Recent Vitamin D Research Focusing on its Functions Beyond Classical Calcium/Phosphate

Regulation
Vitamin D is a vital hormone essential for various physiological functions, obtainable through
dietary sources, supplements or bio-synthetic pathway. Vitamin D includes D2 (ergocalciferol),
derived from the plant sterol ergosterol, and D3 (cholecalciferol), synthesized by humans.[1]

Production, Metabolism and Mechanism

The bio-synthetic pathway initiates with 7-dehydrocholesterol, a crucial intermediate in cholesteryl
synthesis. 7-dehydrocholesterol can either be converted by the enzyme 7-hydrocholesterol reductase
converts into mature cholesterol or undergoes photolysis to form vitamin D. Importantly, 7-
dehydrocholesterol serves as the precursor to vitamin D within this complex pathway.[1]

Fig. 1: Vitamin D production and metabolism in human (cataylst university) Fig. 2: 7-dehyrocholesterol and ergosterol transformation[1]

The first crucial step in vitamin D synthesis occurs in the skin's epidermis when 7-
dehydrocholesterol reacts with UV light of wavelength 290nm - 315nm, converting it into pre-
vitamin D3. This light-dependent reaction emphasizes the importance of sunlight exposure, making
individuals in high latitudes susceptible to vitamin D deficiency due to limited UV light.

Follow is the second reaction, requiring heat which transforms pre-vitamin D3 into cholecalciferol. it
is often referred to as inactive vitamin D. These non-enzymatic reactions underline the significance
of environmental factors in vitamin D production, with sunlight being a primary source of both light
and heat.
The cholecalciferol travels through the bloodstream, binding to specific proteins, and reaches the
liver. Here, the P-450 enzyme 25-hydroxylase adds a hydroxyl group, forming 25-
hydroxycholecalciferol or calcidiol. In the kidneys, another P-450 enzyme, 1-hydroxylase, further
modifies it to produce the active form, 1,25-dihydroxycholecalciferol or calcitriol.
Finally, the calcitriol, activated form of vitamin D, binds to the vitamin D receptor (VDR) in the cell
nucleus. This complex influences gene expression by binding to specific regions of the DNA called
vitamin D response elements, leading to various physiological effects. These include promoting
insulin sensitivity, acting as an anti-inflammatory agent, and balancing serum lipids.

A. Role of Vitamin D supplements in averting Cancer and Cardiovascular disease (CVD)

Vitamin D and Cancer Cure
A New England study investigated the effects of 2000 IU vitamin D supplementation on cancer and
cardiovascular disease in 25,000+ participants aged 50 or older. After 5.3 years, no significant
differences in overall cancer incidence were found across treatment arms. [2] However, an Italian
subgroup focused on BMI, finding that Vitamin D's efficacy in cancer treatment is influenced by
body weight. As Vitamin D is fat-soluble, its effectiveness depends on the body's fat content. [3]

Upon reevaluation, the New England writers noted a significant decrease in advanced cancers among
participants receiving Vitamin D compared to a placebo. Stratifying by BMI, a notable reduction in
metastatic or fatal cancer occurred in the vitamin D group for individuals with a normal BMI (BMI <
25), but this effect was absent in those with obesity. [4]
Vitamin D and Cardiovascular Diseases (CVD)
The European Heart Journal estimated that correcting serum 25(OH)D levels below 50 nmol/L could
potentially lead to a 6.0% reduction in CVD incidence. The conclusion suggests that addressing
vitamin D deficiency may be linked to a heightened risk of CVD, and implementing corrective
measures on a broader scale could potentially alleviate the burden of cardiovascular diseases. [5]

Insufficient 25(OH)D levels associated with an elevated risk of (CVD) [5] Application: Boosting 25(OH)D levels may cut CVD risk by up to 6%.[5]

B. The Relationship Between Vitamin D and Cognitive Decline in Older Individuals

A research involving 858 elderly subjects investigated the correlation between vitamin D deficiency
and cognitive function, using the Mini-Mental State Examination (MMSE) for assessment.
Participants with severely deficient levels of serum 25(OH)D (25 nmol/L) had a 1.60 times higher
relative risk (95% CI, 1.19-2.00) of substantial cognitive decline on the MMSE compared to those
with sufficient levels of 25(OH)D (75 nmol/L). [6]
The results indicated that individuals with vitamin D levels below 50nmol/L, classified as deficient,
had a significantly higher likelihood of cognitive decline, suggesting a potential link to early
dementia. Notably, the study challenged conventional norms by considering vitamin D levels
between 50nmol/L and 75nmol/L as insufficient, emphasizing the importance of maintaining optimal
levels (75nmol/L)

Cognitive function variations in 858 elderly individuals in relation to serum 25(OH)D [6]

Conclusively, Vitamin D's health effects linked to genetics, lifestyle, environment complexity.
individual should consult healthcare professionals for guidance.
References

1. Bikle, D.D. (2020) ‘Vitamin D: Newer concepts of its metabolism and function at the basic and clinical level’, Journal of the
Endocrine Society, 4(2). doi:10.1210/jendso/bvz038.

2. Manson, J.E. et al. (2019) ‘Vitamin D supplements and prevention of cancer and cardiovascular disease’, New England Journal of
Medicine, 380(1), pp. 33–44. doi:10.1056/nejmoa1809944.

3. Infante M. et al. (2019) ‘Vital Study: an incomplete picture?’, European Review for Medical and Pharmacological Sciences, 23, pp.
3142–3147.

4. Chandler, P.D. et al. (2020) ‘Effect of vitamin D3 supplements on development of Advanced Cancer’, JAMA Network Open, 3(11).
doi:10.1001/jamanetwork open.2020.25850.

5. Zhou, A.et al. (2021) ‘Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular
disease risk’, European Heart Journal, 43(18), pp. 1731–1739. doi:10.1093/eurheartj/ehab809.

6. Llewellyn, D.J. (2010) ‘Vitamin D and risk of cognitive decline in elderly persons’, Archives of Internal Medicine, 170(13), p. 1135.
doi:10.1001/archinternmed.2010.173.