Replacement of Reduced Highly Unsaturated Fatty Acids (HUFA Deficiency) in Dilative Heart Failure: Dosage of EPA/DHA and Variability of Adverse Peroxides and Aldehydes in Dietary Supplement Fish Oils

Abstract

Objectives: To explore the rationale for ω-3 fatty acids in heart failure treatment, the dosage of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) for replacing low levels of highly unsaturated fatty acids (HUFA deficiency) was examined. To judge the usefulness of various EPA/DHA preparations, their content of peroxides and aldehydes was determined. Methods: In 298 patients with dilative heart failure, the serum HUFA level was assessed by gas chromatography. In ω-3-acid ethyl esters 90 (Omacor/Lovaza, approved by the Food and Drug Administration and the European Medicines Agency) and 63 dietary supplement fish oils, oxidation products were determined by photometry. Results: Increasing serum HUFA from the lower (4.3 ± 1.0%) to the upper (9.5 ± 1.5%) tertile would be associated with an increased left ventricular (LV) ejection fraction (34.1 ± 9.9 vs. 28.3 ± 9.5%, p < 0.01) and reduced LV enddiastolic diameter (63.5 ± 7.1 vs. 66.9 ± 7.4 mm) requiring at least 2 g EPA/DHA daily. In fish oils, the peroxide and alkenal level varied greatly, i.e. peroxide value ≤5 mEq/kg in only 7 and ≤10 mEq/kg in 38 fish oils. Compared with equivalent doses of ω-3-acid ethyl esters 90, the mean peroxide intake would be 8.6 ± 6.1 and the alkenal intake 10.9 ± 4.4 times higher in fish oils. Conclusions: Levels of adverse oxidation products should be considered when targeting HUFA deficiency or treating patients with myocardial infarction or high triglycerides.

Fish oil supplements, oxidative status, and compliance behaviour: Regulatory challenges and opportunities

“…A number of studies have recently examined fatty acid content and oxidative quality for both liquid and encapsulated formulations of EPA and DHA. Whilst certain studies concluded that the majority of products tested complied with regulations [15][16][17], others found that a notable percentage of products tested fell short in one or more quality parameters [18][19][20][21][22][23][24][25][26][27]. As the dietary supplements market has become increasingly globalized and profitable, increasing levels of dietary supplements are now available to consumers in the United Arab Emirates (UAE), and people have ready access to unfamiliar supplements that can cause unexpected adverse effects.…”

Improving Lipids With Prescription Icosapent Ethyl After Previous Use of Fish Oil Dietary Supplements

“…Recently, the safety of fish oil dietary supplements was questioned in a New Zealand study that documented that 83% of the assessed fish oil dietary supplements exceeded the recommended peroxide value, a marker of oxidation or oil spoilage [26]. The oils in fish oil dietary supplements are highly prone to oxidation; this may render them ineffective or potentially harmful due to altered biologic activity [40,41]. It is no surprise that both the American Diabetes Association and the International Atherosclerosis Society no longer recommend fish oil dietary supplements in the prevention or treatment of cardiovascular diseases [42][43][44].…”

Mechanisms increasing n-3 highly unsaturated fatty acids in the heart

“…Because a lower dietary intake cannot account for this reduction, the endogenous production of n-3 and n-6 HUFA appeared to be involved. It was suggested that systemic HUFA supplementation compensates for an impaired endogenous synthesis in heart failure and thus exhibits beneficial effects (Rupp et al 2013). In the GISSI-Prevenzione trial, omega-3 fatty acids reduced the risk of sudden death to a greater extent in patients with depressed heart function (Macchia et al 2005).…”

“…Particularly, whether an increased synthesis of 22:5n-3 from the precursor 20:5n-3 by activation of elongase-5 (Elovl5) and elongase-2 (Elovl2) (Gregory et al 2013) is parallelized by an increase of 22:4n-6 from its endogenous precursor 20:4n-6 (arachidonic acid). Although peroxisome proliferator-activated receptor (PPAR)-alpha activation was expected to raise n-3 and n-6 HUFA to a similar extent by increased delta(5)-and delta(6)-desaturase activity (Matsuzaka et al 2002a), the PPAR-alpha activator fenofibrate increased 20: 4n-6, while 20:5n-3 and 22:6n-3 were unaffected (Rupp et al 2013).…”

“…Partial inhibition of fatty acid oxidation by etomoxir was shown to reduce 22:6n-3 in the heart, while 20:5n-3 was unaffected (Rupp et al 2013). The question arises (iv) whether an increased betaoxidation leads to increased 22:6n-3.…”