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7-Keto DHEA

Increased hepatic fat metabolism

7-Keto DHEA

Naturally occurring metabolite that declines with age

7-Keto DHEA - what is it?

  • The chemical compound 3-acetyl-7-oxo-dehydroepiandros-terone, is a naturally occurring metabolite of DHEA that is primarily produced in the adrenal glands and skin and some is also produced in the brain as well.
  • This DHEA metabolite is often just called 7-Keto which in fact is actually a brand name for this metabolite and the terms 7-Keto and 7-Keto DHEA are used interchangeably.
  • 7-Keto is actually responsible for many of the beneficial actions of the hormone intermediate DHEA
  • Does 7-Keto have hormone action - the answer is NO.
  • Unlike DHEA which can be converted into either testosterone or estrogen, 7-Keto is an inactive hormone metabolite.

Age decline in 7-Keto DHEA

Reference for the graph: Orentreich et al1

As 7-Keto DHEA drops, Cortisol becomes dominant

  • Many lay individuals know the side-effects of chronic use of prednisone ['steroids'] in the treatment of chronic asthma or arthritic conditions.
  • We know that this steroid prednisone, has a similar action to cortisol - weight gain, thinning of the skin, weakening of the bones etc
  • Thus as DHEA drops, there is a cortisol dominance
  • With higher levels of cortisol around your ability to get rid of body fat becomes that much harder.
  • 7-Keto DHEA has an antiglucocorticoid [anti-cortisol] effect4


Dieting and a drop in Resting Metabolic Rate [RMR]- increased thermogenesis

  • When you diet, your resting metabolic rate can drop significantly as your body thinks nutritional resources are scarce and you are starving.
  • 7-Keto can increase thermogenic [heat producing] proteins in the body


Reference for graph above: Zenk, J., J. Frestedt, et al. (2007)7

  • The Zenk et al study found the following and this related to the graph above:
    "During the placebo treatment, RMR decreased by 3.9% (75±111 kcal/day; mean±S.D.); however, RMR increased significantly by 1.4% (21±115 kcal/day) during the 7-Keto... treatment periods (compared to placebo, P=.001).7"
  • This is why dieting is counterproductive and counter-intuitive. Dieting results in a drop in your resting metabolic rate to conserve energy resources [a drop of 3.9% in this study] and this is why you don't shed the weight you want to so desperately.
  • Survival adaptations kick-in to decrease your use of calories to conserve energy and your body starts to wind-down the cellular mechanisms that control energy expenditure.
  • Enter 7-Keto a DHEA metabolite that has been shown in research studies to increase resting metabolic rate by 1.4% which is a significant amount that can help an individual to shed body fat.
  • Other papers to read with regard to thermogenesis and enzyme induction5, 6


Use of 7-Keto in Obesity

  • Most individuals gain weight as they age due to a decrease in resting metabolic rate [RMR] and other mechanisms. It is difficult indeed to lose weight as one gets older.
  • This compound should be used with an excellent diet such as the NutriDesk: Weight Management Diet and to use this diet in conjunction with an excellent resistance training program such as the NutriDesk: Resistance Training: Once-a-Week program.
  • According to Medline-Plus, the use of 7-Keto/DHEA in obesity has a 'B-Grade' classification in terms of research backing the use of this supplement for use in obesity. [B-Grade - Good scientific evidence for this use]
  • This grading of effectiveness can also be found on the conservative Mayo Clinic's website: Mayo Clinic: DHEA
  • A double-blind, placebo-controlled study on 30 individuals came to the following conclusion:
    'The results of the study suggest that 7-oxo-DHEA combined with moderate exercise and a reduced-calorie diet significantly reduces body weight and body fat compared with exercise and a reduced-calorie diet alone. In addition, 7-oxo-DHEA significantly elevated T3 levels but did not affect TSH or T4 levels, indicating that it does not adversely affect thyroid function in the short term2.'
  • A paper written by Hampl et al from the Institute of Endocrinology, Prague made the following statement:
    'It may thus be concluded that 7-oxo-DHEA is a potent thermomodulating agent, the final effect of which is comparable with thyroid hormones.4.'
  • The same paper by Hampl et al made the following comment about 7-Keto:
    'For years 7-oxygenated DHEA derivatives have been considered only biologically inactive products of DHEA metabolism. In the past decade, however, evidence has accumulated that they may act as potent local immunoprotective agents, being in fact responsible for many immunomodulatory and antiglucocorticoid [anti-cortisol] effects hitherto ascribed to DHEA4.'


Dose

  • Studies on healthy young men of up to 200 mg per day for 4 weeks were shown to be safe8.
  • The study by Davidson et al showed the following:
    "The administered steroid was not detected in the blood but was rapidly converted to 7-oxo-DHEA-S, the concentrations of which were proportional to dose. This steroid sulfate did not accumulate; plasma concentrations 12 hours after the 3beta-acetyl-7-oxo-DHEA dose at 7 and 28 days on the 200 mg/d dose were 15.8 and 16.3 microg/L respectively.8"
  • So if you are significantly overweight or obese and would like a helping hand to help increase thermogenesis and fat loss, at least you have this study to go by and limit the higher intake to 4 weeks or less.
  • There are no studies on the minimum effective dose to be used. In this instance, it would be prudent to limit dosing to 25 mg daily or even 2nd daily [three times a week]
  • The graph above showing a decline in urine excretion of the 7-Keto DHEA metabolite shows that excretion drops from 40 mcg [0.04 mg] to 10 mcg [0.01 mg] per day.
  • Consuming 25 mg is equal to 25, 000 mcg of this metabolite very much higher than that excreted in the urine. However, this 25 mg being consumed will become metabolized and converted into other compounds.We also know from studies on metabolism of 7-Keto DHEA is that this compound is rapidly sufated.
  • Anecdotal reports from users indicate that amounts of 10 - 15 mg a day may be just as beneficial in terms of well-being and weight loss. However, 25 mg seems to be the lowest dose of 7-Keto DHEA that can be obtained. An easy and cost-saving measure would be to purchase empty capsule shells from a pharmacy or health food store and transfer 1/2 the contents of the 25 mg capsule into the empty shell. You will then have a 12.5 mg dose that can be used daily or 2nd daily.
  • Using the lowest effective dose should always be the guiding principle.


Safety

  • This 7-Keto metabolite of DHEA is inactive and thus has no known hormonal activity.
  • 7-Keto is sold under licence by Humanetics Corporation. On this website is a reference to human studies done at the Chicago Center for Clinical Research: Humanetics: Human Studies on the safety of 7-Keto
  • Another link on the safety of 7-Keto DHEA can be found on Discovery Hospital's website: Discovery Communications: 7-Keto a better way to take DHEA?
  • 7-Keto DHEA is also a normal metabolite in the body that can be converted to other active metabolites that don't have hormonal [estrogen or testosterone] effects. In other words, 7-Keto DHEA is a bioidentical hormone that is found naturally in the body. Thus your body has the necessary enzymes to metabolize this compound.
  • An LD50 study in rats in which a dose that would kill 50% of the rats was determined to be 2 grams or more per kg of body weight. In humans this would involve the staggering intake of 160 grams [160, 000 milligrams] which is way beyond the recommended dose of 200 mg a day. Thus you would have to take 800 times the recommended dose to reach the LD50 dose for rats!
  • So is it save to use in individuals with hormone sensitive cancers such as prostate and breast cancer? The answer is unfortunately unknown. Theoretically, there should be no problem as 7-Keto is not converted to testosterone or estrogen but the use of 7-Keto in these specific circumstances has not been researched.
  • The dilemma is that with increasing abdominal fat levels you are much more likely to develop a cancer or diabetes which is associated with an increased risk of cancer. Central abdominal fat produces numerous chemicals [adipokines or cytokines] that increase your risk. 7-Keto helps to increase resting metabolic rate [RMR] as an aid to help you shed the excess weight.
  • So you need to weight up the pros and cons of the use of this metabolite just as you would have to do if you were faced with a surgical problem or a medical problem that required the use of a pharmaceutical that had significant side-effects to consider.
  • In pregnancy and lactation it pays to be on the cautious side and not use any supplementation that is not considered standard in antenatal and postnatal care.

Why don't we have more research on hormone use other than standard Hormone Replacement Treatment [HRT]

  • The simple answer is money!
  • If you can develop a hormone and then patent it so that you have many years for tremendous commercial gain, then you can afford to research the product and hope that there are benefits you can market to the medical establishment.
  • Is HRT without side-effects? Absolutely not! A multitude of life-threatening side effects can occur including thrombosis [blood clots] and possibly cancer.
  • Are there benefits of HRT? - You bet. There are numerous benefits including cardiovascular protection, neuro and bone protection.
  • The problem arises from the fact that natural [bioidentical] hormones cannot be patented. This means that the human race has only been exposed to modified compounds in the clinical setting to a large extent. Your body's receptors and metabolic pathways for hormone metabolism have all evolved to deal with your naturally occurring hormones and not to deal effectively with modified hormones and even artificial hormones designed to act as ligands for hormone receptors. When exposed to these modified/artificial hormones, your body's response will be to metabolize these as best as possible and often there may be numerous active intermediates as a result because the enzyme systems have just not evolved to deal with such artificial compounds.
  • The clinical use of bioidentical hormones that decrease with age has a great deal of potential to modify or prevent disease but the development of this area of medicine is being hampered by commercial realities.
  • The use of hormones in the clinical setting should be seen as no different to any other pharmaceutical created to treat or prevent disease. All medications have been designed to beat Mother Nature at her game in terms of disease states, infections etc. Trying to optimize the hormonal environment in the aging individual is simply trying to delay the senescence process by mimicking the optimal reproductive period in human lives which also happens to be a period of great health and vitality.

Link to Hormone and Hormone Metabolite References

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Hormone & Hormone Metabolite References