Life Extension Magazine May 2005
7-Keto DHEA The Fat-Burning Metabolite of DHEA
By Dave Tuttle
While many anti-aging enthusiasts are familiar with the hormone DHEA (dehydroepiandrosterone), far fewer are likely to be aware of its metabolite, 7-Keto DHEA, which is responsible for many of DHEA’s beneficial actions.
Scientists have documented DHEA’s wide-ranging benefits in numerous clinical studies. DHEA helps to retard the effects of aging and promotes enhanced longevity, exerting a multitude of effects through its conversion to some 150 metabolites, each with unique actions within the body.
One of the most important of these is 7-Keto DHEA (commonly referred to as 7-Keto), a hormone metabolite that can safely boost immune function and help reduce body fat. Unlike DHEA, however, 7-Keto does not convert to estrogen and testosterone. Because DHEA and 7-Keto have separate and unique functions and properties, it is important to understand the differences between these two popular dietary supplements.
Fast-Acting and Safe
The term 7-Keto is in fact a brand name for the chemical compound 3-acetyl-7-oxo-dehydroepiandros-terone, a naturally occurring metabolite primarily produced in the adrenal glands and skin (though some production occurs in the brain as well). It was first discovered in 1958, when it was found in urine.1 As shown in Figure 1, human blood levels of 7-Keto tend to follow the same course over time as those of DHEA, rising until about the age of 20 and then slowly descending beginning around the age of 30. Urinary excretion studies show that average blood concentrations of 7-Keto decline nearly 50% by age 50.2
“This reduction in 7-Keto levels is partially responsible for the increases in body fat and total body weight often seen in older people,” notes Dr. Sergey Dzugan, president of Life Extension Scientific Information, Inc. “This decline also plays a role in the compromised immune function that is a hallmark of the aging process. Moreover, since DHEA and 7-Keto decline at a more rapid rate than cortisol, this creates a period of cortisol dominance that can wreak havoc on the immune system. For these reasons, supplementation with 7-Keto is often appropriate.”
Studies have demonstrated that 7-Keto does not accumulate in the body over time and is free of unhealthy side effects. An analysis of the metabolite at the Chicago Center for Clinical Research found that 7-Keto is rapidly absorbed and sulfated, much like DHEA.3 The sulfated form of 7-Keto DHEA is more stable in plasma, and blood levels can therefore be more accurately measured with laboratory equipment. In the Chicago analysis, peak plasma levels were achieved 2.2 hours after supplementation, and a steady-state level in plasma was reached with twice-daily dosing. Despite 7-Keto DHEA’s rapid elimination by the body, measured as a half-life of 2.17 hours, relatively high blood levels are quickly achieved. For example, after one week of dosing at 200 mg per day, a mean 7-Keto level of 15.8 nanograms per milliliter (ng/ml) was attained; after four weeks of supplementation, the mean level was only modestly higher at 16.3 ng/ml. Supplementation with 7-Keto can therefore have relatively rapid benefits. Lower dosing resulted in proportionally lower blood levels of 7-Keto.3
Toxicology studies have revealed that this level of supplementation is very safe.4 A “LD50” study in rats (used to determine the dose at which 50% of the test subjects would have died) found that the toxic dosage of 7-Keto would have to exceed 2 grams per kilogram of body weight—the equivalent of a daily dose of 160 grams (not milligrams) for the average 176-pound person, or more than a third of a pound of 7-Keto per day! Laboratory analysis of 7-Keto showed that it does not cause DNA mutations, and an escalating dose study of oral supplementation in rhesus monkeys showed no adverse clinical effects at doses as high as 500 mg/kg of body weight, or the equivalent of 40,000 mg daily for the average human.5
Another benefit to 7-Keto is that it does not convert to estrogen or testosterone.6 This makes 7-Keto a safe alternative for persons with hormone-sensitive cancers, for whom regular DHEA may be too risky.”
Aging is associated with a decline in immune system response, with often-dramatic reductions in immune function. This leads to increased susceptibility to infections. For example, people with age-related declines in cellular immunity have an impaired response to influenza vaccine, making them more susceptible to catching the flu, even if they have received a flu shot. A study at the Minnesota Applied Research Center and the Geriatric Research Education and Clinical Center in Minneapolis found that four weeks of 7-Keto supplementation improved immune function in elderly men and women.7 In this randomized, double-blind, placebo-controlled study, 22 women and 20 men over the age of 65 took 100 mg of 7-Keto twice daily or a placebo of identical shape and size. Patients in the 7-Keto group had a significant decrease in immune suppressor cells and a significant increase in immune helper cells. The 7-Keto group also saw reductions in diastolic blood pressure and an increase in neutrophils, the first white blood cells to respond to infection. The scientists concluded that 7-Keto was well tolerated and had no serious adverse effects.
A Czech research team discovered that 7-Keto can counteract the effect of circulating glucocorticoids, such as cortisol, which often rise with age and can suppress immune function.8 This study was performed in vitro on the spleen lymphocytes of mice, which were exposed to an immune-suppressing drug. Without 7-Keto, the drug produced dramatic reductions in spleen lymphocyte levels. However, when 7-Keto was added, cell viability more than doubled and a measure of primary immune response rose by 150%.
A study at the Chinese Academy of Medical Sciences in Beijing confirms the immune-boosting properties of 7-Keto.9 Scientists exposed mice with compromised immune systems to chronic mild stress for four weeks. The traumatic regimen decreased their white blood cell proliferative response and produced other abnormalities in immune function. Additionally, levels of thyroid hormones decreased. However, when the mice were given
7-Keto at a dose of 15 mg/kg of body weight, their blood cell prolifera-tive response and natural killer cell activity were dramatically enhanced. The levels of thyroid hormone also returned to normal.
The Primary Thermogenic Hormone
7-Keto produces fat loss through the process of thermogenesis. This term refers to the creation of heat, which is one of the forms of energy produced when the body’s cells metabolize the food we eat. Greater amounts of thermogenesis boost the body’s metabolic rate which increases the conversion of stored fat into energy.
7-Keto enhances the activity of three thermogenic enzymes that stimulate fatty acid oxidation in the liver. These thermogenic-en-hancing enzymes are fatty acyl CoA oxidase, malic enzyme, and glycerol-3-phosphate dehydrogenase.6,10-12 These enzymes drive the liver cells to burn fatty acids for energy, which causes a lowering of triglycerides in the liver.
Supplementation with 7-Keto has a dramatic effect on boosting levels of these thermogenic-enhancing enzymes. Studies found that fatty acyl CoA oxidase increased by 128%, while malic enzyme jumped 860%. The concentration of glycerol-3-phosphate dehydrogenase increased by 138% as well.6,10-12
A study published in Current Therapeutic Research revealed just how effective 7-Keto is in inducing fat loss.13 In this randomized, double-blind, placebo-controlled study, 30 overweight adults (28 women and 2 men) were divided into two groups. Group 1 received 100 mg of 7-Keto twice daily for eight weeks, while group 2 took a matching pla-cebo capsule. All subjects participated in an exercise program three times a week that consisted of 50 minutes of aerobic and non-aerobic cross training under the supervision of an exercise physiologist. In addition, each subject was instructed by a registered dietitian to follow an 1800-calorie-a-day diet. The subjects underwent testing for blood chemistry, body composition, blood pressure, and dietary analysis at baseline and at weeks four and eight.
The researchers found that the 7-Keto group lost a significant amount of body weight compared to the placebo group—6.3 versus 2.1 pounds. The 7-Keto group also lost a greater percentage of body fat compared to the placebo group—1.8% versus 0.57%.13 Compared to the placebo group, the 7-Keto group saw a significant increase in thyroid hormone activity that targets fat- burning genes in the mitochondria and adipose tissue.14 No adverse effects were reported. The results show that 7-Keto can significantly and safely reduce body weight and body fat when combined with exercise and a reduced-calorie diet. This is due to the greatly increased levels of fat-burning enzymes in the liver as well as the elevation of thyroid hormone. These beneficial changes are known to boost basal metabolic rate, making it easier to shed excess pounds. Supplementation with 7-Keto can therefore help reverse the decline in metabolic rate that makes it so easy to put on weight as we age. Unlike caffeine and ephedrine, 7-Keto does not have a central nervous system stimulating effect caused by nor-adrenalin release, nor does 7-Keto increase heart rate or blood pressure.