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A PROFESSIONAL Response to the Negativity Surrounding Fish Oil Supplements

Concern has been voiced over a number of imprecise, ambiguous, misleading and un-referenced statements, that actually fail to support, A. O’Connor’s conclusion that “the vast majority of clinical trials involving fish oil have found no evidence that it lowers the risk of heart attach and stroke”. The purpose of this brief correspondence is to compare and contrast the superficial nature of this statement and several other claims made in this article – with physiological understanding, known limitations of research methodology, and the weight of scientific evidence.

Title and Major Conclusion: “Fish Oil Claims Not Supported by Research”

When supporting claims in the article, the author makes reference to “clinical trials”, “at least two dozen rigorous studies”, and “several studies”, in addition to other implied scientific work. Ironically, in an article specifically focused on research, not a single reference was provided to support any claim. As a result, all statements and conclusions within this article should be viewed with the utmost caution, and interpreted with extreme care.

Statement / Claim: “at least two dozen rigorous studies of fish oil…most of which looked at whether fish oil could prevent cardiovascular events in high-risk populations…all but two…found that compared to placebo, fish oil showed no benefit” (italics, underline mine)

The accuracy of this claim is simultaneously confounded by 4 different elements:

  • First, clarity within the statement is shielded (see italicized words), leaving the reader to guess the actual number of studies, what proportion of the studies evaluated fish oil, how the fish was evaluated, and what “rigorous” and “no benefit” mean from an experimental design and/or statistical perspective.
  • Second, A. O’Connor notes these high-risk populations had a history of heart disease or the presence of important cardiovascular risk factors (hyperlipidemia, hypertension or Type 2 DM), but fails to explain that patients in both populations are likely to have numerous, serious and long-standing physiological dysfunctions. Many of these dysfunctions may yield mal-adaptive metabolic imbalances within tissues, organs and organ systems. Moreover, nearly all of these high-risk patients are likely being treated with one or more prescription medications. Both of these situations may influence how fish-oil (EPA/DHA) affects are measured in the body.
    • Long-standing metabolic imbalances spanning multiple organ systems treated with biologically insignificant amounts of fish-oil (eg., 1g/d) should not be expected to rapidly return these systems to normal baseline function. The problem begins with digestion and absorption, as fatty acid bioavailability may be less than optimal for many with cardiovascular disease or risk factors [1, 2]. Even if absorbed, high levels of omega-6 fatty acids in the Standard American Diet (SAD) may outcompete EPA and DHA for space in cell membranes [3, 4], significantly reducing availability to influence physiological events. When EPA and DHA are incorporated into cell membranes, they serve as native, foundational building blocks to modulate and regulate normal membrane structure and functions. By modulating such processes as endothelial structure / function, the activities of Na+, K+ and Ca+2 channels, inflammation cascades, beta-oxidation, LDL-particle density, insulin sensitivity, and numerous signal transduction pathways – the affects of EPA and DHA on cells, tissues and organs should be measured differently and on different time scales compared to the rapid and often severe on/off action that define most foreign pharmaceutical agents. Thus, based on the nature and activity of fish-oil, primary and secondary cardiovascular outcome measures and statistics that are strongly influenced by drugs and myriad other variables, should be expected to underestimate the actual cell, tissue and organ-level metabolic benefits that may accrue from EPA and DHA.
  • Generally, standard-of-care includes the prescription of one or more medications to treat specific cardiovascular disease issues or risk factors in a way that significantly alters metabolic activities. When studies give EPA+DHA to such medicated patients with rigorously altered metabolic pathways, a statistically significant change in systemic physiological metrics should not be expected.
    • Interestingly, there are investigations that suggest these two omega-3 fatty acids from fish-oil appear to either act neutrally with cardiovascular medications, or may in fact be synergistic [5].
  • Third, a significant body of clinical evidence that runs counter to this claim – suggesting that higher plasma levels of EPA and DHA [6, 7], and treatment with omega-3 fatty acids from fish oil (EPA+DHA) are associated with reduction in coronary artery disease, stroke, fatal and non-fatal MI, sudden cardiac death, all-cause mortality [8](reviewed in [9-14]).
    • A rapid scan of Pubmed recently found 136 randomized controlled trial on the influence of EPA and DHA on features of cardiovascular disease or risk factors. Information from these studies is instructive:
      • Papers finding one or more positive effects: 123,848 subjects
        • Papers finding no benefit: 22,540 subjects
      • Clinical studies showing beneficial effects: 42,000 patients
        • Clinical studies showing no benefit: 26,000 patients
      • Studies showing a reduction in triglycerides with EPA+DHA: 15,622 patients
        • Study showing no reduction: 18 patients
  • Fourth, the FDA provides strict guidelines on the wording of structure/function claims for fish-oil nutritional supplements. These restrictions result in label claims such as good for ‘heart health’ or ‘blood vessel health’. Thus, as a nutritional supplement, fish-oil makes no medical claim to prevent or cure any cardiovascular disease or condition. Moreover, there is only one FDA approved pharmaceutical claim allowed for fish-oil, and that is related to reducing very high triglycerides. As a result, the author’s claims there is “no evidence that it (fish oil) lowers the risk of heart attach and stroke” – lacks meaning in today’s nutritional and medical landscape.

Statement / Claim: “The vast majority of clinical trials involving fish oil have found no evidence that it lowers the risk of heart attack and stroke”

The accuracy of this claim is confounded by:

  • Problems associated with the design and data collection of nearly all recent meta-analyses evaluating affects of fish oil. Examples of design issues include: (and are represented in [15-19])
    • Low number of studies that meet the selection criteria
    • There are often too few patients within a meta-analysis for sufficiently-powered statistical analysis
    • One or more cardiovascular medications taken by study patients influence the primary study outcome
      • Patients from different studies may be on different medications
    • Tissue-levels of EPA and DHA at the beginning of each individual study are often unknown
    • Dietary patterns of patients are usually unknown, therefore the intake of fish or other seafood, or competitive omega-6 fatty acids is unknown
    • Measurement of EPA and DHA is often limited to plasma, which only reflects dietary exposure over the past 24-48hrs
  • In contrast, almost all randomized controlled trials within recent meta-analyses have demonstrated that an intake of EPA and DHA reduces the risk of coronary death by 10-30%. Examples of these meta-analyses include the following: [17, 20-25].

Statement / Claim: “the era of fish oil as medication could be considered over now” – quote from Dr. Gianni Tognoni, Institute for Pharmacological Research in Milan

The accuracy of this claim is confounded by established FDA guidelines, well-established medical associations, and the weight of laboratory and clinical scientific evidence to the contrary:

  • US Federal Guidelines negate this claim, as EPA and DHA from fish-oil are approved by the FDA as pharmaceutical drugs (Lovaza, Vascepa). The American Heart Association recommends ~1 gram/day for patients with documented cardiovascular disease, and 2-4 grams per day for those with high triglycerides (


  • In this New York Times article specifically focused on research, not a single reference was provided to support any claim. As a result, all statements and conclusions within this article should be viewed with the utmost caution and interpreted with extreme care.
  • The statements and claims made in the article are confounded by multiple important factors – including:
    • Vague and undefined terms
    • A confusion between the structure and function of a foundational cellular design element (membrane fatty acid such as EPA and DHA) and a drug
    • How variables in a study can influence each other and the measured outcome(s) of a study
    • A severe lack of awareness of federal regulations that show the exact opposite of these published statements
    • A failure to mention the hundreds of laboratory and clinical studies showing potentially positive metabolic benefits of EPA and DHA on important cardiovascular risk factors, such as obesity [26-28], hypertension [29-31], dyslipidemia [32-34], and atherosclerosis [9, 35-37] – that may provide significant positive metabolic and physiological benefits to a patient with cardiovascular disease.


Scott Minton, MS, PhD

Scientific Advisor, Nordic Naturals