Saturday, February 13, 2010

7-keto DHEA: is it safe? By Jerry Brainum

As regular readers of this publication know, 7-keto DHEA wasdeveloped and marketed to provide a form of DHEA that would bedevoid of certain side effects linked to regular DHEA usage.While such side effects are rare, most of them are associatedwith the fact that DHEA is a precursor for the primary sexhormones in the body, estrogen and testosterone. Thus, Dr. Henry Lardy, of the University of Wisconsin, searched for a DHEA analog that would provide the recognized health benefits of DHEA minus the major side effects. He found this in 3-acetyl-7-oxo-DHEA, better known as "7-keto DHEA."

Since then, several studies indicate that 7-keto DHEA has a powerful immune system enhancing effect; can increase the efficiency of cognitive function, i.e., memory and intelligence; and provide a thermogenic effect that may aid body fat loss. The latter effect, thermogenesis, induced by 7-keto DHEA may be superior to that of DHEA itself. While DHEA has consistently provided fat-loss benefits in animal studies, the studies with humans are far less conclusive.For example, in one human study with DHEA, men provided with 1,600 milligrams of oral DHEA daily showed some beneficial body
composition changes. However, a follow-up study later released, using the same dose of DHEA, failed to show any fat loss at all in another group of men. Older people provided with DHEA in far smaller doses--averaging 50-100 milligrams daily--show beneficial effects in lean mass (attributed to DHEA promotion of IGF-1 secretion), but virtually no changes in bodyfat levels.Those studies with older people also showed that while the effects of DHEA were beneficial, the fact that DHEA readily
converted into other hormones led to some possible problems. In women, DHEA usually converts into testosterone. Some older women showed increases in basal testosterone levels 9-fold over normal.
While many bodybuilders would rejoice over a comparable testosterone increase, in the older women this level of testosterone often led to a drop in protective high density lipoprotein cholesterol levels (HDL). When HDL levels decline (as they always do when using oral anabolic steroids), the risk of
cardiovascular disease onset increases.

In older and younger men, the fate of DHEA varied depending
of the existing hormonal milieu of the individual. Most often,
the DHEA converted into androstenedione, which is commercially
available as a so-called "pro-hormone." Androstenedione, while
being a direct precursor to testosterone, can also be converted
into either dihydrotestosterone (DHT) or estrogen, depending on
whether it encounters either the 5-alpha reductase enzyme that
converts it into DHT, or the aromatase enzyme that changes it
into estrogen. These conversions can lead to such side effects as
male pattern baldness (if genetically predisposed), acne, or
gynecomastia (male breasts).

The main benefit of 7-keto DHEA is that, because of its
structure, it isn't prone to conversion to either testosterone or
estrogen, thus eliminating any side effects associated with those
hormonal conversions. But while 7-keto appears to retain most of
the beneficial effects of straight DHEA, the question remains--just
how safe is 7-keto DHEA itself?

The toxicology and endocrine effects of 7-keto DHEA were
examined in studies presented at the Experimental Biology 98
meeting. In one study, the safety of 7-keto was examined in rats
and monkeys. In the rat study, 5 groups of rats were given 0,
250, 500, 1,000, or 2,000 milligrams per kilogram of 7-keto in a
single dose. After 15 days, the animals were killed and then
examined. The results showed that even a 2,000 milligram dose of
7-keto didn't produce any observable side effects in the rodents.
The researchers then examined the effects of 7-keto DHEA on
rhesus monkeys, a species closer to humans than rats (at least,
closer in some people). The monkeys were given 7-keto doses of
250, 500, and 1,000 milligrams per kilogram/BW on days 1,3, and
5. On days 7-11, the monkeys got 1,000 milligrams per kilogram of
7-keto. On the 12th day, the monkeys were killed. Once again,
autopsy of the monkeys showed "no adverse clinical or anatomical
pathology results." Other than the fact that they were killed, of

While these animal studies do appear to show a high safety
factor associated with 7-keto DHEA, it still doesn't completely
apply to human usage. So another study presented at the same
scientific conference looked at the hormonal and safety effects
of 7-keto DHEA in human subjects. The study consisted of men
between the ages of 18 and 49, 18 of whom took 7-keto DHEA, while
another 6 took a placebo or inactive substance for 8 weeks.
The dose of 7-keto were gradually increased to 100 milligrams,
twice daily during the final 4 weeks of the study.
The levels of hormones in the men before using 7-keto or the
placebo didn't differ either before or during treatment. However,
at the end of the study, the men taking genuine 7-keto DHEA
showed a small reduction in total testosterone levels in addition
to a clinically insignificant increase in free or active
testosterone levels. Since no significant changes occurred in any
hormone levels in those taking the real 7-keto DHEA, the study
authors concluded that,"This study shows that 7-keto DHEA is
well-tolerated at doses up to 200 milligrams a day, and does not
produce clinically important sex hormone changes in healthy men."

In another rat study presented at the conference, the
effects of 7-keto DHEA on memory was examined. The rats were
given a drug called scopolamine that interferes with the activity
of acetylcholine, a vital brain neurotransmitter required for
memory processes. In rats given 7-keto DHEA at a dose of just 20
milligrams per kilogram of bodyweight, the memory-interference
effects of scopolamine were nullified.

The same study also compared the effects of DHEA to 7-keto
DHEA for memory enhancement in rats trained to locate a foot
pedal. Control rats (not taking either DHEA or 7-keto) found the
pedestal in 34 seconds. Those taking DHEA found the pedestal in
22 seconds. In the 7-keto group, the rats located the pedestal in
7.6 seconds. This indicates that 7-keto shows memory-enhancing
effects that are clearly superior to that of regular DHEA.

Do soy isoflavones affect testosterone in men?

Soy isoflavones, such as genistein and others, have been
touted as having many important preventive health effects. These
include cardiovascular disease prevention through antioxidant
effects, and cancer prevention by interfering with the activity
of hormones such as estrogen that are associated with several
types of cancer in women.
These same isoflavones are linked to a lower prevalence of
prostate cancer in men. But since these isoflavones have a
chemical structure similar to estrogen, and since high levels of
estrogen may interfere with testosterone activity in men, the
question is: do soy isoflavones adversely affect androgen levels
in men?
This question is examined in two studies published in the
American Journal of Clinical Nutrition 1998;68(suppl):1531S-1533S.
In the first study, the effects of phytoestrogens or plant
estrogens (such as the isoflavones) were investigated in 13 older
women and 12 middle-aged men. The subjects were given 40 grams a
day of linseed oil containing a natural precursor to lignan, a
fiber known to have effects on hormones in the body, and 60 grams
a day of textured soy protein containing 45 milligrams of
isoflavones. The study subjects took the linseed for 4-6 weeks
and the soy protein for 4 weeks, both incorporated into bread
The results showed that serum gonadotropin levels (FSH and
LH) were suppressed by both the linseed and soy protein. The
concentrations of luteinizing hormone (LH), a gonadotropin that
controls testosterone synthesis in the body, dropped by 10-13%
with both the linseed and soy diets. While consuming the linseed,
the serum androgen levels dropped in 6 of the male subjects,
although there was no changes in urinary androgen levels. Both
total and low density lipoprotein cholesterol decreased with the
linseed intake, with a significant drop showing up in the female
Note that serum androgen levels i.e., testosterone levels,
were affected only by the linseed ingestion, although both the
linseed and soy did slightly lower gonadotropin output--which
dictates androgen levels in the body. Lignan, found in the
linseed, is a form of fiber, and this accounts for the beneficial
effects shown in lowering plasma lipids, such as total
cholesterol and LDL cholesterol. This would have a preventive
effect on cardiovascular disease onset.

Linseed also locks on to sex hormones in the body, promoting
the excretion of such hormones. This effect may have been more
potent with estrogens in this study, since the male subjects
showed lower serum androgen levels, but no greater excretion of
androgens through the urine. The drop in serum androgens in the
men was probably the result of both the linseed and soy slightly
interfering with gonadotropin release (LH). This may be due to
the estrogen-like structure of isoflavones, since estrogen is
known to be a potent inhibitor of gonadotropin release. In fact,
this is the main mechanism behind oral contraceptives, which
contain synthetic estrogens.
The decrease in gonadatropins shown in the study is
problematic, even though the men didn't appear to be adversely
affected as judged by the lack of change in androgen excretion.
Another study looked closer at this issue of how soy intake
affects hormone levels in the body. Unlike the previous study,
this study was more specific since it only focused on soy
Again, the study involved older women and younger men, who
ingested 12 ounces a day of soy milk with each meal for one
month. The isoflavone intake each day averaged 100 milligrams of
genistein and 100 milligrams of daidzein, considered the most
active and biologically important isoflavones found in soy. In
the women levels of estrogen, progesterone, and DHEA-S (a
circulating, nonactive bound-form of DHEA in the blood) declined
by 60%, 35%, and 30% after one month of consuming the soy.
The men showed no changes in serum testosterone levels. They
did, however, show decreased levels of a metabolite of
dihydrotestosterone (DHT) by 13% after 4 weeks of soy ingestion.
This is a beneficial effect, since DHT, a metabolite of
testosterone, is considered to be responsible for promoting male
pattern baldness, acne, and prostate enlargement. Thus, soy may
provide a DHT reduction effect without adversely affecting normal
testosterone synthesis or release.
In another study, this time involving rats, Chinese
researchers focused on the effects of the soy isoflavone,
daidzein on muscle growth and hormone levels in the rodents. The
daidzein was given to both male and female rats in a dose of 3
milligrams per each 100 grams of bodyweight. The daidzein was
injected subcutaneously into the animals for 16 days. Compared to
a control group not getting the daidzein, male rats showed a
bodyweight gain of 14.7 percent, most of which was muscle.
The rats on daidzein also showed lower nitrogen excretion
(an indication of greater protein retention in the body), and
increased levels of testosterone, estrogen, beta-endorphin, and
growth hormone. In castrated rats, no muscle increase occurred,
despite higher levels of both testosterone and growth hormone
after being injected with daidzein, most likely due to the still
low levels of testosterone, averaging only 8% of the levels shown
by "intact" rats. The study authors concluded that the muscle
growth effects of daidzein appear to be linked to normal
testosterone production.

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