Different omega-3s, different benefits?
Before diving deep into the omega-3 waters it is important to be clear on what we mean by omega-3s: The main omega-3 fatty acids present on the market consist of the marine-sourced eicosapentaenoic acid (EPA, C20:5 n-3) and docosahexaenoic acid (DHA, C22:6 n-3), and alpha-linolenic acid (ALA, C18:3 n-3) from plants like flax and chia.
Omega-3s are not created equal, however, and different fatty acids have been associated with different benefits.
Much attention has been paid to the conversion of ALA to the longer chain EPA, with many experts pegging this conversion at as low as 3% to as much as 20% for vegetarians. The proportion of ALA converted to DHA is small.
In addition, the gender plays an important role with women of reproductive age reportedly converting ALA to EPA at a 2.5-fold greater rate than healthy men. This conversion obviously contributes to the body's pool of EPA and DHA, which play a key role in, amongst other things, maintaining cardiovascular health.
A recent market entrant is Ahiflower oil from Buglossoides arvensis, which reportedly offers the highest levels of non-GM omega-3 essential fatty acids among commercially available dietary plant oils. Ahiflower oil combines ALA and high levels of stearidonic acid (SDA, 18:4 n-3). SDA converts to EPA at ratio of 30% to 35%, and direct consumption of SDA is far more efficient than consuming large amounts of ALA.
The strongest and most established body of science for the marine omega-3 fatty acids is in relation to cardiovascular health, first reported by being first reported in the early 1970s by Dr Jorn Dyerberg and his co-workers in The Lancet and The American Journal of Clinical Nutrition.
To date, the polyunsaturated fatty acids (PUFAs) have been linked to improvements in blood lipid levels, a reduced tendency of thrombosis, blood pressure and heart rate improvements, and improved vascular function.
A recent meta-analysis published in the Mayo Clinic Proceedings indicated that EPA and DHA from food and supplements may reduce the risk of coronary heart disease (CHD). Data from 18 randomized clinical trials (RCTs) indicated that EPA and DHA were associated with a non-statistically significant 6% risk reduction in CHD among all populations, while the risk reduction increased to a statistically significant 18% when data from 16 prospective cohort studies was assessed.
The data also indicated that among RCTs there was a statistically significant reduction in CHD risk in higher risk populations, including a 16% in those with high triglycerides and 14% in those with high LDL cholesterol. The meta-analysis was funded by the Global Organization for EPA and DHA Omega-3s (GOED), but the organization played no role in any part of the analysis.
A 2014 meta-analysis, also financed by GOED, found that for untreated hypertensive subjects, omega-3s were associated with average reductions of systolic and diastolic blood pressure of 4.51 mmHg and 3.05 mmHg, respectively (American Journal of Hypertension).
A 2012 meta-analysis by scientists at the Chinese Academy of Medical Sciences & Peking Union Medical College found that daily supplements of omega-3s for an average of 56 days were associated with a 2.3% improvement in flow-mediated dilation (FMD), a measure of a blood vessel's healthy ability to relax (Atherosclerosis, Vol. 221, pp. 536-543).
The heart health benefits of omega-3s are supported by qualified health claims for dietary supplements containing EPA and DHA and coronary heart disease (CHD) risk (approved in 2000). A similar claim for conventional foods was approved in 2004).
GOED is currently petitioning the FDA for a qualified health claim for EPA and DHA to reduce blood pressure in the general population. On 24 January, the FDA requested a seventh review extension with a new deadline of 27 April 2017.
The second most established area of research, particularly for the marine omega-3 fatty acids, is cognitive performance and reducing the rate of age-related cognitive decline.
The data has not always been consistent in this area, with experts noting that some studies have performed in diseased patients (for example, Alzheimer’s disease) or have used insufficient doses.
Despite these limitations, many clinical trials have shown clear benefits to cognitive health, with a 2015 meta-analysis of randomized, controlled trials showing that daily DHA doses over 1 gram were required to improve some aspects of cognitive function in older adults (PLoS One).
A key area for many is the role of omega-3 fatty acids in the healthy development of a fetus during pregnancy.
A study from Canada, for example, reported that an increased intake of the omega-3 DHA during pregnancy could produce improved motor function in the offspring in later life (The Journal of Pediatrics).
And increased levels were linked to improved visual, cognitive, and motor development in the offspring, report the researchers from Wayne State University School of Medicine, Detroit and Laval University.
Results of a meta-analysis of 15 gold standard randomized controlled trials presented at the Experimental Biology 2016 event in San Diego, CA by scientists from Tufts University and Harvard indicated that EPA+DHA supplementation during pregnancy or infancy was associated with improved motor skills in the children (The FASEB Journal).
Mood and behavior
Linked to cognitive performance are reports that supplements of the fatty acids may improve mood and behavior. Several studies have reported that supplementation with EPA and DHA may result in improvements in behavior and learning of children, although such studies have their critics.
In terms of mood, several studies, such as the French study published in the American Journal of Clinical Nutrition, have reported benefits for EPA and symptoms of depression.
Moreover, a joint Anglo-Iranian study reported that depression ratings were cut by 50% following daily one gram supplements of EPA, an effect similar to that obtained by the antidepressant drug fluoxetine (Australian and New Zealand Journal of Psychiatry).
Researchers have also reported a potential role for EPA in lowering the severity of symptoms of post-traumatic stress disorder (PTSD). According to data published in the Journal of Affective Disorders, increased levels of EPA+DHA (docosahexaenoic acid), EPA only, and the ratio of EPA to the omega-6 arachidonic acid (AA) were all associated with low PTSD severity symptoms in patients receiving omega-3 supplements at 3 months.
Such findings are of obvious interest to the current and former members of the armed forces. Indeed, military interest in omega-3 is nothing new, with the November 2014 edition of Military Medicine focusing on the fatty acids as “nutritional armor”.
Interest has focused on several different endpoints, including improving mood and reducing suicide rates among serving and ex-military personnel, speeding recovery from traumatic brain injury, and improving reaction times of fighter pilots.
While still emerging, there is compelling data to support a link between DHA supplementation and a significant reduction in the risk of early preterm birth.
Data from the Kansas University DHA Outcomes Study (KUDOS) indicated that universal supplementation with DHA (600 mg per day) during the last two trimesters of pregnancy led to significant reductions in early preterm birth. This would result in cost savings of $1,678 per infant. Taking out the $166.48 cost of the DHA supplements for 26 weeks and a $26 increase in maternal care costs, the net saving became $1,484.
For the nearly 4 million live births in the US every year this cost saving would become almost $6 million, reported the researchers in Prostaglandins, Leukotrienes and Essential Fatty Acids.
The anti-inflammatory role of EPA and DHA have been touted to help support joint health, although much of the science in this area has focused on people with osteoarthritis or rheumatoid arthritis.
A systematic review of 23 studies found “fairly consistent, but modest” evidence of a role in rheumatoid arthritis.
“At sufficiently high intakes, marine n-3 PUFAs decrease the production of inflammatory eicosanoids from ARA and promote the production of less inflammatory eicosanoids from EPA and of anti-inflammatory resolvins and related mediators from EPA and DHA,” wrote Elizabeth Miles and Philip Calder in the British Journal of Nutrition. “One reason behind the lack of consistency may be the dose of EPA plus DHA used in many studies which was probably below the ‘anti-inflammatory threshold’. Other contributors would include differences in duration of the intervention, in sample size, and in the age of the subjects studied.
“There have been a number of clinical trials of fish oil in patients with [rheumatoid arthritis]. Most of these trials report some clinical improvements (e.g. improved patient assessed pain, decreased morning stiffness, fewer painful or tender joints, decreased use of NSAIDs), and when the trials have been pooled in meta-analyses statistically significant clinical benefit has emerged. The current systematic review supports the conclusion that there is fairly consistent evidence for a modest clinical efficacy of marine n-3 PUFAs in [rheumatoid arthritis].”
There is some, albeit limited, data supporting the potential benefits of extracts from green-lipped mussel (Perna canaliculus) for osteoarthritis. A systematic review published in 2008 found less than a handful of trials on this subject but the overall evidence suggested the green-lipped mussel extracts were better than placebo for mild to moderate osteoarthritis (QJM).
“As a credible biological mechanism exists for this treatment, further rigorous investigations are required to assess efficacy and optimal dosage,” wrote the authors.
An emerging and intriguing area of research focuses on sports nutrition, with several studies published in recent years looking at a range of end points, from performance to recovery.
A 2014 study by Japanese scientists found that a daily EPA-rich fish oil dose of 3.6 grams for eight weeks increased exercise economy, a predictor of endurance exercise performance (Bioscience, Biotechnology, and Biochemistry).
Another study, this time from Polish scientists and published in the European Journal of Sport Science, found that omega-3 supplementation may boost performance in cyclists by increasing concentrations of NO and boost blood flow.
Data published in the Journal of the International Society of Sports Nutrition in 2015 found that a seal oil-derived omega-3 supplement may improve neuromuscular function and aspects of fatigue for athletes. Researchers from the University of Toronto reported that omega-3s increased in thigh muscle function by 20%, compared with placebo.
“To our knowledge this is the first study to evaluate the effects of an omega-3 PUFA supplement on athletes while measuring changes in both neuromuscular function and performance,” wrote the researchers. “This study found that omega-3 PUFA supplementation increased muscle activation and attenuated fatigue as assessed during a Wingate test after maximal back squat exercise by reducing percent power drop.”
Data from a four week study using extracts from New Zealand green lipped mussels (Lyprinol/Omega XL, Pharmalink International) indicated a reduction in muscle soreness and fatigue after exercise and reduce markers of muscle damage in untrained men (Journal of the International Society of Sports Nutrition).
Finally, higher omega-3 levels have been linked to so-called biological aging, determined by measuring the length of telomeres: The aging and lifespan of normal, healthy cells are linked to the so-called telomerase shortening mechanism, which limits cells to a fixed number of divisions. As we age, our telomeres shorten and therefore longer telomeres are linked to a “younger” biological age.
Data published in 2010 in the JAMA indicated that each 1-standard deviation increase in DHA plus EPA levels was associated with a 32% reduction in the odds of telomere shortening in people with coronary heart disease.
“These findings raise the possibility that omega-3 fatty acids may protect against cellular aging in patients with coronary heart disease,” wrote researchers from the University of California, San Francisco.
Commenting on the potential mechanism, the UCSF researchers noted that this may be linked to oxidative stress, known to drive telomere shortening. Omega-3s have been shown to reduce levels of F2-isoprostanes, a marker of systemic oxidative stress, as well as increasing levels of the antioxidant enzymes catalase and superoxide dismutase, thereby reducing oxidative stress.
Another possible mechanism may involve the enzyme telomerase. The enzyme works to maintain telomere length, and omega-3 may increase its activity.
Editor’s Note: This article is not intended to be an exhaustive review of the potential health benefits of omega-3s, and we apologize for any unintentional omissions. We recommend readers to explore the linked studies in more detail.
Omega-3 - Challenges and opportunities in 2017 and beyond
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