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7-keto-DHEA

Getraw

Getraw

VIP Member
Feb 6, 2011
298
27
#1
7-keto-DHEA - dehydroepiandrosterone, 7-keto-dehydroepiandrosterone
This supplement has been proposed for the following purposes or treating the following conditions. Also given is the current scientific support for use (on a scale of 0-10). Note that a low rating does not necessarily indicate that a supplement does not work, just that research is either unavailable or has not demonstrated a benefit.

Fat loss – 9
Cardiovascular health - 7
Age-related memory impairment – 6
Immune stimulation - 6
HIV/AIDS – 5
Inflammatory bowel disease – 3
Raynaud's - 2

Side effects

This supplement has been found to be very safe in animals at high doses and in humans at up to 200 mg daily.
7-keto-DHEA should not be taken if you are being treated with glucocorticoids, as it may interfere with their effectiveness. If you are unsure if a medication you are taking is a glucocorticoid, consult a doctor.

Introduction

Dehydroepiandrosterone (DHEA) (along with its sulfated metabolite, DHEA-S) is the most abundant naturally occuring steroid in human blood. It is produced in the adrenal cortex and can also be independently synthesized in the brain. Among the biological effects of DHEA are changes in the immune system, inflammation, lipid and carbohydrate metabolism, anticarcinogenic effects, neuroprotection, and antioxidant effects [1-2].

DHEA levels significantly decline with age, and this decline has been correlated to varying degrees with many of the complications associated with aging, such as cardiovascular disease and high cholesterol levels, insulin resistance and diabetes, obesity, and neurodegeneration [3-5]. In humans, DHEA has been reported to reduce body fat, alleviate angina, and reduce LDL ("bad") cholesterol, and it has also been used to treat cancer, multiple sclerosis, coronary artery disease, lupus, Alzheimer's, HIV/AIDS, depression, PMS symptoms, and osteoporosis [6-8]. It has antiproliferative effects on some human cancer cell lines [2]. In animals, DHEA has been reported to decrease body fat and have beneficial effects in rodent models of diabetes, lupus, anemia, atherosclerosis, and breast, colon, lung, and skin cancer [3, 6, 9]. It also improves memory performance and has immunostimulating and antiglucocorticoid properties [10-11]. For these reasons, DHEA has been termed "fountain of youth" [12].

However, DHEA is not without its problems. For example, it converts to both estrogen and testosterone (and subsequently DHT),with the estrogenic conversion generally being greater [10]. This also introduces exogenous hormones into the body, which makes cyclic use necessary. In animal studies, high doses of DHEA increase liver weight and the risk of liver cancer [2-3].

Luckily, many of the biological actions of 7-keto-DHEA may not be due to DHEA itself, but its metabolites. This is supported by numerous observations. First, some of the metabolites of DHEA share its properties but are considerably stronger [1]. Second, a direct mechanism of action of DHEA has yet to be identified, indicating that the metabolites may be responsible for its effects [2]. Third, large doses are generally required for DHEA to have an effect in animal studies, indicating that it may function as a precursor to more active steroids [7]. Research has recently identified a number of DHEA metabolites which do not convert to androgens or estrogens or interact with sex steroid receptors but share many of the in vivo properties of DHEA, such as increased thermogenesis, neuroprotection and memory improvement, increased immune response, and improved cardiovascular health [4, 7, 10]. The most important of these are 7-oxo-DHEA (also known as 7-keto-DHEA),7alpha-hydroxy-DHEA (7alpha-OH-DHEA),and 7beta-hydroxy-DHEA (7beta-OH-DHEA).

Among these DHEA derivatives, 7-keto-DHEA is readily available as a supplement. 7-oxo-DHEA can be converted into both 7alpha-OH-DHEA and 7beta-OH-DHEA in humans, and in human liver microsomes, this occurs at an approximately 1:2 ratio [1, 13]. Both of these steroids can also be converted back into 7-oxo-DHEA [14], although once source indicates that the conversion of 7-oxo-DHEA to 7beta-OH-DHEA is irreversible [1]. A number of enzymes from the 11beta-hydroxysteroid dehydrogenase (11betaHSD) family are responsible for this interconversion process, one or more of which has not yet been identified [1]. Nevertheless, the effects of oral supplementation with 7-oxo-DHEA can be seen as the sum of some of effects of all three of these steroids, and also possibly the effect on enzyme competition with other steroids that convert via the same enzymes.

Fat loss

7-keto-DHEA has been associated with weight loss in multiple human studies. Davidson et al. reported a study involving oral administration of 50-200 mg daily of 3-acetyl-7-oxo-DHEA (which is quickly hydrolyzed to 7-oxo-DHEA in the body) or placebo in 22 men. The body weight of the placebo group increased by 3.0 kg and the body weight of the treatment group decreased by .5 kg over a period of eight weeks, and the difference was statistically significant. This translates to a difference of one pound per week between placebo and treatment groups. However, the study was only designed to assess the safety of the substance, so it did not control for confounding variables [7]. In another study, 30 overweight people were given either placebo or 100 mg of 7-oxo-DHEA twice daily for eight weeks. They exercised three times a week for a set period of time and were instructed to eat 1800 calories per day. Both groups lost weight, but weight loss was an average of 2 lbs greater per month in the 7-oxo-DHEA group (a statistically significant difference). Body fat decreased .89% per month in the treatment group compared to .29% per month with placebo, although this was measured by calipers, as opposed to a more reliable method [15].

In mice, rats, and dogs, DHEA has antiobesity effects and increases metabolic rate and thermogenesis. A decrease in body weight occurs without a change in food intake [6]. Rats fed 7-oxo-DHEA weighed 10% less than control rats in one study [16]. 7alpha-OH-DHEA also lead to a significant decrease in body weight in rats, an effect that was greater than that of DHEA [2]. However, in a study in monkeys, 7-oxo-DHEA failed to have an effect on body weight over the course of a month, although this study was of very limited statistical power, and like the study mentioned above, was primarily intended to evaluate the possible toxicity and side effects of the compound [17].

One study in mouse preadipocytes found that when treated with DHEA, it acted as a thermogenic and decreased fat accumulation, but 7-oxo-DHEA actually promoted lipogenesis. However, the authors pointed out that in live animals, 7-oxo-DHEA acts as a thermogenic [4], and all of the other evidence, both in vivo and in vitro, indicates that the effects of 7-oxo-DHEA on fat loss and thermogenesis are greater than those of DHEA.

There are a number of mechanisms which have been proposed by which 7-oxo-DHEA could increase fat loss. The first is potentiation of thyroid hormone activity and an increase in triiodothyronine (T3) levels. Thyroid hormones are important metabolic regulators, and often decrease when one goes on a diet, slowing metabolic rate and making weight loss efforts more difficult. In the second human study mentioned above, the group treated with 7-oxo-DHEA had significantly higher T3 levels, although they were still within the normal range [15]. Another study examined the association between natural 7beta-OH-DHEA levels and T3 levels in 152 men and women, and found them to be significantly correlated, indicating a possible link between the two factors [18]. 7-oxo-DHEA has also been reported to increase thyroid hormone levels in rats [15] and restore T3 and T4 levels in stressed mice [19].

7-oxo-DHEA, 7alpha-OH-DHEA, and 7beta-OH-DHEA all also increase the liver content of the thermogenic enzymes mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme, and all to a greater extent than DHEA [10]. 7-oxo-DHEA is about 2.5 times as potent as DHEA in inducing these enzymes [7]. These enzymes are also induced by thyroid hormone, and it is thought that either 7-oxo-DHEA or a metabolite acts in a similar manner to thyroid hormone. One observation on which this is based is that 7-oxo-DHEA and DHEA both still increase malic enzyme activity in hypothyroid rats, although one other study with DHEA did not have the same finding [16]. Thus, induction of these enzymes may be due to a direct receptor effect, an increase in thyroid hormones and/or potentiation of thyroid hormone activity, or a combination, the last of which is most likely given the experimental evidence.

Another possible mechanism by which 7-oxo-DHEA leads to fat loss is induction of peroxisome proliferator-activated receptors (PPARs). Specifically, DHEA is a preferential PPAR-alpha ligand, and 7-oxo-DHEA and the 7-OH metabolites have a greater affinity than DHEA. This can have a wide variety of effects, including increased mitochondrial uncoupling, regulation of genes that play a role in lipid metabolism, and increased levels of L-carnitine levels in various tissues [16]. In summary, this effect will have a number of downstream effects that will each increase fat loss in their own right. The extent of PPAR-alpha activation from 7-keto-DHEA supplementation in vivo is not known, and DHEA requires relatively high doses to have this effect [2].

Another possible mechanism contributing to fat loss is sulfation of 7alpha-OH-DHEA, which leads to a greater degree of energy expenditure [2].

Other benefits

DHEA is well known to have antiglucocorticoid activity and increase the immune response. Both 7alpha-OH-DHEA and 7beta-OH-DHEA are more potent than DHEA in enhancing immune response and counteracting glucocorticoid-induced immunosuppression [11]. In some tissues, one or both have been found to counteract the effects of cortisol and the synthetic glucocorticoid dexamethasone [20-21]. Dexamethasone increases the level of 7-hydroxylating enzymes in adipose tissue, and inflammation increased metabolism of DHEA to 7alpha-DHEA in the brain of rats, indicating that metabolism of DHEA through this route may be used as a natural feedback mechanism to stimulate the immune system [21]. 7alpha-OH-DHEA increases resistance against lethal infection in animals and act as an antioxidant [2, 5]. The antiglucocorticoid action does not appear to be due to direct effects on the receptor, and is not yet well understood [11]. 7-oxo-DHEA has also been found to mitigate the immune reduction seen in mice subjected to chronic stress, with the effect being greater than that of DHEA [19].

In the human liver, present evidence suggests that 7-oxo-DHEA is metabolized into 7alpha-OH-DHEA by the enzyme 11beta-hydroxysteroid dehydrogenase 1 (11betaHSD1). 11betaHSD1 also generally serves to convert inactive glucocorticoids to their active form, such as the conversion of cortisone to cortisol. It has been found that 7-oxo-DHEA competes with inactive glucocorticoids for the 11betaHSD1 enzyme [1]. Thus, 7-oxo-DHEA may inhibit the production of cortisol by 11betaHSD1 in in vivo situations, and this may be involved to some degree in the antiglucocorticoid action of 7-oxo-DHEA and related compounds. Sulcova et al. performed a study in men involving transdermal administration of 25 mg 7-oxo-DHEA for five days, and circulating cortisol levels decreased by 7.4%, but the effect was not statistically significant, although it was close [22]. Also, in the results reported by Davidson et al., cortisol levels decreased by 7.7% over eight weeks, but again this was not statistically significant [7]. Thus, the present research suggests that 7-keto-DHEA functionally reduces cortisol levels, but further research should be conducted to confirm this.

DHEA belongs to a class known as "neurosteroids" because it is synthesized de novo in the nervous system. It improves memory performance in aged and beta-amyloid peptide-injected mice [5]. 7-oxo-DHEA, 7alpha-OH-DHEA, and 7beta-OH-DHEA all have neuroprotective properties and improve learning/memory in rodents to a greater degree than DHEA [10]. 7-oxo-DHEA was found to reverse scopolamine-induced amnesia in young mice and improve memory in old mice as measured by the Morris water maze, and was described as much more effective than DHEA [7, 14]. DHEA acts as an antagonist at GABA-A receptors, improving cholinergic transmission, and it has been hypothesized that the effect of the metabolites may be due to the same mechanism [14]. The antiglucocorticoid effects also result in neuroprotection [23].

Other possible benefits from 7-keto-DHEA and its metabolites can be hypothesized. An in vitro study indicated a possible benefit from 7alpha-OH-DHEA in those with inflammatory bowel diseases [2]. In monkeys, 7-oxo-DHEA had beneficial effects in a model of wasting caused by HIV/AIDS [7]. In humans, oral 7-oxo-DHEA was associated with a significant reduction in systolic and diastolic blood pressure at multiple time points, and transdermal administration was associated with a small reduction in total cholesterol and an increase in HDL cholesterol [7, 22].

Dosage and Administration

7-keto-DHEA has been associated with a high degree of safety and a low incidence of side effects. One toxicological study at up to 2 g/kg orally daily found "no observable, serious, adverse effects on either male or female rats" [8]. This study, along with another, found no significant increase in the weight of vital organs such as the liver [2]. However, one study found 7-oxo-DHEA to increase liver weight in rodents (DHEA also has this effect) [16]. Monkeys have also been given up 500 mg/kg daily without any adverse effects or changes in toxicological parameters (for a 175 lb. human, this would equate to 200 times the standard oral dose of 200 mg). 1000 mg/kg was associated with vomiting and salivation, but the vomiting also occured in the same animals on days that 7-oxo-DHEA was not administered, indicating that it may not have been due to the substance [17].

In human studies, 7-keto-DHEA has been well tolerated, with no side effects reported at 200 mg orally [7, 15, 24]. Three studies have examined the effects of 7-oxo-DHEA on endrocrinological parameters. One found no significant change in blood sugar, testosterone, estradiol, or thyroid hormones other than T3, for which there was an increase. There were also no changes in tests of liver and kidney function or vital signs [15]. The other studies, the Sulcova and Davidson studies mentioned earlier (involving 25 mg transdermally for 5 days and escalating doses to 200 mg for eight weeks respectively, both in males),found reductions in total testosterone of approximately 10%, while Davidson et al. found an increase in free (usable) testosterone of about 15%. Estradiol was also decreased over the course of the study by 66% and 8% in these studies, and the second difference was not statistically significant. Overall, the effects on endrocrinological variables were either small or inconsistent, and they always remained within normal parameters [7, 22].

The primary methods of administration for 7-oxo-DHEA are oral and transdermal (for an explanation of transdermal delivery, see this article). Transdermal administration offers multiple advantages. It has been found to be a very effective delivery method for DHEA [20, 22]. Since the half-life after oral administration of 7-oxo-DHEA is only about two hours [24], transdermal administration offers a more sustained release. In terms of which delivery method will be more effective, theoretical arguments have been presented both ways. Since transdermal administration is less likely to reach the liver, there will be less activation of thermogenic enzymes in the liver. On the other hand, 7-oxo-DHEA is metabolized to a large extent in the liver, so transdermal administration will result in more 7-oxo-DHEA reaching other tissues.

The oral dosage recommended in the literature is 200 mg (100 mg twice daily),although some have reported using higher doses. For oral use, it would ideally be taken multiple times throughout the day. Most have used a dose around 100 mg transdermally, although it is clear that even 25 mg transdermally exerts an effect.

In conclusion, 7-oxo-DHEA is a promising agent for fat loss and offers a variety of other potential benefits. It is also safe and generally free of side effects. Further research may find that 7-keto-DHEA shares many of the other beneficial properties of DHEA.

1. Arch Biochem Biophys. 2003 Apr 15;412(2):251-8. Glucocorticoids inhibit interconversion of 7-hydroxy and 7-oxo metabolites of dehydroepiandrosterone: a role for 11beta-hydroxysteroid dehydrogenases? Robinzon B, Michael KK, Ripp SL, Winters SJ, Prough RA.

2. Steroids. 2004 Feb;69(2):137-44. Antioxidant effects of dehydroepiandrosterone and 7alpha-hydroxy-dehydroepiandrosterone in the rat colon, intestine and liver. Pelissier MA, Trap C, Malewiak MI, Morfin R.

3. Drug Metab Dispos. 2004 Mar;32(3):305-13. Stereo- and regioselectivity account for the diversity of dehydroepiandrosterone (DHEA) metabolites produced by liver microsomal cytochromes P450. Miller KK, Cai J, Ripp SL, Pierce WM Jr, Rushmore TH, Prough RA.

4. Biochemistry. 2002 Apr 30;41(17):5473-82. Molecular differences caused by differentiation of 3T3-L1 preadipocytes in the presence of either dehydroepiandrosterone (DHEA) or 7-oxo-DHEA. Gomez FE, Miyazaki M, Kim YC, Marwah P, Lardy HA, Ntambi JM, Fox BG.

5. Brain Res. 2003 Apr 18;969(1-2):117-25. In vitro metabolism of dehydroepiandrosterone (DHEA) to 7alpha-hydroxy-DHEA and Delta5-androstene-3beta,17beta-diol in specific regions of the aging brain from Alzheimer's and non-demented patients. Weill-Engerer S, David JP, Sazdovitch V, Liere P, Schumacher M, Delacourte A, Baulieu EE, Akwa Y.

6. Arch Biochem Biophys. 2001 May 15;389(2):278-87. Metabolism of DHEA by cytochromes P450 in rat and human liver microsomal fractions. Fitzpatrick JL, Ripp SL, Smith NB, Pierce WM Jr, Prough RA.

7. Clin Invest Med. 2000 Oct;23(5):300-10. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Davidson M, Marwah A, Sawchuk RJ, Maki K, Marwah P, Weeks C, Lardy H.

8. Biochem Biophys Res Commun. 1999 Jan 8;254(1):120-3. An acute oral gavage study of 3beta-acetoxyandrost- 5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats. Lardy H, Henwood SM, Weeks CE.

9. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 15;767(2):285-99. Ergosteroids. VI. Metabolism of dehydroepiandrosterone by rat liver in vitro: a liquid chromatographic-mass spectrometric study. Marwah A, Marwah P, Lardy H.

10. Mol Cell Endocrinol. 2003 May 30;203(1-2):13-23. Evidence that dehydroepiandrosterone, DHEA, directly inhibits GnRH gene expression in GT1-7 hypothalamic neurons. Cui H, Lin SY, Belsham DD.

11. J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):307-16. The content of four immunomodulatory steroids and major androgens in human semen. Hampl R, Pohanka M, Hill M, Starka L.

12. Bioorg Chem. 2002 Aug;30(4):233-48. Ergosteroids VII: perchloric acid-induced transformations of 7-oxygenated steroids and their bio-analytical applications--a liquid chromatographic-mass spectrometric study. Marwah A, Marwah P, Lardy H.

13. J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):245-51. Prohormones and sport. Delbeke FT, Van Eenoo P, Van Thuyne W, Desmet N.

14. Steroids. 2000 Mar;65(3):124-9. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Shi J, Schulze S, Lardy HA.

15. J Ex Physiology online. 1999 2(4). Double-Blind Study Evaluating the Effects of Exercise Plus 3-Acetyl-7-oxo-dehydroepiandrosterone on Body Composition and Endocrine System in Overweight Adults. Colker CM, Torina GC, Swain MA, Kalman DS.

16. Arch Biochem Biophys. 1997 May 1;341(1):122-8. The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis. Bobyleva V, Bellei M, Kneer N, Lardy H.

17. Biochem Biophys Res Commun. 1999 Jan 8;254(1):124-6. An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7, 17-dione (7-oxo-DHEA-acetate) in rhesus monkeys. Henwood SM, Weeks CE, Lardy H.

18. Clin Chem Lab Med. 2003 Aug;41(8):1081-6. Relationship of dehydroepiandrosterone and its 7-hydroxylated metabolites to thyroid parameters and sex hormone-binding globulin (SHBG) in healthy subjects. Hampl R, Hill M, Bilek R, Starka L.

19. Yao Xue Xue Bao. 2003 Dec;38(12):881-4. [Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress] [Article in Chinese]. Liu YY, Yang N, Kong LN, Zuo PP.

20. Physiol Res. 2000;49 Suppl 1:S107-12. 7-Hydroxydehydroepiandrosterone--a natural antiglucocorticoid and a candidate for steroid replacement therapy? Hampl R, Lapcik O, Hill M, Klak J, Kasal A, Novacek A, Sterzl I, Sterzl J, Starka L.

21. J Steroid Biochem Mol Biol. 1999 Dec 15;71(3-4):133-7. 7Beta-OH-DHEA counteracts dexamethasone induced suppression of primary immune response in murine spleenocytes. Sterzl I, Hampl R, Sterzl J, Votruba J, Starka L.

22. Physiol Res. 2001;50(1):9-18. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Sulcova J, Hill M, Masek Z, Ceska R, Novacek A, Hampl R, Starka L.

23. Int Rev Neurobiol. 2001;46:79-95. Neurosteroid 7-hydroxylation products in the brain. Morfin R, Starka L.

24. Steroids. 2001 Jul;66(7):581-95. Ergosteroids IV: synthesis and biological activity of steroid glucuronosides, ethers, and alkylcarbonates. Marwah P, Marwah A, Kneer N, Lardy H.

written by David Tolson
 
MAYO

MAYO

Bad Mother
Sep 27, 2010
2,121
613
#3
love 7-Keto, 100mg a day for cortisol suppression.....glad to see it here
 
goldy

goldy

Chutzpah VIP
Jan 17, 2011
1,263
153
#4
i liked it A LOT better when i had it in a dermal. this is way back like 04? It was in Chemo's T-Gel.
 
SJA

SJA

MuscleHead
Feb 24, 2011
611
91
#5
The old Designer Supps Lean Extreme was great. It had Quercetin in it as well which works synergistically with 7-oxo. 7-OH has now replaced most of the cortisol blockers now.
 
barbellbeast

barbellbeast

MuscleHead
Oct 4, 2010
342
43
#6
I only tried it once as part of a PCT after a tren ace cycle. I didn't notice any difference except for my wallet being much lighter.
 
Rider

Rider

TID Board Of Directors
Aug 27, 2010
1,319
577
#7
I only tried it once as part of a PCT after a tren ace cycle. I didn't notice any difference except for my wallet being much lighter.
Hah, it had the same effect on me. I used it for a Test, NPP, Var cycle for pct, didn't notice anything from it, and I remember it costing a lot.
 
marx

marx

MuscleHead
Sep 29, 2010
4,671
625
#8
Very interesting compound- and thread...

More users to chime in?
 
SJA

SJA

MuscleHead
Feb 24, 2011
611
91
#9
The only time I would recommend spending money on products like these would be when you are extremely stressed. If you ever hit the wall with respect to fat loss when trying to lean and keep saying to yourself "WTF.....i should be leaner" since you know your body well and have leaned out many times, take a look at your sleep patterns, stress in your life etc.. This is the only time where you will notice the effect of these supplements.
 
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