Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity--a prospective study of three independent cohorts

Sofus C Larsen, Lars Angquist, Tarunveer Singh Ahluwalia, Tea Skaaby, Nina Roswall, Anne Tjønneland, Jytte Halkjær, Kim Overvad, Oluf Pedersen, Torben Hansen, Allan Linneberg, Lise Lotte N Husemoen, Ulla Toft, Berit L Heitmann, Thorkild I A Sørensen, Sofus C Larsen, Lars Angquist, Tarunveer Singh Ahluwalia, Tea Skaaby, Nina Roswall, Anne Tjønneland, Jytte Halkjær, Kim Overvad, Oluf Pedersen, Torben Hansen, Allan Linneberg, Lise Lotte N Husemoen, Ulla Toft, Berit L Heitmann, Thorkild I A Sørensen

Abstract

Background: Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC).

Methods: A total of 7,569 participants' from MONICA, the Diet Cancer and Health study and the INTER99 study were included in the study. We combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC and WHR) with which the SNPs associate. Linear regression was used to examine the association between ascorbic acid intake and ΔBW or ΔWC. SNP-score × ascorbic acid interactions were examined by adding product terms to the models.

Results: We found no significant associations between dietary ascorbic acid and ∆BW or ∆WC. Regarding SNP-score × ascorbic acid interactions, each additional risk allele of the 14 WHR associated SNPs associated with a ∆WC of 0.039 cm/year (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake. However, the association to ∆WC only remained borderline significant after adjustment for ∆BW.

Conclusion: In general, our study does not support an association between dietary ascorbic acid and ∆BW or ∆WC, but a diet with a high content of ascorbic acid may be weakly associated to higher WC gain among people who are genetically predisposed to a high WHR. However, given the quite limited association any public health relevance is questionable.

Trial registration: ClinicalTrials.gov NCT00289237.

Figures

Figure 1
Figure 1
Interaction between genetic predisposition scores and dietary ascorbic acid in relation to change in body weight. Abbreviations: BMI score, sum of body mass index associated risk-alleles; WC score, sum of waist circumference associated risk-alleles; WHR score, sum of waist-hip ratio associated risk-alleles; Complete score, sum of SNP associated to all three phenotypes. Results presented as annual weight change (kg/year) effect-modification for each additional risk-allele per 100 mg/day higher ascorbic acid intake. The study-specific SNP-score × ascorbic acid interactions were calculated using linear regression and corresponding meta-analysis results were derived using a fixed effect approach, where the effect-estimates where weighted by the inverses of their variances (% weight). The results were adjusted for baseline measure of body weight, height, sex, age, smoking status, alcohol consumption, physical activity, education and menopausal status for women.
Figure 2
Figure 2
Interaction between genetic predisposition scores and dietary ascorbic acid in relation to change in waist circumference. Abbreviations: BMI score, sum of body mass index associated risk-alleles; WC score, sum of waist circumference associated risk-alleles; WHR score, sum of waist-hip ratio associated risk-alleles; Complete score, sum of SNP associated to all three phenotypes. Results presented as annual change in waist circumference (cm/year) for each additional risk-allele per 100 mg/day higher ascorbic acid intake. The study-specific SNP-score × ascorbic acid interactions were calculated using linear regression and corresponding meta-analysis results where derived using a fixed effect approach, were the effect-estimates were weighted by the inverses of their variances (% weight). The results were adjusted for baseline measure of waist circumference, height, sex, age, smoking status, alcohol consumption, physical activity, education and menopausal status for women.

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