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How much vitamin D3 do the elderly need? Viljakainen HT, Palssa A, Kärkkäinen M, Jakobsen J, Lamberg-Allardt C. J Am Coll Nutr. 2006 Oct;25(5):429-35. PMID: 17031013 Conclusions: A clear dose response was noted in S-25-OHD to different doses of vitamin D3. The recommended dietary intake of 15 µg is adequate to maintain the S-25-OHD concentration around 40-55 nmol/L during winter, but if the optimal S-25-OHD is higher than that even higher vitamin D intakes are needed. Interestingly, subjects with lower vitamin D status at baseline responded more efficiently to supplementation than those with more adequate status

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

Together, the earlier data and the data of Heaney et al indicate that an oral dose of vitamin D2 or vitamin D3 would lead to a comparable increase in circulating 25(OH)D concentrations in children and adults when the initial 25(OH)D3 concentrations in the groups are similar and when equivalent oral vitamin D doses expressed per kilogram body weight/d are given. Serum 25-hydroxyvitamin D response to oral vitamin D intake in children. Zittermann A. Am J Clin Nutr. 2003 Sep;78(3):496-7. PMID: 12936937

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.

Vitamin D is safe when used in physiological doses (those used by Nature). Physiological doses are 3,000-5,000 IU/day, from all sources (sun, diet and supplements). Should hypercalcemia occur with such doses, it is due to vitamin D hypersensitivity syndrome, not vitamin D toxicity. Vitamin D hypersensitivity syndromes include conditions such as primary hyperparathyroidism, occult cancers (especially lymphoma) or granulomatous disease (especially sarcoidosis). In such cases, treatment of vitamin D deficiency should be done under the care of a knowledgeable physician. A serum 25(OH)D, serum 1,25(OH)D, PTH and SMA will lead the clinician in the right direction.

Randomized comparison of the effects of the vitamin D3 adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients. Vieth R, Kimball S, Hu A, Walfish PG. Nutr J. 2004 Jul 19;3:8. PMID: 15260882 doi:10.1186/1475-2891-3-8 CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D3 in patients who needed additional vitamin D.

Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Kovacs CS. Am J Clin Nutr. 2008 Aug;88(2):520S-528S. Review. PMID: 18689394 Dosing recommendations for women during pregnancy and lactation might be best directed toward ensuring that the neonate is vitamin D-sufficient and that this sufficiency is maintained during infancy and beyond. A dose of vitamin D that provides 25(OH)D sufficiency in the mother during pregnancy should provide normal cord blood concentrations of 25(OH)D. Research has shown that during lactation, supplements administered directly to the infant can easily achieve vitamin D sufficiency; the mother needs much higher doses (100 µg or 4000 IU per day) to achieve adult-normal 25(OH)D concentrations in her exclusively breastfed infant. In addition, the relation (if any) of vitamin D insufficiency in the fetus or neonate to long-term nonskeletal outcomes such as type 1 diabetes and other chronic diseases needs to be investigated.

Benefits of Vitamin D Supplementation Joel M. Kauffman, Ph.D. Journal of American Physicians and Surgeons Volume 14 Number 2 - Summer 2009 Clinical trials show that vitamin D supplementation at higher levels than previously recommended is beneficial for many conditions. It decreases the frequency of falls and fractures, helps prevent cardiovascular disease, and reduces symptoms of colds or influenza. Benefits are also seen in diabetes mellitus, multiple sclerosis, Crohn disease, pain, depression, and possibly autism. Sunlight does not cause an overdose of vitamin D production, and toxicity from supplementation is rare. Dose recommendations are increasing, but appear to be lagging the favorable trial results. A number of common drugs deplete vitamin D levels, and others may limit its biosynthesis from sunlight. People with adequate levels from sun exposure will not benefit from supplementation. While dietary intake is helpful, supplementation is better able to raise serum 25-hydroxyvitamin D , the major circulating metabolite, to the level now thought adequate, 30-50 ng/mL. Where there is inadequate daily sun exposure, oral doses of 1,000-2,000 IU/d are now considered routine, with much higher doses (up to 50,000 IU) for rapid repletion now considered safe.

"THURSDAY, Dec. 17 (HealthDay News) -- In a surprise finding, Canadian researchers report that the immediate effect of the fish oil fatty acids that are good for the heart is a short-term increase in blood fats and the molecules that help them form clots. "We were surprised to find that the acute response has some potentially negative effects in comparison to what you might expect from chronic, long-term intake," said Lindsay E. Robinson, an associate professor of nutrition at the University of Guelph, and leader of the group reporting the finding in the January issue of the Journal of Nutrition. However, the study results shouldn't affect the current recommendation for eating more oily fish to get the omega-3 polyunsaturated acids that reduce the risk of blood clots that can cause heart attacks and stroke, Robinson said. "The recommendation to increase intake is very well-studied, and this doesn't change it," she said. And the effects were seen in a selected group of middle-aged men with metabolic syndrome, a combination of high blood pressure, obesity and elevated blood fat levels, Robinson noted. In the study, eight men had controlled intake of three regimens: high doses of omega-3 fatty acids, low doses of them and just plain water. Robinson and her colleagues measured several blood components involved in clotting, including fats and clotting factors such as plasminogen-activator inhibitor-1 (PAI-1) for the following eight hours. PAI-1 inhibits the destruction of blood clots, so high levels of it in the blood increase the risk of artery-blocking clots. The researchers found that both omega-3 fatty acid regimens increased blood fat and clotting factor activity. But the increase in clotting factor was greater for the higher doses of omega-3 fatty acids than for the lower intakes. Robinson said her group hopes to do further studies of the immediate effects of omega-3 fatty acid intake. "We need to look at the mechanisms, why blood lipid levels go up," she

"NEW YORK (Reuters Health) - Important news for seniors: A daily dose of vitamin D cuts your risk of falling substantially, researchers reported today. But not just any dose will do. "It takes 700 to 1000 international units (IU) of vitamin D per day and nothing less will work," Dr. Heike A. Bischoff-Ferrari, who directs the Center on Aging and Mobility at the University of Zurich, Switzerland, noted in an email to Reuters Health. Those recommendations - which are higher than those by the U.S. Institute of Medicine -- are based on the results of eight studies that looked at vitamin D supplements for fall prevention among more than 2,400 adults aged 65 and older. Falls were not notably reduced with daily doses of vitamin D lower than 700 IU. An analysis of all eight studies, posted online today in the British Medical Journal, add weight to several others which have shown that vitamin D improves strength and balance, and bone health in the elderly, the researchers note."

A phase 2 trial exploring the effects of high-dose (10,000 IU/day) vitamin D(3) in breast cancer patients with bone metastases. Amir E, Simmons CE, Freedman OC, Dranitsaris G, Cole DE, Vieth R, Ooi WS, Clemons M. Cancer. 2009 Nov 13. [Epub ahead of print] PMID: 19918922 DOI: 10.1002/cncr.24749 METHODS: Patients with bone metastases treated with bisphosphonates were enrolled into this single-arm phase 2 study. Patients received 10,000 IU of vitamin D3 and 1000 mg of calcium supplementation each day for 4 months. The effect of this treatment on palliation, bone resorption markers, calcium metabolism, and toxicity were evaluated at baseline and monthly thereafter. CONCLUSIONS: Daily doses of 10,000 IU vitamin D3 for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use. There did not appear to be a significant palliative benefit nor any significant change in bone resorption. Cancer 2010. © 2009 American Cancer Society.

Safety of vitamin D3 in adults with multiple sclerosis. Kimball SM, Ursell MR, O'Connor P, Vieth R. Am J Clin Nutr. 2007 Sep;86(3):645-51. PMID: 17823429 Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.

Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Am J Clin Nutr. 2003 Jan;77(1):204-10. Erratum in: Am J Clin Nutr. 2003 Nov;78(5):1047. PMID: 12499343

Benefit-risk assessment of vitamin D supplementation. Bischoff-Ferrari HA, Shao A, Dawson-Hughes B, Hathcock J, Giovannucci E, Willett WC. Osteoporos Int. 2009 Dec 3. [Epub ahead of print] PMID: 19957164 Conclusion Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina. Tau C, Ciriani V, Scaiola E, Acuña M. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):651-4. Epub 2007 Jan 25. PMID: 17257830 doi:10.1016/j.jsbmb.2006.12.027 These results disclosed that to prevent vitamin D deficiency for children at zones of risk at the south of our country, double supplementation of 100,000 IU of vitamin D during autumn and winter, would be adequate and safe.

"Lipoprotein(a), or Lp(a), is a problem area in coronary plaque reversal. While our current Track Your Plaque record holder for largest percentage reduction in heart scan score has Lp(a), it remains among the more troublesome lipoprotein patterns. One unique treatment for Lp(a) is high-dose omega-3 fatty acids from fish oil. While the data are relatively meager, there is one solid study from Lp(a) expert, Dr. Santica Marcovina of the University of Washington, called "The Lugalawa Study." In this unique set of observations, 1300 members of a Bantu tribe living in Tanzania were studied. What made this population unusual is the fact that two groups of Bantus lived under different circumstances. One group lived on Nyasa Lake (3rd largest lake in Africa and reputed to have the greatest number of species of fish of any lake in the world) and ate large quantities of freshwater fish providing up to 500 mg of omega-3s, EPA and DHA, per day. Another Bantu group lived away from the lake as farmers, eating a pure vegetarian diet without fish. "

Is a lower dose of vitamin D supplementation enough to increase 25(OH)D status in a sunny country? Pignotti GA, Genaro PS, Pinheiro MM, Szejnfeld VL, Martini LA. Eur J Nutr. 2009 Nov 28. [Epub ahead of print] PMID: 19946776 CONCLUSION: The dose given (400 IU/day) was not enough to achieve 25(OH)D concentration, considered optimal for bone health.

Synergistic anti-inflammatory effects of low doses of curcumin in combination with polyunsaturated fatty acids: docosahexaenoic acid or eicosapentaenoic acid. Saw CL, Huang Y, Kong AN. Biochem Pharmacol. 2010 Feb 1;79(3):421-30. Epub 2009 Sep 8. PMID: 19744468

Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration.\nYeom CH, Jung GC, Song KJ.\nJ Korean Med Sci. 2007 Feb;22(1):7-11.\nPMID: 17297243

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9. Epub 2008 Aug 4. PMID: 18678913 doi: 10.1073/pnas.0804226105