Evidence-Based Nutrient Recommendations

Omega-3s Part 2: Research

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by Jack Norris, RD

More Information on Omega-3s

Introduction to the Omega-3 Fatty Acids

For our purposes, there are three important omega-3 fatty acids:

  • alpha-linolenic acid (ALA) – short-chain (18 carbon) omega-3 fatty acid. Found in small amounts in animal flesh, in very small amounts in a variety of plant products, and in relatively large amounts in soy, walnuts, canola oil, flaxseeds and their oil, hempseed oil, camelina oil, and chia seed oil. The human body cannot make its own ALA—it must be obtained through the diet.
  • eicosapentaenoic acid (EPA) – long-chain (20 carbon) omega-3 fatty acid. Found mostly in fatty fish, in small amounts in eggs, and in very small amounts in seaweed that can be concentrated into supplements. Some EPA is converted into series 3 eicosanoids which can reduce blood clotting, inflammation, blood pressure, and cholesterol. The human body can produce EPA from ALA and, to a lesser extent, from DHA.
  • docosahexaenoic acid (DHA) – long-chain (22 carbon) omega-3 fatty acid. It’s found mostly in fatty fish, in small amounts in eggs, and in very small amounts in seaweed that can be concentrated into supplements. DHA is a major component of the gray matter of the brain, and also found in the retina, testis, sperm, and cell membranes. The body can convert EPA into DHA.

All three of these omega-3 fatty acids might prevent heart arrhythmias, though ALA has been studied the least in clinical trials.

A chart showing the conversion pathways for the omega-3 fatty acids can be found in The Fatty Acids.

Essential Fatty Acids

The Institute of Medicine considers there to be a dietary requirement for two fatty acids for humans over 1 year old:

  • linoleic acid (LA) – the short-chain (18-carbon) omega-6, which is prevalent in most vegan diets due to being abundant in vegetable oils.
  • ALA – the short-chain omega-3 (described above) which can be scarce in vegan diets.

Because they’re essential fatty acids, there’s a dietary reference intake (DRI) for both LA and ALA:

  • LA – 17 g (men age 19-50), 12 (women age 19-50)
  • ALA – 1.6 g (males age 14+), 1.1 g (females age 14+)

Heart Disease

There are two potential, related concerns regarding vegetarians and long-chain omega-3s: a) Do vegetarians have negative health consequences from not eating fish? and b) Should vegetarians supplement with long-chain omega-3s?

Fish Consumption and Heart Disease

As of February 2021, the American Heart Association was still basing its omega-3 fatty acid recommendations on its 2002 position paper, Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease (31) which recommends that adults “Eat a variety of (preferably oily) fish at least twice a week. Include oils and foods rich in alpha-linolenic acid (flaxseed, canola, and soybean oils; flaxseed and walnuts).”

Whether eating fish substantially reduces the risk of cardiovascular disease is a topic mostly beyond the scope of this article. The Linus Pauling Institute at Oregon State University provides a good review of the literature in their article, Essential Fatty Acids, and it’s worth noting that a 2020 meta-analysis of six cohort studies found no correlation between eating fish and a reduced risk of cardiovascular disease or mortality (58).

Omega-3 Supplementation and Heart Disease

In what they called “the most extensive systematic assessment of effects of omega‐3 fats on cardiovascular health to date,” a 2020 Cochrane Review analyzed 86 randomized controlled trials of 12 to 88 months duration using omega-3 capsules, omega-3-enriched food, or dietary advice to eat more omega-3s (61). The review found little to no effect of increasing omega-3s on all-cause or cardiovascular mortality, cardiovascular events, stroke, or arrhythmias. Increased omega-3 intake showed a trend with reduced coronary heart disease mortality (RR 0.90, CI 0.81-1.00) and there was a reduced rate of coronary heart disease events (RR 0.91, CI 0.85-0.97). Increasing long-chain omega-3s reduced triglycerides by ~15% in a dose‐dependent way. Overall, the authors stated that 334 people would need to increase their long-chain omega-3 intake to prevent one person from having a coronary heart disease event and they believed this wasn’t enough of an impact to recommend supplementation. There wasn’t enough evidence to assess the impact of eating fish on cardiovascular health.

On the other hand, a 2019 meta-analysis of omega-3 supplementation did find a benefit from omega-3 supplementation (57). Hu et al. combined the data from 13 randomized controlled trials using about 800 to 1,800 mg of omega-3 fatty acids per day. The participants started out with a mixed risk for cardiovascular disease (40% had diabetes and 73% were using cholesterol-lowering medication). In one set of results (that excluded the REDUCE-IT trial described below), they found a reduced risk of heart attack (RR 0.92, CI 0.86-0.99) and cardiovascular death (RR 0.93, CI 0.88-0.99). The omega-3 supplementation in this set of results is arguably higher than the AHA recommendations of at least 2 servings of fish per week, but not implausible from a dietary perspective (for the omega-3 amounts of fish, see Omega-3 Fatty Acids: Fact Sheet for Health Professionals).

The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) was excluded from Hu et al.’s results above because it used a much higher dose of omega-3s: 4,000 mg/day of a purified form of EPA. It showed markedly better success for heart attack (RR 0.69, CI 0.58-0.81) and cardiovascular death (RR 0.80, CI 0.66-0.98). Participants also had a lower risk of stroke (RR .72, CI 0.55-0.93), but their death from all causes wasn’t significantly lower (RR .87, CI 0.74-1.02) than placebo (65). The extremely high amount of EPA used in REDUCE-IT is a pharmacological dose and not relevant to dietary omega-3 intake.

Vegetarians already have about a 24% lower risk of heart disease (5), and it’s not clear that more EPA or DHA could further benefit them to any significant degree with respect to heart disease. Rather, the main concern for vegetarians with regard to omega-3 fatty acids is the possibility of cognitive problems due to DHA deficiency.

Cognition

A 2012 cross-sectional report from the Framingham Study examined 1,575 people (54% women) with an average age of 67 (SD 9) years with respect to omega-3 status and numerous cognitive-related parameters (40). They compared the EPA plus DHA red blood cell membrane fatty acids in the lowest quartile (≤4.4%) to those in the upper three quartiles (75th percentile was 6.5%). They found that those in the lower omega-3 quartile had a significantly lower cerebral brain volume (equivalent to approximately two years of brain aging), but a similar white matter hyperintensity volume, temporal horn volume, and rate of silent stroke. Low omega-3 status was associated with a poorer score on some, but not all, tests of cognition.

As part of the Women’s Health Initiative Study of Cognitive Aging, Ammann et al. (2013) conducted a cross-sectional analysis of 2,302 women 65 years and older and found no difference in cognition between those in the upper one-third compared to those in the lowest one-third of EPA-plus-DHA percentage of fatty acids in red blood cells (43). However, the lowest one-third had an average EPA-plus-DHA of 3.8% which is quite a bit higher than vegans tend to have, so this finding doesn’t necessarily reassure us about the omega-3 status of vegans. However, a more recent, related study by Ammann et al. (2017) described below, followed a much larger group of participants over time and provides us with more insight into whether higher EPA/DHA percentages are important in preventing cognitive impairment and dementia, especially in older women.

Zhang et al. (2016) conducted a meta-analysis of 21 case-control and prospective studies found that increases of 1-serving/wk increment of fish were associated with a reduced risk of dementia (RR 0.95, CI 0.90-0.99) and Alzheimer’s disease (RR 0.93, CI: 0.90-0.95) (68). DHA intake was also inversely associated with risks of dementia (RR 0.86, CI 0.76-0.96) and Alzheimer’s disease (RR 0.63, CI 0.51-0.76). However, blood levels of omega-3 fatty acids were not associated with a reduced risk of these or other cognitive diseases. In a letter to the editor, Koch and Jensen pointed out that in the six studies looking at the association between fish intake and dementia and Alzheimer’s disease, one study was a 2-year follow-up of another study with a longer follow-up. Koch and Jensen argued (69) that “Appropriate exclusion of the report from Kalmijn et al. would render the meta-analysis of fish intake in relation to dementia risk insignificant (RR: 0.96; 95% CI: 0.91, 1.01; no heterogeneity) and change the RR estimate for AD risk to 0.87 (95% CI: 0.77, 0.98) in a random-effects meta-analysis with significant between-study heterogeneity still present.” The authors of the original report, Zhang and Jiao (70), responded that it was appropriate to include both reports. Overall, it seems perplexing as to why omega-3 intakes but not blood levels would be associated with a reduced risk of dementia if there is a true effect, though it might suggest that blood levels of EPA and DHA aren’t an accurate representation of omega-3 status.

Amman et al. (2017, United States) conducted the largest prospective study to assess the risk of dementia with omega-3 fatty acid status (67). The study was part of the Women’s Health Initiative Memory Study testing the impact of the hormones estrogen and progestin on the memory of women ≥65 years old. Although the hormone part of the study was concluded early, the researchers continued to follow 6,706 women for an average of 9.8 years to see if baseline EPA and DHA levels were associated with a diagnosis of probable dementia (PD) or mild cognitive impairment (MCI). The study compared the risk of PD and MCI among those with EPA/DHA within one standard deviation above the mean (5.27% to 6.79% EPA/DHA) to those within one standard deviation below the mean (3.75% to 5.27% EPA/DHA). In one of their models, the researchers found a statistically significant finding for a reduction in PD (HR 0.91, CI .83-.99), but most models found no significant association including one that adjusted for the APOE genotype associated with Alzheimer’s Disease (HR 0.92, CI 0.83-1.01). There were no significant associations between EPA/DHA and MCI. Examining EPA and DHA separately produced similar results to each other (with no significant findings). The researchers calculated that this increased risk of PD represented a 2% reduced risk (12% vs. 14%) of PD incidence over a 15-year period.

In summary, studies of omega-3 fatty acids conducted on populations of omnivores consistently find some significant associations with better cognition, though they tend to be weak. That dietary intakes are more strongly associated with better cognition, than are blood levels, raises a question about whether omega-3s are truly driving the beneficial association versus some other variable(s) paired with omega-3 intake. While more research could clarify the relationship, it seems unlikely that more studies will drastically impact the findings given how consistent they’ve been.

Depression

Our interest in omega-3s and depression is mostly related to whether vegetarians are at an increased risk of depression due to low EPA or DHA levels.

Risk of Depression

A 2019 meta-analysis and systematic review of 32 randomized controlled trials found no effect of increasing EPA and DHA on the risk of depression symptoms (RR 1.01, CI 0.92-1.10) (62). Studies had a median duration of 12 months with a median dose of 0.95 grams per day (ranging from 0.4 to 3.4 grams per day). One study addressed omega-3s and anxiety and found little to no effect. The researchers recommend against taking omega-3 supplements for reducing depression and anxiety risk.

Treatment for Depression

Whether EPA/DHA can be used to treat people with depression is only loosely related to the omega-3 status of vegetarians, but it’s been where most of the research has focused and so we review it here.

Early research on treating depressive symptoms with supplementation of EPA and DHA was mixed. A 2006 review (9) from Canada found that supplementation improved depression but it wasn’t clear whether it was effective for depressed patients in general or only those with abnormally low concentrations of EPA and DHA. A 2006 review from the UK (10) found “little support” based on the small number of trials and their significant variation. A 2007 meta-analysis (8) found supplementation to be effective but with significant publication bias. There was some evidence that EPA is more effective than DHA (42).

Grosso et al. (2014) conducted a meta-analysis of 11 trials of patients with a DSM-defined diagnosis of major depressive disorder (MDD) and 8 trials of patients with depressive symptomatology but no diagnosis. They found supplementation to have a beneficial effect for the patients diagnosed with MDD and also for those with bipolar disorder. They considered EPA to be more effective and many of the trials used pharmacological doses (59). Hallahan et al. (2016) conducted a meta-analysis and found similar results (60).

A 2020 meta-analysis found a benefit from high-dose (≥2 g/day), but not low-dose (<2 g/day), EPA/DHA supplementation in the early therapy period for MDD (66).

Omega-3 Intakes and Blood Levels of Vegetarians

According to the USDA nutrient database, a medium egg contains about 2 mg of EPA and 16 mg of DHA. That provides lacto-ovo-vegetarians with very small amounts of dietary EPA and DHA. Vegans who are not supplementing with EPA or DHA have an intake of essentially zero.

The table below shows studies that have measured the ALA intakes of vegetarians (who were presumably not taking steps to increase their omega-3 status).

ALA Intake of Vegetarians
Study Population Intake (g/day)
Australia, 1999 (15) 17 vegetarian men, ~26-42 yrs 1.9
UK, 1984 (25) 10 vegan men 1.8
UK, 1984 (25) 10 vegan women 1.2
UK, 2010 (28) 5 vegan men 1.0
UK, 2010 (28) 5 vegan women .9
USA, 2014 (39) 87 vegan women, 80 vegan men 3.4

Vegans and vegetarians have been shown in many studies to have lower blood levels of EPA and DHA than meat-eaters. The table below shows the results of some of these studies. The general trend is that lacto-ovo-vegetarians and vegans have lower levels of EPA and DHA in their blood. In the 2005 UK study (19), time as a vegan wasn’t associated with different EPA or DHA levels, but this was based on plasma levels which likely reflect recent omega-3 intake more than long-term status. The study also found no difference in plasma fatty acid percentages of EPA, DPA, or DHA between meat-eaters who ate oily fish <1 time/month, 2-3 times/month, and ≥1 time/week.

One exception is the 2010 UK study (28) in which vegan women had, on average, higher DHA levels than even the fish-eaters. This finding was likely an anomaly given that there were only 5 vegan women with a DHA level of 286 µmol/l and a very large standard deviation of 211 µmol/l. The researchers didn’t assess how long the vegans had been following their diet.

The 2014 USA study (39) was interesting for two reasons. One, vegans who were older (27 people 70 years or older, up to 85 years) had higher omega-3 levels than younger vegans. It’s usually thought that people have a harder time converting ALA to EPA and DHA as they age. Second, vegan men had similar levels to a segment of military males who didn’t eat fish (vegan women weren’t compared). In this study, vegan ALA intakes averaged 3.4 g per day which is relatively high—vegans usually have average intakes closer to 1.5 g per day.

Lower blood levels of EPA and, especially, DHA in vegetarians doesn’t necessarily mean that they have lower levels of EPA or DHA in other tissues, but it’s something to be careful about until more is known and is the reason why we have a second set of more prudent recommendations beyond the dietary reference intake (DRI) for ALA (see Daily Needs).

EPA and DHA Levels in Vegans
Number EPA DHA
1981 UK17 %PCPG %PCPG
Vegans 4 0.3 1.3
Non-Veg 5 1.4 4.1
%PG %PG
Vegans 4 0.3 0.9
Non-Veg 5 0.8 2.8
1992 UK16 %PTPG %PTPG
Vegans 20 0.2 0.8
Non-Veg 20 0.9 2.1
1999 Chile18 %PFA %PFA
Vegetarians 26 0.35 1.56
Non-Veg 26 0.79 2.58
2002 Australia33 %PPL %PPL
Vegan 18 1.5 0.9
Lacto-Ovo 43 1.9 1.2
Moderate Meat 60 1.9 1.6
High Meat 18 1.9 1.5
2005 UK19 mg/l mg/l
Vegan 232 .34 .70
Lacto-Ovo 231 .52 1.16
Non-Veg 196 .72 1.69
2010 UK28 µmol/l µmol/l
Men
Vegan 5 65 195
Lacto-Ovo 25 56 222
Meat Eaters (no fish) 359 47 215
Fish Eaters 2,257 58 240
Women
Vegan 5 50 286
Lacto-Ovo 51 55 224
Meat Eaters (no fish) 309 57 241
Fish Eaters 1,891 65 271
2014 USA39 %RBC %RBC
Vegan 40 .56 2.28
Meat Eaters
(low fish)
78 .40 2.61
2017 UK41 %PFA %PFA
Vegan 23 .47 .91
Meat Eaters 24 1.03 2.23
%RBC %RBC
Vegan 23 .67 2.07
Meat Eaters 24 1.26 4.19
%PCPG—percentage of plasma choline phosphoglycerides • %PG—percentage of plasma phosphoglycerides • %PFA—percentage of plasma fatty acids • %PTPG—percentage of platelet phosphoglycerides • %PPL—percentage of platelet phospholipids • %RBC—percentage of red blood cell fatty acids

Effects of Low EPA and DHA on Vegetarians

One of the main things that long chain omega-3 fatty acids do, particularly EPA, is reduce blood clotting which protects against heart attacks. There have been some differences noted in blood clotting between vegetarians and meat-eaters.

A 1999 Chile study (18) found that vegetarians had significantly more platelets (242,000 per ul) than non-vegetarians (211,000 per ul) and a shorter bleeding time (4.5 vs. 7.3 min). In a follow-up 2000 Chile study (4), vegetarians were given 700 mg EPA and 700 mg DHA for 8 weeks. EPA went from .2 to 1.8% and DHA went from 1.1 to 3.0%. Some clotting factors did change, but bleeding time remained lower at 5-1/2 minutes.

In a 1992 UK study (16), only one of eight platelet aggregation parameters in the men (but not the women) was different from the non-vegetarians. Bleeding times were similar.

A 2017 study from the UK compared heart rate variability between a group of 23 adult vegans and 24 omnivores (41). Low heart rate variability reflects a reduced capacity for the heart to respond to the body’s physiological demands and is linked to increased risk for heart disease. As expected, the vegans had lower concentrations of DHA and EPA in both red blood cells and plasma. While vegans had a higher heart rate variability over a 24-hour period, their daytime heart rate variability was lower, and their heart rate was greater. It’s not clear if this is an overall better or worse heart variability for vegans.

Thus, of three studies that looked at clotting factors, the results are mixed.

In terms of cognition, a 2002 study (53) on British mortality found vegetarians to have a barely statistically significant, higher risk of death from mental and neurological diseases (DRR 2.21, CI 1.02–4.78). However, in a 2016 EPIC-Oxford report (54), vegetarian deaths from “mental and behavioral disorders” were not statistically different from non-vegetarians (HR 1.22, CI 0.78–1.91). The risk of mortality from neurologic disease in a 2013 report from the Adventist Health Study-2 (55) was also not statistically different for vegetarians compared to non-vegetarians (HR 0.93, CI 0.67-1.29).

Vegetarian Pregnancy and Children

DHA may be important for developing fetuses and infants, and pregnant women more efficiently convert ALA to DHA. Fetuses and infants are able to receive DHA that’s released from the mother’s fat tissues and provided through the umbilical cord or breast milk.

Anthropologist John H. Langdon argues that DHA is not an essential nutrient for the brain development of infants because in cases of very low maternal levels of DHA, infants can utilize other fatty acids for brain tissue which can later be replaced by DHA (32).

A 1994 study measured the DHA levels in umbilical cords of 32 infants born to vegetarian mothers compared to omnivores (30) and found no relationship between the proportions of DHA in plasma or cord artery phospholipids and the birth weight or head circumference of the infants.

In a study comparing breast milk, cow’s milk formula with DHA, soy formula with DHA, and soy formula without DHA, infants who ate soy formula without DHA had indications of slower parasympathetic development, though still within the normal range (87).

Many children have been raised vegan without supplementing with DHA, or even extra ALA, and appear to develop well. Despite this, breastfeeding mothers of vegetarian or vegan children should make sure they’re meeting omega-3 recommendations (see Daily Recommendations) and non-breastfeeding infants should receive an infant formula with 500 mg of omega-3 fats per day.

Traditional Remedy: Increase ALA, Reduce LA

The traditional way that vegetarians were encouraged to raise EPA and DHA levels was by increasing ALA and decreasing linoleic acid (LA), a short-chain omega-6 fatty acid. This is because the enzymes that convert ALA into EPA and DHA also convert short-chain omega-6 fatty acids and there is competition between omega-3s and omega-6s. An ideal ratio of omega-6 to omega-3 in the diet is thought to be about 3:1 or 4:1.

Most vegetable oils are high in omega-6s and vegetarians tend to get plenty in their diets. A 1981 UK study (17) showed that the dietary ratio of omega-6 to omega-3 fats was 16 for vegans and 6 for meat-eaters. A 1992 UK study (16) showed a ratio of 15.8 for vegan men vs. 10.2 for meat-eating men, and 18.3 for vegan women vs. 8.2 for meat-eating women.

A 2021 study from Spain (63) of 55 vegans and 49 lacto-ovo-vegetarians found that those with a blood omega-6 to omega-3 ratio of ≤10 had a higher percentage of blood EPA and DHA than those with a ratio between 10 to 20 or >20 (EPA: 0.60%, 0.27%, and 0.23%; DHA: 2.90%, 1.91%, and 1.19% respectively). Flaxseed intakes of once per day and, especially, 2 or more times per day was associated with a much higher percentage of ALA in the blood (~0.5% vs. ~0.7% and 1.5%, respectively), but not with higher EPA or DHA percentages.

To counteract the high omega-6 to omega-3 ratio, vegetarian health professionals have recommended increasing ALA intakes and decreasing LA intake. Unfortunately, there are no long-term studies looking at vegetarians’ blood EPA and DHA levels after following such recommendations, though we do have some related studies.

A 1999 Australian study (15) of 17 vegetarian men, aged about 26–42 years old, showed that four weeks of 3.7 g of ALA per day (the equivalent of about 1.5 teaspoons of flaxseed oil, and a change in LA:ALA from about 10:1 to 4:1) didn’t significantly increase the percentages of EPA or DHA in the blood. The same study showed that four weeks of 15.4 g of ALA (the equivalent of about 6.5 teaspoons of flaxseed oil, and a change in LA:ALA from about 12:1 to 1:1) did increase EPA levels, but still didn’t increase DHA levels. There were no changes in clotting factors. See the table below for more details.

Effects of ALA Supplementation: 1999 Australian Study
Baseline After 4 wks of 3.7 g ALA per day After 4 wks of 15.4 g ALA per day
%PTPL %PTPL %PTPL
ALA 0.1 0.1 0.3
EPA 0.3 0.3 0.5
DHA 1.1 1 0.9^
%PPL %PPL %PPL
ALA 0.3 0.4 1.4^
EPA 0.8 0.9 1.4^
DHA 2 2.1 1.9
%PTG %PTG %PTG
ALA 1.2 2.5^ 7.4^
EPA 0.2 0.3 .4^
DHA 0.2 0.2 0.2
%PTPL – percentage of platelet phospholipids
%PPL – percentage of plasma phospholipids
%PTG – percentage of plasma triglycerides
^Statistically significant result compared to baseline

In a 2000 study from The Netherlands (20), the ratio of dietary LA:ALA was lowered from 13.7 to 6.7 by adding 2.0 g of ALA per day to the diets of 9 vegans aged 20 to 60 years old. After 4 weeks, there was no change in plasma, red blood cell, or platelet EPA or DHA levels.

In a 2014 study from the USA (38), a group of lacto-ovo-vegetarians were placed on three different daily regimens for 8 weeks each: 1 oz of walnuts (3.0 g of ALA), 1 regular egg (110 mg DHA), and 1 fortified egg (~500 mg DHA, 40 mg EPA, 1 g ALA). The ratio of n-6:n-3 was 6:1 in the walnut phase and DHA levels did not increase.

In a 1981 UK study (17), 4 vegans aged 26 to 37 years took 6.5 g of ALA per day for 2 weeks. They had some increase in EPA and DHA levels. See the table below.

Effects of ALA Supplementation: 1981 UK Study
Baseline 2 weeks of 6.5 g ALA per day
%PCP %PCP
EPA 0.3 1.4^
DHA 1.3 1.3
%PTPG %PTPG
EPA 0.3 0.3
DHA 0.9 1.2^
%PCP – percentage of plasma choline phosphoglycerides
%PTPG – percentage of platelet phosphoglycerides
^Statistically significant result compared to baseline

In a 1992 India study (21), 5 vegetarians, aged 25–40 years old, took 3.7 g of ALA per day. After 6 weeks, this regimen increased blood levels of EPA and DHA, and reduced LDL cholesterol and blood aggregation. See the table below.

Effects of ALA Supplementation: 1992 India Study
Baseline After 6 weeks of 3.7 g ALA per day
PPL (umoles/dl) PPL (umoles/dl)
EPA 0.6 2.7^
DHA 2.1 3.0^
%PTPL %PTPL
EPA TR .4^
DHA 1.5 2.2^
LDL Cholesterol (mg/dl) 106 71^
Blood aggregation (%) 72.2 38.8^
PPL – plasma phospholipids
%PTPL – percentage of platelet phospholipids
TR – trace amount
^Statistically significant result compared to baseline

In summary, it appears that 3.7 grams of ALA per day is needed for vegetarians to see an increase in platelet DHA in the short-term. But, there isn’t any research in which participants were asked to cut their LA intake at the same time that they increased ALA intake and so we don’t know if that combination would boost DHA levels in the blood or other tissues.

The World Health Organization and Food and Agriculture Organization recommend an LA intake between 2.5-9% of calories, saying that the lower number prevents deficiency and the higher end of the range reduces risk for heart disease (52). Although vegans who don’t ensure sources of ALA tend to have a high ratio of omega-6 to omega-3 fats, their percentage of calories as LA has been shown to be 5.1% (41), 7.3% (46), 8.5% (47), and 9.3% (48), well within the range recommended by the WHO. Because of this, we are hesitant to recommend that vegans avoid LA.

Non-vegetarian Conversion Rates

In order to figure out what the ALA to DHA conversion rates are for vegetarians, it might be important to stick with studies that use actual vegetarians rather than meat-eaters (who might have a dietary source of EPA and DHA). But because there’s a lack of long-term studies on vegetarians, we should look at some of the research on meat-eaters.

There have been many studies on meat-eaters’ conversion rates, and for the most part, they’ve shown good conversion rates of ALA to EPA, but very little to DHA. Because small amounts or short terms don’t appear to be promising, we’ll limit this review to studies that used larger amounts and longer time periods.

In a 2010 study from the United States (49), 24 meat-eaters were placed on different omega-3 regimens, for eight weeks each, to manipulate their omega-6 to omega-3 ratios. Achieving an omega-6 to omega-3 ratio of 2:1, by adding 8.6 g ALA per 2,400 kcal via flaxseed oil and walnuts, resulted in higher EPA and DPA levels in red blood cells than an omega-6 to omega-3 ratio of 10:1 plus supplements of 200 mg EPA and 720 mg DHA per 2,400 kcal. There were no differences in DHA levels between a 10:1 ratio diet (with no supplements) and the 2:1 ratio diet with ALA.

In a 2008 study from Canada (22), meat-eaters took 1.2, 2.4, or 3.6 g ALA per day for 12 weeks. For the 2.4 g and 3.6 g groups, EPA increased about 10-20% and 20-30%, respectively, in red blood cells after 2 weeks, and then fluctuated within those ranges for the remaining 12 weeks. There was no change in DHA for the 1.2 g group, but the 2.4 g and 3.6 g groups showed a reduction in DHA. This study used an intention-to-treat method with little information provided about the level of compliance.

A 2007 Canadian study (50) found that with an ALA intake of 1% of energy, increasing LA from 3.8% to 10.5% reduced EPA from .93% to .58%. These effects stabilized after 2 weeks.

In a 1999 study from Japan (23), the cooking oil of older adults (age 67-91) was changed from soybean to perilla oil, which is high in ALA. Fish intake was kept steady at 1 serving per day. Their ALA intake increased from 1.2 to 4.2 g/day and their omega-6 to omega-3 ratio was reduced from 5.9 to 1.4. After 3 months, there was no difference in EPA and DHA levels, but after 10 months, EPA levels had risen significantly from 2.5 to 3.6% of serum lipids, and DHA levels rose from 5.4 to 6.4%.

Welch et al. (24) reported that non-fish-eaters (both vegetarians and meat-eaters) convert ALA to long-chain omega-3s at about a 22% higher rate than do fish-eaters (based on cross-sectional data), so conversion rates of vegetarians might be greater than these studies on meat-eaters indicate.

In summary, it appears that 3 g (the equivalent of about 1-1/2 teaspoons of flaxseed oil) per day of ALA cannot increase blood percentages of DHA in three months time, but can increase blood percentages in 10 months time, assuming intake of omega-6 is low.

Low Omega-6 to Omega-3 Ratio Foods

The table below lists foods with the lowest omega-6 to omega-3 ratios.

Foods with Lowest Omega-6 to Omega-3 Ratios
Food n-6:n-3 ratio ALA
flaxseeds 1:4 1.6 g / tablespoon
flaxseed oil 1:4 2.5 g / teaspoon
chia seeds 1:3 5 g / oz
camelina oil 1:2
canola oil 2:1 1.3 g / tablespoon
English walnutsa 4:1 – 5:1 2.6 g / oz (14 halves)
walnut oil 5:1 1.4 g / tablespoon
soybean oil 7.5:1 .9 g / tablespoon
black walnuts 10:1 .9 g / oz
aEnglish are the typical walnuts found in most grocery stores.

More information on omega-3 sources can be found in the articles The Fatty Acids and Omega-3s Part 3: Plant Sources.

DHA Supplementation in Vegetarians

A 2015 USA study (39) gave 46 vegans, selected on the basis of having low omega-3 status, a daily dose of 172 mg DHA and 82 mg EPA for 4 months. Percent of total red blood cell fatty acids went from about .6% to .8% for EPA and from about 2.3% to 3.25% for DHA.

In a 2009 review paper (29), Sanders describes a placebo-controlled, randomized trial from the UK in which 39 vegan men supplemented with 200 mg of DHA per day for 3 months and increased the proportion of DHA in plasma by 50% (from about .8 to 1.3% of plasma lipids).

In a 2006 study from Germany (35), 87 female and 27 male vegetarians took 940 mg of DHA per day for 8 weeks. Plasma phospholipids went from 2.8% to 7.3% DHA.

In a 2006 study from Taiwan (36), 27 postmenopausal vegetarian women took 2,140 mg of DHA per day for 6 weeks. LDL fatty acid composition went from 1.4% to 3.7% DHA.

In a 2000 study from Chile (4), 10 vegetarians took 700 mg EPA and 700 mg DHA for 8 weeks. Plasma fatty acid EPA went from 0.2% to 1.8% and DHA went from 1.1 to 3.0%.

In a 1996 study from Canada (2), 12 male and 12 female vegetarians took 1,620 mg of DHA per day for 6 weeks. Serum phospholipids went from 2.4% to 8.3% DHA, and platelet phospholipids increased from 1.2% to 3.9%. A 1997 study from the same researchers (1), and same dose and length, increased serum phospholipids from 2.1% to 7.1% DHA, and increased serum platelet phospholipids from 1.1% to 3.4% DHA in vegetarians.

DHA Supplementation Increases EPA Levels

Upon DHA supplementation, EPA levels also increase by a small percentage.

It was previously believed this was due to conversion (or “retroconversion”) of the supplemented DHA to EPA. However, a 2019 Canadian randomized controlled trial used DHA containing labeled carbon and didn’t find any to be converted to EPA. They conclude that “the increase in plasma EPA following DHA supplementation in humans does not occur via retroconversion, but instead from a slowed metabolism and/or accumulation of plasma EPA (56).”

A 1996 Canada study (2) showed an 11–12% increase in EPA after 6 weeks of 1,620 mg of DHA in vegetarians.

A 1997 Canada study (1) of vegetarians and meat-eaters showed a 9.4% increase in EPA after a dose of 1,620 mg DHA per day for 6 weeks, with no differences between groups.

In a 1996 study from France (3), 3 people were given 123 mg of DHA one time and EPA increased 1.4%.

From this research, it’s not clear if someone can rely on modest DHA supplements to create optimal EPA status, but it’s also not clear what an optimal EPA status is or if any effort is required to maintain EPA levels beyond meeting the dietary reference intake for ALA.

Vegan EPA Supplements

If you’re meeting recommended ALA intakes, you shouldn’t need to take an EPA supplement. Fish contain about twice as much DHA as EPA (27), so it’s not unusual for humans to get more DHA than EPA in the diet. But it’s also okay to take a DHA supplement that contains EPA.

You can find a tremendous number of vegan DHA and EPA supplements by doing a Google search. We aren’t able to assess whether any given company is better than another.

Omega-3 Recommendations for Vegans

To sum up the rationale behind our recommendations, it appears that if a vegan is meeting the Dietary Reference Intake for ALA, their EPA status should be adequate. It’s not clear if DHA is a problem for such people but to be safe we recommend either increasing ALA intake or adding a DHA supplement. Please see our article, Daily Needs, for specific recommendations and how to meet them.

Associations of Omega-3s with Increased Risk of Disease

Some studies have associated higher ALA intakes with an increased risk of disease.

Prostate Cancer

A 2009 systematic review and meta-analysis (11) of ALA intake and prostate cancer found:

When examined by study type (i.e., retrospective compared with prospective or dietary ALA compared with tissue concentration) or by decade of publication, only the 6 studies examining blood or tissue ALA concentrations revealed a statistically significant association. With the exception of these studies, there was significant heterogeneity and evidence of publication bias. After adjustment for publication bias, there was no association between ALA and prostate cancer (RR: 0.96; 95% CI: 0.79, 1.17).

A 2010 meta-analysis found that subjects who consumed more than 1.5 g/day of ALA had a significantly decreased risk of prostate cancer (0.95, 0.91-0.99) compared to those who ate less (34).

A 2018 study (44) from Harvard School of Public Health, suggested that the early associations between ALA and prostate cancer might have been due to trans-ALA which has been largely removed from the food supply.

In July of 2013, a study surfaced suggesting the DHA supplementation might cause prostate cancer. This concern is probably unwarranted, though if you are at a high risk for prostate cancer you might want to err on the lower side of the recommendations here. More details can be read in the article, DHA Supplements and Prostate Cancer.

Eyesight

A 2001 analysis (14) from the Nurses Health Study found an almost statistically significant increase in age-related macular degeneration for those with the highest ALA intake. In contrast, a 2013 France study (6) found that higher ALA levels in the blood were associated with a lower risk of late age-related macular degeneration. A 2017 follow-up (45) from the Nurses Health Study found that a high intake of ALA was associated with an increased risk of intermediate age-related macular degeneration before 2002, but not afterward when less trans fats were found in participants’ blood.

A 2005 analysis (12) from the Nurses Health Study found that both the highest intakes of ALA and LA were associated with an increase in lens opacity, which can lead to cataracts. For ALA, the risk ratio was 2.2 (1.2, 4.5) for about 1.26 g compared to .86 g per day. A 2007 analysis (13) of the same group found that the highest category of ALA intake (about 1.26 g per day) was linked to a 16% increase in eye lens nuclear density compared to the lowest category (about .84 g per day) over five years. As of 2018, no follow-up studies appear to have been conducted on ALA and cataracts.

Without more definitive research we don’t believe concerns about eyesight is any reason to avoid plant-based ALA due to the small differences in ALA intake in these studies, the fact that much ALA in meat-based diets comes from animal products, that trans ALA is no longer added to the food supply, and the large number and inconsistencies of associations between different fatty acids and various conditions.

References

Last updated February 2020

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67. Ammann EM, Pottala JV, Robinson JG, Espeland MA, Harris WS. Erythrocyte omega-3 fatty acids are inversely associated with incident dementia: Secondary analyses of longitudinal data from the Women’s Health Initiative Memory Study (WHIMS). Prostaglandins Leukot Essent Fatty Acids. 2017 Jun;121:68-75.

68. Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016 Feb;103(2):330-40.

69. Koch M, Jensen MK. Comment on: Limitations of the review and meta-analysis of fish and PUFA intake and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr. 2016 Aug;104(2):537.

70. Zhang Y, Jiao J. Reply to M Koch and MK Jensen. Am J Clin Nutr. 2016 Aug;104(2):537-8.

Also Reviewed

Agren JJ, Törmälä ML, Nenonen MT, Hänninen OO. Fatty acid composition of erythrocyte, platelet, and serum lipids in strict vegans. Lipids. 1995 Apr;30(4):365-9. (Abstract) Raw food vegans.

Bernstein AM, Ding EL, Willett WC, Rimm EB. A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease. J Nutr. 2012 Jan;142(1):99-104.

Burns-Whitmore B, Froyen E, Heskey C, Parker T, San Pablo G. Alpha-Linolenic and Linoleic Fatty Acids in the Vegan Diet: Do They Require Dietary Reference Intake/Adequate Intake Special Consideration? Nutrients. 2019 Oct 4;11(10):2365.

Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Arch Ophthalmol. 2008 Jun;126(6):826-33.

Craddock JC, Neale EP, Probst YC, Peoples GE. Algal supplementation of vegetarian eating patterns improves plasma and serum docosahexaenoic acid concentrations and omega-3 indices: a systematic literature review. J Hum Nutr Diet. 2017 Dec;30(6):693-699. The six studies included in this review are all summarized in DHA Supplementation in Vegans.

Fisher M, Levine PH, Weiner B, Ockene IS, Johnson B, Johnson MH, Natale AM, Vaudreuil CH, Hoogasian J. The effect of vegetarian diets on plasma lipid and platelet levels. Arch Intern Med. 1986 Jun;146(6):1193-7. No omega-3 data. Found higher LA but similar AA levels among vegans, lacto-ovo-vegetarians, and meat-eaters.

Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006 Apr 1;332(7544):752-60. Epub 2006 Mar 24.

Kris-Etherton PM, Hill AM. N-3 fatty acids: food or supplements? J Am Diet Assoc. 2008 Jul;108(7):1125-30. (No abstract available.)

Lane KE, Wilson M, Hellon TG, Davies IG. Bioavailability and conversion of plant based sources of omega-3 fatty acids – a scoping review to update supplementation options for vegetarians and vegans. Crit Rev Food Sci Nutr. 2021 Feb 12:1-16.

Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest. 2005 Oct;115(10):2774-83.

Mangat I. Do vegetarians have to eat fish for optimal cardiovascular protection? Am J Clin Nutr. 2009 May;89(5):1597S-1601S. Epub 2009 Mar 25.

Muskiet FA, Fokkema MR, Schaafsma A, Boersma ER, Crawford MA. Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized controlled trials. J Nutr. 2004 Jan;134(1):183-6.

Rotolo O, Zinzi I, Veronese N, Cisternino AM, Reddavide R, Inguaggiato R, Leandro G, Notarnicola M, Tutino V, De Nunzio V, De Leonardis G, Guerra V, Donghia R, Fucilli F, Licinio R, Mastrosimini A, Rinaldi CCM, Daddabbo T, Giampaolo N, Iacovazzi PA, Giannico S, Caruso MG. Women in LOVe: Lacto-Ovo-Vegetarian Diet Rich in Omega-3 Improves Vasomotor Symptoms in Postmenopausal Women. An Exploratory Randomized Controlled Trial. Endocr Metab Immune Disord Drug Targets. 2019;19(8):1232-1239.

Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Gunter MJ, Holmes MV, Key TJ, Travis RC. NMR Metabolite Profiles in Male Meat-Eaters, Fish-Eaters, Vegetarians and Vegans, and Comparison with MS Metabolite Profiles. Metabolites. 2021; 11(2):121.

Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006 Jul;84(1):5-17.

Williams CM, Burdge G. Long-chain n-3 PUFA: plant v. marine sources. Proc Nutr Soc. 2006 Feb;65(1):42-50. Review.

Yurko-Mauro K, McCarthy D, Rom D, Nelson EB, Ryan AS, Blackwell A, Salem N Jr, Stedman M; MIDAS Investigators. Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement. 2010 Nov;6(6):456-64.

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