PUFA/MUFA trigger serotonin release, platelet aggregation independently of downstream metabolites; SFA do not
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One of the sneaky arguments that mainstream makes in favor of PUFA is that while they have a known pro-inflammatory effect when consumed regularly, that effect only manifests when those lipids are metabolized downstream into pro-inflammatory metabolites such as prostaglandins, leukotrienes, tromboxanes, etc. In other words, medicine claims that PUFA is harmless unless it enters one of those inflammatory pathways driven by enzymes such as COX, LOX, and thromboxane synthase (TBXS). Even then, medicine claims that there are options for mitigating the pro-inflammatory effects by taking drugs that inhibit COX, LOX, TBXS, etc. Aspirin and other NSAIDs are one of the better known option for inhibiting those pathways. The study below begs to disagree. Namely, it demonstrates that arachidonic, linoleic, and linoleic acids trigger platelet aggregation and serotonin release independently of conversion into downstream inflammatory mediators. Platelet aggregation and increased serotonin release are a known trigger for ischemic events such as heart attacks and strokes, and also contributes to the development/progression of CVD. In fact, in sufficiently “high” concentrations (easily achievable through “normal” Western diets) that direct effect of PUFA on platelet aggregation and serotonin release is irreversible and cannot be mitigated by drugs such as aspirin. Furthermore, the main dietary MUFA oleic acid had virtually the same effects as the PUFA members tested in the study. Saturated fatty acids (SFA) such as palmitic, stearic, arachidic, did not have such pro-CVD effects. Finally, to make matters much worse for the poor humans who eat Western diets laced with PUFA/MUFA, the study found that a combination of two or more of the PUFA/MUFA lipids induced the same platelet aggregation and serotonin release as several-fold higher concentrations of a single PUFA/MUFA. Considering that modern diets almost always contain a mixture of multiple PUFA/MUFA, this is truly a worst-case scenario. So, the moral of the story is that PUFA (and even MUFA) are directly harmful even in their unmodified forms, and should be avoided whenever possible.
https://pubmed.ncbi.nlm.nih.gov/2992603/
“…We examined platelet aggregation and serotonin release, induced by less than 60 micro M arachidonic acid, using washed platelet suspensions in the absence of albumin. The concentration of arachidonic acid used did not cause platelet lysis. Platelet responses induced by less than 20 micro M arachidonic acid were inhibited by aspirin, whereas those induced by above 30 micro M arachidonic acid were not inhibited, even by both aspirin and 5,8,11,14-eicosatetraynoic acid. Although phosphatidic acid and 1,2-diacylglycerol increased after the addition of arachidonic acid in aspirin-treated platelets, the amounts were not parallel to platelet aggregation. Oleic, linoleic and linolenic acids also induced platelet responses, while palmitic, stearic and arachidic acids did not. EDTA, dibutyryl cyclic AMP, apyrase and creatine phosphate/creatine phosphokinase brought about almost the same effects in platelet responses induced by the unsaturated fatty acids, other than arachidonic acid, as those induced by 40 micro M arachidonic acid. These results suggest that the mechanism of the actions of more than 30 micro M arachidonic acid on platelets is the same as that of the other unsaturated fatty acids and is independent of prostaglandin endoperoxides, thromboxane A2 and, perhaps, phosphatidic acid and 1,2-diacylglycerol.”
“…We used oleic, linoleic and linolenic acids as unsaturated fatty acids, and palmitic, stearic and arachidonic acids as saturated ones. The unsaturated fatty acids tested induced an irreversible platelet aggregation and serotonin release dose-dependently at concentrations of more than 30uM. On the other hand, the saturated fatty acids tested did not induce platelet aggregation and serotonin release at concentrations of below 100uM.”
“…The combination of two kinds of unsaturated fatty acid increased the effects on platelets. Fig. 8 shows combined effects of arachidonic acid and oleic acid on platelets treated with aspirin (500uM) and 5,8,11,14-eicosatetraynoic acid (2uM). Platelet aggregation and serotonin release were notinduced by below 15uM arachidonic acid or below 30uM oleic acid, whereas these were induced by the simultaneous addition of 10uM arachidonic acid and 10uM oleic acid. Moreover, platelet responses increased as a function of the concentration of the oleic acid added to a platelet suspension if the concentration of arachidonic acid was held constant at 10uM…Because unsaturated fatty acids work additively on platelets to induce responses, the amounts of unsaturated fatty acids in phospholipids of platelets [1,23] may be enough, as a whole, to induce
platelet responses independent of prostaglandin endoperoxidases and thromboxane A2.”