Vitamin D3

Numerous new studies are being published regarding the health benefits of vitamin D3 and the negative consequences of deficiency. These studies are of particular interest as the National Health and Nutrition Examination Survey (NHANES) showed that prevalence of vitamin D insufficiency jumped from 55 percent in 1988-1994 to 77 percent in 2001-2004.¹

Vitamin D, also known as calciferol, is a fat-soluble vitamin that can be produced by the body as well as obtained in the diet. Ergocalciferol (also known as vitamin D2) and cholecalciferol (vitamin D3) are the two primary forms of vitamin D. Vitamin D3 is the form made in the skin by exposure to ultraviolet light, which converts the precursor 7-dehydrocholesterol to cholecalciferol. Cholecalciferol is initially metabolized in the liver to produce 25-hydroxycholecalciferol (25-hydroxyD3), which is then converted in the kidney to 1,25-dihydroxycholecalciferol (1,25-dihydroxyD3), the primary active form of vitamin D.

Currently, the Recommended Daily Allowance (RDA) for vitamin D is 400 IU per day, which is established by the Food and Nutrition Board at the Institute of Medicine of The National Academies. However, in light of the recent research that suggests the RDA is far below the body’s needs, the Food and Nutrition Board has established a committee to update the current Daily Recommended Intakes for vitamin D by May 2010.² New studies are confirming that vitamin D3 insufficiency plays a role in numerous conditions including cardiovascular disease, cancer, decreased bone density, immune functions, fat deposition, diabetes and many others.

Bone Health

It is well-established that vitamin D3 and its relationship to calcium uptake and deposition plays a significant role in bone metabolism. Extreme vitamin D deficiency results in rickets and osteomalacia. However, long-term vitamin D insufficiency may also result in osteoporosis, which is of particular importance as 10 million Americans are estimated to already have the disease and nearly 34 million more have low bone mass (osteopenia).³ Osteoporosis is a condition in which bone mass is reduced, the structural integrity of the bone is diminished and the risk of fracture is increased.

In a recently published study, data from 7 large randomized trials in which subjects received calcium and/or vitamin D3 was analyzed to evaluate fracture risk. The results showed that the clinical trials using calcium plus vitamin D3 supplementation resulted in a decrease in the overall risk of fracture by 8 percent and a reduction in the risk of hip fracture by 16 percent.⁴ Similarly, another new study found that vitamin D3 supplementation reduced the risk of falls by 19 percent, the risk of hip fracture by 18 percent and the risk of non-vertebral fracture by 20 percent.⁵ In addition, vitamin D3 improves bone mineral density. A new study compared supplementation of vitamin D3 plus calcium to no supplementation in postmenopausal women over a 3-year duration. The results showed that the women receiving both supplements had a significant increase in total-body bone mineral density compared to the women in the control group.⁶

Cardiometabolic Disorders

Cardiometabolic disorders including cardiovascular disease, diabetes, and the metabolic syndrome have been associated with vitamin D3 deficiency. The metabolic syndrome is characterized by a group of risk factors that increase the risk of developing type 2 diabetes, atherosclerosis, coronary artery disease and stroke. These conditions are increasingly common, as it is estimated that 50 million Americans have metabolic syndrome, 58 million Americans have cardiovascular disease and 23.6 million Americans have diabetes.^7-9

In one new study, researchers evaluated the data from 28 previously published studies regarding vitamin D3 serum levels and the risk of developing cardiometabolic disorders. The researchers showed that the subjects with the highest levels of serum 25-hydroxy-vitamin D3 [25(OH)D3] had a 43 percent decreased risk of developing cardiometabolic disorders compared to the subjects with the lowest serum vitamin D3 levels. More specifically, the researchers found that compared to the subjects with the lowest 25(OH)D3 levels, the subjects with the highest levels of 25(OH)D3 had a decreased risk of cardiovascular disease by 33 percent, type-2 diabetes by 55 percent and the metabolic syndrome by 51 percent.¹⁰

Another interesting study investigated the relationship between serum vitamin D3 levels and the development of cardiovascular disease. In this study, subjects with no prior history of cardiovascular disease were evaluated for serum 25-hydroxyD3 levels and then categorized as: normal (over 30 ng/ml), low (15-30 ng/ml), or very low (less than 15 ng/ml). The study found that the subjects with very low levels of 25-hydroxyD3 were 77 percent more likely to die compared to the subjects with normal 25-hydroxyD3 levels. Additionally, the subjects with very low serum 25-hydroxyD3 levels were 45 percent more likely to develop coronary artery disease, 78 percent more likely to have a stroke, and twice as likely to suffer from heart failure compared to the subjects with normal 25-hydroxyD3 levels.¹¹

Similarly, another study showed that the risk of death due to cardiovascular disease in the subjects with the lowest serum 25-hydroxyD3 levels was almost 2.5-times higher than the subjects with the highest serum 25-hydroxyD3 levels.¹² In addition, research has shown that individuals with the highest serum 25-hydroxyD3 levels have a 52 percent decreased risk of death due to a cerebrovascular accident (stroke) when compared to individuals with low serum levels of 25-hydroxyD3.¹³

A recently published study examined the effect of vitamin D3 supplementation in women diagnosed with insulin resistance and serum 25-hydroxyD3 levels less than 50 nmol/l. After 6 months of supplementation with vitamin D3, the study found that insulin sensitivity and insulin resistance significantly improved and fasting levels of insulin decreased compared to the women in the placebo group.¹⁴

Depression

Researchers have linked vitamin D deficiency to depression. In a recent randomized, double blind controlled trial, 441 overweight or obese subjects were given 20,000 or 40,000 IU of vitamin D per week or a placebo for 1 year. Subjects with serum 25(OH)D levels less than 40 nmol L(-1) had significantly more depressive traits as measured by the Beck Depression Inventory (BDI) score compared to those with serum 25(OH)D levels of 40 nmol L(-1) or more.¹⁵

In another study, vitamin D supplementation during the winter was associated with a decline in the BDI scores, averaging 10 points, which is indicative of a reduction in symptoms of depression.¹⁶

Cancer Risk

Vitamin D3 deficiency has also been associated with increased cancer risk. Approximately 1 out of every 2 American men and 1 out of every 3 American women will develop some type of cancer during their lifetime.

A meta-analysis of 11 studies found that individuals with the highest serum levels of 25(OH)D3 had a decreased risk of developing breast cancer by 45 percent compared to the subjects with the lowest serum 25-hydroxyD3 levels.¹⁷ Additionally, another study concluded that the projected number of cancer cases that could be prevented in North America with universal attainment of a serum 25(OH)D level of 55 ng/m or more would be at least 60,000 cases per year of colorectal cancer and 85,000 cases per year of breast cancer. The projected number of cases that could be prevented annually in the world with this serum level of 25(OH)D would be approximately 250,000 cases of colorectal cancer and 350,000 cases of breast cancer.¹⁸

Recent research has also shown that subjects with the highest serum levels of 25-hydroxyD3 have a 40 percent lower risk of developing colorectal cancer compared to individuals with the lowest 25-hydroxyD3 serum levels.¹⁹ Another new study showed that in subjects with colorectal cancer, those with the highest levels of 25-hydroxyD3 in their serum had a 50 percent decrease in the risk of mortality due to colorectal cancer compared to the subjects with the lowest serum levels of 25-hydroxyD3.²⁰

Weight Management, Pregnancy and Others

Two studies have recently been published regarding vitamin D3 deficiency and fat deposition. The studies showed that low serum levels of 25-hydroxyD3 was associated with increased fat infiltration in muscle tissue,²¹ subcutaneous adipose tissue (fat beneath the skin), and visceral adipose tissue (fat surrounding the abdominal organs), as well as increased waist circumference and serum insulin levels compared to subjects with normal 25-hydroxyD3 levels in their serum.²² Furthermore, obese subjects have been found to be at increased risk for vitamin D deficiency syndromes due to reductions in their circulating serum levels of 25-hydroxyD3 as a result of the deposition of this fat soluble vitamin in their body fat compartments.²³

Another interesting area of vitamin D research is related to deficiency during pregnancy. Vitamin D3 deficiency is present in approximately 5-50 percent of women during pregnancy and 10-56 percent of breast-fed infants, despite the women’s use of a prenatal vitamin supplement. Adverse health outcomes such as pre-eclampsia, low birth-weight,²⁴ low calcium in neonatal blood, poor postnatal growth, bone fragility, and increased incidence of autoimmune diseases have been linked to low vitamin D3 serum levels during pregnancy and infancy.²⁵ In fact, vitamin D3 supplementation during pregnancy has been shown to decrease the risk of pre-eclampsia, the most common pregnancy complication, by 27 percent for women supplementing with vitamin D3 compared to women not taking supplements.²⁶

Other interesting recently published studies have associated low levels of vitamin D3 with increased risks of upper respiratory infections,²⁷ chronic fatigue syndrome,²⁸ childhood asthma and allergies^29-30 and decreased cognitive function.³¹

Vitamin D Home Test Kit

A vitamin D3 test kit that uses a patented blood drop technology is now available here. The unique collection device incorporates a serum-separator paper that will immediately remove the red cells from the serum when the drop of blood hits the collection device. This provides a stable serum sample for testing. When compared directly to blood obtained by venipuncture for testing of Vitamin D3 levels, the blood drop test performed accurately and precisely.

Conclusion

Vitamin D3 deficiency is surprisingly common. The vast amount of new research regarding the diverse health benefits of vitamin D3 supplementation makes this essential vitamin an integral part of both health optimization and maintenance programs.

References

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2. Office of Dietary Supplements, National Institutes of Health. Dietary Supplement Fact Sheet: Vitamin D. Available at: http://ods.od.nih.gov/factsheets/vitamind.asp. Accessed on: 03-15-10.

3. National Osteoporosis Foundation. Fast Facts on Osteoporosis. Available at: http://www.nof.org/osteoporosis/diseasefacts.htm. Accessed on: 03-15-10.

4. Abrahamsen B, Masud T, Avenell A, et al. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010 Jan 12;340:b5463.

5. Bischoff-Ferrari H. Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? Best Pract Res Clin Rheumatol. 2009 Dec;23(6):789-95.

6. Kärkkäinen M, Tuppurainen M, Salovaara K, et al. Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65-71 years: a 3-year randomized population-based trial (OSTPRE-FPS). Osteoporos Int. 2010 Mar 4. Published Online Ahead of Print.

7. American Heart Association. Metabolic Syndrome. Available at: http://www.americanheart.org/presenter.jhtml?identifier=4756.

8. Centers for Disease Control and Prevention (CDC). Missed opportunities in preventive counseling for cardiovascular disease–United States, 1995. MMWR Morb Mortal Wkly Rep. 1998 Feb 13;47(5):91-5.

9. American Diabetes Association. Diabetes Statistics. Available at: http://www.diabetes.org/diabetes-basics/diabetes-statistics/.

10. Parker J, Hashmi O, Dutton D, et al. Levels of vitamin D and cardiometabolic disorders: Systematic review and meta-analysis. Maturitas. 2010 Mar;65(3):225-236.

11. Muhlestein JB, et al. American Heart Association Scientific Sessions 2009. Orlando, Florida. November 14-18, 2009.

12. Ginde AA, Scragg R, Schwartz RS, et al. Prospective Study of Serum 25-Hydroxyvitamin D Level, Cardiovascular Disease Mortality, and All-Cause Mortality in Older U.S. Adults. J Am Geriatr Soc. 2009 Sept;57(9):1595-603.

13. Kilkkinen A, Knekt P, Aro A, et al. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol. 2009 Oct 15;170(8):1032-9.

14. von Hurst PR, Stonehouse W, Coad J. Vitamin D supplementation reduces insulin resistance in South Asian women living in New Zealand who are insulin resistant and vitamin D deficient - a randomised, placebo-controlled trial. Br J Nutr. 2009 Sep 28:1-7. Published Online Ahead of Print.

15. Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: randomized double blind trial. J Intern Med. 2008 Dec;264(6):599-609.

16. Shipowick CD, Moore CB, Corbett C, Bindler R. Vitamin D and depressive symptoms in women during the winter: a pilot study. Appl Nurs Res. 2009 Aug;22(3):221-5.

17. Chen P, Hu P, Xie D, et al. Meta-analysis of vitamin D, calcium and the prevention of breast cancer. Breast Cancer Res Treat. 2009 Oct 23. Published Online Ahead of Print.

18. Garland CF, Grant WB, Mohr SB, Gorham ED, Garland FC. What is the Dose-Response Relationship between Vitamin D and Cancer Risk? Nutrition Reviews. August 2007;65(8):S91-S95.

19. Jenab M, Bueno-de-Mesquita HB, Ferrari P, et al. Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study. BMJ. 2010 Jan 21;340.

20. Ng K, Wolpin BM, Meyerhardt JA, et al. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer. 2009 Sep 15;101(6):916-23.

21. Gilsanz V, Kremer A, Mo AO, et al. Vitamin D Status and Its Relation to Muscle Mass and Muscle Fat in Young Women. J Clin Endocrinol Metab. 2010 Feb 17. Published Online Ahead of Print.

22. Cheng S, Massaro JM, Fox CS, et al. Adiposity, cardiometabolic risk, and vitamin D status: the Framingham heart study. Diabetes. 2010 Jan;59(1):242-8.

23. Wortsman J, Matsuoka LY, Chen TC, Lu Z Holick MF. Decreased bioavailability of vitamin D in obesity. American Journal of Clinical Nutrition. September 2000; 72(3):690-693.

24. Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multi-ethnic Amsterdam Born Children and their Development cohort. Br J Nutr. 2010 Mar 2:1-10.

25. Mulligan ML, Felton SK, Riek AE, et al. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. 2009 Oct 19. Published Online Ahead of Print.

26. Haugen M, Brantsaeter AL, Trogstad L, et al. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009 Sep;20(5):720-6.

27. Bartley J. Vitamin D, innate immunity and upper respiratory tract infection. J Laryngol Otol. 2010 Jan 13:1-5.

28. Berkovitz S, Ambler G, Jenkins M, et al. Serum 25-hydroxy Vitamin D Levels in Chronic Fatigue Syndrome: a Retrospective Survey. Int J Vitam Nutr Res. 2009 Jul;79(4):250-4.

29. Brehm JM, Celedón JC, Soto-Quiros ME, et al. Serum vitamin D levels and markers of severity of childhood asthma in Costa Rica. Am J Respir Crit Care Med. 2009 May 1;179(9):765-71.

30. Erkkola M, Kaila M, Nwaru BI, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy. 2009 Jun;39(6):875-82.

31. Lee DM, Tajar A, Ulubaev A, et al. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged and older European men. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):722-9.