta-Mejía, J., et al. (2022). “Understanding of front of package nutrition labels: Guideline daily amount and warning labels in Mexicans with non-communicable diseases.” PLOS ONE 17(6): e0269892.

One strategy for the prevention and treatment of non-communicable diseases (NCDs) is the implementation of the front-of-pack labeling (FoPL) in foods and beverages. In 2020, Mexico adopted the warning label system (WL) as a new public health policy, whose aim is to help consumers make healthier food choices. Previously, the Guideline Daily Amount (GDA) was the labelling used it. This paper aims to compare the understanding of two FoPL, the GDA and the WL, through the identification of unhealthy products in Mexicans with NCDs. We analyzed data from 14,880 Mexican adults older than 20 years old with NCDs (overweight-obesity (OW/O), self-reported diabetes mellitus 2 (DM2), or/and hypertension (HT), or/and dyslipidemia (Dys)). Participants were randomly assigned to one of two groups: the GDA labeling or WL. Each group had to respond to a survey and had to classify food products images as healthy or unhealthy according to the labelling system to which they were assigned. The correct classification was determined according to the criteria of Chile’s labeling nutrient profile stage 3. To evaluate the correct classification in each one of the groups we evaluated the differences in proportions. Logistic regression models were used to assess the likelihood to correctly classify the product according to participants’ number of diseases and WL information, taking GDA label as a reference. Participants who used the information contained in the GDA label misclassified food product labels in greater proportion (70%), mostly participants with three or more NCDs (participants with OW/O+ HT+ Dys, represent 42.3% of this group); compared with those who used WL (50%). The odds of correct classification of food products using WL image were two times greater compared to GDA image in participants with NCDs; being greater in participants with three or more NCDs. The study results highlight the usefulness of WL as it helps Mexicans with NCDs to classify unhealthy food products more adequately compared with GDA.

Sanna, S., et al. (2019). “Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases.” Nat Genet 51(4): 600-605.

Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity(1). However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available(2), then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality(3), we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test (P = 9.8 × 10(-5)), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D (P = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings.

Scheithauer, T. P. M., et al. (2020). “Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes.” Front Immunol 11: 571731.

The gut microbiota has been linked to the development of obesity and type 2 diabetes (T2D). The underlying mechanisms as to how intestinal microbiota may contribute to T2D are only partly understood. It becomes progressively clear that T2D is characterized by a chronic state of low-grade inflammation, which has been linked to the development of insulin resistance. Here, we review the current evidence that intestinal microbiota, and the metabolites they produce, could drive the development of insulin resistance in obesity and T2D, possibly by initiating an inflammatory response. First, we will summarize major findings about immunological and gut microbial changes in these metabolic diseases. Next, we will give a detailed view on how gut microbial changes have been implicated in low-grade inflammation. Lastly, we will critically discuss clinical studies that focus on the interaction between gut microbiota and the immune system in metabolic disease. Overall, there is strong evidence that the tripartite interaction between gut microbiota, host immune system and metabolism is a critical partaker in the pathophysiology of obesity and T2D.

Schutte, S., et al. (2022). “Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.” Am J Clin Nutr 116(1): 132-150.

BACKGROUND: Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES: The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS: A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS: The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS: A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.

Schwarz, J. M., et al. (2017). “Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children With Obesity.” Gastroenterology 153(3): 743-752.

BACKGROUND & AIMS: Consumption of sugar is associated with obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease, and cardiovascular disease. The conversion of fructose to fat in liver (de novo lipogenesis [DNL]) may be a modifiable pathogenetic pathway. We determined the effect of 9 days of isocaloric fructose restriction on DNL, liver fat, visceral fat (VAT), subcutaneous fat, and insulin kinetics in obese Latino and African American children with habitual high sugar consumption (fructose intake >50 g/d). METHODS: Children (9-18 years old; n = 41) had all meals provided for 9 days with the same energy and macronutrient composition as their standard diet, but with starch substituted for sugar, yielding a final fructose content of 4% of total kilocalories. Metabolic assessments were performed before and after fructose restriction. Liver fat, VAT, and subcutaneous fat were determined by magnetic resonance spectroscopy and imaging. The fractional DNL area under the curve value was measured using stable isotope tracers and gas chromatography/mass spectrometry. Insulin kinetics were calculated from oral glucose tolerance tests. Paired analyses compared change from day 0 to day 10 within each child. RESULTS: Compared with baseline, on day 10, liver fat decreased from a median of 7.2% (interquartile range [IQR], 2.5%-14.8%) to 3.8% (IQR, 1.7%-15.5%) (P < .001) and VAT decreased from 123 cm(3) (IQR, 85-145 cm(3)) to 110 cm(3) (IQR, 84-134 cm(3)) (P < .001). The DNL area under the curve decreased from 68% (IQR, 46%-83%) to 26% (IQR, 16%-37%) (P < .001). Insulin kinetics improved (P < .001). These changes occurred irrespective of baseline liver fat. CONCLUSIONS: Short-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity. These findings support efforts to reduce sugar consumption. ClinicalTrials.gov Number: NCT01200043.

Shangguan, S., et al. (2021). “Health Impact and Cost-Effectiveness of Achieving the National Salt and Sugar Reduction Initiative Voluntary Sugar Reduction Targets in the United States: A Microsimulation Study.” Circulation 144(17): 1362-1376.

BACKGROUND: High intake of added sugar is linked to weight gain and cardiometabolic risk. In 2018, the US National Salt and Sugar Reduction Initiative proposed government-supported voluntary national sugar reduction targets. This intervention’s potential effects and cost-effectiveness are unclear. METHODS: A validated microsimulation model, CVD-PREDICT (Cardiovascular Disease Policy Model for Risk, Events, Detection, Interventions, Costs, and Trends), coded in C++, was used to estimate incremental changes in type 2 diabetes, cardiovascular disease (CVD), quality-adjusted life-years (QALYs), costs, and cost-effectiveness of the US National Salt and Sugar Reduction Initiative policy. The model was run at the individual level, incorporating the annual probability of each person’s transition between health statuses on the basis of risk factors. The model incorporated national demographic and dietary data from the National Health and Nutrition Examination Survey across 3 cycles (2011 through 2016), added sugar-related diseases from meta-analyses, and policy costs and health-related costs from established sources. A simulated nationally representative US population was created and followed until age 100 years or death, with 2019 as the year of intervention start. Findings were evaluated over 10 years and a lifetime from health care and societal perspectives. Uncertainty was evaluated in a 1-way analysis by assuming 50% industry compliance and probabilistic sensitivity analyses through a second-order Monte Carlo approach. Model outputs included averted diabetes cases, CVD events and CVD deaths, QALYs gained, and formal health care cost savings, stratified by age, race, income, and education. RESULTS: Achieving the US National Salt and Sugar Reduction Initiative sugar reduction targets could prevent 2.48 million CVD events, 0.49 million CVD deaths, and 0.75 million diabetes cases; gain 6.67 million QALYs; and save $160.88 billion net costs from a societal perspective over a lifetime. The policy became cost-effective (<150 000/QALYs) at 6 years, highly cost-effective (<50 000/QALYs) at 7 years, and cost-saving at 9 years. Results were robust from a health care perspective, with lower (50%) industry compliance, and in probabilistic sensitivity analyses. The policy could also reduce disparities, with greatest estimated health gains per million adults among Black or Hispanic individuals, lower income, and less educated Americans. CONCLUSIONS: Implementing and achieving the US National Salt and Sugar Reduction Initiative sugar reformation targets could generate substantial health gains, equity gains, and cost savings.

Simopoulos, A. P. (2010). “The omega-6/omega-3 fatty acid ratio: health implications.” OCL 17(5): 267-275.

Simopoulos, A. P., et al. (2013). “Bellagio report on healthy agriculture, healthy nutrition, healthy people.” Nutrients 5(2): 411-423.

The Bellagio Report on Healthy Agriculture, Healthy Nutrition, Healthy People is the result of the meeting held at the Rockefeller Foundation Bellagio Center in Lake Como, Italy, 29 October-2 November 2012. The meeting was science-based but policy-oriented. The role and amount of healthy and unhealthy fats, with attention to the relative content of omega-3 and omega-6 fatty acids, sugar, and particularly fructose in foods that may underlie the epidemics of non-communicable diseases (NCD’s) worldwide were extensively discussed. The report concludes that sugar consumption, especially in the form of high energy fructose in soft drinks, poses a major and insidious health threat, especially in children, and most diets, although with regional differences, are deficient in omega-3 fatty acids and too high in omega-6 fatty acids. Gene-nutrient interactions in growth and development and in disease prevention are fundamental to health, therefore regional Centers on Genetics, Nutrition and Fitness for Health should be established worldwide. Heads of state and government must elevate, as a matter of urgency, Nutrition as a national priority, that access to a healthy diet should be considered a human right and that the lead responsibility for Nutrition should be placed in Ministries of Health rather than agriculture so that the health requirements drive agricultural priorities, not vice versa. Nutritional security should be given the same priority as food security.

Softic, S., et al. (2019). “Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins.” Cell Metab 30(4): 735-753.e734.

Dietary sugars, fructose and glucose, promote hepatic de novo lipogenesis and modify the effects of a high-fat diet (HFD) on the development of insulin resistance. Here, we show that fructose and glucose supplementation of an HFD exert divergent effects on hepatic mitochondrial function and fatty acid oxidation. This is mediated via three different nodes of regulation, including differential effects on malonyl-CoA levels, effects on mitochondrial size/protein abundance, and acetylation of mitochondrial proteins. HFD- and HFD plus fructose-fed mice have decreased CTP1a activity, the rate-limiting enzyme of fatty acid oxidation, whereas knockdown of fructose metabolism increases CPT1a and its acylcarnitine products. Furthermore, fructose-supplemented HFD leads to increased acetylation of ACADL and CPT1a, which is associated with decreased fat metabolism. In summary, dietary fructose, but not glucose, supplementation of HFD impairs mitochondrial size, function, and protein acetylation, resulting in decreased fatty acid oxidation and development of metabolic dysregulation.

Srour, B., et al. (2020). “Ultraprocessed Food Consumption and Risk of Type 2 Diabetes Among Participants of the NutriNet-Santé Prospective Cohort.” JAMA Intern Med 180(2): 283-291.

IMPORTANCE: Ultraprocessed foods (UPF) are widespread in Western diets. Their consumption has been associated in recent prospective studies with increased risks of all-cause mortality and chronic diseases such as cancer, cardiovascular diseases, hypertension, and dyslipidemia; however, data regarding diabetes are lacking. OBJECTIVE: To assess the associations between consumption of UPF and risk of type 2 diabetes (T2D). DESIGN, SETTING, AND PARTICIPANTS: In this population-based prospective cohort study, 104 707 participants aged 18 years or older from the French NutriNet-Santé cohort (2009-2019) were included. Dietary intake data were collected using repeated 24-hour dietary records (5.7 per participant on average), designed to register participants’ usual consumption for more than 3500 different food items. These were categorized according to their degree of processing by the NOVA classification system. MAIN OUTCOMES AND MEASURES: Associations between UPF consumption and risk of T2D were assessed using cause-specific multivariable Cox proportional hazard models adjusted for known risk factors (sociodemographic, anthropometric, lifestyle, medical history, and nutritional factors). RESULTS: A total of 104 707 participants (21 800 [20.8%] men and 82 907 [79.2%] women) were included. Mean (SD) baseline age of participants was 42.7 (14.5) years. Absolute T2D rates in the lowest and highest UPF consumers were 113 and 166 per 100 000 person-years, respectively. Consumption of UPF was associated with a higher risk of T2D (multi-adjusted hazard ratio [HR] for an absolute increment of 10 in the percentage of UPF in the diet, 1.15; 95% CI, 1.06-1.25; median follow-up, 6.0 years; 582 252 person-years; 821 incident cases). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet, for other metabolic comorbidities (HR, 1.13; 95% CI, 1.03-1.23), and for weight change (HR, 1.13; 95% CI, 1.01-1.27). The absolute amount of UPF consumption (grams per day) was consistently associated with T2D risk, even when adjusting for unprocessed or minimally processed food intake (HR for a 100 g/d increase, 1.05; 95% CI, 1.02-1.08). CONCLUSIONS AND RELEVANCE: In this large observational prospective study, a higher proportion of UPF in the diet was associated with a higher risk of T2D. Even though these results need to be confirmed in other populations and settings, they provide evidence to support efforts by public health authorities to recommend limiting UPF consumption. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03335644.

Srour, B., et al. (2019). “Ultra-processed food intake and risk of cardiovascular disease: prospective cohort study (NutriNet-Santé).” Bmj 365: l1451.

OBJECTIVE: To assess the prospective associations between consumption of ultra-processed foods and risk of cardiovascular diseases. DESIGN: Population based cohort study. SETTING: NutriNet-Santé cohort, France 2009-18. PARTICIPANTS: 105 159 participants aged at least 18 years. Dietary intakes were collected using repeated 24 hour dietary records (5.7 for each participant on average), designed to register participants’ usual consumption of 3300 food items. These foods were categorised using the NOVA classification according to degree of processing. MAIN OUTCOME MEASURES: Associations between intake of ultra-processed food and overall risk of cardiovascular, coronary heart, and cerebrovascular diseases assessed by multivariable Cox proportional hazard models adjusted for known risk factors. RESULTS: During a median follow-up of 5.2 years, intake of ultra-processed food was associated with a higher risk of overall cardiovascular disease (1409 cases; hazard ratio for an absolute increment of 10 in the percentage of ultra-processed foods in the diet 1.12 (95% confidence interval 1.05 to 1.20); P<0.001, 518 208 person years, incidence rates in high consumers of ultra-processed foods (fourth quarter) 277 per 100 000 person years, and in low consumers (first quarter) 242 per 100 000 person years), coronary heart disease risk (665 cases; hazard ratio 1.13 (1.02 to 1.24); P=0.02, 520 319 person years, incidence rates 124 and 109 per 100 000 person years, in the high and low consumers, respectively), and cerebrovascular disease risk (829 cases; hazard ratio 1.11 (1.01 to 1.21); P=0.02, 520 023 person years, incidence rates 163 and 144 per 100 000 person years, in high and low consumers, respectively). These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet (saturated fatty acids, sodium and sugar intakes, dietary fibre, or a healthy dietary pattern derived by principal component analysis) and after a large range of sensitivity analyses. CONCLUSIONS: In this large observational prospective study, higher consumption of ultra-processed foods was associated with higher risks of cardiovascular, coronary heart, and cerebrovascular diseases. These results need to be confirmed in other populations and settings, and causality remains to be established. Various factors in processing, such as nutritional composition of the final product, additives, contact materials, and neoformed contaminants might play a role in these associations, and further studies are needed to understand better the relative contributions. Meanwhile, public health authorities in several countries have recently started to promote unprocessed or minimally processed foods and to recommend limiting the consumption of ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03335644.

Suez, J., et al. (2022). “Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.” Cell 185(18): 3307-3328.e3319.

Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

Taneri, P. E., et al. (2022). “Association Between Ultra-Processed Food Intake and All-Cause Mortality: A Systematic Review and Meta-Analysis.” Am J Epidemiol 191(7): 1323-1335.

Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.

Templeman, N. M., et al. (2017). “A causal role for hyperinsulinemia in obesity.” J Endocrinol 232(3): R173-r183.

Insulin modulates the biochemical pathways controlling lipid uptake, lipolysis and lipogenesis at multiple levels. Elevated insulin levels are associated with obesity, and conversely, dietary and pharmacological manipulations that reduce insulin have occasionally been reported to cause weight loss. However, the causal role of insulin hypersecretion in the development of mammalian obesity remained controversial in the absence of direct loss-of-function experiments. Here, we discuss theoretical considerations around the causal role of excess insulin for obesity, as well as recent studies employing mice that are genetically incapable of the rapid and sustained hyperinsulinemia that normally accompanies a high-fat diet. We also discuss new evidence demonstrating that modest reductions in circulating insulin prevent weight gain, with sustained effects that can persist after insulin levels normalize. Importantly, evidence from long-term studies reveals that a modest reduction in circulating insulin is not associated with impaired glucose homeostasis, meaning that body weight and lipid homeostasis are actually more sensitive to small changes in circulating insulin than glucose homeostasis in these models. Collectively, the evidence from new studies on genetic loss-of-function models forces a re-evaluation of current paradigms related to obesity, insulin resistance and diabetes. The potential for translation of these findings to humans is briefly discussed.

Ulijaszek, S. J. (2001). “Secular trend in birthweight among the Purari delta population, Papua New Guinea.” Ann Hum Biol 28(3): 246-255.

The aim of this analysis was to examine the extent and possible seasonal nature of the secular trend in mean birthweight in the Purari delta, Papua New Guinea. This is a country undergoing rapid modernization, and with this has come a secular trend toward increased adult body size in some parts of the country but not others. Birthweight data, collected by month of delivery at Kapuna Hospital in the Purari delta between the years 1969 and 1996, was analysed by year of birth and by season, using one-way analysis of variance and post hoc Scheffé tests with the statistical software SPSS-PC+. A total of 927 birthweights for the years 1969, 1972, 1977, 1994 and 1996 were included in the analysis. Twin births were excluded from analysis, as were births below 1.5 kg. There is clear evidence of a secular trend in increasing mean birthweight between the period 1969 and 1996, with the largest significant difference being between 1977 and 1994, from 2.70 to 2.92 kg. There were no significant differences in mean birthweight between the sexes. The rate of birthweight increase between 1977 and 1994 was 130 g per decade, lower than the gain of 200 g per decade in the period 1994-1996. The decline in birthweight of 90 g per decade during the period 1969-1977 is not statistically significant. The proportion of infants born with low birth weight (< 2.5 kg) shows an increase between 1969 and 1972, and a decline thereafter. While seasonal differences in birthweight during any of the years examined is non-significant, significantly greater mean birthweight across the period 1969-1996 was found for births during the wet season (April to July), and the drier season (August to November), respectively. The secular increase in mean birthweight is likely to be a consequence of the improvements in maternal diet and increased maternal body size that have come with economic modernization. The secular trend of seasonality in mean birthweight among the Purari delta population may be a function of seasonally varied displacement of traditional diet by non-local bought foods, as well as reduced seasonality of maternal workload associated with the processing of the traditional staple food.

van der Hee, B. and J. M. Wells (2021). “Microbial Regulation of Host Physiology by Short-chain Fatty Acids.” Trends Microbiol 29(8): 700-712.

Our ancestral diet consisted of much more nondigestible fiber than that of many societies today. Thus, from an evolutionary perspective the human genome and its physiological and nutritional requirements are not well aligned to modern dietary habits. Fiber reaching the colon is anaerobically fermented by the gut bacteria, which produce short-chain fatty acids (SCFAs) as metabolic by-products. SCFAs play a role in intestinal homeostasis, helping to explain why changes in the microbiota can contribute to the pathophysiology of human diseases. Recent research has shown that SCFAs can also have effects on tissues and organs beyond the gut, through their circulation in the blood. SCFAs not only signal through binding to cognate G-protein-coupled receptors on endocrine and immune cells in the body but also induce epigenetic changes in the genome through effects on the activity of histone acetylase and histone deacetylase enzymes. Furthermore, epigenetic imprinting likely occurs in utero, highlighting the importance of the maternal diet in early life. Here we review current understanding of how SCFAs impact on human and animal physiology and discuss the potential applications of SCFAs in the prevention and treatment of human diseases.

Vanderlee, L., et al. (2021). “The efficacy of ‘high in’ warning labels, health star and traffic light front-of-package labelling: an online randomised control trial.” Public Health Nutr 24(1): 62-74.

OBJECTIVE: To examine the impact of front-of-package (FOP) labels on perceived healthfulness, purchasing intentions and understanding of common FOP systems. DESIGN: A parallel, open-label design randomised participants to different FOP labelling conditions: ‘high in’ warning labels (WL), multiple traffic light labelling (TLL), health star ratings (HSR) (all displayed per serving) or control with no interpretive FOP labelling. Participants completed a brief educational session via a smartphone application and two experimental tasks. In Task 1, participants viewed healthy or unhealthy versions of four products and rated healthiness and purchasing intention on a seven-point Likert-type scale. In Task 2, participants ranked three sets of five products from healthiest to least healthy. SETTING: Online commercial panel. PARTICIPANTS: Canadian residents ≥ 18 years who were involved in household grocery shopping, owned a smartphone and met minimum screen requirements. RESULTS: Data from 1997 participants (n 500/condition) were analysed. Task 1: across most product categories, the TLL and HSR increased perceived healthiness of healthier products. All FOP systems decreased perceived healthiness of less healthy products. Similar, albeit dampened, effects were seen regarding purchasing intentions. Task 2: participants performed best in the HSR, followed by the TLL, WL and control conditions. Lower health literacy was associated with higher perceived healthiness and purchasing intentions and poorer ranking task performance across all conditions. CONCLUSIONS: All FOP labelling systems, after a brief educational session, improved task performance across a wide spectrum of foods. This effect differed depending on the nutritional quality of the products and the information communicated on labels.Trial Registration: NCT03290118.

Vreman, R. A., et al. (2017). “Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model.” BMJ Open 7(8): e013543.

OBJECTIVES: Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. METHODS: Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015-2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. FINDINGS: The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. CONCLUSIONS: The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits.

Walker, R. E., et al. (2019). “Predicting the effects of supplemental EPA and DHA on the omega-3 index.” Am J Clin Nutr 110(4): 1034-1040.

BACKGROUND: Supplemental long-chain omega-3 (n-3) fatty acids (EPA and DHA) raise erythrocyte EPA + DHA [omega-3 index (O3I)] concentrations, but the magnitude or variability of this effect is unclear. OBJECTIVE: The purpose of this study was to model the effects of supplemental EPA + DHA on the O3I. METHODS: Deidentified data from 1422 individuals from 14 published n-3 intervention trials were included. Variables considered included dose, baseline O3I, sex, age, weight, height, chemical form [ethyl ester (EE) compared with triglyceride (TG)], and duration of treatment. The O3I was measured by the same method in all included studies. Variables were selected by stepwise regression using the Bayesian information criterion. RESULTS: Individuals supplemented with EPA + DHA (n = 846) took a mean ± SD of 1983 ± 1297 mg/d, and the placebo controls (n = 576) took none. The mean duration of supplementation was 13.6 ± 6.0 wk. The O3I increased from 4.9% ± 1.7% to 8.1% ± 2.7% in the supplemented individuals ( P < 0.0001). The final model included dose, baseline O3I, and chemical formulation type (EE or TG), and these explained 62% of the variance in response (P < 0.0001). The model predicted that the final O3I (and 95% CI) for a population like this, with a baseline concentration of 4.9%, given 850 mg/d of EPA + DHA EE would be ∼6.5% (95% CI: 6.3%, 6.7%). Gram for gram, TG-based supplements increased the O3I by about 1 percentage point more than EE products. CONCLUSIONS: Of the factors tested, only baseline O3I, dose, and chemical formulation were significant predictors of O3I response to supplementation. The model developed here can be used by researchers to help estimate the O3I response to a given EPA + DHA dose and chemical form.

Wang, L., et al. (2021). “Trends in Consumption of Ultraprocessed Foods Among US Youths Aged 2-19 Years, 1999-2018.” Jama 326(6): 519-530.

IMPORTANCE: The childhood obesity rate has been steadily rising among US youths during the past 2 decades. Increasing evidence links consumption of ultraprocessed foods to excessive calorie consumption and weight gain, but trends in the consumption of ultraprocessed foods among US youths have not been well characterized. OBJECTIVE: To characterize trends in the consumption of ultraprocessed foods among US youths. DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional analysis using 24-hour dietary recall data from a nationally representative sample of US youths aged 2-19 years (n = 33 795) from 10 cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2000 to 2017-2018. EXPOSURES: Secular time. MAIN OUTCOMES AND MEASURES: Percentage of total energy consumed from ultraprocessed foods as defined by NOVA, an established food classification system that categorizes food according to the degree of food processing. RESULTS: Dietary intake from youths were analyzed (weighted mean age, 10.7 years; 49.1% were girls). From 1999 to 2018, the estimated percentage of total energy from consumption of ultraprocessed foods increased from 61.4% to 67.0% (difference, 5.6% [95% CI, 3.5% to 7.7%]; P < .001 for trend), whereas the percentage of total energy from consumption of unprocessed or minimally processed foods decreased from 28.8% to 23.5% (difference, -5.3% [95% CI, -7.5% to -3.2%]; P < .001 for trend). Among the subgroups of ultraprocessed foods, the estimated percentage of energy from consumption of ready-to-heat and -eat mixed dishes increased from 2.2% to 11.2% (difference, 8.9% [95% CI, 7.7% to 10.2%]) and from consumption of sweet snacks and sweets increased from 10.7% to 12.9% (difference, 2.3% [95% CI, 1.0% to 3.6%]), but the estimated percentage of energy decreased for sugar-sweetened beverages from 10.8% to 5.3% (difference, -5.5% [95% CI, -6.5% to -4.5%]) and for processed fats and oils, condiments, and sauces from 7.1% to 4.0% (difference, -3.1% [95% CI, -3.7% to -2.6%]) (all P < .05 for trend). There was a significantly larger increase in the estimated percentage of energy from consumption of ultraprocessed foods among non-Hispanic Black youths (from 62.2% to 72.5%; difference, 10.3% [95% CI, 6.8% to 13.8%]) and Mexican American youths (from 55.8% to 63.5%; difference, 7.6% [95% CI, 4.4% to 10.9%]) than the increase among non-Hispanic White youths (from 63.4% to 68.6%; difference, 5.2% [95% CI, 2.1% to 8.3%]) (P = .04 for trends). CONCLUSIONS AND RELEVANCE: Based on the NHANES cycles from 1999 to 2018, the estimated proportion of energy intake from consumption of ultraprocessed foods has increased among youths in the US and has consistently comprised the majority of their total energy intake.

White, M., et al. (2020). “What role should the commercial food system play in promoting health through better diet?” Bmj 368: m545.

Martin White and coauthors consider that the commercial food system has the potential to show leadership and support for dietary public health, but systemic change is needed first and this is likely to require governmental action

Wölnerhanssen, B. K., et al. (2015). “Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study.” PLOS ONE 10(6): e0130280.

Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones. Recent studies have begun to elucidate brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging (MRI), but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear. In this paper, we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system. Using a cross-over, double-blind, placebo-controlled design, we compared resting state functional connectivity (rsFC) strengths within the basal ganglia/limbic network in 12 healthy lean males. Each subject was administered fructose, glucose and placebo on three separate occasions. Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite. Glucose ingestion induced significantly greater elevations in plasma glucose, insulin, GLP-1 and GIP, while feelings of fullness increased and prospective food consumption decreased relative to fructose. Furthermore, glucose increased rsFC of the left caudatus and putamen, precuneus and lingual gyrus more than fructose, whereas within the basal ganglia/limbic network, fructose increased rsFC of the left amygdala, left hippocampus, right parahippocampus, orbitofrontal cortex and precentral gyrus more than glucose. Moreover, compared to fructose, the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin. Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network, which are probably mediated by different insulin levels. A larger study would be recommended in order to confirm these findings.

Yakoob, M. Y., et al. (2016). “Circulating Biomarkers of Dairy Fat and Risk of Incident Diabetes Mellitus Among Men and Women in the United States in Two Large Prospective Cohorts.” Circulation 133(17): 1645-1654.