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Why would vitamin D be prescribed when vitamin D3 is available over-the-counter? Let's review the known differences between vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol): --D3 is the human form; D2 is the non-human form found in plants. --Dose for dose, D3 is more effective at raising blood levels of 25-hydroxy vitamin D than D2. It requires roughly twice to 250% of the dose of D2 to match that of D3 (Trang H et al 1998). --D2 blood levels don't yield long-term sustained levels of 25-hydroxy vitamin D as does D3. When examined as a 28-day area under the curve (AUC--a superior measure of biologic exposure), D3 yields better than a 300% increased potency compared to D2. This means that it requires around 50,000 units D2 to match the effects of 15,000 units D3 (Armas LA et al 2004). --D2 has lower binding affinity for vitamin D-binding protein, compared to D3 --Mitochondrial vitamin D 25-hydroxylase converts D3 to the 25-hydroxylated form five times more rapidly than D2. --As we age, the ability to metabolize D2 is dramatically reduced, while D3 is not subject to this phenomenon

Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients. Zhou W, Suk R, Liu G, Park S, Neuberg DS, Wain JC, Lynch TJ, Giovannucci E, Christiani DC. Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2303-9. PMID: 16214909 In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients. In summary, for early-stage NSCLC patients, patients who had surgery in summer with "high" recent vitamin D intake have a statistically significantly improved RFS and OS than patients who had surgery in winter with "low" vitamin D intake. These results should be confirmed in a prospective study to assess the serum vitamin D levels at time of surgery. If the results are confirmed, our results, combined with findings in other studies, suggest that dietary vitamin D supplementation may be advisable for early stages of lung cancer patients, particularly during the winter season and in groups that tend to be deficient in vitamin D.

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects

The role of vitamin D in cancer prevention. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PMID: 16380576 DOI: 10.2105/AJPH.2004.045260 Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

Vitamin D deficiency is the cause of common obesity. Foss YJ. Med Hypotheses. 2009 Mar;72(3):314-21. Epub 2008 Dec 2. PMID: 19054627 doi:10.1016/j.mehy.2008.10.005 Common obesity and the metabolic syndrome may therefore result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D. The synthesis of vitamin D is dependent upon the absorption of radiation in the ultraviolet-B range of sunlight. At ground level at mid-latitudes, UV-B radiation falls in the autumn and becomes negligible in winter. It has previously been proposed that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor with the function of signaling changes in sunlight intensity. It is here proposed that a fall in vitamin D in the form of circulating calcidiol is the stimulus for the winter response, which consists of an accumulation of fat mass (obesity) and the induction of a winter metabolism (the metabolic syndrome). vitamin D deficiency can account for the secular trends in the prevalence of obesity and for individual differences in its onset and severity. It may be possible to reverse the increasing prevalence of obesity by improving vitamin D status.

"Retinol-induced Intestinal Tumorigenesis in Min/+ Mice and Importance of Vitamin D Status. Hetland RB, Alexander J, Berg JP, Svendsen C, Paulsen JE. Anticancer Res. 2009 Nov;29(11):4353-60. PMID: 20032378 The effects of life-long dietary exposure, starting in utero, to high retinol, low vitamin D, or high retinol in combination with low Vitamin D on intestinal tumorigenesis in Min/+ mice were investigated. In males, high retinol alone significantly increased the number (2.6-fold) and size (1.3-fold) of small intestinal tumours; in females no significant increase in tumour number or size was seen. In both genders, low Vitamin D intake alone did not affect intestinal tumorigenesis. In males, intake of the combined high retinol/low Vitamin D diet did not further increase the effects caused by high retinol alone. In females, however, the high retinol/low vitamin D-induced increase in tumour number (3.1-fold) and tumour size (1.5-fold) exceeded that of high retinol alone. In conclusion, a high dietary intake of retinol stimulated intestinal tumorigenesis in Min/+ mice. Furthermore, the results indicate a combined effect of high retinol and low Vitamin D on tumorigenesis in females"

Food chain as origin of vitamin D in fish D. Sunita Rao and N. Raghuramulu. Comparative Biochemistry and Physiology Part A: Physiology Volume 114, Issue 1, May 1996, Pages 15-19 doi:10.1016/0300-9629(95)02024-1 Plankton, the chief food source of fish, was assessed as the possible dietary origin of vitamin D in fish. The presence of vitamin D compounds were examined in fresh water phytoplankton and zooplankton employing a series of chromatographic procedures. Abundant amounts of provitamins D and vitamins D (D2 and D3) were found in the fresh water plankton. The high amount of vitamin D observed may be due to exposure of plankton to sunlight because the plankton were caught during the summer month. Thus, plankton may be an important contributor to vitamin D in fish.

Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Eur J Clin Nutr. 2001 Dec;55(12):1091-7. PMID: 11781676 INTERPRETATION: The self-reported vitamin D intake from milk and/or multivitamins does not relate to prevention of low vitamin D nutritional status of young women in winter. Recommended vitamin D intakes are too small to prevent insufficiency. vitamin D nutrition can only be assessed by measuring serum 25(OH)D concentration.

Vitamin D supplementation. Eveleigh B. Can Fam Physician. 2007 Sep;53(9):1435; author reply 1435. PMID: 17872869 My concern regarding vitamin D2 is that it is a synthetic analogue and might interact with the vitamin D receptor differently in various cell systems. It has been reported that vitamin D3 might improve glycemic control.7 Vitamin D2 has been reported to cause worsening of glycemic control in people of East Indian descent.8 Is this because of vitamin D receptor polymorphism, or because of enhanced 24-hydroxylase enzyme activation, or is it due to how vitamin D2 interacts with the receptor? Until this has been sorted out, I feel safest using vitamin D3. There are about 2000 synthetic analogues of vitamin D. The search is on for one that can cross the blood-brain barrier to treat certain types of brain cancers without causing hypercalcemia.9 But then again, what other effects would this compound have? There are still so many unknowns

Vitamin D is a fat-soluble vitamin that is essential for maintaining normal calcium metabolism (1). Vitamin D3 (cholecalciferol) can be synthesized by humans in the skin upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize ergosterol, which is converted to vitamin D2 (ergocalciferol) by ultraviolet light. Vitamin D2 is less active in birds than vitamin D3 and may also be less active in humans (2). When exposure to UVB radiation is insufficient for the synthesis of adequate amounts of vitamin D3 in the skin, adequate intake of vitamin D from the diet is essential for health.

Assessment of dietary vitamin D requirements during pregnancy and lactation. Hollis BW, Wagner CL. Am J Clin Nutr. 2004 May;79(5):717-26. Review. PMID: 15113709 We found that high-dose maternal vitamin D supplementation not only improves the nutritional vitamin D status of breastfeeding infants but also elevates the maternal concentrations into the mid-normal range. Thus, a dual benefit is achieved from high-dose maternal supplementation. It is noteworthy that in the Finnish study, the authors added a disclaimer, "A sufficient supply of vitamin D to the breastfed infant is achieved only by increasing the maternal supplementation up to 2000 IU/d. Such a dose is far higher than the RDA [DRI] for lactating mothers [and therefore] its safety over prolonged periods is not known and should be examined by further study." This point of concern was valid when this study was conducted in 1986 (92); however, on the basis of the current findings of Vieth et al (2) and of Heaney et al (3)-which showed that vitamin D intakes <= 10 000 IU/d (250 µg) are safe for prolonged periods (up to 5 mo)-we believe that it is time to reexamine the understated DRI of vitamin D for lactating mothers. This work is now being conducted in our clinics and laboratory.

Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. Abnet CC, Chen W, Dawsey SM, Wei WQ, Roth MJ, Liu B, Lu N, Taylor PR, Qiao YL. Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1889-93. PMID: 17855710 doi: 10.1158/1055-9965.EPI-07-0461 Background: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. Conclusions: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. In conclusion, we found that a higher serum 25(OH)D concentration was associated with an increased risk of esophageal squamous dysplasia, the precursor lesion for ESCC. This finding concurs with our previous prospective study which found that higher vitamin D status was associated with increased risk of incident ESCC in this same population. These unexpected findings suggest that further studies of the association of vitamin D and digestive tract cancers are needed before the effect of vitamin D in different populations can be elucidated.

March 27, 2009 - A significant decrease in serum 25-hydroxyvitamin D (25[OH]D) levels has led to an increase in vitamin D insufficiency in the US population, especially in racial and ethnic groups, according to results of a population-based study reported in the March 23 issue of the Archives of Internal Medicine. "Vitamin D insufficiency has been associated with increases in cardiovascular disease, cancer, and infection," write Adit A. Ginde, MD, from the Department of Emergency Medicine at the University of Colorado Denver School of Medicine, Aurora, Colorado, and colleagues. "Vitamin D supplementation appears to mitigate the incidence and adverse outcomes of these diseases and may reduce all-cause mortality." [...] "These findings have important implications for health disparities and public health," the study authors conclude. "Our data provide additional evidence that current recommendations for vitamin D supplementation (200-600 IU/d) are inadequate to achieve optimal serum 25(OH)D levels in most of the US population." They add that large, randomized controlled trials of higher doses of vitamin D supplementation are needed to evaluate their effect on general health and mortality.

Vitamin D and living in northern latitudes--an endemic risk area for vitamin D deficiency. Huotari A, Herzig KH. Int J Circumpolar Health. 2008 Jun;67(2-3):164-78. Review. PMID: 18767337 CONCLUSIONS: vitamin D plays a fundamental role in calcium and phosphate homeostasis. A deficiency of vitamin D has been attributed to several diseases. Since its production in the skin depends on exposure to UVB-radiation via the sunlight, the level of vitamin D is of crucial importance for the health of inhabitants who live in the Nordic latitudes where there is diminished exposure to sunlight during the winter season. Therefore, fortification or supplementation of vitamin D is necessary for most of the people living in the northern latitudes during the winter season to maintain adequate levels of circulating 25(OH)D3 to maintain optimal body function and prevent diseases.

"One of the surprises over the past year has been all the research regarding Vitamin D and brain health. Give that many people are spending less time outdoors and more time in front of their computers, we all should be concerned, as Vitamin D comes in part from our exposure to the sun. Low Vitamin D levels have been associated with pain, depression, MS, cancer and now perhaps even dementia. Here are the results of a new study that should cause all of us to pay attention. I frequently check the Vitamin D levels in my patients and frrequently see that they are below the optimal level. Get your levels checked if you have any of these concerns. A new large-scale senior population study has found that a lack of Vitamin D in the elderly could be linked to cognitive impairment. The study, conducted on almost 2,000 adults over the age of 65, is the first of its scale to identify this relationship, and prompted researchers to suggest Vitamin D supplementation as a possible means of reducing the risk of dementia. "

"For what reason I don't know, but this January 2009 editorial by William Faloon of the Life Extension Foundation is making the rounds. Perhaps it just came available on the web. It's a good read, particularly in light of the billions and trillions of dollars the thieves & thugs in DC are about to flush down the crapper on your behalf. Some notable excerpts. A large number of new vitamin D studies have appeared in the scientific literature since I wrote my plea to the federal government. These studies don't just confirm what we knew 16 months ago-they show that optimizing vitamin D intake will save even more lives than what we projected. For instance, a study published in June 2008 showed that men with low vitamin D levels suffer 2.42 times more heart attacks. Now look what this means in actual body counts. Each year, about 157,000 Americans die from coronary artery disease-related heart attacks. Based on this most recent study, if every American optimized their vitamin D status, the number of deaths prevented from this kind of heart attack would be 92,500. To put the number of lives saved in context, tens of millions of dollars are being spent to advertise that Lipitor® reduces heart attacks by 37%. This is certainly a decent number, but not when compared with how many lives could be saved by vitamin D. According to the latest study, men with the higher vitamin D levels had a 142% reduction in heart attacks."

Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. Cranney A, Weiler HA, O'Donnell S, Puil L. Am J Clin Nutr. 2008 Aug;88(2):513S-519S. Review. PMID: 18689393 We found inconsistent evidence of an association between serum 25-hydroxyvitamin D [25(OH)D] concentration and bone mineral content in infants and fair evidence of an association with bone mineral content or density in older children and older adults. The evidence of an association between serum 25(OH)D concentration and some clinical outcomes (fractures, performance measures) in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH)D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher doses of vitamin D.

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. Viljakainen HT, Natri AM, Kärkkäinen M, Huttunen MM, Palssa A, Jakobsen J, Cashman KD, Mølgaard C, Lamberg-Allardt C. J Bone Miner Res. 2006 Jun;21(6):836-44. PMID: 16753014 doi: 10.1359/jbmr.060302 We conclude that the current vitamin D recommendation for adolescent girls, at least in the northern latitudes, is too low to ensure sufficient vitamin D status during winter. Intake of vitamin D at rates of 10-15 μg/day aids to maintain stable S-25(OH)D concentrations during winter. vitamin D induced BMC augmentation by decreasing bone resorption, but not affecting bone formation, which was reflected by the biochemical markers of bone turnover. Optimizing bone mineral gain in adolescence is crucial to the prevention of osteoporosis later in life. Increasing vitamin D intake to 10-15 μg/day aids in attaining this goal.

Vitamin D Toxicity Fears Unwarranted Is vitamin D toxic? Not if we take the same amount nature intended when we go out in the sun. Vieth R. vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842-56. Vieth attempted to dispel unwarranted fears in medical community of physiological doses of vitamin D in 1999 with his exhaustive and well-written review. D-Lite, Renew, & SunSplash UV/Tanning Systems Sunsplash Tanning System Is toxicity a concern for you? If so, then increase your levels the way nature intended, with ultraviolet B light! His conclusions: fear of vitamin D toxicity is unwarranted, and such unwarranted fear, bordering on hysteria, is rampant in the medical profession. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001 Feb;73(2):288-94. Even Ian Monroe, the chair of the relevant IOM committee, wrote to the Journal to compliment Vieth's work and to promise his findings will be considered at the time of a future Institute of Medicine review. Munro I. Derivation of tolerable upper intake levels of nutrients. Letter, Am J Clin Nutr. 2001;74:865. That was more than two years ago.

Vitamin D and cancer mini-symposium: the risk of additional vitamin D. Vieth R. Ann Epidemiol. 2009 Jul;19(7):441-5. Epub 2009 Apr 11. Review. PMID: 19364661 Conclusion The results of well-conducted trials of vitamin D lead to the conclusion that the current U.S. National Academy of Sciences-Institute of Medicine upper limit for vitamin D intake of 2000IU per day 1, 37 is excessively conservative. That intake would raise serum 25(OH)D by an average of about 50 nmol/L (20 ng/mL), well within the safe range of serum 25(OH)D concentrations that extends to 500 nmol/L (200 ng/mL). Intake of 4,000IU per day would raise serum 25(OH)D by an average of about 100 nmol/L (40 ng/mL). Even prolonged physiologic-replacement intake of 10,000IU per day of vitamin D3 would pose no known risk of adverse effects in virtually all adults.