Levels of 25-hydroxy vitamin D [25(OH)D] are reported to be decreased in cardiovascular
disease (CVD) and in other chronic immunopathologies. Vitamin D (vitD) has been shown to be significantly
linked to mortality, and is thought to be a predictor of survival. Therefore, supplementation
with vitD has been suggested as an option to improve clinical outcomes.
In contrast to the causal assumption, we hypothesize that the decreased vitD levels, seen in patients with CVD and chronic
immunopathologies is secondary to inflammation and not as pathophysiologically relevant as currently suggested. Under
these conditions, low vitD might be mainly caused by oxidative stress that results from chronic, immune-mediated vascular
and systemic inflammation seen in patients with CVD. The oxidative environment most likely causes biodegradation
of vitD and interferes with key enzymes, disturbing the biosynthesis of 25(OH)D and 1,25(OH)D. Thus far, no clear evidence
of a beneficial effect of vitD supplements exists, beyond treating vitD deficiency to improve skeletal health.
Moreover, a prolonged and/or high dose vitD supplementation, unless needed to correct actual vitD deficiency [levels of
25(OH)D<20 ng/ml)] may even be immunologically harmful by downregulating Th1 immune responses and indirectly
upregulating Th2 immune activation with potential detrimental metabolic and cardiovascular effects. Large randomized
controlled studies of vitD with multiple outcomes (skeletal, metabolic, cardiovascular and mental) are urgently needed.