Nutrigenomic Studies Research Articles

Nutrigenomics: the role of nutrients in gene expression

Improved understanding of the mechanism behind periodontal tissue destruction, the potential protective role of nutrients and the advent of modern genomic measurement tools has led to an increased interest in the association between nutrition and periodontal disease. To date, evidence for a direct link between periodontal disease and nutrition has come mainly from large observational cross-sectional studies or very small double-blind randomized supplementation trials, with a large proportion finding no significant association between the nutrient being analyzed and markers of periodontal disease status. The advent of the 'genomic era' has introduced the concept of nutrigenomic studies, which aim to reveal the relationship between nutrition and the genome to provide a scientific basis for improved public health through dietary means. Used alongside relatively inexpensive high-throughput technology, this will allow the effect of diet on the etiology of periodontal disease to be studied in greater detail. As it is extremely likely that interactions between genotype and diet are important in determining the risk of the most common complex diseases, it is highly probable that these interactions will be important in determining periodontal disease risk. Numerous nutritional genetic studies where the outcome measures have been markers of disease risk, most notably cardiovascular disease and cancer, provide proof of principle, highlight the importance of understanding these interactions and illustrate where the effect of dietary modification on periodontal disease progression may have been overlooked previously by observational studies.

Association Between Caffeine Intake and the Plasma Proteome in Humans

Background: Caffeine intake has been associated with both an increased and decreased risk of various health conditions. However, many of the physiological pathways affected remain unclear. CYP1A2 is the major enzyme that metabolizes caffeine, and a single nucleotide polymorphism (rs762551) affects the rate of caffeine metabolism. Objective: The aim of this study was to determine the association between caffeine intake and the plasma proteome, and whether CYP1A2 genotype modifies any association. Methods: Subjects (n=1,095) aged 20–29 years from the Toronto Nutrigenomics and Health Study completed a 196-item semi-quantitative food frequency questionnaire and provided a fasting blood sample from which DNA and plasma were obtained for genotyping and proteomics analysis. Fifty-four proteins were measured by mass spectrometry multiple reaction monitoring (MS-MRM). Subjects were categorized into three groups according to habitual caffeine intake ( 200 mg/d) and stratified by CYP1A2 ...

Plasma concentration of cis 9trans 11 CLA in males and females is influenced by SCD1 genetic variations and hormonal contraceptives: a cross-sectional study

BackgroundThe conjugated linoleic acid isomer cis9trans11 CLA can be endogenously synthesized from trans vaccenic acid (C18:1 t11) via desaturation at the delta 9 position catalyzed by the stearoyl-CoA desaturase 1 (SCD1), also known as delta-9 desaturase (D9D). Diet, hormonal regulation of gene expression and single nucleotide polymorphisms (SNPs) have been implicated in altering circulating levels of fatty acids. Hormonal contraceptives (HC) have also been shown to influence levels of some fatty acids. SNPs in SCD1 have been associated with altered levels of palmitoleic and oleic acids; however, associations between SCD1 SNPs and D9D desaturation index have not been previously examined in relation to CLA. Herein, we investigated the effects of sex and HC use on circulating concentrations of c9t11 CLA and D9D desaturation index. Furthermore, we determined the effects of ten SCD1 SNPs on D9D desaturation indices estimated by product to precursor ratio of c9t11 CLA to C18:1 t11.MethodsPlasma samples were collected from subjects (Caucasian males: n = 113; Caucasian females: n = 298; Asian males: n = 98; Asian females: n = 277) from the Toronto Nutrigenomics and Health Study. Circulating fatty acids levels were measured by gas chromatography.ResultsResults show that circulating c9t11 CLA concentrations are significantly higher in females than males and they are further elevated in females using HC. In addition, a significant sex- and ethnic-specific association was found between SCD1 SNP rs10883463 (p = 0.0014) and altered D9D activity in Caucasian males.ConclusionFindings from the present study identify SCD1 SNPs and hormonal contraceptives as factors altering endogenous c9t11 CLA levels in a sex- and ethnic-specific manner.

Identifying markers of insulin resistance in the plasma proteome

Type 2 diabetes (T2D) represents a significant global health problem. The plasma proteome comprises numerous high‐abundance proteins that may be associated with the development of T2D. The objective was to determine the association between HOMA‐IR, a common measure of insulin resistance, and 54 plasma proteins belonging to disease‐associated pathways in a population of healthy young adults (n=488) from the Toronto Nutrigenomics and Health Study. Protein concentrations were measured by a multiple reaction monitoring HPLC‐MS/MS assay. General linear models were used to assess the association between plasma proteins and HOMA‐IR. Analyses were adjusted for age, sex, ethnicity, waist circumference, physical activity, and contraceptive use among women. Hemopexin, complement factor H, heparin cofactor II, afamin, α1‐anti‐trypsin, α2‐HS‐glycoprotein, apolipoprotein L1, complement C3, serum amyloid P‐component, vitronectin, and transthyretin were significantly (p<0.0009) positively correlated with HOMA‐IR. Adiponectin, an anti‐inflammatory protein, was inversely correlated with HOMA‐IR. These results suggest that a number of plasma proteins may be useful biomarkers of insulin resistance and T2D risk. Research support from the Advanced Foods and Materials Network.

A genome‐wide association study (GWAS) of the human plasma proteome

High‐abundance plasma proteins are involved in disease‐associated pathways and are useful biomarkers of disease states and dietary exposures. The concentrations of these proteins vary across individuals, but it is unclear whether the observed differences are related to inter‐individual genetic variation. The objective was to explore associations between genome‐wide genetic variants and 54 plasma proteins belonging to disease‐associated pathways in healthy young adults (n=488) from the Toronto Nutrigenomics and Health Study. We report the first GWAS to be conducted on the human plasma proteome. Protein concentrations were measured by a multiple reaction monitoring HPLC‐MS/MS assay. Linear regressions with an additive mode of inheritance were used to explore the associations between genetic variants and plasma proteins. We identified 40 variants in 12 genes that were significantly (p< 1.13×10−9) associated with the proteins analyzed. Variants in genes that encode α1B‐glycoprotein, gelsolin isoform 1, histidine‐rich glycoprotein, and α2‐HS‐glycoprotein were each associated with circulating levels of their respective protein. These results suggest that common genetic variants modify circulating levels of plasma proteins involved in actin scavenging, inflammation, and other immune responses. Research support from the Advanced Foods and Materials Network.

Nutrigenomic studies of orange juice and vitamin C on gene expressions in neuronal tissues of Sprague Dawley rats.

Nutrigenomics, a nascent field in nutrition and molecular biology plays a pivotal role in understanding the influence of bioactive dietary components on the structure, integrity and functions of the genome. In this study, the comparative effects of vitamin C (Vit C) and Nigerian local orange juice on the gene expression levels of superoxide dismutase (sod), tumour necrosis factor receptor (tnfr), p53 protein (p53), estrogen receptor (esr) and progesterone receptor (pgr) genes were evaluated in rat neuronal tissues. 5 ml/Kg bodyweight of freshly extracted orange juice and 20 mg/Kg bodyweight Vit C were administered orally to Sprague Dawley rats distributed into orange, vitamin C and control groups, respectively. Expressions of sod, tnfr, p53,esr and pgr genes were measured by relative quantification PCR using SYBR green chemistry. Data were analyzed using Applied Biosystems SDS software 1.4 and Graphpad prism 5.0. A 57.01 ± 6.37 fold significant (P 0.05). Orange juice has been shown to posses the ability to increase significantly mRNA expression levels oftnfr gene in the brain neuronal tissues of male rats. The increase is probably mediated by other bioactive components in the orange juice rather than vitamin C. Key words: Vitamin C, orange juice, relative quantification PCR, gene expression, brain tissue.

Up-to date knowledge on the in vivo transcriptomic effect of the Mediterranean diet in humans

The present review discusses and summarizes the up-to-date body of knowledge concerning human nutrigenomic studies with Mediterranean diet (MedDiet) and olive oil (OO) interventions, at real-life doses and conditions. A literature review was carried out until March 2012. Original articles assessing the nutrigenomic effect of the MedDiet and its main source of fat, OO, on gene expression were selected. State-of-the-art data in this field, although scarce, are promising. Despite a great diversity among studies, the attributed health benefits of the MedDiet and its components, such as OO, could be explained by a transcriptomic effect on atherosclerosis, inflammation, and oxidative stress-related genes (i.e. ADRB2, IL7R, IFNγ, MCP1, TNFα). Gene expression changes toward a protective mode were often associated with an improvement in systemic markers for oxidation and inflammation. The suggested underlying molecular pathways responsible for these changes, and the extent to which evidence exists of a MedDiet and OO nutrigenomic effect, are also discussed.

Essential fatty acids deficiency promotes lipogenic gene expression and hepatic steatosis through the liver X receptor

Nutrients influence non-alcoholic fatty liver disease. Essential fatty acids deficiency promotes various syndromes, including hepatic steatosis, through increased de novo lipogenesis. The mechanisms underlying such increased lipogenic response remain unidentified. We used wild type mice and mice lacking Liver X Receptors to perform a nutrigenomic study that aimed at examining the role of these transcription factors. We showed that, in the absence of Liver X Receptors, essential fatty acids deficiency does not promote steatosis. Consistent with this, Liver X Receptors are required for the elevated expression of genes involved in lipogenesis in response to essential fatty acids deficiency. This work identifies, for the first time, the central role of Liver X Receptors in steatosis induced by essential fatty acids deficiency.

UP780, a Chromone-Enriched <i>Aloe</i> Composition, Enhances Adipose Insulin Receptor Signaling and Decreases Liver Lipid Biosynthesis

Nutrigenomic studies were conducted to uncover the mechanism of action for the hypoglycemic and insulin sensitizing effects of UP780. From high fat diet-induced obesity mouse model for UP780, livers and white adipose tissues (WAT) from groups of lean control, high fat diet (HFD), and HFD treated with UP780 were collected for microarray study. Microarray generated gene expression changes were applied to Ingenuity Pathway Analysis for changes in canonical metabolic and signaling pathways. Microarray was validated by quantitative reverse transcriptase-polymerase chain reaction (QPCR), Western blots, liver triglyceride, liver cholesterol, liver steatosis, and insulin ELISA. UP780 treatment decreased liver gene expressions for multiple enzymes involved in fatty acid biosynthesis and triglyceride production. UP780 treatment increased gene expressions globally for the insulin receptor signaling pathway in WAT. Both liver triglyceride and liver cholesterol levels were significantly reduced by UP780 over HFD. The reduction of liver fat was confirmed by microscopic analysis of liver steatosis. Finally, UP780 significantly decreased fasting plasma insulin level over HFD. The mechanism of action for UP780 indicated a reduction of liver fat accumulation and an enhancement in adipose tissue insulin signaling pathway. This provided mechanistic explanation for the in vivo UP780 effects of enhanced insulin sensitiveity and decreased blood glucose in mouse diabetes and prediabetes models.

Prediabetic changes in gene expression induced by aspartame and monosodium glutamate in Trans fat-fed C57Bl/6J mice.

BackgroundThe human diet has altered markedly during the past four decades, with the introduction of Trans hydrogenated fat, which extended the shelf-life of dietary oils and promoted a dramatic increase in elaidic acid (Trans-18.1) consumption. Food additives such as monosodium glutamate (MSG) and aspartame (ASP) were introduced to increase food palatability and reduce caloric intake. Nutrigenomics studies in small-animal models are an established platform for analyzing the interactions between various macro- and micronutrients. We therefore investigated the effects of changes in hepatic and adipose tissue gene expression induced by the food additives ASP, MSG or a combination of both additives in C57Bl/6 J mice fed a Trans fat-enriched diet.MethodsHepatic and adipose tissue gene expression profiles, together with body characteristics, glucose parameters, serum hormone and lipid profiles were examined in C57Bl/6 J mice consuming one of the following four dietary regimens, commencing in utero via the mother’s diet: [A] Trans fat (TFA) diet; [B] MSG + TFA diet; [C] ASP + TFA diet; [D] ASP + MSG + TFA diet.ResultsWhilst dietary MSG significantly increased hepatic triglyceride and serum leptin levels in TFA-fed mice, the combination of ASP + MSG promoted the highest increase in visceral adipose tissue deposition, serum free fatty acids, fasting blood glucose, HOMA-IR, total cholesterol and TNFα levels. Microarray analysis of significant differentially expressed genes (DEGs) showed a reduction in hepatic and adipose tissue PPARGC1a expression concomitant with changes in PPARGC1a-related functional networks including PPARα, δ and γ. We identified 73 DEGs common to both adipose and liver which were upregulated by ASP + MSG in Trans fat-fed mice; and an additional 51 common DEGs which were downregulated.ConclusionThe combination of ASP and MSG may significantly alter adiposity, glucose homeostasis, hepatic and adipose tissue gene expression in TFA-fed C57Bl/6 J mice.

Association between the plasma proteome and plasma α-tocopherol concentrations in humans

Vitamin E is a lipophilic antioxidant that has been inversely associated with certain chronic diseases; however, the biological processes regulated by this vitamin have not been fully elucidated. The objective of the present study was to examine the association between the most biologically active and abundant form of vitamin E in the circulation, α-tocopherol, and the plasma proteome. Subjects were from the Toronto Nutrigenomics and Health Study and included men and women (n=1,022) who completed a general health and lifestyle questionnaire and 196-item food frequency questionnaire, and provided a fasting blood sample. Plasma α-tocopherol concentrations were measured by high-performance liquid chromatography and 54 plasma proteins were assayed by a mass spectrometry-based multiple reaction monitoring method. Analysis of covariance was used to compare mean concentrations of plasma proteins across tertiles of α-tocopherol. Plasma concentrations of apolipoprotein C-III, fibrinogen alpha, beta, and gamma chains, fibronectin and fibrinopeptide A were significantly and positively associated with plasma α-tocopherol, while intermediate levels of α-tocopherol were significantly associated with higher levels of alpha-1B-glycoprotein (all P<.0009). These findings show that circulating levels of α-tocopherol are significantly associated with specific plasma proteins and suggest novel physiological effects of vitamin E.

Association between circulating ascorbic acid, α-tocopherol, 25-hydroxyvitamin D, and plasma cytokine concentrations in young adults: a cross-sectional study

BackgroundInflammation and oxidative stress are associated with the development of numerous chronic diseases. Circulating ascorbic acid, α-tocopherol, and 25-hydroxyvitamin D (25(OH)D) may help reduce concentrations of pro-inflammatory cytokines through their antioxidant and anti-inflammatory properties. These micronutrients may act synergistically, and they may have different anti-inflammatory effects, but previous studies have assessed the link between each of these micronutrients and inflammation in isolation without controlling for the other micronutrients. Our objective was to examine the association between circulating concentrations of ascorbic acid, α-tocopherol, and 25(OH) D and a panel of pro-inflammatory cytokines in an ethnically diverse population of young adults.MethodsParticipants (n = 1,007) from the Toronto Nutrigenomics and Health study provided fasting blood samples for biomarker measurements and were subsequently categorized into tertiles for each micronutrient based on their circulating concentrations. We conducted Pearson’s correlation analyses across all micronutrients and cytokines. The associations between individual micronutrients and cytokines were examined using analysis of covariance with age, sex, waist circumference, ethnicity, physical activity, season of blood collection, total cholesterol, hormonal contraceptive use among women, and the other two micronutrients as covariates.ResultsWe observed weak micronutrient-cytokine correlations, moderate correlations between certain cytokines, and strong correlations between specific cytokines, particularly interleukin 1- receptor antagonist (IL-1RA), interferon-γ (IFN-γ), and platelet-derived growth factor BB (PDGF-bb). After full covariate adjustment, circulating α-tocopherol was inversely associated with IFN-γ and regulated upon activation normal T-cell expressed and secreted (RANTES). We observed an unexpected positive association between ascorbic acid and IFN-γ. 25(OH)D was not associated with altered concentrations of any inflammatory biomarkers.ConclusionsThese findings suggest that α-tocopherol, but not ascorbic acid or 25(OH)D, is inversely associated with inflammation in healthy young adults.

Genetic Variation in Putative Salt Taste Receptors and Salt Taste Perception in Humans

The objective of this study was to determine whether single nucleotide polymorphisms (SNPs) in the SCNN1A (3), SCNN1B (12), SCNN1G (6), and TRPV1 (10) genes affect salt taste perception. Participants were men (n = 28) and women (n = 67) from the Toronto Nutrigenomics and Health study aged 21-31 years. Taste thresholds were determined using a 3-alternative forced-choice staircase model with solutions ranging from 9×10(-6) to 0.5 mol/L. Suprathreshold taste sensitivity to 0.01-1.0 mol/L salt solutions was assessed using general labeled magnitude scales. None of the SNPs in the SCNN1A and SCNN1G genes were significantly associated with either outcome. In the SCNN1B gene, 2 SNPs in intronic regions of the gene modified suprathreshold taste sensitivity (mean iAUC ± SE). Those homozygous for the A allele of the rs239345 (A>T) polymorphism and the T allele of the rs3785368 (C>T) polymorphism perceived salt solutions less intensely than carriers of the T or C alleles, respectively (rs239345: 70.82±12.16 vs. 96.95±3.75, P = 0.02; rs3785368: 57.43±19.85 vs. 95.57±3.66, P = 0.03) In the TRPV1 gene, the rs8065080 (C>T, Val585Ile) polymorphism modified suprathreshold taste sensitivity where carriers of the T allele were significantly more sensitive to salt solutions than the CC genotype (98.3±3.8 vs. 74.1±8.3, P = 0.008). Our findings show that variation in the TRPV1 and the SCNN1B genes may modify salt taste perception in humans.

Impact of Grapefruit Flavanone Consumption on Vascular Protection and Bone Metabolism: Clinical and Nutrigenomic Study

Impact of Grapefruit Flavanone Consumption on Vascular Protection and Bone Metabolism: Clinical and Nutrigenomic Study

Novel Effects of Hormonal Contraceptive Use on the Plasma Proteome

BackgroundHormonal contraceptive (HC) use may increase cardiometabolic risk; however, the effect of HC on emerging cardiometabolic and other disease risk factors is not clear.ObjectivesTo determine the association between HC use and plasma proteins involved in established and emerging disease risk pathways.MethodConcentrations of 54 high-abundance plasma proteins were measured simultaneously by LC-MRM/MS in 783 women from the Toronto Nutrigenomics and Health Study. C-reactive protein (CRP) was measured separately. ANCOVA was used to test differences in protein concentrations between users and non-users, and among HC users depending on total hormone dose. Linear regression was used to test the association between duration (years) of HC use and plasma protein concentrations. Principal components analysis (PCA) was used to identify plasma proteomic profiles in users and non-users.ResultsAfter Bonferroni correction, 19 proteins involved in inflammation, innate immunity, coagulation and blood pressure regulation were significantly different between users and non-users (P<0.0009). These differences were replicated across three distinct ethnocultural groups. Traditional markers of glucose and lipid metabolism were also significantly higher among HC users. Neither hormone dose nor duration of use affected protein concentrations. PCA identified 4 distinct proteomic profiles in users and 3 in non-users.ConclusionHC use was associated with different concentrations of plasma proteins along various disease-related pathways, and these differences were present across different ethnicities. Aside from the known effect of HC on traditional biomarkers of cardiometabolic risk, HC use also affects numerous proteins that may be biomarkers of dysregulation in inflammation, coagulation and blood pressure.

Association between the plasma proteome and serum ascorbic acid concentrations in humans

Vitamin C has been associated with a reduced risk of chronic diseases, but the biological pathways regulated by vitamin C are not all known. The objective was to use a proteomics approach to identify plasma proteins associated with circulating levels of ascorbic acid. Men and women (n=1022) 20–29 years of age from the Toronto Nutrigenomics and Health Study completed a general health and lifestyle questionnaire and a 196-item food frequency questionnaire and provided a fasting blood sample. Circulating ascorbic acid was analyzed by high-performance liquid chromatography, and a mass-spectrometry-based multiple reaction monitoring method was used to measure 54 proteins abundant in plasma that are involved in numerous physiologic pathways. Mean protein concentrations were compared across tertiles of serum ascorbic acid using analysis of covariance adjusted for sex, ethnocultural group, season of blood draw, hormonal contraceptive use among women, waist circumference and tertiles of plasma α-tocopherol. A Bonferroni significance level of P<.0009 was applied, and analyses were adjusted for multiple comparisons using the Tukey–Kramer procedure. Levels of complement C9, ceruloplasmin, alpha-1-anti-trypsin, angiotensinogen, complement C3, vitamin D binding protein and plasminogen were inversely associated with levels of ascorbic acid. The inverse association between ascorbic acid and vitamin D binding protein was highest in those with higher levels of serum 25-hydroxyvitamin D. In conclusion, several plasma proteins from various physiologic pathways are significantly associated with circulating levels of ascorbic acid. These findings suggest that vitamin C may have novel physiological effects.

Nutrigenomics and Its Approaches for Control of Chronic Diseases

Nutrigenomics studies the impact of nutrients on genome and response of individual genetic makeup to diet. On the other hand nutrigenetics studies the impact of nutrient on a single gene. Some single nucleotide polymorphisms (SNPs) are determinants of individual requirement of nutrients but some others may be responsible for causing diseases. System biology approach is mainly used in nutrigenomics whereas individual nutrition is the major subject of nutrigenetics. Diet active molecules and human genetics are two major factors which govern the development of chronic diseases, namely cancer, cardiovascular diseases, diabetes, hypertension and obesity. Adequate and proper amount of nutrients prevent us from developing chronic diseases. The nutrients should keep desired balance between total oxidation status and total antioxidant response of the genome to maintain a balanced level between these two variables. If this balance is disturbed by our eating habits, our genomic system may become prone to development of chronic diseases. Nutrigenomic approach for control of such diseases is to enhance antioxidant status of body by supplementing food with antioxidants which become deficient in a diseased person.

Prevalence of cilantro (Coriandrum sativum) disliking among different ethnocultural groups

Cilantro, the leaf of the Coriandrum sativum plant, is an herb that is widely consumed globally and has purported health benefits ranging from antibacterial to anticancer activities. Some individuals report an extreme dislike for cilantro, and this may explain the different cilantro consumption habits between populations. However, the prevalence of cilantro dislike has not previously been reported in any population. The objective of this study was to determine the prevalence of cilantro dislike among different ethnocultural groups from a population of young adults living in Canada. Subjects (n = 1,639) between the ages of 20 and 29 years were participants of the Toronto Nutrigenomics and Health Study. Individuals rated their preference for cilantro on a 9-point scale from ‘dislike extremely’ to ‘like extremely’. Subjects also had the option to select ‘have not tried’ or ‘would not try’. Subjects who selected 1 to 4 were classified as disliking cilantro. The prevalence of dislike ranged from 3 to 21%. The proportion of subjects classified as disliking cilantro was 21% for East Asians, 17% for Caucasians, 14% for those of African descent, 7% for South Asians, 4% for Hispanics, and 3% for Middle Eastern subjects. These findings show that the prevalence of cilantro dislike differs widely between various ethnocultural groups.

A Case-Control Nutrigenomic Study on the Synergistic Activity of Folate and Vitamin B12 in Cervical Cancer Progression

The present study was designed to identify the role of folate, B12, homocysteine, and polymorphisms of methylene tetrahydrofolatereductase (MTHFR) gene in cervical carcinogenesis among 322 women from Kerala, South India. Serum folate, vitamin B12 (chemiluminescence assay), and homocysteine (EIA) along with genetic polymorphisms of MTHFR gene (polymerase chain reaction/restriction fragment length polymorphism) were analyzed for 136 control subjects, 92 low-grade squamous intraepithelial lesions (LSIL) subjects, and 94 invasive cervical cancer cases (ICC). Statistically significant associations between MTHFR polymorphisms, serum homocysteine, and folate levels with cervical carcinogenesis were not evident, but we found that these parameters acted as effect modifiers of serum vitamin B12. The risk estimates observed for B12 became prominent only when there was a deficiency in serum folate levels [LSIL–odds ratio (OR): 14.9 (95% CI: 2.65 to 84.4); ICC–OR = 8.72 (95% CI = 1.55 to 48.8)] or when MTHFR A1298C polymorphic variant was present [LSIL–OR = 9.8 (95% CI = 2.61 to 36.7); ICC–OR = 10.0 (95%CI = 2.5 to 39.3)]. The statistical significance of this effect modification was further studied using an interaction model, where only folate was observed to have an influence on B12 levels as suggested by the odds ratio of 7.11 (95% CI = 0.45 to 111.9) obtained for ICC group, implicating a synergistic role of these 2 vitamins in invasive cervical cancer.

Effect of vitamin D on aging in Caenorhabditis elegans

Nutrigenomics, also referred to as nutritional genomics, aims to discover how nutrients interact with the genome and potentially alter genetic expression. One nutrient of particular interest is vitamin D3. In addition to its role in bone health, recent literature suggests a role for vitamin D3 in the prevention of various cancers, such as colon, prostate, and breast cancer, as well as the prevention of multiple chronic diseases, including cardiovascular disease, multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. Based on its extensive actions within the body, vitamin D3 supplementation is sometimes warranted. We are using Caenorhabditis elegans as a model organism to study the effect of vitamin D3 on aging. In addition to the fact that this nematode has a relatively short lifespan, the DAF‐12 nuclear hormone receptor in C. elegans is homologous to the Vitamin D Receptor (VDR) in humans. Our hypothesis was that vitamin D3 supplementation would increase the lifespan of Caenorhabditis elegans as a result of vitamin D3's interaction with the DAF‐12 receptor. A dose‐response curve was completed to identify an effective concentration of vitamin D3, and our preliminary results indicate that the vitamin D3 significantly increases lifespan at a concentration of 1000 μg/ml. We are also in the process of comparing the longevity of wild‐type worms and daf‐12 mutants after exposure to vitamin D3. Results from these on‐going experiments will be presented. Our studies appear to be the first to utilize C. elegans as a model system to study vitamin D3. We anticipate that our work will demonstrate the utility of this approach, and that others may find this model system beneficial in nutrigenomic studies. This research was supported by an NIH grant to J. Schisa.