New clinical review overlooked a large body of encouraging evidence, and its authors acknowledge weaknesses 09/09/2019
People typically associate fish oil with heart health, and secondarily with brain health.
But there’s good evidence that diets rich in the “long-chain” omega-3s found only in fish and fish, krill, and other marine-source oils — EPA and DHA — bring significant metabolic benefits.
Those metabolic benefits probably flow in large part from the fact that — in addition to performing essential brain and immune functions — the body relies on EPA and DHA to end unnecessary inflammation — including the chronic, disease-promoting kind associated with the standard American diet.
That idea fits with a recent finding that the anti-inflammatory effects of plant-source antioxidants appear to explain their anti-diabetes benefits: see Top 5 Diets for Reducing Diabetes Risk.
Sadly, the standard American diet contains excessive, pro-inflammatory amounts of sugars, refined starches, and omega-6 fats, which come mostly from cheap vegetable oils such as soy, corn, safflower, and sunflower. Healthier, low-omega-6 alternatives include olive, canola, macadamia, coconut, and “high-oleic” sunflower oils.
Making matters worse, the excess of omega-6 fats in the American diet also impairs absorption of the “short-chain”, plant-source omega-3 fat known as ALA, which the body uses to make small amounts of EPA and DHA. The leading low-omega-6 sources of ALA in the average American’s diet are canola oil, avocados, walnuts, dark, leafy greens (e.g., spinach), and flaxseed or flaxseed oil.
The fact that the body uses omega-3 EPA and DHA to end unnecessary or excessive inflammation probably helps explain why so many studies link higher intakes of these fishy fats to reduced risk for, and severity of, metabolic disorders, including unhealthful blood fat profiles.
There’s also significant evidence that — over the long term — regular supplemental fish oil and/or diets rich in fatty fish may help reduce risk factors for diabetes: see Omega-3s May Slash Men's Diabetes Risk, Omega-3s Reduced Diabetes Risk Markers, Fish & Omega-3s May Help Deter Diabetes, Omega-3s Deter Diabetes Signs in Clinical Trial, Omega-3s Seen to Fight Metabolic Syndrome, Omega-3s Show Genetic Benefits, Diabetes Study Debacle: Can Fishy Nutrients Help?, Omega-6/Omega-3 Imbalance Pushes Heart/Diabetes Perils, and related articles in the Omega-3s & Metabolic Health section of our news archive.
And although omega-3 fish oil doesn’t appear to enhance insulin sensitivity or stabilize blood sugar levels — two key goals of diabetes prevention and care — it may influence key “working” genes called PPARs in potentially beneficial ways: see Drug May Help Prevent Diabetes: Omega-3s Exert Comparable Effects.
Interestingly, emerging evidence suggests that krill oil may be more effective at reducing metabolic risks, including diabetes, because its omega-3 EPA and DHA occur in the phospholipid form, which is significantly better-absorbed than the triglyceride-form EPA and DHA in most fish and fish oil: see Krill Oil Wins Again for Blood Fat-Sugar Benefits.
Let’s look at the new evidence review, and reasons to view its findings with caution, especially regarding the potential long-term anti-diabetic effects of fish oil and/or diets high in fatty, omega-3-rich fish.
Those potential anti-diabetic effects include the ability — shown in long-term human studies — of seafood-source omega-3s (and supplemental curcumin) to stimulate production of a key messenger protein called adiponectin, higher levels of which are linked to reduced risks for diabetes and cardiovascular disease.
Review of clinical trials finds no evidence that fish oil might prevent diabetes
The new review of evidence from clinical trials — conducted by researchers at Britain’s University of East Anglia — was commissioned by the World Health Organization (WHO) of the United Nations (Brown TJ et al. 2019).
The goal of the review was to analyze the outcomes of clinical trials that had tested the effects of three different categories of polyunsaturated fats — omega-3 EPA + DHA (singly or combined), omega-3 ALA, and omega-6 fats — on diabetes and metabolism of glucose (blood sugar).
The review included evidence from clinical trials that tested the effects either of dietary supplements or of foods naturally rich in or fortified with one of the three kinds of fat.
Out of all the clinical trials published from the 1960s to 2018, the authors of the new review selected 83 trials that involved 121,070 people with and without diabetes.
All the included trials lasted at least six months, and more than 58,000 (48%) of the 121,070 participants took part in trials lasting longer than six months.
Most of those longer trials were ones that tested the effects of long-chain omega-3 fats (EPA + DHA, EPA alone, or DHA alone), which lasted an average of nearly three years (33 months).
The participants in the 83 selected trials included men and women from North America, South America, Europe, Australia and Asia, who were randomly assigned to either increase their intakes of one of the three categories of fats or to maintain their usual intakes.
After analyzing the data from the 83 included trials, the authors could find no clear effect on diabetes risk from consuming at least 2,000 mg per day of long-chain omega-3s (EPA + DHA, EPA alone, or DHA alone) from supplemental fish oil.
Likewise, the review’s authors didn’t find that higher intakes of omega-3 EPA + DHA influenced key risk factors for diabetes, including glucose (blood sugar) metabolism, blood glucose levels, and fasting blood levels of insulin.
Note: The authors of the evidence review admitted that the weaknesses of the underlying evidence mean that their findings aren’t necessarily the final word: see “Review’s authors acknowledged weaknesses that command caution”, below.
The authors of the evidence review reported finding some weak evidence suggesting that high daily doses of fish oil — 4,400 mg or more — might worsen glucose metabolism.
Unfortunately, they couldn’t find enough good-quality clinical evidence to allow clear conclusions about the negative or positive effects of plant-source omega-3 ALA, omega-6 fats, or total polyunsaturated fats (omega-3 + omega-6) on diabetes risk factors or the risk for diabetes.
Overall, as they concluded, “No convincing evidence suggests that altering intakes of long chain omega-3 [EPA + DHA], alpha-linolenic acid [ALA], omega-6 [fat], or total PUFA [polyunsaturated fats] alters glucose metabolism or risk of diabetes.”
However, as we noted at the beginning of this article, seafood-source omega-3s may exert beneficial long-term effects on factors that promote diabetes and related metabolic disorders: see Omega-3s Seen to Fight Metabolic Syndrome, Omega-3s Show Genetic Benefits, and related articles in the Omega-3s & Metabolic Health section of our news archive.
No effect seen from varying omega-3/omega-6 intake ratios
There’s ample evidence of the negative health effects of the average American’s extremely high — and historically unprecedented — intakes of omega-6 fats and low intakes of omega-3 fats: see our Omega-3/6 Balance page and the Omega-3/6 Balance section of our news archive.
The authors of the evidence review said that they “… did not find evidence of the importance of the omega-3/omega-6 ratio …”. However, they noted that “… doses of omega-6 were often small, so we could be missing important effects of the ratio …”.
And they acknowledged that the quantity and quality of evidence needed to gauge the possible effects of varying omega-3/6 intake ratios were both low, which precluded clear conclusions.
Review’s authors acknowledged weaknesses that command caution
The results of this clinical evidence review should be taken seriously — especially because they echo those of the only other such evidence review (Hartweg J et al. 2008) — but there are good reasons to view them with caution.
As the authors said, “Weaknesses of the review include limited data on effects of increasing alpha-linolenic acid [ALA], omega-6, and total PUFA [polyunsaturated fats], as well as potentially serious risk of bias in many included trials.”
And, as they acknowledged, “… missing data may be a serious threat to our understanding in this review. For example, we … are aware of 15 further trials with data that could not be included. This volume of missing data could considerably alter the findings of the review.”
Only 10 of the 83 included trials could be seen as basically unbiased. That’s because the authors of and/or participants in the other 73 trials probably knew or may have known whether the participants were getting placebo capsules or capsules containing the fats being tested.
Importantly, the authors of the review couldn’t find or therefore analyze any trials that tested the effects of increased consumption of fatty, omega-3-rich fish — probably because such trials haven’t been conducted due to the difficulty of conducting them over sufficiently long periods of time.
Finally, one of the co-authors of the evidence review — Dr. Julii Brainard — made an important point: “We would also have liked to find out whether taking more omega-3 might be useful in those people with low omega-3 intakes — as giving more omega-3 is more likely to be useful in adults with low intakes. But unfortunately, most trials didn’t report omega-3 intake levels of participants at the start of the trial, so we still don’t know.”
As she said, “Future trials need to measure and assess baseline omega-3 intakes and assess effects of eating more oily fish — not just supplements.”
- Brown TJ, Brainard J, Song F, Wang X, Abdelhamid A, Hooper L; PUFAH Group. Omega-3, omega-6, and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review and meta-analysis of randomised controlled trials. BMJ. 2019 Aug 21;366:l4697. Doi: 10.1136/bmj.l4697.
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- Forouhi NG et al. Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study. PLoS Med. 2016 Jul 19;13(7):e1002094. doi: 10.1371/journal.pmed.1002094. eCollection 2016 Jul.
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- Zhu Y, Li M, Rahman ML, Hinkle SN, Wu J, Weir NL, Lin Y, Yang H, Tsai MY, Ferrara A, Zhang C. Plasma phospholipid n-3 and n-6 polyunsaturated fatty acids in relation to cardiometabolic markers and gestational diabetes: A longitudinal study within the prospective NICHD Fetal Growth Studies. PLoS Med. 2019 Sep 13;16(9):e1002910. doi: 10.1371/journal.pmed.1002910. eCollection 2019 Sep.