Supplements

7-Keto-DHEA

Updated · 27 sources · Editorial policy

7-Keto-DHEA (7-oxo-dehydroepiandrosterone) is a natural metabolite of DHEA, the adrenal steroid that sits downstream of pregnenolone in the body’s hormone pathway. It is sold in the US as a dietary supplement, usually as its 3-acetate ester, and is marketed mainly for weight loss and “metabolism support.” Its selling point is that, unlike DHEA, it is not converted into testosterone or estrogen.

The human evidence is thin. A 2023 systematic review found only four small, short randomized trials in overweight adults, three of them testing multi-ingredient products, and concluded that no clear answer can be given on weight loss. FDA has proposed not to allow it in compounded drugs because there are too few data on safety and effectiveness. It is also on the WADA Prohibited List as an anabolic agent.

This page summarizes what the clinical trials, safety studies and regulators report. It is for education only and is not medical advice.

Property Detail
Class 7-oxygenated DHEA metabolite (“ergosteroid”); sold as a dietary supplement
Natural form 3β-hydroxyandrost-5-ene-7,17-dione, C₁₉H₂₆O₃, 302.4 g/mol
Supplement form 3-acetate ester (3β-acetoxyandrost-5-ene-7,17-dione), C₂₁H₂₈O₄, 344.4 g/mol
Route studied Oral capsules; a 25 mg/day skin gel in Czech volunteer studies
Doses in trials 100–200 mg/day orally, for 1–8 weeks
Half-life ≈2.2 h (7-oxo-DHEA sulfate, the form found in blood after oral dosing)
Conversion to sex hormones Not converted to DHEA in a human isotope study; described as not convertible to testosterone or estrogens
FDA status Not an approved drug; FDA proposed in 2019 to exclude it from the list of substances allowed in compounding
US schedule Not listed as a Schedule III anabolic steroid
WADA status Prohibited at all times (S1.1, anabolic androgenic steroids); non-Specified

What it is

The body makes small amounts of 7-keto-DHEA from DHEA. Two enzymes are involved (Hennebert et al., J Steroid Biochem Mol Biol 2007):

  • CYP7B1 adds a hydroxyl group at carbon 7, producing 7α-hydroxy-DHEA;
  • 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) then interconverts 7α- and 7β-hydroxy-DHEA through 7-keto-DHEA as the intermediate.

Circulating levels are low. In 215 people aged 5–71 without endocrine disease, mean serum 7-keto-DHEA was 0.280 nmol/L (median 0.239 nmol/L), with no significant difference between the sexes (Kazihnitková et al., Steroids 2007).

The two forms differ as follows (PubChem CID 193313; PubChem CID 9798229):

Form Chemical name Formula Molecular weight
7-Keto-DHEA (natural metabolite) 3β-hydroxyandrost-5-ene-7,17-dione C₁₉H₂₆O₃ 302.4 g/mol
7-Keto-DHEA acetate (supplement form) 3β-acetoxyandrost-5-ene-7,17-dione C₂₁H₂₈O₄ 344.4 g/mol

“7-Keto” is a trademarked name for the acetate (Ihler and Chami-Stemmann, Med Hypotheses 2003). Much of the early research came from Henry Lardy’s group at the University of Wisconsin, which called these DHEA derivatives “ergosteroids.”

Proposed mechanism

Most of the mechanistic work was done in rats:

  • Thermogenic liver enzymes. Fed to rats, DHEA induces two liver enzymes tied to heat production: mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme. The 7-oxo derivatives were more active inducers than DHEA itself (Lardy et al., PNAS 1995; Lardy et al., Steroids 1998).
  • Mitochondrial “proton leak.” Liver mitochondria from rats given 7-keto-DHEA behaved like those from rats given thyroid hormone, losing membrane potential faster. This suggests that more energy is released as heat rather than stored (Bobyleva et al., Arch Biochem Biophys 1997).
  • Cortisol balance. In human skin tissue in the lab, 7-keto-DHEA inhibited the 11β-HSD1 reaction that turns inactive cortisone into active cortisol (Hennebert et al., 2007). Whether this matters at supplement doses in people is not known.

The claim that it is not converted to sex hormones rests on Lardy’s work and on a human urine study. Using carbon isotope ratio testing, an anti-doping laboratory confirmed that 7-keto-DHEA taken by volunteers was not converted to DHEA (Martinez-Brito et al., Drug Test Anal 2019).

Pharmacokinetics

The only formal human pharmacokinetic study gave the acetate orally to healthy men (Davidson et al., Clin Invest Med 2000). The acetate itself was not detected in blood. It was rapidly converted to 7-oxo-DHEA-3β-sulfate, the only metabolite measured, with levels proportional to the dose.

Parameter (7-oxo-DHEA sulfate, after 100 mg) Value
Time to peak 2.2 h
Half-life 2.17 h
Apparent clearance 172 L/h
Apparent volume of distribution 540 L
Level 12 h after dosing, day 7 of 200 mg/day 15.8 µg/L
Level 12 h after dosing, day 28 of 200 mg/day 16.3 µg/L

The similar 12-hour levels on days 7 and 28 indicate that the sulfate did not accumulate with daily dosing.

In urine, many further metabolites appear. After a single 100 mg oral dose, isotope-ratio testing could tell supplemental from natural 7-keto-DHEA for more than 50 hours, and a newly identified metabolite extended that window by about 25 hours (Piper et al., Rapid Commun Mass Spectrom 2020).

Regulatory status

  • Dietary supplement, not a drug. 7-Keto-DHEA is not an FDA-approved drug. It is sold over the counter as a supplement.
  • Compounding. FDA’s Pharmacy Compounding Advisory Committee voted on November 20, 2017 not to add 7-keto-DHEA to the list of bulk substances that pharmacies may use in compounded drugs. In a 2019 proposed rule, FDA agreed. It found no safety signal but “minimal data,” so it could not adequately assess safety, and insufficient data to show effectiveness for Raynaud’s phenomenon or obesity (84 FR 46688).
  • Controlled substance status. 7-Keto-DHEA is not named among the anabolic steroids in Schedule III (21 CFR 1308.13).
  • Sport. WADA lists 7-keto-DHEA by name under S1.1, anabolic androgenic steroids, when administered exogenously. It is prohibited in and out of competition and is a non-Specified substance (WADA 2026 Prohibited List).

What the research shows

Weight loss in overweight adults

A 2023 systematic review searched eight databases and trial registries and found only four eligible randomized, double-blind, placebo-controlled trials, all from the US and published 2000–2007 (Jeyaprakash et al., Arch Gynecol Obstet 2023). Together they enrolled 131 people. Three were led by the same investigator, and only two tested 7-keto-DHEA on its own; the rest used commercial blends.

Trial Product n (active/placebo) Duration 7-keto-DHEA dose Weight change vs placebo
Kalman et al., 2000 7-Keto-DHEA alone 13/10 8 weeks 200 mg/day −2.88 vs −0.97 kg (p = 0.01)
Zenk et al., 2002 7-Keto Naturalean (blend) 17/16 8 weeks 200 mg/day −2.15 vs −0.72 kg (p = 0.038)
Zenk et al., 2005 Lean System 7 (blend) 19/16 8 weeks 102 mg/day −2.26 vs −2.34 kg (not significant)
Zenk et al., 2007 7-Keto-DHEA alone; HUM5007 (blend) 40, crossover 7 days per period 200 mg/day No significant difference

Data as summarized by Jeyaprakash et al. 2023. Three trials also prescribed diet and exercise; the 2007 trial prescribed a calorie-restricted diet.

Other outcomes were mixed:

  • Body fat. Only the Kalman trial found a significant drop in body fat percentage, 1.80% vs 0.57% (p = 0.02). The change was not seen at week 4, only at week 8.
  • BMI. Only the 2002 blend trial found a significant BMI drop, 0.71 vs 0.01 kg/m² (p = 0.036).
  • Thyroid. Kalman reported a rise in T3 (triiodothyronine, the active thyroid hormone) that stayed within the normal range. The two later 8-week trials did not see this.

The blends contained other active ingredients. Lean System 7, for example, also contained yerba mate, guarana, citrus aurantium and coleus forskohlii. Their results cannot be credited to 7-keto-DHEA alone. The review’s conclusion was that the evidence is mixed and more studies are needed before any therapeutic use can be recommended.

Resting metabolic rate

Metabolic rate is the main claimed mechanism, so it is the most relevant outcome. Two trials found an effect:

  • 7-Keto-DHEA alone, 1 week. In the 2007 crossover trial, 45 overweight adults (40 completers, 30 of them women, mean BMI 32.0) on a calorie-restricted diet took 7-keto-DHEA, a blend or placebo for 7 days each. Resting metabolic rate fell by 3.9% (75 kcal/day) on placebo but rose by 1.4% (21 kcal/day) on 7-keto-DHEA (p = 0.001 vs placebo). Body weight did not differ (Zenk et al., J Nutr Biochem 2007).
  • Lean System 7, 8 weeks. Resting metabolic rate rose 7.2% on the blend vs a 0.7% fall on placebo (p = 0.03), with 35 of 47 participants completing. Hip circumference fell more on the blend, but no other outcome differed, including weight (Zenk et al., Nutrition 2005).

The 2002 blend trial measured basal metabolic rate and found no significant change.

Other proposed uses

These have no controlled human trial data:

  • Raynaud’s phenomenon. A 2003 hypothesis paper proposed 7-keto-DHEA for preventing attacks by raising metabolic rate (Ihler and Chami-Stemmann, 2003). FDA found insufficient data to establish effectiveness for this use.
  • Posttraumatic stress disorder. A 2006 journal letter described five case reports in women (Sageman and Brown, J Clin Psychiatry 2006). Case reports cannot show whether a treatment works.
  • Memory. In mice, 7-keto-DHEA acetate reversed drug-induced memory impairment and helped old mice retain a learned task (Shi et al., Steroids 2000). This has not been tested in people.
  • Immune function. In blood cells from patients with HIV and tuberculosis, 7-keto-DHEA added in the lab shifted T cell responses toward a profile linked to better tuberculosis control (Vecchione et al., J Biomed Sci 2020). No treatment trial has followed.

Side effects and risks

Tolerability in trials

The trials were small and short, so they can only detect common, short-term effects:

  • Oral safety study. In 22 healthy men (16 active, 6 placebo) given 50 mg/day for 7 days, 100 mg/day for 7 days, then 200 mg/day for 28 days, there were no differences from placebo in lab values, vital signs, urinalysis or reported adverse events. Testosterone, free testosterone, DHT, estradiol, cortisol, thyroxine and insulin generally stayed unchanged and within the normal range (Davidson et al., 2000).
  • Weight-loss trials. No serious adverse events were reported and none led to dropping out. Nausea and vertigo were noted as possibly related to 7-keto-DHEA, and the blends added reports such as heartburn, palpitations and metallic taste (Jeyaprakash et al., 2023).

No trial lasted longer than 8 weeks, and the oral safety study included only men. Long-term safety is unknown.

Hormone changes with skin application

The “no hormonal effects” claim comes from the oral study. Czech researchers who applied a 25 mg/day 7-keto-DHEA gel to men’s skin found measurable changes:

Study Design Findings
Sulcová et al., Physiol Res 2001 10 men aged 27–72; 5 days Testosterone and estradiol fell; LH, HDL cholesterol and apolipoprotein A-I rose
Sulcová et al., Clin Chem Lab Med 2005 21 men aged 20–70; 8 days, followed 100 days Testosterone and gonadotropins fell after the first dose only. After stopping, testosterone, estradiol and SHBG were lower for weeks, up to day 63–91
Hampl et al., Physiol Res 2006 Same 21 men Small, significant rises in TSH and thyroid hormones during treatment, soon back to baseline

The review authors suggested these differences may reflect the skin route or the unconjugated form reaching the blood. They also noted that the hormone studies only enrolled men, so effects in women are uncertain.

Animal toxicity

In rats, a single oral dose of the acetate up to 2,000 mg/kg caused no observable adverse effects (Lardy et al., BBRC 1999). In four rhesus monkeys given escalating doses up to 1,000 mg/kg/day for several days, the 1,000 mg/kg dose caused vomiting and excess salivation, but no lesions were found in 42 organs and tissues (Henwood et al., BBRC 1999). These were short, high-dose animal studies and do not establish long-term safety in people.

Drug testing in sport

Because 7-keto-DHEA is also made naturally, there is no simple concentration cutoff. Anti-doping labs use carbon isotope ratio testing to show it came from outside the body, and this method confirmed exogenous use in two routine doping-control samples (Piper et al., 2020). Some lab procedures also convert 7-keto-DHEA into arimistane, another prohibited compound, which complicates interpretation of results (Martínez Brito et al., Drug Test Anal 2021).

Groups without data

The weight-loss trials excluded people with the following, so there are no data in these groups (Jeyaprakash et al., 2023):

  • kidney, liver or heart disease;
  • cancer, diabetes or thyroid disease;
  • eating disorders;
  • pregnancy or breastfeeding;
  • use of weight-loss medications.

Athletes subject to WADA rules face an anti-doping violation regardless of the supplement’s label claims.

Key takeaways

  • A natural DHEA metabolite sold as a supplement. It is made in the body from DHEA in small amounts and sold mainly as the 3-acetate. It is not converted back into DHEA.
  • Short-lived in the blood. Its main circulating form, the sulfate, has a half-life of about 2.2 hours and does not accumulate with daily dosing.
  • Weight-loss evidence is weak. Four small trials of 1–8 weeks gave mixed results, and most tested multi-ingredient blends. The one 8-week trial of 7-keto-DHEA alone reported 2.88 kg lost vs 0.97 kg on placebo.
  • Metabolic-rate effects are small. The best single-ingredient result was a 1.4% rise vs a 3.9% fall on placebo over one week of dieting.
  • Not hormone-neutral on the skin. Oral dosing up to 200 mg/day for 4 weeks generally did not change hormones in men, but a skin gel lowered testosterone and estradiol for weeks in two small studies.
  • Banned in sport, unapproved in medicine. WADA prohibits it at all times, and FDA proposed excluding it from compounding for lack of safety and effectiveness data.

Sources

  1. Jeyaprakash N, Maeder S, Janka H, Stute P. A systematic review of the impact of 7-keto-DHEA on body weight. Arch Gynecol Obstet. 2023;308(3):777–785. PubMed; PMC.
  2. Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med. 2000;23(5):300–310. PubMed.
  3. Kalman DS, Colker CM, Swain MA, Torina GC, Shi Q. A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Ther Res. 2000;61(7):435–442. DOI.
  4. Zenk JL, Helmer TR, Kassen LJ, Kuskowski MA. The effect of 7-Keto Naturalean on weight loss: a randomized, double-blind, placebo-controlled trial. Curr Ther Res. 2002;63(4):263–272. DOI.
  5. Zenk JL, Leikam SA, Kassen LJ, Kuskowski MA. Effect of lean system 7 on metabolic rate and body composition. Nutrition. 2005;21(2):179–185. PubMed.
  6. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007;18(9):629–634. PubMed.
  7. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci U S A. 1995;92(14):6617–6619. PubMed.
  8. Lardy H, Kneer N, Wei Y, Partridge B, Marwah P. Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone. Steroids. 1998;63(3):158–165. PubMed.
  9. Bobyleva V, Bellei M, Kneer N, Lardy H. The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis. Arch Biochem Biophys. 1997;341(1):122–128. PubMed.
  10. Hennebert O, Chalbot S, Alran S, Morfin R. Dehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes. J Steroid Biochem Mol Biol. 2007;104(3–5):326–333. PubMed.
  11. Kazihnitková H, Zamrazilová L, Hill M, Lapcík O, Pouzar V, Hampl R. A novel radioimmunoassay of 7-oxo-DHEA and its physiological levels. Steroids. 2007;72(4):342–350. PubMed.
  12. Sulcová J, Hill M, Masek Z, et al. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Physiol Res. 2001;50(1):9–18. PubMed.
  13. Sulcová J, Hampl R, Hill M, Stárka L, Novácek A. Delayed effects of short-term transdermal application of 7-oxo-dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant proteohormones in healthy male volunteers. Clin Chem Lab Med. 2005;43(2):221–227. PubMed.
  14. Hampl R, Sulcová J, Bílek R, Hill M. How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone influence thyroid function. Physiol Res. 2006;55(1):49–54. PubMed.
  15. Lardy H, Henwood SM, Weeks CE. An acute oral gavage study of 3beta-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats. Biochem Biophys Res Commun. 1999;254(1):120–123. PubMed.
  16. Henwood SM, Weeks CE, Lardy H. An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in rhesus monkeys. Biochem Biophys Res Commun. 1999;254(1):124–126. PubMed.
  17. Ihler G, Chami-Stemmann H. 7-oxo-DHEA and Raynaud’s phenomenon. Med Hypotheses. 2003;60(3):391–397. PubMed.
  18. Sageman S, Brown RP. 3-acetyl-7-oxo-dehydroepiandrosterone for healing treatment-resistant posttraumatic stress disorder in women: 5 case reports. J Clin Psychiatry. 2006;67(3):493–496. PubMed.
  19. Martinez-Brito D, de la Torre X, Colamonici C, Curcio D, Botrè F. 7-keto-DHEA metabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field. Drug Test Anal. 2019;11(11–12):1629–1643. PubMed.
  20. Martínez Brito D, Leogrande P, Colamonici C, Curcio D, Botre F, de la Torre X. Arimistane: degradation product or metabolite of 7-oxo-DHEA? Drug Test Anal. 2021;13(7):1430–1439. PubMed.
  21. Piper T, Fusshöller G, Geyer H, Toboc A, Dănilă MG, Thevis M. Detecting the misuse of 7-oxo-DHEA by means of carbon isotope ratio mass spectrometry in doping control analysis. Rapid Commun Mass Spectrom. 2020;34(12):e8776. PubMed.
  22. Food and Drug Administration. Amendments to the list of bulk drug substances that can be used to compound drug products in accordance with section 503A of the Federal Food, Drug, and Cosmetic Act; proposed rule. Federal Register. September 5, 2019;84:46688–46703 (FR Doc 2019-18951). govinfo.
  23. National Center for Biotechnology Information. 7-Keto-dehydroepiandrosterone, PubChem CID 193313; 7-Oxodehydroepiandrosterone 3-acetate, PubChem CID 9798229. PubChem; PubChem.
  24. 21 CFR 1308.13, Schedule III. eCFR.
  25. World Anti-Doping Agency. 2026 Prohibited List. WADA 2026 Prohibited List.
  26. Shi J, Schulze S, Lardy HA. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids. 2000;65(3):124–129. PubMed.
  27. Vecchione MB, Laufer N, Sued O, Corti M, Salomon H, Quiroga MF. 7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection. J Biomed Sci. 2020;27(1):20. PubMed.