Attenuation of niacin-induced prostaglandin D2 generation by omega-3 fatty acids in THP-1 macrophages and Langerhans dendritic cells

Abstract

Niacin, also known as nicotinic acid, is an organic compound that has several cardio-beneficial effects. However, its use is limited due to the induction of a variable flushing response in most individuals. Flushing occurs from a niacin receptor mediated generation of prostaglandins from arachidonic acid metabolism. This study examined the ability of docosahexaenoic acid, eicosapentaenoic acid, and omega-3 polyunsaturated fatty acids (PUFAs), to attenuate niacin-induced prostaglandins in THP-1 macrophages. Niacin induced both PGD2 and PGE2 generation in a dose-dependent manner. Niacin also caused an increase in cytosolic calcium and activation of cytosolic phospholipase A2. The increase in PGD2 and PGE2 was reduced by both docosahexaenoic acid and eicosapentaenoic acid, but not by oleic acid. Omega-3 PUFAs efficiently incorporated into cellular phospholipids at the expense of arachidonic acid, whereas oleic acid incorporated to a higher extent but had no effect on arachidonic acid levels. Omega-3 PUFAs also reduced surface expression of GPR109A, a human niacin receptor. Furthermore, omega-3 PUFAs also inhibited the niacin-induced increase in cytosolic calcium. Niacin and/or omega-3 PUFAs minimally affected cyclooxygenase-1 activity and had no effect on cyclooxygenase -2 activity. The effects of niacin on PGD2 generation were further confirmed using Langerhans dendritic cells. Results of the present study indicate that omega-3 PUFAs reduced niacin-induced prostaglandins formation by diminishing the availability of their substrate, as well as reducing the surface expression of niacin receptors. In conclusion, this study suggests that the regular use of omega-3 PUFAs along with niacin can potentially reduce the niacin-induced flushing response in sensitive patients.

Long Way of Evaluating Niacin for Atherosclerosis Treatment

“…However, this method only allowed to suppress one of the pathways causing the side effect, which made it impossible to eliminate it completely. Some researchers were concerned that suppression of PGD2 could potentially impact the antiinflammatory action of nicotinic acid, such as PGD2induced inhibition of antigen-presenting Dendritic Cells (DC) activation in inflammation (VanHorn et al, 2012). A study involving mouse models has demonstrated that shortterm administration of niacin can suppress the retention of DC in lymph nodes and that this effect is not abolished by naproxen-induced suppression of prostaglandin generation (Krmeska et al, 2022).…”

The relationship between B vitamin supplementation and pruritus incidence in adults a systematic review and meta-analysis

“…However, the predominant side effect of NA includes flushing which occurs mostly due to immediate-release nicotinic acid (IRNA) and the initial doses of extended-release nicotinic acid (ERNA) [5] . Flushing occurs when the body releases prostaglandin D2 and prostaglandin E2 from cells called Langerhans cells, which is found in the skin, as well as macrophages [7] .…”