Nutrigenetics of Sunshine vitamin (D)

An individual’s vitamin D status depends on their Vitamin D uptake from food and supplements, time outside in the sun, their genetic disposition and interaction with their gut microbiome. Vitamin D deficiency has been historically defined and recently recommended by the Institute of Medicine (IOM) as a 25(OH)D of less than 20 ng/ml.

The global prevalence of vitamin D deficiency appears to be increasing (Figure.1), and the impact of this on human health is important. There is an ever-expanding list of communicable and non- communicable diseases being associated with vitamin D deficiency, including types 1 and 2 diabetes mellitus, rheumatoid arthritis, cardiovascular disease, osteoporosis, multiple sclerosis, depression, irritable bowel disease, asthma, colorectal, lung and breast cancers, upper respiratory tract infections, tuberculosis (TB), and HIV/AIDS progression and mortality (1).

Figure.1 Prevalence of low vitamin D status in adults worldwide (2)

 Different factors affecting vitamin D status:

* Wearing a sunscreen with a sun protection factor of 30 reduces vitamin D synthesis in the skin by more than 95%.(3)

* People with a naturally dark skin tone have natural sun protection and require at least three to five times longer exposure to make the same amount of vitamin D as a person with a white skin tone.(4)

* Migration can have a significant impact. White women living in the south of England had median 25(OH)D levels of 62.5 nmol/l in the summer and 39.9 nmol/l in the winter. In Asian women living in the same geographical location the median levels were considerably less at 24.9 nmol/l and 16.9 nmol/l respectively.(5)

* Women have often been found to have lower levels of 25(OH)D levels than men. Potential causes include differences in body fat composition, resulting in greater fat storage of vitamin D in women. Lower levels in women are a particular concern around the time of childbearing as the vitamin D status of women during pregnancy is an important factor in the determination of the vitamin D status in her child.(6).

Figure.2 Summary of different factors affecting vitamin D status

What happens to vitamin D inside our body?

Vitamin D is obtained from diet in the form of Ergocalciferol (Vitamin D2) or from the interaction of UVB from the sun and cholesterol in the skin to form cholecalciferol (Vitamin D3),biologically inactive form (7). This has to be converted to the active form that our  body uses. The first step in the conversion takes place in the liver, where cholecalciferol is converted into calcifediol (25 (OH)D) and then converted in the kidneys to calcitriol, the biologically active form of vitamin D. Then it is transported to the cells by binding to vitamin D receptor.

Genes and Vitamin D

Vitamin D levels have a significant hereditable component suggesting a possible role for genetics in the etiology of insufficiency. The genetic influence on vitamin D status is estimated to be around 80%, much higher than the dietary and environmental influences of around 25%. (8).Recent advances in the methodology of large-scale genetic association studies, including coordinated international collaboration, have identified associations of CG, DHCR1, CYP2R1, VDR, and CYP24A1 with serum levels of vitamin D. (9)

Understanding the vitamin D pathway

Figure. 4. Vitamin D pathway illustration

* The Vitamin D pathway starts with the conversion of 7-dehydrocholesterol in the skin to a precursor of vitamin D3 on exposure to sunlight.

* The DHCR7 converts 7-dehydrocholesterol to cholesterol, thereby removing the cholesterol pathway from the synthetic pathway of vitamin D3. The pre-vitamin D3 in turn is converted to vitamin D3 in a heat-dependent process.

* The first step in activation, 25-hydroxylation occurring primarily in the liver, is mediated mostly by the microsomal 25-hydroxylase, CYP2R1, and possibly to some extent by mitochondrial hydroxylase, CYP27A1.

* 25-hydroxyvitamin D (25(OH)D) is bound to the VDBP, transported to the kidneys and converted by CYP27B1 to the biologically active form 1,25-dihydroxyvitamin D3 (calcitriol), which further activates the VDR to interact with RXRG leading to the activation/suppression of the target gene expression. Calcitriol can up-regulate the expression of CYP24A1, which catabolises 25(OH)D and calcitriol to water-soluble, biologically inactive metabolites for excretion in the bile (10).

Various dietary factors and its influence on vitamin D levels (11)

Natural Ways to increase calcitrol and vitamin D receptor gene expression 

FACTORS THAT INHIBIT THE VITAMIN D RECEPTOR(VDR):

Dietitian’s guide to provide gene specific recommendations: (34)

Conclusion:

Genes play a huge role in determining vitamin D levels and activity. It is therefore essential to eat specific nutrients according to their genes to ensure adequate vitamin D levels. Genetic testing for personalised nutrition enables an individual to understand the genetic tendency that may affect absorption, metabolism, usage and elimination of vitamin D. This information could serve as a vital tool for clinicians, especially dietitians and nutritionists in diagnosis and management of vitamin D status as it helps in understanding the causes of deficiency at a molecular level and provide more targeted and specific solutions to maintain healthy vitamin D status.

Acknowledgement: Ms. Harinivashini, Intern, a Postgraduate student in Food Science & Nutrition, Avinashilingam Institute of Higher Education for Women was involved in data curation related to gene specific diet recommendations.