Estrogen Steroid Hormone 7-Ketodehydroepiandrosterone 7-keto-DHEA
7-Ketodehydroepiandrosterone (7-keto-DHEA), also known as
7-oxoprasterone, is a steroid produced by metabolism of the
prohormonedehydroepiandrosterone (DHEA). 7-Keto-DHEA is not
directly converted to testosterone or estrogen, and has thus been
investigated as a potentially more useful relative of DHEA. It is
often used as the acetate ester prodrug 7-keto-DHEA acetate.
While in vitro and animal studies have suggested potential uses for
7-keto-DHEA in humans, there is currently limited scientific
evidence to support its use as a weight-loss aid, muscle-builder,
immune stimulant, or for any other clinical use. One randomized,
placebo-controlled research study on dieting and exercising healthy
overweight individuals found 7-keto-DHEA significantly increased
body-weight loss and fat-loss. 7-Keto-DHEA is marketed as a dietary
supplement with the implication that it may accelerate weight loss,
increase metabolism, enhance memory, or prevent age-related
When used in a topical (skin lotion) product 7-keto-DHEA caused
long-lasting changes in the body's levels of testosterone,
epitestosterone, estradiol, and other steroid hormones. Researchers
have raised concern that supplements may trigger positive tests for
The World Anti-Doping Agency lists 7-keto-DHEA as a prohibited
Effects and uses
7-Keto-DHEA is unique among other derivatives of DHEA because of
its oxygenated 7-position. This molecular configuration imparts
different characteristics to the molecule, and research reveals
7-keto-DHEA has multiple distinct effects in the body.
Increased metabolism/weight loss
7-Keto-DHEA demonstrates documented thermogenic activity in rats.
This is accomplished through the activation of three thermogenic
enzymes: Glycerol-3-Phosphate Dehydrogenase, Malic Enzyme and Fatty
Acyl CoA Oxidase. In keeping with the biological definition of
thermogenesis, all three of these enzyme activations drive
energy-producing substrates in a direction of less efficient ATP
production relative to heat production. The enzymes also promote
the utilization of fat stores for energy and heat production.
This is the basis for the ability of 7-keto-DHEA to enhance
thermogenesis and, through that mechanism, accelerate the
utilization of fat stores for energy.
A 2007 study demonstrated that administration of 7-keto-DHEA to
overweight adults in conjunction with a calorie-restricted diet
effectively reverses the decline in resting metabolic rate (RMR)
normally associated with dieting. 7-Keto-DHEA demonstrated an
ability to increase RMR by 1.4% above baseline levels and
demonstrated a 5.4% increase in daily RMR when administered with a
calorie-restricted diet. 7-Keto-DHEA achieves this thermogenic
effect without cardiovascular or central nervous system side
effects, which are commonly seen with stimulant-associated
Age-related immune enhancement
Although the aging process affects all of the segments of the
immune system, investigators have identified abnormalities in the
cellular or T-cell mediated immune function in the elderly.The
decline in T-cell immune function is associated with an increased
susceptibility to infections. For example, individuals with
age-related declines in cellular immunity have an impaired response
to influenza vaccine, making them more susceptible to getting the
“flu” even though they have had their flu shot.
In a clinical study presented at the Federation of American
Societies for Experimental Biology meeting in April 2004, the
effect of 7-keto-DHEA was evaluated in regard to its effect on
elderly immune function.
7-Keto-DHEA has been the subject of a series of toxicological
evaluations. These studies include: AMES Mutagenicity Test, Acute
Oral Dose LD50 in Rats, Escalating Dose Oral Gavage in Rhesus
Monkeys and 28 Day Oral Gavage in Rhesus Monkeys.
There were no adverse effects in any of these studies. This
pre-clinical work was followed by a Phase I safety study in humans
performed by Davidson and colleagues at the Chicago Center for
Clinical Research. This study was published in Clinical
Investigative Medicine and indicated that 7-keto-DHEA was safe for
human consumption at doses up to 200 mg per day for 4 weeks. As in
the toxicological studies, there were no serious adverse reactions
or hormone related side effects reported. Data on the safety of
long-term use (beyond 4 weeks) are lacking.
In addition, a complete pharmacokinetic analysis was completed as
part of this study. This pharmacokinetic analysis describes exactly
how the body absorbs, metabolizes, distributes and excretes
7-keto-DHEA. It reveals that 7-keto-DHEA is rapidly absorbed and
converted to its sulfate derivative, it reaches peak plasma
concentrations in 2.2 hours and has a half-life of 2.17 hours and
there is no accumulation with repeated dosing.
To date, there have been two pre-market notifications filed with
the FDA announcing intent to market 7-keto-DHEA as a dietary
ingredient. These notifications had to demonstrate to FDA’s
satisfaction that there is no issue with the safety of the subject
ingredient. The FDA had no objection, in each of these
notifications, to the marketing and sale of 7-keto-DHEA.
Similar to DHEA, 7-keto-DHEA is rapidly sulfated to 7-keto-DHEA
sulfate in the body. An analytical method was developed for
quantification of 7-keto-DHEA sulfate in human plasma. This was an
HPLC method, which utilized calibration curves for 7-keto-DHEA
sulfate in the range of 10 to 500 ng/ml.
Trough levels were measured after each escalating dose sequence; 0,
50, 100 and 200 mg per day. Trough plasma concentrations increased
proportionally to the daily dose. Mean trough levels (15.8 ng/ml)
after 1 week of dosing at 200 mg/day were similar to those
determined after 4 weeks of dosing (16.3 ng/ml). This indicated
that the ratio of the formation rate of this metabolite to its
elimination clearance is constant during multiple dosing and does
After a twelve-hour washout period, all 22 subjects were given a
single dose of 7-keto-DHEA at 100 mg and plasma levels were
obtained at 0.25, 0.50, 1.0, 2.0, 4.0, 6.0 and 12.0 hrs after the
dose. The mean plasma concentrations as measured in the study
demonstrated a peak plasma level of 158 ng/ml, which occurred at
2.2 hours after the dose. The average elimination half-life was
determined to be 2.17 hours. Based on the data, the dosing regime
of twice per day was recommended as the ideal dosing schedule with
steady state blood levels being the goal.
A one-compartment model was assumed with first order absorption and
no lag phase. The results of these simulations using this
pharmacokinetic model showed that there was good agreement between:
a) the simulated and measured means of the trough plasma levels,
and b) the plasma concentrations of a single 100 mg oral dose.
The pharmacokinetic analysis revealed that 7-keto-DHEA is rapidly
absorbed and converted to its sulfate derivative, it reaches peak
plasma concentrations in 2.2 hours, and it has a half-life of 2.17
hours. There is no accumulation with repeated dosing and, with
twice daily dosing, should reach a steady state plasma level in 11
To search for possible metabolites of DHEA that might have greater
biological activity, greater specificity, and fewer propensities to
form sex hormones, Dr. Lardy initiated a program assaying the
derivatives of DHEA. The activity of 150 of these metabolites was
monitored by measuring the induction of two thermogenic enzymes,
mitochondrial glycerol-3-phosphate dehydrogenase and cytosolic
The results of this landmark study were published in the journal
Steroids in 1998 and revealed that many of these steroids did not
induce the activity of these thermogenic enzymes, whereas the
7-keto-DHEA metabolite did. In fact, 7-keto-DHEA was 2.5 times more
active than DHEA at inducing the activity of these thermogenic
enzymes. In later work by Marenich, it was discovered that the
urinary excretion of 7-keto-DHEA declines with age in a similar
manner to its parent compound, DHEA. Based on these discovered
advantages, the 7-keto-DHEA metabolite was chosen for further study
as a weight loss ingredient.
1. All Essential Benefits/Effects/Facts &
7-oxodehydroepiandrosterone (7-oxo DHEA and more commonly known as
the brand name 7-keto) is one of three oxygenated metabolites of Dehydroepiandrosterone, and these three oxygenated metabolites interconvert with one
another but do not convert back into parent DHEA; 7-keto
supplementation is a way to get these three oxygenated metabolites
without using DHEA supplementation, and DHEA may form androgenic
and estrogenic hormones via an alternate metabolic pathway (which
7-keto does not participate in).
7-keto supplementation is mostly known to not be hormonal; it can
interact with steroid metabolism but the exact manner in which it
does it not fully elucidated. It does appear to have anti-cortisol
mechanisms as the enzymes that activate cortisol (from the
relatively inactive precursors of cortisone and corticosterone) are
the same that interconvert these oxygenated metabolites. Although
it appears to be anti-cortisol by its mechanisms, there is
insufficient evidence to support these mechanisms in the body
following oral supplementation.
Studies using 7-keto supplementation tend to note an increased
metabolic rate later on during a caloric restriction period (which
is secondary to reducing the rate of metabolic rate decline
associated with dieting, and becoming a relative increase) although
the quantity of data on this is pretty minimal if we exclude
studies with possible conflicts of interest or those that use
7-keto alongside a multitude of supplements.
7-keto appears to be a somewhat promising non-hormonal fat burning
agent but requires more evidence on both of those claims.
2. Things To Know
Also Known As 7-ketodehydroepiandrosterone, 7-oxodehydroepiandrosterone,
7-ketoDHEA, 7-oxoDHEA, 7-oxo, 7-keto. Do Not Confuse With Dehydroepiandrosterone (parent molecule)
3. Things to Note
For the most part, 7-keto supplementation is neither
estrogenic nor androgenic.
4. How to Take
Recommended dosage, active amounts, other details.
A typical supplemental dosage of 7-keto is 200-400mg daily in two
divided doses (100-200mg), some limited evidence suggests that
lower doses of 50-100mg may be effective for neural purposes.
The optimal dosing schedule and overall dose of 7-keto is not yet
known, and the above dosages are just based on what is known to
7-Keto DHEA (henceforth 7-keto) is a molecule derived from Serum DHEA (3β-Hydroxy-5-Androstene-17-one). 7-keto is synonymous with 7-oxo
or 7-oxo DHEA as the ketone group added contains any oxygen
molecule; 7-keto is more commonly used but is a brand name, while
7-oxo is the technically accurate name.
7-keto is naturally occurring (as DHEA is naturally occurring and
the enzymes that mediate the conversion present in the human body)
at a highly variable level of 0.280+/-0.227nmol/L in serum with
undetectable levels in some persons, with this one study
failing to note any differences between gender or age after
25 (DHEA itself is known to decline with age).
Supplementation of 7-keto is sometimes used with the acetyl ester,
known fully as 3β-Acetyl-7-ketoDHEA. Supplementation of 7-keto
is sometimes used in place of supplementation of DHEA if the
androgenic and estrogenic effects of DHEA are not desired, as
7-keto is incapable of converting to these active steroid hormones.
6. Safety and Toxicology
7-Keto does not appear to be associated with side-effects at up to
doses of 200mg daily for 4 weeks in otherwise healthy young males.