The balance between food and dietary supplements in the general population

Abstract: In the past, vitamins and minerals were used to cure deficiency diseases. Supplements nowadays are used with the aim of reducing the risk of chronic diseases of which the origins are complex. Dietary supplement use has increased in the UK over recent decades, contributing to the nutrient intake in the population, but not necessarily the proportion of the population that is sub optimally nourished; therefore, not reducing the proportion below the estimated average requirement and potentially increasing the number at risk of an intake above the safety limits. The supplement nutrient intake may be objectively monitored using circulation biomarkers. The influence of the researcher in how the supplements are grouped and how the nutrient intakes are quantified may however result in different conclusions regarding their nutrient contribution, the associations with biomarkers in general, and dose-response associations specifically. The diet might be sufficient in micronutrients, but lacking in a balanced food intake. Since public health nutrition guidelines are expressed in terms of foods, there is potentially a discrepancy between the nutrient-orientated supplement and the quality of the dietary pattern. To promote health, current public health messages only advocate supplements in specific circumstances, but not in optimally nourished populations.The author reports programme grants from Cancer Research UK (G0401527, G1000143) and the Medical Research Council (MRC) (C864/A8257, C864/A14136)

Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort.

BACKGROUND: Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations. METHODS: Seven-day diet diaries and blood samples were taken from two subsets of the European Prospective Investigation into Cancer (EPIC-Norfolk) cohort (age range 39-79 years; n = 1400 for vitamin D; n = 6656 for remaining nutrients). TNI was calculated for the subgroups: nonsupplement users, those consuming the nutrient in supplement form and those consuming a supplement without this nutrient. RESULTS: CLO-related nutrients were supplemented by 15%-33%, which approximately doubled median intakes. Almost everyone in the supplement + vitamin A group reached the estimated average requirement; however, guideline levels were likely to be exceeded. Partial correlations between intake of vitamins A and D and biomarkers were low and modestly strengthened by the inclusion of supplement sources (correlation = 0.01-0.13). Correlations between biomarker and TNI of vitamin E and EPA+DHA were in the range 0.40-0.46; however, vitamin E exceeding food intake resulted in attenuated coefficients. Linear associations between food or TNI EPA+DHA and plasma were weak but consistent across subgroups. CONCLUSIONS: CLO-related nutrients contribute substantially to nutrient intake, with a risk of over-consumption. Apart from EPA+DHA, biomarker data suggest that CLO-related nutrients in supplements are not linearly associated with vitamin status.All authors report grants from Cancer Research UK and grants from the Medical Research Council (MRC) during the study.This is the final published manuscript, first published by Wiley in the Journal of Human Nutrition and Dietetics here: http://dx.doi.org/10.1111/jhn.1227

Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), β-carotene intake (P=0·003), β-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and β-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.The EPIC-Norfolk study received grants from the Medical Research Council (G9502233) and from Cancer Research UK (SP2024-0201 and SP2024-0204)

Fracture Risk in Relation to Serum 25-Hydroxyvitamin D and Physical Activity: Results from the EPIC-Norfolk Cohort Study.

Vitamin D deficiency and physical inactivity have been associated with bone loss and fractures, but their combined effect has scarcely been studied either in younger or older adults. Therefore, we aimed to assess the associations between physical activity, age and 25-hydroxyvitamin D (25(OH)D) status separately and in combination with the incidence of fracture risk in the EPIC-Norfolk cohort study. Baseline (1993-1998) self-reported physical activity and serum 25(OH)D concentrations at follow-up (1998-2000) were collected in 14,624 men and women (aged 42-82 y between 1998 and 2000). Fracture incidence was ascertained up to March 2015. Cox proportional hazard model was used to determine HRs of fractures by plasma 25(OH)D (90 nmol/L), age (65 y) and physical activity (inactive and active) categories, by follow-up time per 20 nmol/L increase in serum 25(OH)D and to explore age-25(OH)D and physical activity-25(OH)D interactions. The age-, sex-, and month-adjusted HRs (95% CIs) for all fractures (1183 fractures) by increasing vitamin D category were not significantly different. With additional adjustment for body mass index, smoking status, alcohol intake, supplement use and history of fractures, the fracture risk was 29% lower in those participants with 50 to 70 nmol/L compared with those in the lowest quintile (<30 nmol/L). Physical inactivity based on a single baseline assessment was not associated with fracture risk. Vitamin D status appeared inversely related to fractures in middle aged adults. In older adults, the relationship between vitamin D status and fracture risk was observed to be J-shaped. Clinical and public health practice in vitamin D supplementation could partially explain these findings, although definitive conclusions are difficult due to potential changes in exposure status over the long follow up period.This work was supported by Medical Research Council (MRC) - MKS/S16 (RG19715) / Sponsor Funding Ref: G9502233; Cancer Research UK (CRUK) - MKS/R07 (RG14230) / Sponsor Funding Ref: SP2024/0201; and Cancer Research UK (CRUK) - MKS/T21 (RG23772) / Sponsor Funding Ref: SP2024/0204. CJA received a Grant FPU13/00421 from the Government of Spain “Ministerio de Educación, Cultura y Deporte”

Longitudinal associations between marine omega-3 supplement users and Coronary Heart Disease in a UK population-based cohort

Objectives: Assess the association between marine omega-3 polyunsaturated fatty acid (n 3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart disease (CHD) mortality. Design: Prospective cohort study, with three exposure measurements over 22 y. Setting: Norfolk-based European Prospective Investigation into Cancer (EPIC-Norfolk, UK). Participants: 22,035 men and women from the general population, 39-79 y at recruitment. Exposure: Supplement use was assessed in three questionnaires (1993-1998; 2002-2004; 2004-2011). Participants were grouped into non-supplement users (NSU), n 3 PUFA supplement users (SU+n3) and non n 3 PUFA supplement users (SU n3). Cox regression adjusted for time-point specific variables: age, smoking, prevalent illnesses, BMI, alcohol consumption, physical activity and season and baseline assessments of sex, social class, education and dietary intake (7-day diet diary). Primary and secondary outcome measures: During a median of 19 y follow-up, 1562 CHD deaths were registered for 22,035 included participants. Results: Baseline supplement use was not associated with CHD mortality, but baseline food and supplement intake of n 3 PUFA was inversely associated with CHD mortality after adjustment for fish consumption. Using time-varying covariate analysis, significant associations were observed for SU+n3 (HR: 0.74, 95%CI: 0.66, 0.84), but not for SU n3 vs. NSU. In further analyses, the association for SU+n3 persisted in those who did not take other supplements (HR: 0.83, 95%CI: 0.71, 0.96) and those who did (HR: 0.74, 95%CI: 0.60, 0.91). Those who became SU+n3 over time or were consistent SU+n3 vs. consistent NSU had a lower hazard of CHD mortality; no association with CHD was observed in those who stopped using n 3 PUFA-containing supplements. Conclusions: Recent use of n 3 PUFA supplements was associated with a lower hazard of CHD mortality in this general population with low fish consumption. Residual confounding cannot be excluded, but the findings observed may be explained by postulated biological mechanisms and the results were specific to SU+n3.All authors report grants from Cancer Research UK programme grants (G0401527, G1000143) and grants from the Medical Research Council (MRC) programme grants (C864/A8257, C864/A14136) during the study. RHK is supported by a MRC Fellowship (MR/M014827/1)

The circadian rhythm of corticosteroid-binding globulin has little impact on cortisol exposure after hydrocortisone dosing

CONTEXT: Optimisation of hydrocortisone replacement therapy is important to prevent under- and over dosing. Hydrocortisone pharmacokinetics is complex as circulating cortisol is protein bound mainly to corticosteroid-binding globulin (CBG) that has a circadian rhythm. OBJECTIVE: A detailed analysis of the CBG circadian rhythm and its impact on cortisol exposure after hydrocortisone administration. DESIGN AND METHODS: CBG was measured over 24 h in 14 healthy individuals and, employing a modelling and simulation approach using a semi-mechanistic hydrocortisone pharmacokinetic model, we evaluated the impact on cortisol exposure (area under concentration-time curve and maximum concentration of total cortisol) of hydrocortisone administration at different clock times and of the changing CBG concentrations. RESULTS: The circadian rhythm of CBG was well described with two cosine terms added to the baseline of CBG: baseline CBG was 21.8 μg/mL and inter-individual variability 11.9%; the amplitude for the 24 h and 12 h cosine functions were relatively small (24 h: 5.53%, 12 h: 2.87%) and highest and lowest CBG were measured at 18:00 and 02:00, respectively. In simulations, the lowest cortisol exposure was observed after administration of hydrocortisone at 23:00-02:00, whereas the highest was observed at 15:00-18:00. The differences between the highest and lowest exposure were minor (≤12.2%), also regarding the free cortisol concentration and free fraction (≤11.7%). CONCLUSIONS: CBG has a circadian rhythm but the difference in cortisol exposure is ≤12.2% between times of highest and lowest CBG concentrations; therefore hydrocortisone dose adjustment based on time of dosing to adjust for the CBG concentrations is unlikely to be of clinical benefit

Correcting for measurement error in fractional polynomial models using Bayesian modelling and regression calibration, with an application to alcohol and mortality

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Exposure measurement error can result in a biased estimate of the association between an exposure and outcome. When the exposure–outcome relationship is linear on the appropriate scale (e.g. linear, logistic) and the measurement error is classical, that is the result of random noise, the result is attenuation of the effect. When the relationship is non-linear, measurement error distorts the true shape of the association. Regression calibration is a commonly used method for correcting for measurement error, in which each individual's unknown true exposure in the outcome regression model is replaced by its expectation conditional on the error-prone measure and any fully measured covariates. Regression calibration is simple to execute when the exposure is untransformed in the linear predictor of the outcome regression model, but less straightforward when non-linear transformations of the exposure are used. We describe a method for applying regression calibration in models in which a non-linear association is modelled by transforming the exposure using a fractional polynomial model. It is shown that taking a Bayesian estimation approach is advantageous. By use of Markov chain Monte Carlo algorithms, one can sample from the distribution of the true exposure for each individual. Transformations of the sampled values can then be performed directly and used to find the expectation of the transformed exposure required for regression calibration. A simulation study shows that the proposed approach performs well. We apply the method to investigate the relationship between usual alcohol intake and subsequent all-cause mortality using an error model that adjusts for the episodic nature of alcohol consumption