The Challenge of Reforming Nutritional Epidemiologic Research

Ioannidis, John P. A.

doi:10.1001/jama.2018.11025

Cited by 321 publications

(204 citation statements)

References 10 publications

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“…There were few hip fractures in men ( n = 190) and we may not have had sufficient power to examine the association of dietary niacin intake with hip fractures in men. Finally, a recent editorial indicated the numerous challenges in nutritional epidemiological research that remain a potential issue in this study, including that relatively uncommon chemicals within food or components that appear only under specific conditions, genetic background, and other environmental exposures which may be influencing our findings that we were not able to account for. Our findings are strictly that there is an epidemiological association of dietary intake of niacin with osteoporosis and in no way should this be misconstrued as a causative effect.…”

Section: Discussionmentioning

confidence: 99%

Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study

Carbone

Bůžková

Fink

et al. 2019

Journal of Bone and Mineral Research

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Interest in niacin has increased in the setting of reports suggesting that niacin plays a role in diseases of aging. No study to date has examined the association of dietary niacin intake with multiple skeletal health parameters including bone mineral density (BMD), hip fractures, and body composition, and none have included both African American and white men and women. Participants included 5187 men and women ≥65 years from the Cardiovascular Health Study (CHS). Mean daily dietary niacin intake was 32.6 mg, with quartiles 1 through 4 defined as 3.6 to 21.8 mg/day, 21.9 to 30.2 mg/day, 30.3 to 40.9 mg/day, and 41.0 to 102.4 mg/day, respectively. Risk of incident hip fracture per 10 mg increment of daily dietary niacin intake was estimated using proportional hazards models. During a median follow‐up of 13 years, 725 participants had an incident hip fracture. In models adjusted for demographic and clinical characteristics and diet, dietary niacin intake was significantly associated with an increased risk of hip fractures (hazard ratio [HR] 1.12; 95% CI, 1.01 to 1.24) with spline models suggesting a U‐shaped association. In post hoc analyses, both the lowest (HR 1.31; 95% CI, 1.04 to 1.66) and highest (HR 1.53; 95% CI, 1.20 to 1.95) quartiles of niacin intake were associated with an increased risk of incident hip fracture versus quartiles 2 and 3. There was a trend for a significant inverse association of dietary niacin intake with hip BMD (p = 0.06), but no significant association with total body BMD or any body composition measures. In this cohort of elderly, community‐dwelling African American and white men and women, both high and low dietary niacin intakes were associated with a significantly increased risk of subsequent hip fracture, suggesting a possible U‐shaped association. By comparison, dietary niacin may have an inverse linear association with hip BMD. © 2018 American Society for Bone and Mineral Research.

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Section: Discussionmentioning

confidence: 99%

Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study

Carbone

Bůžková

Fink

et al. 2019

Journal of Bone and Mineral Research

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“…Further, it is hypothesized that confounding and model misspecification occurs at higher rate in non-genetic vs. genetic studies 19 . Third, while easy to measure, some of the exposures considered included self-reported variables, such as diet, which may be prone to measurement error and recall bias 20 . If these errors occur at random across all variables considered in the PXS, the association sizes and PXSs will be diluted.…”

Section: Discussionmentioning

confidence: 99%

Poly-Exposure and Poly-Genomic Scores Implicate Prominent Roles of Non-Genetic and Demographic Factors in Four Common Diseases in the UK

Lakhani

Manrai

et al. 2019

Preprint

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While polygenic risk scores (PRSs) have been shown to identify a small number of individuals with increased clinical risk for several common diseases , non-genetic factors that change during a lifetime, such as lifestyle, employment, diet, and pollution, have a larger role in clinical prediction. We analyzed data from 459,613 participants of the UK Biobank to investigate the independent and combined roles of demographics (e.g., sex and age), 96 environmental exposures, and common genetic variants in atrial fibrillation, coronary artery disease, inflammatory bowel disease, and type 2 diabetes. We develop an additive modelling approach to estimate and validate a poly-exposure score (PXS) that goes beyond consideration of a handful of factors such as smoking and pollution. PXS is able to identify groups with high prevalence of the four common disease comparable to, if not better, than the PRS. Type 2 diabetes has the largest discrepancy in PXS and PRS performance, defined as the maximum area under the receiver-operator curve (AUC) (PXS AUC of 0.828 [0.821-0.836], PRS AUC of 0.711 [0.702-0.720]). Most importantly, we show that PXS identifies individuals that have low genetic risk but high overall risk for disease. While PRS is useful for screening genetically exceptional individuals in a time-invariant way, broader consideration of multiple non-genetic and modifiable factors is required to fully translate risk scores to the bedside for precision medicine .All results and the PXS calculator can be found in our web application http://apps.chiragjpgroup.org/pxs/ .

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“…However, concerns were raised about suitability of doubly labelled water technique to measure energy expenditure in diets of varying carbohydrate and fat distribution as in above mentioned study of Ebbeling et al (2018) (16)(17)(18). Human nutritional epidemiologic research addressing comparisons of different composition diets have also been plague by methodological difficulties which mainly concern assessment of food intake (19).…”

Section: Introductionmentioning

confidence: 99%

Low Carbohydrate and Low Fat Diets with Equal Protein Content Lead to Similar Improvements in Body Composition and Glucose Tolerance in Obese Mice subjected to Caloric Restriction

Minderis

Fokin

Dirmontas

et al. 2019

Preprint

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Background. Reported differences in effects of low and high carbohydrate diets on weight control and metabolic health are controversial. We aimed to examine if such diets induce different improvements in body composition and glucose tolerance under conditions of caloric restriction (CR) in obese mice.Methods. Male C57BL/6J mice (n = 20) were fed obesogenic diet (45 and 17.5% kcal from fat and sugar) ad libitum for 18 weeks and then subjected to 6-week CR which progressively increased up to 40% using either Low Fat diet (20, 60, 20% kcal from fat, carbohydrate, protein, n = 10) or Low Carb diet (20, 60, 20% kcal from carbohydrate, fat, protein, n = 10). Mice fed regular chow diet ad libitum served as controls (n = 10). Body mass, hind limb muscle mass, fat mass, energy expenditure and glucose tolerance were compared between the groups.Results. Low Fat and Low Carb groups had similar body mass (p > 0.05) prior to CR which was 30% greater compared to control group (p < 0.001). CR resulted in weight loss with no differences between Low Fat and Low Carb groups (30.0 ± 5.6 and 23.8 ± 7.5%, p > 0.05).Weight loss was mainly due to fat loss in both groups. Energy expenditure of freely moving mice did not differ between the groups (p > 0.05). Intraperitoneal glucose tolerance test improved compared to control group (p < 0.05) and values before CR (p < 0.01) but without differences between Low Fat and Low Carb groups (p > 0.05). Conclusions.Dietary carbohydrate or fat content when protein is equated does not play a significant role for body composition and metabolic health benefits of caloric restriction in obese mice.

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The Challenge of Reforming Nutritional Epidemiologic Research

Cited by 321 publications

References 10 publications

Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study

Association of Dietary Niacin Intake With Incident Hip Fracture, BMD, and Body Composition: The Cardiovascular Health Study

Poly-Exposure and Poly-Genomic Scores Implicate Prominent Roles of Non-Genetic and Demographic Factors in Four Common Diseases in the UK

Low Carbohydrate and Low Fat Diets with Equal Protein Content Lead to Similar Improvements in Body Composition and Glucose Tolerance in Obese Mice subjected to Caloric Restriction

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