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Arachidonic acid in the body
[edit] Muscle growth
Arachidonic acid is necessary for the repair and growth of skeletal muscle tissue. One of the lead researchers of the Baylor study on arachidonic acid, Mike Roberts MS, CSCS, has authored an article published under the title Arachidonic Acid, The New Mass Builder explaining the role of this nutrient in muscle anabolism, and its potential for the enhancement of muscle size and strength.[9]
Roberts claims that for optimal muscle growth a training stimulus must elicit localized inflammation and soreness. He also shows that arachidonic acid (AA, 20:4n-6) is an essential Omega-6 (1-6) polyunsaturated fatty acid that is abundant in skeletal muscle membrane phospholipids (figure 2). It is also the body's principle building block for the production of prostaglandins, which are known to have various physiological roles including a close involvement in inflammation. Also, the prostaglandin isomer PGF2a has a potent ability to stimulate muscle growth. As such, Roberts says that arachidonic acid is a regulator of localized muscle inflammation, and he claims that it may be a central nutrient controlling the intensity of the anabolic/tissue-rebuilding response to weight training.
[edit] Brain
Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in similar quantities to DHA (docosahexaenoic acid). The two account for approximately 20% of its fatty acid content[10]. Like DHA, neurological health is reliant upon sufficient levels of arachidonic acid. Among other things, arachidonic acid helps to maintain hippocampal cell membrane fluidity[11]. It also helps protect the brain from oxidative stress by activating perioxisomal proliferator-activated receptor-y[12]. ARA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons[13].
Arachidonic acid is also involved in early neurological development. In one study funded by the U.S. National Institute of Child Health and Human Development, infants (18 months) given supplemental arachidonic acid for 17 weeks demonstrated significant improvements in intelligence, as measured by the Mental Development Index (MDI)[14]. This effect is further enhanced by the simultaneous supplementation of ARA with DHA.
In adults, the disturbed metabolism of ARA may be associated with neurological disorders such as Alzheimer’s Disease and Bipolar Disorder[15]. This may involve the increased consumption of ARA at the cellular level, and significant alterations in its conversion to other bioactive molecules (overexpression or disturbances in the ARA enzyme cascade). The increased consumption of dietary arachidonic acid is not believed to cause these neurological disorders. In the Journal of Lipid Research, an American Society for Biochemical and Molecular Biology journal, a study dated 2005-05-25 used the Flinders Sensitive Line rats to investigate the link between omega-3 fatty acids and depression. An examination of the brains of depressed rats compared them with brains from normal rats. Surprisingly, they found that the main difference between the two types of rats was in omega-6 fatty acid levels and not omega-3 fatty acid levels. Specifically, they discovered that brains with depression had higher concentrations of arachidonic acid, a long-chain unsaturated metabolite of omega-6 fatty acid. The findings suggest that it is not a lack of omega-3 fatty acids but a higher increase of arachidonic that is implicated in depression.
[edit] Bodybuilding supplement
Arachidonic acid is marketed under patent (#6,841,573) as an anabolic bodybuilding supplement in products such as X-Factor (Molecular Nutrition), Halodrol Liquigels (Gaspari Nutrition), Animal Test (Universal Nutrition), Hemodraulix (Axis Labs), Mass Caps (IDS), Max Out (iForce), and Thermaphoria (EST Nutrition). The first clinical study concerning the use of arachidonic acid as a sport supplement was conducted at Baylor University and published in the 'Journal of the International Society of Sports Nutrition'."[16]
The performance data results from the paper include the following statistically significant improvement, and statistically strong trends:
A significant group × time interaction for relative Wingate peak power was observed among groups (P = 0.02) with gains in peak power being significantly greater in the AA group (0.3 ± 1.2 W·kg-1) vs. PLA (0.2 ± 0.7 W·kg-1, Figure 1). Using repeated measures ANOVA with delta scores, AA experienced significantly greater increases in comparison to the PLA group at day 50 (P < 0.05). Statistical trends were seen in Wingate total work (AA: 1,292 ± 1,206 vs. PLA: 510 ± 1,249 J, P = 0.09, ηp 2 = 0.052), favoring the AA group.
WIth regard to inflammation, the paper reported a statistiically significant reduction in resting IL-6 levels (a central regulator of inflammation):
IL-6 levels experienced a significant group × time interaction (P = 0.04) among groups with subsequent post-hoc analyses revealing that IL-6 was significantly lower at day 25 of the study. One way ANOVA of IL-6 delta values at day 25 revealed significantly greater increases in PLA when compared to AA group (AA: 0.8 ± 13.5 pg·ml-1 vs. PLA: 52.5 ± 1.6 pg·ml-1, P = 0.01; Figure 2)
Arachidonic acid was shown to improve peak muscle power, reduce resting IL-6 levels, and produce statistically strong trends of improvements in muscle endurance, average power, and bench press 1-rep maximum lift. This study provides preliminary evidence supporting the use of arachidonic acid in sports nutrition. Further research is needed.
[edit] Dietary arachidonic acid and inflammation
Under normal metabolic conditions, the increased consumption of arachidonic acid is unlikely to increase inflammation[citation needed]. ARA is metabolized to both pro-inflammatory and anti-inflammatory molecules[17]. Studies giving between 840 mg and 2,000 mg per day to healthy individuals for up to 50 days have shown no increases in inflammation or related metabolic activities[18][17][19][20]. Increased arachidonic acid levels are actually associated with reduced pro-inflammatory IL-6 and IL-1 levels, and increased anti-inflammatory tumor-necrosis factor-beta[21]. This may reduce inflammation under certain conditions.
Arachidonic acid does still play a central role in inflammation related to many diseased states. How it is metabolized in the body dictates its inflammatory or anti-inflammatory activity. Individuals suffering from joint pains or active inflammatory disease may find that increased arachidonic acid consumption exacerbates symptoms, probably because it is being more readily converted to inflammatory compounds. Likewise, high arachidonic acid consumption is not advised for individuals with a history of inflammatory disease, or that are in compromised health. It is also of note that while ARA supplementation does not appear to have pro-inflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of omega-3 EFA supplementation[22].
[edit] Health effects of arachidonic acid supplementation
Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health including kidney and liver function[19], serum lipids[23], immunity[24], and platelet aggregation[18] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity[25]. Arachidonic acid supplementation by healthy adults appears to offer no toxicity or significant safety risk. The safety of arachidonic acid supplementation in patients suffering from inflammatory or other diseased states is unknown, and is not recommended.
# 16790296.
# ^ Wang, Z.; Liang, C.; Li, G.; Yu, C.; Yin, M. (2006). "Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices". Chemico-biological interactions 163 (3): 207–217. doi:10.1016/j.cbi.2006.08.005. PMID 16982041. edit
# ^ Darios, F.; Davletov, B. (2006). "Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3". Nature 440 (7085): 813–817. doi:10.1038/nature04598. PMID 16598260. edit
# ^ Developmental Medicine and Child Neurology, March 2000
# ^ Rapoport, SI (2008). "Arachidonic acid and the brain". The Journal of nutrition 138 (12): 2515–20. PMID 19022981. edit
# ^ Effects of arachidonic acid supplementation on training adaptations in resistance-trained males [1]
# ^ a b Harris, W.; Mozaffarian, D.; Rimm, E.; Kris-Etherton, P.; Rudel, L.; Appel, L.; Engler, M.; Engler, M. et al. (2009). "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". Circulation 119 (6): 902–907. doi:10.1161/CIRCULATIONAHA.108.191627. PMID 19171857. edit
# ^ a b Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Kyle, D (1997). "The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans". Lipids 32 (4): 421–5. PMID 9113631. edit
# ^ a b Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training. Wilborn, C, M Roberts, C Kerksick, M Iosia, L Taylor, B Campbell, T Harvey, R Wilson, M. Greenwood, D Willoughby and R Kreider. Proceedings of the International Society of Sports Nutrition (ISSN) Conference June 15-17, 2006.
# ^ Pantaleo, P.; Marra, F.; Vizzutti, F.; Spadoni, S.; Ciabattoni, G.; Galli, C.; La Villa, G.; Gentilini, P. et al. (2004). "Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis". Clinical science (London, England : 1979) 106 (1): 27–34. doi:10.1042/CS20030182. PMID 12877651. edit
# ^ Ferrucci, L.; Cherubini, A.; Bandinelli, S.; Bartali, B.; Corsi, A.; Lauretani, F.; Martin, A.; Andres-Lacueva, C. et al. (2006). "Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers". The Journal of clinical endocrinology and metabolism 91 (2): 439–446. doi:10.1210/jc.2005-1303. PMID 16234304. edit
# ^ Li, B; Birdwell, C; Whelan, J (1994). "Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo". Journal of lipid research 35 (10): 1869–77. PMID 7852864. edit
# ^ Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Phinney, SD; Kyle, D; Silbermann, S; Schaefer, EJ (1997). "The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans". Lipids 32 (4): 427–33. PMID 9113632. edit
# ^ Kelley, DS; Taylor, PC; Nelson, GJ; MacKey, BE (1998). "Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men". Lipids 33 (2): 125–30. PMID 9507233. edit
# ^ Borkman, M; Storlien, LH; Pan, DA; Jenkins, AB; Chisholm, DJ; Campbell, LV (1993). "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids". The New England journal of medicine 328 (4): 238–44. PMID 8418404. edit
[edit] Muscle growth
Arachidonic acid is necessary for the repair and growth of skeletal muscle tissue. One of the lead researchers of the Baylor study on arachidonic acid, Mike Roberts MS, CSCS, has authored an article published under the title Arachidonic Acid, The New Mass Builder explaining the role of this nutrient in muscle anabolism, and its potential for the enhancement of muscle size and strength.[9]
Roberts claims that for optimal muscle growth a training stimulus must elicit localized inflammation and soreness. He also shows that arachidonic acid (AA, 20:4n-6) is an essential Omega-6 (1-6) polyunsaturated fatty acid that is abundant in skeletal muscle membrane phospholipids (figure 2). It is also the body's principle building block for the production of prostaglandins, which are known to have various physiological roles including a close involvement in inflammation. Also, the prostaglandin isomer PGF2a has a potent ability to stimulate muscle growth. As such, Roberts says that arachidonic acid is a regulator of localized muscle inflammation, and he claims that it may be a central nutrient controlling the intensity of the anabolic/tissue-rebuilding response to weight training.
[edit] Brain
Arachidonic acid is one of the most abundant fatty acids in the brain, and is present in similar quantities to DHA (docosahexaenoic acid). The two account for approximately 20% of its fatty acid content[10]. Like DHA, neurological health is reliant upon sufficient levels of arachidonic acid. Among other things, arachidonic acid helps to maintain hippocampal cell membrane fluidity[11]. It also helps protect the brain from oxidative stress by activating perioxisomal proliferator-activated receptor-y[12]. ARA also activates syntaxin-3 (STX-3), a protein involved in the growth and repair of neurons[13].
Arachidonic acid is also involved in early neurological development. In one study funded by the U.S. National Institute of Child Health and Human Development, infants (18 months) given supplemental arachidonic acid for 17 weeks demonstrated significant improvements in intelligence, as measured by the Mental Development Index (MDI)[14]. This effect is further enhanced by the simultaneous supplementation of ARA with DHA.
In adults, the disturbed metabolism of ARA may be associated with neurological disorders such as Alzheimer’s Disease and Bipolar Disorder[15]. This may involve the increased consumption of ARA at the cellular level, and significant alterations in its conversion to other bioactive molecules (overexpression or disturbances in the ARA enzyme cascade). The increased consumption of dietary arachidonic acid is not believed to cause these neurological disorders. In the Journal of Lipid Research, an American Society for Biochemical and Molecular Biology journal, a study dated 2005-05-25 used the Flinders Sensitive Line rats to investigate the link between omega-3 fatty acids and depression. An examination of the brains of depressed rats compared them with brains from normal rats. Surprisingly, they found that the main difference between the two types of rats was in omega-6 fatty acid levels and not omega-3 fatty acid levels. Specifically, they discovered that brains with depression had higher concentrations of arachidonic acid, a long-chain unsaturated metabolite of omega-6 fatty acid. The findings suggest that it is not a lack of omega-3 fatty acids but a higher increase of arachidonic that is implicated in depression.
[edit] Bodybuilding supplement
Arachidonic acid is marketed under patent (#6,841,573) as an anabolic bodybuilding supplement in products such as X-Factor (Molecular Nutrition), Halodrol Liquigels (Gaspari Nutrition), Animal Test (Universal Nutrition), Hemodraulix (Axis Labs), Mass Caps (IDS), Max Out (iForce), and Thermaphoria (EST Nutrition). The first clinical study concerning the use of arachidonic acid as a sport supplement was conducted at Baylor University and published in the 'Journal of the International Society of Sports Nutrition'."[16]
The performance data results from the paper include the following statistically significant improvement, and statistically strong trends:
A significant group × time interaction for relative Wingate peak power was observed among groups (P = 0.02) with gains in peak power being significantly greater in the AA group (0.3 ± 1.2 W·kg-1) vs. PLA (0.2 ± 0.7 W·kg-1, Figure 1). Using repeated measures ANOVA with delta scores, AA experienced significantly greater increases in comparison to the PLA group at day 50 (P < 0.05). Statistical trends were seen in Wingate total work (AA: 1,292 ± 1,206 vs. PLA: 510 ± 1,249 J, P = 0.09, ηp 2 = 0.052), favoring the AA group.
WIth regard to inflammation, the paper reported a statistiically significant reduction in resting IL-6 levels (a central regulator of inflammation):
IL-6 levels experienced a significant group × time interaction (P = 0.04) among groups with subsequent post-hoc analyses revealing that IL-6 was significantly lower at day 25 of the study. One way ANOVA of IL-6 delta values at day 25 revealed significantly greater increases in PLA when compared to AA group (AA: 0.8 ± 13.5 pg·ml-1 vs. PLA: 52.5 ± 1.6 pg·ml-1, P = 0.01; Figure 2)
Arachidonic acid was shown to improve peak muscle power, reduce resting IL-6 levels, and produce statistically strong trends of improvements in muscle endurance, average power, and bench press 1-rep maximum lift. This study provides preliminary evidence supporting the use of arachidonic acid in sports nutrition. Further research is needed.
[edit] Dietary arachidonic acid and inflammation
Under normal metabolic conditions, the increased consumption of arachidonic acid is unlikely to increase inflammation[citation needed]. ARA is metabolized to both pro-inflammatory and anti-inflammatory molecules[17]. Studies giving between 840 mg and 2,000 mg per day to healthy individuals for up to 50 days have shown no increases in inflammation or related metabolic activities[18][17][19][20]. Increased arachidonic acid levels are actually associated with reduced pro-inflammatory IL-6 and IL-1 levels, and increased anti-inflammatory tumor-necrosis factor-beta[21]. This may reduce inflammation under certain conditions.
Arachidonic acid does still play a central role in inflammation related to many diseased states. How it is metabolized in the body dictates its inflammatory or anti-inflammatory activity. Individuals suffering from joint pains or active inflammatory disease may find that increased arachidonic acid consumption exacerbates symptoms, probably because it is being more readily converted to inflammatory compounds. Likewise, high arachidonic acid consumption is not advised for individuals with a history of inflammatory disease, or that are in compromised health. It is also of note that while ARA supplementation does not appear to have pro-inflammatory effects in healthy individuals, it may counter the anti-inflammatory effects of omega-3 EFA supplementation[22].
[edit] Health effects of arachidonic acid supplementation
Arachidonic acid supplementation in daily dosages of 1,000-1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health including kidney and liver function[19], serum lipids[23], immunity[24], and platelet aggregation[18] appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity[25]. Arachidonic acid supplementation by healthy adults appears to offer no toxicity or significant safety risk. The safety of arachidonic acid supplementation in patients suffering from inflammatory or other diseased states is unknown, and is not recommended.
# 16790296.
# ^ Wang, Z.; Liang, C.; Li, G.; Yu, C.; Yin, M. (2006). "Neuroprotective effects of arachidonic acid against oxidative stress on rat hippocampal slices". Chemico-biological interactions 163 (3): 207–217. doi:10.1016/j.cbi.2006.08.005. PMID 16982041. edit
# ^ Darios, F.; Davletov, B. (2006). "Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3". Nature 440 (7085): 813–817. doi:10.1038/nature04598. PMID 16598260. edit
# ^ Developmental Medicine and Child Neurology, March 2000
# ^ Rapoport, SI (2008). "Arachidonic acid and the brain". The Journal of nutrition 138 (12): 2515–20. PMID 19022981. edit
# ^ Effects of arachidonic acid supplementation on training adaptations in resistance-trained males [1]
# ^ a b Harris, W.; Mozaffarian, D.; Rimm, E.; Kris-Etherton, P.; Rudel, L.; Appel, L.; Engler, M.; Engler, M. et al. (2009). "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". Circulation 119 (6): 902–907. doi:10.1161/CIRCULATIONAHA.108.191627. PMID 19171857. edit
# ^ a b Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Kyle, D (1997). "The effect of dietary arachidonic acid on platelet function, platelet fatty acid composition, and blood coagulation in humans". Lipids 32 (4): 421–5. PMID 9113631. edit
# ^ a b Changes in whole blood and clinical safety markers over 50 days of concomitant arachidonic acid supplementation and resistance training. Wilborn, C, M Roberts, C Kerksick, M Iosia, L Taylor, B Campbell, T Harvey, R Wilson, M. Greenwood, D Willoughby and R Kreider. Proceedings of the International Society of Sports Nutrition (ISSN) Conference June 15-17, 2006.
# ^ Pantaleo, P.; Marra, F.; Vizzutti, F.; Spadoni, S.; Ciabattoni, G.; Galli, C.; La Villa, G.; Gentilini, P. et al. (2004). "Effects of dietary supplementation with arachidonic acid on platelet and renal function in patients with cirrhosis". Clinical science (London, England : 1979) 106 (1): 27–34. doi:10.1042/CS20030182. PMID 12877651. edit
# ^ Ferrucci, L.; Cherubini, A.; Bandinelli, S.; Bartali, B.; Corsi, A.; Lauretani, F.; Martin, A.; Andres-Lacueva, C. et al. (2006). "Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers". The Journal of clinical endocrinology and metabolism 91 (2): 439–446. doi:10.1210/jc.2005-1303. PMID 16234304. edit
# ^ Li, B; Birdwell, C; Whelan, J (1994). "Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo". Journal of lipid research 35 (10): 1869–77. PMID 7852864. edit
# ^ Nelson, GJ; Schmidt, PC; Bartolini, G; Kelley, DS; Phinney, SD; Kyle, D; Silbermann, S; Schaefer, EJ (1997). "The effect of dietary arachidonic acid on plasma lipoprotein distributions, apoproteins, blood lipid levels, and tissue fatty acid composition in humans". Lipids 32 (4): 427–33. PMID 9113632. edit
# ^ Kelley, DS; Taylor, PC; Nelson, GJ; MacKey, BE (1998). "Arachidonic acid supplementation enhances synthesis of eicosanoids without suppressing immune functions in young healthy men". Lipids 33 (2): 125–30. PMID 9507233. edit
# ^ Borkman, M; Storlien, LH; Pan, DA; Jenkins, AB; Chisholm, DJ; Campbell, LV (1993). "The relation between insulin sensitivity and the fatty-acid composition of skeletal-muscle phospholipids". The New England journal of medicine 328 (4): 238–44. PMID 8418404. edit
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