The FDA recently announced limited health claims for the use of omega-3 fatty acids in the treatment of hypertension and heart disease. These are qualified health claims since each of the allowed claims must carry the following language, “FDA has concluded that the evidence is inconsistent and inconclusive”. Nonetheless this indicates the FDA is beginning to acknowledge that omega-3 fatty acids have potential in the treatment of hypertension and cardiovascular disease. These health claims can only be used if a single-serving size contains at least 0.8 g of EPA and DHA.
It took more than five years of study by the FDA to even allow these limited health claims as the petition for them was launched in 2014. The primary scientific document that used was a meta-analysis of various clinical trials published in the American Journal of Hypertension (1). More than 70 clinical trials were included in the analysis. Although the average reduction in systolic blood pressure by 1.5 mm Hg and diastolic blood pressure by 1 mm Hg was seemingly small, the effects in untreated hypertensive subjects was far greater (4.5 mm Hg reduction in systolic pressure and 3.1 mm Hg reduction in diastolic pressure). Furthermore, the reduction in the diastolic pressure was only observed if the daily dose of EPA and DHA was greater than 2 grams per day. Ironically, a lower dose of EPA and DHA between 1 and 2 grams per day had no effect on diastolic blood pressure. Therefore, it seems that the FDA qualified health claim would be far stronger if the minimum omega-3 dosage was greater than 2 grams per day as opposed to the stated 0.8 grams per day. Of course, there might be a problem since at those levels of daily EPA and DHA, intake of commercially available omega3s may contain too many toxins such as PCBs.
The benefits of a higher dose of EPA and DHA for treating hypertension has been confirmed in more recent studies (2,3). In these studies, there were equivalent drops in systolic blood pressure at 0.7 and 1.8 grams of EPA and DHA per day, but the higher dose (1.8 grams per day) had a drop in diastolic pressure, but not with the lower dose (0.7 grams per day) (4).
This differential effect of omega-3 fatty acids on risk of heart disease was illustrated in two recent trials (5,6). At a low dose of 0.8 grams of omega-3 fatty acids per day, there was no clinical benefits. At a higher dose of 3.9 grams of omega-3 fatty acids, there was a strong cardiovascular benefit. Further analysis of the high-dose omega-3 data indicated that among statin-treated individuals, the addition of the high-dose omega-3 fatty acids reduced the occurrence of a first heart attack, secondary heart attack, and total ischemic events by approximately 30 percent compared to statins alone (7). As pointed out in a recent commentary by me, the appropriate dose of omega-3 fatty acids are best measured by the reduction in the arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratio in the blood (8). Unfortunately, the AA/EPA ratio was not reported in any of the hypertension or cardiovascular trials.
Hopefully future clinical investigators will use the levels of omega-3 fatty acids required to reach an appropriate AA/EPA ratio (1.5 to 3) to obtain much stronger research findings so that the health claim for omega-3 fatty acids in hypertension and cardiovascular disease is not followed by the qualifier, “FDA has concluded that the evidence is inconsistent and inconclusive” .
- Miller PE et al. “Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: A meta-analysis of randomized controlled trials.” American Journal of Hypertension 27:885-896 (2014)
- Yang B et al. “Lowering effect of n-3 fatty acid supplements on blood pressure in Inner Mongolia hypertensive patients.” J Agric Food Chem 67: 184-192 (2019)
- Casanova MA et al. “Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk.” J Am Soc Hypertension 11; 10-19 (2017).
- Minihane AM et al. “Consumption of fish oil provide eicosapentaenoic acid and docosahexaenoic acid reduces blood pressure in adults with systolic hypertension.” J Nutr 146: 516-523 (2016)
- Manson JE et al. “Marine n-3 fatty acids and prevention of cardiovascular disease and cancer.” N Engl J Med 380: 23-32 (2019)
- Bhatt DL et al. “Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.” N Engl J Med 380: 11-22 (2019)
- Bhatt DL et al. “Effects of icosapent ethyl on total ischemic events.” Am Coll Cardiol 73: 2791-2802 (2019)
- Sears B. “Appropriate doses of omega-3 fatty acids for therapeutic results.” CellR4 6: e2578 (2018)