Docosahexaenoic acid (DHA) is anomega−3 fatty acid that is an important component of the humanbrain,cerebral cortex,skin, andretina. It is given thefatty acid notation22:6(n−3).[1] It can be synthesized fromalpha-linolenic acid or obtained directly from maternal milk (breast milk), fatty fish, fish oil, or algae oil.[1][2] The consumption of DHA (e.g., from fatty fish such as salmon, herring, mackerel and sardines) contributes to numerous physiological benefits, including cognition.[3][4] As a component ofneuronal membranes, the function of DHA is to support neuronal conduction and to allow the optimal functioning of neuronal membrane proteins (such as receptors and enzymes).[5]
Structurally, DHA is acarboxylic acid (-oic acid) with a 22-carbon chain (docosa- derives from theAncient Greek for 22) and six (hexa-)cisdouble bonds (-en-);[6] with the first double bond located at the third carbon from the omega end.[7] Itstrivial name iscervonic acid (from theLatin wordcerebrum for "brain"), itssystematic name isall-cis-docosa-4,7,10,13,16,19-hexa-enoic acid.
In organisms that do not eatalgae containing DHA nor animal products containing DHA, DHA is instead produced internally fromα-linolenic acid, a shorter omega−3 fatty acid manufactured by plants (and also occurring in animal products as obtained from plants).[8] Limited amounts ofeicosapentaenoic anddocosapentaenoic acids are possible products of α-linolenic acid metabolism in young women[9] and men.[8] DHA inbreast milk is important for the developing infant.[10] Rates of DHA production in women are 15% higher than in men.[11]
DHA is the most abundant omega−3 fatty acid in the brain and retina.[14] DHA comprises 40% of thepolyunsaturated fatty acids (PUFAs) in the brain and 60% of the PUFAs in the retina. Fifty percent of aneuronalplasma membrane is composed of DHA.[15] DHA modulates the carrier-mediated transport of choline, glycine, and taurine, the function of delayed rectifierpotassium channels, and the response ofrhodopsin contained in thesynaptic vesicles.[16][17]
Aerobic eukaryotes, specifically microalgae,mosses,fungi, and some animals, perform biosynthesis of DHA as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongaseenzymes. This pathway, originally identified inThraustochytrium, applies to these groups:[21]
In humans, DHA is either obtained from the diet or may be converted in small amounts fromeicosapentaenoic acid (EPA, 20:5, ω-3). With the identification ofFADS2 as a human Δ4-desaturase in 2015, it is now known that humans follow the same synthesis pathway as aerobic eukaryotes, involving Δ5-elongation to DPA and Δ4-desaturation to DHA.[22]
A "Sprecher's shunt" hypothesis, proposed in 1991, postulates that EPA is twice elongated to 24:5 ω-3, then desaturated to 24:6 ω-3 (viadelta 6 desaturase) in the mitochondria, then shortened to DHA (22:6 ω-3) viabeta oxidation in theperoxisome. The hypothesis was accepted in the absence of an identified Δ4-desaturase in mammals prior to 2015.[23][24] The shunt model does not match clinical data, specifically that patients with beta oxidation defects do not display issues in DHA synthesis. With the identification of a Δ4-desaturase, it is considered outdated.[22]
DHA can be metabolized into DHA-derivedspecialized pro-resolving mediators (SPMs), DHA epoxides, electrophilic oxo-derivatives (EFOX) of DHA, neuroprostanes, ethanolamines, acylglycerols, docosahexaenoyl amides of amino acids or neurotransmitters, and branched DHA esters of hydroxy fatty acids, among others.[25]
Though mixed and plagued by methodological inconsistencies, there is now convincing evidence from ecological, RCTs, meta-analyses and animal trials that shows a benefit for omega−3 dietary intake for cardiovascular health.[1][13] Of then−3 FAs, DHA has been argued to be the most beneficial due to its preferential uptake in the myocardium, its strongly anti-inflammatory activity and its metabolism toward neuroprotectins and resolvins, the latter of which directly contribute to cardiac function.[27]
DHA is associated with its role in cardiovascular protection and lowering the risk of coronary artery disease. DHA supplementation has been shown to improve high-density lipoprotein (‘good cholesterol’), and lower total cholesterol as well as blood pressure levels.[28]
Foods high in omega−3 fatty acids may be recommended to women who want to become pregnant or when nursing.[29] A working group from the International Society for the Study of Fatty Acids and Lipids recommended 300 mg/day of DHA for pregnant and lactating women, whereas the average consumption was between 45 mg and 115 mg per day of the women in the study, similar to a Canadian study.[30]
A major structural component of the mammalian central nervous system, DHA is the most abundant omega−3 fatty acid in the brain and retina.[31] Brain and retinal function rely on dietary intake of DHA to support a broad range ofcell membrane andcell signaling properties, particularly ingrey matter and retinalphotoreceptor cell outer segments, which are rich in membranes.[32][33]
Ordinary types of cookedsalmon contain 500–1500 mg DHA and 300–1000 mg EPA per 100 grams.[37] Additional rich seafood sources of DHA includecaviar (3400 mg per 100 grams),anchovies (1292 mg per 100 grams),mackerel (1195 mg per 100 grams), and cookedherring (1105 mg per 100 grams).[37]
Brains from mammals taken as food are also a good direct source. Beef brain, for example, contains approximately 855 mg of DHA per 100 grams in a serving.[38] While DHA may be the primary fatty acid found in certain specialized tissues, these tissues, aside from the brain, are typically small in size, such as the seminiferous tubules and the retina. As a result, animal-based foods, excluding the brain, generally offer minimal amounts of preformed DHA.[39]
In the early 1980s,NASA sponsored scientific research on a plant-based food source that could generate oxygen and nutrition on long-durationspace flights. Certain species of marinealgae produced rich nutrients, leading to the development of an algae-based, vegetable-like oil that contains two polyunsaturated fatty acids, DHA andarachidonic acid.[40]
DHA is widely used as afood supplement. It was first used primarily in infant formulas.[41] In 2019, the US Food and Drug Administration published qualifiedhealth claims for DHA.[42]
Some manufactured DHA is avegetarian product extracted from algae, and it competes on the market with fish oil that contains DHA and other omega−3s such asEPA. Both fish oil and DHA are odorless and tasteless after processing as a food additive.[43]
Vegetarian diets typically contain limited amounts of DHA, andvegan diets typically contain no DHA.[44] In preliminary research, algae-basedsupplements increased DHA levels.[45] While there is little evidence of adverse health or cognitive effects due to DHA deficiency in adult vegetarians or vegans,breast milk levels remain a concern for supplying adequate DHA to the infant.[44]
Fish oil is widely sold incapsules containing a mixture of omega−3 fatty acids, including EPA and DHA.Oxidized fish oil in supplement capsules may contain lower levels of EPA and DHA.[46][47] Light, oxygen exposure, and heat can all contribute to oxidation of fish oil supplements.[46][47] Buying a quality product that is kept cold in storage and then keeping it in a refrigerator can help minimize oxidation.[48]
As optimal DHA level is important for brain development and maturation, there are established daily recommendations for DHA intake in children.[1][medical citation needed]
The table below shows the daily DHA / DHA + EPA intake recommended for children of different ages:
PUFAs
Age (years)
Recommended daily intake
DHA
1−2
10 – 12 mg/day
DHA + EPA
2−4
100 – 150 mg/day
4−6
150 – 200 mg/day
6−10
200 – 250 mg/day
Experts recommend DHA intake of 10–12 mg/day for children 12–24 months, 100–150 mg/day of DHA+EPA for children 2–4 years old and 150–200 mg/day of DHA+EPA for children 4–6 years old.[1][medical citation needed]
^abcdefg"Omega-3 fatty acids". Office of Dietary Supplements, US National Institutes of Health. 15 February 2023. Retrieved6 March 2024.
^Guesnet P, Alessandri JM (2011). "Docosahexaenoic acid (DHA) and the developing central nervous system (CNS) - Implications for dietary recommendations".Biochimie.93 (1):7–12.doi:10.1016/j.biochi.2010.05.005.PMID20478353.
^McNamara RK, Hahn CG, Jandacek R, et al. (2007). "Selective deficits in the omega-3 fatty acid docosahexaenoic acid in the postmortem orbitofrontal cortex of patients with major depressive disorder".Biol. Psychiatry.62 (1):17–24.doi:10.1016/j.biopsych.2006.08.026.PMID17188654.S2CID32898004.
^Westphal C, Konkel A, Schunck WH (Nov 2011). "CYP-eicosanoids--a new link between omega-3 fatty acids and cardiac disease?".Prostaglandins & Other Lipid Mediators.96 (1–4):99–108.doi:10.1016/j.prostaglandins.2011.09.001.PMID21945326.
^SanGiovanni JP, Chew EY (January 2005). "The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina".Progress in Retinal and Eye Research.24 (1):87–138.doi:10.1016/j.preteyeres.2004.06.002.PMID15555528.S2CID13757616.
^Lane, K; Derbyshire, E; Li, W; Brennan, C (2014). "Bioavailability and potential uses of vegetarian sources of omega-3 fatty acids: A review of the literature".Critical Reviews in Food Science and Nutrition.54 (5):572–9.doi:10.1080/10408398.2011.596292.PMID24261532.S2CID30307483.
^Zargar, Atanaz; Ito, Matthew K. (1 August 2011). "Long chain omega-3 dietary supplements: a review of the National Library of Medicine Herbal Supplement Database".Metabolic Syndrome and Related Disorders.9 (4):255–271.doi:10.1089/met.2011.0004.ISSN1557-8518.PMID21787228.
