7-Keto DHEA Capsules

Overview of 7-Keto DHEA Capsules

Dosage Strengths of 7-Keto DHEA Capsules

5 mg
10 mg
12.5 mg
25 mg
50 mg
100 mg

General Information

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.23 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.234 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.26

Like DHEA, 7-keto-DHEA is produced endogenously in the adrenal glands, gonads, brain, liver, and skin.57 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 age8; it then decreases with increasing age.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 acetate11 ); this form (also often referred to as 7-keto-DHEA) is less susceptible to oxidation than 7-keto-DHEA during manufacturing and storage.31213 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.614

7-keto-DHEA has been shown to promote weight loss and increase resting metabolic rate in people who are overweight.151617 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=.0115 and 2002 study: mean, -2.15 kg vs -0.72 kg, respectively; P=.03816).

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

Mechanisms of Action

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.2318  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.318

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.23 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

Pharmacokinetics

When 3β-acetyl-7-oxo-DHEA was administered orally to healthy male volunteers it was rapidly converted to 7-oxo-DHEA-S, the concentrations of which were proportional to dose.6 The steroid sulfate did not accumulate over time; trough plasma concentrations, 12 hours after 3β-acetyl-7-oxo-DHEA administration (200 mg), on day 7 and day 28 were similar (15.8 mg/L and 16.3 mg/L, respectively), indicating that the ratio of the formation rate to clearance is constant during multiple dosing.6 The mean half-life of 3β-acetyl-7-oxo-DHEA was 2.17 hours, and the mean time to 7-oxo-DHEA-S peak plasma level was 2.2 hours, indicating rapid absorption of 3β-acetyl-7-oxo-DHEA and conversion to the sulfate ester.6 The apparent clearance for 7-oxo-DHEA-S averaged 172 L/h, and the apparent mean volume of distribution was 540 L.6

In human liver microsomal fractions, 7-oxo-DHEA was reduced mainly to 7β-OH-DHEA and to 7α-OH-DHEA (2:1 ratio), and after 120 minutes, the reaction showed some reversibility.5 Multiple enzymes appear to reduce 7-oxo-DHEA in the presence of NADP+/NADPH.5 The reversible conversion of 7-oxo-DHEA to 7α-OH-DHEA is mediated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in the liver and by 11β-HSD2 in the kidney.5 Though, several enzymes appear to be capable of reducing 7-oxo-DHEA to both 7-hydroxy-isomers;5  in vitro studies showed that 11β-HSD1 reduces 7-oxo-DHEA to both 7α-OH-DHEA and 7β-OH-DHEA.7

Contraindications / Precautions

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.

Indications

7-keto-DHEA is used as a supplement for weight loss or maintenance in conjunction with a calorie-restricted diet and exercise program.

Pregnancy

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.

Breast Feeding

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

Interactions

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

Adverse Reactions / Side Effects

Adverse reactions and side effects of 7-keto-DHEA may include but are not limited to gastrointestinal upset/nausea617, headache6, decreased hemoglobin and hematocrit levels6, sensitivity to mosquito bite6, vertigo17, and increased serum triiodothyronine (T3) levels.16 Short-term studies in preclinical models revealed no adverse effects with 7-keto-DHEA.202122 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 vertigo17 and increased serum triiodothyronine (T3) levels16 have also been reported as adverse events and side effects, respectively, related to 7-keto-DHEA supplementation.

Storage

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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