7-Keto DHEA Capsules

7-keto-dehydroepiandrosterone (7-keto-DHEA), also called 7-oxo-DHEA, is a metabolite of the steroid hormone precursor DHEA.^[1] DHEA, in the form of its sulfate conjugate (DHEA-S), is the most abundant steroid present in human blood and has generated interest as a potential therapeutic agent in age-related and other health conditions based on studies in preclinical models.^[2][3] However, DHEA is converted to androgens and estrogens, including testosterone and estradiol, and can result in sex steroid-associated side effects, such as polycystic ovaries and signs of masculinization in females.^[2][3][4] Thus, 7-keto-DHEA has arisen as a promising alternative to DHEA because metabolites of DHEA, including 7-keto-DHEA, may mediate some the biological functions and physiological and clinical benefits of DHEA.^[5] Importantly, unlike DHEA, 7-keto-DHEA is not converted into testosterone or estradiol.^[2][6]

Like DHEA, 7-keto-DHEA is produced endogenously in the adrenal glands, gonads, brain, liver, and skin.^[5][7] Physiological (serum) levels of 7-keto-DHEA vary widely among individuals; however, they appear to be similar among men and women.^[8] In a 2007 study of 215 individuals without endocrine disorders (91 males and 124 females; aged 5-71 years), no significant differences in 7-keto-DHEA levels were observed between males and females.^[8] The overall mean (±SD) and median of 7-keto-DHEA levels were 0.280 (±0.39) nmol/L and 0.239 nmol/L, respectively.^[8]

At puberty, the level of 7-keto-DHEA rapidly increases and plateaus until approximately 35 years of age; it then decreases with increasing age.^[8][9] Because the level of 7-keto-DHEA is directly related to the level of DHEA, decreasing 7-keto-DHEA levels are likely a reflection of decreasing DHEA levels, which are also known to decrease with age.^[10] Therefore, it is believed that DHEA and 7-keto-DHEA supplementation may help the body maintain a more youthful state and may be beneficial to individuals with low levels of DHEA or 7-keto-DHEA.^[6]

7-keto-DHEA is typically administered orally as an acetyl ester of 7-oxo-DHEA (3β-acetyl-7-oxo-DHEA or 7-oxo-dehydroepiandrosterone-3 acetate^[11] ); this form (also often referred to as 7-keto-DHEA) is less susceptible to oxidation than 7-keto-DHEA during manufacturing and storage.^[3][12][13] After administration, the 7-oxo-DHEA acetyl ester is rapidly converted to 7-oxo-DHEA-sulfate (7-keto-DHEA-S) in a concentration proportional to the administered dose.^[6][14]

7-keto-DHEA has been shown to promote weight loss and increase resting metabolic rate in people who are overweight.^[15][16][17] In two placebo-controlled double-blind trials, participants who received 7-keto-DHEA acetyl ester lost significantly more weight than those who received placebo (2000 study: mean, -2.88 kg vs -0.97 kg, respectively; P=.01^[15] and 2002 study: mean, -2.15 kg vs -0.72 kg, respectively; P=.038^[16]).

Another placebo-controlled double-blind study with a 3-way cross-over design evaluated the effect of 7-keto-DHEA on resting metabolic rate in adults who were overweight.^[17] Participants received the 7-keto-DHEA acetyl ester (50 mg twice daily), HUM5007 (another 7-keto-DHEA acetyl ester containing supplement; 50 mg twice daily), or placebo in conjunction with a calorie-restricted diet for 7 days (each study period was followed by a 7-day washout period).^[17]

7-keto-DHEA treatment increased resting metabolic rate compared with baseline levels (3.4% increase with HUM5007 and 1.4% increase with 7-keto-DHEA).^[17] Treatment with either 7-keto-DHEA product significantly increased the resting metabolic rate (+134 kcal/day [7.3% increase] with HUM5007 and +96 kcal/day [5.4% increase] with 7-keto-DHEA) compared with placebo (-75 kcal/day [3.9% decrease]; P=.001 for both).^[17] Therefore, in combination with a calorie-restricted diet, 7-keto-DHEA appears to not only reverse the decline in resting metabolic rate associated with dieting but to enhance it and may benefit individuals who are overweight or with impaired energy expenditure.^[17]

7-keto-DHEA is believed promote weight maintenance or loss by increasing resting metabolic rate.^[17] On a molecular level, studies in preclinical animal models showed that 7-keto-DHEA increased the activity of enzymes involved in thermogenesis, including mitochondrial and cytosolic sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme.^[2][3][18] It also increased the rate of mitochondrial substrate oxidation and the activity of enzymes involved in fatty acid oxidation, including liver catalase and fatty acyl-CoA oxidase.^[18] It is unknown how 7-keto-DHEA mediates these changes; however, it is believed the metabolites of 7-keto-DHEA, 7α-OH-DHEA and 7β-OH-DHEA, may be involved.^[3][18]

Other effects of DHEA and 7-keto-DHEA, such as increased immune response, may also be mediated by 7α-OH-DHEA and 7β-OH-DHEA.^[2][3] Both 7α-OH-DHEA and 7β-OH-DHEA have been shown to inhibit the reduction of cortisone to cortisol in human skin; however, 7β-OH-DHEA was seven times more potent than 7α-OH-DHEA.^[19] Thus, it is possible that part of the physiological activity of 7-keto-DHEA and its metabolites is mediated by their ability to act as anti-glucocorticoids.^[19] However, given that cortisone and cortisol are present in substantially higher levels than 7α-OH-DHEA and 7β-OH-DHEA, these 7-keto-DHEA metabolites may not have a systemic effect, but they may act locally in tissues through autocrine or paracrine processes.^[19]

7-keto-DHEA may increase T3 levels.^[16] People interested in starting 7-keto-DHEA supplementation, particularly those who have a thyroid disorder or who are taking thyroid hormone, should consult a physician.

7-keto-DHEA may lower blood pressure.^[6] Individuals with low blood pressure should consult with a physician prior to use of this supplement.^[6]

At the time of writing, there were no other reported contraindications/precautions for 7-keto-DHEA. Individuals with known allergy to any of the capsule components or DHEA should not use this product.

At the time of writing, there were no reported interactions for 7-keto-DHEA. It is possible that unknown interactions exist.

Adverse reactions and side effects of 7-keto-DHEA may include but are not limited to gastrointestinal upset/nausea, headache, decreased hemoglobin and hematocrit levels, sensitivity to mosquito bite, vertigo, and increased serum triiodothyronine (T3) levels.^[6][16][17] Short-term studies in preclinical models revealed no adverse effects with 7-keto-DHEA.^[20][21][22] Short-term studies in humans 7-keto-DHEA, administered as 3β-acetyl-7-oxo-DHEA, is safe and well tolerated.^[6] The long-term safety of 7-keto-DHEA, in any form, or its metabolites have not been conducted.

A safety study of 7-keto-DHEA administered as the acetyl ester (dose escalation: 50 mg/day for 7 days, 100 mg/day for 7 days, and 200 mg/day for 28 days) concluded that 3-acetyl-7-oxo-DHEA is safe and well tolerated.^[6] In this study of 22 healthy male participants, 82% of participants in the 7-keto-DHEA group (n=16) and 100% of those in the placebo group (n=6) reported mild adverse events. The most common adverse event was gastrointestinal upset, occurring in 18% of the 7-keto-DHEA recipients and 33% of the placebo recipients. Headaches (n=4) were reported in the 7-keto-DHEA group. Two adverse events were deemed as possibly related to 7-keto-DHEA therapy, decreased hemoglobin and hematocrit levels (n=1) and heightened sensitivity to mosquito bite (n=1). Participants who received the 7-keto-DHEA acetyl ester also had significantly decreased blood pressure during treatment compared with their baseline values.^[6]

Nausea and vertigo and increased serum triiodothyronine (T3) levels have also been reported as adverse events and side effects, respectively, related to 7-keto-DHEA supplementation.^[17][16]

The safety 7-keto-DHEA has not been evaluated in pregnant women. Due to this lack of safety data, pregnant women should avoid the use of 7-keto-DHEA.

The safety 7-keto-DHEA has not been evaluated in women who are breastfeeding or children. Due to this lack of safety data, women who are breastfeeding and children should avoid the use of 7-keto-DHEA.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.

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9. Kazihnitková H, Zamrazilová L, Hill M, Lapcík O, Pouzar V, Hampl R. A novel radioimmunoassay of 7-oxo-DHEA and its physiological levels. Steroids. 2007;72(4):342-350. doi:10.1016/j.steroids.2006.12.005
10. Marenich LP. Excretion of testosterone, epitestosterone, androstenedione and 7-keto-dehydroepiandrostenedione in healthy men of different ages. Probl Endokrinol (Mosk). 1979;25(4):28-31. https://www.ncbi.nlm.nih.gov/pubmed/157483
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12. Orentreich N, Brind JL, Rizer RL, Vogelman JH. Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J Clin Endocrinol Metab. 1984;59(3):551-555. doi:10.1210/jcem-59-3-551
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14. Worrel ME, Gurkovskaya O V, Leonard ST, Lewis PB, Winsauer PJ. Effects of 7-keto dehydroepiandrosterone on voluntary ethanol intake in male rats. Alcohol. 2011;45(4):349-354. doi:10.1016/j.alcohol.2010.08.020
15. Lund-Pero M, Jeppson B, Arneklo-Nobin B, Sjögren HO, Holmgren K, Pero RW. Non-specific steroidal esterase activity and distribution in human and other mammalian tissues. Clin Chim Acta. 1994;224(1):9-20. doi:10.1016/0009-8981(94)90116-3
16. Marwah A, Marwah P, Lardy H. Development and validation of a high-performance liquid chromatography assay for the quantitative determination of 7-oxo-dehydroepiandrosterone-3β-sulfate in human plasma. J Chromatogr B Biomed Sci Appl. 1999;721(2):197-205. doi:10.1016/S0378-4347(98)00474-5
17. Kaiman 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 Ther Res. 2000;61(7):435-442. doi:10.1016/S0011-393X(00)80026-0
18. Zenk JL, Helmer TR, Kassen LJ, Kuskowski MA. The effect of 7-Keto NaturaleanTM on weight loss: A randomized, double-blind, placebo-controlled trial. Curr Ther Res. 2002;63(4):263-272. doi:10.1016/S0011-393X(02)80031-5
19. Zenk JL, Frestedt JL, Kuskowski MA. HUM5007, a novel combination of thermogenic compounds, and 3-acetyl-7-oxo-dehydroepiandrosterone: each increases the resting metabolic rate of overweight adults. J Nutr Biochem. 2007;18(9):629-634. doi:10.1016/J.JNUTBIO.2006.11.008
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21. Hennebert O, Chalbot S, Alran S, Morfin R. Dehydroepiandrosterone 7alpha-hydroxylation in human tissues: possible interference with type 1 11beta-hydroxysteroid dehydrogenase-mediated processes. J Steroid Biochem Mol Biol. 2007;104(3-5):326-333. doi:10.1016/j.jsbmb.2007.03.026
22. Weeks C, Lardy H, Henwood S. Preclinical toxicology evaluation of 3-acetyl-7-oxo-dehydroepiandrosterone (7-Keto DHEA). FASEB J. 1998;12:A4428. https://www.researchgate.net/publication/287827628_Preclinical_toxicology_evaluation_of_3-acetyl-7-oxo-dehydroepiandrosterone_7-Keto_DHEA. Accessed August 7, 2020.
23. 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;254(1):120-123. doi:10.1006/bbrc.1998.9907
24. Henwood SM, Weeks CE, Lardy H. An Escalating Dose Oral Gavage Study of 3β-Acetoxyandrost-5-ene-7,17-dione (7-oxo-DHEA-acetate) in Rhesus Monkeys. Biochem Biophys Res Commun. 1999;254(1):124-126. doi:10.1006/bbrc.1998.9908