Essential fatty acid

Functions

In the body, essential fatty acids serve multiple functions. In each of these, the balance between dietary ω−3 and ω−6 strongly affects function.

• They are modified to make
  • the classic eicosanoids (affecting inflammation and many other cellular functions)
  • the endocannabinoids (affecting mood, behavior and inflammation)
  • the lipoxins which are a group of eicosanoid derivatives formed via the lipoxygenase pathway from ω−6 EFAs and resolvins from ω−3 (in the presence of acetylsalicylic acid, downregulating inflammation)
  • the isofurans, neurofurans, isoprostanes, hepoxilins, epoxyeicosatrienoic acids (EETs) and neuroprotectin D
• They form lipid rafts (affecting cellular signaling)
• They act on DNA (activating or inhibiting transcription factors such as NF-κB, which is linked to pro-inflammatory cytokine production)

Nomenclature and terminology

Main article: Fatty acid#Nomenclature

Fatty acids comprise an aliphatic hydrocarbon chain plus a carboxyl group (–COOH) at one end, and terminated by a methyl group (–CH3) at the other end. They are almost always straight-chained. The carbon next to the carboxylate is known as α, the next carbon β, and so forth. Since biological fatty acids can be of diverse lengths, the last position is often labelled as "ω", the last letter in the Greek alphabet. In the expression ω−x, the minus symbol represents subtraction, indicating how many carbons away from the terminal end (ω) of the chain that the first unsaturated carbon-carbon bond appears. Typically, the number of carbons and the number of double bonds are also listed in short descriptions of unsaturated fatty acids. For instance, ω−3 18:4, or 18:4 ω−3, or 18:4 n−3 indicate stearidonic acid, an 18-carbon chain with 4 double bonds, and with a double bond between the third and fourth carbon atoms from the CH3 end. Double bonds are cis (on the same side of the double bond) and separated by a single methylene (CH2) group unless otherwise noted. In free fatty acid form, the chemical structure of stearidonic acid is: :[[Image:Fatty acid carbon numbering.svg|500px|Chemical structure of [[stearidonic acid]] showing physiological (red) and chemical (blue) numbering conventions]]

Examples

Polyunsaturated fatty acids with 16- and 18-carbon chains are sometimes classified as short chain polyunsaturated fatty acids (SC-PUFA), as opposed to long-chain polyunsaturated fatty acids (LC-PUFA), which have more than 18 carbon atoms.

Both the essential fatty acids are SC-PUFA with an 18-carbon chain:

• ω−3 fatty acid:
  • α-linolenic acid or ALA (18:3n−3)
• ω−6 fatty acid:
  • linoleic acid or LA (18:2n−6) These two fatty acids cannot be synthesized by humans because humans lack the desaturase enzymes required for their production.

They form the starting point for the creation of more desaturated fatty acids, most of which also have a longer carbon chain:

• ω−3 fatty acids:
  • eicosapentaenoic acid or EPA (20:5n−3)
  • docosahexaenoic acid or DHA (22:6n−3)
• ω−6 fatty acids:
  • gamma-linolenic acid or GLA (18:3n−6)
  • dihomo-gamma-linolenic acid or DGLA (20:3n−6)
  • arachidonic acid or AA (20:4n−6) Except for GLA, which has a short 18-carbon chain, these fatty acids have more than 18 carbon atoms and are typically classified as LC-PUFA.

ω−9 fatty acids are not essential in humans because they can be synthesized from carbohydrates or other fatty acids.

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.

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. 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.

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. The longer chain derivatives particularly, however, have pharmacological properties that can modulate disease processes, but this should not be confused with dietary essentiality.

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. Metabolites from the ω−3 pathway, mainly from eicosapentaenoic acid, are mostly inactive.

Reviews by the European Food Safety Authority 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.

Food sources

Some of the food sources of ω−3 and ω−6 fatty acids are fish and shellfish, seaweed oil, flaxseed (linseed) and flaxseed oil, hemp seed, olive oil, soya oil, canola (rapeseed) oil, chia seeds, pumpkin seeds, sunflower seeds, leafy vegetables, and walnuts.

Essential fatty acids play a part in many metabolic processes, and there is evidence to suggest that low levels of essential fatty acids, or the wrong balance of types among the essential fatty acids, may be a factor in a number of illnesses, including osteoporosis.

Fish is the main source of the longer omega−3 fats; eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), though they initially acquire these fats through the consumption of algae and seaweed. Some plant-based foods contain omega−3 in the form of alpha-linolenic acid (ALA), which appears to have a modest benefit for cardiovascular health. The human body can (and in case of a purely vegetarian diet often must unless certain algae or supplements derived from them are consumed) convert ALA to EPA and subsequently DHA. The conversion of ALA to DHA is sufficient in the adult and additional DHA is not required in the diet. In the infant, the case is less clear; preformed DHA may be required in breastmilk or formula for adequate development, as DHA supplementation in formula was found to improve cognitive development up to one year of age. The effects of DHA supplementation in early childhood after one year are unclear.

The IUPAC Lipid Handbook provides a very large and detailed listing of fat contents of animal and vegetable fats, including ω−3 and −6 oils. The National Institutes of Health's EFA Education group publishes Essential Fats in Food Oils. This lists 40 common oils, more tightly focused on EFAs and sorted by n−6:3 ratio. Vegetable Lipids as Components of Functional Food lists notable vegetable sources of EFAs as well as commentary and an overview of the biosynthetic pathways involved. However, these sources are not in perfect agreement. EFA content of vegetable sources varies with cultivation conditions. Animal sources vary widely, both with the animal's feed and that the EFA makeup varies markedly with fats from different body parts.

Human health

Main article: Diet and heart disease

Essential fatty acids play an important role in the life and death of cardiac cells. Additionally, essential fatty acids are crucial for the development of several endocannabinoids with a multitude of functions in the body, such as docosahexaenoyl ethanolamide (DHA-EA/synaptamide).

Reference intake values

Reference intake values for as published by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority (EFSA).

In the United States, the Adequate Intake (AI) for omega−3 fatty acids is for ALA. It is based on the median intake, and for adults the values are 1.6 g/day for men and 1.1 g/day for women. EPA and DHA contribute about 10 percent of total omega−3 intake. The AI for omega−6 fatty acids is for linoleic acid and is also based on the median intake: 17 g/day for younger men, dropping to 14 g/day for men over 50 years old; for younger women 12 g/d, and 11 g/day for women over 50. Studies have shown that smaller intakes reverse the symptoms of deficiency, but there is inadequate information to set an Estimated Average Requirement (EAR) for either.

Essential fatty acid deficiency

Essential fatty acid deficiency results in a dermatitis similar to that seen in zinc or biotin deficiency.

References

--

References

1. (15 February 2023). "Omega-3 Fatty Acids". Office of Dietary Supplements, US National Institutes of Health.
2. (1980). "Modern Nutrition in Health and Disease". Lea and Febinger.
3. (2009). "The new Oxford book of food plants". Oxford University Press US.
4. (October 2014). "Essential fatty acids as functional components of foods- a review". Journal of Food Science and Technology.
5. (2008). "Understanding Nutrition". Thomson Wadsworth.
6. (April 1930). "On the nature and role of the fatty acids essential in nutrition". J. Biol. Chem..
7. (2005). "Docosahexaenoic acid affects cell signaling by altering lipid rafts". Reproduction, Nutrition, Development.
8. Calder PC. (December 2004). "n-3 fatty acids, inflammation, and immunity--relevance to postsurgical and critically ill patients". Lipids.
9. (2017). "Selection in Europeans on Fatty Acid Desaturases Associated with Dietary Changes". Mol Biol Evol.
10. (1999). "Essential fatty acids in health and chronic disease". The American Journal of Clinical Nutrition.
11. (2006). "Essential Fatty Acids: Biochemistry, Physiology and Pathology". Biotechnology Journal.
12. (2009). "DHA Status of vegetarians". Prostaglandins Leukotrienes Essential Fatty Acids.
13. (2019-03-12). "The Effect of an Infant Formula Supplemented with AA and DHA on Fatty Acid Levels of Infants with Different FADS Genotypes: The COGNIS Study". Nutrients.
14. 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
15. (22 August 2003). "The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis". Cell Death & Differentiation.
16. (2003). "Molecular Basis of Human Nutrition". Taylor Frances.
17. (2010). "EFSA Scientific Opinion on Dietary Reference Values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids and cholesterol". EFSA Journal.
18. (June 1996). "Tissue prostaglandin levels in familial adenomatous polyposis patients treated with sulindac". Diseases of the Colon and Rectum.
19. (December 1986). "Pathological regulation of arachidonic acid release in cystic fibrosis: the putative basic defect". Proceedings of the National Academy of Sciences of the United States of America.
20. (September 1997). "Calcium metabolism, osteoporosis and essential fatty acids: a review". Progress in Lipid Research.
21. (December 2012). "α-Linolenic acid and risk of cardiovascular disease: a systematic review and meta-analysis". Am. J. Clin. Nutr..
22. (July 2015). "Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?". Progress in Lipid Research.
23. "IUPAC Lipid Handbook".
24. "Essential Fats in Food Oils".
25. [http://publib.upol.cz/~obd/fulltext/Biomedic146-2/LF11_2002-1.pdf Vegetable Lipids as Components of Functional Food] {{webarchive. link. (2006-03-20 , Stuchlik and Zak)
26. (March 1994). "External blockade of the major cardiac delayed-rectifier K+ channel (Kv1.5) by polyunsaturated fatty acids". Proceedings of the National Academy of Sciences of the United States of America.
27. (August 2006). "Antiarrhythmic effects of omega-3 fatty acids". The American Journal of Cardiology.
28. (November 2006). "[Alpha-linolenic acid, cardiovascular disease and sudden death]". Tidsskrift for den Norske Lægeforening.
29. Herbaut C. (September 2006). "[Omega-3 and health]". Revue Médicale de Bruxelles.
30. European Food Safety Authority (EFSA). (2009-07-01). "Labelling reference intake values for n-3 and n-6 polyunsaturated fatty acids". EFSA Journal.
31. Food and Nutrition Board. (2004). "Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids".
32. (2019-01-18). "Andrews' Diseases of the Skin: Clinical Dermatology". Elsevier Health Sciences.