Background: Although there is interest in popular diets such as vegan and vegetarian, Paleo, and ... more Background: Although there is interest in popular diets such as vegan and vegetarian, Paleo, and other "whole food" diets, existing cohort studies lack data for these subgroups. The use of electronic data capture and Web-based surveys in nutrition research may be valuable for future studies by allowing targeting of specific dietary subgroups. Objective: The aim was to perform a Feasibility Survey (FS) to assess the practicality of Web-based research methods to gather data and to maximize response rates among followers of popular diets. Methods: The FS was an open, voluntary, 15-min survey conducted over 8 wk in the summer of 2015. Recruitment targeted self-identified followers of popular diets from a convenience sample, offering no incentives, via social media and e-newsletters shared by recruitment partners. Feasibility was assessed by number of responses, survey completion rate, distribution of diets, geographic location, and willingness to participate in future research. Results: A total of 14,003 surveys were initiated; 13,787 individuals consented, and 9726 completed the survey (71% of consented). The numbers of unique visitors to the questionnaire site, view rate, and participation rate were not captured. Among respondents with complete demographic data, 83% were female and 93% were white. Diet designations were collapsed into the following groups: whole-food, plant-based (25%); vegan and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and pescatarian (9%); whole food (8%); Weston A Price (5%); and low-carbohydrate (low-carb) (4%). Forced-response, multiple-choice questions produced the highest response rates (0-2% selected "prefer not to answer"). The percentage who were willing to complete future online questionnaires was 86%, diet recall was 93%, and food diary was 75%; the percentages willing to provide a finger-stick blood sample, venipuncture blood sample, urine sample, and stool sample were 60%, 44%, 58%, and 42%, respectively. Conclusions: This survey suggests that recruiting followers of popular diets is feasible with the use of Web-based methods. The unbalanced sample with respect to sex and race/ethnicity could be corrected with specific recruitment strategies using targeted online marketing techniques.
Background The conjoint associations of adherence to the recent physical activity (PA) and dietar... more Background The conjoint associations of adherence to the recent physical activity (PA) and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods We evaluated 2,379 Framingham Heart Study Third Generation participants (mean age 47 years, 54.4% women) attending examination cycle 2. We examined the cross-sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (PAG, binary; moderate to vigorous PA [MVPA] ≥ 150 minutes/week vs. <150 minutes/week) and 2015 Dietary Guidelines for Americans (DGA, binary; 2015 DGA adherence Index [DGAI-2015] ≥ median vs. <median [score 62.1/100]) with prevalence of the MetS using generalized linear models. We also related adherence to guidelines with the incidence of MetS prospectively, using Cox proportional hazards regression with discrete time intervals. Results Adherence to the 2018 PAG (odds ratio [OR] 0.49, 95% CI 0.40-0.60) and 2015 DGA (OR 0.67, 95% CI 0.51-0.90) were individually associated with lower odds of prevalent MetS, while conjoint adherence to both guidelines was associated with the lowest odds of MetS (OR 0.35, 95% CI 0.26-0.47) compared to the referent group (non-adherence to both guidelines). Adherence to the 2018 PAG (hazards ratio [HR] 0.66, 95% CI 0.50-0.88) and 2015 DGA (HR 0.68, 95% CI 0.51-0.90) were associated with lower risk of MetS, prospectively. Additionally, we observed a 52% lower risk of MetS in individuals who adhered to both guidelines compared to the referent group. Conclusions Maintaining both regular physical activity and a healthy diet in midlife may be required for optimal cardiometabolic health in later life.
BackgroundLittle is known about the interaction between parents and children in dietary supplemen... more BackgroundLittle is known about the interaction between parents and children in dietary supplement (DS) use.ObjectiveDetermine if parental use of dietary supplements predicted child use.Methods4556 parent‐child pairs who responded to questions about DS use over the past 30 days and participated in the CAM supplement of the 2007 National Health Interview Survey. DS were categorized as multivitamin mineral (MVM) (2 or more vitamins +/or minerals) only; single vitamin or mineral DS (SVM) with or without use of MVM; non‐vitamin non‐mineral DS with or without use of MVM or SVM (NVNM) and DS nonusers. Prevalence of use and standard errors were calculated using SUDAAN PROC DESCRIPT to account for the complex sampling design and standardized to the 2000 census.ResultsIn the pairs, 46.4% of the parents and 36.6% of the children took DS, and use of MVM and SVM was much more common than NVNM. For parents who used any DS, fully 55% of their children used them as well. Among parents who used MVM, 50% of the children used MVM, for parents who used SVM, only 10% of the children used SVM and for parents who used NVNM, only 13% of the children used them.ConclusionParents who use DS are more likely to give them to their children than those who do not. In most cases the children took micronutrient DS (MVM and SVM). Parents who used NVNM were more likely to have children who used NVNM.Support: Office of Dietary Supplements, NIH, and Jean Mayer USDA HNRC on Aging at Tufts University
BackgroundPublic interest in nutrition is at the forefront of health and wellness and a major dri... more BackgroundPublic interest in nutrition is at the forefront of health and wellness and a major driver of popular diet adoption. Cohort studies lack specific data from followers of popular diets. Adh...
Journal of the American Heart Association, Apr 6, 2021
Background The conjoint associations of adherence to the recent physical activity and dietary gui... more Background The conjoint associations of adherence to the recent physical activity and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods and Results We evaluated 2379 FHS (Framingham Heart Study) Third Generation participants (mean age, 47 years; 54.4% women) attending examination cycle 2. We examined the cross‐sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (binary; moderate‐to‐vigorous physical activity ≥150 versus &lt;150 min/wk) and 2015 Dietary Guidelines for Americans (binary; 2015 Dietary Guidelines for Americans Adherence Index ≥median versus
Objective: To describe the influence of type of dietary fat on the activity of metabolic pathways... more Objective: To describe the influence of type of dietary fat on the activity of metabolic pathways, as measured by gene expression profiles, and the relation to plasma lipids. Background: Metabolic studies have demonstrated strong associations of dietary fatty acid composition with plasma lipids. Relatively little is known about the pathways and gene expression changes that mediate these relationships in the general population. Methods: We analyzed self-reported dietary intake of fatty acids, plasma lipid levels, and genome-wide gene expression data from Framingham Heart Study Offspring and Third Generation cohort participants. We excluded participants on lipid therapy. Multivariable linear regression models were conducted with plasma lipids as separate outcomes, energy-adjusted residuals of dietary fats as predictors, and adjustment for clinical and dietary covariates. Normalized gene expression from whole blood derived RNA was similarly modeled with additional adjustment for cell count and batch effects. Results: Among 3681 participants, higher polyunsaturated fatty acid (PUFA) intake is associated with lower LDL-C (estimated β [regression coefficient] = -0.5, p=0.002), higher HDL-C (β= 0.4, p&amp;lt;0.0001), and lower triglyceride (β= -0.009, p=0.0003) concentrations after adjustment for age, sex, carbohydrate, protein, and alcohol intake. Higher PUFA intake was associated with differential gene expression of cholesterol efflux transporters (ABCA1/ABCG1), LDL receptor degrader (IDOL), and non-lipoprotein metabolism related transcripts (FDR &amp;lt; 0.05). In contrast, higher saturated fat intake (SFA) showed inverse associations with ABCA1 expression levels and HDL cholesterol ( Figure 1 ). Conclusions: Higher PUFA intake is associated with a less atherogenic lipid profile and higher ABCA1 expression with inverse associations for higher SFA intake. Gene expression analysis reveals important links between dietary fat type, specific cholesterol metabolism pathways, and lipids in a community cohort.
Background: Inconsistent evidence describes the association between dietary intake of dairy and m... more Background: Inconsistent evidence describes the association between dietary intake of dairy and milk-based products and type 2 diabetes (T2D) risk. Objective: Our objective was to assess associations between consumption of milk-based products, incident prediabetes, and progression to T2D in the Framingham Heart Study Offspring Cohort. Methods: Total dairy and milk-based product consumption was assessed by #4 food-frequency questionnaires across a mean of 12 y of follow-up in 2809 participants [mean 6 SD age: 54.0 6 9.7 y; body mass index (in kg/m 2): 27.1 6 4.7; 54%
The American Journal of Clinical Nutrition, Sep 1, 2019
ABSTRACT Background Genes in metabolic and nutrient signaling pathways play important roles in li... more ABSTRACT Background Genes in metabolic and nutrient signaling pathways play important roles in lifespan in model organisms and human longevity. Objective The aim of this study was to examine the relation of a quantitative measure of healthy diet to gene expression in a community-based cohort. Methods We used the 2015 Dietary Guidelines for Americans Adherence Index (DGAI) score to quantify key dietary recommendations of an overall healthy diet. Our current analyses included 2220 Offspring participants (mean age 66 ± 9 y, 55.4% women) and 2941 Third-Generation participants (mean age 46 ± 9 y, 54.5% women) from the Framingham Heart Study. Gene expression was profiled in blood through the use of the Affymetrix Human Exon 1.0 ST Array. We conducted a transcriptome-wide association study of DGAI adjusting for age, sex, smoking, cell counts, and technical covariates. We also constructed a combined gene score from genes significantly associated with DGAI. Results The DGAI was significantly associated with the expression of 19 genes (false discovery rate &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The most significant gene, ARRDC3, is a member of the arrestin family of proteins, and evidence in animal models and human data suggests that this gene is a regulator of obesity and energy expenditure. The DGAI gene score was associated with body mass index (P = 1.4 × 10−50), fasting glucose concentration (P = 2.5 × 10−11), type 2 diabetes (P = 1.1 × 10−5), and metabolic syndrome (P = 1.8 × 10−32). Conclusions Healthier diet was associated with genes involved in metabolic function. Further work is needed to replicate our findings and investigate the relation of a healthy diet to altered gene regulation.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, ... more Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to methionine. The C677T MTHFR polymorphism is associated with mild hyperhomocysteinemia, but only in the presence of low folate status. Because MTHFR contains flavin adenine dinucleotide (FAD) as a prosthetic group, riboflavin status may also influence homocysteine metabolism. The objective of this study was to examine the association between riboflavin status and fasting plasma total homocysteine (tHcy) concentration while also considering MTHFR C677T genotype and folate status. The study was conducted using fasting plasma samples (n ϭ 450) from the fifth examination of the Framingham Offspring Study cohort. All persons with the TT genotype and age-and sex-matched sets of individuals with the CT and CC genotypes were selected for determination of plasma riboflavin and flavin mono-and dinucleotide levels. Plasma riboflavin was associated with tHcy concentrations, but the association was largely confined to persons with plasma folate Ͻ12.5 nmol/L and TT genotype. In these persons, the mean tHcy among individuals with riboflavin levels Ͻ6.89 nmol/L was 14.5 mol/L, whereas the mean tHcy for those with riboflavin Ն11 nmol/L was 11.6 mol/L (P-trend Ͻ0.03). Plasma flavin nucleotides were unrelated to tHcy concentrations. Our data suggest that riboflavin status may affect homocysteine metabolism, but only in a small segment of the population who have both low folate status and are homozygotes for the MTHFR C677T mutation.
Background: Although there is interest in popular diets such as vegan and vegetarian, Paleo, and ... more Background: Although there is interest in popular diets such as vegan and vegetarian, Paleo, and other "whole food" diets, existing cohort studies lack data for these subgroups. The use of electronic data capture and Web-based surveys in nutrition research may be valuable for future studies by allowing targeting of specific dietary subgroups. Objective: The aim was to perform a Feasibility Survey (FS) to assess the practicality of Web-based research methods to gather data and to maximize response rates among followers of popular diets. Methods: The FS was an open, voluntary, 15-min survey conducted over 8 wk in the summer of 2015. Recruitment targeted self-identified followers of popular diets from a convenience sample, offering no incentives, via social media and e-newsletters shared by recruitment partners. Feasibility was assessed by number of responses, survey completion rate, distribution of diets, geographic location, and willingness to participate in future research. Results: A total of 14,003 surveys were initiated; 13,787 individuals consented, and 9726 completed the survey (71% of consented). The numbers of unique visitors to the questionnaire site, view rate, and participation rate were not captured. Among respondents with complete demographic data, 83% were female and 93% were white. Diet designations were collapsed into the following groups: whole-food, plant-based (25%); vegan and raw vegan (19%); Paleo (14%); try to eat healthy (11%); vegetarian and pescatarian (9%); whole food (8%); Weston A Price (5%); and low-carbohydrate (low-carb) (4%). Forced-response, multiple-choice questions produced the highest response rates (0-2% selected "prefer not to answer"). The percentage who were willing to complete future online questionnaires was 86%, diet recall was 93%, and food diary was 75%; the percentages willing to provide a finger-stick blood sample, venipuncture blood sample, urine sample, and stool sample were 60%, 44%, 58%, and 42%, respectively. Conclusions: This survey suggests that recruiting followers of popular diets is feasible with the use of Web-based methods. The unbalanced sample with respect to sex and race/ethnicity could be corrected with specific recruitment strategies using targeted online marketing techniques.
Background The conjoint associations of adherence to the recent physical activity (PA) and dietar... more Background The conjoint associations of adherence to the recent physical activity (PA) and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods We evaluated 2,379 Framingham Heart Study Third Generation participants (mean age 47 years, 54.4% women) attending examination cycle 2. We examined the cross-sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (PAG, binary; moderate to vigorous PA [MVPA] ≥ 150 minutes/week vs. <150 minutes/week) and 2015 Dietary Guidelines for Americans (DGA, binary; 2015 DGA adherence Index [DGAI-2015] ≥ median vs. <median [score 62.1/100]) with prevalence of the MetS using generalized linear models. We also related adherence to guidelines with the incidence of MetS prospectively, using Cox proportional hazards regression with discrete time intervals. Results Adherence to the 2018 PAG (odds ratio [OR] 0.49, 95% CI 0.40-0.60) and 2015 DGA (OR 0.67, 95% CI 0.51-0.90) were individually associated with lower odds of prevalent MetS, while conjoint adherence to both guidelines was associated with the lowest odds of MetS (OR 0.35, 95% CI 0.26-0.47) compared to the referent group (non-adherence to both guidelines). Adherence to the 2018 PAG (hazards ratio [HR] 0.66, 95% CI 0.50-0.88) and 2015 DGA (HR 0.68, 95% CI 0.51-0.90) were associated with lower risk of MetS, prospectively. Additionally, we observed a 52% lower risk of MetS in individuals who adhered to both guidelines compared to the referent group. Conclusions Maintaining both regular physical activity and a healthy diet in midlife may be required for optimal cardiometabolic health in later life.
BackgroundLittle is known about the interaction between parents and children in dietary supplemen... more BackgroundLittle is known about the interaction between parents and children in dietary supplement (DS) use.ObjectiveDetermine if parental use of dietary supplements predicted child use.Methods4556 parent‐child pairs who responded to questions about DS use over the past 30 days and participated in the CAM supplement of the 2007 National Health Interview Survey. DS were categorized as multivitamin mineral (MVM) (2 or more vitamins +/or minerals) only; single vitamin or mineral DS (SVM) with or without use of MVM; non‐vitamin non‐mineral DS with or without use of MVM or SVM (NVNM) and DS nonusers. Prevalence of use and standard errors were calculated using SUDAAN PROC DESCRIPT to account for the complex sampling design and standardized to the 2000 census.ResultsIn the pairs, 46.4% of the parents and 36.6% of the children took DS, and use of MVM and SVM was much more common than NVNM. For parents who used any DS, fully 55% of their children used them as well. Among parents who used MVM, 50% of the children used MVM, for parents who used SVM, only 10% of the children used SVM and for parents who used NVNM, only 13% of the children used them.ConclusionParents who use DS are more likely to give them to their children than those who do not. In most cases the children took micronutrient DS (MVM and SVM). Parents who used NVNM were more likely to have children who used NVNM.Support: Office of Dietary Supplements, NIH, and Jean Mayer USDA HNRC on Aging at Tufts University
BackgroundPublic interest in nutrition is at the forefront of health and wellness and a major dri... more BackgroundPublic interest in nutrition is at the forefront of health and wellness and a major driver of popular diet adoption. Cohort studies lack specific data from followers of popular diets. Adh...
Journal of the American Heart Association, Apr 6, 2021
Background The conjoint associations of adherence to the recent physical activity and dietary gui... more Background The conjoint associations of adherence to the recent physical activity and dietary guidelines with the metabolic syndrome (MetS) are incompletely understood. Methods and Results We evaluated 2379 FHS (Framingham Heart Study) Third Generation participants (mean age, 47 years; 54.4% women) attending examination cycle 2. We examined the cross‐sectional relations of adherence to the 2018 Physical Activity Guidelines for Americans (binary; moderate‐to‐vigorous physical activity ≥150 versus &lt;150 min/wk) and 2015 Dietary Guidelines for Americans (binary; 2015 Dietary Guidelines for Americans Adherence Index ≥median versus
Objective: To describe the influence of type of dietary fat on the activity of metabolic pathways... more Objective: To describe the influence of type of dietary fat on the activity of metabolic pathways, as measured by gene expression profiles, and the relation to plasma lipids. Background: Metabolic studies have demonstrated strong associations of dietary fatty acid composition with plasma lipids. Relatively little is known about the pathways and gene expression changes that mediate these relationships in the general population. Methods: We analyzed self-reported dietary intake of fatty acids, plasma lipid levels, and genome-wide gene expression data from Framingham Heart Study Offspring and Third Generation cohort participants. We excluded participants on lipid therapy. Multivariable linear regression models were conducted with plasma lipids as separate outcomes, energy-adjusted residuals of dietary fats as predictors, and adjustment for clinical and dietary covariates. Normalized gene expression from whole blood derived RNA was similarly modeled with additional adjustment for cell count and batch effects. Results: Among 3681 participants, higher polyunsaturated fatty acid (PUFA) intake is associated with lower LDL-C (estimated β [regression coefficient] = -0.5, p=0.002), higher HDL-C (β= 0.4, p&amp;lt;0.0001), and lower triglyceride (β= -0.009, p=0.0003) concentrations after adjustment for age, sex, carbohydrate, protein, and alcohol intake. Higher PUFA intake was associated with differential gene expression of cholesterol efflux transporters (ABCA1/ABCG1), LDL receptor degrader (IDOL), and non-lipoprotein metabolism related transcripts (FDR &amp;lt; 0.05). In contrast, higher saturated fat intake (SFA) showed inverse associations with ABCA1 expression levels and HDL cholesterol ( Figure 1 ). Conclusions: Higher PUFA intake is associated with a less atherogenic lipid profile and higher ABCA1 expression with inverse associations for higher SFA intake. Gene expression analysis reveals important links between dietary fat type, specific cholesterol metabolism pathways, and lipids in a community cohort.
Background: Inconsistent evidence describes the association between dietary intake of dairy and m... more Background: Inconsistent evidence describes the association between dietary intake of dairy and milk-based products and type 2 diabetes (T2D) risk. Objective: Our objective was to assess associations between consumption of milk-based products, incident prediabetes, and progression to T2D in the Framingham Heart Study Offspring Cohort. Methods: Total dairy and milk-based product consumption was assessed by #4 food-frequency questionnaires across a mean of 12 y of follow-up in 2809 participants [mean 6 SD age: 54.0 6 9.7 y; body mass index (in kg/m 2): 27.1 6 4.7; 54%
The American Journal of Clinical Nutrition, Sep 1, 2019
ABSTRACT Background Genes in metabolic and nutrient signaling pathways play important roles in li... more ABSTRACT Background Genes in metabolic and nutrient signaling pathways play important roles in lifespan in model organisms and human longevity. Objective The aim of this study was to examine the relation of a quantitative measure of healthy diet to gene expression in a community-based cohort. Methods We used the 2015 Dietary Guidelines for Americans Adherence Index (DGAI) score to quantify key dietary recommendations of an overall healthy diet. Our current analyses included 2220 Offspring participants (mean age 66 ± 9 y, 55.4% women) and 2941 Third-Generation participants (mean age 46 ± 9 y, 54.5% women) from the Framingham Heart Study. Gene expression was profiled in blood through the use of the Affymetrix Human Exon 1.0 ST Array. We conducted a transcriptome-wide association study of DGAI adjusting for age, sex, smoking, cell counts, and technical covariates. We also constructed a combined gene score from genes significantly associated with DGAI. Results The DGAI was significantly associated with the expression of 19 genes (false discovery rate &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). The most significant gene, ARRDC3, is a member of the arrestin family of proteins, and evidence in animal models and human data suggests that this gene is a regulator of obesity and energy expenditure. The DGAI gene score was associated with body mass index (P = 1.4 × 10−50), fasting glucose concentration (P = 2.5 × 10−11), type 2 diabetes (P = 1.1 × 10−5), and metabolic syndrome (P = 1.8 × 10−32). Conclusions Healthier diet was associated with genes involved in metabolic function. Further work is needed to replicate our findings and investigate the relation of a healthy diet to altered gene regulation.
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, ... more Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine to methionine. The C677T MTHFR polymorphism is associated with mild hyperhomocysteinemia, but only in the presence of low folate status. Because MTHFR contains flavin adenine dinucleotide (FAD) as a prosthetic group, riboflavin status may also influence homocysteine metabolism. The objective of this study was to examine the association between riboflavin status and fasting plasma total homocysteine (tHcy) concentration while also considering MTHFR C677T genotype and folate status. The study was conducted using fasting plasma samples (n ϭ 450) from the fifth examination of the Framingham Offspring Study cohort. All persons with the TT genotype and age-and sex-matched sets of individuals with the CT and CC genotypes were selected for determination of plasma riboflavin and flavin mono-and dinucleotide levels. Plasma riboflavin was associated with tHcy concentrations, but the association was largely confined to persons with plasma folate Ͻ12.5 nmol/L and TT genotype. In these persons, the mean tHcy among individuals with riboflavin levels Ͻ6.89 nmol/L was 14.5 mol/L, whereas the mean tHcy for those with riboflavin Ն11 nmol/L was 11.6 mol/L (P-trend Ͻ0.03). Plasma flavin nucleotides were unrelated to tHcy concentrations. Our data suggest that riboflavin status may affect homocysteine metabolism, but only in a small segment of the population who have both low folate status and are homozygotes for the MTHFR C677T mutation.
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Papers by Paul Jacques