European regulators recognize effects of vitamin D beyond bone health

To date EFSA (the European Food Safety Agency), has published positive opinions on article 13.1 health claims relating to beneficial effects of vitamin D supplements not only on bones and teeth, but also relating to muscles, immunity, inflammation, and reproduction. * Yet the United States' Institute of Medcicine (IOM) committee did not reach similar conclusions and therefore did not consider the need for amounts higher than needed just for bone health when recently resetting the recommended and upper limits for vitamin D. (* from nutraingredients.com). For more on the FDA decision, see:
http://honestnutrition.blogspot.com/2010/11/us-increases-recommendations-for.html

Here's what the EFSA has published about these positive benefits (I bolded some text to highlight these points):


"The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin D and contribution to the normal function of the immune system and healthy inflammatory response, and maintenance of normal muscle function."
http://www.efsa.europa.eu/en/scdocs/scdoc/1468.htm

"The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin D and maintenance of normal bone and teeth, absorption and utilisation of calcium and phosphorus and normal blood calcium concentrations, and normal cell division."
http://www.efsa.europa.eu/en/scdocs/scdoc/1227.htm

U.S. Increases Recommendations for Vitamin D Intake but Misses the Mark

U.S. Increases Recommendations for Vitamin D Intake but Misses the Mark

As you probably know from news reports, the recommendations for individual consumption of vitamin D has now increased, as has the tolerable Upper Limit (UL) that indicates a higher intake level at which the vast majority of people will not suffer any unpleasant side effects. But these recommendations are controversial for being too conservative, and at the same time the report has been sensationalized in the popular media with an inappropriate emphasis on possible side effects of megadoses.

The Institute of Medicine (IOM), the health arm of the National Academy of Sciences, is an independent, nonprofit organization that works outside of government to provide unbiased and authoritative advice to decision makers and the public. Through more than three dozen sets of guidelines, known as Dietary Reference Intakes (DRIs), IOM provides estimates of the amounts of nutrients that individuals need to consume each day. Health care professionals and policy makers, including federal nutrition officials who develop nutrition programs as well as the food industry, rely on this guidance from the IOM. The reference numbers that you see on food and dietary supplement labels, such as Daily Values (DV), DRIs, and Recommended Daily Allowances (RDAs), are generated by IOM. (1) These values are also utilized by some foreign governments as authoritative references on which to base their own food and supplement regulations.

The good news is that, in a report issued by IOM on November 30, 2010, the RDA has now increased by 50% (from 400 IU to 600 IU) and the tolerable Upper Limit has now doubled (from 2,000 IU to 4,000 IU). Also, the RDA for adults over 71 years old has increased to 800 IU daily. (2) This means that the new recommendations are often higher than the 400 IU that is found in a typical multivitamin or calcium+D formula, thus requiring additional supplementation to meet the RDA. And the leeway for safe use at the upper end is now double what it was before, making such supplementation at higher levels still within a margin generally accepted as safe; at least up to 4,000 IU, though as usual that number is deliberately set low and has a large safety margin.

IOM’s report stating that most Americans have adequate circulating levels of vitamin D is somewhat controversial, as it utilizes a standard of 20 ng/mL (equivalent to a measure of 50 nmol/L) (3) that is not universally accepted as adequate for optimal health by many modern vitamin D researchers. While that amount may adequately support bone health, which was (as usual) the primary focus of the IOM committee, there are vitamin D receptors on many other human cells and this vitamin reportedly plays an important role in cardiovascular disease (4), immune health (5), prostate and breast health (7), blood sugar metabolism (6), cancer prevention (7,8) , and a host of natural processes. One recent report stated that, “The desirable serum 25 (OH) D levels is at least 100 nmol/L, a level that has generally been found to provide most of the health benefits of vitamin D.” (9) This recommendation is twice as high as the new RDA, evidencing the controversial nature of IOM’s RDA process.

However, the IOM committee admittedly based its recommendations solely on vitamin D’s effects on bone health after reviewing numerous studies on other benefits and concluding that more study is required to generate the level of evidence that IOM requires to set its recommendations. Committee chair Catharine Ross was quoted as saying, “Amounts higher than those specified in this report are not necessary to maintain bone health.” (10) As the amount of science in these other areas grows, so should the levels recommended for general health. But statements such as that by Dr. Ross that “people don't need more than the amounts established in this report” refer only to bone health and should not be construed as denying the fact that other benefits at higher levels of intake have been reported, though not as consistently as the IOM committee would need to accept them as conclusive enough to revise its recommended levels upward.

Based on current research, natural health advocates typically recommend levels 50-100% higher than the IOM report recommends in order for people to obtain the full protective benefits of vitamin D, and many physicians who test for this vitamin ask their patients to meet or exceed that higher level. This is perhaps the most controversial part of the report, and I predict that a barrage of higher numbers appearing in medical reports as protective will force another overdue round of RDA changes in perhaps another 10-15 years. In my opinion, the IOM is always behind the times in the area of nutrient recommendations, being by nature super cautious. We dared to hope, but nobody really expected the IOM panel to accept the evidence of recent published review studies in medical journals and raise both the RDA and UL to the recommended five times their previous levels, and frankly we were not surprised that they didn't. These special panels are typically very conservative and hesitant to make dramatic changes, and are comprised with well-qualified general nutrition experts but not with experts in the particular area in question who might push for acceptance of higher levels.

People have already been taking over 2,000 IU daily, the old tolerable Upper Limit, without apparent harm and will probably continue to take over the new 4,000 IU UL as well. Clinical science indicates that higher levels are still quite safe, at least up to 10,000 IU daily for most adults. In 2007 a review published in the American Journal of Clinical Nutrition applied the same risk assessment methodology used by the Food and Nutrition Board (FNB) to derive a proposed revision of the safe Tolerable Upper Intake Level (UL) for vitamin D. (11) Noting an absence of toxicity in trials conducted in healthy adults that used a vitamin D dose ≥250 µg/d (up to 10,000 IU of vitamin D3), a new UL of 10,000 IU was confidently proposed, but was apparently not accepted by the IOM. Nor was the recommendation for a new RDA to be raised to 2,000 IU.

In fact, the 10,000 IU daily UL proposal may have been conservatively low; so what does that make the revised tolerable UL of only 4,000 IU? According to a report in the journal Nutrition Reviews, "The input needed for efficacy, in addition to typical food and cutaneous [sunlight] inputs, will usually be 1000-2000 IU/day of supplemental cholecalciferol [vitamin D3]. Toxicity is associated only with excessive supplemental intake (usually well above 20,000 IU/day)." (12) [Italicized words added for clarity]

Dietary supplement manufacturers already were not allowed to make disease claims on dietary supplements without (always reluctant) FDA approval, so the IOM’s report that vitamin D has not been proven to prevent various diseases is not news for them. However, consumers will continue to be exposed to positive reports on the vitamin and most will understand that just because it has not yet been "proven" to prevent certain diseases doesn't mean that it doesn't, especially at levels higher than needed purely for bone health, nor does it suggest that there is no supporting evidence that it still may be an important preventative factor.

The government standard of proof in the dietary supplement area has been frequently criticized and the FDA in fact has lost several federal court cases, where courts have ordered the agency to comply with the law allowing such claims where substantial evidence already exists for some supplements’ role in disease prevention (for example, selenium and cancer). (13,14) Of course, almost never is anything "proven" in a scientific field; theories rule most scientific endeavors. But that should not suffice to allow the government to muzzle legitimate science nor to prevent the public from taking natural nutrients at levels that they may require due to their own individual biochemistry and relevant environmental factors. In this case, the new RDA and UL are simply baby steps in the right direction, but perhaps the full knowledge of vitamin D’s health benefits is still in its infancy.

REFERENCES:

1. http://www.iom.edu/About-IOM.aspx Accessed November 30, 2010
2. Dietary Reference Intakes for Calcium and Vitamin D. Food and Nutrition Board, Institute of Medicine, National Academies. Released: November 30, 2010
3. http://ods.od.nih.gov/factsheets/VitaminD-Consumer/ Accessed November 30, 2010
4. Wallis DE, Penckofer S, Sizemore GW. The "sunshine deficit" and cardiovascular disease. Circulation. 2008 Sep 30;118(14):1476-85. Review. Erratum in: Circulation. 2009 Jun 2;119(21):e550. PubMed PMID: 18824654.
5. Cannell JJ, Zasloff M, Garland CF, Scragg R, Giovannucci E. On the epidemiology of influenza. Virol J. 2008 Feb 25;5:29. Review. PubMed PMID: 18298852; PubMed Central PMCID: PMC2279112.
6. de Boer IH. Vitamin D and glucose metabolism in chronic kidney disease. Curr Opin Nephrol Hypertens. 2008 Nov;17(6):566-72. Review. PubMed PMID: 18941348; PubMed Central PMCID: PMC2882033.
7. Skinner HG, Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS. Vitamin D intake and the risk for pancreatic cancer in two cohort studies. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1688-95. PubMed PMID: 16985031.
8. Garland CF, Garland FC, Gorham ED, Lipkin M, Newmark H, Mohr SB, Holick MF. The role of vitamin D in cancer prevention. Am J Public Health. 2006 Feb;96(2):252-61. Epub 2005 Dec 27. Review. PubMed PMID: 16380576; PubMed Central PMCID: PMC1470481.
9. Grant WB, Schwalfenberg GK, Genuis SJ, Whiting SJ. An estimate of the economic burden and premature deaths due to vitamin D deficiency in Canada. Mol Nutr Food Res. 2010 Aug;54(8):1172-81. PubMed PMID: 20352622.
10. http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=13050 Accessed November 30, 2010
11. Hathcock JN, Shao A, Vieth R, Heaney R. Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. Review. PubMed PMID: 17209171.
12. Heaney RP. Vitamin D: criteria for safety and efficacy. Nutr Rev. 2008. Oct;66(10 Suppl 2):S178-81. Review. PubMed PMID: 18844846.
13. http://www.emord.com/FDA_Agrees_to_Allow_Selenium_Qualified_Health_Claims.html Accessed November 30, 2010
14. http://www.kelleydrye.com/publications/client_advisories/0576 Accessed November 30, 2010

Folic Acid: Risks or Myths?

There are theoretical risks for isolated folic acid in high doses. But these supposed risks fly in the face of established science and are controversial, not at all conclusive. There is also confusion over the significance of the supposed risks of high dose isolated folic acid in test tube and animal studies which do not identify a danger for moderate level supplementation - or even higher dose supplementation if combined with multivitamins or vitamin B-12. In other words, if the theoretical risks do not reflect real world human activities and the way that people actually obtain essential vitamins from their diet, including supplementation, aren’t these improbable risks really irrelevant to us? On the other hand, these negative reports may stop people from taking essential vitamins in quite reasonable amounts even though they are known to promote human health. Published human clinical science has determined that folic acid can reduce birth defects and has been proven to do so. Clinical science has also found mechanisms by which folic acid can prevent cancers, as well as the theoretical possibility that very high doses given in isolation can stimulate colorectal cancers including prostate cancer. There is stronger evidence that taking B-12 or a multivitamin along with high folic acid actually reduces rates of prostate and colon cancers. For example, in one human clinical trial where food intake, blood and plasma levels of folic acid were considered, Multivitamin users had about 2/3 the risk of subsequent prostate cancer as Non-Multivitamin users; only the independent use of folic acid was considered a risk factor. The report concluded, “…on the whole, the biological and epidemiological evidence supports the potential for folate supplementation to prevent colorectal neoplasia in humans.” (Cole) This shows that single nutrient studies, especially if unpublished and not peer reviewed or subjected to subsequent comments by experts in the field, should not be given overinflated importance when they are merely preliminary studies that may conflict with more relevant published human clinical studies. In the case of such conflicts, the human clinicals should bear more weight and be seen as more convincing, especially those that mimic the full range of variables (nutrients) in the human diet. Folic acid itself is considered non-toxic. Also, “data from in vitro and in vivo studies indicate that folic acid is not genotoxic [damaging to genetic material]”. (UK Food Standards Agency) There have been reports of levels as high as 50,000 micrograms per day given with no signs of toxicity in humans. There are accepted problems associated with levels exceeding 5,000 micrograms a day, which resulted in a far more conservative Upper Limit of 1,000 micrograms daily being set. This effect has been demonstrated in patients suffering from pernicious anemia taken off of their successful medicine (vitamin B-12), which was replaced by 5,000 mcg/day of folic acid. The substitution of one vitamin for another was unsuccessful in treating pernicious anemia, but did mask some symptoms. This test – and a large safety margin - provided the rationale given for the current Upper Limit. But it does not logically imply danger to those who are not severely anemic and who obtain B-12 in adequate amounts. (Oakley) It is very uncommon for people to take folic acid singly in doses of thousands of micrograms daily, but this is the method which test tube and animal studies often use. Overemphasizing unproven cancer risks requires ignoring valid studies showing reductions of cancers by taking folic acid and multivitamins. Needlessly scaring people from taking their vitamins, which have in human clinical trials shown significant improvements in birth defect and cancer rates, is not helpful to our common goal of protecting public health. Neil E. Levin, CCN, DANLA QUOTES & REFERENCES: Dr. Gideon Koren, director of the Motherisk Program at the Hospital for Sick Children in Toronto , note that rates of birth defects such as spina bifida and cancers such as neuroblastoma have plummeted since folic acid supplementation was begun. He believes that the known benefits outweigh theoretical risks. "I think it is very important to remember that the scares about cancer are mostly from animal studies and laboratory studies, not from human experience," he says. "We are still awaiting to see such human experience." http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090417/folic_acid_090418/20090419?hub=SciTech Health Canada recommends all women of childbearing age take 0.4 mg of folic acid a day, but says taking more than 1 mg a day of folic acid without the advice of a doctor is not recommended. "We continue to encourage all women who could become pregnant to take a daily supplement," the agency says on its website. "We caution against taking more than one multivitamin tablet a day, as excess amounts of certain vitamins can be toxic." http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20090417/folic_acid_090418/20090419?hub=SciTech “All women who could become pregnant should take a multivitamin containing 0.4 mg of Folic Acid every day. To help reduce the risk of NTDs, you should start taking the vitamin supplement at least three months before you get pregnant and continue through the first three months of your pregnancy. Talk to your health professional to find the supplement best for you…If you have had a previous pregnancy affected by an NTD or have a family history of this problem, see your doctor. You may be advised to take a higher dosage of Folic Acid. If you have diabetes, obesity or epilepsy, you may be at higher risk of having a baby with an NTD, and you should see your doctor before planning pregnancy… Do not take more than one daily dose of vitamin supplement as indicated on the product label. Increasing your dose of Folic Acid beyond 1 mg per day without the advice of a doctor is not recommended.” (Public Health Agency of Canada , 2/27/08; http://www.phac-aspc.gc.ca/fa-af/index-eng.php) The NIH’s Office of Dietary Supplement reports on the prevention of cancer with the use of supplemental folic acid as part of a multivitamin: “Over 88,000 women enrolled in the Nurses' Health Study who were free of cancer in 1980 were followed from 1980 through 1994. Researchers found that women ages 55 to 69 years in this study who took multivitamins containing folic acid for more than 15 years had a markedly lower risk of developing colon cancer.” (Giovannucci E, et al. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129:517-24; http://ods.od.nih.gov/factsheets/folate.asp) Cole BF, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. Polyp Prevention Study Group. JAMA. 2007 Jun 6;297(21):2351-9. PMID: 17551129 Figueiredo JC, et al. Folic acid and risk of prostate cancer: results from a randomized clinical trial. J Natl Cancer Inst. 2009 Mar 18;101(6):432-5. Epub 2009 Mar 10. PMID: 19276452 Folic Acid, CASRN: 59-30-3. NLM TOXNET Hazardous Substances Database accessed online 28 March, 2009. http://toxnet.nlm.nih.gov/cgi-bin/sis/search/r?dbs+hsdb:@term+@na+folic+acid Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, McQueen MJ, Probstfield J, Fodor G, Held C, Genest J Jr; Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. N Engl J Med. 2006 Apr 13;354(15):1567-77. Epub 2006 Mar 12. Erratum in: N Engl J Med. 2006 Aug 17;355(7):746. PMID: 16531613 Oakley GP Jr. When will we eliminate folic acid-preventable spina bifida? Epidemiology. 2007 May;18(3):367-8. PMID: 17435446 http://www.food.gov.uk/multimedia/pdfs/evm_folicacid.pdf