Related article: Diseases associated with low levels of 25-D
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Related article: Diseases associated with low levels of 25-D
Many vitamin D studies suffer from methodological errors including bias inherent to using self-selected subjects and insufficient followup, but perhaps their most egregious liability comes in mistaking correlation for causation.
It's undisputed that a wide array of studies point to the fact that 25-hydroxyvitamin D (25-DThe vitamin D metabolite widely (and erroneously) considered best indicator of vitamin D "deficiency." Inactivates the Vitamin D Nuclear Receptor. Produced by hydroxylation of vitamin D3 in the liver.) – typically referred to in the media as vitamin D – is low in people with numerous chronic inflammatory diseases. However, these studies fail to prove that low 25-D causes disease.
In fact, molecular science has revealed that the levels of the vitamin D metabolites through a series of intricate and carefully controlled feedback pathways, mechanisms that belie the simplistic first-order mass-action model used to guide the short-sighted vitamin studies. Also, epidemiological evidence suggests that while 25-D is low in chronic disease, 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. (1,25-dihydroxyvitamin DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol.) tends to be very high, an observation which is at odds with the theory that vitamin D deficiency causes or exacerbates disease.
There have been lots of observational studied showing an association between various diseases and vitamin D deficiency, but there is not any evidence yet that that is a casual relationship… it may be that vitamin D deficiency is a marker of ill health.
Dr. Ruth McQuillan, University of Edinburgh
There are a number of examples where low levels of a substance are known to be associated with but not cause disease.
Of course, the study does not suggest that low and high estradiol concentrations themselves were the cause of increased mortality.
Vasan Ramachandran, MD, Heartwire
Even among those who support widespread supplementation with vitamin D on the basis of the “deficiency” studies, there is wide acknowledgement that the understanding of vitamin D metabolism is “imprecise.”3)
Causation should never be assumed to be self-evident.4) Rigorous analysis is required, especially for a system as complicated as vitamin D metabolism.
Actually, there is no experience of causation: events do not wear their causal credentials on their faces.
L.R. Karhausen 5)
In the absence of an understanding grounded in molecular and clinical evidence, the comprehension of how vitamin D affects disease becomes “black box epidemiology.” 6)
As suggestive as any set of data might seem, absent a precise understanding of underlying disease mechanisms, researchers could just as well conclude, for example, that:
Related article: Evidence for high 1,25-D in patients with chronic disease
Most published epidemiological research looking at levels of vitamin D in those with chronic diseases fail to note any measure of 1,25-D, a metabolite which is often elevated in those with chronic disease. Dr. Greg Blaney, a physician who practices in Vancouver, British Columbia (a setting with relatively infrequent sunlight), found that of a group of 100 patients with a variety of chronic inflammatory diseases, 85 had elevated measures of 1,25-D, which was defined as greater than or equal to 110 pmol/L.
The practice of failing to measure 1,25-D is pervasive: the NIH continues to accept studies and a number of journals continue to publish papers.
One of the reasons that 1,25-D isn't measured may be that it is harder to test. But another reason may be that a high 1,25-D is inconsistent with reports of vitamin D “deficiency.” How can patients be said to be “deficient” in vitamin D when one of its metabolites, 1,25-D, is often several standard deviations greater than normal?
TECHEDIT