New Medical Study Challenges Concept of Vitamin D Deficiency

[Ezliving_Jim]

New Results Challenge Concept of Vitamin D Deficiency

Low blood levels of vitamin D have long been associated with disease, and the assumption has been that vitamin D supplements may protect against disease.

However, this new research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D may be actually a result of the disease process. Supplementation may make the disease worse.

In a report published online in advance of February's issue of the journal BioEssays, Trevor Marshall, Ph.D., professor at Australia’s Murdoch University School of Biological Medicine and Biotechnology, explains how increased vitamin D intake affects much more than just nutrition or bone health. The paper explains how the Vitamin D Nuclear Receptor (VDR) acts in the repression or transcription of hundreds of genes, including genes associated with diseases ranging from cancers to multiple sclerosis.

"The VDR is at the heart of innate immunity, being responsible for expression of most of the antimicrobial peptides, which are the body’s ultimate response to infection," Marshall said.

"Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics of chronic disease, such as heart disease and obesity, are just getting worse."

"Our disease model has shown us why low levels of vitamin D are observed in association with major and chronic illness," Marshall added. "Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune system so that the body cannot fight disease and infection effectively."

Marshall's research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine.

Instead of a positive effect on gene expression, Marshall reported that his own work, as well as the work of others, shows that quite nominal doses of ingested vitamin D can suppress the proper operation of the immune system.

It is a different metabolite, a secosteroid hormone called 1,25-dihydroxyvitamin D, which activates the VDR to regulate the expression of the genes.

Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to indicate vitamin D status.

Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse.

"Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune," said J.C. Waterhouse, Ph.D., lead author of a book chapter on vitamin D and chronic disease (1).

"We have found that vitamin D supplementation, even at levels many consider desirable, interferes with recovery in these patients."

"We need to discard the notion that vitamin D affects a disease state in a simple way," Marshall said. "Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect between vitamin D supplementation and disease. The comprehensive studies are just not showing that supplementary vitamin D makes people healthier."

Trevor Marshall is currently executive director of Autoimmunity Research, Inc., a 501(c)(3) non-profit organization chartered in California. Its mission is to conduct scientific research into the cause and cure of disease, and to educate physicians and the public on science related to disease. More information can be obtained from http://AutoimmunityResearch.org


Source

[solarmeter®]

The TRUTH and rebuttle to this garbage:

January 22, 2008


The health benefits of vitamin D supplementation and fortification greatly outweigh the health risks

William B. Grant, Ph.D.,1 Cedric F. Garland, Dr. P.H., F.A.C.E.2


1 Sunlight, Nutrition, and Health Research Center (SUNARC)
P.O. Box 641603
San Francisco, CA 94164-1603, USA
www.sunarc.org
wbgrant@infionline.net
1-415-409-1980 – voice and fax (call first)


2Department of Family and Preventive Medicine 0631C, University of California San Diego, La Jolla, CA


Draft version
For: BioEssays as a letter to the editor (already looking for it)

Text: 606 (600 permitted)

References: 10




In his recent essay, Trevor G. Marshall explores how vitamin D supplementation may be contributing to the current epidemics of obesity and chronic disease [1]. Unfortunately, he has overlooked many important papers that disagree with his hypothesis. This letter points out some of the omissions.

The health benefits of vitamin D3 have been reviewed recently [2]. The benefits for bone health have been known for nearly a century. Benefits for cancer, infectious diseases, autoimmune diseases, and metabolic diseases have been identified in the past three decades.

Starting in the 1980s, largely observational evidence mounted that solar ultraviolet-B (UVB) irradiance and vitamin D reduce the risk of many types of cancer [3]. Based on observational studies, it is estimated that 1500 and 3600 International Units (IU) of vitamin D3 are required for a 50% reduction in risk of colorectal and breast cancer, respectively [4]. A recent randomized, double-blind, placebo-controlled study involving post-menopausal women in Nebraska found a 77% reduction in all-cancer incidence between the ends of the first and fourth years [5], thereby adding strong support to the observational studies.

As mentioned in [1], vitamin D enhances the innate immune system through induction of human cathelicidin, LL-37. LL-37 fights both bacterial and viral infections. A recent post-hoc analysis of vitamin D3 supplementation for post-menopausal women living in New York State found substantial benefits in reducing the common cold and influenza for 800 IU/day, and very strong benefits for 2000 IU/day [6]. Benefits also appear to be strong for septicaemia [Grant, submitted] and enteric viral infections such as norovirus [Grant, submitted], both of which are more common in winter than in summer.

Autoimmune diseases appear to arise from an improper immune response to viral infections. Since LL-37 reduces the risk of viral infections, it follows that LL-37 also reduces the risk of autoimmune diseases such as multiple sclerosis. The well-known increase in prevalence of multiple sclerosis with increasing latitude supports this hypothesis.

There is also a growing body of literature that low vitamin D status is a risk factor for many metabolic diseases including hypertension, type 2 diabetes, and cardiovascular disease [2]. A recent observational study found that vitamin D deficiency is associated with incident cardiovascular disease [7].

Admittedly there are some cases where vitamin D supplementation may be contraindicated. One of these cases is granulomatous diseases such as sarcoidosis where local production of 1,25-dihydroxyvitamin D (calcitriol) can leak into the serum and dysregulate calcium metabolism [8].

The current vitamin D3 fortification of food in the United States contributed 250-300 IU/day to the average American person. This amount is too low to have much of a beneficial effect on cancer. Intake or production of vitamin D3 of between 1000 and 2000 IU/day seems required for optimal health, and will raise serum 25-hydroxyvitamin D (calcidiol) levels to 40-60 ng/mL [4,6,9]. There have not been more prospective vitamin D supplementation studies for the simple reason that there is little profit to be made from selling vitamin D3 (a year’s supply of 1500 IU/day costs less than $20 U.S.). However, with the very positive benefits found in several recent studies, there should be more studies reported in the near future. In the mean time, most people will obtain a health benefit from increased vitamin D3 fortification and supplementation.

The rising prevalence of obesity in the United States can be traced to two primary factors: replacing fat with simple carbohydrates in processed food and the farm subsidy program for corn and soybeans in particular, which leads to overproduction of energy-dense foods [10].

Disclosure
WBG receives funding from the UV Foundation (McLean, VA), the Vitamin D Society (Canada), and the European Sunlight Association.

References
1. Marshall TG. Vitamin D discovery outpaces FDA decision making. Bioessays. 2008;30(2):173-182.
http://TrevorMarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf
2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.

3. 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;96(2):252-61.

4. Garland CF, Grant WB, Mohr SB, Gorham ED, Garland FC. What is the dose-response relationship between vitamin D and cancer risk? Nutr Rev. 2007;65(8 Pt 2):S91-5.

5. Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007;85(6):1586-91.

6. Aloia JF, Li-Ng M. Re: epidemic influenza and vitamin D. Epidemiol Infect. 2007;135(7):1095-6; author reply 1097-8.

7. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D Deficiency and Risk of Cardiovascular Disease. Circulation. 2008 Jan 7; [Epub ahead of print]

8. Hewison M, Burke F, Evans KN, Lammas DA, Sansom DM, Liu P, Modlin RL, Adams JS. Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease. J Steroid Biochem Mol Biol. 2007;103(3-5):316-21.

9. Cannell J, Hollis B, Zasloff M, Heaney R. Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother. 2008;9(1):107-118.

10. Pollan M. The Omnivore’s Dilemma; Natural History of Four Meals. Penguin Press, New York. 2006. 430 pp.

Reserve:

Falk S, Kratzsch J, Paschke R, Koch CA. Hypercalcemia as a result of sarcoidosis with normal serum concentrations of vitamin D. Med Sci Monit. 2007 Nov;13(11):CS133-136.

Grant WB, Garland CF. A critical review of studies on vitamin D in relation to colorectal cancer. Nutr Cancer. 2004;48(2):115-23.

Grant WB. Hypothesis-Ultraviolet-B irradiance and vitamin D reduce the risk of viral infections and thus their sequelae, including autoimmune diseases and some cancers. Photochem Photobiol. 2008 Jan 7; [Epub ahead of print]

Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets. 2007;11(8):993-1004.

Mullin GE, Dobs A. Vitamin D and its role in cancer and immunity: a prescription for sunlight. Nutr Clin Pract. 2007 Jun;22(3):305-22.


Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B. Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr. 2006 Jul;84(1):18-28.

Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005 May 11;293(18):2257-64. Review.




Med Sci Monit. 2007 Nov;13(11):CS133-136.Links
Hypercalcemia as a result of sarcoidosis with normal serum concentrations of vitamin D.

Falk S, Kratzsch J, Paschke R, Koch CA.
Division of Endocrinology and Nephrology, University of Leipzig, Leipzig, Germany.
BACKGROUND: Hypercalcemia can occur in patients with granulomatous disorders such as sarcoidosis, and is commonly related to high serum 1,25-dihydroxyvitamin D (OHD) concentrations. CASE REPORT: We here report a 68-year-old man with a history of mild renal insufficiency who presented with hypercalcemia (serum calcium of 3.11 mmol) and normal 1,25-OHD levels (38 pg/ml, RIA/IDS, Boldon, UK, measuring both 1,25-OH D2 and D3). Imaging and laboratory investigations were suggestive of sarcoidosis. After hydration and prednisone therapy (40 mg/day) for 7 days, serum calcium dropped to 2.7 mmol and 1,25-OHD levels to 13.4 pg/ml. Six weeks after prednisone therapy, serum calcium was 2.41 mmol (normal) and 1,25-OHD 6.2 pg/ml (low). Computed tomography of the chest showed shrinkage of the right hilar mass. CONCLUSIONS: This case illustrates that hypercalcemia can occur in granuloma-forming disorders such as sarcoidosis in the setting of inappropriately normal (and not elevated) 1,25-OHD levels. Contributing factors may include dehydration, increased uptake of oral calcium and/or decreased calcium excretion, especially in mild renal insufficiency. Therapy of choice are hydration and glucocorticoid (prednisone) therapy. In this setting, prednisone may lead to a decline of activated mononuclear cells (in the lung and lymph nodes) that are able to produce extrarenal PTH-independent 1,25-OHD.

[Ezliving_Jim]

...

[Ezliving_Jim]

The Marshall Protocol and other fairy tales


True to form, Dr. John Cannell has published yet another wonderfully insightful Vitamin D Newsletter.

One item caught my eye, a response to a question about the Marshall Protocol. I, like Dr. Cannell, was inundated with questions about this so-called protocol, which amounts to little more than the unfounded speculations of a non-physician, actually someone not even involved in health care.

In all honesty, I blew the whole issue off after I read Dr. Marshall's rants. They smack of pure quackery, though from somebody who clearly has a command of scientific lingo. To Dr. Cannell's credit, he took the time and effort to construct a rational response in the latest issue of the newsletter. I reproduce his response here:



Dear Dr. Cannell:

I understand Dr. Marshall conducted a study and found vitamin D is bad for you. What kind of study did he do?

Mary, Minneapolis, Minnesota


Dear Mary:

I have been inundated with letters asking about Professor Marshall's recent "discovery." Some have written that to say they have stopped their vitamin D and are going to avoid the sun in order to begin the "Marshall protocol." The immediate cause of this angst is two publications, a press article in Science Daily about Professor Marshall's "study" (which is no study but simply an opinion) in BioEssays. Dr. Trevor Marshall has two degrees, both in electrical engineering. Before I begin, I want to again remind you that I am a psychiatrist who works at a state mental hospital. In my duty to full disclosure, I must say that I have known a lot of psychiatrists in my life and a few electrical engineers. If I knew nothing else of a disagreement between two people but their professions, I would believe the electrical engineer, not the psychiatrist.

In reading his two articles, Dr. Marshall's main hypotheses are simple. (1) Vitamin D from sunlight is different than vitamin D from supplements. (2) Vitamin D is immunosuppressive and the low blood levels of vitamin D found in many chronic diseases are the result of the disease and not the cause. (3) Taking vitamin D will harm you, that is, vitamin D will make many diseases worse, not better. If you read his blog, you discover that the essence of the Marshall protocol is: "An angiotensin II receptor blocker medication, Benicar, is taken, and sunlight, bright lights and foods and supplements with vitamin D are diligently avoided. This enables the body's immune system, with the help of small doses of antibiotics, to destroy the intracellular bacteria. It can take approximately one to three years to destroy all the bacteria." That is, Dr. Marshall has his "patients" become very vitamin D deficient.

Again, Dr. Marshall conducted no experiment and published no study. He wrote an essay. He presented no evidence for his first hypothesis (sunlight's vitamin D is different than supplements). From all that we know, cholecalciferol is cholecalciferol, regardless if it is made in the skin or put in the mouth. His second hypothesis is certainly possible and that is why all scientists who do association studies warn readers that they don't know what is causing what. Certainly, when low levels of vitamin D are found in certain disease states, it is possible that the low levels are the result, and not the cause, of the disease. Take patients with severe dementia bedridden in a nursing home. At least some of their low 25(OH)D levels are likely the result of confinement and lack of outdoor activity. However, did dementia cause the low vitamin D levels or did low 25 (OH)D contribute to the dementia? One way to look at that question is to look at early dementia, before the patient is placed in a nursing home. On the first day an older patient walks into a neurology clinic, before being confined to a nursing home, what is the relationship between vitamin D levels and dementia? The answer is clear, the lower your 25(OH)D levels the worse your cognition.

Wilkins CH, Sheline YI, Roe CM, Birge SJ, Morris JC. Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.

Przybelski RJ, Binkley NC. Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007 Apr 15;460(2):202-5. Epub 2007 Jan 8.

These studies suggest that the low 25(OH)D levels are contributing to the dementia but do not prove it. Only a randomized controlled trial will definitively answer the question, a trial that has not been done. So you will have to decide if vitamin D is good for your brain or not. Dr. Marshall seems to be saying demented patients should lower their 25(OH)D levels. Keep in mind, an entire chapter in Feldman's textbook is devoted to the ill effects low vitamin D levels have on brain function.

Brachet P, et al. Vitamin D, a neuroactive hormone: from brain development to pathological disorders. In Feldman D., Pike JW, Glorieux FH, eds. Vitamin D. San Diego : Elsevier, 2005.

It is true that in some diseases, high doses of vitamin D may be harmful. For example, in the early part of last century, the AMA specifically excluded pulmonary TB from the list of TB infections that ultraviolet light helps. They did so because many of the early pioneers of solariums reported that acutely high doses of sunlight caused some patients with severe pulmonary TB to bleed to death. Thus, these pioneers developed very conservative sun exposure regimes for pulmonary TB patients in which small areas of the skin were progressively exposed to longer and longer periods of sunlight. Using this method, sunlight helped pulmonary TB, often to the point of a cure. Furthermore, it is well known that sunlight can cause high blood calcium in patients with sarcoidosis. In fact, sarcoidosis is one of several granulomatous diseases with vitamin D hypersensitivity where the body loses its ability to regulate activated vitamin D production, causing hypercalcemia.

Cronin CC, et al. Precipitation of hypercalcaemia in sarcoidosis by foreign sun holidays: report of four cases. Postgrad Med J. 1990 Apr;66(774):307-9.

Furthermore, although medical science is not yet convinced, some common autoimmune diseases may have an infectious etiology. I recently spoke at length with a rheumatologist who suffers from swollen and painful joints whenever he sunbathes or takes high doses of vitamin D. As long as he limits his vitamin D input his joints are better. To the extent vitamin D upregulates naturally occurring antibiotics of innate immunity, sunlight or vitamin D supplements may cause the battlefield (the joints) to become hot spots. I know of no evidence this is the case but it is certainly possible.

However, If Dr. Marshall's principal hypothesis is correct, that low vitamin D levels are the result of disease, then he is saying that cancer causes low vitamin D levels, not the other way around. The problem is that Professor Joanne Lappe directly disproved that theory in a randomized controlled trial when she found that baseline vitamin D levels were strong and independent predictors of who would get cancer in the future. The lower your levels, the higher the risk. Furthermore, increasing baseline levels from 31 to 38 ng/ml reduced incident cancers by more than 60% over a four year period. Therefore, advising patients to become vitamin D deficient, as the Marshall protocol clearly does, will cause some patients to die from cancer.

Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr. 2007 Jun;85(6):1586-91.

I will not write again about Dr. Marshall's theories. No one in the vitamin D field takes him seriously. Personally, I admire anyone willing to swim against the tide and raise alternative theories. I have done the same with influenza and autism. However, I agree with the New York Times, An Oldie Vies for Nutrient of the Decade and Jane Brody's conclusion, "In the end, you will have to decide for yourself how much of this vital nutrient to consume each and every day and how to obtain it." I agree. You will have to decide for yourself.

John Cannell, MD
The Vitamin D Council

Source: http://heartscanblog.blogspot.com/20...iry-tales.html