Review of heart-cancer studies omits key evidence and questions 03/05/2020
The authors of two new clinical evidence reviews conclude that seafood-source omega-3 fatty acids don’t significantly reduce cancer or cardiovascular risks.
Their authors' conclusions regarding cancer risks rest on a small number of low-quality trials, and omit a far larger body of encouraging non-clinical evidence.
And their findings regarding cardiovascular risk-reduction appear to grossly underweigh and undervalue the very positive outcomes of several recent well-designed clinical trials.
No nutrient — including omega-3s — constitutes a miracle remedy or cure for heart disease or cancer.
Let's take a broad look at the pair of recent evidence reviews, then delve more deeply into each one.
Omega-3s vs. cancer and heart disease: Two clinical reviews miss the mark
Last week, a team from Britain’s University of East Anglia (UEA) published two separate reviews of the clinical evidence, regarding the effects of omega-3s on the risks for cancer and heart disease.
Both evidence reviews were funded by the UN’s World Health Organization, and — like previous evidence reviews from the UEA team regarding the preventive health potential of omega-3s — this one was led by Dr. Lee Hooper.
The University characterized the team's conclusions in a press release: “… two systematic reviews … find that omega 3 supplements may slightly reduce coronary heart disease mortality and events, but slightly increase risk of prostate cancer. Both beneficial and harmful effects are small.” (Their conclusion on prostate cancer seems dubious: see Omega-3 Diet Reduced Prostate Risk Factors and its links to related articles.)
Lead author Lee Hooper, M.D., did add two important caveats: “The evidence on omega-3s mostly comes from trials of fish oil supplements, so health effects of oily fish, a rich source of long-chain omega-3s, are unclear. Oily fish is a very nutritious food as part of a balanced diet, rich in protein and energy as well as important micronutrients such as selenium, iodine, vitamin D, and calcium — it is much more than an omega-3 source.”
The key conclusions of the UEA team’s heart-evidence review seem to ignore the very positive findings of several recent clinical trials that tested the ability of omega-3 fish oil to reduce the risks for adverse cardiovascular events such as heart attacks.
Review concludes — wrongly — that omega-3s don't cut heart risks
The UEA team reviewed the evidence from 86 clinical studies involving 162,796 participants that examined omega-3s’ effects on the risks for heart disease death and adverse events (e.g., heart attacks).
They concluded that higher omega-3 intakes slightly reduce the risk of heart-related death and adverse events (such as heart attacks) and lower blood triglyceride levels — a conclusion they say was based on “moderate- and low-certainty [clinical] evidence”.
Perhaps unsurprisingly — because long-term trials involving diet changes are notoriously difficult to conduct and yield unreliable results — they didn't find strong clinical evidence that diets higher in fish reduce cardiovascular risks. But there's a huge amount of epidemiological evidence linking diets higher in fish to reduced cardiovascular risks.
Unsurprisingly, they also found that higher omega-3 intakes lower high blood triglyceride levels — a major cardiovascular risk factor — by about 15%, in a dose-dependent way.
They also found that higher takes of the sole plant-source omega-3, called ALA, slightly reduce the risk of adverse cardiovascular events and arrhythmia.
The UEA team say that theirs was “the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date”. However, they focused on analyzing 28 trials they deemed at low risk of bias (Abdelhamid AS et al. 2020).
The trials included in the UEA team’s review ranged in length from one to 7.3 years and involved people with varying cardiovascular risks, mainly in high-income countries.
Most of the trials employed omega-3 fish oil capsules, but some used foods enriched with the weaker plant-source omega-3 fatty acid called ALA, or simply compared the effects of advising people to raise their seafood intakes versus continuing their normal diets.
The daily omega-3 doses used in the clinical trials ranged from 0.5 grams (500mg) to more than 5 grams (5000mg), and 19 trials employed daily doses of at least 3 grams.
Reasons to doubt the heart-trials review: Dose, size, and duration
The UEA team was essentially trying to identify the average heart-health effects of omega-3s, but based on data from 86 widely different trials.
And wide variations in the doses used in the 86 clinical trials reviewed by the UEA team go a long way toward explaining their downbeat conclusions:
- The varying degrees of benefit seen in omega-3/heart trials are clearly related to dose: two recent large placebo-controlled trials reported conflicting results, but the more successful trial used an 3992mg daily dose, versus the 840mg daily dose used in the less successful trial.
- Two other recent omega-3/heart trials found low omega-3 doses ineffective at reducing adverse cardiovascular events like heart attacks.
- A recent meta-analysis of data from 13 controlled clinical trials found better outcomes with higher omega-3 doses.
Weirdly, the UEA team’s analysis grossly undervalued the strikingly positive outcomes of several recent large, lengthy, placebo-controlled clinical trials testing the effects of supplemental omega-3 fish oil on the risks for heart disease death and adverse events: see Omega-3 Heart Benefits Affirmed by Big New Review and its links to related articles.
British review team claims omega-3s don’t curb cancer risks
For their review of the evidence regarding the potential anti-cancer effects of omega-3s, the UEA team examined 47 clinical trials involving adults in three categories: people with cancer, people without cancer, and people at relatively high risk of cancer (Hanson S et al. 2020).
Those trials involved 108,194 participants in trials lasting at least one year who were randomly assigned to consume more omega-3 fats (typically from fish oils) or maintain their usual intake.
The UEA researchers analyzed the number of people who either received a new diagnosis of cancer or died from some form of cancer.
In line with the conclusions of most prior reviews of evidence on the same subject, the UEA team concluded that higher omega-3 intakes didn’t reduce the risk for any cancers during the duration of any of the trials: “Our review concurs with a systematic review of observational [i.e., epidemiological] data and two including fewer trials (10 and 19 to our 34) suggesting omega-3 intake is not associated with [higher or lower] total cancer risk.”
But the findings of the UEA team’s cancer-evidence review should be taken with a substantial grain of salt, for several reasons:
- Their conclusions underplay the short length of most of the trials included in their review — a very big shortcoming, given the long periods of time over which most cancers develop.
- A huge amount of evidence from clinical, epidemiological, and lab studies supports the idea that seafood-source omega-3s tend to curb the risk of common cancers, slow their growth, and/or enhance treatment outcomes.
- As the review’s authors noted, the reliability of their conclusions is limited by the short duration of the included trials, and the fact that the trials provided little information about participants’ intakes of omega-6 fatty acids, excess intakes of which are linked to higher cancer risks.
- Hundreds of clinical, epidemiological, and lab studies indicate that seafood-source omega-3s (EPA and DHA) possess cancer-curbing properties. For example, see Omega-3s Target Toughest Breast Tumors, Fish and Omega-3s Linked to Breast Cancer Survival, Omega-3s May Curb Common Cancer Type, Omega-3s Restrain Breast Cancer Risk, and Cancer Findings Bolster Omega-3s' Breast and Prostate Potential.
A key but ignored cancer factor: Extremely high omega-6 fat intakes
The UEA team noted that the amounts of omega-3 and omega-6 fats — most of which were almost certainly omega-6 — consumed by trial participants varied widely, from 0.8% of calories to almost 38% of calories.
But the researchers failed to account for the likely effects of that wide variation, which is a major flaw of their evidence review.
For many years now, high omega-6 fat intakes — which are typical of the standard American diet — have been persuasively linked to higher cancer risks (Thiébaut AC et al. 2009). For example, see Breast Cancer Tied to Omega Imbalance ... Again.
As Pennsylvania State University researchers wrote earlier this year, “… the benefits of consuming omega-3 fatty acid supplements such as fish oil with the goal of reducing the incidence of … cancer remain controversial. Critical review of the published data … strongly suggests that customized clinical prevention trials are needed to resolve [this] controversy … more attention should be given to multiple factors including the [omega-3] dose, the specific placebo used, [the] duration of [omega-3] administration … [and] the ratio of omega-3: omega-6 fatty acids ...”. (El-Bayoumy K, Manni A 2020)
Sadly, because it's very difficult to patent an omega-3 supplement, funding for large, lengthy trials testing fish oils for cancer prevention is scarce.
- Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KH, Summerbell CD, Worthington HV, Song F, Hooper L. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Feb 29;3:CD003177. doi: 10.1002/14651858.CD003177.pub5. Review.
- El-Bayoumy K, Manni A. Customized Prevention Trials Could Resolve the Controversy of the Effects of Omega-3 Fatty Acids on Cancer. Nutr Cancer. 2020;72(2):183-186. doi: 10.1080/01635581.2019.1651348. Epub 2019 Aug 13
- Hanson S, Thorpe G, Winstanley L, Abdelhamid AS, Hooper L; PUFAH group. Omega-3, omega-6 and total dietary polyunsaturated fat on cancer incidence: systematic review and meta-analysis of randomised trials. Br J Cancer. 2020 Feb 29. Doi: 10.1038/s41416-020-0761-6. [Epub ahead of print]
- Thiébaut AC, Chajès V, Gerber M, Boutron-Ruault MC, Joulin V, Lenoir G, Berrino F, Riboli E, Bénichou J, Clavel-Chapelon F. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer. 2009 Feb 15;124(4):924-31. doi: 10.1002/ijc.23980.