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HomeEditor's PickStudies show little or no benefit from omega-3 supplements and slight risk

Studies show little or no benefit from omega-3 supplements and slight risk

Two large, randomised UK studies found that taking daily omega-3 fats in supplement form have no significant overall impact on a person's health, no demonstrable effect on the prevention or treatment of depression or anxiety and may very slightly increase cancer risk.

Consumption of fish oil supplements is promoted as having a wide range of positive impacts on health. These are purported to include lowering the risk of strokes, as well as diseases such as cancer and dementia. But, BBC News reports, researchers at University of East Anglia (UEA) found taking daily supplements will likely have no significant impact on a person's health. The research relates specifically to supplements, rather than omega-3 derived from eating fish, with experts still suggesting the latter is good for the heart, as well as general health.

More than 100,000 participants were randomised to either consume more omega-3 fats in supplement form, or maintain their usual intake, for at least a year. Researchers found that if 1,000 people took supplements for approximately four years, the actual effects on their health, both positively or negatively, would be minimal at best.

Dr Lee Hooper, from UEA's Norwich Medical School, said that the study – funded by the World Health Organisation (WHO) – adds to mounting evidence that omega-3 supplements are failing to offer consumers the benefits they advertise. "Our previous research has shown that long-chain omega 3 supplements, including fish oils, do not protect against conditions such as anxiety, depression, stroke, diabetes or death," he said.

"In fact, we found that they may very slightly increase cancer risk, particularly for prostate cancer. With the harmful environmental factors associated with over-fishing, Hooper added that it seems "unhelpful" for people to continue taking supplements that give" little or no benefit".

Hooper added that the environmental damage associated with decreasing fish stocks is not comparative with the minimal health benefits associated with supplements.

Abstract
Background: The relationship between long-chain omega-3 (LCn3), alpha-linolenic acid (ALA), omega-6 and total polyunsaturated fatty acid (PUFA) intakes and cancer risk is unclear.
Methods: We searched Medline, Embase, CENTRAL and trials registries for RCTs comparing higher with lower LCn3, ALA, omega-6 and/or total PUFA, that assessed cancers over ≥12 months. Random-effects meta-analyses, sensitivity analyses, subgrouping, risk of bias and GRADE were used.

Results: We included 47 RCTs (108,194 participants). Increasing LCn3 has little or no effect on cancer diagnosis (RR1.02, 95% CI 0.98–1.07), cancer death (RR0.97, 95% CI 0.90–1.06) or breast cancer diagnosis (RR1.03, 95% CI 0.89–1.20); increasing ALA has little or no effect on cancer death (all high/moderate-quality evidence). Increasing LCn3 (NNTH 334, RR1.10, 95% CI 0.97–1.24) and ALA (NNTH 334, RR1.30, 95% CI 0.72–2.32) may slightly increase prostate cancer risk; increasing total PUFA may slightly increase risk of cancer diagnosis (NNTH 125, RR1.19, 95% CI 0.99–1.42) and cancer death (NNTH 500, RR1.10, 95% CI 0.48–2.49) but total PUFA doses were very high in some trials.
Conclusions: The most extensive systematic review to assess the effects of increasing PUFAs on cancer risk found increasing total PUFA may very slightly increase cancer risk, offset by small protective effects on cardiovascular diseases.

Authors
Sarah Hanson, Gabrielle Thorpe, Lauren Winstanley, Asmaa S. Abdelhamid, Lee Hooper

UEA research found that omega-3 fats have little or no effect on anxiety and depression. Increased consumption of omega 3 fats is widely promoted globally because of a common belief that it will protect against, or even reverse, conditions such as anxiety and depression. But a systematic review finds that omega 3 supplements offer no benefit.

Omega 3 is a type of fat. Small amounts are essential for good health and can be found in the food that we eat including nuts and seeds and fatty fish, such as salmon. Omega 3 fats are also readily available as over-the-counter supplements and they are widely bought and used.

The research team looked at 31 trials of adults with and without depression or anxiety. More than 41,470 participants were randomised to consume more long-chain omega-3 fats (fish oils), or maintain their usual intake, for at least six months. They found that the supplements had little or no effect in preventing depression or anxiety symptoms.

Hooper said: “Our previous research has shown that long-chain omega 3 supplements, including fish oils, do not protect against conditions such as heart disease, stroke, diabetes or death. This large systematic review included information from many thousands of people over long periods. Despite all this information, we don’t see protective effects. The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on depression or anxiety, and they should not be encouraged as a treatment.”

Dr Katherine Deane, from the UEA School of Health Sciences, said “Oily fish can be a very nutritious food as part of a balanced diet. But we found that there is no demonstrable value in people taking omega 3 oil supplements for the prevention or treatment of depression and anxiety. Considering the environmental concerns about industrial fishing and the impact it is having on fish stocks and plastic pollution in the oceans, it seems unhelpful to continue to swallow fish oil tablets that give no benefit."

The research was funded by the WHO.

Abstract
Background: There is strong public belief that polyunsaturated fats protect against and ameliorate depression and anxiety.
Aims: To assess effects of increasing omega-3, omega-6 or total polyunsaturated fat on prevention and treatment of depression and anxiety symptoms.
Method: We searched widely (Central, Medline and EMBASE to April 2017, trial registers to September 2016, ongoing trials updated to August 2019), including trials of adults with or without depression or anxiety, randomised to increased omega-3, omega-6 or total polyunsaturated fat for ≥24 weeks, excluding multifactorial interventions. Inclusion, data extraction and risk of bias were assessed independently in duplicate, and authors contacted for further data. We used random-effects meta-analysis, sensitivity analyses, subgrouping and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment.

Results: We included 31 trials assessing effects of long-chain omega-3 (n = 41 470), one of alpha-linolenic acid (n = 4837), one of total polyunsaturated fat (n = 4997) and none of omega-6. Meta-analysis suggested that increasing long-chain omega-3 probably has little or no effect on risk of depression symptoms (risk ratio 1.01, 95% CI 0.92–1.10, I2 = 0%, median dose 0.95 g/d, duration 12 months) or anxiety symptoms (standardised mean difference 0.15, 95% CI 0.05–0.26, I2 = 0%, median dose 1.1 g/d, duration 6 months; both moderate-quality evidence). Evidence of effects on depression severity and remission in existing depression were unclear (very-low-quality evidence). Results did not differ by risk of bias, omega-3 dose, duration or nutrients replaced. Increasing alpha-linolenic acid by 2 g/d may increase risk of depression symptoms very slightly over 40 months (number needed to harm, 1000).
Conclusions: Long-chain omega-3 supplementation probably has little or no effect in preventing depression or anxiety symptoms.

Authors
Katherine HO Deane, Oluseyi F Jimoh, Priti Biswas, Alex O'Brien, Sarah Hanson, Asmaa S Abdelhamid, Chris Fox, Lee Hooper

UEA researchers have also found that omega-3 fats have little or no effect on risk of type 2 diabetes. Increased consumption of omega 3 fats is widely promoted globally because of a common belief that it will protect against, or even reverse, conditions such as diabetes. But a systematic review commissioned by the WHO finds that omega 3 supplements offer no benefit.

Despite over 58,000 participants being randomised into long-term trials, and 4% of those participants developing diabetes, the people who were randomised to consume more long-chain omega-3 fats (fish oils) had the same risk of diabetes diagnosis as the control group who did not take more fish oil.

Blood glucose, insulin and glycated haemoglobin, measures of how well our bodies handle sugars (glucose metabolism) and important measures of diabetes risk, are also similar in people taking and not taking additional fish oils. There was a consistent lack of effect of fish oils (long-chain omega-3 fats) on any of these factors related to diabetes risk.

However, there was some (weak) evidence that when people take high doses of fish oils they may experience worsening glucose metabolism.

Omega 3 is a type of fat. Small amounts are essential for good health and can be found in the food that we eat. The main types of omega 3 fatty acids are alpha¬linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

The research team assessed the effects of long-chain omega-3 fats, ALA, omega-6 and polyunsaturated fatty acids (PUFAs) – taken as supplementary capsules, or via enriched or naturally rich foods.

The systematic review combines the results of 83 randomised controlled trials involving 121,070 people with and without diabetes, all of at least six months duration. Participants included men and women, some healthy and others with existing diabetes, from North America, South America, Europe, Australia and Asia, in studies published from the 1960s until 2018.

The research assessed the effects of increasing long-chain omega-3 fats, ALA, omega-6 and polyunsaturated fatty acids (PUFAs) on diabetes and glucose metabolism.

Participants were randomly assigned to increase their polyunsaturated fats or to maintain their usual intake for at least six months. There was clearly no effect of increasing long-chain omega-3 fats on diabetes, but there was insufficient information from trials of ALA, omega-6 or total polyunsaturated fats to assess either protective or harmful effects.

The reviewers double-checked their data using sensitivity analyses. For example, they checked that the results did not alter when only the very highest quality trials (those at least risk of bias) were included. They used subgrouping to check whether results differed with different doses of long-chain omega-3 (not finding different effects at different doses except a suggestion of harm at doses over 4.4 grams per day) or by trial duration (there was no suggestion of different effects in longer or shorter trials).

The results show that increasing long-chain omega-3 had little or no effect on diabetes diagnosis or glucose metabolism, but high doses, at levels found in some supplements, could worsen glucose metabolism.

Hooper said: “Our previous research has shown that long-chain omega 3 supplements, including fish oils, do not protect against conditions such as heart disease, stroke or death. This review shows that they do not prevent or treat diabetes either.

“Omega-3 supplements should not be encouraged for diabetes prevention or treatment. If people do choose to take supplementary fish oil capsules to treat or prevent diabetes, or to reduce levels of triglycerides in their blood, then they should use doses of less than 4.4 grams per day to avoid possible negative outcomes.

“This large systematic review included information from many thousands of people over long periods. Despite all this information, we don’t see protective effects. The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on diabetes.”

Joint first author, Dr Julii Brainard also from Norwich Medical School, said: “Oily fish can be a very nutritious food as part of a balanced diet, but we did not find enough trials that encouraged participants to eat more oily fish to know whether it is useful in preventing diabetes or improving glucose metabolism.

“What we did find is that there is no demonstrable value in ordinary people taking omega 3 oil supplements for the prevention or treatment of diabetes.

“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.

“Future trials need to measure and assess baseline omega-3 intakes, and assess effects of eating more oily fish – not just supplements,” she added.

Abstract
Objective: To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism.
Design: Systematic review and meta-analyses.
Data sources: Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews.

Eligibility criteria: Randomised controlled trials of at least 24 weeks’ duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA1c), and/or homoeostatic model assessment for insulin resistance (HOMA-IR).
Data synthesis: Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE.

Results: 83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA1c mean difference −0.02%, 95% confidence interval −0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, −4.34 to 6.37, pmol/L; HOMA-IR 0.06, −0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism.
Conclusions: This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus.

Authors
Tracey J Brown, Julii Brainard, Fujian Song, Xia Wang, Asmaa Abdelhamid, Lee Hooper

Omega 3 supplements have little or no effect on the risk of heart disease, stroke or death, UEA researchers have found. Increased consumption of omega 3 fats is widely promoted globally because of a common belief that that it will protect against heart disease. But a new UEA-led Cochrane review – the international gold standard for high quality, trusted health information – finds that omega 3 supplements offer little, if any, benefit.

Omega 3 is a type of fat. Small amounts are essential for good health, and they can be found in the food that we eat. The main types of omega 3 fatty acids are alpha¬linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

The new Cochrane systematic review combines the results of 79 trials involving 112,059 people. These studies assessed the effects of consuming additional omega 3 fat, compared to usual or lower omega 3, on diseases of the heart and circulation.

The studies recruited men and women, some healthy and others with existing illnesses from North America, Europe, Australia and Asia. Participants were randomly assigned to increase their omega 3 fats or to maintain their usual intake of fat for at least a year.

Hooper said: “The findings of this review go against the popular belief that long-chain omega 3 supplements, including fish oils, protect the heart. This large systematic review included information from many thousands of people over long periods. Despite all this information, we don’t see protective effects.

“The review provides good evidence that taking long-chain omega 3 (fish oil, EPA or DHA) supplements does not benefit heart health or reduce our risk of stroke or death from any cause.

“The most trustworthy studies consistently showed little or no effect of long-chain omega 3 fats on cardiovascular health. On the other hand, while oily fish is a healthy food, it is unclear from the small number of trials whether eating more oily fish is protective of our hearts.

“This systematic review did find moderate evidence that ALA, found in plant oils such as rapeseed or canola oil, and nuts, particularly walnuts, may be slightly protective of some diseases of the heart and circulation.

“However, the effect is very small, 143 people would need to increase their ALA intake to prevent one person developing arrhythmia.

“One thousand people would need to increase their ALA intake to prevent one person dying of coronary heart disease or experiencing a cardiovascular event.”

Abstract
Background: Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this.
Objectives: To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids.

Search methods: We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors.
Selection criteria: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake.
Data collection and analysis: Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression.

Main results: We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). A meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression.
Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence), cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear.
Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by ~15% in a dose-dependent way (high-certainty evidence).
Authors' conclusions: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia.

[link url="https://www.bbc.com/news/health-51674313"]BBC News report[/link]

[link url="https://www.nature.com/articles/s41416-020-0761-6"]British Journal of Cancer abstract[/link]

[link url="https://www.uea.ac.uk/about/-/fish-oil-supplements-have-no-effect-on-anxiety-and-depression"]University of East Anglia (UEA) material[/link]

[link url="https://www.cambridge.org/core/journals/the-british-journal-of-psychiatry/article/omega3-and-polyunsaturated-fat-for-prevention-of-depression-and-anxiety-symptoms-systematic-review-and-metaanalysis-of-randomised-trials/B074BDC1CF8D59D234E30B961E9EADF8"]British Journal Psychiatry abstract[/link]

[link url="https://www.uea.ac.uk/about/-/fish-oil-supplements-have-no-effect-on-type-2-diabetes"]UEA material[/link]

[link url="https://www.bmj.com/content/366/bmj.l4697"]BMJ abstract[/link]

[link url="https://www.uea.ac.uk/about/-/omega-3-supplements-have-little-or-no-heart-or-vascular-health-benefit"]UEA material[/link]

[link url="https://www.cochrane.org/news/omega-3-fatty-acids-primary-and-secondary-prevention-cardiovascular-disease"]Cochrane Database of Systematic Reviews abstract 5th update[/link]

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