Introduction

Eicosapentaenoic acid (or EPA) and docosahexaenoic acid (or DHA) are long-chain omega-3 fatty acids (long-chain omega-3) which are necessary for physiological function. Vegans are unable to obtain (non-negligible amounts of) EPA and DHA from their diet, because these fatty acids are generally only found in animal-based foods (especially oily fish). Without supplementation, vegans have to rely on the body's ability to convert alpha-linolenic acid (or ALA) to EPA and DHA. ALA (which is present in various plants, such as chia, soy, walnuts, flax and hemp) is a shorter chain omega-3 fatty acid which needs to be elongated by enzymatic processes. [For completeness, I should add that some animal-free foods contain stearidonic acid (SDA) which can also be converted to EPA/DHA]. 

However, research suggests that the human body converts ALA to EPA and DHA at low rates1-5 (although the rate of conversion differs between individuals and females – generally speaking – convert more efficiently than males 1). What’s more, several studies have indicated that vegans have the lowest blood concentrations of EPA and DHA (in terms of both red blood cells and plasma) compared to vegetarians and non-vegetarians6-8. I believe it’s likely that lower blood concentrations of these long-chain fatty acids reflect lower overall tissue levels: human9 and animal models10-11 indicate that this may be the case.  
 
I think we can deduce that most vegans are synthesising enough EPA and DHA through ALA for basic physiological requirements from the fact that they don’t seem to suffer from neurological/cardiological problems early in life. I am not aware of any case reports on vegans (or non-vegans for that matter) in the scientific literature describing a medical problem which could be attributed to a deficiency of long-chain omega-3. 

However, it's less clear whether supplementing vegan diets with long-chain omega-3 could lead to better health in middle-age and older adulthood – especially in relation to cognitive and cardiovascular outcomes. Additionally, there are concerns about low levels of DHA in pregnant and breastfeeding women; in terms of the impact this may have on the development and cognitive skills of their children.  
 
In this article, I will do my best to shed some light on the question of whether vegan adults should supplement their diets with long-chain omega-3 (in the form of algal oil).  

Cognitive/Neurological Health

DHA is found throughout the body. It’s by far the most abundant omega-3 fatty acid in our nervous system and its role in the brain is particularly important.  DHA is a building block of neurons and as such it’s safe to assume that a constant supply is required to maintain the structure of the brain. DHA is also needed to support brain function (e.g., in terms of signaling pathways, plasticity and cell survival). EPA is associated with better brain function too: it appears to improve the efficiency of the brain12; it may increase the levels of growth factors and reduce inflammation and cell death in the brain13.  

 
While animal models suggest that blood levels of long-chain omega-3 generally speaking tend to correlate with tissue levels; it’s less clear whether blood markers of EPA/DHA correlate with levels in the brain specifically. It’s possible that EPA/DHA is preferentially incorporated by the brain. Indeed, it’s plausible that the body might do this in light of the great importance of long-chain omega-3 for brain structure and function. If this is true, lower levels of long-chain omega-3 in the blood following the ingestion of ALA (compared to EPA/DHA) may not reflect lower levels in the brain. Support for this idea comes from a series of experiments which indicate that rats are able to accumulate similar levels of long-chain omega-3 in the brain through conversion of ALA14. I certainly think that this research gives us some reason to think that vegans may not require preformed long-chain omega-3 for optimal brain health. However, I’m not entirely convinced. Firstly, while the brains of DHA-fed and ALA-fed rats accumulated a similar amount of DHA; the brains of the DHA-fed rats took up twice as much DHA from the blood (I speculate that this may be advantageous). Secondly, other research based on rats found that the ingestion of preformed long-chain omega-3 (compared to ALA) resulted in larger dose-dependent increases in brain levels of DHA11. Thirdly, animal models are low down on the evidence hierarchy and therefore we should not put too much stock in these experiments.  

It is estimated that a healthy adult human brain requires about 4mg of DHA per day15-16. On paper, 3 grams of ALA should easily meet this requirement. Even at a sluggish conversion rate of 0.5-1%, 3g of ALA would provide between 15-30mg of DHA. Furthermore, although the precise requirement for EPA is unknown, the conversion of ALA to EPA is thought to be higher in comparison to DHA. On this basis, it doesn’t seem improbable that moderate amounts of ALA can supply the brain with adequate amounts of EPA+DHA. However, adequate amounts of long-chain omega-3 may not be optimal.  
 
Some evidence suggests that high doses of EPA+DHA may slow down atrophy of the brain and may even enlarge certain regions (such as the hippocampus – well known for its role in memory). For example, one randomised controlled trial found that older adults given 2.2g of EPA+DHA per day for 6 months suffered significantly less brain shrinkage compared to those taking a placebo17. Moreover, a similar RCT involving individuals with mild cognitive impairment and lasting 1 year, found that 2g of DHA (derived from algae) was associated with an increase in hippocampal volume (whereas decreases were seen in the placebo group)18.  

These results are fairly striking, but how relevant are they to the question of whether vegans would benefit from long-chain omega-3 supplementation?  Both studies used pharmaceutical doses that exceed the amount one would expect to get from 1-2 portions of oily fish per week (the amount typically recommended by various medical and dietetic associations). It would be inappropriate for the average vegan to take such large doses of preformed long-chain omega-3, as this is associated with serious side-effects (I will expand on this later). Additionally, the participants in these studies had relatively high long-chain omega-3 blood levels at baseline – much higher than I’d expect those on a non-supplemented animal-free diet to have.  
 
Other lines of research have linked long-chain omega-3 with better brain volume. For example, EPA/DHA seems to improve the structure and function of certain regions of the brain in aged mice19-20. However, the experimenters used large doses (about 400mg/kg/day). Moreover, the very fact that this is an animal model further reduces the relevance of this data.  
 
Several cross-sectional studies have found associations between long-chain omega-3 and smaller brain volumes21-23.However, because this type of study measures exposure and outcome at the same time, it’s not possible to determine whether low EPA/DHA is a cause or a consequence of low brain volume. For instance, individuals with cognitive impairment are at greater risk of malnutrition and this may partly explain why EPA/DHA is observed to be lower in this population.   
 
Longitudinal studies have found a positive correlation between blood levels of DHA and EPA and less cortical thinning24, as well as improved white matter quality25. A prospective cohort study26 based on the Three City Cohort is probably the best observational study on this subject that I’m aware of. 1200 older adults were followed for an impressive 17 years. The researchers measured plasma levels of EPA & DHA (omega-3 index) at baseline and performed cognitive tests every 2-3 years. They found that a higher omega-3 index was linked with a lower rate of medial temporal lobe atrophy (this part of the brain is involved in memory processing); lower incidence rate of dementia; and a slower decline in global cognition. The authors state that these results were not significantly attenuated after adjustment for diet quality.  
 
A meta-analysis of prospective cohort studies found fish and DHA intake inversely associated with vascular and Alzheimer’s dementia27. However, many of these studies failed to control for diet quality and other confounders. It’s possible that these associations could be at least partly the result of: 

  • Other beneficial constituents of fish (e.g., selenium, zinc).  
  • Replacement effects (fish may be a better choice compared to many commonly eaten foods) 
  • Healthy-user bias (fish may serve as an indicator of a healthier lifestyle). 

While the two RCTs mentioned earlier indicate a potential benefit in term of brain volume and function; on the whole RCTs have provided little support for the idea that long-chain omega-3 improves cognitive health. The three most recent meta-analyses of clinical trials that I’m aware of all found little to no benefit28-30. Now, one could speculate that this might be due to:  

  • The trials being too short (they often last a matter of weeks).  
  • Not using a high-enough dose of EPA/DHA to elicit a clear response. 
  • Failing to identify individuals with low baseline omega-3 levels.  

A recent RCT that recruited younger adults that consume low levels of fish suggests that baseline long-chain omega-3 intake may be important31. Interestingly, the researchers found that EPA-rich oil (in comparison to DHA-rich oil and placebo) did better in terms of several cognitive tasks. Further, the EPA-rich oil seemed to improve the efficiency of one region of the brain. Whereas, DHA-rich oil was only associated with an improvement in the speed at which participants were able to recognize words. 

In summary, animal models, cross-sectional studies, prospective cohorts and a couple of RCTs indicate that there may be a relationship between long-chain omega-3 and greater brain volume. Furthermore, observational research has consistently linked higher fish and DHA intake to a reduced risk neurogenerative diseases. However, these associations may be spurious. Moreover, RCTs investigating the impact of EPA/DHA on cognitive function have been on the whole disappointing. 
 
What does all of this mean for vegans? Frankly, I’m not entirely sure. But I think that the “precautionary principle” is relevant here (which I interpret as: ‘in situations of scientific uncertainty, err on the side of caution’). Multiple lines of evidence indicate that higher EPA/DHA intake (and status) may lead to more favourable brain morphology and function. For this reason, it doesn’t seem outlandish for vegans to take a moderate dose for brain health. I hope to see more high-quality studies on this topic in the near future. We need more large, long and well-adjusted cohort studies as well as RCTs which stratify for baseline omega-3 status/intake to get a better sense of whether vegans stand to benefit from preformed EPA/DHA with reference to brain health. But for now, I think it’s prudent for those eating an animal-free diet to take a daily algal oil supplement for the potential neuroprotective benefits.   

Pregnancy/Breastfeeding

Since vegans in general seem to have lower blood concentrations of EPA/DHA, I think it’s highly likely that pregnant vegan women will also have lower levels (compared to non-vegan pregnant women). Indeed, one study revealed that fetal blood taken from the umbilical cords of expecting vegetarian mothers was lower in DHA32. Moreover, several studies indicate that vegan mothers have lower levels of DHA in their breastmilk33-35. What’s more, it would seem that increasing the consumption of ALA-rich foods may be a poor strategy to rectify this: one study found that consuming high amounts of ALA (10.7g per day) for four weeks had no effect on breast milk DHA concentration36. 

A 2020 study observed that higher maternal intakes of long-chain omega-3 correlated with greater regional brain volumes in infants37. This lines up with the many other studies alluded to in the previous section.  

However, a Cochrane group meta-analysis did not find evidence in support of giving healthy preterm infants long-chain omega-3 enriched formula for improved neurodevelopmental outcomes38. Although a recent study  found that pre-term infants (born before 29 weeks' gestation) that were given 60mg of DHA per kilogram per day, performed better on an intelligence tested five years later62. Moreover, there is evidence that term infants may benefit from supplementation in terms of improved visual acuity61. 

Three meta-analyses of clinical trials failed to find evidence that supplementation of EPA and DHA among pregnant and lactating women offer any cognitive advantages to their offspring39-41. However, one could speculate that the researchers may not have identified the population that could benefit most from supplementation: none of the aforementioned meta-analyses stratified their results by baseline omega-3 levels.  

Two meta-analyses of trials on long-chain omega-3 supplementation and the risk of premature birth also failed to find evidence of benefit42,43. Yet, a 2018 Cochrane meta-analysis41 of 70 RCTs found that (dietary and supplemental) LCO3FA may: 

  • Decrease the risk of premature birth  
  • Lower the risk of perinatal death.  
  • Result in fewer neonatal care admissions.  
  • Decrease the risk of low birth weight.  
  • Reduce the risk of preeclampsia  

However, it also indicates that LC03FA may lead to babies being larger and may extend pregnancy duration beyond 42 weeks.  

A recent large RCT (involving 5544 pregnancies) failed to find a statistically significant relationship between omega-3 and the risk of early preterm delivery (delivery before 34 weeks of pregnancy)44. However, exploratory analysis found that women with a baseline omega-3 index below 4.1% seemed to benefit from supplementation in terms of risk reduction of early preterm delivery45. Additionally, those with a baseline status above 4.9% were at a greater risk of early delivery; but I would not expect vegan mothers to have a baseline level above this figure when not supplementing their diet with algal oil.  

It’s my view that lactating vegan mothers should consider supplementing their diets with algal oil to correct for lower levels of EPA/DHA in their blood and breast milk. I mentioned earlier that long-chain omega-3 are crucial for brain structure and function: fetal/infant brains are no exception. In fact, the requirement for DHA in the early stages of development is thought to be higher, due to the speed at which the brain is growing. Admittedly, the available evidence does not provide much support for the benefits of maternal EPA/DHA supplementation for improved neurodevelopment in infants. But I think that more research is needed and in the meantime, taking a supplement is the more cautious approach. 

But there are compelling reasons to supplement during pregnancy: the research from clinical trials shows benefits in terms of pregnancy outcomes as, mentioned above. As such, I think the default position (for the time being) has to be that pregnant vegan women ought to supplement their diets with long-chain omega-3.  

Cardiovascular Health

Several meta-analyses of prospective cohorts have found associations between fish/long-chain omega-3 and better heart health46-49. Moreover, higher blood levels of long chain omega-3 are linked to a lower risk of all-cause, cardiovascular and cancer mortality50. But I strongly suspect that this data is confounded; especially as many studies did not adjust their results for diet quality.  
 
However, one particular cohort study by Mozaffarian et al.51 caught my attention partly because it went to considerable lengths to control for potential confounders. The researchers followed 2,692 older adults for an impressive 16 years. After adjusting the results for key dietary variables (including fish and meat consumption; as well as various demographic, cardiovascular and lifestyle factors) they found that higher plasma levels of long-chain omega-3 were associated with lower total mortality (mostly due to reduced cardiovascular disease deaths).  

While observational studies consistently link EPA/DHA (intake and blood levels) to improved cardiovascular health; the results of clinical trials have been somewhat mixed. A 2021 meta-analysis of 40 studies suggests that substantial doses (1-2 grams per day) of EPA alone or combined EPA+DHA may reduce the likelihood of having a heart attack in high-risk populations52. Another recent meta-analysis of 16 clinical trials also indicates that large doses (>1g) may be effective for secondary prevention53.  

On the other hand, a 2020 Cochrane review showed little to no benefits in terms of primary and secondary prevention54. This meta-analysis revealed possible small benefits for long-chain omega-3 in terms of reduced risk of cardiovascular mortality, cardiovascular events, coronary heart disease mortality and events, but when limiting the analysis to the studies with a lower risk of bias the results approached no effect for cardiovascular mortality and events. But as before, we might wonder whether the trials were lengthy enough to get a decent estimate on the impact of EPA/DHA on cardiovascular health.  

I think that the VITAL study may be of particular interest to the question of whether vegans could stand to benefit from long-chain omega-355. Sub-group analysis showed that fish oil supplementation (460mg of EPA and 380 mg of DHA) in low-fish eaters was associated with a statistically significant 19% reduction in major cardiovascular disease events and a 40% reduction in heart attacks. Whereas, higher fish eaters did not seem to benefit. This suggests that those with low baseline EPA/DHA (intake or status) may benefit more from supplementation. The comparison between low and higher fish consumers was a prespecified part of the authors’ analysis, which adds to the credibility of these results. Other virtues of this study include its relatively long duration (5.3 years); its large sample size; and the fact that it was a double-blind, placebo-controlled clinical trial. Furthermore, the dose used is more appropriate for widespread use compared to many trials of this nature. I think that VITAL is an intriguing study which advances the case for vegans to supplement their diets with EPA/DHA to some extent. However, it is only one study: replication of this subgroup effect is needed to increase the credibility of this finding.
 
There is very little research on cardiovascular outcomes in vegans. But following a vegan diet is associated with lower levels of cardiometabolic risk factors56. Because vegans have better cardiometabolic profiles on average, it’s plausible that they will suffer from cardiovascular disease at a lower rate. Now, this doesn't preclude the possibility that vegans could further improve their cardiovascular health via one or more of the potential mechanisms of action of EPA/DHA (it has been hypothesised that long-chain omega-3 may decrease cardiovascular disease risk via anti-inflammatory, anti-thrombotic and triglyceride lowering effects, among others). But it does suggest that health conscious vegans with low markers of cardiovascular/metabolic disease risk may not benefit as much from preformed EPA/DHA. 
 
A large body of epidemiological evidence has found a consistent link between higher EPA/DHA intake and blood levels to better cardiovascular disease outcomes. Admittedly, most of this research offers low-certainty evidence. Despite RCTs on this topic being somewhat mixed, the VITAL study in particular strengthens my conviction that vegans who take algal oil may reduce their cardiovascular disease risk. 

On Dosing

Throughout this article I have taken the position that algal oil should be taken as a precaution.  However, when it comes to the question of dosage, I think the potential benefits have to be weighed against the potential harms. 
 
EPA/DHA supplementation is well-associated with an increase in the risk of atrial fibrillation57, 63. Higher doses (more than 1g per day) have been associated with a 49% increase in the risk of atrial fibrillation. While “lower doses” (about 850mg) appear to increase the risk by about 12%57. Further, EPA monotherapy (without DHA) may increase the risk of both atrial fibrillation and bleeding events58.  
 
Somewhat paradoxically, a prospective cohort study with 14 years of follow up found an inverse association between higher omega-3 status and hospitalisation due to bleeding or atrial fibrillation59. It would seem that the participants in this study were consuming “nonpharmacologic doses” of long-chain omega-3 (via food or supplements).  
 

I think that 250-350mg of (combined) EPA+DHA per day strikes a nice balance between the potential benefits and risks. It equates – roughly speaking – to about one portion of oily fish per week. 
 
Algal oil (the oil extracted from marine algae) is a vegan-friendly source of EPA/DHA. It has been shown to increase the concentration of long-chain omega-3 in the blood60. 

Conclusion

I think that adult vegans should consider taking a low-dose EPA+DHA supplement in the form of algal oil. This judgement is not based on very strong evidence, but I think that there is enough data suggestive of potential neuroprotective (and to a lesser extent) cardioprotective benefits to justify it.  
 
But in my view, pregnant vegan women ought to supplement their diets with algal oil as there is high-quality data indicating that it improves pregnancy outcomes.  Additionally, their offspring may not receive optimal amounts of EPA/DHA during a critical stage of their development.  

And importantly...

EPA/DHA may exert some benefits in terms of neurological and cardiovascular health, but it is not the be-all and end-all. An algal oil supplement is not a substitute for a good overall lifestyle. Factors like eating a well-planned diet; maintaining a healthy weight; regular exercise; smoking cessation and so on, almost certainly play a bigger role in slowing brain atrophy and reducing the risk of cardiovascular disease. 

[Last updated: 04/11/2022]

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References:

1. Burdge, G.C. and Wootton, S.A., 2002. Conversion of α-linolenic acid to eicosapentaenoic, docosapentaenoic and docosahexaenoic acids in young women. British Journal of Nutrition, 88(4), pp.411-420. 

2. Zhang, J.Y., Kothapalli, K.S. and Brenna, J.T., 2016. Desaturase and elongase limiting endogenous long chain polyunsaturated fatty acid biosynthesis. Current opinion in clinical nutrition and metabolic care, 19(2), p.103. 

3. Burdge, G.C., Jones, A.E. and Wootton, S.A., 2002. Eicosapentaenoic and docosapentaenoic acids are the principal products of α-linolenic acid metabolism in young men. British Journal of Nutrition, 88(4), pp.355-363. 

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

12. Patan, M.J., Kennedy, D.O., Husberg, C., Hustvedt, S.O., Calder, P.C., Khan, J., Forster, J. and Jackson, P.A., 2021. Supplementation with oil rich in eicosapentaenoic acid, but not in docosahexaenoic acid, improves global cognitive function in healthy, young adults: results from randomized controlled trials. The American Journal of Clinical Nutrition,114(3), pp.914-924 

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18. Zhang, Y.P., Miao, R., Li, Q., Wu, T. and Ma, F., 2017. Effects of DHA supplementation on hippocampal volume and cognitive function in older adults with mild cognitive impairment: A 12-month randomized, double-blind, placebo-controlled trial. Journal of Alzheimer's Disease, 55(2), pp.497-507. 

19. Cutuli, D., Pagani, M., Caporali, P., Galbusera, A., Laricchiuta, D., Foti, F., Neri, C., Spalletta, G., Caltagirone, C., Petrosini, L. and Gozzi, A., 2016. Effects of omega-3 fatty acid supplementation on cognitive functions and neural substrates: a voxel-based morphometry study in aged mice. Frontiers in aging neuroscience, 8, p.38. 

20. Cutuli, D., De Bartolo, P., Caporali, P., Laricchiuta, D., Foti, F., Ronci, M., Rossi, C., Neri, C., Spalletta, G., Caltagirone, C. and Farioli-Vecchioli, S., 2014. n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice. Frontiers in aging neuroscience, 6, p.220. 

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22. Pottala, J.V., Yaffe, K., Robinson, J.G., Espeland, M.A., Wallace, R. and Harris, W.S., 2014. Higher RBC EPA+ DHA corresponds with larger total brain and hippocampal volumes: WHIMS-MRI study. Neurology, 82(5), pp.435-442. 

23. Tan, Z.S., Harris, W.S., Beiser, A.S., Au, R., Himali, J.J., Debette, S., Pikula, A., DeCarli, C., Wolf, P.A., Vasan, R.S. and Robins, S.J., 2012. Red blood cell omega-3 fatty acid levels and markers of accelerated brain aging. Neurology, 78(9), pp.658-664. 

24. Walhovd, K.B., Storsve, A.B., Westlye, L.T., Drevon, C.A. and Fjell, A.M., 2014. Blood markers of fatty acids and vitamin D, cardiovascular measures, body mass index, and physical activity relate to longitudinal cortical thinning in normal aging. Neurobiology of aging, 35(5), pp.1055-1064. 

25. Virtanen, J.K., Siscovick, D.S., Lemaitre, R.N., Longstreth Jr, W.T., Spiegelman, D., Rimm, E.B., King, I.B. and Mozaffarian, D., 2013. Circulating omega-3 polyunsaturated fatty acids and subclinical brain abnormalities on MRI in older adults: the cardiovascular health study. Journal of the American Heart Association, 2(5), p.e000305.  

26. Thomas, A., Baillet, M., Proust?Lima, C., Féart, C., Foubert?Samier, A., Helmer, C., Catheline, G. and Samieri, C., 2021. Blood polyunsaturated omega-3 fatty acids, brain atrophy, cognitive decline, and dementia risk. Alzheimer's & Dementia, 17(3), pp.407-416 

27. Zhang, Y., Chen, J., Qiu, J., Li, Y., Wang, J. and Jiao, J., 2015. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: a dose-response meta-analysis of 21 cohort studies–3. The American journal of clinical nutrition, 103(2), pp.330-340. 

28. Balachandar, R., Soundararajan, S. and Bagepally, B.S., 2020. Docosahexaenoic acid supplementation in age-related cognitive decline: a systematic review and meta-analysis. European journal of clinical pharmacology, 76(5), pp.639-648. 

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