7-Keto DHEA

7-Keto DHEA, a derivative of the hormone dehydroepiandrosterone (DHEA), is produced naturally in the body and does not convert into sex hormones like estrogen or testosterone.  This distinct feature makes it an appealing option for therapeutic applications without the hormonal side effects associated with DHEA. 

Generated through a two-step enzymatic process involving cytochrome P450 7B1 and 11 𝛽-hydroxysteroid dehydrogenase type 1, 7-Keto DHEA has attracted attention for its potential benefits in metabolism regulation and weight loss, particularly when combined with exercise and diet control. 

Moreover, it is involved in modulating immune responses and may enhance memory and alleviate symptoms in conditions like post-traumatic stress disorder (PTSD). 

This article explores the complex biological functions and clinical applications of 7-Keto DHEA, setting the stage for a deeper understanding of its role in health and disease management.

What is 7-Keto DHEA?  [5.] 

7-Keto-DHEA, a metabolite of the hormone dehydroepiandrosterone (DHEA), is naturally produced in the body. 

It is synthesized through a two-step enzymatic process involving cytochrome P450 7B1 (CYP7B1) and 11 𝛽-hydroxysteroid dehydrogenase type 1 (11 𝛽-HSD 1), which converts DHEA into 7-keto-DHEA via intermediary compounds. 

Unlike DHEA, 7-keto-DHEA does not convert to sex hormones such as estrogen or testosterone, making it a potential candidate for safe therapeutic uses without the hormonal side effects associated with DHEA.

Biological Functions of 7-Keto DHEA

Understanding the biological functions of 7-Keto DHEA is crucial for comprehending its potential health benefits and physiological effects. 

Metabolic and Weight Loss Effects of 7-Keto DHEA

One of the primary areas of interest regarding 7-Keto DHEA is its purported role in metabolism regulation and weight loss.  Results regarding the effects of 7-keto DHEA for weight loss are mixed, although it may have its strongest effects in obese or overweight adults in combination with exercise and calorie restriction.  [6.] 

7-Keto DHEA has been implicated in enhancing metabolic rate, which could contribute to its reported effects on fat loss and body composition improvement.  [6.]  7-Keto DHEA seems to induce certain thermogenic enzymes, including those stationed in mitochondria as well as cytosolic enzymes.  [1., 7., 8.]

7-Keto DHEA may also support healthy T3 levels without negatively impacting overall thyroid function.  [6.] 

Another potential mechanism involves the enzyme 11 𝛽-HSD 1, which is responsible for converting cortisone into active cortisol: high levels of cortisol are linked to insulin resistance and obesity.  [3.] 

It is proposed that 7-Keto-DHEA may regulate cortisol activity by competitively inhibiting 11 𝛽-HSD 1, thereby promoting the production of 7 𝛽-OH-DHEA instead of active glucocorticoids.  

This action might counteract the glucocorticoids' effect of reducing uncoupling proteins—proteins that allow protons to flow into the mitochondrial matrix without generating ATP, thus converting energy into heat and enhancing thermogenesis. 

Additionally, 7-Keto-DHEA could directly increase the levels of these uncoupling proteins, further supporting its role in promoting thermogenesis.  [4.]

Immune Modulation  [13.]

7-Keto DHEA has shown significant effects as an immune modulator in the context of HIV and tuberculosis (TB) co-infection. 

Research indicates that 7-Keto DHEA enhances Th1 immune responses, crucial for fighting TB. In studies, 7-Keto DHEA treatment improved the function of CD4+ T cells by increasing their proliferation and boosting the production of key cytokines like IFN-γ and TNF-α, which are vital for controlling mycobacterial infection. 

Furthermore, 7-Keto DHEA shifted the immune response by reducing the proportion of regulatory T cells and increasing the Th1 cells, which are associated with better disease outcomes in TB. 

This adjustment in immune cell dynamics suggests that 7-Keto DHEA could serve as a beneficial adjunct therapy in managing TB, particularly in individuals co-infected with HIV, by reinforcing the body's response to infection.

Clinical Applications of 7-Keto DHEA

Understanding the clinical applications of 7-Keto DHEA is essential for assessing its potential therapeutic value in various health conditions. 

Weight Management

One of the most widely studied clinical applications of 7-Keto DHEA is its role in weight management.  Research suggests that supplementation with 7-Keto DHEA may promote weight loss by increasing metabolic rate and thermogenesis, leading to enhanced calorie expenditure.

Research indicated that optimal weight loss results without a decrease in metabolic rate occur in conjunction with exercise and calorie restriction, particularly in overweight or obese individuals.  [6.]

However, other studies do not show the same benefits.  [5.]  While further research is needed to confirm these findings and elucidate the mechanisms underlying its effects on weight, 7-Keto DHEA may be a potential adjunctive therapy for obesity management in conjunction with diet and exercise.

Memory  [12.]

7-Keto DHEA has shown promising effects in enhancing memory, particularly in reversing memory deficits induced by the anticholinergic agent scopolamine in animal models. 

In experiments using young mice, a single dose of 24 mg/kg of 7-Keto DHEA-acetate completely reversed memory impairment caused by scopolamine, showcasing a more potent effect compared to DHEA itself.  

These findings suggest that 7-Keto DHEA could be a valuable agent for investigating human memory enhancement, particularly because it does not convert to sex hormones and thus avoids the hormonal side effects associated with DHEA.

Post-Traumatic Stress Disorder (PTSD)  [9., 11.]

In a study on post-traumatic stress disorder (PTSD), benefits were observed when patients received 7-keto DHEA at doses ranging from 25 to 150 mg per day. This treatment, given in an open-label trial, was effective for those with PTSD who had resisted multiple previous treatments. 

The choice of 7-keto DHEA over DHEA was due to its non-aromatizable nature and potentially superior anti-glucocorticoid properties.  This form of DHEA provided rapid, noticeable improvements in PTSD symptoms, suggesting its potential for larger, more rigorous clinical trials.

Safety and Side Effects of 7-Keto DHEA

7-Keto DHEA seems to be safe when used appropriately.  Doses of up to 200 mg/day have been well-tolerated in healthy males for up to 4 weeks.  [2.]  However, it is essential to monitor for side effects and discontinue use if they occur or consult a healthcare professional for guidance.

Lab Testing for 7-Keto DHEA

7-Keto DHEA levels can be assessed in saliva or blood.  Blood testing requires a blood draw via venipuncture.

Salivary testing may be done from the comfort of home or in a clinical setting.  

Saliva Testing for 7-Keto DHEA

It is important to note that supplementing with 7-keto DHEA will raise supplement levels in saliva, resulting in a high 7-Keto DHEA/DHEA ratio, without raising the levels of androgens or estrogen.  [10.] 

In contrast, supplementation with DHEA will also raise levels of androgens and estrogen.  

Interpreting 7-Keto DHEA Results

Optimal Levels of 7-Keto DHEA

It is important to consult with the laboratory company used for testing 7-keto DHEA levels.  Optimal ranges for salivary 7-Keto DHEA have been given as: [10.] 

41-130 pg/mL 

Low Levels of 7-Keto DHEA

Low levels of 7-Keto DHEA may correlate with low levels of DHEA, which naturally declines in production with age.  This can manifest as difficulty with weight loss, memory problems, and other symptoms of low hormones such as low libido.  Low levels of 7-Keto DHEA, especially in the setting of symptoms of hormone deficiency, may warrant additional assessment of hormones such as estrogen, testosterone, and DHEA.  

High Levels of 7-Keto DHEA

High levels of 7-Keto DHEA most commonly occur in the setting of excessive supplementation with DHEA or 7-Keto DHEA.  With 7-Keto DHEA supplementation, only increases in 7-Keto DHEA are seen.  [10.] 

In contrast, supplementation with DHEA may also raise levels of androgens and estrogen.  [10.] 

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