Retinol (Vitamin A) - A Re-Discovered Weapon in the Battle Against Atherosclerosis: Reduced Progression in Patients, Protection For Healthy Subjects From 25,000IU/Day Retinol

No it's not fish oil that's going to save your a** from dying of heart attack. It's vitamin A! 25,000IU/day for those who are already suffering from atherosclerotic lesions and heard disease could do the trick.

600,000 people die of heart disease in the United States every year–that’s 1 in every 4 deaths; and at least some could have been prevented, if vitamin A had not been demonized as bone-dissolving kidney and liver killer for decades. That's at least what the results of a recent study from the Shahid Beheshti University of Medical Sciences in the - at least in terms of medical paradigms - open-minded Iran (Mottaghi. 2014). Unlike their Western colleagues who would probably considered the provision of 25,000IU of retinyl palmitate per day an act of personal injury, Azadeh Mottaghi and his colleagues dared administering the said amount of pre-formed vitamin A to 31 atherosclerotic patients and 15 healthy controls for 4 full months; and the results were... Impressive!
In the atherosclerotic patients, the provision of extra vitamin A supplementation resulted in significant decrease in IL-17 gene expression (-47%) in fresh cell, 18% in PHA activated cells and 35% in ox-LDL activated cells (p<0.05 for all).

RORc gene expression (indicative of the progression of atherosclerosis) in fresh cells as well as ox-LDL activated cells decreased significantly after vitamin A supplementation in atherosclerotic patients (p=0.0001 for both).

Figure 1: IL-17 & RORc levels in LDL- and PHA activated cells relative to baseline (Mottaghi. 2014)

No wonder, I mean, most people tend to be so high on vitamin D (figuratively) that they totally forget about Vitamin A and its crucial roles in mediating immune responses (Winoto. 2002). Retinoic acid and its metabolits and analogues are capable of ameliorating various models of autoimmune diseases such as rheumatoid arthritis (Miyagawa. 2002), type 1 diabetes (Zunino. 2007) and ulceratative colitis (Bai. 2009). A strong suppressive effect of retinoids on pro inflammatory Th17 cells function via down regulation of RORc, as it was observed in the study at hand, has been demonstrated in vitro, before. Retinoids have  can also suppress Th17 function via interactions with the retinoid alpha receptor right on the cell surface.

In vivo, it has been demonstrated that retinoic acid (RA) enhances TGF-β and Foxp3 expression and will thus decrease the differentiation of the rampant Th17 cells and downregulate their IL-17 production (Mucida. 2007) The exact underlying mechanism is not that important in this context, what is important though, is the fact that it worked in fresh cells (see above) and in phytohemagglutinin (PHA) activated cells, i.e. immune cells on a rampage that have been activated by the bean-lectin phytohemagglutinin (the reason you should never eat raw beans).

Apropos rampage, it's worth noticing that the provision of extra vitamin A led to a significant reduction in RORc gene activity and thus atherosclerotic potential in both, the already active, and activated Th-17 cells of the atherosclerotic subjects, and the PHA- and LDL-activated Th-17 cells of the healthy subjects - in conjunction with the increase in RORc in the placebo group (see Figure 1), this observation provides convincing evidence that vitamin A can also protect healthy individuals from developing atherosclerosis.
References:

• Bai, Aiping, et al. "All-trans retinoic acid down-regulates inflammatory responses by shifting the Treg/Th17 profile in human ulcerative and murine colitis." Journal of leukocyte biology 86.4 (2009): 959-969.
• Miyagawa, Naoki, et al. "Effect of synthetic retinoid, TAC-101, on experimental autoimmune disease." Pharmacology 67.1 (2002): 21-31.
• Mottaghi, Azadeh, et al. "Vitamin A supplementation reduces IL‐17 and RORc gene expression in atherosclerotic patients." Scandinavian Journal of Immunology (2014).
• Winoto, Astar, and Dan R. Littman. "Nuclear hormone receptors in T lymphocytes." Cell 109.2 (2002): S57-S66.
• Zunino, Susan J., David H. Storms, and Charles B. Stephensen. "Diets rich in polyphenols and vitamin A inhibit the development of type I autoimmune diabetes in nonobese diabetic mice." The Journal of nutrition 137.5 (2007): 1216-1221.