Randomized clinical trials of oral vitamin D supplementation in need of a paradigm change: The vitamin D autacoid paradigm.

Abstract:

:Epidemiological studies highlight the negative correlation between vitamin D levels and the incidence of many non-skeletal diseases including inflammatory diseases, cancer, and metabolic and neurological disorders. However, most randomized controlled trials (RCTs) with oral vitamin D supplementation give mixed results or are inconclusive. It has been said that "discovery commences with the awareness of anomaly". The "anomaly" between our preclinical and clinical data provides the opportunity to propose an alternative paradigm to the vitamin D endocrine system: the vitamin D autacoid paradigm. In the vitamin D autacoid paradigm, the extra-skeletal effects of vitamin D depend on the tissue reserves of vitamin D metabolites. These vitamin D autacoid systems are inducible oscillatory ecosystems in which 1,25D is produced, acts and is inactivated locally. In the vitamin D autacoid paradigm, attaining adequacy of vitamin D in the systemic circulation is necessary but not sufficient; we must also ensure the repletion of the tissue stores. The co-existence of two different vitamin D systems, endocrine and autacoid, with different functions and regulations leads to "significant shifts in the criteria determining the legitimacy both of problems and of proposed solutions". With respect to our clinical trials of vitamin D supplementation for unconventional effects, the proposed solution is administering and quantifying vitamin D metabolites directly to the target tissue.

journal_name

Med Hypotheses

journal_title

Medical hypotheses

authors

Chabrol T,Wion D

doi

10.1016/j.mehy.2019.109417

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

109417

eissn

0306-9877

issn

1532-2777

pii

S0306-9877(19)30971-5

journal_volume

134

pub_type

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