VITAMIN D3: D-FENCE YOUR HEALTH

Deficiency of Vitamin D3 affects approximately 50% of the worldwide population (Holick MF. 2007). It has been proved by scientific evidence-based researches that approximately 1 billion people worldwide, across all ethnicity and age groups, have vitamin D deficiency (Gordon CM et.al. 2004). The low vitamin D levels can mainly be attributed to the lifestyle and environmental factors like reduced sunlight exposure. The high prevalence of low vitamin D is particularly an important public health issue because it is an incipient risk factor for total mortality in the general population (Melamed ML. 2008). A meta-analysis of a randomised controlled trial published in 2007 showed that Vitamin D supplementation is associated with reduced mortality (Autier P. 2007). Sunshine vitamin D is a very unique vitamin as it is synthesised in our body under the exposure of sufficient sunlight. Vitamin D2 is made by the UV rays of the yeast sterol-ergosterol and naturally found in sun-exposed mushrooms. UVB light from the sun strikes the exposed skin, and the synthesis of vitamin D3 takes place in humans, thus it is the most “natural” form.

 Biology of Vitamin D

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When UV rays of the sun strikes the skin it causes a chemical change and the pro-vitamin D3 (7-dehydrocholesterol) changes to its active form that is Vitamin D3 (cholecalciferol). Vitamin D is absorbed by the small intestine along with fat. Dietary vitamin D is incorporated into chylomicrons and travels to the liver via the lymphatic system and bloodstream. Then, both the dietary and skin produced vitamin D after coming into the liver converts into calcidiol (25(OH)D3) and travels to the kidney. When stimulated by parathyroid hormones, the kidney converts calcidiol (25(OH)D3) to calcitriol (1,25(OH)2D3). This calcitriol is the primary active form of vitamin D, it enhances the absorption of calcium and phosphorus in the small intestine. It assists the parathyroid hormone in stimulating osteoclasts to break down bone and releases calcium into the blood or stimulate the bone calcification. In the absence of Vitamin D, only 10-15% of dietary calcium and about 60% of phosphorus is absorbed by the body. Vitamin D sufficiency enhances calcium and phosphorus absorption by 30–40% and 80%, respectively (Lips P et al. 2006; Lappe JM et al. 2007). According to the Harvard School of Public Health Nutrition  (2010), vitamin D receptor (VDR) is present in most tissues and cells of the body. Calcitriol has a wide range of biological actions, such as inhibition of cellular proliferation and inducing terminal differentiation, inhibiting angiogenesis, stimulating insulin production, inhibiting renin production, and stimulating macrophage cathelicidin production (Chlebowski RT. et al. 2008;  Stolzenberg-Solomon RZ. et al. 2009).

 Sources :

 A major source of vitamin D for most humans is the synthesis from the exposure of the skin to sunlight typically between 1000 h and 1500 h in the spring, summer, and fall (Moan J. et al., 2008; Holick MF., 2008). Vitamin D produced in the skin may last at least twice as long as in the blood compared with ingested vitamin D (Haddad JG. et al., 1993).

Here are a few foods with natural and fortified Vitamin D:

  • salmon
  • sardines
  • egg yolk
  • shrimp
  • milk (fortified)
  • cereal (fortified)
  • yoghurt (fortified)
  • orange juice (fortified)

 Benefits 

  • Calcium Absorption - Vitamin D3 and calcium are co-related in terms of their absorption. Whenever serum calcium level falls in our body, it results in increased conversion of vitamin D to its activated form for the absorption of calcium (Lips P. 2006; Lappe JM. 2007). Therefore, even if our calcium intake is appropriate but vitamin D lacks in our diet then also there will be no absorption of calcium, leading to weak bones and osteoporosis. Similarly, if there is no calcium intake in our diet then as soon as serum calcium drops down, it provokes calcium absorption from our bones. Hence, a depleting bone calcium store to maintain blood levels. This eventually results in weak bones that are more prone to fractures.
  • Prevent Bone Demineralisation - To maintain bone density, we need certain nutrients like calcium, vitamin D3, phosphorus, magnesium and zinc. Of all the phosphorus in our body, approximately 80% is found in our bones and teeth. Activated vitamin D3 not only results in the absorption of calcium, but also helps absorb phosphorus. Vitamin D sufficiency enhances calcium and phosphorus absorption by 30–40% and 80%, respectively (Lips P. 2006; Lappe JM. 2007). Thus to maintain the mineral content of our bones and teeth, we need vitamin D3. Several studies provide evidence that sufficient vitamin D status is important for bone health and prevention of bone injury in athletic populations (Lappe, J. et al. 2008; Ruohola. J.P. et al. 2006).
  • Regulates Immune System - Vitamin D functions as an important regulator of inflammation and innate immunity. Our immune system has special types of cells called T-cells which are referred to as killer cells of the body. These cells protect us from foreign bodies as they are perfect in differentiating between outside invaders and “self-cells”. Vitamin D strengthens our immune system by regulating these T-cells. As soon as they sense the presence of any foreign pathogen in the presence of vitamin D, “naive” T-cells gets transitioned into active killer T-cells. Hence, vitamin D3 protects our body from infections and boosts immunity. Vitamin D increases the production of several anti-inflammatory cytokines that includes transforming growth factor and interleukins-4, -10 & -13; while reducing the production of pro-inflammatory cytokines such as interleukin-6, interferon-γ, interleukin-2 and tumour necrosis factor (TNF-α) (Barker, T. et al. 2014; Larson-Meyer, D.E., and K.S. Willis. 2010; Willis, K.S. et al.2012).
  • Reduces the risk of Cardiovascular diseases - Studies have provided evidence that the protective effect of vitamin D on the heart could be via the renin-angiotensin hormone system, through the suppression of inflammation, or directly on the cells of the heart and blood vessel walls (Wang TJ. et al. 2008). Vitamin D gets converted into its activated form in the presence of certain receptors and 1-alpha-hydroxylase. It has been shown that 1-alpha-hydroxylase is produced by various cells including cardiomyocytes (heart muscle cells). So, to have a healthy heart, vitamin D intake is also a crucial factor.
  • Protection against cancer - Vitamin D helps to decrease cell proliferation and increase the cell differentiation, stops the growth of new blood vessels, and has significant anti-inflammatory effects (Ahn J. et al. 2008; Anderson LN. et al. 2010). Many studies have suggested a link between low vitamin D levels and an increased risk of cancer, with the strongest evidence for colorectal cancer (Ahn J. et al. 2008). A definitive conclusion cannot yet be made about the association between vitamin D concentration and cancer risk, but there are many promising results from various studies. Anderson LN. et al.(2010) published evidence-based studies which links the higher vitamin D intake to a lower risk for breast cancer.
  • Protects Kidney Function - Prolonged vitamin D deficiency has been shown to result in chronic kidney disease. Healthy kidneys are rich in vitamin D receptors which helps in conversion to the activated form. In vitamin D deficiency the parathyroid gland is unable to sense that there is enough calcium and phosphorus in our blood, which results in over secretion of parathyroid hormone. This malfunction drains out excess calcium from our bones resulting in weak and fragile bones. Vitamin D3 helps in providing sufficient vitamin to prevent any malfunctioning of the kidneys.
  • Improves Sleep Quality - Vitamin D3 also helps in maintaining a healthy sleep and prevents mood disorders. Several studies have found a significant association between lack of vitamin D and sleep disorders like insomnia and daylight sleepiness. The underlying reason could be due to Melamine, which is known to affect sleep patterns and also holds a key role in the synthesis of the first form of vitamin D.
  • Beneficial for Cognitive Functioning - Low vitamin D levels are associated with various psychiatric conditions. Mood fluctuations and depression are also associated with vitamin D levels of our body. It is because vitamin D regulates the enzyme that converts amino acid tryptophan to serotonin. Serotonin is a neurotransmitter which affects our mood and brain development. Hence, an active and relaxed mind might indicate the optimum levels of vitamin D3.
  • Muscle Strength - A study conducted in California stated that low or deficit vitamin D levels lead to fatty skeletal muscles (Vicente Gilsanz et.al. 2010). Fitness freaks or athletes who are looking to gain lean mass and reduce the body fat percentage should ensure that they have an optimum intake of vitamin D to get that additional kick for achieving their fitness goal.

 Optimum Dosage:

 Regular consumption of Vitamin D containing foods alone is not sufficient to maintain the Vitamin D levels. Sensible sun exposure (5 - 30 min of exposure to arms, legs, back, etc., at noontime several times a week), regular Vitamin D supplementation (1500 - 2000 IU/day) or a combination with dietary intake, sun exposure and supplementations are required to achieve the optimum level. Vitamin D supplementation is especially needed in both winter and rainy season.

The current DV for Vitamin D is 400IU and many do not meet this minimal requirement (Larson-Meyer DE, Willis KS.,2010). RDA of 600-800 IU is recommended to maintain sufficient levels of vitamin D. A recommendation by the Institute of Medicine to increase the DV for vitamin D to 600 IU for most adults based on needs for bone health, has not been adopted by the FDA to date. However, for optimal overall health, blood levels of at least 40 ng/mL of the active intermediate 25-hydroxyvitamin D are recommended, and from 2000 to 4000 IU of vitamin D are needed daily to achieve this level (Holick MF. 2011). In our country, the Indian Council of Medical Research (ICMR) in 2010, recommended a daily supplement dosage of 400 IU/day of vitamin D for Indians under situations of minimal exposure to sunlight.

Current Scenario:

It has been accepted worldwide that vitamin D deficiency (VDD) is a global health problem that impacts not only musculoskeletal health but also varied acute and chronic diseases (Hossein-nezhad A. Holick MF. 2013). Low vitamin D has been associated with an increased risk of diabetes mellitus, cardiovascular diseases, certain cancers, cognitive decline, autoimmune disorders and pregnancy complications (Holick MF. 2007). It has been recorded that 20 to 80% of US, Canadian and European men and women are vitamin D deficient (Hossein-nezhad A, Holick MF. 2013; Ganji V, Zhang X, Tangpricha V. 2012; Greene-Finestone LS. et al. 2011). In the Middle East and Asia, Vitamin D deficiency is highly prevalent in both children and adults (Holick MF. 2007; Hossein-nezhad A, Holick MF. 2013; Fields J. et al. 2011). Even in India, various studies conducted in different regions of the country indicate that approximately 70-90% of the healthy population is vitamin D deficient (Gupta A. et al. 2014; Goswami R. et al. 2008; Zargar AH. et al. 2007; Harinarayan CV. et al. 2017). Low vitamin D level is prevalent irrespective of age, sex, profession, rural or urban settings or regional distribution (Garg MK. et al. 2013. Agarwal KS. et al. 2002).

VITAMIN-D SERUM LEVELS IN DIFFERENT POPULATION GROUPS ACROSS INDIA

Recommendation

Recommended intake (adults >18 0 19 years)

USA and Canada : 600 IU

Australia and New Zealand : 200 IU

ICMR : 400 IU

Status and reference range

Serum circulation 25(OH)D is in the market of vitamin D status.

Deficiency : 25(OH)D < 50 nmol/l (20 ng/ml)

Insufficient : 25(OH)D < 75-80 nmol/l (30-32 ng/ml)

Sufficient : 25(OH)D > 75-80 nmol/l (30-32 ng/ml)

Optimal : 25(OH)D = 100-120 nmol/l (40-100 ng/ml)

Toxic : 25(OH)D > 375 nmol/l (150 ng/ml) + hypercalcemia

Signs and symptoms of deficiency

Elevated parathyroid concentration

Weak bones

Bone/ joint pain

Decreased bone density

Increased bone fracture risk

Muscle weakness and discomfort

Atrophy of muscle fibre (fast twitch)

High frequency of infectious illness

Signs and symptoms of toxicity

Elevated serum calcium

Fatigue

Constipation

Back pain

Nausea

Vomiting

Complication of prolonged elevated serum calcium include soft tissue calcification

Hypertension

Cardiac arrhythmia

 

Conclusion:

Widespread Vitamin D deficiency among the Indian population is a cause of grave concern. Adequate measures have to be taken to prevent VDD at the outset. There is a need of educating people about the sensible sun exposure for vitamin D synthesis and the importance of dietary intake of vitamin D rich foods. Fortification of commonly used foods could prevent vitamin D insufficiency in our large population. There is an urgent need to prioritise the development of ‘national-level programs’ to provide regulated vitamin D fortified foods at affordable prices for the Indian population at large.

Reference :

 1.Holick, M.F.(2007) Vitamin D deficiency. N Engl J Med.357,266–81

 2.Gordon, C.M., DePeter, K.C., Feldman, H.A., Grace, E., & Emans, S.J. (2004).Prevalence of vitamin D deficiency among healthy adolescents.Arch Pediatr Adolesc Med.158,531–7

 3.Melamed, M.L., Michos, E.D., Post, W., & Astor, B. (2008).25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med.,168,1629–37

 4. Autier, P., & Gandini, S. (2007).Vitamin D supplementation and total mortality: A meta-analysis of randomised controlled trials. Arch Intern Med.,167,1730–7

 5. Lips, P., Hosking, D., Lippuner, K., Norquist, J.M., Wehren, L., et al.(2006).The prevalence of vitamin D inadequacy amongst women with osteoporosis: An international epidemiological investigation. J Intern Med.,260,245–54

 6. Lappe, J.M., Travers-Gustafson, D., Davies, K.M., Recker RR, Heaney RP. (2007).Vitamin D and calcium supplementation reduces cancer risk: Results of a randomized trial. Am J Clin Nutr.,85,1586–91.

 7. Chlebowski, R.T., Johnson, K.C., Kooperberg, C., Pettinger, M., Wactawski-Wende, J., Rohan, T., et al. (2008).J Natl Cancer Inst.,100,1581–91.

 8. Stolzenberg-Solomon, R.Z., Hayes, R.B., Horst, R.L., Anderson, K.E., Hollis, B.W., Silverman DT. (2009).Serum vitamin D and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial. Cancer Res.,69,1439–47.

 9.Moan J, Porojnicu AC, Dahlback A, Setlow RB. Addressing the health benefits and risks, involving vitamin D or skin cancer, of increased sun exposure. Proc Natl Acad Sci USA. 2008;105:668–73. [PMC free article] [PubMed]

10. Holick MF. Vitamin D: A D-lightful health perspective. Nutr Rev. 2008;66(10 Suppl 2):S182–94. [PubMed]

11. Haddad JG, Matsuoka LY, Hollis BW, Hu YZ, Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J Clin Invest. 1993;91:2552–5. [PMC free article] [PubMed]

12. Lappe, J., D. Cullen, G. Haynatzki, R. Recker, R. Ahlf, and K. Thompson (2008). Calcium and vitamin D supplementation decreases incidence of stress fractures in female navy recruits. J. Bone Miner. Res. 23:741-749.

13. Ruohola, J.P., I. Laaksi, T. Ylikomi, R. Haataja, V.M. Mattila, T. Sahi, P. Tuohimaa, and H. Pihlajamaki (2006). Association between serum 25(OH)D concentrations and bone stress fractures in Finnish young men. J. Bone Miner. Res. 21:1483-1488.

14. Barker, T., T.B. Martins, H.R. Hill, C.R. Kjeldsberg, B.M. Dixon, E.D. Schneider, V.T. Henriksen, and L.K. Weaver (2014). Vitamin D sufficiency associates with an increase in anti-inflammatory cytokines after intense exercise in humans. Cytokine 65,134-137

15. Larson-Meyer, D.E., and K.S. Willis (2010). Vitamin D and athletes. Curr. Sports Med. Rep. 9,220-226.

16. Willis, K.S., D.T. Smith, K.S. Broughton, and D.E. Larson-Meyer (2012). Vitamin D status and biomarkers of inflammation in runners. Open Access J. Sports Med. 3:35-42.

17. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. (2008).Vitamin D deficiency and risk of cardiovascular disease.Circulation. 117,503–11

18. Ahn J, Peters U, Albanes D, Purdue MP, Abnet CC, Chatterjee N, et al.(2008) Serum vitamin D concentration and prostate cancer risk: A nested case-control study. J Natl Cancer Inst.,100,796–804

19. Anderson LN, Cotterchio M, Vieth R, Knight JA. Vitamin D and calcium intakes and breast cancer risk in pre- and postmenopausal women.(2010).Am J Clin Nutr.91,1699–707.

20. Vicente Gilsanz et.al. (2010).Vitamin D Status and Its Relation to Muscle Mass and Muscle Fat in Young Women.JCEM,95(4)

 21. Larson-Meyer, D.E., & Willis, K.S.(2010).Vitamin D and athletes. Curr Sports Med Rep, 9,2206

22. Holick, M.F..(2011).Vitamin D: evolutionary, physiological and health perspectives. Curr Drug Targets,12,418

23. Hossein-nezhad, A., & Holick, M.F.(2013).Vitamin D for health: A global perspective. Mayo Clin Proc.,88,720–55

24. Ganji, V., Zhang, X., & Tangpricha, V.(2012).Serum 25-hydroxyvitamin D concentrations and prevalence estimates of hypovitaminosis D in the U.S. population based on assay-adjusted data. J Nutr.,142,498–507

25. Greene-Finestone, L.S., Berger, .C, de. Groh, M., Hanley, D.A., Hidiroglou, N., Sarafin, K. et al.(2011).25-Hydroxyvitamin D in Canadian adults: Biological, environmental, and behavioral correlates. Osteoporos Int. 22,1389–99

26. Fields J, Trivedi NJ, Horton E, Mechanick JI. (2011).Vitamin D in the Persian Gulf: Integrative physiology and socioeconomic factors. Curr Osteoporos Rep.,9:243–50

27. Gupta, A., & Gupta, R.(2014).Vitamin D deficiency in India: Prevalence, causalities and interventions. Nutrients.,6,729–75.

28. Goswami, R., Kochupillai, N., Gupta, N., Goswami, D Singh., N, Dudha A. (2008).Presence of 25(OH) D deficiency in a rural North Indian village despite abundant sunshine. J Assoc Physicians India.,56:755–7

29. Zargar, A.H., Ahmad, S., Masoodi, S.R., Wani, A.I., Bashir, M.I., Laway, B.A., et al. (2007).Vitamin D status in apparently healthy adults in Kashmir Valley of Indian subcontinent. Postgrad Med J., 83,713–6

30. Harinarayan, C.V., Ramalakshmi, T., Prasad, U.V., Sudhakar, D., Srinivasarao, P.V., Sarma, K.V., et al.(2007).High prevalence of low dietary calcium, high phytate consumption, and Vitamin D deficiency in healthy South Indians. Am J Clin Nutr. 85:1062–7

31. Garg, M.K., Marwaha, R.K., Khadgawat, R., Ramot, R., Obroi, A.K., Mehan, N., et al. (2013).Efficacy of Vitamin D loading doses on serum 25-hydroxy Vitamin D levels in school going adolescents: An open label non-randomised prospective trial. J Pediatr Endocrinol Metab.26:515–23

32. Agarwal, K.S., Mughal, M.Z., Upadhyay, P., Berry, J.L., Mawer, E.B., Puliyel, J.M.(2002) The impact of atmospheric pollution on Vitamin D status of infants and toddlers in Delhi, India. Arch Dis Child., 87:111–3

33. Ross, A.C., Manson, J.E., Abrams, S.A., Aloia, J.F., Brannon, P.M., Clinton, S.K., et al.(2011).The 2011 report on dietary reference intakes for calcium and Vitamin D from the Institute of Medicine: What clinicians need to know. J Clin Endocrinol Metab.,96,53–8

34. A Report of the Expert Group of the Indian Council of Medical Research.(2009) Jamai-Osmania PO, Hyderabad: National Institute of Nutrition, Indian Council of Medical Research, Nutrient Requirements and Recommended Dietary Allowances for Indians.

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