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Vitamin D3 (cholecalciferol) is a nutrient that is critical to many bodily functions. Vitamin D3 is beneficial for supporting bone health, immune wellness, cardio- vascular function, and cellular metabolism, among others.* Mounting research is highlighting the ever-increasing benefits of optimal vitamin D3 status.* Vitamin D3 is known to interact with over 200 different genes and thus plays a crucial regulatory role as a metabolic activator for a multitude of metabolic processes.*
Vitamin D from dietary intake or sun exposure requires two activation steps in the body. The first activation occurs in the liver, while the second activation occurs in the kidneys, allowing for regulation of calcium metabolism. However, vitamin D receptors are present throughout the body, in tissue such as the skin, cartilage, heart, prostate, bones and intestines. Thus, the second activation step also takes place in local tissues. Recent discoveries have highlighted the important modulatory effects of vitamin D on various cells of the immune system.
Studies show that vitamin D has important immunomodulatory effects. It is known that various cells of the immune system, such as T lymphocytes and antigen presenting cells, express the vitamin D receptor on their surface when activated. Recently, it has been found that treatment of these immune cells with vitamin D influences their expression of cytokines, which are chemical messengers of the immune system. The immune modulating effects of vitamin D extend to monocytes and dendritic cells of the immune system as well. Dendritic cells are important antigen-processing cells of the immune system that function to initiate the immune response. By altering the cytokine expression of dendritic cells, vitamin D may prevent overactivity of the immune response and keep the immune system in a normal healthy state of vigilance.4
Research has uncovered the role vitamin D plays in supporting cardiac function. Heart myocytes (cells) express the vitamin D receptor, as do smooth muscle cells of blood vessels. The benefits of vitamin D on the heart are potentially far-reaching. Studies on mice heart cells have shown that vitamin D administration impacts their growth and proliferation. In these cells, vitamin D inhibited the release of a protein that could be detrimental to the function of these cells, displaying cardioprotective properties. It has also been shown that vitamin D has a modulatory effect on heart rhythm. Again, in mouse heart cells, knocking out the effects of the vitamin D receptors led to an increased rate of contraction and relaxation. In normal mouse cardiac myocytes, administration of vitamin D led to normalization of heart contractility. Further studies in mice have led researchers to conclude that vitamin D supports the overall structure and function of the heart in terms of shape, size and performance.5
Studies in humans have confirmed the importance of vitamin D for heart function. In a study consisting of 1,739 participants from the Framingham Offspring Study, those individuals with the highest levels of vitamin D had superior cardiac function in relation to those with low vitamin D levels.5 These results make sense when taken in context of the overall effects of low vitamin D. These effects include an imbalance in the immune production of inflammatory markers, disturbing the normal inflammatory response and leading to potential effects on all tissues, including the heart and blood vessels. Restoration of optimal vitamin D status supports a healthy, normal inflammatory response and may thus restore the optimal health of the heart and cardiovascular system.
Furthermore, recent research highlights the profound benefits of vitamin D sufficiency in the realm of markers of cardiovascular wellness. Studies have previously shown that vitamin D supplementation has no effect on weight loss. However a recent study conducted in 200 healthy overweight individuals has shown that vitamin D supplementation can enhance the cardiovascular benefits associated with weight loss. The individuals participating in a 12-month weight reduction program were divided into two groups – one received placebo while the other group received supplemental vitamin D on a daily basis. At the end of the study, it was found that neither placebo nor vitamin D had a measurable effect on weight loss, as both groups lost similar amounts of weight. However, cardiovascular markers and blood lipid markers significantly improved in the vitamin D group, indicating enhanced cardiovascular support with vitamin D supplementation.6
A further way in which vitamin D may influence the health of the cardiovascular system is through its potential blood pressure regulatory effect. While the mechanism of vitamin D’s effect on blood pressure regulation is unclear, it is known that vitamin D regulates calcium balance, supports endothelial function, activates gene transcription, and influences the sodium-potassium balance and aldosterone system in the kidneys. It is likely that vitamin D exerts its blood pressure regulatory effect in one or more of these ways. A study was conducted to assess the effects of vitamin D status on blood pressure. In this study, data from the Third US National Health and Nutrition Examination Survey was used to determine the association of blood pressure levels with vitamin D status in healthy individuals. The results of this study, which included data from 12,644 people, showed that those individuals with the highest vitamin D status had an increased ability to maintain their blood pressure levels in the normal range. By supporting blood pressure levels within a range that is already normal, vitamin D promotes the health and wellness of the cardiovascular system.7
The role of vitamin D for bone health (alongside that of calcium) has been well-characterized in published literature. Vitamin D is obviously required for optimal calcium absorption. Recent studies have shown that possibly a majority of women with bone health issues have low levels of vitamin D. In some studies, this number is well over 60%. One such study found that out of a total of 2,606 postmenopausal women assessed, more than 64% had levels of vitamin D of less than 30 ng/mL (measured as serum levels of 25(OH) D, a common blood measure of vitamin D sufficiency). These authors state that, according to a recent review article, the optimal vitamin D levels as measured by 25(OH) D are between 50 and 80 ng/mL.8 Thus, levels near 30 ng/mL are significantly below those considered optimal.
An interesting study was performed recently in Finland in which 212 adolescent females were divided into three groups – a placebo group receiving no vitamin D, a low-dose vitamin D group (200 IU per day) and a higher dose vitamin D group (400 IU per day). The study aimed to measure the effects of vitamin D intake on bone mineral density in these young healthy females who also had adequate calcium status. At the end of the one year study, both vitamin D groups had significant improvements in bone density measured at the femur bone, whereas the 400 IU group also had significantly higher mineral density at the lumbar spine.9 These findings indicate the importance of vitamin D in bone structure and formation and also indicate the role of vitamin D in bone health independent of calcium intake.
Given its role as a promoter of gene expression, vitamin D affects numerous systems throughout the body. Research unmistakably shows that vitamin D is also a regulator of cellular health and wellness. Aged, unhealthy cells tend to lose their ability to differentiate and perform their original intended function due to the cumulative effects of oxidative damage. Vitamin D, acting as a pro-hormone, promotes the ability of cells to maintain their normal life cycle of birth, differentiation, functional performance and death, when they have become overly damaged.10 Damaged cells can lead to damaged tissue function. By promoting the normal cell cycle, vitamin D ensures the progression of cells through their functionality and their healthy renewal.
The second common source of vitamin D is from dietary intake. However, few foods are naturally high in vitamin D, with fish and seafood being the richest source.2 Adequate intake levels for vitamin D have been established by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies. For adults between 19 and 50 years of age, the FNB advises an intake of 200 IU per day, while for individuals aged 51 to 70 years, an intake of 400 IU per day is recommended. Recent studies have shown that these levels are often woefully inadequate for assuring optimal vitamin D status and for achieving the health benefits associated with adequate vitamin D levels. Some researchers suggest that a minimum daily intake of 1,000 IU is necessary to maintain barely adequate blood levels of vitamin D.3 Others agree that significantly higher doses are needed to ensure levels are optimal enough to promote health.1
1. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008 Mar;13(1):6-20.
2. Office of Dietary Supplements. Dietary Supplement Fact Sheet: Vitamin D. http://ods.od.nih.gov/factsheets/vitamind.asp#h3
3. Holick MF, Chen TC, Lu Z, Sauter E. Vitamin D and skin physiology: a D-lightful story. J Bone Miner Res. 2007 Dec;22 Suppl 2:V28-33.
4. van Etten E, Stoffels K, Gysemans C, Mathieu C, Overbergh L. Regulation of vitamin D homeostasis: implications for the immune system. Nutr Rev. 2008 Oct;66(10 Suppl 2):S125-34.
5. Zittermann A, Koerfer R. Vitamin D in the prevention and treatment of coronary heart disease. Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):752-7.
6. Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, Stehle P, Koertke H, Koerfer R. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr. 2009 May;89(5):1321-7.
7. Scragg R, Sowers M, Bell C. Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens. 2007 Jul;20(7):713-9.
8. Lips P, Hosking D, Lippuner K, Norquist JM, Wehren L, Maalouf G, Ragi-Eis S, Chandler J. The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation. J Intern Med. 2006 Sep;260(3):245-54.
9. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. A positive dose-response effect of vitamin D supplementation on site-specific bone mineral augmentation in adolescent girls: a double-blinded randomized placebo-controlled 1-year intervention. J Bone Miner Res. 2006 Jun;21(6):836-44.
10. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79(3):362-371.
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