Background

In additiona to the below information, you may also read and download the official 7-Keto broshure on additional information on how this amazing, all natural ingredient works and how you can benefit from it.

7-Keto is the registered trademark for the compound 3-Acetyl-7-oxo-dehydroepiandrosterone or 7-oxo DHEA. 7-Keto is a substance found naturally in the body. Its presence in human urine was documented in 1958. It is metabolized from the hormone DHEA, and like DHEA, it is known to decline with age. Supplementing with 7-Keto is simply putting back what time and Mother Nature has taken away.

Humanetics Corporation, the developer of 7-Keto, has invested significant time and money into a methodical research program that has spanned over the past 16 years. Among other things, this research has included rigorous toxicology, pharmacokinetic and human safety trials.

These studies strongly support that 7-Keto is non-toxic, cannot accumulate in the body over time, does not affect any hormone levels and is free of any serious side effects. Of even more importance, 7-Keto has been sold commercially as a dietary supplement since 1998 and, in this time, has not been linked to any serious adverse effects.

Being safe is of utmost importance; however, to market a compound requires that it have a benefit to the consumer. A patent was issued in 1994 for the use of 7-Keto for effecting weight loss and preventing weight gain. The patent is built upon the discovery that 7-Keto is a potent activator of 3 important thermogenic enzymes. These enzymes are known to play an important role in helping the body convert stored fat to energy.

The first of several randomized, double-blinded, placebo-controlled (“RDBPC”) weight loss clinical trials was conducted in 1999. This study indicated that 7-Keto was responsible for increasing weight loss over an eight week period by a factor of three times versus placebo.

A second trial was commissioned in 2000 to confirm these results. The second trial, also RDBPC, confirmed that weight loss over a eight week period could be increased by a factor of 3 times. Importantly, each of these studies confirmed that more than 80% of the weight lost was fat.

Each study controlled for diet, exercise and diuresis effects and both have been published in international peer reviewed journals.

There have been three additional double-blind weight loss trials conducted on 7-Keto and formulas which contain 7-Keto. All clinical data strongly supports the efficacy of this compound and its ability to increase metabolic rate and thus accelerate weight loss. The documented science behind 7-Keto provides strong support that it is safe and effective for helping in the weight loss process.

Additional Fat Loss Benefits

7-oxo-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-oxo-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-oxo-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-oxo-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].