Ácidos grasos omega-3: EPA, DHA y lo que muestran las pruebas en humanos

Key Takeaways

• EPA and DHA are long-chain omega-3 fatty acids classified as essential because the body cannot synthesise them efficiently from precursors. They must be obtained through diet or supplementation.¹
• DHA is a major structural component of brain tissue and retinal photoreceptors. EPA is involved in the production of signalling molecules called eicosanoids and specialised pro-resolving mediators (SPMs).¹
• A 2024 global survey of 342,864 subjects across 48 countries found that omega-3 blood levels were low to very low in most populations worldwide.²
• Human RCTs and meta-analyses have examined EPA and DHA supplementation in relation to inflammatory biomarkers, lipid profiles, blood pressure, cognitive function, and cardiovascular outcomes. Results are mixed and depend on dose, duration, population, and formulation.^3,5
• Omega-3 supplements are available as fish oil, krill oil, and algae-derived forms. Purity, EPA:DHA ratio, and third-party testing are important quality considerations.
• There are no EFSA-approved health claims for omega-3 fatty acids in the Longevity Complete formulation. All information presented here is educational.

What Are Omega-3 Fatty Acids?

Omega-3 fatty acids are a family of polyunsaturated fatty acids (PUFAs) characterised by a double bond at the third carbon from the methyl end of their carbon chain. Three forms are most commonly discussed in nutrition science: alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA).

ALA is a short-chain omega-3 found in plant-based sources such as flaxseeds, chia seeds, and walnuts. It is considered the parent omega-3 because the body can theoretically convert it into EPA and DHA. However, human conversion rates are very low, estimated at less than 5% for EPA and less than 0.5% for DHA in most adults. This inefficiency is one reason researchers focus primarily on preformed EPA and DHA from marine sources.¹

EPA (20 carbons, 5 double bonds) and DHA (22 carbons, 6 double bonds) are long-chain omega-3s found predominantly in fatty fish (salmon, mackerel, sardines, anchovies, herring), shellfish, and certain algae. They are classified as conditionally essential because the body cannot produce them in meaningful quantities and depends on dietary intake.

Structural and Functional Roles of EPA and DHA

EPA and DHA are incorporated into cell membrane phospholipids throughout the body, where they influence membrane fluidity, receptor function, and cell signalling. Their distribution differs by tissue type.

DHA is particularly concentrated in the brain and retina. It constitutes approximately 40% of the polyunsaturated fatty acids in the brain and up to 60% in the retinal photoreceptors. This structural role has led researchers to investigate whether DHA status is associated with aspects of cognitive function and visual processing across the lifespan.⁶

EPA plays a more prominent role in the production of eicosanoids, a class of signalling molecules derived from 20-carbon fatty acids. EPA-derived eicosanoids are generally considered less pro-inflammatory than those derived from arachidonic acid (an omega-6 fatty acid). Both EPA and DHA serve as precursors to specialised pro-resolving mediators (SPMs), including resolvins, protectins, and maresins, which are involved in the active resolution phase of the inflammatory response.⁵

It is important to note that these are descriptions of known biochemistry, not claims about supplement efficacy. The biological roles of EPA and DHA in cell membranes and signalling pathways are well established. Whether supplementation with these fatty acids produces measurable outcomes in a given individual depends on many factors, including baseline status, dose, duration, and overall dietary context.

Global Omega-3 Status: What Population Data Shows

One of the most striking findings in omega-3 research is how low blood levels are in most populations worldwide. The Omega-3 Index, defined as the percentage of EPA plus DHA in red blood cell membranes, has emerged as a biomarker for assessing omega-3 status. It was first described in 2004 and has since been used in hundreds of published studies.²

The 2024 update of the Omega-3 World Map, encompassing 328 studies and 342,864 subjects from 48 countries, categorised national Omega-3 Index levels into four ranges: very low (4% or below), low (above 4% to 6%), moderate (above 6% to 8%), and desirable (above 8%). The findings showed that most countries fell into the low to very low range. Only a handful of countries, including Japan, South Korea, Norway, Finland, and Iceland, reached the desirable category. Large parts of North America, Europe, and Asia were classified as low.²

The original 2016 global survey of 298 studies in healthy adults also found that very low blood EPA and DHA levels were common across North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. Only populations near the Sea of Japan and in Scandinavia consistently showed high levels.¹

These population-level observations are descriptive. They indicate a gap between the omega-3 blood levels commonly observed and those used in research settings, but they do not by themselves establish that supplementation is necessary or beneficial for any individual. The Omega-3 Index is a research tool and biomarker, not a diagnostic test.

What Has Been Studied in Human Trials?

Omega-3 supplementation is among the most extensively studied dietary interventions in human research. Below is a summary of the major areas of investigation. These are descriptions of what researchers have examined, not statements about what omega-3s do.

Cardiovascular-Related Outcomes

A 2021 meta-analysis pooled data from 38 randomised controlled trials examining omega-3 fatty acids and cardiovascular outcomes. The analysis stratified results by EPA monotherapy and combined EPA plus DHA formulations. Individual trial results have been inconsistent; some large-scale RCTs reported statistically significant differences between omega-3 and placebo groups, while others did not. The authors noted that heterogeneity in outcomes may stem from differences in baseline risk, dietary intake, dosing, and formulation type.³

Lipid Biomarkers

A 2023 dose-response meta-analysis published in the Journal of the American Heart Association examined the relationship between EPA and DHA intake and lipid profiles across a large number of RCTs. The analysis found an approximately linear dose-response relationship between combined EPA plus DHA supplementation and changes in triglyceride levels. Changes in other lipid markers (LDL-cholesterol, HDL-cholesterol) were also examined, with more complex relationships observed.⁴

Inflammatory Biomarkers

An umbrella meta-analysis published in 2022 synthesised findings from 32 prior meta-analyses examining n-3 PUFA supplementation and inflammatory biomarkers in adults with various conditions. The pooled analysis reported statistically significant differences between supplementation and control groups for C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). The combined use of EPA and DHA showed more consistent differences than either fatty acid alone.⁵

It is important to note that changes in circulating inflammatory biomarkers do not automatically translate to meaningful differences for the individual. Biomarker studies are one piece of a larger evidence picture.

Cognitive Function

DHA's structural role in the brain has led to considerable research interest in omega-3s and cognitive function. A 2024 dose-response meta-analysis of RCTs examined the relationship between omega-3 supplementation and various cognitive domains in adults. The authors reported that higher-dose supplementation was associated with differences in some cognitive measures, though the certainty of evidence varied by domain.⁷

A narrative review covering 15 RCTs in cognitively healthy individuals over 55 found that approximately half reported differences between omega-3 and placebo groups, while half did not. The authors noted that potential explanations for this inconsistency include differences in dose, trial duration, genetic factors (such as apolipoprotein E genotype), sex, the rate of cognitive change in the study population, and the sensitivity of cognitive tests used.⁶

A 2015 systematic review focusing specifically on DHA and adult memory found that the pooled results from RCTs did not show a statistically significant change in memory function overall, though individual studies reported positive findings, particularly in participants with low baseline DHA status.⁸

Blood Pressure

An umbrella meta-analysis of 10 prior meta-analyses (20 effect sizes) examined the relationship between n-3 PUFA supplementation and blood pressure. Pooled estimates reported small but statistically significant differences between supplementation and control groups for both systolic and diastolic blood pressure. The authors noted that differences were more pronounced in studies involving older participants and smaller sample sizes.⁹

Overall, the evidence base for omega-3 supplementation in humans is large but mixed. Some meta-analyses report statistically significant differences between omega-3 and placebo groups for various biomarkers, while individual trial results vary considerably. Dose, formulation, baseline omega-3 status, and population characteristics all influence outcomes. Larger, longer-term studies with clinically relevant endpoints continue to be published.

Fish Oil, Krill Oil, and Algae: Choosing a Source

Omega-3 supplements are available in several forms, each with different characteristics.

Fish oil is the most widely studied and commonly consumed form. It typically provides EPA and DHA in triglyceride or ethyl ester form. The EPA:DHA ratio varies by product and by the fish species used. Standard fish oil concentrates typically contain 30% EPA plus DHA by weight (approximately 180 mg EPA and 120 mg DHA per 1,000 mg softgel), though concentrated formulations with higher percentages are also available.

Krill oil delivers EPA and DHA partly bound to phospholipids rather than triglycerides. Some pharmacokinetic studies have examined whether this phospholipid-bound form affects absorption, though the clinical significance of any differences remains an area of investigation. Krill oil also naturally contains the carotenoid astaxanthin.

Algae oil is a plant-based source of EPA and DHA derived from microalgae cultivation. It provides an alternative for individuals who prefer not to consume fish-derived products. Algae-derived DHA and EPA are chemically identical to those found in fish oil. The environmental sustainability of algae cultivation is also an area of interest.

Regardless of source, the key considerations are the total amount of EPA and DHA per serving (not just the total "fish oil" weight), the purity profile (freedom from contaminants such as heavy metals, PCBs, and dioxins), and whether the product has been independently tested.

Evaluating Omega-3 Supplement Quality

The quality of omega-3 supplements varies considerably across the market. Several factors are worth evaluating:

EPA and DHA content per serving: The total milligrams of EPA plus DHA per serving is the relevant metric, not the total weight of fish oil. A product labelled as "1,000 mg fish oil" may contain as little as 300 mg of combined EPA and DHA if it uses a standard 30% concentrate.

Third-party testing: Independent laboratory verification confirms that the product contains what the label states and meets purity standards. Brands that make Certificates of Analysis (COAs) publicly available demonstrate a commitment to transparency. Longevity Complete, for example, provides Eurofins third-party testing results and makes its COA available, reflecting the kind of transparency consumers can look for when evaluating any supplement.

Purity and contaminants: Marine-derived oils carry the potential for environmental contaminants including mercury, PCBs, and dioxins. Molecular distillation and purification processes are used to reduce these to levels well below regulatory limits. Third-party testing verifies the effectiveness of these purification steps.

Oxidation status: Omega-3 oils are susceptible to oxidation, which can produce off-flavours and may reduce the quality of the fatty acids. Freshness markers include peroxide value, anisidine value, and total oxidation (TOTOX) value. Products tested against these markers provide greater assurance of freshness.

Form and delivery: Triglyceride-form omega-3s are generally considered to have higher bioavailability than ethyl ester forms, though both deliver EPA and DHA effectively. Softgel encapsulation helps protect the oil from oxygen exposure.

Dosing, Safety, and Practical Considerations

Human clinical trials have used a wide range of EPA plus DHA doses, from less than 500 mg per day up to 4,000 mg per day or more. The dose used depends on the specific research question being investigated. There is no single universally established "optimal" dose for the general population.^4,3

Several international bodies have published intake recommendations ranging from 250 mg to 500 mg of combined EPA plus DHA per day for general health maintenance, though these vary by organisation and are not universally adopted.

Dietary sources of EPA and DHA include fatty fish (salmon, mackerel, sardines, anchovies, herring), shellfish, and to a much lesser extent certain fortified foods such as omega-3 enriched eggs. Two servings of fatty fish per week is a common dietary guideline, which typically provides approximately 250 to 500 mg of EPA plus DHA per day, depending on the fish species and preparation method.

In published clinical trials, omega-3 supplementation has been generally well tolerated. The most commonly reported side effects are mild gastrointestinal symptoms (fishy aftertaste, nausea, loose stools), particularly at higher doses. Omega-3s have been studied for their influence on platelet aggregation; individuals scheduled for surgery or taking anticoagulant agents should discuss omega-3 supplementation with their healthcare provider.³

As with any supplement, individuals who are pregnant, breastfeeding, taking medication, or managing a health condition should consult a qualified healthcare professional.

Questions and Answers

What are omega-3 fatty acids?

Omega-3 fatty acids are a family of polyunsaturated fats that the body cannot produce efficiently on its own. The three most discussed forms are ALA (from plant sources), EPA, and DHA (from marine sources). EPA and DHA are the forms most extensively studied in human research.¹

Why are EPA and DHA considered essential?

The human body can theoretically convert the plant-based omega-3 ALA into EPA and DHA, but conversion rates are very low (less than 5% for EPA and less than 0.5% for DHA in most adults). This means dietary intake of preformed EPA and DHA is the primary way to obtain meaningful amounts of these fatty acids.¹

What is the Omega-3 Index?

The Omega-3 Index is the percentage of EPA plus DHA in red blood cell membranes, expressed as a proportion of total fatty acids. It was first proposed in 2004 and is used in research as a biomarker of omega-3 status. A 2024 global update found that most countries have low to very low Omega-3 Index levels.²

What has omega-3 supplementation been studied for?

Human RCTs and meta-analyses have examined omega-3s in relation to cardiovascular outcomes, lipid profiles, inflammatory biomarkers, blood pressure, and cognitive function.^3,5,7 Results are mixed and depend on many factors including dose, duration, population, formulation, and baseline omega-3 status.

How much EPA and DHA do most people consume?

Global surveys indicate that most populations consume far less EPA and DHA than the amounts used in clinical research. Typical Western diets may provide 100 to 200 mg per day, compared to the 1,000 to 4,000 mg per day used in many intervention trials. Most countries have low to very low omega-3 blood levels.^2,1

What is the difference between fish oil, krill oil, and algae oil?

All three provide EPA and DHA. Fish oil is the most studied form. Krill oil delivers some EPA and DHA bound to phospholipids. Algae oil is a plant-based alternative that provides chemically identical EPA and DHA. The most important factor is the total EPA plus DHA per serving, regardless of source.

What should I look for in an omega-3 supplement?

Key quality markers include: total EPA plus DHA per serving (not just total oil weight), third-party testing with publicly available COA, purity testing for contaminants (heavy metals, PCBs, dioxins), oxidation markers (TOTOX value), and clear labelling of form (triglyceride vs ethyl ester).

Are omega-3 supplements well tolerated?

In published clinical trials, omega-3 supplementation has been generally well tolerated. The most common reports are mild gastrointestinal symptoms such as fishy aftertaste and nausea, particularly at higher doses.³ Consult a healthcare professional before starting any supplement, especially if you take medication or have a health condition.

Frequently Asked Questions

References

1. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016;63:132-152. View on PubMed ↗
2. Schuchardt JP, Beinhorn P, Hu XF, et al. Omega-3 world map: 2024 update. Prog Lipid Res. 2024;95:101286. View on PubMed ↗
3. Khan SU, Lone AN, Khan MS, et al. Effect of omega-3 fatty acids on cardiovascular outcomes: a systematic review and meta-analysis. EClinicalMedicine. 2021;38:100997. View on PubMed ↗
4. Wang T, Zhang X, Zhou N, et al. Association between omega-3 fatty acid intake and dyslipidemia: a continuous dose-response meta-analysis of randomized controlled trials. J Am Heart Assoc. 2023;12(9):e029512. View on PubMed ↗
5. Kavyani Z, Musazadeh V, Fathi S, Faghfouri AH, Dehghan P, Sarmadi B. Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: an umbrella meta-analysis. Int Immunopharmacol. 2022;111:109104. View on PubMed ↗
6. Kothapalli KSD, Park HG, Brenna JT. Omega-3 fatty acids and cognitive function. Curr Opin Clin Nutr Metab Care. 2023;26(2):92-98. View on PubMed ↗
7. Wei BZ, Li L, Dong CW, Tan CC, Xu W; Alzheimer's Disease Neuroimaging Initiative. The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis. J Nutr Health Aging. 2024;28(3):100168. View on PubMed ↗
8. Yurko-Mauro K, Alexander DD, Van Elswyk ME. Docosahexaenoic acid and adult memory: a systematic review and meta-analysis. PLoS One. 2015;10(3):e0120391. View on PubMed ↗
9. Musazadeh V, Kavyani Z, Naghshbandi B, Dehghan P, Vajdi M. The beneficial effects of omega-3 polyunsaturated fatty acids on controlling blood pressure: an umbrella meta-analysis. Front Nutr. 2022;9:985451. View on PubMed ↗