HackTwat
MuscleChemistry Registered Member
[h=1]Fat Attack: DHEA and 7-Keto DHEA[/h]
0 Comments
Our circulatory system carries many hormones and their metabolites throughout our bodies. We as bodybuilders tend to focus closely on hormones like insulin, testosterone and GH because of the powerful effect they exert on muscle growth.
Testosterone has been the subject of many articles in Muscular Development, obviously because of its importance in maintaining lean muscle mass. Additionally, recent studies suggest that testosterone is a very powerful fat-burning hormone.
Testosterone is made from conversion of cholesterol by a number of enzymes with a few precursors along the way:
Cholesterol→Pregnenolone→17-OH Pregnenolone→DHEA→Androstenedione→Testosterone
Something that is very frequently overlooked is that precursors to testosterone and even metabolites of those precursors have intrinsic metabolic effects that may be of significant interest to bodybuilders. In particular, the precursor dehydroepiandrosterone (DHEA) has been marketed heavily as a Fountain of Youth and a testosterone booster.
DHEA is the most abundant steroid hormone in the circulatory system and it has direct biological effects on tissues by binding to cell surface and nuclear receptors.[SUP]1[/SUP] Even though DHEA functions mainly as a precursor for androgens like testosterone and dihydrotestosterone (DHT), DHEA has its own ability to bind to the androgen receptor.[SUP]2[/SUP] Unfortunately, DHEA's intrinsic activity at the androgen receptor is quite low and thus it really just acts as an antagonist, which means it could be detrimental to your goals. In normal conditions, this is likely a very negligible effect because DHEA's actual affinity for the receptor is also quite weak.
Since there is a gradual age-related decline in DHEA that correlates with a similar decline in testosterone, many studies have evaluated supplementation with DHEA in older populations.[SUP]3[/SUP] Low levels of DHEA have also been correlated with accumulation of fat in the abdomen of men, and DHEA's role in regulating fat stores has been supported by numerous animal studies. One particular study in rats demonstrated that DHEA actually prevented fat accumulation in rats that were fed a high-fat diet.[SUP]4[/SUP] Clinical trials have examined the effect of DHEA on body fat in young, old and athletic populations with mixed results. One of the most highly quoted studies is by Nester et al. in 1988 that found remarkable results of an extraordinary dosage of 1,600 milligrams per day for 28 days.[SUP]5[/SUP] Compared to a placebo, they found that the threefold increase in circulating DHEA decreased body fat by 30 percent without a change in bodyweight, although there were no significant changes in testosterone or estrogen levels. Unfortunately other researchers have not been able to replicate this effect, and the follow-up studies are variable in dose, age, sex and fatness. Lower doses in obese subjects have been unsuccessful in improving body composition, and this may be related to fat's ability to metabolize androgens.[SUP]6[/SUP] Also, more recent double-blinded and placebo-controlled studies have shown benefits on insulin resistance, triglycerides and body composition, especially in elderly men.[SUP]7,8[/SUP]
Clinical studies of DHEA have been a little inconsistent, which has made DHEA less popular in the supplement industry, but more recent animal and laboratory studies suggest that DHEA deserves another look. DHEA appears to exert multiple effects on fat tissue including inhibition of fat cell growth, increased resting metabolic rate and inhibition of the actions of cortisol.[SUP]9[/SUP] A study in 2012 by Karbowska and Kochan (K&K) examined a more interesting ability of DHEA to mobilize fat from its stores while increasing the burning of fat.[SUP]9[/SUP] Other studies have demonstrated that DHEA and/or its metabolites have an ability to increase resting metabolic rate (RMR), even in a calorie-restricted/dieted state where the RMR usually decreases.[SUP]10[/SUP]
Let's take a step back and examine this a little closer. The goal of a bodybuilder who is dieting is to burn as much fat as possible while keeping his muscle. This means that the exercise you perform is intended to get fat out of its stores and burn it for energy or heat. Enzymes called "lipases" degrade triglycerides stored in fat cells into free fatty acids and glycerol that enter circulation, a process called lipolysis. These lipases are ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase). ATGL in particular is the rate-limiting enzyme in mobilization of fat stores, thus speeding it up is beneficial to losing fat. The K&K study examined the effects of DHEA on these lipases and made some intriguing observations in their rats.
First of all, the rats given DHEA for two weeks ate the same amount of chow as the control rats but gained significantly less weight and decreased fat stores by greater than 20 percent. Second, the rats had more fat mobilized in their blood than the controls. Third, DHEA appears to increase the activity of the fat metabolism regulator PPAR-g, which leads to stimulation of fat metabolism.
Once the fat is mobilized from stores, it needs to be burned. This is where a metabolite of DHEA comes into play. As we discussed earlier, even the metabolites of steroid hormones can have intrinsic activity, and this is really the basis of the "prohormone" market. Supplement companies may promote these metabolites as precursors or boosters of testosterone, but they often have metabolic activities even without conversion to testosterone. One of the DHEA metabolites has been marketed for fat loss and has some science to back it up. This metabolite is called 7-Keto DHEA. 7-Keto, DHEA is the acetyl ester of 7-oxo-DHEA, a naturally occurring oxidized metabolite of DHEA. This is a metabolite of DHEA that can't be converted to testosterone or estrogen, which removes some concerns one might have about DHEA increasing estrogen (despite lack of good evidence to suggest it will).
The oxygenation of DHEA at the "7" position imparts different characteristics to the molecule versus DHEA. Basic science has elucidated that 7-Keto DHEA has some unique effects with regard to lipid metabolism. Since numerous studies had already found that DHEA has fat-reducing capabilities, researchers set out to discover if any of its metabolites had an effect on fat metabolism. In addition, clinical studies show that DHEA levels and urine metabolites decrease with age, just as fat mass increases with age.[SUP]11[/SUP]
A study in the journal Steroids published in 1998 assayed the activity of 150 different metabolites from DHEA, and evaluated whether any of these stimulated thermogenic enzymes.[SUP]12[/SUP] In that study, researchers found that the metabolite 7-Keto DHEA was more than two times more active at inducing the thermogenic fat-burning enzymes than DHEA. As mentioned above, this is the metabolite of DHEA that has the ability to restore and even improve RMR in dieting subjects, and doesn't convert to testosterone.[SUP]10[/SUP] This avoids the problem that administration of exogenous DHEA has been found to cause acne, hirsutism, and altered menses in women, likely due to its capacity for increasing testosterone levels in women more so than men.[SUP]13,14[/SUP]
A recent study from the Institute of Endocrinology in Prague, Czech Republic revisited the 7-Keto DHEA metabolite of DHEA and its role in fat formation.[SUP]15[/SUP] The researchers note the ability of 7-oxo DHEA to compete with 1 lb-hydroxysteroid dehydrogenase (11 b-HSD 1), which affects conversion of cortisol to cortisone and vice versa. The anti-glucocorticoid effects of DHEA may be elicited through its metabolites. Their results showed a positive correlation between 7-oxo DHEA and obesity in adolescent boys. By acting as a competitive inhibitor of the conversion of inactive cortisone into active cortisol, 7-Keto DHEA may elicit beneficial reduction of the stress hormone in the dieting bodybuilder.
In conclusion, DHEA and its metabolite 7-Keto DHEA have many possible metabolic effects. Studies support the safety of administration of both of these compounds, and demonstrate diverse effects at various doses. A high-level study and placebo-controlled trial of 7-Keto DHEA and its benefit to the bodybuilder such as improvement in lean body mass or fat loss has not been done. The little data we have supports that 7-Keto DHEA may be a safe alternative to stimulants in improving RMR, while dieting and helping to maintain lean mass via stress hormone inhibition. But as studies in athletes have shown, the results are not miraculous despite rises in circulating testosterone and DHEA.[SUP]16[/SUP]
0 Comments
Our circulatory system carries many hormones and their metabolites throughout our bodies. We as bodybuilders tend to focus closely on hormones like insulin, testosterone and GH because of the powerful effect they exert on muscle growth.
Testosterone is made from conversion of cholesterol by a number of enzymes with a few precursors along the way:
Cholesterol→Pregnenolone→17-OH Pregnenolone→DHEA→Androstenedione→Testosterone
Something that is very frequently overlooked is that precursors to testosterone and even metabolites of those precursors have intrinsic metabolic effects that may be of significant interest to bodybuilders. In particular, the precursor dehydroepiandrosterone (DHEA) has been marketed heavily as a Fountain of Youth and a testosterone booster.
DHEA is the most abundant steroid hormone in the circulatory system and it has direct biological effects on tissues by binding to cell surface and nuclear receptors.[SUP]1[/SUP] Even though DHEA functions mainly as a precursor for androgens like testosterone and dihydrotestosterone (DHT), DHEA has its own ability to bind to the androgen receptor.[SUP]2[/SUP] Unfortunately, DHEA's intrinsic activity at the androgen receptor is quite low and thus it really just acts as an antagonist, which means it could be detrimental to your goals. In normal conditions, this is likely a very negligible effect because DHEA's actual affinity for the receptor is also quite weak.
Since there is a gradual age-related decline in DHEA that correlates with a similar decline in testosterone, many studies have evaluated supplementation with DHEA in older populations.[SUP]3[/SUP] Low levels of DHEA have also been correlated with accumulation of fat in the abdomen of men, and DHEA's role in regulating fat stores has been supported by numerous animal studies. One particular study in rats demonstrated that DHEA actually prevented fat accumulation in rats that were fed a high-fat diet.[SUP]4[/SUP] Clinical trials have examined the effect of DHEA on body fat in young, old and athletic populations with mixed results. One of the most highly quoted studies is by Nester et al. in 1988 that found remarkable results of an extraordinary dosage of 1,600 milligrams per day for 28 days.[SUP]5[/SUP] Compared to a placebo, they found that the threefold increase in circulating DHEA decreased body fat by 30 percent without a change in bodyweight, although there were no significant changes in testosterone or estrogen levels. Unfortunately other researchers have not been able to replicate this effect, and the follow-up studies are variable in dose, age, sex and fatness. Lower doses in obese subjects have been unsuccessful in improving body composition, and this may be related to fat's ability to metabolize androgens.[SUP]6[/SUP] Also, more recent double-blinded and placebo-controlled studies have shown benefits on insulin resistance, triglycerides and body composition, especially in elderly men.[SUP]7,8[/SUP]
Let's take a step back and examine this a little closer. The goal of a bodybuilder who is dieting is to burn as much fat as possible while keeping his muscle. This means that the exercise you perform is intended to get fat out of its stores and burn it for energy or heat. Enzymes called "lipases" degrade triglycerides stored in fat cells into free fatty acids and glycerol that enter circulation, a process called lipolysis. These lipases are ATGL (adipose triglyceride lipase) and HSL (hormone-sensitive lipase). ATGL in particular is the rate-limiting enzyme in mobilization of fat stores, thus speeding it up is beneficial to losing fat. The K&K study examined the effects of DHEA on these lipases and made some intriguing observations in their rats.
First of all, the rats given DHEA for two weeks ate the same amount of chow as the control rats but gained significantly less weight and decreased fat stores by greater than 20 percent. Second, the rats had more fat mobilized in their blood than the controls. Third, DHEA appears to increase the activity of the fat metabolism regulator PPAR-g, which leads to stimulation of fat metabolism.
Once the fat is mobilized from stores, it needs to be burned. This is where a metabolite of DHEA comes into play. As we discussed earlier, even the metabolites of steroid hormones can have intrinsic activity, and this is really the basis of the "prohormone" market. Supplement companies may promote these metabolites as precursors or boosters of testosterone, but they often have metabolic activities even without conversion to testosterone. One of the DHEA metabolites has been marketed for fat loss and has some science to back it up. This metabolite is called 7-Keto DHEA. 7-Keto, DHEA is the acetyl ester of 7-oxo-DHEA, a naturally occurring oxidized metabolite of DHEA. This is a metabolite of DHEA that can't be converted to testosterone or estrogen, which removes some concerns one might have about DHEA increasing estrogen (despite lack of good evidence to suggest it will).
The oxygenation of DHEA at the "7" position imparts different characteristics to the molecule versus DHEA. Basic science has elucidated that 7-Keto DHEA has some unique effects with regard to lipid metabolism. Since numerous studies had already found that DHEA has fat-reducing capabilities, researchers set out to discover if any of its metabolites had an effect on fat metabolism. In addition, clinical studies show that DHEA levels and urine metabolites decrease with age, just as fat mass increases with age.[SUP]11[/SUP]
A study in the journal Steroids published in 1998 assayed the activity of 150 different metabolites from DHEA, and evaluated whether any of these stimulated thermogenic enzymes.[SUP]12[/SUP] In that study, researchers found that the metabolite 7-Keto DHEA was more than two times more active at inducing the thermogenic fat-burning enzymes than DHEA. As mentioned above, this is the metabolite of DHEA that has the ability to restore and even improve RMR in dieting subjects, and doesn't convert to testosterone.[SUP]10[/SUP] This avoids the problem that administration of exogenous DHEA has been found to cause acne, hirsutism, and altered menses in women, likely due to its capacity for increasing testosterone levels in women more so than men.[SUP]13,14[/SUP]
A recent study from the Institute of Endocrinology in Prague, Czech Republic revisited the 7-Keto DHEA metabolite of DHEA and its role in fat formation.[SUP]15[/SUP] The researchers note the ability of 7-oxo DHEA to compete with 1 lb-hydroxysteroid dehydrogenase (11 b-HSD 1), which affects conversion of cortisol to cortisone and vice versa. The anti-glucocorticoid effects of DHEA may be elicited through its metabolites. Their results showed a positive correlation between 7-oxo DHEA and obesity in adolescent boys. By acting as a competitive inhibitor of the conversion of inactive cortisone into active cortisol, 7-Keto DHEA may elicit beneficial reduction of the stress hormone in the dieting bodybuilder.
In conclusion, DHEA and its metabolite 7-Keto DHEA have many possible metabolic effects. Studies support the safety of administration of both of these compounds, and demonstrate diverse effects at various doses. A high-level study and placebo-controlled trial of 7-Keto DHEA and its benefit to the bodybuilder such as improvement in lean body mass or fat loss has not been done. The little data we have supports that 7-Keto DHEA may be a safe alternative to stimulants in improving RMR, while dieting and helping to maintain lean mass via stress hormone inhibition. But as studies in athletes have shown, the results are not miraculous despite rises in circulating testosterone and DHEA.[SUP]16[/SUP]
