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Immunosuppression and insufficient followup in vitamin D studies

One of the abiding weaknesses of studies on the effects of vitamin D on health is that researchers simply do not follow subjects consuming the secosteroid for a sufficient period of time. Instead, they tend to track subjects over the course of weeks, months, or one or two years, during the period of time when study participants are usually feeling the palliative effects of the steroid.

This practice is a mistake as it does not account for the long-term immunosuppressive effects of a steroid. For example, the U-shaped relationship between vitamin D levels and long-term outcome in large cohort 1)

Immunosuppression by high doses of vitamin D

The effects of vitamin D in various doses is only in this century becoming apparent.

In the February 2016 edition of JAMA Internal Medicine attention is drawn to two studies showing an increase in falls associated with high doses of vitamin D. A Cautionary Tale of Vitamin Supplements Retold

A previous RCT4 in women of the same age showed that 500 000 IU of vitamin D per year achieved serum 25(OH)D levels of at least 30 ng/mL in most participants but significantly increased risk of falls by 15% and fractures by 26%.

Steven R. Cummings, MD; Douglas P. Kiel, MD, MPH; Dennis M. Black, PhD, in Vitamin D Supplementation and Increased Risk of Falling

In a CBS interview on video (17 March, 2015) Dr David Agus discussed the finding that vitamin D was useless for lowering blood pressure. Supplementation was also found to be associated with more cancer and heart disease. “Nobody should be taking it…that's the data” said the doctor, who also drew attention to increased risk of bone fracture and kidney stone.

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Short-term and long-term effects of vitamin D

People who consume vitamin D through supplements or food are suppressing their innate immune response.2) In the absence of a robust immune response, fewer bacteria killed. As a consequence, inflammation declines as does the amount of toxins released into the tissues. This contributes to symptom relief and feelings of temporary well-being. Without knowing anything else, researchers might erroneously conclude that supplementing with vitamin D is therapeutic.

At a certain point, however, consuming the secosteroid starts to have an effect on those symptoms which researchers typically focus their attention. A person's pathogen load increases to the point such that it cannot be offset by a mitigated immune response. This tipping point occurs at different times for different patient groups. For someone who is young and has a robust immune response, it may take decades for chronic pathogens to escalate to the point where they become symptoms of disease. On the other hand, the time to experience a negative effect for a person who is sick with a chronic disease or elderly (and presumably has a higher bacterial load), is relatively shorter.

The failure to appreciate the molecular metabolism of vitamin D has unfortunate repercussions when it comes to interpreting the data for epidemiological studies.

Research with short-term followup

There are a number of studies, too many to review in the context of this article. Generally speaking, research noting a therapeutic effect of vitamin D tend to be short-term or in patients whose immune systems are yet to be suppressed.

A study out of Creighton University recently received attention, because the researchers found that vitamin D might lower the incidence of colorectal cancer.3) The length of the observation: only four years.

Jacques Rossouw at the National Institutes of Health criticized the finding. His group conducted a similar study that tracked the effects of vitamin D in a larger cohort (36,282 vs. 1,179 subjects) over a longer period of time (seven vs. four years).4)

In our study we found absolutely no indication of an effect of calcium or vitamin D [on cancer] — zero. And that’s over a seven-year period. It was a much larger study and a much longer study.

Jacques Rossouw, in a comment to the press

A 2000 study found that five patients confined to wheelchairs with severe weakness and fatigue were able to walk after supplementing with 300,000 IU’s of vitamin D (150 times higher than the U.S. Institute of Medicine of the National Academy of Sciences' tolerable upper intake level) over a period of six weeks. But the patients were not “cured,“ and no follow-up study was conducted published on the group. Based on what is known about vitamin D metabolism, these patients were simply feeling the effect of a temporary decrease in cytokine and toxin release that resulted after the high levels of vitamin D completely shut down their innate immune systems. In fact, one of the patients actually died in the weeks during which vitamin D was administered.5)

Research with long-term followup

Those researchers, which have followed subjects who have supplemented with vitamin D over the course of decades, have found that the secosteroid does have harmful effects and especially in patients with chronic disease.

One 2004 study found a clear association between high-dose vitamin D supplementation in infancy and an increased risk of atopy, allergic rhinitis, and asthma later in life.6) Those subjects given higher levels of vitamin D during infancy were found to suffer from higher levels of atopy, rhinitis and asthma. However the results were not apparent until the research team checked back with them at 31 years of age.

According to another group of researchers, patients consuming vitamin D are significantly more likely to have greater volumes of brain lesions, indicating regions of damage that can increase risk of cognitive impairment, dementia, depression and death. Vitamin D intake – mean 341 IU and maximum intake 1014 IU – was the only variable that retained a significant correlation with the brain lesions when analyzed by a multivariate analysis.7) In this case, the negative effective could be easily documented, because the subjects were older (average age 71) and presumably had a longer period to build up their pathogenic load.

It is worth noting that studies of certain other classes of steroids, substances which are nearly biochemically identical to vitamin D, have opted to focus on the long-term harm the drugs cause. One study of anabolic steroids is typical. Graham et al documented how rates of cardiovascular disease are significantly higher in former users.8) The study's authors sensibly chose to study subjects only after at least 20 years of previous or current use.

A 2010 study found that Danish neonates with the highest measurable levels of 25-D had a two-fold elevated risk of developing schizoprhenia. The relationship was not explained by a wide range of potential confounding or interacting variables.9) This result is consistent with the explanation that higher rates of disease were caused by the immunosuppressive effects of heavy supplementation with vitamin D.

CorticosteroidsA first-line treatment for a number of diseases. Corticosteroids work by slowing the innate immune response. This provides some patients with temporary symptom palliation but exacerbates the disease over the long-term by allowing chronic pathogens to proliferate., which have a more profound effect on the immune system as well, have a well-documented effect in increasing symptoms of disease if not disease itself. One study found that disease relapse was significantly higher in patients trying to ease their dose of Prednisone.10)

Notes and comments

Sallie Q 09.14.2016 lead section added re High Dose v.D supplementation i need to follow up with references

:-( JAMA articles become unavailable after 12 months, just missed out on getting a permanent quote in from David Agus, and can find no article in pubmed

A Cautionary Tale of Vitamin Supplements Retold leads nowhere :-(

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References

1)
U-shaped relationship between vitamin D levels and long-term outcome in large cohort of survivors of acute myocardial infarction.
Aleksova A, Beltrami AP, Belfiore R, Barbati G, Di Nucci M, Scapol S, De Paris V, Carriere C, Sinagra G
Int J Cardiol223p962-966(2016 Aug 24)
2)
Vitamin D discovery outpaces FDA decision making.
Marshall TG
Bioessays30p173-82(2008 Feb)
3)
Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial.
Lappe JM, Travers-Gustafson D, Davies KM, Recker RR, Heaney RP
Am J Clin Nutr85p1586-91(2007 Jun)
4)
Calcium plus vitamin D supplementation and the risk of breast cancer.
Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, Rossouw J, Lane D, O'Sullivan MJ, Yasmeen S, Hiatt RA, Shikany JM, Vitolins M, Khandekar J, Hubbell FA
J Natl Cancer Inst100p1581-91(2008 Nov 19)
5)
Severe myopathy associated with vitamin D deficiency in western New York.
Prabhala A, Garg R, Dandona P
Arch Intern Med160p1199-203(2000 Apr 24)
6)
Infant vitamin d supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966.
Hyppönen E, Sovio U, Wjst M, Patel S, Pekkanen J, Hartikainen AL, Järvelinb MR
Ann N Y Acad Sci1037p84-95(2004 Dec)
8)
Homocysteine induced cardiovascular events: a consequence of long term anabolic-androgenic steroid (AAS) abuse.
Graham MR, Grace FM, Boobier W, Hullin D, Kicman A, Cowan D, Davies B, Baker JS
Br J Sports Med40p644-8(2006 Jul)
9)
Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study.
McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, Burne TH, Norgaard-Pedersen B, Hougaard DM, Mortensen PB
Arch Gen Psychiatry67p889-94(2010 Sep)
10)
Outcome in sarcoidosis. The relationship of relapse to corticosteroid therapy.
Gottlieb JE, Israel HL, Steiner RM, Triolo J, Patrick H
Chest111p623-31(1997 Mar)
home/pathogenesis/vitamind/longterm.txt · Last modified: 03.15.2017 by sallieq
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