Arachidonic Acid (X-FactorTM)

Description:

Arachidonic acid (ARA) is a fatty acid from the omega-6 family. It is also one of the most important dietary components in the musclebuilding process. This fatty acid is found in animal products, and is especially rich in meats such as beef, chicken, salmon, duck, and lamb.1 ARA serves as a precursor to several hormone-like compounds in the body, notably prostaglandins, leukotrienes, lipoxins, and thromboxanes.2 Because of this, it is integral to a series of biological functions including nutrient metabolism, neurological activity, immunity, inflammation, insulin sensitivity, bone mineral density, and vascular homeostasis.3 4 5 It is also necessary for the adaptive (growth) response to training.6 7 In sports nutrition, ARA is widely supplemented (as X-FACTORT) to increase muscle size, strength, and power, especially at times of training stagnation.

The role arachidonic acid plays in the process of muscle growth appears to be largely mediated by its conversion to prostaglandins. These are locally acting hormones, which can shift cell physiology to favor repair and growth. The main focus here is PGF2alpha, which is a known regulator of muscle protein synthesis.8 Among other things, it may enhance muscle cell sensitivity to anabolic hormones like IGF-1,9 testosterone, 10 and insulin.11 PGF2alpha also appears to support the satellite cell cycle, particularly satellite cell proliferation and nuclear accretion.12 13 This is very important to continued muscle hypertrophy. Muscle cells grow very large next to other cells in the body. This necessitates they contain many nuclei, not just one. These regulate a myriad of cell activities. However, these cells cannot grow past a certain point unless more nuclei are added. Intracellular metabolism becomes inefficient otherwise. Therefore, by increasing the number of nuclei within these cells, arachidonic acid may support increases in the overall capacity of these cells to grow.

Clinical Studies:

A study published in the Public Library of Science journal PLOSONE in 2016 examined the effects of 8 weeks of XFACTORTM supplementation with a group of 30 experienced weightlifters.14 This placebo-controlled study was immediately quite unique, because it examined the men in a state of training stagnation (plateau, common in experienced lifters). A dose of 1,500 mg of arachidonic acid was taken each day, and the study period progressed for 8 weeks. The men also followed a controlled resistance training program. At the end of the study, only the men taking arachidonic acid noticed significant increases in lean body mass, muscle strength, and power.

Those taking placebo remained stuck in a training plateau. The science magazine Examine.com summarized the results of this study, including the following:

‘Lean body mass significantly increased in the ARA group only (+1.6 kilograms; 3%), with almost no change in the placebo group. Similarly, while both groups significantly increased muscle thickness compared to baseline, the increase was marginally greater in the ARA group (8% vs. 4% increase; p=0.08). Neither group showed a significant change or difference from one another in fat mass. Leg press 1RM was significantly increased in both groups without significant difference between them. In contrast, bench press 1RM (+8.7%), Wingate peak power (+12.7%), and average peak power (+13.2%) significantly increased in the ARA group only, leading to a significant difference in performance compared to the placebo group, which experienced no significant changes. When bench press and leg press 1RMs were combined to represent total-body strength, only the ARA group showed a significant increase.’

The Exercise & Sport Nutrition Laboratory at Baylor University had also conducted a placebo-controlled study on X-FACTORTM supplementation in weightlifters several years earlier.15 This study was published by the Journal of the International Society of Sports Nutrition. Here, 31 trained men were each given 1,000 mg of ARA per day (or placebo) during a 50-day resistance-training program. Again, there was a clear effect of supplementation. At the end of this investigation, only those subjects taking ARA noticed a significant increase in muscle Peak Power (+8.5%). There were also statistical trends of improvement in Bench Press 1-rep max (+25 lbs.) and Total Work capacity in the supplemented group.

Pharmacology:

Arachidonic acid is richly stored in your muscles. It gets released when the fibers are damaged by training or other stress, which triggers a local reaction. This response supports inflammation and repair (anabolism), as well as delayed onset muscle soreness. ARA explains why pain relievers such as ibuprofen and acetaminophen can sometimes blunt muscle growth, and reminds us that the old adage ‘no pain, no gain’ is a fundamentally true one. Arachidonic acid liberation from damaged muscle fibers is, similarly, the first anabolic trigger in a long but highly localized cascade that will control the rebuilding and strengthening of muscle tissue after exercise.16 17 18 As a crude explanation, arachidonic acid helps direct the body to where it needs muscle tissue repair, by facilitating the localized actions of certain anabolic hormones.

The level of arachidonic acid stored in muscle phospholipids is directly tied to the anabolic productivity of our workouts. It partly dictates how much will be liberated by training, as does training intensity. Further, muscle levels of ARA levels fluctuate. Regular exercise has been shown to significantly lower the content of arachidonic acid in many cases.19 20 21 Since prostaglandin synthesis is tied to the amount of available arachidonic acid, lower levels result in less arachidonic acid being released during exercise.

This results in a lower concentration of prostaglandins being formed, and thus a less intense anabolic response. In such a state, you will need to workout more vigorously to receive the same level of ARA release and anabolic stimulation. This makes ARA depletion a key concern when a plateau arises.

How Supplied:

Arachidonic acid is available in 250 mg softgels under the brand name X-FACTORTM by Molecular Nutrition. ARA is a patented (#6,841,573) sports nutrition ingredient, and carries the ingredient trade name ARASYNTM.

Administration:

As a short-term anabolic agent, arachidonic acid is generally supplemented at a dose of 500-1,500 mg per day. This is taken for a period of 7-8 weeks, with the full dose taken about one hour before training (on lifting days). It is recommended to follow this program 1 to 2 times per year, when training has become stagnated. Arachidonic acid is often taken in lower supplemental doses (250 mg every 1-2 days) as well, particularly when training intensity is high, or the diet is low in animal products.

Safety:

In clinical studies involving the supplementation of up to 1,700 mg of arachidonic acid per day for extended periods, general markers of health were unaffected. This includes no notable change in HDL, LDL, or total cholesterol values, immune system response functioning, or platelet aggregation values.22 23 24 Furthermore, the investigation at Baylor University noted a significant reduction in IL-6 in the X-FACTOR supplemented group. This is a principle inflammatory cytokine, and a stimulus for the production of C-reactive protein. High levels of IL6 are correlated with systemic inflammation, poor health, and mortality. The results suggest that when combined with resistance training, ARA supplementation may actually produce a reduction in systemic inflammation. More research is needed to confirm this potential benefit.

On a more general note, the American Heart Association announced its position on omega-6 EFA consumption in 2009.25 In reviewing some of the more current data, they found that diets low in omega-6 fats were associated with an increased risk of heart disease compared to diets with higher intakes. The paper also discusses arachidonic acid, and how this essential fat is normally not proinflammatory, nor outwardly unhealthy to consume. The American Heart Association now recommends that 5-10% of your calories each day come from Omega-6 fats, including ARA. Diets rich in Omega-3’s are also believed to be very healthy, but this should not come at the exclusion of omega-6’s.

Side Effects:

Arachidonic acid (X-Factor) often produces an amplification of residual post-workout muscle soreness. This is due to an intensification of the normal physiological response to training, and represents increased intensity of the anabolic cascade. Those with existing minor muscle, connective tissue, or joint injuries may notice more pain during supplementation. In such case, one may wish to avoid supplementation until the injury is healed. Arachidonic acid may also produce a greater incidence of headaches in a small percentage of users, which may be due to its effect as a vasodilator. Increasing daily water consumption often alleviates this side effect.

Contraindications:

Those with an existing medical condition related to inflammation may find that the added arachidonic acid exacerbates symptoms of their disorder, and should avoid supplementation. This supplement should also only be used after the approval of a physician if you are taking any medication(s), have an existing medical condition, or have a familial predisposition for cardiovascular disease, high blood pressure, inflammatory disease, or other disorder that may require the limiting of dietary arachidonic acid.

1 Contribution of meat fat to dietary arachidonic acid. Li D, Ng A, Mann NJ, Sinclair AJ. Lipids. 1998 Apr;33(4):437-40.

2 The Eicosanoids: Prostaglandins, thromboxanes, leukotrienes, & related compounds. E Smith, G FitzGerald. Chapter 18. Basic & Clinical Pharmacology. Bertram Katzung. (LANGE Basic Science). 2007.

3 Prenatal long-chain polyunsaturated fatty acid status: the importance of a balanced intake of docosahexaenoic acid and arachidonic acid. Hadders-Algra M. J Perinat Med. 2008;36(2):1019.

4 Arachidonic acid metabolism in brain physiology and pathology: lessons from genetically altered mouse models. Bosetti F. J Neurochem. 2007 Aug;102(3):577-86. Epub 2007 Apr 2. Review.

5 Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology. Harizi H, Corcuff JB, Gualde N. Trends Mol Med. 2008 Oct;14(10):461-9. Epub 2008 Sep 4.

6 Arachidonic acid, prostaglandin E2 and F2 alpha influence rates of protein turnover in skeletal and cardiac muscle. Rodemann HP, Goldberg AL. J Biol Chem. 1982 Feb 25;257(4):1632-8.

7 Effect of ibuprofen and acetaminophen on postexercise muscle protein synthesis. Trappe TA, White F, Lambert CP, Cesar D, Hellerstein M, Evans W. Am J Physiol Endocrinol Metab. 2002 Mar;282(3):E551-6.

8 Protein synthesis in isolated forelimb muscles. The possible role of metabolites of arachidonic acid in the response to intermittent stretching. Smith, Palmer et al. Biochem J. 1983 214,153-61

9 Prostaglandin F2 alpha stimulates proliferation of clonal osteoblastic MC3T3-E1 cells by up-regulation of insulin-like growth factor I receptors. Hakeda Y, Harada S, Matsumoto T, Tezuka K, Higashino K, Kodama H, Hashimoto-Goto T, Ogata E, Kumegawa M. J Biol Chem. 1991 Nov 5;266(31):21044-50.

10 Dietary effects of arachidonate-rich fungal oil and fish oil on murine hepatic and hippocampal gene expression. Berger A, Mutch DM, German JB, Roberts MA. Lipids Health Dis. 2002 Oct 21;1:2.

11 The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campbell LV. N Engl J Med. 1993 Jan 28;328(4):238-44.

12 Role of cyclooxygenase-1 and -2 in satellite cell proliferation, differentiation, and fusion. Mendias CL, Tatsumi R, Allen RE. Muscle Nerve. 2004 Oct;30(4):497-500.

13 Arachidonic acid supplementation enhances in vitro skeletal muscle cell growth via a COX-2-dependent pathway. James F. Markworth and David Cameron-Smith. Am J Physiol Cell Physiol 304:C56-C67, 2013.

14 Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations. Eduardo O. De Souza, et al. PLOS ONE, May 16, 2016

15 Effects of arachidonic acid supplementation on training adaptations in resistance-trained males. Michael D Roberts et al. J Int Soc Sports Nutr. 2007; 4:21.

16 Protein synthesis in isolated forelimb muscles. The possible role of metabolites of arachidonic acid in the response to intermittent stretching. Smith, Palmer et al. Biochem J. 1983 214,153-61

17 The influence of changes in tension on protein synthesis and prostaglandin release in isolated rabbit muscles. Palemr, Reeds et al. Biochem J. 1983 214,1011-14

18 Protein synthesis and degradation in isolated muscle. Effect of n3 and no fatty acids. Palmer, Wahle. Biochem J. 1987 242,615-18.

19 Regular exercise modulates muscle membrane phospholipid profile in rats. Helge et al.J. Nutr. 1999 129:1636-42.

20 Exercise training reduces skeletal muscle membrane arachidonate in obese (fa/fa) Zucker rat. Ayre et al.J. Appl. Physiol. 1998 85(5):18981902.

21 Effects of physical exercise on phospholipid fatty acid composition in skeletal muscle. Andersson et al. Am. J. Physiol. 274 (Endocrinol. Metab. 37):E432-38 1998.

22 The effect of dietary arachidonic acid on plasma lipoprotein distribution, apoproteins, blood lipid levels, and tissue fatty acid composition in humans. G.J. Nelson, P.C. Schmidt et al. Lipids 32: 42733 (1997).

23 The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans. Nelson CJ, Schmidt PC et al. Lipids 32(4):421-5 (1997).

24 Effects of dietary arachidonic acid on human immune response. Kelley DS, Taylor PC et al. Lipids 32(4):449-56 (1997).

25 Omega-6 Fatty Acids and Risk for Cardiovascular Disease. A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention. William S. Harris et al. Circulation. 2009;119:902-907.