Study Spotlight Take-Away with Chef Dr. Mike

by Michael S. Fenster, MD

Nothing Like The Real Thing; Fish Oil Supplements

“You can’t supplement your way to good health.”

― Chef Dr. Mike

As of 2023, there were approximately 82 million people aged 60 and older in the United States. Approximately 20%, or over 16 million, of these seniors took fish oil supplements in a quest for better health, and that’s a bit of a shame. That’s because just enjoying some delicious fish as a regular gastronomic treat has been shown to correlate with an almost 10% reduction in cardiovascular events like heart attacks. It has also been shown to correlate with a roughly 15% reduction in death from cardiovascular causes and early mortality.[1],[2] Excluding considerations for certain species due to mercury toxicity, there doesn’t seem to be a health-related downside to gobbling up such piscine pleasures. It seems a tasty way to invest always precious food-health dollars. In fact, the UK National Institute for Health and Care Excellence goes so far as to recommend that “people with or at high risk for cardiovascular disease consume at least one portion of oily fish a week.”

However, the same cannot be said for supplements, specifically fish oil supplements. Conventional wisdom holds that the health benefits associated with regular fish consumption derive from fish oils. In typical reductionist logic, simply consuming a capsule full of fish oil should confer the same health benefit – sans the pleasure of a beautifully oceanic-derived dinner – as regularly eating fish.

It doesn’t.

Inconsistent study results over the last half-century have made the whole idea of recommending fish oil supplements for cardiovascular benefits controversial. Several studies and meta-analyses have suggested negative health-related consequences of supplement consumption.  Others, like a review of almost 100 observational and randomized controlled trials performed by the Agency For Healthcare Research And Quality, found no increased risk but also no benefit. The recently performed REDUCE-IT trial found a decreased risk of major adverse cardiovascular events utilizing Icosapent Ethyl, but such industry-sponsored research always requires closer scrutiny. For the over 16 million seniors spending hard-earned and valuable dollars looking for health benefits, it seems important to be able to supply some reasonable direction.

This week’s study utilizing participants from the UK biobank perhaps gets us a wee bit closer.

The Study:

  • The study analyzed data from 415,737 adult participants of the UK Biobank study.
  • The study was a longitudinal cohort study with a median follow-up of 11.9 years.
  • The participants ranged from 40-69 years old, with 55% being female and a mean age of 55.9 years.
  • Regular fish oil supplementation use was reported by 31.4% of the participants.
  • All participants were free from cardiovascular disease at baseline.

The Take-Away:

  • The analysis was conducted uniquely. Many prior studies have evaluated only one particular endpoint. This study examined six different pathways (or Transitions as they are labeled in the study protocol).
    • Pathway A: Previously healthy people developed atrial fibrillation.
    • Pathway B: Previously healthy people suffered a major adverse cardiovascular event (MACE).
    • Pathway C: Previously healthy people died.
    • Pathway D: People with atrial fibrillation suffered a MACE.
    • Pathway E: People with atrial fibrillation died.
    • Pathway F: People with a previous MACE died.
  • Pathways A and B are primary prevention.
  • Pathway D is secondary prevention.
  • MACE was further subdivided into three individual cardiovascular disease categories, heart failure, stroke, and myocardial infarction.

The Caveat:

The study results were intriguing. If you were otherwise healthy, taking fish oil supplements correlated to an increased risk of developing atrial fibrillation by 13%.

But if you already had atrial fibrillation, then taking fish oil supplements correlated to a decreased risk of suffering a major adverse cardiovascular event by about 8%. It specifically correlated to a reduced risk of suffering a myocardial infarction by about 15%. If you had underlying atrial fibrillation, then taking fish oil supplements also decreased your risk of early mortality by about 10%.

If you had underlying heart failure (one of the three types of MACE), then taking fish oil supplements decreased your risk of early mortality by the same 10% margin.

The study highlights many of the difficulties in determining relationships between what we eat, health and wellness, or disability and disease. First and foremost, it is important to remember that this was an observational study, so no causal relations can be drawn from the data. It also points out that not all groups are equivalent. In this particular study, people who were otherwise healthy had an increased risk of developing atrial fibrillation when they took fish oil supplements. However, those already suffering from atrial fibrillation appeared to derive cardiovascular benefits from consuming fish oil supplements. A further difficulty with this particular study is that there was no control in terms of what fish oil supplements (and thus what compounds, what fatty acids, and in what proportion) were consumed. For some of the observed correlations, like those seen in patients with underlying atrial fibrillation, “no proven biological mechanism for this explanation [currently] exists.”

The push to recommend and use supplements like omega-3 fish oils is substantial and growing. The U.S. dietary supplements market was approximately $48.8 billion in 2022. The global omega-3 products market alone, which includes fish oil supplements, was valued at around $12.3 billion in 2022 and is expected to reach approximately $23.8 billion by 2032. Blurring the distinction between supplements and prescription medications are prescription brands of available fish oils, including Lovaza (Omega-3-Acid Ethyl Esters and prescribed for very high triglyceride levels of 500 mg/dL or more), Vascepa (Icosapent Ethyl and prescribed to reduce the risk of cardiovascular events in patients with elevated triglycerides and other risk factors for heart disease), Epanova (Omega-3-Carboxylic Acids and prescribed for the treatment of severe hypertriglyceridemia), Omtryg (Omega-3-Acid Ethyl Esters A and prescribed to lower very high triglyceride levels in adults).

What you may notice is that all prescription fish oil supplements are essentially approved for the treatment of hypertriglyceridemia, which is extremely high blood triglycerides. With Big Pharma often encouraging off-label use, like for those with a previous heart attack or sometimes just multiple risk factors, it becomes a tide that lifts all fish oil boats. With the potential for not just no effect but for very real harm, it becomes a slippery slope indeed. Without evidence of a clear benefit, I prefer my fish oil the way Mother Nature originally packaged it – in fish!


[1] (Zhang, 2020)

[2] (This excludes deep-fried fish, which is associated with an increased risk; Krittanawong, 2021)

Study:

Chen G, Qian Z, Zhang J, Zhan S, Zhang Z, Vaughn MG, Aaron HE, Wang C, Lip GYH, Lin H. Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study. BMJ Medicine 2024;3:e000451. doi: 10.1136/bmjmed-2022-000451.

Additional Resources:

Assadourian JN, Peterson ED, McDonald SA, Gupta A, Navar AM. Health Claims and Doses of Fish Oil Supplements in the US. JAMA Cardiol. 2023 Oct 1;8(10):984-988. doi: 10.1001/jamacardio.2023.2424.

Krittanawong, Chayakrit; Isath, Ameesh; Hahn, Joshua; Wang, Zhen; Narasimhan, Bharat; Kaplin, Scott; Jneid, Hani; Virani, Shazana; Tang, W.H. (2021). Fish Consumption and Cardiovascular Health: A Systematic Review. The American Journal of Medicine. 134. Doi: 10.1016/j.amjmed.2020.12.017.

Zhang B, Xiong K, Cai J, Ma A. Fish Consumption and Coronary Heart Disease: A Meta-Analysis. Nutrients. 2020 Jul 29;12(8):2278. doi: 10.3390/nu12082278.

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