Evidence-Based Nutrient Recommendations

Omega-3s Part 2: Research

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by Jack Norris, RD, LD

More Information on Omega-3s

Introduction to the Omega-3 Fatty Acids

There are two questions regarding vegetarians and omega-3s: Do vegetarians have negative health consequences from not eating fish and should vegetarians supplement with omega-3s?

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 seeds. 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 possibly from DHA.
  • docosahexaenoic acid (DHA) – long-chain (22 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. DHA is a major component of the gray matter of the brain, and also found in the heart, retina, testis, sperm, and cell membranes. The body can convert EPA into DHA.

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

See the video below for an excellent overview of omega-3 fatty acids from omega-3 researcher Dr. Richard Bazinet of the University of Toronto (2021).

Essential Fatty Acids: ALA and LA

The Institute of Medicine considers there to be a dietary requirement for two fatty acids for people age 1 year and older:

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

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

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

Essential Fatty Acid Intakes of Vegans

The table below shows the weighted averages of studies measuring vegan ALA intakes. Calculations and citations are in our ALA Intakes spreadsheet.

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The World Health Organization and Food and Agriculture Organization (2010) 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 the risk for heart disease.

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% (Pinto, 2017, United Kingdom), 7.3% (Allès, 2017, France), 8.5% (Kornsteiner, 2008, Austria), and 9.3% (Rizzo, 2013, USA), well within the range recommended by the WHO. Because of this, we’re hesitant to recommend that vegans avoid LA.

Long-chain Omega-3 Fatty Acid Blood Levels of Vegetarians

Summary: The differences in long-chain omega-3 blood levels between vegans, lacto-ovo-vegetarians, and omnivores aren’t obviously physiologically significant, especially with regard to omnivores who don’t regularly eat fish. Red blood cell DHA of vegetarians and vegans is roughly 72-75% of that of omnivores, but it’s not clear if this has clinical significance.

There is no standardized method for measuring omega-3 fatty acids: no one knows what levels of fatty acids in any given medium represent a deficient, healthy, or optimal level. It could even be that blood levels of fatty acids have little bearing on omega-3 fatty acid status. The purpose of this section is to determine whether vegans do indeed have lower blood levels of long-chain omega-3 fatty acids than omnivores. Early studies found that vegans have lower EPA and DHA blood levels, but these studies were conducted on very few people; more recent studies haven’t shown nearly the difference.

As of early 2022, we’ve tracked 27 studies measuring the blood levels of omega-3 fatty acids in vegetarians. We list these studies and their measurements in the Cross-sectional tab of our spreadsheet, Omega-3s Part 2: Research.

The way omega-3s are measured among these studies varies considerably.

Fatty acids can be measured in various components of plasma such as phospholipids, triglycerides, or cholesterol esters. Fatty acids may also be measured in the adipose tissue, platelets, or red blood cells. Because red blood cells have a lifespan of 120 days, red blood cell fatty acids might be a more accurate long-term representation of omega-3 status.

In the plasma, omega-3s are usually measured as a percentage of total fatty acids, but Welch et al. (2010) measured omega-3s as a concentration in plasma and Rosell et al. (2005) provided the data to calculate a concentration. Concentrations might be a more accurate reflection of the body’s omega-3 stores since they represent an absolute rather than a relative amount.

DPA is a long-chain omega-3 fatty acid that is an intermediary between EPA and DHA. We emphasize studies that included DPA in their measurements because DPA represents a significant fraction of long-chain omega-3s that vegans have converted from ALA and which can potentially be converted to DHA.

The graph below plots all measurements that compared total long-chain omega-3 levels (EPA+DPA+DHA) of vegetarians or vegans to omnivores. It includes measurements of percentages and concentrations for each medium. While there’s considerable overlap between diet groups, individual studies generally find that omnivores have higher levels of long-chain omega-3s than vegans with the differences being statistically significant.

 

The graphs below compare only the EPA or DHA levels of vegans and vegetarians in all studies that measured EPA or DHA.

 

 

Arguably the most important metric is red blood cell omega-3s, shown in the graph below.

 

It’s hard to conclude much regarding vegan long-chain omega-3 levels from these studies given that the measurements aren’t standardized, aren’t well understood, and contain significant overlap. Arguably a more accurate way to assess this data is to weight the comparisons of vegetarians both proportional to the omnivores in the same studies and proportional to how many people were in each diet group while limiting the measurements to one per population studied.

In order to get the most accurate picture of how long-chain omega-3 blood levels of vegans compare to those of omnivores, we decided to calibrate the measurements by creating a ratio of the levels of vegans to those of omnivores rather than using an absolute amount. We did this by simply dividing the vegan level by the omnivore level.

For example, the study by Kornsteiner et al. found an EPA+DPA+DHA percentage of total fatty acids in red blood cells of 1.96% for vegans and 3.34% for omnivores. The study by Li et al. found an EPA+DPA+DHA percentage of total fatty acids in plasma of 3.6% for vegans and 5.5% for omnivores. We don’t know if we can compare the percentage of fatty acids in red blood cells to the fatty acids in plasma, but we can compare the ratio of vegan to omnivore long-chain omega-3s in both studies, which was .59 in Kornsteiner et al. and .65 in Li et al. We can then multiply these two ratios by the number of vegans in their respective study, divide by the total number of vegans in both studies, and get a weighted average of the ratio of vegan to omnivore long-chain omega-3s across both studies. By weighting all of the studies in this way, we can obtain the most accurate picture of how blood levels of long-chain omega-3 fatty acids compare for vegans and omnivores.

Most studies measured omega-3s as a percentage of total fatty acids; to be as consistent as possible, we weighted the percentage of total fatty acids rather than the concentration for studies that measured both. For studies with multiple measurements, we chose in this order: red blood cells, plasma, platelets, and adipose tissue.

The table below shows the weighted proportions of omega-3s for vegetarians and vegans compared to omnivores for all studies and for red blood cell (RBC) measurements only. Calculations and citations are in the Cross-sectional tab of our spreadsheet, Omega-3s Part 2: Research.

 

Based on the table above, vegans generally have lower blood levels of long-chain omega-3s than omnivores. Since plasma levels of omega-3s are at least in part a representation of dietary fatty acids, as distinct from representing only the body’s ability to convert dietary short-chain to long-chain omega-3s, it’s not surprising that people who have an intake of long-chain omega-3s have higher blood levels.

Vegetarians vs. Fish-Eaters

Among people who don’t supplement with long-chain omega-3s, regular fish-eaters will be the only dietary group with a significant source of long-chain omega-3s. 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.

There are two studies that measured omega-3 levels among fish-eaters (Welch, 2010; Miles, 2019), but neither measured it in red blood cells. We analyze these studies in the Fish-eaters tab of our spreadsheet Omega-3s Part 2: Research and summarize the results in the three charts below. Participants in the studies didn’t use long-chain omega-3 supplements.

Welch et al. (2010) measured omega-3 plasma concentrations and separated omnivores into groups who did and did not eat fish. There were only 10 vegans.

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We combined the male and female long-chain omega-3 plasma concentrations to determine how vegans compared to both fish-eating and non-fish-eating omnivores. Because there were so few vegans, we also combined the lacto-ovo-vegetarians (LOV) with the vegans for a “vegetarian” category. The table below shows that lacto-ovo-vegetarians, vegans, or the combined group had levels slightly below fish-eaters and either similar or higher levels than non-fish-eaters.

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Miles et al. (2019) compared the percentage of omega-3 fatty acids in the adipose tissue of pescatarians to other dietary groups, as shown in the table below. Vegetarians and vegans had lower levels than omnivores and even somewhat lower levels than fish-eaters. Although vegans had substantially lower levels than fish-eaters in this study, it’s not clear what the percentages of fatty acids in adipose tissue represent; possibly nothing of clinical significance.

 

Fatty Acid Levels of Older vs. Younger Vegans

It’s normally thought that people have a harder time converting ALA to EPA and DHA as they age. Sarter et al. (2015) found that 69 vegans aged 60 to 85 had EPA+DHA levels of about 4.0% compared to about 3.6% for 97 vegans aged 20 to 59 (p for trend = 0.009).

Impacts of Lower EPA and DHA on Vegetarians

A possible benefit of long-chain omega-3 fatty acids, especially EPA, is to reduce blood clotting which protects against heart attacks. There have been some differences noted in blood clotting between vegetarians and omnivores.

Mezzano et al. (1999, Chile), 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 study, Mezzano et al. (2000, Chile) gave vegetarians 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 changed, but bleeding time remained lower at 5-1/2 minutes.

Sanders and Roshani (1992, United Kingdom) found that only one of eight platelet aggregation parameters in vegan men, but not women, was different from the non-vegetarians. Bleeding times were similar.

Pinto et al. (2017, United Kingdom) compared heart rate variability between a group of 23 adult vegans and 24 omnivores. Low heart rate variability reflects a reduced capacity for the heart to respond to the body’s physiological demands and is linked to an 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. The clinical significance of these findings aren’t clear.

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

In terms of cognition, in their study of British mortality, Appleby et al. (2002) 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). In contrast, a more recent report from EPIC-Oxford (Appleby, 2016) found that vegetarian deaths from mental and behavioral disorders were not statistically different from non-vegetarians (HR 1.22, CI 0.78–1.91). And a report from the Adventist Health Study-2 (Orlich, 2013, USA) found no difference in mortality from neurologic diseases between vegetarians and non-vegetarians (HR 0.93, CI 0.67-1.29); pescatarians and semi-vegetarians were included in their vegetarian category so the results can’t be extrapolated to vegetarians who don’t eat fish.

Conversion of ALA to EPA and DHA

Measurements of the percentage of total fatty acids as EPA and DHA in the blood are generally considered a marker of omega-3 status. This assumes that higher percentages of total fatty acids in the blood reflect higher and more optimal amounts in the tissues that utilize omega-3s. It also assumes that when blood percentages change due to changes in dietary intake, levels in tissues respond similarly.

In this section, we examine these assumptions. Evidence of omega-3 conversion enzymes in tissues and down-regulation of omega-3 conversion in response to dietary omega-3s suggest that the body can regulate the conversion of omega-3 fatty acids in tissues independent of the percentage in the blood.

There’s evidence that high intakes of EPA and DHA will increase their percentages in both blood and tissues, but it’s not clear if higher percentages are necessary for optimal health. We assess the evidence in our sections Impacts of Lower EPA and DHA on Vegetarians and Omega-3s and Chronic Disease.

ALA Supplementation Results in Little Increase in Blood DHA

Our ALA Trials spreadsheet lists a handful of clinical trials, including all of the trials with vegetarians of which we’re aware, investigating whether increasing dietary ALA subsequently increases the percentage of long-chain omega-3s in the blood. The changes in total fatty acids as long-chain omega-3s show a wide variation with no clear pattern; some even found a decrease in DHA. On average, EPA+DPA+DHA increased by 43.5% while DHA only increased by 4.6%.

It’s safe to say that supplementing with ALA is unlikely to substantially increase the blood percentage of fatty acids as DHA in most adults.

EPA and DHA Correlate between Plasma and the Heart but not the Brain

Summary: Based on limited, mostly cross-sectional data, there appears to be a robust correlation between the blood and tissue percentages of EPA+DHA in the human heart but not the brain or sperm.

Studies of ALA supplementation result in very little increase of DHA in the blood, but how much evidence is there to suggest that this reflects the body’s inability to convert ALA to DHA for tissue utilization?

A basic question is, without any dietary changes, how much do blood levels of omega-3 fatty acids typically correlate with tissue levels? It’s difficult to study the omega-3 content of tissues in living humans. In our spreadsheet, Tissue Correlations, we list the correlations between blood and tissue percentages of omega-3s in both humans and animals. A summary of the results follows.

Harris et al. (2004) measured the correlation between the percentage of EPA+DHA in red blood cells and the percentage of EPA+DHA in the hearts of 20 heart transplantation patients having routine heart biopsies, 13 of whom were considered to be high consumers of EPA and DHA; they found a statistically significant, strong correlation (R = 0.82, P ≤ 0.0001).

Harris et al. (2004) also performed an intervention: Heart transplantation patients (n=25) with low EPA+DHA intakes were provided 1,000 mg of EPA+DHA for 6 months. These patients had weaker correlations between red blood cell and heart EPA+DHA at baseline (R = 0.47, P = 0.031). Post-intervention measurements showed that EPA+DHA percentages increased in plasma, red blood cells, heart, and cheek tissue; the correlation between red blood cell and heart EPA+DHA remained the same (R = 0.47, P = 0.06).

Cunnane et al. (2012) performed autopsies on cognitively normal people and found a correlation between percentages of DHA in plasma phosphatidylethanolamine and the angular gyrus region of the brain DHA (R = 0.77, P ≤ 0.005). However, they failed to find correlations between DHA and other regions or in cognitively impaired people stating, “No significant correlations were observed for DHA (% or mg/g) or any other fatty acids in the other brain regions or in the [Alzheimer’s disease] and [mildly cognitively impaired] groups (data not shown).”

Carver et al. (2001) performed autopsies on 58 people and found a negative correlation between the DHA percentage in red blood cells and the cerebral cortex of people aged >18 years; it’s likely this correlation doesn’t achieve statistical significance after a Bonferroni correction for the large number of correlations tested.

Chamorro et al. (2020) measured the fatty acid percentages of young men, comparing vegans (n=34) and omnivores (n=33). They didn’t test for a correlation between the percentage of omega-3s in plasma or red blood cells and sperm. The ratio of the percentage of EPA in sperm to that in plasma and red blood cells was similar at 0.54 for each, but the ratios for DPA and DHA were not. See the table below.

There’s much more data from animals than humans. Our spreadsheet, Tissue Correlations, lists 24 correlations between blood and tissue percentages of EPA+DHA among rats, pigs, and mice. The strength of the correlations varies considerably with some being negative.

There’s one other study on animals worth mentioning. Talahalli et al. (2010) fed two groups of rats a reasonable amount of ALA (2.5% and 5.0% of calories). After 60 days, the percentage of fatty acids as DHA in the brain of the rats fed 2.5% and 5.0% ALA was, respectively, 9.4% and 10.4% compared to 8.3% in the control group (see the table, Talahalli 2010). This suggests that ALA supplementation increased the amount of DHA in their brains.

One significant caveat for comparing the conversion of omega-3s in rats, pigs, and mice to humans is that rats, pigs, and mice normally don’t have a dietary source of EPA or DHA and, therefore, would normally rely entirely on the conversion from ALA for any EPA or DHA.

Tissues Contain Enzymes that Convert Omega-3s

Two critical enzymes, delta-5 desaturase and delta-6 desaturase, convert short-chain omega-3 and omega-6 fatty acids into long-chain versions.

Previously, the liver was considered the primary site of EPA and DHA production for peripheral tissue utilization, but studies by Cho et al. (1999a and 1999b) found substantial amounts of mRNA for the delta-5 and delta-6 desaturase enzymes in many tissues of human cadavers.

Cho et al. (1999a) found that delta-5 desaturase mRNA was greatest in the human liver, but that the heart, brain, and lung also contained substantial amounts. They found low but detectable levels in the placenta, skeletal muscle, kidney, and pancreas. Cho et al. (1999b) found that the amount of delta-6 desaturase mRNA in the human liver was comparable to that found in the human lung and heart, while the adult brain had a level several times greater than the liver.

Cho et al. (1999a) point out that the expression of these enzymes can vary greatly among individuals. The authors hypothesize that this might be due to age or, more likely in their view, regulation of the enzymes in response to the dietary intake of fatty acids.

Using cross-sectional data based on the percentage of plasma phospholipids, Welch et al. (2008, United Kingdom) estimated that non-fish-eaters (both vegetarians and meat-eaters) convert ALA to long-chain omega-3s at about a 22% higher rate than fish-eaters.

Dietary DHA Reduces ALA Conversion

In a series of three studies, researchers used a carbon tracer to track the conversion of a 700 mg dose of ALA to long-chain omega-3s in the blood of three different groups of people. The results are in the table below. Only females (all of whom were of reproductive age) showed a substantial conversion of ALA to DHA in the blood.

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In addition to the baseline measurements listed in the table above, Burdge et al. (2003) included an 8-week intervention on three groups of older men: a control group (n=5), a group whose daily ALA was increased from their normal intake of 1.7 g to 10 g (n=4), and a group whose daily EPA+DHA was increased from their normal intake of 264 mg to 1.6 g (n=5). After 8 weeks, they fed each person 700 mg of ALA with a carbon tracer and found that the ALA supplemented group’s conversion of ALA to long-chain omega-3s hadn’t increased whereas the EPA+DHA supplemented group’s conversion had decreased.

Vermunt et al. (2000) fed carbon-labeled ALA to humans and found that the conversion of ALA to EPA, DPA, and DHA was much greater after 9 weeks of a diet high in oleic acid compared to after a diet high in ALA or EPA+DHA.

The two trials mentioned above by Burdge et al. (2003) and Vermunt et al. (2000) suggest that there’s a down-regulation of ALA conversion to long-chain omega-3s in humans who have a regular supply of ALA or EPA and DHA. The simplest explanation for this down-regulation is that their tissues had sufficient long-chain omega-3 levels.

Further evidence for enzymatic regulation due to dietary intake is a study by Metherel et al. (2019) who conducted a randomized controlled trial using carbon-labeled DHA. While plasma levels of EPA increased, it wasn’t due to DHA being converted to EPA, suggesting that the dietary supply of DHA resulted in the down-regulation of the conversion of EPA to DHA.

Burdge and Wootton’s data (2002) showed an uneven distribution of omega-3 fatty acids among the different components of plasma lipids (cholesterol esters, phosphatidylcholine, triglycerides, and non-esterified fatty acids). They surmised that plasma cholesterol esters act as a long-term source of ALA within circulation that may provide tissues containing active desaturation and elongation pathways (brain, heart, and skeletal muscles) a steady source of ALA for conversion to EPA, DPA, and DHA while tissues with low expressions of these enzymes, such as the kidney and pancreas, may be dependent upon the supply of pre-formed EPA, DPA, and DHA.

Lower Omega-6 Intake is Associated with Higher Serum EPA and DHA

The traditional way vegetarians have been encouraged to raise blood EPA and DHA levels is by increasing ALA and decreasing the omega-6 fatty acid, linoleic acid (LA). This is because the enzymes that convert ALA into EPA and DHA also convert the omega-6 fatty acids and there is competition for these enzymes. Some evidence for this theory is from a clinical trial by Liou et al. (2007, Canada) who found increasing LA intake resulted in a lower percentage of EPA in plasma phospholipids

Most vegetable oils are high in omega-6s and vegetarians tend to get plenty in their diets. Sanders and Younger (1981, United Kingdom) found a dietary ratio of omega-6s to omega-3s of 16 for vegans and 6 for meat-eaters. Sanders and Roshanai (1992, United Kingdom) found a dietary ratio of 15.8 for vegan men, 10.2 for meat-eating men, 18.3 for vegan women, and 8.2 for meat-eating women.

There are no clinical trials that increase the ALA intake of vegetarians while also decreasing their LA intake, to see what impact this has on blood levels of EPA and DHA.

Salvador et al. (2019, Spain) studied 55 vegans and 49 lacto-ovo-vegetarians and found that those with a serum omega-6 to omega-3 ratio of ≤ 10 had a higher percentage of serum EPA and DHA than those with a ratio between 10 and 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 were associated with a much higher percentage of serum ALA (~0.5% vs. ~0.7% and 1.5%, respectively), but not with higher EPA or DHA percentages.

Based on limited research, lowering LA intake could increase blood levels of long-chain omega-3s, but it’s not known if doing so impacts tissues or provides health benefits.

Low Omega-6 to Omega-3 Ratio Foods

At this time, the research indicates that vegetarians with lower dietary omega-6 to omega-3 ratios tend to have higher blood levels of EPA and DHA. For that reason, it’s prudent, when adding ALA to the diet, to choose foods that don’t also substantially increase omega-6 intake, listed in the table below.

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

Studies consistently show that supplementing vegetarians and vegans with DHA from algal sources increases their blood percentage of DHA (Sanders, 2009; Geppert, 2006; Wu, 2006; Conquer, 1996; Conquer, 1997). Studies also show that supplementing with both EPA and DHA increases vegetarians EPA and DHA percentages (Sarter, 2015; Mezzano, 2000).

Fish contains about twice as much DHA as EPA (Kris-Etherton, 2009), so it’s not unusual for fish-eaters to eat more DHA than EPA. Conquer and Holub (1996, Canada) showed an 11–12% increase in EPA after 6 weeks of 1,620 mg of DHA in vegetarians.

Upon DHA supplementation, EPA levels also increase by a small percentage. Using a carbon tracer, Brossard et al. (1996, France) found a 1.4% conversion of DHA to EPA in three people given one dose of 123 mg of DHA over the course of 20 hours. In contrast, Metherel et al. (2019, Canada) conducted a randomized controlled trial using 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.”

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. To be cautious 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.

There are many vegan DHA and EPA supplements available via the Internet. We aren’t able to assess whether any given company is better than another.

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 (Langdon, 2006).

Reddy and Sanders (1994, United Kingdom) measured the DHA levels in umbilical cords of 32 infants born to vegetarian mothers compared to omnivores 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.

Many children have been raised vegan without supplementing with DHA, or even extra ALA, and appear to develop well. Even so, it’s prudent for breastfeeding mothers of vegetarian or vegan children to ensure they’re meeting omega-3 recommendations (see Daily Recommendations) and non-breastfeeding infants should receive infant formula with 500 mg of EPA+DHA per day.

Omega-3s and Chronic Disease

Most of the concern with regard to low plasma levels of EPA and DHA among vegetarians is due to studies that have found an association between low EPA and DHA blood levels and an increased risk of chronic diseases such as cardiovascular, cognitive decline, and depression. These associations have generally been consistent but weak. There have also been some associations between omega-3 blood levels and an increase in some chronic diseases. In this section we review the evidence.

Omega-3s and Cardiovascular Disease

Research on omega-3s and cardiovascular disease has examined the associations with fish consumption, blood levels of omega-3s, and omega-3 supplementation.

Fish Consumption and Cardiovascular 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 (Kris-Etherton, 2002) 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).”

Some recent reports include:

  • A 2020 meta-analysis of six cohort studies found no correlation between eating fish and a reduced risk of cardiovascular disease or mortality (Zhong, 2020).
  • A 2020 Cochrane review determined that there wasn’t enough evidence to assess the impact of eating fish on cardiovascular health (Abdelhamid, 2020).
  • A 2016 meta-analysis of 12 prospective studies found a reduced risk of mortality with increasing fish intake (Zhao, 2016).

Omega-3 Supplementation and Cardiovascular 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 (Abdelhamid, 2020). 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.

In contrast, a 2019 meta-analysis of omega-3 supplementation found a benefit from omega-3 supplementation in the combined results from 13 randomized controlled trials using about 800 to 1,800 mg of omega-3 fatty acids per day (Hu et al.). At baseline, the participants had 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. For the omega-3 content 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 the placebo (Bhatt, 2019). The extremely high amount of EPA used in REDUCE-IT is a pharmacological dose and not relevant to dietary omega-3 intake.

Omega-3s and 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 blood levels and numerous cognitive-related parameters (Tan, 2012). They compared the EPA+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 lowest 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 blood EPA+DHA was associated with a poorer score on some tests of cognition.

As part of the Women’s Health Initiative Study of Cognitive Aging, Ammann et al. (2013, USA) 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+DHA percentage of fatty acids in red blood cells. 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. A 2017 study by Ammann et al. (described below), followed a much larger group of participants over time and provides more insight into whether higher EPA and 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 and found that increases of 1-serving/wk increments 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). 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 point 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 argue 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.” Zhang and Jiao responded that it was appropriate to include both reports. It’s perplexing that 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, USA) conducted the largest prospective study to assess the risk of dementia with omega-3 fatty acid status. 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 (5.3-6.8% EPA+DHA) to those within one standard deviation below the mean (3.8-5.3% EPA+DHA). In one of their models, the researchers found a statistically significant 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). The researchers calculated that the increased risk of PD represented a 2% reduced risk (12% vs. 14%) of PD incidence over a 15-year period. There were no significant associations between EPA+DHA and MCI. Examining EPA and DHA separately produced no significant findings.

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 responsible for the beneficial association rather than other variables paired with omega-3 intake.

Omega-3s and Depression

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

Risk of Depression

Deane et al. (2019) conducted a meta-analysis and systematic review of 32 randomized controlled trials and found no effect of increasing EPA and DHA on the risk of depressive symptoms (RR 1.01, CI 0.92-1.10). 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 or DHA can be used to treat people with depression is only loosely related to the omega-3 status of vegetarians, but it’s 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. In a 2006 review, Sontrop and Campbell 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. In another 2006 review, Appleton et al. found “little support” based on the small number of trials with significant variation. In a 2007 meta-analysis Lin and Sue found a positive effect of supplementation but with significant publication bias. In a 2009 meta-analysis, Martins found evidence that EPA is more effective than DHA.

Grosso et al. (2014) conducted a meta-analysis of 11 trials of patients with a DSM-defined diagnosis of a 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, with many trials using pharmacological doses. Hallahan, et al. (2016) found similar results in their meta-analysis.

In their meta-analysis, Luo et al. (2020) 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.

Omega-3s and 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 (Simon, 2009) 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 (Carayol, 2010).

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

A 2013 study suggested that 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 moderate any supplementation. More details can be read in the article, DHA Supplements and Prostate Cancer.

Eyesight

A 2001 analysis from the Nurses Health Study found an almost statistically significant increase in age-related macular degeneration for those with the highest ALA intake (Cho, 2001, USA).

In contrast, a 2013 study found that higher ALA levels in the blood were associated with a lower risk of late age-related macular degeneration (Merle, 2013, France). And a 2017 follow-up 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 (Wu, 2017, USA).

A 2005 analysis 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 (Lu, 2005, USA). 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 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 (Lu, 2007, USA).

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.

Last updated May 2022

Bibliography

Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, Deane KHO, Summerbell CD, Worthington HV, Song F, Hooper L. Omega‐3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews 2020, Issue 3.

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. Not cited.

Albert BB, Cameron-Smith D, Hofman PL, Cutfield WS. Oxidation of marine omega-3 supplements and human health. Biomed Res Int. 2013;2013:464921. Not cited.

Allès B, Baudry J, Méjean C, Touvier M, Péneau S, Hercberg S, Kesse-Guyot E. Comparison of Sociodemographic and Nutritional Characteristics between Self-Reported Vegetarians, Vegans, and Meat-Eaters from the NutriNet-Santé Study. Nutrients. 2017 Sep 15;9(9).

Ammann EM, Pottala JV, Harris WS, Espeland MA, Wallace R, Denburg NL, Carnahan RM, Robinson JG. ω-3 fatty acids and domain-specific cognitive aging: secondary analyses of data from WHISCA. Neurology. 2013 Oct 22;81(17):1484-91.

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.

Appleby PN, Crowe FL, Bradbury KE, Travis RC, Key TJ. Mortality in vegetarians and comparable nonvegetarians in the United Kingdom. Am J Clin Nutr. 2016 Jan;103(1):218-30.

Appleby PN, Key TJ, Thorogood M, Burr ML, Mann J. Mortality in British vegetarians. Public Health Nutr. 2002 Feb;5(1):29-36.

Appleton KM, Hayward RC, Gunnell D, Peters TJ, Rogers PJ, Kessler D, Ness AR. Effects of n-3 long-chain polyunsaturated fatty acids on depressed mood: systematic review of published trials. Am J Clin Nutr. 2006 Dec;84(6):1308-16.

Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1467S-1476S. Not cited.

Attar-Bashi NM, Frauman AG, Sinclair AJ. Alpha-linolenic acid and the risk of prostate cancer. What is the evidence? J Urol. 2004 Apr;171(4):1402-7. Not cited.

Bäck M. Omega-3 fatty acids in atherosclerosis and coronary artery disease. Future Sci OA. 2017 Oct 5;3(4):FSO236. Not cited.

Barcelo-Coblijn G, Murphy EJ, Othman R, Moghadasian MH, Kashour T, Friel JK. Flaxseed oil and fish-oil capsule consumption alters human red blood cell n-3 fatty acid composition: a multiple-dosing trial comparing 2 sources of n-3 fatty acid. Am J Clin Nutr. 2008 Sep;88(3):801-9.

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. Not cited.

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT Jr, Juliano RA, Jiao L, Granowitz C, Tardif JC, Ballantyne CM; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22.

Brossard N, Croset M, Pachiaudi C, Riou JP, Tayot JL, Lagarde M. Retroconversion and metabolism of [13C]22:6n-3 in humans and rats after intake of a single dose of [13C]22:6n-3-triacylglycerols. Am J Clin Nutr. 1996 Oct;64(4):577-86.

Brouwer IA, Katan MB, Zock PL. Dietary alpha-linolenic acid is associated with reduced risk of fatal coronary heart disease, but increased prostate cancer risk: a meta-analysis. J Nutr. 2004 Apr;134(4):919-22. Not cited.

Burdge GC, Finnegan YE, Minihane AM, Williams CM, Wootton SA. Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]alpha-linolenic acid to longer-chain fatty acids and partitioning towards beta-oxidation in older men. Br J Nutr. 2003 Aug;90(2):311-21.

Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr. 2002 Oct;88(4):411-20.

Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentaenoic acids are the principal products of alpha-linolenic acid metabolism in young men*. Br J Nutr. 2002 Oct;88(4):355-63.

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. Not cited.

Burns-Whitmore B, Haddad E, Sabaté J, Rajaram S. Effects of supplementing n-3 fatty acid enriched eggs and walnuts on cardiovascular disease risk markers in healthy free-living lacto-ovo-vegetarians: a randomized, crossover, free-living intervention study. Nutr J. 2014 Mar 27;13(1):29.

Carayol M, Grosclaude P, Delpierre C. Prospective studies of dietary alpha-linolenic acid intake and prostate cancer risk: a meta-analysis. Cancer Causes Control. 2010 Mar;21(3):347-55. Review. (Abstract)

Carver JD, Benford VJ, Han B, Cantor AB. The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brian Res Bull 2001;56:79 – 85.

Chamorro R, Gonzalez MF, Aliaga R, Gengler V, Balladares C, Barrera C, Bascuñan KA, Bazinet RP, Valenzuela R. Diet, Plasma, Erythrocytes, and Spermatozoa Fatty Acid Composition Changes in Young Vegan Men. Lipids. 2020 Nov;55(6):639-648.

Cho E, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA, Hankinson SE. Prospective study of dietary fat and the risk of age-related macular degeneration. Am J Clin Nutr. 2001 Feb;73(2):209-18.

Cho, 1999a. Cho HP, Nakamura M, Clarke SD. Cloning, expression, and fatty acid regulation of the human delta-5 desaturase. J Biol Chem. 1999 Dec 24;274(52):37335-9.

Cho, 1999b. Cho HP, Nakamura MT, Clarke SD. Cloning, expression, and nutritional regulation of the mammalian Delta-6 desaturase. J Biol Chem. 1999 Jan 1;274(1):471-7.

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. Not cited.

Conquer JA, Holub BJ. Dietary docosahexaenoic acid as a source of eicosapentaenoic acid in vegetarians and omnivores. Lipids. 1997 Mar;32(3):341-5.

Conquer JA, Holub BJ. Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr. 1996 Dec;126(12):3032-9.

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. Not cited.

Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA, Morris MC. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2012;29(3):691-7.

Deane KHO, Jimoh OF, Biswas P, et al. Omega-3 and polyunsaturated fat for prevention of depression and anxiety symptoms: systematic review and meta-analysis of randomised trials [published online ahead of print, 2019 Oct 24]. Br J Psychiatry. 2019;1‐8.

Ezaki O, Takahashi M, Shigematsu T, Shimamura K, Kimura J, Ezaki H, Gotoh T. Long-term effects of dietary alpha-linolenic acid from perilla oil on serum fatty acids composition and on the risk factors of coronary heart disease in Japanese elderly subjects. J Nutr Sci Vitaminol (Tokyo). 1999 Dec;45(6):759-72.

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. Not cited.

Fokkema MR, Brouwer DA, Hasperhoven MB, Martini IA, Muskiet FA. Short-term supplementation of low-dose gamma-linolenic acid (GLA), alpha-linolenic acid (ALA), or GLA plus ALA does not augment LCP omega 3 status of Dutch vegans to an appreciable extent. Prostaglandins Leukot Essent Fatty Acids. 2000 Nov;63(5):287-92.

Food and Agriculture Organization of the United Nations. Fats and fatty acids in human nutrition. Report of an expert consultation. Food and Nutrition Paper 91. Rome, 2010. (PDF)

Geppert J, Kraft V, Demmelmair H, Koletzko B. Microalgal docosahexaenoic acid decreases plasma triacylglycerol in normolipidaemic vegetarians: a randomised trial. Br J Nutr. 2006 Apr;95(4):779-86.

Grosso G, Pajak A, Marventano S, Castellano S, Galvano F, Bucolo C, Drago F, Caraci F. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS One. 2014 May 7;9(5):e96905.

Hallahan B, Ryan T, Hibbeln JR, Murray IT, Glynn S, Ramsden CE, SanGiovanni JP, Davis JM. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. Br J Psychiatry. 2016 Sep;209(3):192-201.

Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, Porter CB, Borkon AM. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation. 2004 Sep 21;110(12):1645-9.

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. Not cited.

Hu Y, Hu F, Manson JE. Marine Omega-3 Supplementation and Cardiovascular Disease: An Updated Meta-Analysis of 13 Randomized Controlled Trials Involving 127 477 Participants. J Am Heart Assoc. 2019 Oct;8(19):e013543.

Indu M, Ghafoorunissa. n-3 Fatty acids in Indian diets – comparison of the effects of precursor (alpha-linolenic acid) vs. product (long chain n-3 polyunsaturated fatty acids). Nutrition Research. 1992;12:569-82.

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.

Kornsteiner M, Singer I, Elmadfa I. Very low n-3 long-chain polyunsaturated fatty acid status in Austrian vegetarians and vegans. Ann Nutr Metab. 2008;52(1):37-47. Epub 2008 Feb 28. 10:1 n-6/n-3 for vegetarian diets and lower LC n-3 levels.

Kris-Etherton PM, Grieger JA, Etherton TD. Dietary reference intakes for DHA and EPA. Prostaglandins Leukot Essent Fatty Acids. 2009 Jun 12. [Epub ahead of print]

Kris-Etherton PM, Harris WS, Appel LJ; American Heart Association. Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002 Nov 19;106(21):2747-57. Erratum in: Circulation. 2003 Jan 28;107(3):512.

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.) Not cited.

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. Not cited.

Langdon JH. Has an aquatic diet been necessary for hominin brain evolution and functional development? Br J Nutr. 2006 Jul;96(1):7-17.

Li D, Sinclair A, Mann N, Turner A, Ball M, Kelly F, Abedin L, Wilson A. The association of diet and thrombotic risk factors in healthy male vegetarians and meat-eaters. Eur J Clin Nutr. 1999 Aug;53(8):612-9. Same measurements as provided in Li, 2002.

Li D, Sinclair A, Wilson A, Nakkote S, Kelly F, Abedin L, Mann N, Turner A. Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men. Am J Clin Nutr. 1999 May;69(5):872-82.

Li D, Turner A, Sinclair AJ. Relationship between platelet phospholipid FA and mean platelet volume in healthy men. Lipids. 2002 Sep;37(9):901-6. Same measurements as provided in Li, 1999.

Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-1. (Abstract)

Liou YA, King DJ, Zibrik D, Innis SM. Decreasing linoleic acid with constant alpha-linolenic acid in dietary fats increases (n-3) eicosapentaenoic acid in plasma phospholipids in healthy men. J Nutr. 2007 Apr;137(4):945-52.

Lu M, Taylor A, Chylack LT Jr, Rogers G, Hankinson SE, Willett WC, Jacques PF. Dietary fat intake and early age-related lens opacities. Am J Clin Nutr. 2005 Apr;81(4):773-9.

Lu M, Taylor A, Chylack LT Jr, Rogers G, Hankinson SE, Willett WC, Jacques PF. Dietary linolenic acid intake is positively associated with five-year change in eye lens nuclear density. J Am Coll Nutr. 2007 Apr;26(2):133-40.

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. Not cited.

Luo XD, Feng JS, Yang Z, Huang QT, Lin JD, Yang B, Su KP, Pan JY. High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis. BMC Psychiatry. 2020 May 20;20(1):248.

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. Not cited.

Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009 Oct;28(5):525-42. Review.

Merle BM, Delyfer MN, Korobelnik JF, Rougier MB, Malet F, Féart C, Le Goff M, Peuchant E, Letenneur L, Dartigues JF, Colin J, Barberger-Gateau P, Delcourt C. High concentrations of plasma n3 fatty acids are associated with decreased risk for late age-related macular degeneration. J Nutr. 2013 Apr;143(4):505-11.

Metherel AH, Irfan M, Klingel SL, Mutch DM, Bazinet RP. Compound-specific isotope analysis reveals no retroconversion of DHA to EPA but substantial conversion of EPA to DHA following supplementation: a randomized control trial. Am J Clin Nutr. 2019 Oct 1;110(4):823-831.

Mezzano D, Kosiel K, Martinez C, Cuevas A, Panes O, Aranda E, Strobel P, Perez DD, Pereira J, Rozowski J, Leighton F. Cardiovascular risk factors in vegetarians. Normalization of hyperhomocysteinemia with vitamin B(12) and reduction of platelet aggregation with n-3 fatty acids. Thromb Res. 2000 Nov 1;100(3):153-60.

Mezzano D, Munoz X, Martinez C, Cuevas A, Panes O, Aranda E, Guasch V, Strobel P, Munoz B, Rodriguez S, Pereira J, Leighton F. Vegetarians and cardiovascular risk factors: hemostasis, inflammatory markers and plasma homocysteine. Thromb Haemost 1999 Jun;81(6):913-7.

Miles FL, Lloren JIC, Haddad E, Jaceldo-Siegl K, Knutsen S, Sabate J, Fraser GE. Plasma, Urine, and Adipose Tissue Biomarkers of Dietary Intake Differ Between Vegetarian and Non-Vegetarian Diet Groups in the Adventist Health Study-2. J Nutr. 2019 Apr 1;149(4):667-675.

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. Not cited.

Orlich MJ, Singh PN, Sabaté J, Jaceldo-Siegl K, Fan J, Knutsen S, Beeson WL, Fraser GE. Vegetarian dietary patterns and mortality in Adventist Health Study 2. JAMA Intern Med. 2013 Jul 8;173(13):1230-8.

Ottestad I, Vogt G, Retterstøl K, Myhrstad MC, Haugen JE, Nilsson A, Ravn-Haren G, Nordvi B, Brønner KW, Andersen LF, Holven KB, Ulven SM. Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial. Br J Nutr. 2012 Jul;108(2):315-26. Not cited.

Peskin BS. Why fish oil fails: a comprehensive 21st century lipids-based physiologic analysis. J Lipids. 2014;2014:495761. (Retracted) Not cited.

Pinto AM, Sanders TA, Kendall AC, Nicolaou A, Gray R, Al-Khatib H, Hall WL. A comparison of heart rate variability, n-3 PUFA status and lipid mediator profile in age- and BMI-matched middle-aged vegans and omnivores. Br J Nutr. 2017 Mar;117(5):669-685.

Reddy S, Sanders TA, Obeid O. The influence of maternal vegetarian diet on essential fatty acid status of the newborn. Eur J Clin Nutr. 1994 May;48(5):358-68. (Abstract)

Rizzo NS, Jaceldo-Siegl K, Sabate J, Fraser GE. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. J Acad Nutr Diet. 2013 Dec;113(12):1610-9.

Rosell MS, Lloyd-Wright Z, Appleby PN, Sanders TA, Allen NE, Key TJ. Long-chain n-3 polyunsaturated fatty acids in plasma in British meat-eating, vegetarian, and vegan men. Am J Clin Nutr. 2005 Aug;82(2):327-34.

Roshanai F, Sanders TA. Assessment of fatty acid intakes in vegans and omnivores. Hum Nutr Appl Nutr. 1984 Oct;38(5):345-54. Same study population as Sanders, 1992.

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. Not cited.

Salvador AM, García-Maldonado E, Gallego-Narbón A, Zapatera B, Vaquero MP. Fatty Acid Profile and Cardiometabolic Markers in Relation with Diet Type and Omega-3 Supplementation in Spanish Vegetarians. Nutrients. 2019 Jul 20;11(7):1659.

Sanders TA, Roshanai F. Platelet phospholipid fatty acid composition and function in vegans compared with age- and sex-matched omnivore controls. Eur J Clin Nutr. 1992 Nov;46(11):823-31. Same study population as Roshani, 1984.

Sanders TA, Younger KM. The effect of dietary supplements of omega 3 polyunsaturated fatty acids on the fatty acid composition of platelets and plasma choline phosphoglycerides. Br J Nutr. 1981 May;45(3):613-6.

Sanders TA. DHA status of vegetarians. Prostaglandins Leukot Essent Fatty Acids. 2009 Aug-Sep;81(2-3):137-41.

Sarter B, Kelsey KS, Schwartz TA, Harris WS. Blood docosahexaenoic acid and eicosapentaenoic acid in vegans: Associations with age and gender and effects of an algal-derived omega-3 fatty acid supplement. Clin Nutr. 2015 Apr;34(2):212-8.

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. Not cited.

Simon JA, Chen YH, Bent S. The relation of alpha-linolenic acid to the risk of prostate cancer: a systematic review and meta-analysis. Am J Clin Nutr. 2009 May;89(5):1558S-1564S.

Sontrop J, Campbell MK. Omega-3 polyunsaturated fatty acids and depression: a review of the evidence and a methodological critique. Prev Med. 2006 Jan;42(1):4-13. Epub 2005 Dec 7.

Talahalli RR, Vallikannan B, Sambaiah K, Lokesh BR. Lower efficacy in the utilization of dietary ALA as compared to preformed EPA + DHA on long chain n-3 PUFA levels in rats. Lipids. 2010 Sep;45(9):799-808.

Tan ZS, Harris WS, Beiser AS, Au R, Himali JJ, Debette S, Pikula A, Decarli C, Wolf PA, Vasan RS, Robins SJ, Seshadri S. Red blood cell ω-3 fatty acid levels and markers of accelerated brain aging. Neurology. 2012 Feb 28;78(9):658-64.

Vermunt SH, Mensink RP, Simonis MM, Hornstra G. Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid. Lipids. 2000 Feb;35(2):137-42.

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. Not cited.

Welch AA, Bingham SA, Khaw KT. Estimated conversion of alpha-linolenic acid to long chain n-3 polyunsaturated fatty acids is greater than expected in non-fish-eating vegetarians and non-fish-eating meat-eaters than in fish-eaters. J Hum Nutr Diet. 2008;21:373.

Welch AA, Shakya-Shrestha S, Lentjes MA, Wareham NJ, Khaw KT. Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the precursor-product ratio of alpha-linolenic acid to long-chain n-3 polyunsaturated fatty acids: results from the EPIC-Norfolk cohort. Am J Clin Nutr. 2010 Nov;92(5):1040-51.

Wien M, Rajaram S, Oda K, Sabaté J. Decreasing the linoleic acid to alpha-linolenic acid diet ratio increases eicosapentaenoic acid in erythrocytes in adults. Lipids. 2010 Aug;45(8):683-92. doi: 10.1007/s11745-010-3430-3. Epub 2010 May 22.

Williams CM, Burdge G. Long-chain n-3 PUFA: plant v. marine sources. Proc Nutr Soc. 2006 Feb;65(1):42-50. Review. Not cited.

Wu J, Cho E, Giovannucci EL, Rosner BA, Sastry SM, Schaumberg DA, Willett WC. Dietary intake of α-linolenic acid and risk of age-related macular degeneration. Am J Clin Nutr. 2017 Jun;105(6):1483-1492.

Wu J, Wilson KM, Stampfer MJ, Willett WC, Giovannucci EL. A 24-year prospective study of dietary α-linolenic acid and lethal prostate cancer. Int J Cancer. 2018 Jan 8. [Epub ahead of print]

Wu WH, Lu SC, Wang TF, Jou HJ, Wang TA. Effects of docosahexaenoic acid supplementation on blood lipids, estrogen metabolism, and in vivo oxidative stress in postmenopausal vegetarian women. Eur J Clin Nutr. 2006 Mar;60(3):386-92.

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. Not cited.

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.

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

Zhao LG, Sun JW, Yang Y, Ma X, Wang YY, Xiang YB. Fish consumption and all-cause mortality: a meta-analysis of cohort studies. Eur J Clin Nutr. 2016 Feb;70(2):155-61.

Zhong VW, Van Horn L, Greenland P, Carnethon MR, Ning H, Wilkins JT, Lloyd-Jones DM, Allen NB. Associations of Processed Meat, Unprocessed Red Meat, Poultry, or Fish Intake With Incident Cardiovascular Disease and All-Cause Mortality. JAMA Intern Med. 2020 Feb 3.

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