Vitamin D3

Vitamin D May Reduce Risk of Falls in the Elderly

Taking vitamin D supplements may reduce the risk of falls in elderly people in residential care facilities, results of a study published in the Journal of the American Geriatrics Society suggest. In the study, Australian researchers examined the effect of vitamin D supplementation in 625 residents of 149 residential care facilities. The subjects were not vitamin D deficient.

The participants were randomly assigned to receive vitamin D supplements or inactive "placebo" for 2 years. All of the residents were prescribed 600 mg of calcium daily. Care staff recorded falls and fractures in diaries. At the start of the study, patient characteristics were similar in both groups.

The researchers report that vitamin D use cut the risk of falls by 27 percent to 37 percent compared with placebo. This study supports the use of vitamin D supplements in older people in residential care. The demonstrated benefits in this study on the rates of falls for individuals with marginal vitamin D levels, even without vitamin D deficiency, highlights the potential benefits of vitamin D supplementation in this population.

Extra Calcium Unnecessary with Adequate Vitamin D

For maintaining calcium metabolism, intake of calcium levels above 800 milligrams daily is probably unnecessary provided that vitamin D status is adequate, according to a report in the Journal of the American Medical Association this week. Vitamin D is essential to healthy teeth and bones, and it helps the body absorb and use calcium, but the ideal intake of vitamin D has been unclear, senior author Dr. Gunnar Sigurdsson. The researchers assessed calcium intake and serum vitamin D levels with respect to optimal parathyroid hormone (PTH) levels in 944 healthy Icelandic adults. PTH is a major hormone maintaining normal serum concentrations of calcium and phosphate and is itself regulated through levels of calcium. An insufficiency of vitamin D or calcium is generally associated with an increase in PTH, but the relative importance of each nutrient to this process has not been addressed.

In their study, Sigurdsson and colleagues noticed that in the presence of low vitamin D levels, maintaining calcium intake above 800 mg/d seems to help normalize calcium metabolism, as determined by the PTH level. By contrast, in the presence of higher vitamin D levels, there appears to be no benefit for achieving calcium intake above 800 mg/d.

Our study suggests that vitamin D sufficiency may be more important than high calcium intake in maintaining desired values of serum PTH," the authors conclude. "Vitamin D may have a calcium-sparing effect and as long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. The report also indicates that vitamin D supplements are needed to achieve an adequate status for people living in northern climates.

Vitamin D: Importance in the Prevention of Cancers

Lack of sufficient vitamin D can increase the risk of many common and serious conditions - some cancers, type 1 diabetes, cardiovascular disease, and osteoporosis.

This vitamin is not widely available in foods. Oily fish, such as salmon, mackerel, and sardines are good sources, as well as cod liver oil. Some foods may be fortified with vitamin D; these include milk, orange juice, cereals, and breads. Easting oily fish three or four times a week will provide enough vitamin D for most people. Otherwise, the body must rely on exposure to sunlight.

The skin can produce large amounts of vitamin D3, although this ability decreases with age. The vitamin D3 produced by casual exposure to sunlight during the spring, summer, and fall, is stored in the body fat, and becomes available in the winter, when required.

Who's at risk of vitamin D deficiency? Lack of vitamin D is seen commonly in the very young and the very old. Encouraging breast feeding of infants is partially responsible for a resurgence of this deficiency, as breast milk contains very little vitamin D. Infants usually require a vitamin D supplement. The elderly are at risk, because of poor dietary intake, decreased exposure to sunlight, and reduced formation in the skin; by age 70, the amount of vitamin D3 formed in the skin decreases by as much as 75%. Race also plays a role, especially in the elderly. Deficiency was reported in white, Hispanic, and black elderly Bostonians at the end of August in 30%, 42% and 84%, respectively; presumably the differences are largely related to skin pigmentation. Obesity is another risk factor. It's thought that the vitamin D deposited in large body fat stores is not readily accessible to the rest of the body.

Consequences of vitamin D deficiency: without vitamin D, the small intestine only absorbs about 10% to 15% of dietary calcium, instead of the normal 30% in someone without a deficiency. (In fact, absorption of calcium usually increases to about 80% during growth, lactation, and pregnancy; these periods are obviously time of increased risk for deficiency, too.) Lack of vitamin D in childhood causes rickets. In adults bone growth stops and deformities can occur, and there is an attempt by the parathyroid glands to counteract this, by producing more parathormone. This hormone tries to maintain the serum calcium, but it causes loss of phosphorus in the urine instead; this results in softening of the bone (osteomalacia), and the risk of fractures is increased.

Apart from effects on bone, lack of vitamin D has been associated with an increased risk of colon, prostate, and breast cancer. This was discovered because of the increase in these tumors seen in people living at high latitudes, i.e. with fewer hours of sunshine. And it's been shown that a breakdown product of vitamin D can slow the multiplication rate of very active cell growth. This action of vitamin D has led to its successful use in treating the skin disease psoriasis, in which the skin cells multiply too quickly.

Although the way it works is not always understood, there is some evidence that vitamin D is able to reduce the chances of development of autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. An interesting finding is the reduction in blood pressure in hypertensive patients when they are exposed to ultraviolet B radiation that raises their circulating vitamin D. Exposure to ultraviolet A radiation had no effect on these patients' vitamin D levels, or their raised blood pressure.

Finally, some people are mistakenly diagnosed with fibromyalgia, when they really have a deficiency of vitamin D deficiency. Muscle weakness and bone pain, often reported in fibromyalgia patients, may be presenting symptoms of this vitamin deficiency.

What should be done to avoid vitamin D deficiency? Without exposure to sunlight, Doctor recommends a minimum of 1000 IU vitamin D daily. And they believes that the blood concentration of 25(OH)D - the actual active form of vitamin D - should be measured once a year, just as we measure cholesterol levels. Early correction of a deficiency may prevent some of the conditions outlined in the previous section.

The best way to get enough vitamin D is by moderate exposure to sunlight. Exposure of the hands, face and arms, or arms and legs to sunlight for a period of time equal to a quarter of that required to make the skin pink is quite sufficient. There's no need to increase the risk of skin damage and skin cancer by 'overdosing'. And it can't hurt to consume foods fortified with vitamin D, as well as oily fish a few times a week.

Doctors warns against taking more than one multivitamin a day, as too much vitamin A would be consumed, increasing the risk of birth defects and osteoporosis. But one daily multivitamin containing 400 IU vitamin D is quite appropriate.

1. Colli E, Rigatti P, Montorsi F, Artibani W, Petta S, Mondaini N, Scarpa R, Usai P, Olivieri L, Maggi M. A Novel Vitamin D3 Analog Arrests Prostate Growth in Patients with Benign Prostatic Hyperplasia: A Randomized Clinical Trial. Eur Urol. 2005 Nov 15.

Objective: To evaluate the effect of BXL628, a vitamin D3 analog, on prostate volume in patients with benign prostatic hyperplasia (BPH). METHODS: We conducted a phase II, double blind, randomized, placebo controlled, clinical study. Patients eligible were aged >/=50 years, had a diagnosis of BPH and a prostate volume >/=40ml. Eligible patients were randomized and given either BXL628 150mcg daily or placebo for 12 weeks. All randomized patients underwent at baseline and at the end of study pelvic MRI to measure prostatic volume, uroflowmetry (Q(max)), American Urological Association Symptom Index (AUASI), serum PSA, testosterone, dihydrotestosterone and luteizing hormone. RESULTS: A total of 119 patients were randomized: 57 patients to BXL628 and 62 to placebo.

The percentage change of prostate volume at 12 week was -2.90 in the BXL628 group vs. +4.32 in the placebo group (p-value <0.0001). The estimated difference between treatments (BXL628 minus placebo) was -7.22% (95% confidence limit -9.27 to -5.18). Considering Q(max), mean change vs. baseline was -0.30 in BXL628 vs. +1.50 in the placebo group: this finding was not statistically significant. The mean change of the AUASI total score at final visit vs. baseline was -1.77 in the BXL628 group vs. -3.45 in the placebo group (p= not significant). Conclusion: BXL628 was able to arrest prostate growth within 12 weeks in men aged >/=50 years with prostatic volume >/=40ml. Its unprecedented mechanism of action may offer a new opportunity for the treatment of BPH.

2. Morishita M, Ohtsuru A, Kumagai A, Namba H, Sato N, Hayashi T, Yamashita S. Vitamin D3 Treatment for Locally Advanced Thyroid Cancer: A Case Report. Endocr J. 2005 Oct;52(5):613-6.

There are many intricacies in the surgical treatment of locally advanced thyroid cancer, including the medical management of the remaining functional organ and any cosmetic impairments, which are sometimes very difficult to manage and eventually carry a relatively high morbidity and mortality. Here, we report on a case of a 65-year-old female with an extremely locally-advanced thyroid cancer involving both lobes of the thyroid, blood vessels, trachea and esophagus. Despite the severity of her condition, oral administration of vitamin D3 (alphacalcido) has stalled both the tumor growth and further increases of serum thyroglobulin (Tg) level, and has led to a good preservation of quality of life for the last two years. Several reports have previously demonstrated the efficacy of vitamin D3 to inhibit the proliferation of thyroid cancer cell lines in vitro, but clinical evidence has been limited so far. Therefore, this case report provides important evidence for the effectiveness of vitamin D3 therapy against advanced thyroid cancers.

3. Tokar EJ, Webber MM. Chemoprevention of Prostate Cancer by Cholecalciferol (vitamin D3): 25-hydroxylase (cyp27a1) in Human Prostate Epithelial Cells. Clin Exp Metastasis. 2005;22(3):265-73.

The 20-30 year latency period for prostate cancer provides an important opportunity to prevent the development of invasive cancer. A logical approach for chemoprevention to reduce incidence is to identify agents, such as, vitamin D, which can inhibit cell proliferation and induce differentiation, are safe, and readily available to the public at low cost. Epidemiological evidence suggests that vitamin D deficiency is associated with increased risk for prostate cancer. We examined the ability and mechanisms of action of cholecalciferol, a precursor of the most biologically active hormone calcitriol, to block or reverse premalignant changes. The immortalized, non-tumorigenic, RWPE-1 human prostate epithelial cell line, was used.

Results show that cholecalciferol, at physiological levels: (i) inhibits anchorage-dependent growth (ii) induces differentiation by increasing PSA expression and (iii) exerts its effects by up-regulating vitamin D receptor (VDR), retinoid-X receptors (RXRs), and androgen receptor (AR). Furthermore, we discovered that human prostate epithelial cells constitutively express appreciable levels of 25-hydroxylase CYP27A1 protein, the enzyme which catalyzes the conversion of cholecalciferol to 25(OH)D(3), and that CYP27A1 is up-regulated by cholecalciferol. Recent studies show that human mitochondrial CYP27A1 can also catalyze 1alpha-hydroxylation of 25(OH)D(3) to calcitriol. The presence of 25-hydroxylase in human prostate epithelial cells has not previously been shown. Since human prostate epithelial cells have the necessary enzymes and the rare ability to locally convert cholecalciferol to the active hormone calcitriol, we propose that they are a prime target for chemoprevention of prostate cancer with cholecalciferol whose safety is well established as a supplement in vitamins and fortified foods.

4. Guilhou JJ. The Therapeutic Effects of Vitamin D3 and its Analogues in Psoriasis. Expert Opin Investig Drugs. 1998 Jan;7(1):77-84.

Psoriasis is a common skin disease which is characterised by the proliferation and abnormal differentiation of keratinocytes, coupled with complex immune disturbances. The beneficial effects of vitamin D derivatives in this disease are due to their capacity to inhibit proliferation, their ability to induce normal differentiation and their immunomodulatory properties. Since the systemic administration of these compounds is limited by their effect on calcium metabolism, topical preparations have become available in most countries. Topical calcipotriol and/or tacalcitol are now considered as first-line treatment for mild-to-moderate psoriasis and can be taken in combination with other systemic therapies in more severe cases of the disease. Novel orally active vitamin D analogues, with minimal calcitropic effercts, are, however, required for more effective treatment.

5. Moore ME, Piazza A, McCartney Y, Lynch MA. Evidence that Vitamin D3 Reverses Age-related Inflammatory Changes in the Rat Hippocampus. Biochem Soc Trans. 2005 Aug;33(Pt 4):573-7.

One of the major challenges in neuroscience is to identify the changes which accompany aging and which contribute to the well-documented age-related deterioration in cognitive function. This is a particular challenge in the light of the vast array of reported changes, which include morphological changes like synaptic and perhaps cell loss, alteration in membrane composition and the resultant changes in function of membrane proteins, modulation of the hypothalamo-pituitary axis, impaired calcium homoeostatic mechanisms, alteration in enzyme function and decreased neurotransmitter release. In the past few years, evidence suggesting that an aged brain exhibits signs of oxidative stress and inflammatory stress has been accumulating, and recent evidence using microarray analysis has added support to this view. In this paper, we provide evidence to suggest that vitamin D3 acts as an anti-inflammatory agent and reverses the age-related increase in microglial activation and the accompanying increase in IL-1beta (interleukin-1beta) concentration.

6. Holick MF. Vitamin D: Importance in the Prevention of Cancers, Type 1 Diabetes, Heart Disease, and Osteoporosis. Am J Clin Nutr. 2004 Mar;79(3):362-71.

The purpose of this review is to put into perspective the many health benefits of vitamin D and the role of vitamin D deficiency in increasing the risk of many common and serious diseases, including some common cancers, type 1 diabetes, cardiovascular disease, and osteoporosis. Numerous epidemiologic studies suggest that exposure to sunlight, which enhances the production of vitamin D(3) in the skin, is important in preventing many chronic diseases. Because very few foods naturally contain vitamin D, sunlight supplies most of our vitamin D requirement. 25-Hydroxyvitamin D [25(OH)D] is the metabolite that should be measured in the blood to determine vitamin D status.

Vitamin D deficiency is prevalent in infants who are solely breastfed and who do not receive vitamin D supplementation and in adults of all ages who have increased skin pigmentation or who always wear sun protection or limit their outdoor activities. Vitamin D deficiency is often misdiagnosed as fibromyalgia. A new dietary source of vitamin D is orange juice fortified with vitamin D. Studies in both human and animal models add strength to the hypothesis that the unrecognized epidemic of vitamin D deficiency worldwide is a contributing factor of many chronic debilitating diseases. Greater awareness of the insidious consequences of vitamin D deficiency is needed. Annual measurement of serum 25(OH)D is a reasonable approach to monitoring for vitamin D deficiency. The recommended adequate intakes for vitamin D are inadequate, and, in the absence of exposure to sunlight, a minimum of 1000 IU vitamin D/d is required to maintain a healthy concentration of 25(OH)D in the blood.

7. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of Vitamin D and Risk of Type 1 Diabetes: A Birth-cohort Study. Lancet. 2001 Nov 3;358(9292):1500-3.

Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes in animals. Our aim was to ascertain whether or not vitamin D supplementation or deficiency in infancy could affect development of type 1 diabetes. A birth-cohort study was done, in which all pregnant women (n=12055) in Oulu and Lapland, northern Finland, who were due to give birth in 1966 were enrolled. Data was collected in the first year of life about frequency and dose of vitamin D supplementation and presence of suspected rickets. Our primary outcome measure was diagnosis of type 1 diabetes by end of December, 1997. 12058 of 12231 represented live births, and 10821 (91% of those alive) children were followed-up at age 1 year. Of the 10366 children included in analyses, 81 were diagnosed with diabetes during the study.

Vitamin D supplementation was associated with a decreased frequency of type 1 diabetes when adjusted for neonatal, anthropometric, and social characteristics (rate ratio [RR] for regular vs no supplementation 0.12, 95% CI 0.03-0.51, and irregular vs no supplementation 0.16, 0.04-0.74. Children who regularly took the recommended dose of vitamin D (2000 IU daily) had a RR of 0.22 (0.05-0.89) compared with those who regularly received less than the recommended amount. Children suspected of having rickets during the first year of life had a RR of 3.0 (1.0-9.0) compared with those without such a suspicion. Dietary vitamin D supplementation is associated with reduced risk of type 1 diabetes. Ensuring adequate vitamin D supplementation for infants could help to reverse the increasing trend in the incidence of type 1 diabetes.

8. Blutt SE, Weigel NL. Vitamin D and Prostate Cancer. Proc Soc Exp Biol Med. 1999 Jun;221(2):89-98.

Classically, the actions of vitamin D have been associated with bone and mineral metabolism. More recent studies have shown that vitamin D metabolites induce differentiation and/or inhibit cell proliferation of a number of malignant and nonmalignant cell types including prostate cancer cells. Epidemiological studies show correlations between the risk factors for prostate cancer and conditions that can result in decreased vitamin D levels. The active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), inhibits growth of both primary cultures of human prostate cancer cells and cancer cell lines, but the mechanism by which the cells are growth-inhibited has not been clearly defined. Initial studies suggest that calcitriol alters cell cycle progression and may also initiate apoptosis. One of the disadvantages of using vitamin D in vivo is side-effects such as hypercalcemia at doses above physiological levels. Analogs of calcitriol have been developed that have comparable or more potent antiproliferative effects but are less calcemic. Further research into the mechanisms of vitamin D action in prostate and identification of suitable analogs for use in vivo may lead to its use in the treatment or prevention of prostate cancer.

9. Zittermann A. Vitamin D in Preventive Medicine: Are We Ignoring the Evidence? Br J Nutr. 2003 May;89(5):552-72.

Vitamin D is metabolised by a hepatic 25-hydroxylase into 25-hydroxyvitamin D (25(OH)D) and by a renal 1alpha-hydroxylase into the vitamin D hormone calcitriol. Calcitriol receptors are present in more than thirty different tissues. Apart from the kidney, several tissues also possess the enzyme 1alpha-hydroxylase, which is able to use circulating 25(OH)D as a substrate. Serum levels of 25(OH)D are the best indicator to assess vitamin D deficiency, insufficiency, hypovitaminosis, adequacy, and toxicity. European children and young adults often have circulating 25(OH)D levels in the insufficiency range during wintertime. Elderly subjects have mean 25(OH)D levels in the insufficiency range throughout the year. In institutionalized subjects 25(OH)D levels are often in the deficiency range. There is now general agreement that a low vitamin D status is involved in the pathogenesis of osteoporosis. Moreover, vitamin D insufficiency can lead to a disturbed muscle function. Epidemiological data also indicate a low vitamin D status in tuberculosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases, hypertension, and specific types of cancer.

Some intervention trials have demonstrated that supplementation with vitamin D or its metabolites is able: (i) to reduce blood pressure in hypertensive patients; (ii) to improve blood glucose levels in diabetics; (iii) to improve symptoms of rheumatoid arthritis and multiple sclerosis. The oral dose necessary to achieve adequate serum 25(OH)D levels is probably much higher than the current recommendations of 5-15 microg/d.

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