7-Keto

Also sold as: 7-Keto DHEA, 3-Acetyl-7-Oxo-DHEA, 7-oxo-DHEA

A DHEA metabolite that is genuinely not converted back to DHEA — confirmed by isotope ratio mass spectrometry rather than by a hormone panel — and therefore carries none of the parent steroid's androgenic chemistry. It also has the most complete human pharmacokinetics in this aisle, and its best resting-metabolic-rate result is 21 kcal a day.

How 7-Keto actually works

3-acetyl-7-oxo-DHEA, a DHEA metabolite modified at carbon 7 so it cannot be converted into testosterone or estrogen — the selling point, and the part that appears to hold. The thermogenic claim rests on induction of two hepatic enzymes, mitochondrial glycerophosphate dehydrogenase and malic enzyme, both of which increase the liver's capacity to burn substrate rather than store it. There is a second and less-advertised mechanism: it is a potent inhibitor of 11-beta-hydroxysteroid dehydrogenase type 1, the enzyme that regenerates active cortisol inside fat and liver, which is a genuinely interesting place to interfere.

Where to get 7-Keto

The evidence for 7-Keto

Graded by what exists behind each claim.

✅ Clinically validated

• In 22 healthy men given 50, then 100, then 200 mg/day for 28 days, the administered steroid was never detected in blood; the only detectable product was its 3-sulfate. Half-life 2.17 hours, time to peak 2.2 hours, no accumulation between day 7 and day 28, and total and free testosterone, DHT, estradiol, cortisol, thyroxine and insulin all unchanged and within range.
• In a randomized crossover trial in 40 overweight adults on a calorie-restricted diet, resting metabolic rate fell 3.9% on placebo and rose 1.4% on 7-Keto — 21 plus or minus 115 kcal/day, at p = 0.001. Statistically significant and physiologically negligible are both true of that number.
• A systematic review of 686 records found 4 eligible trials, all at low risk of bias. Two showed a significant fall in body weight, two reported an increase in resting metabolic rate, no serious adverse effects were reported, and the reviewers concluded that no clear answer can be given.

📊 Correlative data

• The advertised thermogenic mechanism is thyroid-dependent, which is in the original 1991 paper and on no label: induction of mitochondrial glycerophosphate dehydrogenase and cytosolic malic enzyme was smallest in thyroidectomized rats and highest in rats treated with triiodothyronine.

🧪 Theoretical / extrapolated benefits

• Its best-characterized pharmacology is not the one on the label. 7-keto-DHEA inhibits 11-beta hydroxysteroid dehydrogenase type 1 — the enzyme that regenerates cortisol from cortisone — potently and dose-dependently in differentiated human macrophages, in cells and in lysates.
• What circulates is a sulfate and every mechanistic result was obtained with the free steroid or its esters. The desulfation step inside a target tissue has never been measured in any species.

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What 7-Keto actually does

The molecule is 3-acetyl-7-oxo-dehydroepiandrosterone — 3-beta-acetoxyandrost-5-ene-7,17-dione — which is dehydroepiandrosterone carrying 2 modifications: a ketone at carbon 7 and an acetate ester at carbon 3. Both were put there deliberately, and the reason for each is a measured result rather than a marketing choice.

The advertised mechanism is 2 liver enzymes, and it is a real, transcriptional, dose-dependent finding. Feeding dehydroepiandrosterone to rats induces mitochondrial sn-glycerol-3-phosphate dehydrogenase to 3 to 5 times control within 7 days and confirms the older report of raised cytosolic malic enzyme. The induction is detectable at 0.01% of the diet, plateaus between 0.1% and 0.2%, and is completely blocked by simultaneous actinomycin D, which places it at transcription rather than at enzyme activity Su 1991. The 7-oxygenated derivatives do the same thing and the 7-oxo compounds do it harder than the parent steroid Lardy 1995.

What those 2 enzymes do together is the part worth understanding, because 'thermogenic enzyme' is otherwise just a word. Mitochondrial glycerol-3-phosphate dehydrogenase is the inner-membrane arm of the glycerol phosphate shuttle: it oxidizes cytosolic sn-glycerol-3-phosphate and passes the electrons straight to ubiquinone, entering the respiratory chain below complex I and therefore pumping fewer protons per electron than the malate-aspartate route would. Malic enzyme regenerates NADPH on the cytosolic side. Run the pair together and you have a cycle that oxidizes substrate at a reduced phosphate-to-oxygen ratio — carbon spent as heat rather than as ATP. That is a specific, checkable claim about a futile cycle, and it is what the word thermogenic is doing in this literature.

Now the condition on that mechanism, which is printed in the original 1991 paper and on no label anywhere. The ability of the steroid to induce mitochondrial glycerophosphate dehydrogenase and malic enzyme was smallest in thyroidectomized rats and highest in rats treated with triiodothyronine Su 1991. Both enzymes are classical thyroid-hormone-responsive genes; the steroid is amplifying a transcriptional signal that thyroid hormone sets. A compound whose mechanism is permissive on triiodothyronine does not have one effect size. It has an effect that scales with the reader's own thyroid status, and no human trial has ever stratified for it.

The second mechanism was found more than a decade later, has nothing to do with thermogenesis, and is the more interesting one. 7-keto-dehydroepiandrosterone is a substrate for 11-beta hydroxysteroid dehydrogenase type 1, the enzyme that regenerates cortisol from cortisone inside liver, fat and macrophages. In intact cells that enzyme interconverts 7-keto- and 7-beta-hydroxy forms reversibly, and when hexose-6-phosphate dehydrogenase is co-expressed to supply NADPH the equilibrium is pushed toward the 7-beta-hydroxy metabolite Nashev 2007. Being a substrate at that active site means competing there, and the competition was measured: 7-keto-dehydroepiandrosterone inhibits 11-beta hydroxysteroid dehydrogenase type 1 potently and dose-dependently in differentiated human THP-1 macrophages, in HEK-293 cells with or without hexose-6-phosphate dehydrogenase, and in cell lysates — while 7-ketocholesterol, tested alongside it, did not inhibit the enzyme in HEK-293 cells at all Balazs 2009. So this supplement has a documented action on local cortisol regeneration, which is a target the pharmaceutical industry spent a decade pursuing for metabolic disease, and it is not the action on the label.

Cell, rodent, human — and where it stops

Start with the human pharmacokinetics, because unusually for a supplement they exist and they are complete. Twenty-two healthy men took placebo or 3-acetyl-7-oxo-dehydroepiandrosterone in a randomized, double-blind, escalating-dose design: 50 mg/day for 7 days, a 7-day washout, 100 mg/day for 7 days, a 7-day washout, then 200 mg/day for 28 days. The administered steroid was never detected in blood. The only detectable metabolic product was 7-oxo-dehydroepiandrosterone-3-beta-sulfate, and its concentrations were proportional to dose. Time to peak was 2.2 hours, the half-life 2.17 hours, apparent clearance 172 L/h and apparent volume of distribution 540 L. The 12-hour trough on 200 mg/day was 15.8 µg/L at day 7 and 16.3 µg/L at day 28, so nothing accumulated Davidson 2000.

That single finding reorganizes the whole evidence base. What is swallowed is a prodrug; what circulates is a sulfate. Every cell and rodent result above was obtained with free 7-oxo-dehydroepiandrosterone or its esters Lardy 1995 Lardy 1998, and the bridge between the circulating sulfate and the active free steroid is a sulfatase step inside a target tissue that nobody has measured in a person.

The hormone question was answered in the same study, and answered again by a better method. Total testosterone, free testosterone, dihydrotestosterone, estradiol, cortisol, thyroxine and insulin were unaffected and stayed within the normal range at up to 200 mg/day for 4 weeks Davidson 2000. Note what was measured there: thyroxine, not triiodothyronine — and triiodothyronine is the hormone the rat mechanism depends on Su 1991. Separately, urine collected before and after a single administration to healthy volunteers was run by gas chromatography coupled to isotope ratio mass spectrometry, which confirmed that there is no formation of dehydroepiandrosterone from 7-keto-dehydroepiandrosterone Martinez-Brito 2019. A carbon-isotope answer is a stronger answer than a hormone panel, and it settles the back-conversion question that the whole 'non-androgenic' claim rests on.

Then the efficacy number, and it deserves to be read slowly. In a randomized, double-blind, placebo-controlled crossover trial, 45 overweight adults enrolled and 40 completed — 30 women and 10 men, mean age 38.5 years, mean body mass index 32.0 kg/m2 — taking 7-Keto, a multi-ingredient combination, or placebo for 7-day periods on a calorie-restricted diet, with resting metabolic rate measured by indirect calorimetry. On placebo, resting metabolic rate fell 3.9%, which is 75 plus or minus 111 kcal/day. On 7-Keto alone it rose 1.4%, which is 21 plus or minus 115 kcal/day, at p = 0.001 against placebo Zenk 2007.

Twenty-one kilocalories a day, with a standard deviation of 115. The effect is about one fifth of its own dispersion. Over the 7-day period it is 147 kcal in total, which is roughly 16 g of fat. The result is statistically significant and physiologically negligible, and both of those are true at once. That is the honest translation of the thermogenic mechanism into a person, and it is the number the category never prints.

The systematic review is the last word so far and it is short. A search of Medline, Embase, the Cochrane Library, CINAHL, Web of Science, Scopus, ICTRP and ClinicalTrials.gov returned 686 records and yielded 4 eligible studies, all judged at low risk of bias. Half showed a significant reduction in body weight; 1 found a fall in body fat percentage; 1 reported a fall in body mass index; 2 reported an increase in resting metabolic rate; no serious adverse effects were reported; and the reviewers concluded that no clear answer can be given Jeyaprakash 2023. Four trials for a compound that has been on shelves since the late 1990s is itself the finding.

7-Keto — which form, and does it matter

What is in the capsule is never what is in the blood, and this is one of the few supplements where that has been demonstrated rather than assumed. The label says 7-Keto or 7-Keto DHEA. The material is the 3-acetate ester. The plasma species is the 3-sulfate Davidson 2000. Three different molecules, one name.

Why the acetate, specifically. The structure-activity work behind this product is unusually explicit. On the rat thermogenic-enzyme assay, activity is retained by the 17-beta-hydroxy reduction and by 7-alpha or 7-beta hydroxylation, and is considerably enhanced when the 17-hydroxy or 17-carbonyl steroid is converted to the 7-oxo derivative. Both short-chain and long-chain acyl esters of 7-oxo-dehydroepiandrosterone are active when fed, and 7-oxo-dehydroepiandrosterone-3-sulfate is as active as the free steroid or its 3-acetyl ester — whereas dehydroepiandrosterone-3-sulfate is much less active than dehydroepiandrosterone itself. Steroids carrying a 3-carbonyl, a 7-methyl, a hydroxyl at position 1, 2, 4, 11 or 19, or a saturated B ring were inactive Lardy 1998. The 3-position tolerates conjugation for the 7-oxo series and does not for the parent. That is a chemical reason for the marketed form, not a commercial one.

The conversion chain, step by step. An acetate ester at carbon 3 is cleaved by carboxylesterase in the gut wall and liver — a hydrolysis step, and a fast one — and the freed 3-hydroxy group is immediately conjugated by a cytosolic sulfotransferase. That sequence is why first-pass metabolism leaves only the sulfate to measure Davidson 2000. The oral bioavailability question for this product is therefore not how much crosses the gut. It is what fraction of the circulating sulfate is desulfated again inside a liver or fat cell, and no study in any species has measured it.

What the pharmacokinetics say about the dosing schedule, which no label follows. A half-life of 2.17 hours means 5 half-lives is under 11 hours: a morning dose is essentially gone by evening, and the 12-hour trough was identical at day 7 and day 28, confirming no accumulation Davidson 2000. An apparent volume of distribution of 540 L in a roughly 80 kg man is about 6.8 L/kg, which is far larger than body water and says the sulfate leaves plasma for tissue rather than sitting in it. Put those together and a once-daily 100 mg capsule gives a 2-hour spike and then 16 hours of nothing, while the human trial that produced the only positive resting-metabolic-rate number dosed across the day Zenk 2007. Whether twice- or thrice-daily dosing changes the result has never been tested, and it is the cheapest unanswered question about this product.

Dose and route, briefly. The human studies used 100 to 200 mg/day Davidson 2000 Zenk 2007, and the retail capsule is usually 100 mg — one of the rare cases where the shelf dose and the studied dose agree. There is no injectable form and no reason to want one; the pharmacology of interest is the hydrolysis and the sulfation, and both happen on the oral route by design.

And it is not dehydroepiandrosterone. It is sold beside it, at a higher price, and the difference is the point: 7-keto is not converted back to dehydroepiandrosterone in a person Martinez-Brito 2019, so it carries none of the parent steroid's androgenic or estrogenic downstream chemistry. Anyone buying one expecting the other has bought the wrong molecule in both directions.

What would have to be true, and how you would know it was not

1. Cortisol, measured the way the mechanism demands rather than the way it is usually measured. Because this compound inhibits 11-beta hydroxysteroid dehydrogenase type 1 Balazs 2009, predict a fall in the urinary tetrahydrocortisol-to-tetrahydrocortisone ratio within 2 weeks at 100 to 200 mg/day, with morning serum cortisol unchanged. The enzyme acts inside tissue, so the ratio should move before the circulating hormone does. If the ratio does not move at all, the 11-beta hydroxysteroid dehydrogenase mechanism is not operating at supplement doses, and the second half of this page's mechanism section is wrong.

2. Free T3, free T4 and TSH at baseline and 8 weeks, with the resting metabolic rate result read against free T3 rather than against the group mean. Predict free T4 and TSH unchanged, consistent with the thyroxine measurements in the pharmacokinetic study Davidson 2000. Predict that whatever metabolic-rate effect exists is larger in people in the upper half of the free T3 reference range, because the enzyme induction was smallest in thyroidectomized rats and largest in triiodothyronine-treated ones Su 1991. If a euthyroid person at the bottom of the free T3 range gets the same response as one at the top, the thermogenic-enzyme mechanism is not the mechanism.

3. Resting metabolic rate by indirect calorimetry, with a pre-registered effect size. Predict a change on the order of 20 to 60 kcal/day, not 200 Zenk 2007. This is the prediction that cuts against the product, and it is falsifiable in either direction: if a properly powered 7-day crossover reproduces more than 100 kcal/day for 7-keto alone, the number on this page is wrong and the compound is more interesting than it looks.

4. Free testosterone, total testosterone and estradiol at 4 and 8 weeks. Predict no change at 100 to 200 mg/day Davidson 2000, and predict no dehydroepiandrosterone formation on isotope-ratio testing Martinez-Brito 2019. This prediction is useful precisely because it is expected to be negative: a rise in testosterone on a 7-keto product is evidence that the capsule contains something other than what it says.

5. Fasting insulin and HOMA-IR at 12 weeks. Inhibitors of 11-beta hydroxysteroid dehydrogenase type 1 were developed as insulin sensitizers, so if this compound reaches that enzyme at achievable concentrations Balazs 2009, fasting insulin is the endpoint most likely to move — and it is not an endpoint any of the 4 trials in the systematic review was designed around Jeyaprakash 2023. Predict a small fall, and predict it is more reproducible than the weight result.

What nobody has tested yet

Nobody has measured what fraction of the circulating sulfate is converted back to the active steroid inside a tissue. The only human pharmacokinetics describe 7-oxo-dehydroepiandrosterone-3-sulfate Davidson 2000 and every mechanistic result describes the free steroid or its esters Lardy 1995 Lardy 1998. The step joining them is assumed, not measured, in any species.

Nobody has run this against thyroid status. The rat data say the induction depends on triiodothyronine Su 1991, the human safety study measured thyroxine only Davidson 2000, and the obvious study — the same 7-day crossover stratified by free T3 — has never been done. It would explain the heterogeneity in the 4 trials that exist Jeyaprakash 2023 more cheaply than a new trial would.

Nobody has measured the 11-beta hydroxysteroid dehydrogenase endpoint in a person taking the supplement. The inhibition is documented in human macrophages and in cell lysates Balazs 2009, and the interconversion is documented in intact cells Nashev 2007. No trial has drawn a urinary steroid profile on anyone taking 100 mg a day, which means the best-characterized pharmacology this molecule has is entirely unmeasured in its actual users.

Nobody has dosed a human for longer than a month at the top of the range. The longest documented exposure in the pharmacokinetic literature is 28 days at 200 mg/day in 16 men Davidson 2000. Whatever the 4 reviewed trials ran for Jeyaprakash 2023, no long-term human safety data exist for a compound that inhibits an enzyme controlling intracellular glucocorticoid availability.

And nobody has reported the resting-metabolic-rate result by sex. The crossover cohort was 30 women and 10 men Zenk 2007, sex differences in resting metabolic rate and in 11-beta hydroxysteroid dehydrogenase expression are both well described, and the pharmacokinetic study enrolled men only Davidson 2000. There is no published number for what this does in a woman on its own.

7-Keto — its own safety story, not its category's

The non-hormonal claim is the one claim here with a real answer, and it holds. Isotope-ratio mass spectrometry confirms no formation of dehydroepiandrosterone from 7-keto-dehydroepiandrosterone Martinez-Brito 2019, and total and free testosterone, dihydrotestosterone, estradiol, cortisol, thyroxine and insulin were all unchanged and in range at up to 200 mg/day for 4 weeks in 22 men Davidson 2000. That is a better-evidenced negative than most supplements can offer.

And it is a prohibited substance in sport regardless. 7-keto-dehydroepiandrosterone is included in section S1 of the World Anti-Doping Agency List of Prohibited Substances, and it is naturally present in urine, which makes detection of its misuse a technical problem rather than a simple one Martinez-Brito 2019. The same work described 10 previously unreported metabolites, including reduced and hydroxylated structures that are not part of the routine antidoping steroid profile and that showed considerable responses in all fractions analyzed, and found that some deoxidation products — arimistane, androst-5-ene-7,17-dione, among them — most probably arise during sample preparation or instrumental analysis. A tested athlete taking this can produce a finding whose interpretation depends on the laboratory's method. Anyone subject to drug testing should treat this as a banned steroid, not as a supplement.

The interaction that actually matters is the one nobody lists. This compound inhibits the enzyme that regenerates cortisol from cortisone in liver, adipose tissue and macrophages Balazs 2009. That places anyone taking exogenous glucocorticoids, anyone with adrenal insufficiency, and anyone currently being investigated for a cortisol disorder in a different position from a healthy adult — because the compound perturbs the exact system the investigation is measuring. A urinary steroid profile drawn while somebody is taking 7-keto is not a clean test.

Thyroid is the second conversation, for the same reason the mechanism section gave. The enzyme induction is triiodothyronine-dependent Su 1991 and the human study measured thyroxine Davidson 2000. On levothyroxine or any thyroid replacement, that is a prescriber's call rather than a self-directed experiment.

What is genuinely unknown is duration. The systematic review found 4 trials, all at low risk of bias, and none reported serious adverse effects Jeyaprakash 2023; the longest documented dosing anywhere is 28 days Davidson 2000. That is a reassuring short-term record and no evidence at all about a year. There are no controlled data in pregnancy or lactation for a steroid metabolite that acts on intracellular glucocorticoid handling, and that is the population in which an absence of data should be read as a no. Nothing here is medical advice, and none of these statements has been evaluated by the Food and Drug Administration.

Sources read for this page

• Su CY. Induction of hepatic mitochondrial glycerophosphate dehydrogenase in rats by dehydroepiandrosterone.. J Biochem 1991 · PMID 1837017
• Lardy H. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone.. Proc Natl Acad Sci U S A 1995 · PMID 7604042
• Lardy H. Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone.. Steroids 1998 · PMID 9558717
• Nashev LG. Hexose-6-phosphate dehydrogenase modulates 11beta-hydroxysteroid dehydrogenase type 1-dependent metabolism of 7-keto- and 7beta-hydroxy-neurosteroids.. PLoS One 2007 · PMID 17593962
• Balazs Z. Hexose-6-phosphate dehydrogenase modulates the effect of inhibitors and alternative substrates of 11beta-hydroxysteroid dehydrogenase 1.. Mol Cell Endocrinol 2009 · PMID 19010388
• Davidson M. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers.. Clin Invest Med 2000 · PMID 11055323
• Zenk JL. 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 · PMID 17418559
• Jeyaprakash N. A systematic review of the impact of 7-keto-DHEA on body weight.. Arch Gynecol Obstet 2023 · PMID 36566478
• Martinez-Brito D. 7-keto-DHEA metabolism in humans. Pitfalls in interpreting the analytical results in the antidoping field.. Drug Test Anal 2019 · PMID 31701664

How you would know if it worked

7-Keto — safety & side effects

Bloodwork to run alongside 7-Keto

Baseline first, then again at 8–12 weeks.

The Metabolic Health & Prediabetes panel covers these in one order — 8 markers, $81.45 with the discount applied.

Check results you already have → · All 103 markers A–Z

7-Keto — frequently asked questions

What 7-Keto is used for

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