Editing Essential fatty acid (section)

==Essentiality in human diet==
Mammals lack the ability to introduce double bonds in fatty acids beyond carbon 9 and 10, hence the omega−6 linoleic acid (18:2n−6; LA) and the omega−3 [[alpha-linolenic acid]] (18:3n−3; ALA) are essential for humans in the diet. However, humans can convert both LA and ALA to fatty acids with longer carbon chains and a larger number of double bonds, by alternative desaturation and chain elongation.<ref>{{cite journal |doi=10.1093/ajcn/70.3.560s|title=Essential fatty acids in health and chronic disease |year=1999 |last1=Simopoulos |first1=Artemis P. |journal=The American Journal of Clinical Nutrition |volume=70 |issue=3 |pages=560s–569s |pmid=10479232 |doi-access=free }}</ref><ref name=Das>{{cite journal |doi=10.1002/biot.200600012|title=Essential Fatty Acids: Biochemistry, Physiology and Pathology |year=2006 |last1=Das |first1=Undurti N. |journal=Biotechnology Journal |volume=1 |issue=4 |pages=420–439 |pmid=16892270 |s2cid=25945627 }}</ref>

In humans, arachidonic acid (20:4n−6; AA) can be synthesized from LA. In turn, AA can be converted to an even longer fatty acid, the docosapentaenoic acid (22:5n−6; DPA). Similarly, ALA can be converted to docosahexaenoic acid (22:6n−3; DHA), although the latter conversion is limited, resulting in lower blood levels of DHA than through direct ingestion. This is illustrated by studies in vegans and vegetarians.<ref>{{cite journal | vauthors = Sanders TA | year = 2009 | title = DHA Status of vegetarians | journal = Prostaglandins Leukotrienes Essential Fatty Acids | volume = 81 | issue = 2–3| pages = 137–41 | doi = 10.1016/j.plefa.2009.05.013 | pmid = 19500961 }}</ref> If there is relatively more LA than ALA in the diet it favors the formation of DPA from LA rather than DHA from ALA. This effect can be altered by changing the relative ratio of LA:ALA, but is more effective when total intake of polyunsaturated fatty acids is low.

In preterm infants, the capacity to convert LA to AA and ALA to DHA is limited, and preformed AA and DHA may be required to meet the needs of the developing brain. Both AA and DHA are present in breastmilk and contribute along with the parent fatty acids LA and ALA to meeting the requirements of the newborn infant. Many infant formulas have AA and DHA added to them with an aim to make them more equivalent to human milk.{{Citation needed|date=April 2025}}

''Essential nutrients'' are defined as those that cannot be synthesized ''de novo'' in sufficient quantities for normal physiological function. This definition is met for LA and ALA but not the longer chain derivatives in adults.<ref>FAO/WHO Fats and fatty acids in human nutrition. Report of an expert consultation. FAO Food and Nutrition Paper 91, Rome 2011. ISSN 0254-4725</ref> The longer chain derivatives particularly, however, have pharmacological properties that can modulate disease processes, but this should not be confused with dietary essentiality.

One study demonstrated linoleic acid deficiency in adults. They found that patients undergoing intravenous nutrition with glucose became isolated from their fat supplies and rapidly developed biochemical signs of essential fatty acid deficiency (an increase in 20:3n−9/20:4n−6 ratio in plasma) and skin symptoms.<ref>{{cite journal | pmid = 5001758 | volume=13 | issue=3 | title=Plasma lipids in human linoleic acid deficiency. | year=1971 | journal=Nutr Metab | pages=150–67 | doi=10.1159/000175332 | vauthors=Collins FD, Sinclair AJ, Royle JP, Coats DA, Maynard AT, Leonard RF}}</ref> This could be treated by infusing lipids, and later studies showed that topical application of sunflower oil would also resolve the dermal symptoms.<ref>{{cite journal | last1 = Prottey | first1 = C | last2 = Hartop | first2 = PJ | last3 = Press | first3 = M | year = 1975 | title = Correction of the cutaneous manifestations of essential fatty acid deficiency in man by application of sunflower-seed oil to the skin.| journal = J Invest Dermatol | volume = 64 | issue = 4| pages = 228–34 | pmid = 1117180 | doi=10.1111/1523-1747.ep12510667| doi-access = free }}</ref> Linoleic acid has a specific role in maintaining the skin water-permeability barrier, probably as constituents of acylglycosylceramides. This role cannot be met by any ω−3 fatty acids or by arachidonic acid.

The main physiological requirement for ω−6 fatty acids is attributed to [[arachidonic acid]], which is the major precursor of [[prostaglandins]], [[leukotrienes]] that play a vital role in cell signaling, and an endogenous cannabinoid [[anandamide]].<ref>{{cite journal|title=The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis|first1=M|last1=Maccarrone|first2=A|last2=Finazzi-Agró|date=22 August 2003|journal=Cell Death & Differentiation|volume=10|issue=9|pages=946–955|doi=10.1038/sj.cdd.4401284|pmid=12934069|doi-access=free}}</ref> Metabolites from the ω−3 pathway, mainly from eicosapentaenoic acid, are mostly inactive.<ref>{{cite book |last1=Sanders |first1=Tom |last2=Emery |first2=Peter |url=https://books.google.com/books?id=M9sCyAEACAAJ |publisher=Taylor Frances |location=London |title=Molecular Basis of Human Nutrition |isbn=9780367806323 |year=2003 }}</ref>

Reviews by the European Food Safety Authority<ref>{{cite journal | last1 = Jones | first1 = A | year = 2010 | title = EFSA Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids and cholesterol | journal = EFSA Journal | volume = 8 | issue = 3| page = 1461 | doi = 10.2903/j.efsa.2010.1461 | doi-access = free }}</ref> made recommendations for minimal intakes of LA and ALA and have also recommended intakes of longer chain ω−3 fatty acids based on the association of oily fish consumption with a lower risk of cardiovascular disease.<ref name=Nugent>{{cite journal |vauthors=Nugent KP, Spigelman AD, Phillips RK |title=Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac |journal=Diseases of the Colon and Rectum |volume=39 |issue=6 |pages=659–62 |date=June 1996 |pmid=8646953 |quote=Arachidonic acid is an essential fatty acid... |doi=10.1007/BF02056946|s2cid=25642190 }}</ref><ref name=Carlstedt>{{cite journal |vauthors=Carlstedt-Duke J, Brönnegård M, Strandvik B |title=Pathological regulation of arachidonic acid release in cystic fibrosis: the putative basic defect |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=83 |issue=23 |pages=9202–6 |date=December 1986 |pmid=3097647 |pmc=387103 |doi=10.1073/pnas.83.23.9202 |quote=[T]he turnover of essential fatty acids is increased (7). Arachidonic acid is one of the essential fatty acids affected.|bibcode=1986PNAS...83.9202C |doi-access=free }}</ref>