Prostaglandins and Protein Synthesis 2
(Arachidonic Acid Loading)
In a previous article we investigated the role that prostaglandins play in muscle growth (see: “Prostaglandins and Protein Synthesis,” March, 2003). In it, we discussed how these hormones are among the most vital regulators of protein synthesis following exercise, so much so, that they essentially control the core process of muscle growth itself. Everything subsequent to training, from anabolic steroids to protein supplementation, feeds off of the intensity of prostaglandin release during exercise. This month I’d like to share some of my research on arachidonic acid, which sits at the very center of the prostaglandin system. More specifically, I’ve struck on the concept of loading high levels of this nutrient in order to make the prostaglandin system much more responsive to physical training (enhancing protein synthesis for any given level of exercise stimulus). I am excited to say that this will soon segue in to the release of X-Factorä, an arachidonic acid supplement from my company, Molecular Nutrition. After reviewing the research, I trust you’ll agree that we have tapped a drastically new, and vitally important, method for the support of new muscle growth.
What is Arachidonic Acid?
Arachidonic acid is an essential fatty acid that is consumed in very small amounts in our regular diets. It’s found mainly in the fatty parts of meat, so vegetarians usually have lower levels of arachidonic acid in the body than those with omnivorous diets.[1] The intake even in meat-eaters is still small, with the average animal-product-rich western diet providing only about 230 milligrams of this important nutrient to each of us per day.[2] Arachidonic acid is considered an “essential” fatty acid because it is an absolute requirement for the proper functioning of the human body (in this case, it’s vital to the prostaglandin system). More specifically, it is the base material used by the body to synthesize a key series of hormones referred to collectively as dienolic prostaglandins. This includes the prostaglandins PGE2 and PGF2a, which are integral to protein turnover and muscle accumulation. As discussed in the first prostaglandin article, these two hormones operate right at the very core of muscle growth, and are responsible for regulating the direct local (muscular) response to physical exercise.
Release During Exercise
Skeletal muscle tissue has no capacity to store prostaglandins, so the only local source for these hormones is the arachidonic acid that’s retained in the outer phospholipid layer of each cell. Even more importantly, we find that it’s the stretching of muscle fibers during intense physical exercise that causes arachidonic acid to be released and metabolized to active prostaglandins. Arachiconic acid release is therefore the very first trigger in a long cascade that controls the rebuilding and strengthening of muscle tissue after exercise.
A study conducted at the Rowett Research Institute in the UK illustrates this relationship.[3] Here, researchers incubated and stimulated muscle tissue explants to demonstrate that it is arachidonic acid release, not stored prostaglandins, that serves as the base stimulus for protein synthesis. Their work was summarized by the participants well when they noted, “…the link between mechanical activity and protein synthesis… is most simply explained by the assumption that free arachidonic acid is released by stretching, is retained intracellularly and continues to be metabolized to the prostaglandins.” Two additional studies by Palmer and colleagues at the Rowett Institute support the same conclusion.[4] [5]
Exercise and AA Concentrations
Animal and human studies also show that exercise lowers the content of arachidonic acid in skeletal muscle tissue.[6] [7] [8] One such investigation divided human subjects into exercise and sedentary (inactive) groups, giving both the same standardized diet with an equivalent makeup of fatty acids and arachidonic acid (total food intake varied slightly between groups). The sedentary group noticed a slight increase in arachidonic acid concentrations, while the exercise group exhibited a mild depletion of this fatty acid. This was in spite of the fact that the exercise group actually consumed 13 percent more food on average, compared with the sedentary group, which would account for a slightly greater total intake of fatty acids. Since dienolic prostaglandin synthesis is inextricably tied to the amount of available arachidonic acid, lower levels will only result in less arachidonic acid being release with the stretching of exercise, and less muscle-building PGF2a being synthesized to increase muscle protein synthesis. Logic suggests that this might be one of the factors in the slowing down of new muscle growth that is noted with continued regular exercise.
AA Loading
Now that the importance of arachidonic acid to muscle anabolism has been established, I needed to go one step further and investigate what, if anything, we could expect from taking higher than normal levels of this vital fatty acid. Would it increase arachidonic acid stores in body tissues, or would the body just excrete the excess? And if tissue stores of this nutrient did increase, would this actually translate into greater prostaglandin formation (and protein synthesis) in the body?
To answer these questions, we can first look at a paper published in the journal Lipids in June, 2001, which reviewed many of the medical studies over the past few decades concerning the sources of arachidonic acid in the body.[9] Among other things, this paper discussed several studies that looked at the effect of short-term diets very rich in arachidonic acid. In going over both animal and human data, the authors did consistently note strong increases in the arachidonic acid content of various body tissues with supplementation of higher levels than the normal diet would provide.[10] [11] [12] [13] Clearly, this fatty acid has a very strong affinity to build in tissue lipids when taken in high doses. Another investigation went on to specifically look at what effect high doses, and high tissue concentrations, of arachidonic acid would have on the prostaglandin system.[14] In this study, subjects consumed six grams of ethyl arachidonate (an ester of AA) and noted a significant retention of arachidonic acid in the lipids of all tissues measured. A significant increase in the output of prostaglandin metabolites was also reported, with 3 of the 4 subjects having PGE2 metabolites spike by almost 50 percent. The results indicated a dramatic rise in the synthesis rate of these hormones in the body. The authors were left to conclude that supplementing precursor fatty acids in high levels augments the biosynthesis and function of prostaglandins. These two studies help us establish that we can enhance our level of stored arachidonic acid in muscle tissue with proper supplementation (AA loading), and furthermore, that we can heighten the sensitivity of the prostaglandin system as a result.
What the Research Tells Us
The studies presented have been gathered from several different areas of medical research, and tie in together to reveal the importance of arachidonic acid to the muscle-building process. More specifically, they suggest a strong role this nutrient may play as a muscle-building supplement. To summarize what we have learned in the review, we can highlight several very important key points. 1) Prostaglandins are core regulators of protein synthesis following exercise. 2) The production of prostaglandins is dependent on levels of available arachidonic acid. 3) The body retains stores of arachidonic acid in muscle tissue instead of active prostaglandins. 4) Arachidonic acid is released from muscle cells when stretched during exercise, where it is rapidly converted to active prostaglandins. 5) Exercise lowers the levels of arachidonic acid stored in muscle tissue. 6) Arachidonic acid can be “loaded” by supplementation, which should markedly enhance the responsiveness of the prostaglandin system to physical exercise.
References
[1] Reduced arachidonate in serum phospholipids and cholesterol esters associated with vegetarian diets in humans. Phinney et al. AM. J. Clin. Nutr. 51:385-92
[2] A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design. Lipids 32:415-20
[3] 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
[4] 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
[5] Protein synthesis and degradation in isolated muscle. Effect of n3 and n6 fatty acids. Palmer, Wahle. Biochem J. 1987 242, 615-18
[6] Regular exercise modulates muscle membrane phospholipid profile in rats. Helge et al. J. Nutr. 1999 129:1636-42
[7] Exercise training reduces skeletal muscle membrane arachidonate in obese (fa/fa) Zucker rat. Ayre et al. J. Appl. Physiol. 1998 85(5):1898-1902
[8] 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
[9] Sources of eicosanoid precursor fatty acid pools in tissues. Zhou, Nilsson. L. Lipid Res. 2001. 42:1521-42
[10] A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design. Lipids 32:415-20
[11] Effects of dietary arachidonic acid on human immune response. Nelson et al. Lipids 32:449-56
[12] Effects of dietary arachidonic acid on metabolism of deuterated linoleic acid by adult male subjects. Nelson et al. Lipids 33:471-80
[13] Influence of dietary arachidonic acid on metabolism in-vivo of 8cis,11cis,14-eicosatrienoic acid in humans. Nelson et al. Lipids 32:441-48
[14] Increased arachidonate in lipids after administration to man: Effects on prostaglandin biosynthesis. Seyberth et al. Clin. Pharm Ther. 1975 18(5) 521-9
Black Market Update: Hologram Help
Mexico is likely the world Mecca of anabolic steroids. The products made in this country dominate the U.S. black market now, making them obvious targets for counterfeit steroid manufacturers. Historically, this has been a problem for any popular steroid company, and indeed many Mexican products have fallen victim to such operations already. In an effort to stop this problem, many Mexican firms have been instituting security measures, such as the use of hologram stickers on their boxes and/or vials. These stickers usually bear the company name or logo, and offer assurance that the product you see is legitimately from that drug company. They offer protection simply because these stickers are expensive to print and extremely difficult to duplicate. So far the practice has been an extremely effective one for the companies involved, greatly benefiting consumers who know to look for these when shopping. We must be careful though; it isn’t difficult to get any old hologram sticker and put it on a fake steroid product. Hologram stickers saying “Security” are generic and pretty easy to obtain. In this issue, I therefore thought it would be a good idea to display, as best as I could (these shiny silvery hologram stickers do not reproduce well), the security stickers from the more popular Mexican steroid companies. Brovel Quality Vet Denkall Ttokkyo Labs
(Arachidonic Acid Loading)
In a previous article we investigated the role that prostaglandins play in muscle growth (see: “Prostaglandins and Protein Synthesis,” March, 2003). In it, we discussed how these hormones are among the most vital regulators of protein synthesis following exercise, so much so, that they essentially control the core process of muscle growth itself. Everything subsequent to training, from anabolic steroids to protein supplementation, feeds off of the intensity of prostaglandin release during exercise. This month I’d like to share some of my research on arachidonic acid, which sits at the very center of the prostaglandin system. More specifically, I’ve struck on the concept of loading high levels of this nutrient in order to make the prostaglandin system much more responsive to physical training (enhancing protein synthesis for any given level of exercise stimulus). I am excited to say that this will soon segue in to the release of X-Factorä, an arachidonic acid supplement from my company, Molecular Nutrition. After reviewing the research, I trust you’ll agree that we have tapped a drastically new, and vitally important, method for the support of new muscle growth.
What is Arachidonic Acid?
Arachidonic acid is an essential fatty acid that is consumed in very small amounts in our regular diets. It’s found mainly in the fatty parts of meat, so vegetarians usually have lower levels of arachidonic acid in the body than those with omnivorous diets.[1] The intake even in meat-eaters is still small, with the average animal-product-rich western diet providing only about 230 milligrams of this important nutrient to each of us per day.[2] Arachidonic acid is considered an “essential” fatty acid because it is an absolute requirement for the proper functioning of the human body (in this case, it’s vital to the prostaglandin system). More specifically, it is the base material used by the body to synthesize a key series of hormones referred to collectively as dienolic prostaglandins. This includes the prostaglandins PGE2 and PGF2a, which are integral to protein turnover and muscle accumulation. As discussed in the first prostaglandin article, these two hormones operate right at the very core of muscle growth, and are responsible for regulating the direct local (muscular) response to physical exercise.
Release During Exercise
Skeletal muscle tissue has no capacity to store prostaglandins, so the only local source for these hormones is the arachidonic acid that’s retained in the outer phospholipid layer of each cell. Even more importantly, we find that it’s the stretching of muscle fibers during intense physical exercise that causes arachidonic acid to be released and metabolized to active prostaglandins. Arachiconic acid release is therefore the very first trigger in a long cascade that controls the rebuilding and strengthening of muscle tissue after exercise.
A study conducted at the Rowett Research Institute in the UK illustrates this relationship.[3] Here, researchers incubated and stimulated muscle tissue explants to demonstrate that it is arachidonic acid release, not stored prostaglandins, that serves as the base stimulus for protein synthesis. Their work was summarized by the participants well when they noted, “…the link between mechanical activity and protein synthesis… is most simply explained by the assumption that free arachidonic acid is released by stretching, is retained intracellularly and continues to be metabolized to the prostaglandins.” Two additional studies by Palmer and colleagues at the Rowett Institute support the same conclusion.[4] [5]
Exercise and AA Concentrations
Animal and human studies also show that exercise lowers the content of arachidonic acid in skeletal muscle tissue.[6] [7] [8] One such investigation divided human subjects into exercise and sedentary (inactive) groups, giving both the same standardized diet with an equivalent makeup of fatty acids and arachidonic acid (total food intake varied slightly between groups). The sedentary group noticed a slight increase in arachidonic acid concentrations, while the exercise group exhibited a mild depletion of this fatty acid. This was in spite of the fact that the exercise group actually consumed 13 percent more food on average, compared with the sedentary group, which would account for a slightly greater total intake of fatty acids. Since dienolic prostaglandin synthesis is inextricably tied to the amount of available arachidonic acid, lower levels will only result in less arachidonic acid being release with the stretching of exercise, and less muscle-building PGF2a being synthesized to increase muscle protein synthesis. Logic suggests that this might be one of the factors in the slowing down of new muscle growth that is noted with continued regular exercise.
AA Loading
Now that the importance of arachidonic acid to muscle anabolism has been established, I needed to go one step further and investigate what, if anything, we could expect from taking higher than normal levels of this vital fatty acid. Would it increase arachidonic acid stores in body tissues, or would the body just excrete the excess? And if tissue stores of this nutrient did increase, would this actually translate into greater prostaglandin formation (and protein synthesis) in the body?
To answer these questions, we can first look at a paper published in the journal Lipids in June, 2001, which reviewed many of the medical studies over the past few decades concerning the sources of arachidonic acid in the body.[9] Among other things, this paper discussed several studies that looked at the effect of short-term diets very rich in arachidonic acid. In going over both animal and human data, the authors did consistently note strong increases in the arachidonic acid content of various body tissues with supplementation of higher levels than the normal diet would provide.[10] [11] [12] [13] Clearly, this fatty acid has a very strong affinity to build in tissue lipids when taken in high doses. Another investigation went on to specifically look at what effect high doses, and high tissue concentrations, of arachidonic acid would have on the prostaglandin system.[14] In this study, subjects consumed six grams of ethyl arachidonate (an ester of AA) and noted a significant retention of arachidonic acid in the lipids of all tissues measured. A significant increase in the output of prostaglandin metabolites was also reported, with 3 of the 4 subjects having PGE2 metabolites spike by almost 50 percent. The results indicated a dramatic rise in the synthesis rate of these hormones in the body. The authors were left to conclude that supplementing precursor fatty acids in high levels augments the biosynthesis and function of prostaglandins. These two studies help us establish that we can enhance our level of stored arachidonic acid in muscle tissue with proper supplementation (AA loading), and furthermore, that we can heighten the sensitivity of the prostaglandin system as a result.
What the Research Tells Us
The studies presented have been gathered from several different areas of medical research, and tie in together to reveal the importance of arachidonic acid to the muscle-building process. More specifically, they suggest a strong role this nutrient may play as a muscle-building supplement. To summarize what we have learned in the review, we can highlight several very important key points. 1) Prostaglandins are core regulators of protein synthesis following exercise. 2) The production of prostaglandins is dependent on levels of available arachidonic acid. 3) The body retains stores of arachidonic acid in muscle tissue instead of active prostaglandins. 4) Arachidonic acid is released from muscle cells when stretched during exercise, where it is rapidly converted to active prostaglandins. 5) Exercise lowers the levels of arachidonic acid stored in muscle tissue. 6) Arachidonic acid can be “loaded” by supplementation, which should markedly enhance the responsiveness of the prostaglandin system to physical exercise.
References
[1] Reduced arachidonate in serum phospholipids and cholesterol esters associated with vegetarian diets in humans. Phinney et al. AM. J. Clin. Nutr. 51:385-92
[2] A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design. Lipids 32:415-20
[3] 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
[4] 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
[5] Protein synthesis and degradation in isolated muscle. Effect of n3 and n6 fatty acids. Palmer, Wahle. Biochem J. 1987 242, 615-18
[6] Regular exercise modulates muscle membrane phospholipid profile in rats. Helge et al. J. Nutr. 1999 129:1636-42
[7] Exercise training reduces skeletal muscle membrane arachidonate in obese (fa/fa) Zucker rat. Ayre et al. J. Appl. Physiol. 1998 85(5):1898-1902
[8] 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
[9] Sources of eicosanoid precursor fatty acid pools in tissues. Zhou, Nilsson. L. Lipid Res. 2001. 42:1521-42
[10] A human dietary arachidonic acid supplementation study conducted in a metabolic research unit: rationale and design. Lipids 32:415-20
[11] Effects of dietary arachidonic acid on human immune response. Nelson et al. Lipids 32:449-56
[12] Effects of dietary arachidonic acid on metabolism of deuterated linoleic acid by adult male subjects. Nelson et al. Lipids 33:471-80
[13] Influence of dietary arachidonic acid on metabolism in-vivo of 8cis,11cis,14-eicosatrienoic acid in humans. Nelson et al. Lipids 32:441-48
[14] Increased arachidonate in lipids after administration to man: Effects on prostaglandin biosynthesis. Seyberth et al. Clin. Pharm Ther. 1975 18(5) 521-9
Black Market Update: Hologram Help
Mexico is likely the world Mecca of anabolic steroids. The products made in this country dominate the U.S. black market now, making them obvious targets for counterfeit steroid manufacturers. Historically, this has been a problem for any popular steroid company, and indeed many Mexican products have fallen victim to such operations already. In an effort to stop this problem, many Mexican firms have been instituting security measures, such as the use of hologram stickers on their boxes and/or vials. These stickers usually bear the company name or logo, and offer assurance that the product you see is legitimately from that drug company. They offer protection simply because these stickers are expensive to print and extremely difficult to duplicate. So far the practice has been an extremely effective one for the companies involved, greatly benefiting consumers who know to look for these when shopping. We must be careful though; it isn’t difficult to get any old hologram sticker and put it on a fake steroid product. Hologram stickers saying “Security” are generic and pretty easy to obtain. In this issue, I therefore thought it would be a good idea to display, as best as I could (these shiny silvery hologram stickers do not reproduce well), the security stickers from the more popular Mexican steroid companies. Brovel Quality Vet Denkall Ttokkyo Labs