7-keto dhea; citrulline malate

There are some reaction involved in 7-oxo-dhea taht I can't understand.
This is why I sent a letter to A. Tagliaferro, one of the greatest expert on DHEA, asking him some clarifications.

Dear Prof.
[omissis]
Following your research, Lardy et al. figured that DHEA can activate fat loss trought his metabolite, 7-oxo-dhea, increasing malic enzyme activity. From my undestanding, the activation of malic enzyme results in the conversion of malic acid to pyruvate and NADPH in the cytosol. This results in an excess of NADPH in the cytosol, which is subsequently transported into the mitochondria where it is converted to ATP and heat. This is a thermogenic effect since more heat is produced relative to ATP production due to the cytosolic origin of the reaction.
BUT, on my bio-chemestry test-book, malic enzyme is considered a LIPOGENIC enzyme.
So, I don't understand why malic enzyme activation leads to fat loss instead of fat gain.
During the reaction we lose 1 mol. of ATP but we create more substrates for lipogenesis.

Thank you for your attention,
R.C.

I'll let you know about his answer....
In the meantine, answer to my question!

citrulline malate also works via the conversion of the citrulline to arginine which promotes nitrogen balance as well as promoting ph balance for prevention of fatigue.. you can always swtich to l-citrulline or use vitamin D3(cholecalciferol instead of the 7-keto

jb

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Citrulline: a new player in the control of nitrogen homeostasis.Moinard C, Cynober L.
Laboratoire de Biologie de la Nutrition, EA 2498, Faculté de Pharmacie, Université Paris Descartes, and Laboratoire Biochimie, Hôtel-Dieu, AP-HP, Paris 75004, France. [email protected]

Citrulline (CIT) is an amino acid that is not involved in protein synthesis but that is tightly linked to arginine (ARG) metabolism. CIT displays a very specific metabolism: In the 1980s, Windmuller demonstrated that the small intestine releases CIT, which is mainly taken up by the kidney and metabolized into ARG. Because CIT is not taken up by the liver, this ARG-CIT-ARG cycle can be seen as a means of protecting dietary ARG from liver degradation and of sustaining protein homeostasis. These observations have led to the concept that plasma CIT concentration would be a good marker of intestinal failure in short bowel syndrome. Hence, in massive intestinal resection, citrullinemia is greatly reduced, and this is proportional to the severity of the intestinal disease. This concept was then extended to other situations in which the intestinal function is compromised. The data strongly suggest that CIT may be a conditionally essential amino acid in situations where the intestinal function is compromised. Recent data support this idea. Thus, CIT supplementation is able to restore nitrogen balance, generate large amounts of ARG in rats with short bowel syndrome, and increase muscle protein content (+20%) as well as muscle protein synthesis (+90%) in elderly malnourished rats. Finally, recent data indicate that CIT per se could be able to stimulate muscle protein synthesis. Hence, CIT could play a pivotal role in maintaining protein homeostasis, and the determination of the underlying mechanisms involved in its action should be important for the development of new nutritional strategies in malnourished patients with compromised intestinal functions.

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Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man.Callis A, Magnan de Bornier B, Serrano JJ, Bellet H, Saumade R.
Department of Medical Biophysics, Institut de Biologie, Montpellier, France.

An experimental evaluation of citrulline malate (Stimol, CAS 54940-97-5), an anti-fatigue compound, was undertaken in man and in the animal in order to study the pharmacological activity of the substance at hepatic and renal level. In man, the protocol involved a double-blind randomized, placebo-controlled cross-over technique. The study in the animal was blind and placebo-controlled with two randomized parallel groups. Results showed that citrulline malate stimulates hepatic ureogenesis and favorizes the renal reabsorption of bicarbonates. These metabolic actions had a protective effect against acidosis and ammonia poisoning and explain the anti-fatigue properties of citrulline malate in man.

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HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults.Zenk JL, Frestedt JL, Kuskowski MA.
Department of Clinical Affairs, Minnesota Applied Research Center, Edina, MN 55435, USA.

This study tested the hypothesis that 3-acetyl-7-oxo-dehydroepiandrosterone alone (7-Keto) and in combination with calcium citrate, green tea extract, ascorbic acid, chromium nicotinate and cholecalciferol (HUM5007) will increase the resting metabolic rate (RMR) of overweight subjects maintained on a calorie-restricted diet. In this randomized, double-blind, placebo-controlled, crossover trial, overweight adults on a calorie-restricted diet were randomized to three 7-day treatment periods with 7-Keto, HUM5007 or placebo. Resting metabolic rate was measured by indirect calorimetry at the beginning and end of each treatment period with a 7-day washout between testing periods. Of 45 subjects enrolled, 40 completed the study (30 women, 10 men; mean age, 38.5 years; mean basal mass index, 32.0 kg/m(2)). During the placebo treatment, RMR decreased by 3.9% (75+/-111 kcal/day; mean+/-S.D.); however, RMR increased significantly by 1.4% (21+/-115 kcal/day) and 3.4% (59+/-118 kcal/day) during the 7-Keto and HUM5007 treatment periods, respectively (each compared to placebo, P=.001). No significant differences were found between the treatment periods with respect to compliance or adverse events. In this study, the administration of HUM5007 or 7-Keto reversed the decrease in RMR normally associated with dieting. HUM5007 and 7-Keto increased RMR above basal levels and may benefit obese individuals with impaired energy expenditure. HUM5007 and 7-Keto were generally well tolerated and no serious adverse events were reported.

Posted by: jboldman

citrulline malate also works via the conversion of the citrulline to arginine which promotes nitrogen balance as well as promoting ph balance for prevention of fatigue.. you can always swtich to l-citrulline or use vitamin D3(cholecalciferol instead of the 7-keto

jb

Thank you, JB: I really appreciate your answer.

I try to clarify to myself:
1)citrulline increase perfermance, so it is a worth using it;
2)if I want to use 7-keto, I can switch to l-citrulline;
3)if I want to use citrulline malate, I can use vit. D3 istead of 7-keto.

To sum up:
it doesn't make sense using both 7-keto and citrulline malate (or other "malate-containing" products: tricreatine malate etc.). Right?

I think that the study you posted above on vit. D 3 is quite interesting, but we can't understand how and how much D3 can rise RMR:HUM5007 contained vit. D3 among other fat-loss aid.
From the paper:

"Each capsule of HUM5007 contained 250 mg calcium citrate, 150 mg green tea extract (standardized for 50% epigallocatechin gallate), 50 mg 3-acetyl-7-oxo-dehydroepiandrosterone, 50 mg ascorbic acid, 0.1 mg chromium nicotinate and 0.0025 mg cholecalciferol;
Each capsule of 7-Keto contained 50 mg 3-acetyl-7-oxo-dehydroepiandrosterone and 450 mg rice powder. Placebo capsules contained 500 mg rice powder.

Compared to the placebo treatment period, the increase in RMR following HUM5007 treatment was 134 kcal/day (7.3%) and 96 kcal/day (5.4%) after similar treatment with 7-Keto. No significant differences between treatment groups with respect to the quantities of carbohydrate, protein, fat or total calories consumed at baseline or during any of the treatment periods were found. Therefore, the significant increases in RMR associated with the administration of HUM5007 and 7-Keto in this study appear to be due to pharmacologically induced increases in resting energy expenditure in these individuals.
Although the change in RMR produced by HUM5007 was numerically superior to that of 7-Keto, this difference was not statistically significant."

futher studies are required to establish the role of vit. D3 for fat loss.

good point. i just reviewed 200 studies of vit d3 and found loads of interesting stuff but nothing for our purpose.

jb