Serum 25-hydroxyvitamin D response to vitamin D supplementation using different lipid delivery systems in middle-aged and older adults: a randomised controlled trial.

Food fortification improves vitamin D intakes but is not yet mandated in many countries. Combining vitamin D with different dietary lipids altered vitamin D absorption in in vitro and postprandial studies. This randomised, placebo-controlled trial examined the effect of the lipid composition of a vitamin D-fortified dairy drink on change in 25-hydroxyvitamin D (25(OH)D) concentrations. Sixty-three healthy adults aged 50+ years were randomised to one of the following for 4 weeks: vitamin D-fortified olive oil dairy drink, vitamin D-fortified coconut oil dairy drink, vitamin D supplement or placebo control dairy drink. All vitamin D groups received 20 µg of vitamin D3 daily. Serum was collected at baseline and post-intervention to measure 25(OH)D concentrations and biomarkers of metabolic health. Repeated-measures general linear model ANCOVA (RM GLM ANCOVA) compared changes over time. There was a significant time × treatment interaction effect on 25(OH)D concentrations for those classified as vitamin D-insufficient (P < 0·001) and -sufficient at baseline (P = 0·004). 25(OH)D concentrations increased significantly for all insufficient participants receiving vitamin D3 in any form. However, for vitamin D-sufficient participants at baseline, 25(OH)D concentrations only increased significantly with the coconut oil dairy drink and supplement. There was no effect of vitamin D on biomarkers of metabolic health. Vitamin D fortification of lipid-containing foods may be used in lieu of supplementation when supplement adherence is low or for individuals with dysphagia. These results are important given the recent recommendation to increase vitamin D intakes to 15-20 µg for older adults in Ireland.

Influence of Vitamin D Status and Supplementation on Metabolomic Profiles of Older Adults.

Metabolomics can identify metabolite patterns associated with different nutrition phenotypes and determine changes in metabolism in response to nutrition interventions. Vitamin D insufficiency is associated with increased metabolic disease risk; however, the role of vitamin D in metabolic health is not fully understood. This randomised, placebo-controlled trial (RCT) examined the influence of vitamin D status and the effect of vitamin D supplementation on metabolomic profiles in older adults. Healthy adults aged 50+ were randomly assigned to consume 20 µg vitamin D3 or a placebo daily for 4 weeks. Serum samples were collected at baseline and post-intervention for 25(OH)D and metabolomics analysis via liquid chromatography tandem mass spectrometry (LC-MS/MS). Pearson's correlation examined relationships between 25(OH)D and metabolite concentrations. GLM ANCOVA compared metabolite concentrations between vitamin D-insufficient (<50 nmol/L) and -sufficient (>50 nmol/L) participants. The repeated-measures general linear model of covariance (RM GLM ANCOVA) examined changes in metabolites over time. Out of 132 metabolites, 2 short chain fatty acid concentrations were higher in the insufficient participants compared to sufficient participants, and 11 glycerophospholipid concentrations were lower in insufficient participants compared to sufficient participants at baseline. Three acylcarnitine concentrations decreased with vitamin D supplementation in vitamin D-insufficient participants. Our findings suggest that vitamin D status influences lipid metabolism in healthy older adults and supports the use of metabolomics in vitamin D research.

Postprandial 25-hydroxyvitamin D response varies according to the lipid composition of a vitamin D3 fortified dairy drink.

In-vitro evidence suggests that the lipid component of foods alters vitamin D absorption. This single-blinded, cross-over postprandial study examined the effect of changing the lipid component of a 20 µg vitamin D3 fortified dairy drink on postprandial 25(OH)D concentrations. Participants consumed one dairy drink per visit: a non-lipid, a pre-formed oleic acid micelle, an olive oil and a fish oil dairy drink. There was a significant time*drink*baseline status effect on 25(OH)D concentrations (p = 0.039). There were no time*drink, time or drink effects on 25(OH)D in vitamin D sufficient participants (>50nmol/L). However, there was an effect of time on changes in 25(OH)D concentrations after the olive oil dairy drink (p = 0.034) in vitamin D insufficient participants (<50nmol/L). There were no effects after the other diary drinks. Olive oil may improve vitamin D absorption from fortified foods. Further research is needed to examine the practical implications of changing the lipid component of fortified foods.

Efficacy and safety of food fortification to improve vitamin D intakes of older adults.

OBJECTIVES: The aim of this study was to determine the best foods for potential vitamin D food fortification and to model the efficacy and safety of different food fortification scenarios in adults ≥50 y of age in Ireland. METHODS: National Adult Nutrition Survey vitamin D data for participants ≥50 y of age were updated. Vitamin D from foods with natural and added vitamin D was estimated and daily vitamin D intake patterns were examined. Data modeling was used to estimate the effects of target food fortification scenarios. RESULTS: Almost two-thirds of the mean daily vitamin D intake of adults ≥50 y of age (7 ± 7 µg) comes from foods with added vitamin D. Milk and bread are the most frequently consumed foods across all meals and were subsequently targeted for the data modeling exercise. Results from the data modeling show that vitamin D intake increased between 9 and 17 µg/d, depending on the fortification scenario. Fortifying milk or bread resulted in ∼30% or ∼55% of individuals meeting the Recommended Daily Allowance (RDA); however, fortifying both simultaneously resulted in ∼70% meeting the RDA. CONCLUSIONS: Currently, the majority of Irish adults ≥50 y of age are not meeting dietary recommendations for vitamin D. Fortification of commonly consumed foods such as milk and bread could improve daily intakes such that ∼70% of the cohort would meet the minimum recommendation. Future research should examine the efficacy of different food fortification scenarios to improve vitamin D intakes for older adults.

21st century toolkit for optimizing population health through precision nutrition.

Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of "big data" to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individual's unique phenotype, or the current state of health, as determined by the interactions among biology, environment, and behavior. The tools of precision nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health.

Habitual diets rich in dark-green vegetables are associated with an increased response to ω-3 fatty acid supplementation in Americans of African ancestry.

Although substantial variation exists in individual responses to omega-3 (ω-3) (n-3) fatty acid supplementation, the causes for differences in response are largely unknown. Here we investigated the associations between the efficacy of ω-3 fatty acid supplementation and a broad range of nutritional and clinical factors collected during a double-blind, placebo-controlled trial in participants of African ancestry, randomly assigned to receive either 2 g eicosapentaenoic acid (EPA) + 1 g docosahexaenoic acid (n = 41) or corn/soybean oil placebo (n = 42) supplements for 6 wk. Food-frequency questionnaires were administered, and changes in erythrocyte lipids, lipoproteins, and monocyte 5-lipoxygenase-dependent metabolism were measured before and after supplementation. Mixed-mode linear regression modeling identified high (n = 28) and low (n = 13) ω-3 fatty acid response groups on the basis of changes in erythrocyte EPA abundance (P < 0.001). Compliance was equivalent (∼88%), whereas decreases in plasma triglycerides and VLDL particle sizes and reductions in stimulated monocyte leukotriene B4 production were larger in the high-response group. Although total diet quality scores were similar, the low-response group showed lower estimated 2005 Healthy Eating Index subscores for dark-green and orange vegetables and legumes (P = 0.01) and a lower intake of vegetables (P = 0.02), particularly dark-green vegetables (P = 0.002). Because the findings reported here are associative in nature, prospective studies are needed to determine if dietary dark-green vegetables or nutrients contained in these foods can enhance the efficacy of ω-3 fatty acid supplements. This trial was registered at clinicaltrials.gov as NCT00536185.

Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations.

Immunoglobulin A nephropathy (IgAN) is a leading cause of chronic kidney disease, frequently associated with hypertension and renal inflammation. ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fish oil (FO) improve kidney function in animal models, but have inconsistent metabolic effects in humans. Oxylipin profiles in serum from IgAN patients supplemented with either FO or corn oil (CO) placebo were analyzed by liquid chromatography coupled to tandem mass spectrometry. EPA cyclooxygenase and lipoxygenase metabolites, and EPA and DHA epoxides and diols were increased in response to FO supplementation, as were total epoxides and epoxide/diol ratios. Several of these metabolites were drivers of separation as assessed by multivariate analysis of FO patients pre- vs. post-supplementation, including 17,18-dihydroxyeicosatrienoic acid, prostaglandin D3, prostagalandin E3, Resolvin E1, 12-hydroxyeicosapentaenoic acid, and 10(11)-epoxydocosapentaenoic acid. In patients whose proteinuria improved, plasma total oxylipins as well as several hydroxyoctadecadienoic acids, hydroxyeicosatetraenoic acids, and leukotriene B4 metabolites were among the metabolites that were significantly lower than in patients whose proteinuria either did not improve or worsened. These data support the involvement of oxylipins in the inflammatory component of IgAN as well as the potential use of oxylipin profiles as biomarkers and for assessing responsiveness to ω-3 fatty acid supplementation in IgAN patients.

Effect of supplementation with vitamin D3 on glucose production pathways in human subjects.

SCOPE: Research reports suggest that vitamin D affects glucose and insulin metabolism; however, the exact mechanisms are unclear. ²H NMR analysis of monoacetone glucose (MAG) after tracer administration provides a non-invasive method of profiling hepatic glucose metabolism. This study examined the effects of supplementation with vitamin D3 on contribution of glycogenolysis to glucose production. METHODS AND RESULTS: Tracer administration and biofluid collections were performed with eight healthy females before and following a 4-wk vitamin D3 administration period. Following an overnight fast subjects ingested deuterated water and acetaminophen. Full void urine samples were collected after 4 h. ²H NMR spectra of urinary monoacetone glucose were acquired to determine the contribution of glycogenolysis to glucose production. The mean contribution of glycogenolysis to glucose production was 60±13%. Supplementation with vitamin D3 had no effect on hepatic glucose production. Regression analysis revealed a significant relationship between carbohydrate intake and the contribution of glycogenolysis (ß=0.914, p=0.004). CONCLUSION: In conclusion, we saw no changes in the percentage contribution of glycogenolysis following supplementation with vitamin D3. The reproducibility of our results and the non-invasive nature of the method highlight the potential for this method in assessing mechanistic modes of action in future nutritional interventions.

Biochemical and metabolomic phenotyping in the identification of a vitamin D responsive metabotype for markers of the metabolic syndrome.

SCOPE: Metabolic phenotyping promises to be a useful tool in human intervention studies. This study examined whether metabolic phenotyping could identify responders to vitamin D supplementation in terms of the metabolic syndrome. METHODS AND RESULTS: In a double-blind, randomised placebo-controlled dietary intervention subjects were assigned to receive 15 µg vitamin D(3) or placebo daily. Serum 25-hydroxyvitamin D (25(OH)D) and biochemical markers of the metabolic syndrome were measured at baseline and following the 4-wk intervention. k-means clustering and (1) H-NMR metabolomic analysis were used to explore responsive phenotypes. Vitamin D supplementation significantly increased serum 25(OH)D to an endpoint concentration of 78.1 ± 20.0 nmol/L (p<0.001). There was no effect of supplementation on the measured markers of the metabolic syndrome. k-means cluster analysis based on 13 biochemical markers of the metabolic syndrome and 25(OH)D concentrations revealed five discrete biomarker clusters. One of these clusters, characterised by lower serum 25(OH)D and higher levels of adipokines, showed significant responses in insulin (15% decrease), homestatic model assessment scores (19% decrease) and c-reactive protein (54% decrease). Metabolomic analysis revealed further changes and the extent of change in serum vitamin D correlated negatively with changes in glucose. CONCLUSION: Overall, metabolic phenotyping revealed a phenotype that was responsive to vitamin D supplementation.