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Vitamin D

Function of Vitamin D

Vitamin D (cholecalciferol), a fat-soluble vitamin, assists in the transport of calcium from the intestines to the bloodstream. Though able to be obtained from diet, most vitamin D is synthesized in the skin. The main function of vitamin D is to regulate blood calcium. Calcium has important neuromuscular and cardiac functions and having a physiologic acceptable range in the bloodstream is crucial to our survival.

When blood calcium levels drop, vitamin D acts as a catabolic hormone by stimulating osteoclasts (cells that breakdown bone)  and release calcium into the blood stream. Vitamin D also enhances calcium absorption in the intestines. If blood calcium levels are high, vitamin D stimulates bone proteins and interacts with osteoblasts (cells that build bone).

Obtaining Vitamin D

7-DHC (7-dehydrocholesterol) exists in the skin, absorbs ultraviolet radiation, and converts 7-DHC to Vitamin D3. We can also obtain vitamin D3 from the diet, although not an active form. Vitamin D3 must go to the liver to be converted to 25-hydroxyvitamin D3 (25(OH)D). This compound must be transported to the kidney to have another hydroxyl group added and becomes the biologically active form of Vitamin D, which is 1,25 dihydroxyvitaminD3 (1,25(OH)2D). Some will argue that vitamin D is not a vitamin, but is rather a hormone since it is made and released by an organ and has actions on organs in the body. Vitamin D is made the by skin, but without adequate sunlight, research suggests that not enough is synthesized for optimum health.
Season and region are major determinants of vitamin D levels. During the winter months, the skin makes very little vitamin D from the sun, except at below latitudes of 37 degrees (also known as the 37th parallel). This means that everyone who lives in the grey areas shaded on this map are receiving little to no vitamin D from the sun during the winter months, regardless of how much time spent out in the sun.
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Image from Harvard Health
The minimal erythemal dose (MED) is the minimum amount of UVB light that produces redness 24 hours after exposure. The necessary dose of sunlight needed for adequate vitamin D synthesis is 1/4 of a MED per day, 2-3 days a week. The general rule is about 10-15 minutes with arms and legs exposed mid-day, during the summer months, but this can vary with geography, clothing, skin pigmentation and age. An individual with deep skin pigmentation will produce about 5-10% of the vitamin D in their skin that a light skin individual will produce. When the sun is directly overhead (noon), the distance the UV radiation needs to travel is much shorter.

Vitamin D2 (ergocalciferol), derived from plants, is not as preferred as vitamin D3, produced in animals. Vitamin D2 has a lower affinity for vitamin D binding protein which means it has a shorter circulating half life and thus a lower rate of conversion. Conversion from vitamin D to 25(OH)D in the liver occurs up to 5 times as fast for vitamin D3 than for D2 (Houghton
& Vieth, 2006).

Recommendations

The Institute of Medicine recommends:
  • 600 IU for children and adults;
  • 800 IU for those greater than 70 years.
Dr. Michael Holick, considered to be one of the world's leading Vitamin D researchers, recommends:
  • 1000 IU of vitamin D a day for children;
  • 2000-3000 IU of vitamin D for adults.

Food Sources

Aiming for 600 IU, foods like yogurt, fortified milk, tuna fish and fatty fish are all a good source or high in vitamin D. Aiming for 2000 IU, only the fatty fish will be a good source of vitamin D. Unfortunately, the vitamin D in fatty fish varies greatly, so you can't rely on fatty fish to give a consistent amount of vitamin D. Irradiated mushrooms, which are mushrooms that have been exposed to UV light, also contain vitamin D. Researchers have observed that consuming UV treated mushrooms elevated vitamin D levels in the body as much as supplements with the same amount of vitamin D (Keegan, Lu, Bogusz, Williams & Holick, 2013).

Supplementation

Supplementation is dependent on geography, skin color, time outside, use of sunscreen, air quality, age and diet. Vitamin D deficiency is widely prevalent throughout the United States with the advent of sunscreen, keeping covered, avoiding mid-day sunlight and considering that half the country lives north of the 37th parallel. Dr. Holick recommends that everyone supplement with a minimum of 1000 IU per day. It is well established that supplementing with calcium and vitamin D minimizes bone losses and reduces fracture rates in post-menopausal women (Reid, Ames, Evans, Gamble, Sharpe, 1993).

Vitamin D will also enhance the uptake of toxic metals like lead, cadmium, aluminum and strontium if calcium, magnesium and phosphorus are not present in adequate amounts. Vitamin D supplementation should never be implemented unless calcium intake is sufficient or supplemented at the same time.

Influence on Cancer

A growing body of evidence suggests that raising your vitamin D level can significantly reduce your risk of cancer.
Most recently, a randomized clinical trial by researchers at Creighton University observed vitamin D and calcium supplementation lowered participants' overall cancer risk by 30%. The study, which included more than 2,300 postmenopausal women from Nebraska who were followed for four years, looked at the effects of vitamin D supplementation on all types of cancer. Participants were randomly assigned to receive either 2,000 IUs of vitamin D3 in combination with 1,500 mg of calcium, or a placebo for the duration of the study. Blood testing revealed that 25(OH)D levels were significantly lower in those who did develop cancer. This study provides evidence that higher concentrations of 25(OH)D in the blood, in the context of vitamin D3 and calcium supplementation, decreases the risk of cancer. While people can make their own vitamin D3, people spend more time indoors and when outdoors people use sunscreen, which blocks most vitamin D production. Thus, many individuals are lacking adequate levels of vitamin D compounds in their blood (Lappe et al., 2017).

Previous research has shown that once you reach a serum vitamin D level of 40 ng/mL, your risk for cancer diminishes by 67%, compared to having a level of 20 ng/ml or less. The researchers observed that most cancers occurred in people with a vitamin D blood level between 10 and 40 ng/mL. The optimal level for cancer protection was identified as being between 40 and 60 ng/mL (McDonnell et al., 2016).

Another group of researchers found women with vitamin D concentrations of at least 30 ng/mL had a 55% lower risk of colorectal cancer than those who had a blood level concentrations below 18 ng/mL (Chandler et al., 2015).

Even earlier research, published in 2005, showed women with vitamin D levels above 60 ng/mL had an 83% lower risk of breast cancer than those with levels below 20 ng/mL (Lowe et al., 2005).

The Health and Medicine Division of the National Academies of Sciences, Engineering and Medicine has also reported an association between vitamin D and overall mortality risk from all causes, including cancer (Dror et al., 2013; Institute of Medicine, 2011).

Vitamin D also increases your chances of surviving cancer if you do get it (Garland, French, Baggerly & Heaney, 2011).
The results of these varied studies lend credence to a call for more attention to the importance of vitamin D in human health and specifically in preventing cancer

Influence on Health

The benefits of vitamin D are not restricted to cancer prevention. In fact, the list of health benefits of vitamin D is exceedingly long. Researchers have discovered that vitamin D affects virtually every cell and tissue in your body, so it might be easier to list what it will not affect, rather than what it will impact.

Compelling evidence suggests that optimizing your vitamin D can reduce your risk of death from any cause, making it a foundational component of optimal health (Afzal, Brondum-Jacobsen, Bojesen & Nordestgaard, 2014).

Megadoses of vitamin D have also been shown to decrease the length of time critical care patients must remain hospitalized. Participants who received 250,000 IUs for five days were released after an average of 25 days, compared to the average 36 days for those receiving placebo. Patients who received 500,000 IUs of vitamin D for five days were released after an average of just 18 days, effectively cutting their hospital stay in half (Han et al., 2016).

Certainly, for the average person, optimizing your vitamin D level is one of the least expensive preventive care strategies. If you suffer from any of the following ailments, it it advised to check your vitamin D levels, as research into vitamin D has found it can help prevent and/or address:
  • Asthma (Confino-Cohen, Brufman, Goldberg & Feldman, 2014).
  • Osteoporosis, osteomalacia (bone softening) and hip fractures
  • Type 1 and type 2 diabetes
  • Cancer, including cancers of the breast, colon, prostate, ovaries, esophagus and lymphatic system.
  • Hypertension (high blood pressure), cardiovascular disease and heart attacks. (According to vitamin D researcher Dr. Michael Holick, deficiency can raise your risk of heart attack by 50 percent. What's worse, if you have a heart attack while vitamin D deficient, your risk of dying is nearly guaranteed)
  • Obstructive sleep apnea. In one study, 98% of patients with sleep apnea had vitamin D deficiency, and the more severe the sleep apnea, the more severe the deficiency (Kerley et al., 2016).
  • Multiple sclerosis (MS). Research shows MS patients with higher levels of vitamin D tend to experience less disabling symptoms (Runia, Hop, de Rijke, Buljevac & Hintzen, 2012; Sortirchos et al., 2015).
  • Rheumatoid arthritis
  • Reduced immune function
  • Autoimmune diseases, including psoriasis
  • Infections, including influenza
  • Depression, Seasonal Affective Disorder (Gloth, Alam & Hollis, 1999)
  • Psychiatric conditions such as schizophrenia
  • Neurological disorders, including autism, dementia and Alzheimer's (Littlejohns et al., 2014).

References

Afzal, S., Brondum-Jacobsen, P., Bojesen, S. and Nordestgaard, B. (2014). Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts. BMJ, 349(nov18 2), pp.g6330-g6330. https://doi.org/10.1136/bmj.g6330

Chandler, P., Buring, J., Manson, J., Giovannucci, E., Moorthy, M., Zhang, S., Lee, I. and Lin, J. (2015). Circulating Vitamin D Levels and Risk of Colorectal Cancer in Women. Cancer Prevention Research, 8(8), pp.675-682. https://doi.org/
10.1158/1940-6207.CAPR-14-0470

Confino-Cohen, R., Brufman, I., Goldberg, A. and Feldman, B. (2014). Vitamin D, asthma prevalence and asthma exacerbations: a large adult population-based study. Allergy, 69(12), pp.1673-1680. https://doi.org/10.1111/all.12508

Dror, Y., Giveon, S., Hoshen, M., Feldhamer, I., Balicer, R. and Feldman, B. (2013). Vitamin D Levels for Preventing Acute Coronary Syndrome and Mortality: Evidence of a Nonlinear Association. The Journal of Clinical Endocrinology & Metabolism, 98(5), pp.2160-2167. https://doi.org/10.1210/jc.2013-1185

Keegan, R., Lu, Z., Bogusz, J., Williams, J. and Holick, M. (2013). Photobiology of vitamin D in mushrooms and its bioavailability in humans. Dermato-Endocrinology, 5(1), pp.165-176. https://doi.org/10.4161/derm.23321

Garland, C., French, C., Baggerly, L. and Heaney, R. (2011). Vitamin D Supplement Doses and Serum 25-Hydroxyvitamin D in the Range Associated with Cancer Prevention. [online] Ar.iiarjournals.org. Available at: http://ar.iiarjournals.org/content/31/2/607.full.pdf+html [Accessed 2 Nov. 2017].

Gloth, F., Alam, W. & Hollis, B. (1999) Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder. Journal of Nutrition Health and Aging, 3(1), pp.5-7. https://www.ncbi.nlm.nih.gov/pubmed/10888476

Han, J., Jones, J., Tangpricha, V., Brown, M., Hao, L., Hebbar, G., Lee, M., Liu, S., Brown, L., Ziegler, T. and Martin, G. (2016). High dose vitamin D administration in ventilated intensive care unit patients: A pilot double blind randomized controlled trial. Journal of Clinical & Translational Endocrinology, 4, pp.59-65. https://doi.org/10.1016/j.jcte.2016.04.004

Holick, M. (2017). Dr. Holick - The Vitamin D Solution. [online] Drholick.com. Available at: http://drholick.com/#table-section [Accessed 20 Oct. 2017].

Houghton
, L., Vieth, R. (2006). The case against ergocalciferol (vitamin D2) as a vitamin supplement. American Society for Clinical Nutrition, 84(4), pp.694-697. http://ajcn.nutrition.org/content/84/4/694.full

Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium; Ross AC, Taylor CL, Yaktine AL, et al. (2011). Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US). Available from: https://www.ncbi.nlm.nih.gov/books/NBK56070/ doi: 10.17226/13050

Kerley, C., Hutchinson, K., Bolger, K., McGowan, A., Faul, J. and Cormican, L. (2016). Serum Vitamin D Is Significantly Inversely Associated with Disease Severity in Caucasian Adults with Obstructive Sleep Apnea Syndrome. Sleep, 39(2), pp.293-300. https://doi.org/10.5665/sleep.5430

Lappe, J., Watson, P., Travers-Gustafson, D., Recker, R., Garland, C., Gorham, E., Baggerly, K. and McDonnell, S. (2017). Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women. JAMA, 317(12), p.1234. https://doi.org/10.1001/jama.2017.2115

Littlejohns, T., Henley, W., Lang, I., Annweiler, C., Beauchet, O., Chaves, P., Fried, L., Kestenbaum, B., Kuller, L., Langa, K., Lopez, O., Kos, K., Soni, M. & Llewellyn, D. (2014). Vitamin D and the risk of dementia and Alzheimer disease. Neurology, 83, pp.1-9. https://doi.org/10.1212/WNL.0000000000000755

Lowe, L., Guy, M., Mansi, J., Peckitt, C., Bliss, J., Wilson, R. and Colston, K. (2005). Plasma 25-hydroxy vitamin D concentrations, vitamin D receptor genotype and breast cancer risk in a UK Caucasian population. European Journal of Cancer, 41(8), pp.1164-1169. https://doi.org/10.1016/j.ejca.2005.01.017

McDonnell, S., Baggerly, C., French, C., Baggerly, L., Garland, C., Gorham, E., Lappe, J. and Heaney, R. (2016). Serum 25-Hydroxyvitamin D Concentrations ≥40 ng/ml Are Associated with >65% Lower Cancer Risk: Pooled Analysis of Randomized Trial and Prospective Cohort Study. PLOS ONE, 11(4), p.e0152441. https://doi.org/10.1371/journal.pone.0152441 

Reid, I., Ames, R., Evans, M., Gamble, G., Sharpe, S. (1993). Effect of calcium supplementation on bone loss in postmenopausal women. New England Journal of Medicine, 328(7), pp.460-4. https://www.ncbi.nlm.nih.gov/pubmed/8421475

Runia, T., Hop, W., de Rijke, Y., Buljevac, D. and Hintzen, R. (2012). Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis. Neurology, 79(3), pp.261-266. https://doi.org/10.1212/WNL.0b013e31825fdec7

Sotirchos, E., Bhargava, P., Eckstein, C., Van Haren, K., Baynes, M., Ntranos, A., Gocke, A., Steinman, L., Mowry, E. and Calabresi, P. (2015). Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology, 86(4), pp.382-390. https://doi.org/10.1212/WNL.0000000000002316
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