No, Fish Oil Supplements Do NotRepresent False Promise

0
12

Having had the privilege to introduce to the scientific community the benefits of omega-3 fatty acids in cardiovascular disease though my work on Greenland Inuits in the 1970s, I read with some concern the August 22, 2019, opinion piece entitled “The False Promise of Fish Oil Supplements,” by R. Preston Mason. What concerns me the most is the failure to disclose the conflict of interest that Dr. Mason has with Amarin Pharmaceuticals, the maker of an omega-3 based drug called Vascepa. (The first FDA-approved omega-3 pharmaceutical was Lovaza, which is called Omacor in most of the rest of the world.)


Dr. Mason has been an author on 12 papers on fish oil in the past four years [see list at end of blog]—Amarin is listed as the study supporter on ten of them and another was “critically reviewed” by employees of Amarin.

Amarin Pharma has been marketing the FDA-approved pharmaceutical Vascepa, which is much more expensive version of omega-3 than over-the-counter dietary supplements. Dr. Mason’s piece in Scientific American appears to be yet another effort to portray “dietary supplements” as having failed to reduce risk for cardiovascular disease, in contrast to Vascepa which was shown to reduce risk in the REDUCE-IT study—which was funded and run by Amarin.

During the past decade several large studies of omega-3 on heart risk have failed to demonstrate a benefit, although it should be noted that many did reduce risk for certain heart outcomes. Dr. Mason refers to studies such as ORIGIN, OMEGA, and VITAL, and concludes that “dietary supplements” are ineffective, but he apparently fails to appreciate that these studies were NOT done with dietary supplements but with Lovaza/Omacor—which are pharmaceutical products.

The most likely reason that many of these studies failed to show benefit was the low dose of omega-3 fatty acids used (typically 840 mg a day). Whether they were pharmaceuticals or supplements is not the point—dose is the point! In the REDUCE-IT study using Vascepa, the dose was 4,000 mg a day—almost five times higher than the 840 mg a day of omega-3 fatty acids in other studies. Implying that these trials were null because “supplements” were used is, in my view, disingenuous.

Further, Dr. Mason states, “to the contrary, all studies of fish oil supplements conducted to date have failed to show any significant clinical benefits beyond those of standard-of-care therapy.” This is untrue, with two of the most recent studies (ASCEND and VITAL) that both used Lovaza/Omacor (again providing only 840 mg a day of omega-3) reporting statistically significant benefits on certain heart outcomes. Effects depend on the amount of omega-3 provided, not on whether a product has or has not been vetted through the FDA and is thus christened a “drug.” Of course, federal regulations prevent dietary supplements from being prescribed by doctors as a treatment for a disease, but that does not change biology.

Dr. Mason refers multiple times in his article to a recent paper by Safi Khan of West Virginia University and his coworkers as confirmation that omega-3 “dietary supplements” don’t work. The irony here is that these authors concluded that the use of omega-3 fatty acids was associated with significantly reduced risk for coronary heart disease and specifically heart attacks. Mason ignores the statistical significance of the findings and instead emphasizes that these were of “low certainty.”

The readers of Scientific American should have been made aware that this writer has been doing work funded by a company that touts the benefit of a pharmaceutical that is competing in the marketplace with omega-3 dietary supplements.

REFERENCES

[1] Mason RP, Dawoud H, Jacob RF, Sherratt SCR, Malinski T. Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;103:1231-7. 10.1016/j.biopha.2018.04.118.


[2] Sherratt SCR, Mason RP. Eicosapentaenoic acid inhibits oxidation of high density lipoprotein particles in a manner distinct from docosahexaenoic acid. Biochemical and biophysical research communications. 2018;496:335-8. 10.1016/j.bbrc.2018.01.062.

[3] Mason RP, Sherratt SC. Omega-3 fatty acid fish oil dietary supplements contain saturated fats and oxidized lipids that may interfere with their intended biological benefits. Biochemical and biophysical research communications. 2017;483:425-9. 10.1016/j.bbrc.2016.12.127.

[4] Nelson JR, True WS, Le V, Mason RP. Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk? Postgraduate medicine. 2017;129:822-7. 10.1080/00325481.2017.1385365.

[5] Borow KM, Mason RP, Vijayaraghavan K. Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A Review. Cardiorenal medicine. 2017;8:18-30. 10.1159/000479391.

[6] Brinton EA, Mason RP. Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA). Lipids in health and disease. 2017;16:23. 10.1186/s12944-017-0415-8.

[7] Mason RP, Jacob RF, Shrivastava S, Sherratt SCR, Chattopadhyay A. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes. Biochimica et biophysica acta. 2016;1858:3131-40. 10.1016/j.bbamem.2016.10.002.

[8] Mason RP, Sherratt SC, Jacob RF. Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents. Journal of cardiovascular pharmacology. 2016;68:33-40. 10.1097/fjc.0000000000000379.

[9] Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242:357-66. 10.1016/j.atherosclerosis.2015.07.035.

[10] Mason RP, Jacob RF. Eicosapentaenoic acid inhibits glucose-induced membrane cholesterol crystalline domain formation through a potent antioxidant mechanism. Biochimica et biophysica acta. 2015;1848:502-9. 10.1016/j.bbamem.2014.10.016.

[11] Sherratt SCR, Mason RP. Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations and lipid interactions as determined by X-ray diffraction. Chem Phys Lipids. 2018;212:73-9. 10.1016/j.chemphyslip.2018.01.002.

[12] Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management. J Am Coll Cardiol. 2018;72:330-43. 10.1016/j.jacc.2018.04.061.


Source link
Originally posted by: Jørn Dyerberg

LEAVE A REPLY

Please enter your comment!
Please enter your name here