Background: The relation between sugar-sweetened beverages (SSBs) and body weight remains controversial. Objective: We conducted a systematic review and meta-analysis to summarize the evidence in children and adults. Design: We searched PubMed, EMBASE, and Cochrane databases through March 2013 for prospective cohort studies and randomized controlled trials (RCTs) that evaluated the SSB-weight relation. Separate meta-analyses were conducted in children and adults and for cohorts and RCTs by using random-and fixed-effects models. Results: Thirty-two original articles were included in our meta-analyses: 20 in children (15 cohort studies, n = 25,745; 5 trials, n = 2772) and 12 in adults (7 cohort studies, n = 174,252; 5 trials, n = 292). In cohort studies, one daily serving increment of SSBs was associated with a 0.06 (95% CI: 0.02, 0.10) and 0.05 (95% CI: 0.03, 0.07)-unit increase in BMI in children and 0.22 kg (95% CI: 0.09, 0.34 kg) and 0.12 kg (95% CI: 0.10, 0.14 kg) weight gain in adults over 1 y in random- and fixed-effects models, respectively. RCTs in children showed reductions in BMI gain when SSBs were reduced [random and fixed effects: -0.17 (95% CI: -0.39, 0.05) and -0.12 (95% CI: -0.22, -0.2)], whereas RCTs in adults showed increases in body weight when SSBs were added (random and fixed effects: 0.85 kg; 95% CI: 0.50, 1.20 kg). Sensitivity analyses of RCTs in children showed more pronounced benefits in preventing weight gain in SSB substitution trials (compared with school-based educational programs) and among overweight children (compared with normal-weight children). Conclusion: Our systematic review and meta-analysis of prospective cohort studies and RCTs provides evidence that SSB consumption promotes weight gain in children and adults.
Background: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys. Objective: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe. Design: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data. Results: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations. Conclusions: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency in the majority of the European population.
Background Childhood obesity is associated with serious health problems and the risk of premature illness and death later in life Monitoring related trends is important Objective The objective was to quantify the worldwide prevalence and trends of overweight and obesity among preschool children on the basis of the new World Health Organization standards Design A total of 450 nationally representative cross-sectional surveys from 144 countries were analyzed Overweight and obesity were defined as the proportion of preschool children with values >2 SDs and >3 SDs respectively from the World Health Organization growth standard median Being at risk of overweight was defined as the proportion with values >1 SD and <= 2 SDs respectively Linear mixed-effects modeling was used to estimate the rates and numbers of affected children Results In 2010 43 milion children (35 million in developing countries) were estimated to be overweight and obese 92 million were at risk of overweight The worldwide prevalence of childhood overweight and obesity increased from 4 2% (95% CI 3 2% 5 2%) in 1990 to 67% (95% CI 5 6% 7 7%) in 2010 This trend is expected to reach 91% (95% CI 73% 10 9%) or approximate to 60 million in 2020 The estimated prevalence of childhood overweight and obesity in Africa in 2010 was 8 5% (95% CI 7 4% 9 5%) and is expected to leach 12 7% (95% CI 106% 14 8%) in 2020 The prevalence is lower in Asia than in Africa (4 9% in 2010) but the number of affected children (18 million) is higher in Asia Conclusions Childhood overweight and obesity have increased dramatically since 1990 These findings confirm the need for effective interventions starting as early as infancy to reverse anticipated trends Am J Clin Nutr 2010, 92 1257-64
Background The Mediterranean diet has long been reported to be protective against the occurrence of several different health outcomes Objective We aimed to update our previous meta analysis of published cohort prospective studies that investigated the effects of adherence to the Mediterranean diet on health status Design We conducted a comprehensive literature search through electronic databases up to June 2010 Results The updated review process showed 7 prospective studies published in the past 2 y that were not Included in the previous meta analysis (1 study for overall mortality 3 studies for cardiovascular incidence or mortality 1 study for cancer incidence or mortality and 2 studies for neurodegenerative diseases) These recent studies included 2 health outcomes not previously investigated (ie mild cognitive impairment and stroke) The meta-analysis for all studies with a random-effects model that was conducted after the inclusion of these recent studies showed that a 2-point increase in adherence to the Mediterranean diet was associated with a significant reduction of overall mortality [relative risk (RR) = 0 92 95% Cl 0 90 0 94] cardiovascular incidence or mortality (RR = 0 90 95% Cl 0 87 093), cancer incidence or mortality (RR = 094 95% CI 0 92 0 96) and neurodegenerative diseases (RR = 0 87, 95% CI 081 0 94) The meta regression analysis showed that sample size was the most significant contributor to the model because it significantly influenced the estimate of the association for overall mortality Conclusion This updated meta analysis confirms in a larger number of subjects and studies the significant and consistent protection provided by adherence to the Mediterranean diet in relation to the occurrence of major chronic degenerative diseases Am J Clin Nutr 2010, 92 1189-96
Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations. Objective: The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations. Design: A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training. Results: Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects. Conclusion: Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects. Am J Clin Nutr 2012;96:1454-64.
Background: There is evidence that reducing blood glucose concentrations, inducing weight loss, and improving the lipid profile reduces cardiovascular risk in people with type 2 diabetes. Objective: We assessed the effect of various diets on glycemic control, lipids, and weight loss. Design: We conducted searches of PubMed, Embase, and Google Scholar to August 2011. We included randomized controlled trials (RCTs) with interventions that lasted >= 6 mo that compared low-carbohydrate, vegetarian, vegan, low glycemic index (GI), high-fiber, Mediterranean, and high-protein diets with control diets including low-fat, high-GI, American Diabetes Association, European Association for the Study of Diabetes, and low-protein diets. Results: A total of 20 RCTs were included (n = 3073 included in final analyses across 3460 randomly assigned individuals). The low-carbohydrate, low-GI, Mediterranean, and high-protein diets all led to a greater improvement in glycemic control [glycated hemoglobin reductions of -0.12% (P = 0.04), -0.14% (P = 0.008), -0.47% (P < 0.00001), and -0.28% (P < 0.00001), respectively] compared with their respective control diets, with the largest effect size seen in the Mediterranean diet. Low-carbohydrate and Mediterranean diets led to greater weight loss [0.69 kg (P = 0.21) and 1.84 kg (P < 0.00001), respectively], with an increase in HDL seen in all diets except the high-protein diet. Conclusion: Low-carbohydrate, low-GI, Mediterranean, and high-protein diets are effective in improving various markers of cardiovascular risk in people with diabetes and should be considered in the overall strategy of diabetes management. Am J Clin Nutr 2013;97:505-16.
Background: Breast milk is recognized as the most important postpartum element in metabolic and immunologic programming of health of neonates. The factors influencing the milk microbiome and the potential impact of microbes on infant health have not yet been uncovered. Objective: Our objective was to identify pre- and postnatal factors that can potentially influence the bacterial communities inhabiting human milk. Design: We characterized the milk microbial community at 3 different time points by pyrosequencing and quantitative polymerase chain reaction in mothers (n = 18) who varied in BMI, weight gain, and mode of delivery. Results: We found that the human milk microbiome changes over lactation. Weisella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus were predominant in colostrum samples, whereas in 1- and 6-mo milk samples the typical inhabitants of the oral cavity (eg, Veillonella, Leptotrichia, and Prevotella) increased significantly. Milk from obese mothers tended to contain a different and less diverse bacterial community compared with milk from normal-weight mothers. Milk samples from elective but not from nonelective mothers who underwent cesarean delivery contained a different bacterial community than did milk samples from individuals giving birth by vaginal delivery, suggesting that it is not the operation per se but rather the absence of physiological stress or hormonal signals that could influence the microbial transmission process to milk. Conclusions: Our results indicate that milk bacteria are not contaminants and suggest that the milk microbiome is influenced by several factors that significantly skew its composition. Because bacteria present in breast milk are among the very first microbes entering the human body, our data emphasize the necessity to understand the biological role that the milk microbiome could potentially play for human health. Am J Clin Nutr 2012;96:544-51.
Background: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). Objective: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. Design: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. Results: We included 42 acute or short-term chronic (50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low-to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. Conclusions: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols. Am J Clin Nutr 2012; 95: 740-51.
Background: Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity. However, it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans. Objective: With the use of a carefully monitored inpatient study cohort, we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest. Design: We investigated dynamic changes of gut microbiota during diets that varied in caloric content (2400 compared with 3400 kcal/d) by pyrosequencing bacterial 16S ribosomal RNA (rRNA) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry. Results: The alteration of the nutrient load induced rapid changes in the gut microbiota. These changes were directly correlated with stool energy loss in lean individuals such that a 20% increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of approximate to 150 kcal. A high degree of over-feeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss. Conclusions: These results show that the nutrient load is a key variable that can influence the gut (fecal) bacterial community structure over short time scales. Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest. This trial was registered at clinicaltrials. gov as NCT00414063. Am J Clin Nutr 2011;94:58-65.
Background: Sedentary behaviors predominate modern life, yet we do not fully understand the adverse effects of these behaviors on mortality after considering the benefits of moderate-vigorous physical activity (MVPA). Objective: We tested the hypotheses that higher amounts of overall sitting time and television viewing are positively associated with mortality and described the independent and combined effects of these sedentary behaviors and MVPA on mortality. Design: In the NIH-AARP Diet and Health Study, we examined 240,819 adults (aged 50-71 y) who did not report any cancer, cardiovascular disease, or respiratory disease at baseline. Mortality was ascertained over 8.5 y. Results: Sedentary behaviors were positively associated with mortality after adjustment for age, sex, education, smoking, diet, race, and MVPA. Participants who reported the most television viewing (>= 7 h compared with 7 h/wk), high amounts of television viewing (>= 7 h/d) remained associated with increased risk of all-cause (HR: 1.47; 95% CI: 1.20, 1.79) and cardiovascular (HR: 2.00; 95% CI: 1.33, 3.00) mortality compared with those reporting the least television viewing (<1 h/d). Conclusions: Time spent in sedentary behaviors was positively associated with mortality, and participation in high levels of MVPA did not fully mitigate health risks associated with prolonged time watching television. Adults should be encouraged to reduce time spent in sedentary behaviors, when possible, and to participate in MVPA at recommended levels. The NIH-AARP Diet and Health Study was registered at clinicaltrials.gov as NCT00340015. Ant J Clin Nutr 2012;95:437-45.
Background: Studies of single nutrients on depression have produced inconsistent results, and they have failed to consider the complex interactions between nutrients. An increasing number of studies in recent years are investigating the association of overall dietary patterns and depression. Objective: This study aimed to systematically review current literature and conduct meta-analyses of studies addressing the association between dietary patterns and depression. Design: Six electronic databases were searched for articles published up to August 2013 that examined the association of total diet and depression among adults. Only studies considered methodologically rigorous were included. Two independent reviewers completed study selection, quality rating, and data extraction. Effect sizes of eligible studies were pooled by Using random-effects models. A summary of the findings was presented for studies that could not be meta-analyzed. Results: A total of 21 studies were identified. Results from 13 observational studies were pooled. Two dietary patterns were identified. The healthy diet pattern was significantly associated with a reduced odds of depression (OR: 0.84; 95% CI: 0.76, 0.92; P < 0.001). No statistically significant association was observed between the Western diet and depression (OR: 1.17; 95% CI: 0.97, 1.68; P = 0.094); however, the studies were too few for a precise estimate of this effect. Conclusions: The results suggest that high intakes of fruit, vegetables, fish, and whole grains may be associated with a reduced depression risk. However, more high-quality randomized controlled trials and cohort studies are needed to confirm this finding, specifically the temporal sequence of this association.
Background: A reduction in dietary saturated fat has generally been thought to improve cardiovascular health. Objective: The objective of this meta-analysis was to summarize the evidence related to the association of dietary saturated fat with risk of coronary heart disease (CHD), stroke, and cardiovascular disease (CVD; CHD inclusive of stroke) in prospective epidemiologic studies. Design: Twenty-one studies identified by searching MEDLINE and EMBASE databases and secondary referencing qualified for inclusion in this study. A random-effects model was used to derive composite relative risk estimates for CHD, stroke, and CVD. Results: During 5-23 y of follow-up of 347,747 subjects, 11,006 developed CHD or stroke. Intake of saturated fat was not associated with an increased risk of CHD, stroke, or CVD. The pooled relative risk estimates that compared extreme quantiles of saturated fat intake were 1.07 (95% CI: 0.96, 1.19; P = 0.22) for CHD, 0.81 (95% CI: 0.62, 1.05; P = 0.11) for stroke, and 1.00 (95% CI: 0.89, 1.11; P = 0.95) for CVD. Consideration of age, sex, and study quality did not change the results. Conclusions: A meta-analysis of prospective epidemiologic studies showed that there is no significant evidence for concluding that dietary saturated fat is associated with an increased risk of CHD or CVD. More data are needed to elucidate whether CVD risks are likely to be influenced by the specific nutrients used to replace saturated fat. Am J Clin Nutr 2010;91:535-46.
The food metabolome is defined as the part of the human metabolome directly derived from the digestion and biotransformation of foods and their constituents. With >25,000 compounds known in various foods, the food metabolome is extremely complex, with a composition varying widely according to the diet. By its very nature it represents a considerable and still largely unexploited source of novel dietary biomarkers that could be used to measure dietary exposures with a high level of detail and precision. Most dietary biomarkers currently have been identified on the basis of our knowledge of food compositions by using hypothesis-driven approaches. However, the rapid development of metabolomics resulting from the development of highly sensitive modern analytic instruments, the availability of metabolite databases, and progress in (bio)informatics has made agnostic approaches more attractive as shown by the recent identification of novel biomarkers of intakes for fruit, vegetables, beverages, meats, or complex diets. Moreover, examples also show how the scrutiny of the food metabolome can lead to the discovery of bioactive molecules and dietary factors associated with diseases. However, researchers still face hurdles, which slow progress and need to be resolved to bring this emerging field of research to maturity. These limits were discussed during the First International Workshop on the Food Metabolome held in Glasgow. Key recommendations made during the workshop included more coordination of efforts; development of new databases, software tools, and chemical libraries for the food metabolome; and shared repositories of metabolomic data. Once achieved, major progress can be expected toward a better understanding of the complex interactions between diet and human health.
Mechanisms responsible for energy management in the cell and in the whole organism require a complex network of transcription factors and cofactors. Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) has emerged as a master regulator of mitochondrial biogenesis and function, thus becoming a crucial metabolic node. We present an overview of the mechanisms by which PGC-1 alpha is regulated, including the transcriptional regulation of PGC-1 alpha expression and the fine-tuning of its final activity via posttranslational modifications. Am J Clin Nutr 2011; 93 (suppl):884S-90S.
Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (>= 102 cm for men, >= 88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA x BMI and PA x WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.
Background: Early nutrition is recognized as a target for the effective prevention of childhood obesity. Protein intake was associated with more rapid weight gain during infancy a known risk factor for later obesity. Objective: We tested whether the reduction of protein in infant formula reduces body mass index (BMI; in kg/m(2)) and the prevalence of obesity at 6 y of age. Design: The Childhood Obesity Project was conducted as a European multicenter, double-blind, randomized clinical trial that enrolled healthy infants born between October 2002 and July 2004. Formula-fed infants (n = 1090) were randomly assigned to receive higher protein (HP) or lower protein (LP) content formula (within recommended amounts) in the first year of life; breastfed infants (n = 588) were enrolled as an observational reference group. We measured the weight and height of 448 (41%) formula-fed children at 6 y of age. BMI was the primary outcome. Results: HP children had a significantly higher BMI (by 0.51; 95% Cl: 0.13, 0.90; P = 0.009) at 6 y of age. The risk of becoming obese in the HP group was 2.43 (95% Cl: 1.12,5.27; P = 0.024) times that in the LP group. There was a tendency for a higher weight in HP children (0.67 kg; 95% CI: 0.04, 1.39 kg; P = 0.064) but no difference in height between the intervention groups. Anthropometric measurements were similar in the LP and breastfed groups. Conclusions: Infant formula with a lower protein content reduces BMI and obesity risk at school age. Avoidance of infant foods that provide excessive protein intakes could contribute to a reduction in childhood obesity. This trial was registered at clinicaltrials.gov as NCT00338689.
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 a-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. Am J Clin Nutr 2011;93:950-62.
BACKGROUND: Epidemiologic studies have suggested that most cases of sporadic colon cancer can be attributed to diet. The recognition that colonic microbiota have a major influence on colonic health suggests that they might mediate colonic carcinogenesis. OBJECTIVE: To examine the hypothesis that the influence of diet on colon cancer risk is mediated by the microbiota through their metabolites, we measured differences in colonic microbes and their metabolites in African Americans with a high risk and in rural native Africans with a low risk of colon cancer. DESIGN: Fresh fecal samples were collected from 12 healthy African Americans aged 50-65 y and from 12 age- and sex-matched native Africans. Microbiomes were analyzed with 16S ribosomal RNA gene pyrosequencing together with quantitative polymerase chain reaction of the major fermentative, butyrate-producing, and bile acid-deconjugating bacteria. Fecal short-chain fatty acids were measured by gas chromatography and bile acids by liquid chromatography-mass spectrometry. RESULTS: Microbial composition was fundamentally different, with a predominance of Prevotella in native Africans (enterotype 2) and of Bacteroides in African Americans (enterotype 1). Total bacteria and major butyrate-producing groups were significantly more abundant in fecal samples from native Africans. Microbial genes encoding for secondary bile acid production were more abundant in African Americans, whereas those encoding for methanogenesis and hydrogen sulfide production were higher in native Africans. Fecal secondary bile acid concentrations were higher in African Americans, whereas short-chain fatty acids were higher in native Africans. CONCLUSION: Our results support the hypothesis that colon cancer risk is influenced by the balance between microbial production of health-promoting metabolites such as butyrate and potentially carcinogenic metabolites such as secondary bile acids
The prevalence and severity of obesity have increased in recent years, likely the result of complex interactions between genes, dietary intake, physical activity, and the environment. The expression of genes favoring the storage of excess calories as fat, which have been selected for over many millennia and are relatively static, has become maladaptive in a rapidly changing environment that minimizes opportunities for energy expenditure and maximizes opportunities for energy intake. The consequences of childhood and adolescent obesity include earlier puberty and menarche in girls, type 2 diabetes and increased incidence of the metabolic syndrome in youth and adults, and obesity in adulthood. These changes are associated with cardiovascular disease as well as with several cancers in adults, likely through insulin resistance and production of inflammatory cytokines. Although concerns have arisen regarding environmental exposures, there have been no formal expert recommendations. Currently, the most important factors underlying the obesity epidemic are the current opportunities for energy intake coupled with limited energy expenditure. Am J Clin Nutr 2010; 91(suppl):1499S-1505S.
Background: Obesity is a serious chronic disease. Controlled-release phentermine/topiramate (PHEN/TPM CR), as an adjunct to lifestyle modification, has previously shown significant weight loss compared with placebo in a 56-wk study in overweight and obese subjects with >= 2 weight-related comorbidities. Objective: This study evaluated the long-term efficacy and safety of PHEN/TPM CR in overweight and obese subjects with cardiometabolic disease. Design: This was a placebo-controlled, double-blind, 52-wk extension study; volunteers at selected sites continued with original randomly assigned treatment [placebo, 7.5 mg phentermine/46 mg controlled-release topiramate (7.5/46), or 15 mg phentermine/92 mg controlled-release topiramate (15/92)] to complete a total of 108 wk. All subjects participated in a lifestyle-modification program. Results: Of 866 eligible subjects, 676 (78%) elected to continue in the extension. Overall, 84.0% of subjects completed the study, with similar completion rates between treatment groups. At week 108, PHEN/TPM CR was associated with significant, sustained weight loss (intent-to-treat with last observation carried forward; P = 5%, >= 10%, >= 15%, and >= 20% weight loss compared with placebo (P < 0.001). PHEN/TPM CR improved cardiovascular and metabolic variables and decreased rates of incident diabetes in comparison with placebo. PHEN/TPM CR was well tolerated over 108 wk, with reduced rates of adverse events occurring between weeks 56 and 108 compared with rates between weeks 0 and 56. Conclusion: PHEN/TPM CR in conjunction with lifestyle modification may provide a well-tolerated and effective option for the sustained treatment of obesity complicated by cardiometabolic disease. This trial was registered at clinicaltrials.gov as NCT00796367. Am J Clin Nutr 2012;95:297-308.