Is the healing power of Vitamin C too good to be true? Can this inexpensive and convenient vitamin improve and heal the toughest of ailments? 

by Thomas E. Levy, MD, JD

by Gert E. Schuitemaker, PhD

There are few subjects on which opinions are as divided as nutrition. Nearly everyone agrees: an excellent diet with lots of fruits and vegetables is healthy and will prevent many diseases. Such a diet is chock full of essential nutrients and antioxidants. Then, how come condemnation of supplemental antioxidants gets so much press coverage worldwide?

How antioxidants work

Written by Ron Hunninghake, M.D.

"...it takes much more than logic and clear-cut demonstrations to overcome the inertia and dogma of established thought." -- Irving Stone

Vitamin Supplement Safety Confirmed by America's Largest Database

(OMNS Jan 30, 2013) The new annual report of the American Association of Poison Control Centers shows zero deaths from multiple vitamins; zero deaths from vitamin A, niacin, vitamin B-6, vitamin D, or vitamin E.

Two people are alleged to have died from vitamin supplements in the year 2011, according to AAPCC's interpretation of the most recent information collected by the U.S. National Poison Data System. One death was allegedly because of vitamin C; the other supposedly because of "Other B-Vitamins." As the AAPCC report specifically indicates no deaths from niacin (B-3) or pyridoxine (B-6), that leaves folic acid, thiamine (B-1), riboflavin (B-2), biotin, and B-12 as the remaining B-vitamins that could be implicated. However, the safety record of these vitamins is extraordinarily good; no fatalities have been confirmed for any of them. Vitamin C is also an extraordinarily safe nutrient. No deaths have ever been confirmed from supplementation with vitamin C.

Even allowing that the AAPCC data is correct (and we do not), two deaths in a year associated with vitamins, nationwide, is a very small number. Well over half of the U.S. population takes daily nutritional supplements. Even if each of those people took only one single tablet daily, that makes 165,000,000 individual doses per day, for a total of over 60 billion doses annually. Since many persons take far more than just one single vitamin tablet, actual consumption is considerably higher, and the safety of nutritional supplements is all the more remarkable.

(OMNS Aug 8, 2012)

by Howard Straus

Controversy over Genetically Modified Organisms (GMOs) has been increasing in intensity.

(Orthomolecular Medicine News Service, June 11, 2012)

by Steve Hickey, PhD, Andrew W. Saul, PhD, and Robert G. Smith, PhD

(OMNS June 11, 2012) There is a global tendency to popularize pharmaceutical industry pseudoscience that harms patients and prevents health. Far from being critical, the media are easily taken in by corporate medicine. Two recent examples give food for thought. Like so many others in the media, Alex Hutchinson was misinformed about the underlying science when he wrote "Three Reasons to Reconsider Vitamin Pills." [1] Sometimes the lack of scholarship in medical research is astounding. A recent paper by María Martínez and colleagues illustrates this well. It is bizarrely titled "Dietary Supplements and Cancer Prevention: Balancing Potential Benefits Against Proven Harms." [2]

The media uncritically accept claims by the Cochrane Collaboration because it is a "gold-standard." However, Cochrane supports bad science because it accepts the methods and bias of corporate medicine. In this case, a review combined the results of 78 randomized trials, but in the selection of these trials ignored a larger set of data to give a required but biased answer. [1] One of the first lessons for a science student is not to select your data. When information is selected it is prone to bias because it doesn't represent the full data set. In this case, thousands of studies have provided a prior probability that vitamin supplements are safe and can prevent chronic disease. Further, the claim that large randomized interventional trials give the "strongest form" of medical data is simply wrong. There is little if any scientific support for this oft-repeated myth.

A "cargo cult" (i.e. obtaining value through magical rituals) has taken hold of medical science. [3] So-called evidence-based medicine looks like science, but fails to deliver rational results. Hutchinson reports that the size of the vitamin review included 297,000 people, which is supposed to give a sense of solidity and reliability from the law of large numbers. However, what we are not told is that large numbers are not appropriate, as these studies emphasize weaknesses (background noise) in the data. If you need a quarter of a million people to show an effect, that's a mighty small effect.

Top Vitamin D Papers of 2011
Dosage Recommendations and Clinical Applications

by William B. Grant, Ph.D.

(OMNS April 10, 2012) The biggest vitamin D story in 2011 was the report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine (IOM) [1]. This report was prepared during a two-year process by 14 nutrition experts, with funding from the U.S. Food and Drug Administration and the National Institutes of Health and Health Canada. The committee reviewed the evidence for beneficial and harmful effects of vitamin D, relying solely on randomized controlled trials (RCTs) of its liking for benefits, and prospective cohort studies for adverse effects. RCTs were considered to have the highest quality, with observational studies of moderate quality and ecological studies of very low quality. However, the case can be made that since solar UVB is the primary source of vitamin D for most people, observational and ecological studies are the most relevant and therefore are of high quality, and in fact, have provided most of the information on the health benefits of vitamin D. However, the committee appeared to have a bias of excluding RCTs on such outcomes as cancer and influenza incidence and effects during pregnancy that were not in line with its eventual recommendations. The only benefit the committee found for vitamin D was for bone health. The committee recommended 600 IU/d vitamin D and a serum 25(OH)D concentration (a precursor to the active form of vitamin D) of 20 ng/ml (50 nmol/l) for those aged 1-70 years, and 800 IU/d for those 71 years or older. One-third of Americans have serum 25(OH)D concentrations below 20 ng/ml. The consensus from a wide variety of studies for the optimal concentration is at least 30 ng/ml and more likely over 40 ng/ml based on observational studies. The committee also noted that some prospective studies found increased risk of some health outcomes for higher serum 25-hydroxyvitamin D [25(OH)D] concentrations. However, such studies are bedeviled by changes in serum 25(OH)D concentration during the follow-up period since only one value from the time of enrollment is used.

Recommendations Still Too Low

This report has been severely criticized by the vitamin D research community, with over 125 journal publications to date disagreeing with the recommendations. A representative paper stated: "The IOM recommendations for vitamin D fail in a major way on logic, on science, and on effective public health guidance. Moreover, by failing to use a physiological referent, the IOM approach constitutes precisely the wrong model for development of nutritional policy." [2]. The case could be made that the IOM committee, by setting the recommended dose so unreasonably low, is putting the U.S. population at greatly increased health risk. Further, much of the rest of the world's countries look to the IOM report for guidance, placing a major portion of the world's population at risk.

More recently, a committee of the U.S. Endocrine Society comprised of vitamin D researchers reviewed the evidence and issued their recommendations. They considered both skeletal and non-skeletal effects. They recommended 600-1000 IU/d vitamin D for those aged 1-18 years and 1500-2000 IU/d for those aged 19 years or older [3]. These doses are preferable because they have a reasonable likelihood of raising serum 25(OH)D concentrations above 30 ng/ml (75 nmol/l).

Pregnancy

Meanwhile, the evidence of beneficial effects of vitamin D continues to grow. One RCT ignored by the IOM committee was that of supplementing pregnant and nursing women with 4000 IU/d vitamin D3 [4]. The study was completed before the IOM report was completed and brought to the committee's attention, but was not yet published. Important findings from the study include that it took about 4000 IU/d to increase 25(OH)D concentrations to over 40 ng/ml. The study explained that at this concentration, 1,25-dihydroxyvitamin D concentrations reached equilibrium with 25(OH)D, and higher doses did not increase 1,25-dihydroxyvitamin D concentrations much more, which alleviated many concerns about overdoses. The study found no evidence of hypercalcemia or hypercalcuria even with these large doses. Further, this higher dose generated a sufficient concentration of unconverted vitamin D3 in breast milk that the nursing infant could produce its own 25(OH)D. The effects of vitamin D during fetal development are largely mediated through 1,25-dihydroxyvitamin D (the active form of vitamin D) binding to vitamin D receptors, which then regulate the expression of over 200 genes, upregulating about two-thirds, downregulating one-third.

Cancer

One of the important benefits of vitamin D is a reduction of cancer risk. There are many ecological observational studies and two RCTs supporting a role of vitamin D in reducing risk of about 15 types of cancer and increasing survival in about seven types of cancer. A meta-analysis of case-control and prospective studies for breast, colorectal and prostate cancer found that an increase of serum 25(OH)D concentration of 10 ng/ml was associated with a 15% reduction in colorectal cancer incidence, an 11% reduction in breast cancer incidence, but no effect for prostate cancer [5]. Ecological studies support a role of UVB in reducing risk of prostate cancer, so it could be that observational studies have not looked at the right period of life or serum 25(OH)D concentrations.

Another paper on women diagnosed with breast cancer found increased survival for those with higher serum 25(OH)D concentrations. In those with lower vitamin D concentrations, overall mortality rate increased by 8% while distant disease rates decreased by 14% per 10 nmol/l decrement in 25(OH)D [6].

HIV-AIDS

A study in the U.S. found those with HIV not using vitamin D supplements were very likely to be vitamin D deficient [7]. As vitamin D has important immune protection properties, this finding suggests that those with HIV or AIDS should be supplementing with vitamin D.

Dementia and Cognitive Impairment

A cross-sectional study in the U.S. found a significant inverse correlation between serum 25(OH)D concentration and cognitive impairment [8]. Since it was a cross-sectional study, the serum 25(OH)D concentration could be influenced by the disease state rather than vise versa. However, other studies suggest that low 25(OH)D concentrations are a risk factor for cognitive impairment and dementia.

Tuberculosis

A RCT study in the UK involving four doses of 2.5 mg (100,000 IU) adjunctive vitamin D in adults, raising serum 25 with pulmonary tuberculosis found a reduction in sputum conversion time of 36.0 days vs 43.5 days for the controls [9]. However, the effect depended on vitamin D receptor genotype. Those with TaqI or tt genotype had statistically significant reductions, while those with FokI genotype did not receive a benefit. This study indicates that vitamin D receptor alleles affect how effective vitamin D can be against infections.

Life Expectancy

A recent population study estimated, for the six geopolitical regions of the world the reduction in all-cause mortality rates from increasing mean serum 25(OH)D concentrations. [10]. The current understanding of the serum 25(OH)D-disease outcome relations for cancers, cardiovascular disease, respiratory infections, respiratory diseases, tuberculosis, diabetes mellitus, Alzheimer's disease, falls and fractures, meningitis, Parkinson's disease, maternal sepsis and hypertension, and multiple sclerosis was used in the calculations. Estimated reductions in mortality rates from increasing serum 25(OH)D from 20 ng/ml to over 40 ng/ml ranged from 7% for Africa to 17% for Europe. Since life expectancies varied by region, the estimated increase in life expectancy was about two years in all regions.

Supplements and Serum 25(OH)D

The relation between oral vitamin D intake and serum 25(OH)D concentration was explored based on individuals ordering 25(OH)D test kits [11]. The important finding was that there is a very large spread in the serum 25(OH)D concentration for any given oral intake: the value can be about 45 ng/ml either side of the regression fit to the data. Another recent paper based on serum 25(OH)D concentration measurements at six Veterans Administration Medical Centers found that serum 25(OH)D concentrations could not be predicted on readily identifiable factors [12]. These findings strongly suggests that those interested in achieving an optimal 25(OH)D concentration should have their serum 25(OH)D concentration measured after taking vitamin D supplements for a couple of months, and, preferably, both before dosing and again after dosing for four to six months. Also included in the paper was a graph showing that the increase in 25(OH)D is up to 12 ng/ml per 1000 IU/d for those with starting 25(OH)D concentrations near 5 ng/ml, dropping to less than 2 ng/ml for those with greater than 80 ng/ml.

While the evidence of beneficial effects of vitamin D continues to expand, the IOM committee members continue to defend their original report. Thus, it seems to be up to individuals and their doctors to review the evidence and respond as they see fit. For those interested in obtaining additional information, these websites may be helpful:

http://www.VitaminDCouncil.org
http://www.GrassrootsHealth.net
http://www.VitaminDWiki.com
http://www.pubmed.gov
http://www.scholar.google.com

The first two are organizations devoted to educating the public about vitamin D; the third is a resource trying to put online as much information about vitamin D as possible; the last two are sites where titles, abstracts, and, in some cases, complete papers on vitamin D can be found by use of search words.

Disclosure:

William B. Grant, Ph.D. is affiliated with the Sunlight, Nutrition and Health Research Center (SUNARC) and receives funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).

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References:

1. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-8.

2. Heaney RP, Holick MF. Why the IOM recommendations for vitamin D are deficient. J Bone Miner Res. 2011;26(3):455-7.

3. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2011;96(7):1911-30.

4. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011;26(10):2341-57.

5. Gandini S, Boniol M, Haukka J, Byrnes G, Cox B, Sneyd MJ, Mullie P, Autier P. Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer. 2011;128(6):1414-24.

6. Vrieling A, Hein R, Abbas S, Schneeweiss A, Flesch-Janys D, Chang-Claude J. Serum 25-hydroxyvitamin D and postmenopausal breast cancer survival: a prospective patient cohort study. Breast Cancer Res. 2011;13(4):R74.

7. Dao CN, Patel P, Overton ET, Rhame F, Pals SL, Johnson C, Bush T, Brooks JT; Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN) Investigators. Low vitamin D among HIV-infected adults: prevalence of and risk factors for low vitamin D Levels in a cohort of HIV-infected adults and comparison to prevalence among adults in the US general population. Clin Infect Dis. 2011;52(3):396-405.

8. Llewellyn DJ, Lang IA, Langa KM, Melzer D. Vitamin D and cognitive impairment in the elderly U.S. population. J Gerontol A Biol Sci Med Sci. 2011;66(1):59-65.

9. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet. 2011;377(9761):242-50.

10. Grant WB. An estimate of the global reduction in mortality rates through doubling vitamin D levels. Eur J Clin Nutr, 2011;65:1016-26.

11. Garland CF, French CB, Baggerly LL, Heaney RP. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res 2011;31(2):617-22.

12. Peiris AN, Bailey BA, Guha BN, Copeland R, Manning T. Can a model predictive of vitamin D status be developed from common laboratory tests and demographic parameters? South Med J. 2011;104(9):636-9.

Evidence-based medicine requires evidence before medicating. Fluoridation of water is not evidence-based. It has not been tested in well-controlled studies. Fluoridation of public water is a default medication, since you have to deliberately avoid it if you do not want to take it." ~ Andrew W. Saul

Editorial by Andrew W. Saul, Orthomolecular Medicine News Service

Oddly enough, the Journal of Orthomolecular Medicine has not published a single article on pizza. At least not so far. Maybe if it did, it would make the cut at Medline.

by Andrew W. Saul
Editor-In-Chief, Orthomolecular Medicine News Service

About 170 years ago our ancestors forced the repeal of licensing laws which had created a monopoly over the practice of medicine for orthodox physicians. Ordinary people, farmers, artisans, tradesmen and others got together and forced politicians to act on their behalf. They were tired of bloodletting, and harsh medications like mercury compounds that ruined their teeth and weakened their bodies. They opted for kinder and gentler alternatives with lower casualty rates, particularly the newly introduced homeopathy. They were impressed that tiny doses of medicine were able to cure cholera much better than the massive doses used by orthodox physicians.