What is Arachidonic Acid (AA)?
AA is also an important part of the normal inflammatory process, which gets activated during injury or irritation. It gets converted into important inflammatory molecules through different pathways. This process helps heal and restore the function of damaged tissues [1, 2, 3, 4].
Excess omega 6’s are often seen as bad because they get converted to arachidonic acid, which can increase inflammation in some situations.
Most of the functions of AA is attributed to its conversion into other molecules (leukotrienes, prostaglandins, and more) through the action of enzymes (oxygenases). While some research has been conducted on the function of non-converted arachidonic acid, no direct mechanisms have been determined [5, 3].
AA is naturally produced in the body from another molecule (linoleic acid), and can also be supplemented through different foods. It is most popular for its exercise and bodybuilding but also has other benefits in the body such as boosting the immune response [6, 7, 8, 9].
It is also key for the development and growth of infants and is a major component in breast milk .
Arachidonic Acid Pathways and Metabolism
Arachidonic acid (AA) is one of the most highly regulated fatty acids in cells. Even during extreme fat-free diets low in AA, it is difficult to reduce levels of it past a certain point. This compound gets released when cells are stimulated, and rapidly gets metabolized in most tissues .
Arachidonic acid is obtained through two main pathways. The first is production through reactions (desaturation and elongation) of shorter fatty acids (n-6) like linoleic acid. This mainly occurs in the liver. The second pathway is through food, especially fish and poultry .
Arachidonic Acid Metabolism Can Cause Inflammation
A small portion of released arachidonic acid (AA) gets converted back into fats (triglycerides and phospholipids), allowing cells to remodel their fat composition. But most of the released AA (from cells) is metabolized into a variety of compounds through a number of different pathways. Some of these include [11, 11]:
- Metabolized by COX-1 and COX-2 (cyclooxygenase) enzymes into prostaglandins
- Converted into leukotrienes, lipoxins, and hydroxyeicosatetraenoic acids (HETE) through the action of the enzyme lipoxygenase.
- Oxidized by P450 enzymes into eicosatrienoic acid products
Different cell types produce different active metabolites from AA. The variety of products differs based on the contents and activators (agonists) within the cells. This relates to the overall function of the cell, where different products of arachidonic acid metabolism have different functions. These functions can be potent and opposite to each other. For example, both prostaglandins and leukotrienes can be pro-inflammatory agents while lipoxin A4 negates the pro-inflammatory response [11, 12, 11, 13].
The main products of metabolized arachidonic acid in red blood cells is thromboxane, a hormone involved in blood clots and constriction of the arteries. Whereas in white blood cells, the main products are leukotrienes, which are involved in inflammation [11, 12, 14, 11].
While the inflammatory response is inherently protective (against pathogens and injury), high levels of inflammation are correlated with many different disease states, such as cancer, arthritis, stroke, neurodegenerative disorders, and cardiovascular disease. Because several of AA’s metabolites (prostaglandins and leukotrienes) are part of the inflammatory response, it may be important to monitor AA intake under certain conditions [4, 15].
How Does Arachidonic Acid Work?
As mentioned, most of the effects of arachidonic acid are through the action of its products. The main active components derived from arachidonic acid (AA) are prostaglandins, leukotrienes, and thromboxanes [5, 1].
AA is converted into prostaglandin H2 (PGH2), which is a precursor to all four primary prostaglandins. Prostaglandins are involved in the inflammatory signaling processes and transfer of energy within cells (increase the concentration of cAMP, calcium ions, and activate G-protein coupled receptors) [4, 16, 5, 1].
Leukotrienes are chemical messengers that powerfully activate the immune response. Conversion of AA into leukotrienes helps activate immune cells, boost microbial defense, and control the inflammatory response .
Thromboxane is a member of the lipid family called eicosanoids. It is made in platelets through another compound (thromboxane synthetase) that is produced from AA (via COX enzyme). Thromboxane is involved in muscle (smooth) contractions and blood clotting, which is especially important for blocking wounds and other areas of tissue damage [18, 19].
Additionally, AA is enriched in a type of fat (inositol phospholipid) that is involved in the transmission of signals throughout the body. It also modulates the activity of channels (kinases and ion channels) within cells [20, 21, 22].
Health Benefits of Arachidonic Acid
1) Necessary for Infant Development
Arachidonic acid (AA) is a very important part of infant development and is found at consistent levels in breast milk. Breast milk is vital for infants because the amount of AA naturally supplemented (through production and diet) is less than their bodies require. AA has been added into infant formulas in developed countries for a number of years now (since 2001 in the US) .
Even before birth, AA is supplemented to the fetus through the placenta. A study involving 2474 women found that the average concentration of AA in breast milk is 0.47%. AA is important for infant growth, brain development, and health [10, 23].
A meta-analysis (19 studies of 1949 infants total) evaluated the effects of long-chain unsaturated fatty acids (LCPUFA) supplementation (which includes arachidonic acid) in infant formulas on vision. They concluded that supplementation of infant formulas improves vision (visual acuity) in infants .
Two studies evaluated the use of different infant formulas on preterm (194) or low birth weight infants. In both studies, the author’s concluded that AA supplementation (along with docosahexaenoic acid) enhanced growth and weight-gain, without any side effects [10, 25].
AA also plays a role in the hormonal regulation of bone formation in developing infants. During development, eicosanoids produced by AA relay signals that balance calcium and phosphate levels which are required for building bones .
Another product of AA, prostaglandin PGE2, is a strong regulator of cartilage formation. It also promotes bone formation by increasing the production of a protein (insulin-like growth factor), which powerfully stimulates the growth of bones, cartilage, and muscles. Although at high levels PGE2 may actually reduce bone formation (animal and cell studies) .
AA may potentially play a role in maintaining the health of infants through its effects on the immune system. Compounds (eicosanoids) produced by AA regulate the inflammatory response during immune responses [10, 27, 28, 27].
2) Bodybuilding and Training
Arachidonic acid supplementation (1 g/day) increased energy levels (anaerobic capacity) and reduced inflammation but had no significant effects on muscle mass or strength in 31 resistance-trained males .
In another study, 30 strength-trained males were supplemented with AA (1.5 g/day) or a placebo for 8 weeks. In the AA group, there was an increase in lean body mass, upper-body strength, and peak power. The authors concluded that more long-term studies should be conducted with AA supplementation .
A common assertion of AA supplementation is that it causes muscle inflammation, but a study involving 20 healthy males showed this is not always the case. Additionally, AA supplementation (1.5 g/day) for four weeks had positive effects on the development and fat levels of muscles .
3) Treats Parasitic Infections
Two studies evaluated the effectiveness and safety of arachidonic acid (AA) in the treatment of parasites (Schistosoma mansoni) in otherwise healthy school children (66 and 268) in Egypt. When supplemented with AA (10 mg/kg per day for 15 days) alone, a moderate number of the students were cured (65% and 30%) [31, 8].
But when AA supplementation was combined with an anti-parasitic drug (praziquantel), cure rates significantly improved (91% and 72%). The cure rates were higher than with praziquantel alone (85% and 45%) [31, 8].
The following studies were conducted only on animal models.
4) Vital for the Brain
Arachidonic acid and its products are involving in a wide array of functions in the brain, including signal transmission (neuronal firing and synaptic signaling), neurotransmitter release, brain cell (neuronal) gene expression, blood flow to the brain, sleep/wake cycle, and appetite [32, 10].
Abnormal metabolism of AA is implicated in a number of brain and psychological disorders such as epilepsy, stroke, Alzheimer’s, Parkinson’s, schizophrenia, and mood disorders (based on animal and cell studies) [32, 10].
5) May Protect the Liver
Supplementation with an oil-rich in arachidonic acid significantly reduced liver damage in ethanol-treated rats .
The following studies were only conducted on cell lines.
6) May Potentially Benefit Diabetes
A common cause of type 2 diabetes is the abnormal function of beta-cells, which release insulin required for glucose regulation. In two studies, arachidonic acid-stimulated beta-cell growth and insulin secretion. Both concluded that AA regulates and protects beta-cells, which may potentially be useful in patients with type 2 diabetes [34, 35].
Limitations and Caveats
While the studies outlining the importance of arachidonic acid for infant development is very strong, studies covering working out with arachidonic acid are limited. While the few studies do report some benefits of arachidonic acid during workouts, they are not comprehensive enough to definitively conclude that it will boost muscle power and building in adults.
Health Risks of AA Consumption
One review paper said arachidonic acid does not increase the concentration of inflammatory markers and may even reduce inflammation. However, there is also evidence suggesting omega-6 fatty acids negate the anti-inflammatory effect of omega-3 fatty acids. One AA metabolite, PGE2, is involved in both pro-inflammatory and also anti-inflammatory responses [15, 36].
In a mouse model with Alzheimer’s disease, food with 2% arachidonic acid resulted in higher levels of Abeta (a protein involved in Alzheimer’s disease) and amyloid plaques in their brain .
However, a review study suggested AA supplementation might be helpful for Alzheimer’s patients in combination with cognitive therapy .
Arachidonic acid (AA) supplementation does not seem to cause any side effects or adverse events. In all the clinical studies mentioned, there have been no reports of any unexpected effects on any of the participants. More long-term studies need to be conducted on humans to evaluate whether AA supplementation causes any unwanted side effects [8, 39, 7, 40].
Fatty acids levels in our bodies can be interconnected, where a deficiency in one fatty acid might cause or be caused by a deficiency in another fatty acid. Arachidonic acid deficiency in preterm infants will be exacerbated after birth while they are rapidly growing. This may lead to fragile and weakened vessels that could damage the central nervous system [41, 10].
Additionally, AA deficiency may also compromise the immune response of infants (and possibly adults, too). In a study on healthy preterm infants, AA levels were significantly lower than in term infants. Preterm infants also had significantly fewer immune cells (leukocytes and T-cells) [42, 10].
Several other studies found that both children and adults with learning disorders including ADHD, dyslexia, and autism have abnormally low blood levels of AA. The “normal range” for control subjects in one of the studies was 10.79 (wt%) versus 10.06 (wt%) in individuals with ADHD [43, 44, 45, 46, 10].
A meta-analysis of pooled data from blood samples found that AA concentrations were lower than normal in individuals with learning and developmental disorders. Their data also suggest that AA deficiency may only truly occur in children, whereas in adults the body can resist large fluctuations [47, 10].
A mutation was induced in mice in order to evaluate the results of AA deficiency. These mice were unable to produce prostaglandins, leukotrienes, and blood clot proteins (thrombocytes) .
A study evaluated 229 participants with diabetes/metabolic syndrome and compared individuals of European-American and African-American descent. It was concluded that rs174537, an SNP near the FADS1 gene is most strongly associated with AA levels [48, 49].
Individuals homozygous for the minor allele had significantly lower AA levels than individuals homozygous to the major allele .
Foods and Supplementation
AA can be found at high levels in the visible fat of meat products, especially in pork fat (180 mg per 100 g fat) and the highest level of AA in lean meat was duck (99 mg per 100 g). Meats, in general, are a great source of AA .
Diets high in lean beef (500 g) significantly increased the concentration of AA in the blood compared to diets with less lean beef (30-100 g). Other good protein sources of AA are eggs and turkey breast .
For infants, breast milk (and formula) is the best and most essential source of arachidonic acid .
Powder and Capsules
There are arachidonic acid supplementation products available online for purchase. Most of these are directed towards individuals who are bodybuilding and want fitness improvement.
We do not recommend AA supplements.
While there is no specified supplemental guideline for arachidonic acid, none of the studies reported any adverse effects at any dosages. In the studies mentioned above, male athletes received about 1-1.5 grams per day of arachidonic supplementation with benefits in their performance [6, 29, 30].
However, certain populations may want to limit their intake of AA due to its correlation to inflammation.
Reviews (User Experiences)
One user reported that arachidonic supplementation allows them to gain more muscle, although they did feel more sore than usual.
Another user reported that they became very sore 4 days later, but it was a feeling of soreness after a powerful workout. They mention it is a good supplement for trained athletes who want a little extra gain. After they took it for 3-4 weeks, the positives began to wear off and found it was useful to cycle on and off.
Other users did not feel any extra soreness and reported that they felt extra power during their workouts.
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