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Life Extension Magazine

LE Magazine May 2005
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7-Keto DHEA The Fat-Burning Metabolite of DHEA

By Dave Tuttle

Cholesterol Reduction and Other Benefits

Scientists have known for some time that DHEA supplementation can decrease blood cholesterol levels.15 The question then became which DHEA metabolite or metabolites are responsible for this action. A study at the Institute of Endocrinology in Prague, Czech Republic, revealed that 7-Keto contributes to this cholesterol-lowering activity.16 Ten volunteers aged 27 to 72 years applied a gel containing 25 mg of 7-Keto to their abdominal skin for five consecutive days.

While the subjects’ reduction in total cholesterol was of only borderline significance, very beneficial changes occurred in cholesterol composition. Beneficial HDL (high-density lipoprotein) rose significantly, even though harmful LDL (low-density lipoprotein) was only slightly diminished. These changes produced a strong improvement in the atherogenic index, which measures the risk of cardiovascular disease. A significant rise in beneficial apolipo-protein A-1, a protector of cardiovascular health, also occurred. These findings indicate that 7-Keto has cholesterol-lowering effects at a dosage that is even lower than that required to achieve the same effects with DHEA.16

A study with mice suggests that 7-Keto can boost memory as well.17 In this experiment, researchers at the University of Wisconsin in Madison trained young mice in the use of a water maze. They found that a single injection of 7-Keto (at 24 mg/kg of body weight) reversed experimentally induced memory loss. The scientists then fed 7-Keto or DHEA to old mice that had learned the maze. They discovered that memory of the water-maze training was retained during a four-week test period in the mice receiving 7-Keto but not in those treated with DHEA.17

7-Keto may also provide benefits for people with Raynaud’s syndrome, a condition marked by cold, painful fingers and toes. Medical researchers believe that Raynaud’s represents an abnormal response to cold by blood vessels. A paper published in Medical Hypotheses suggests that 7-Ketomay be helpful in preventing primary Raynaud’s attacks by increasing the basal metabolic rate.18 Given what is known know about 7-Keto’s ability to boost levels of thyroid hormone T3, this hypothesis seems reasonable. Further studyis warranted.

Combination DHEA and 7-Keto Therapy

Because of the overwhelming scientific literature supporting the benefits of DHEA supplementation in older people, Life Extension has advocated DHEA replacement therapy since 1981. While this has been a dramatic step forward for many people, the newest research shows that additional benefits can be obtained through a combination of DHEA and 7-Keto therapy.

“Co-supplementation with these hormones can be a very important part of hormone-restorative therapy,” explains Dr. Dzugan. “There are times when the use of regular DHEA can boost estrogen and testosterone concentrations to appropriate levels but still not be enough to put DHEA in the optimal range. Supplementation with 7-Keto can permit additional progress in optimizing immune function, cholesterol reduction, weight loss, and memory enhancement without raising these ‘downstream’ hormones, estrogen and testosterone, to an inappropriate degree.

“Also, women sometimes experience hair loss or growth in facial hair when they take large amounts of DHEA due to its conversion to testosterone. The use of 7-Keto and a smaller, more suitable intake of DHEA can eliminate this problem while still giving them many of DHEA’s benefits, which in reality are due to its 7-Keto metabolite. Moreover, DHEA supplementation is contraindicated for hormone-sensitive cancers such as prostate cancer and many breast cancers. In these instances, dosing with 7-Keto is a viable alternative.”

As shown earlier in Figure 1, average blood levels of 7-Keto decline with age. This reduction is responsible for some of the negative changes that occur during our mature years. As a result, 7-Keto supplementation becomes increasingly important with age.

The best time to take 7-Keto is in the morning, when the body’s natural production peaks. This ensures that more plentiful levels of this hormone will be available consistent with the body’s natural cycle.

People should avoid taking 7-Keto in the evening, as high blood levels at bedtime could stimulate brain activity and cause insomnia. Those who take more than one capsule daily should consume all of them around breakfast time. Because 7-Keto is a natural hormone metabolite and is easily assimilated, it can be taken with a meal or on an empty stomach. Consistent daily dosing is important to ensure a stable level of 7-Keto in the bloodstream.

With all of the newly recognized benefits of 7-Keto, this workhorse metabolite is sure to become a standard part of hormone replacement therapy in the future. By offering many of the advantages of DHEA supplementation without conversion to estrogen and testosterone, 7-Keto affords older adults the opportunity to further promote their health and longevity even when their levels of the so-called “downstream” hormones are already optimal. Moreover, considering 7-Keto’s demonstrated ability to improve body composition, it is highly likely that this DHEA metabolite will become a staple supplement for many aging adults. After all, how many among us could not afford to lose a few pounds around the middle?

References

1. Gallagher TF. Adrenocortical carcinoma in man; the effect of amphenone on individual ketosteroids. J Clin Endocrinol Metab. 1958 Sep;18(9):937-49.

2. Marenich LP. Excretion of testosterone, epitestosterone, androstenedione and 7-ketodehydroepiandrostenedione in healthy men of different ages. Probl Endokrinol (Mosk). 1979 Jul;25(4):28-31.

3. Davidson M, Marwah A, Sawchuk RJ, et al. Safety and pharmacokinetic study with escalating doses of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy male volunteers. Clin Invest Med. 2000 Oct;23(5):300-10.

4. Lardy H, Henwood SM, Weeks CE. An acute oral gavage study of 3beta-acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in rats. Biochem Biophys Res Commun. 1999 Jan 8;254(1):120-3.

5. Henwood SM, Weeks CE, Lardy H. An escalating dose oral gavage study of 3beta-acetoxyandrost-5-ene-7, 17-dione (7-oxo-DHEA-acetate) in rhesus monkeys. Biochem Biophys Res Commun. 1999 Jan 8;254(1):124-6.

6. Lardy H, Partridge B, Kneer N, Wei Y. Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone. Proc Natl Acad Sci USA. 1995 Jul 3;92(14):6617-9.

7. Zenk JL, Kuskowski MA. The use of 3-acetyl-7-oxo-dehydroepiandrosterone for augmenting immune response in the elderly. Presented at meeting of FASEB, April 17, 2004.

8. Hampl R, Lapcik O, Hill M, et al. 7-Hydroxydehydroepiandrosterone—a natural antiglucocorticoid and a candidate for steroid replacement therapy? Physiol Res. 2000;49 Suppl 1S107-12.

9. Liu YY, Yang N, Kong LN, Zuo PP. Effects of 7-oxo-DHEA treatment on the immunoreactivity of BALB/c mice subjected to chronic mild stress. Yao Xue Xue Bao. 2003 Dec;38(12):881-4.

10. Lardy H, Kneer N, Wei Y, Patridge B, Marwah P. Ergosteroids. II: Biologically active metabolites and synthetic derivatives of dehydroepiandrosterone. Steroids. 1998 Mar;63(3):158-65.

11. Bobyleva V, Kneer N, Bellei M, Battelli D, Lardy HA. Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone. J Bioenerg Biomembr. 1993 Jun;25(3):313.21.

12. Bobyleva V, Bellei M, Kneer N, Lardy H. The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis. Arch Biochem Biophys. 1997 May 1;341(1):122-8.

13. Kalman DS, Colker CM, Swain MA, Torina GC, Shi Q. A randomized, double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Therap Res. 2000;61(7):435-42.

14. Karakoc A, Ayvaz G, Taneri F, et al. The effects of hypothyroidism in rats on serum leptin concentrations and leptin mRNA levels in adipose tissue and relationship with body fat composition. Encocr Res. 2004 May;30(2):247-55.

15. Nestler JE, Barlascini CO, Clore JN, Blackard WG. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab. 1988 Jan;66(1):57-61.

16. Sulcova J, Hill M, Masek Z, et al. Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men. Physiol Res. 2001;50(1):9-18.

17. Shi J, Schulze S, Lardy HA. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids. 2000 Mar;65(3):124-9.

18. Ihler G, Chami-Stemmann H. 7-oxo-DHEA and Raynaud’s phenomenon. Med Hypotheses. 2003 Mar;60(3):391-7.