In today’s weight loss marketplace, both manufacturers and consumers are looking for products that are safe as well as effective. 7-Oxo DHEA has filled this space by offering four key benefits:

• Excellent safety profile.
• Industry leading efficacy.
• Boosting metabolism without stimulants.
• World-class clinical trial pedigree.

7-Oxo DHEA is a substance found naturally in the body and its presence in human was documented in 1958. It is metabolized from the hormone DHEA, and like DHEA, it is known to decline with age. Supplementing with 7-Oxo DHEA is simply putting back what time and Mother Nature have taken away.

The DHEA Dilemma

DHEA, also known as dehydroepiandrosterone, is synthesized in the adrenal cortex from cholesterol via pregnenolone by the action of an enzyme called cytochrome P450. It is the most abundant adrenal steroid in humans and is the precursor for many important steroid hormones, which includes estrogen and testosterone. In contrast to cortisol and other adrenal steroids, DHEA levels decline with age. Levels of DHEA increase through the second decade of life and then begin to decline to negligible amounts at ages greater than 70 years. We experience a 40% reduction in DHEA levels between ages 20 and 40. Since DHEA is the major androgen precursor in humans, men have 30% higher DHEA levels than women throughout their lives.

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The Search for a Better DHEA

Recognizing that the bioactivity of DHEA must rest with one or more of its many metabolites, Dr. Henry Lardy led the search for more specific and active metabolites
of DHEA. Dr. Lardy is Vilas Professor Emeritus of the Institute for Enzyme Research at the University of Wisconsin in Madison. Dr. Lardy is renowned for his research on DHEA derivatives and has published over 400 studies in peer-reviewed scientific journals.

To search for possible metabolites of DHEA that might have greater biological activity, greater specificity, and fewer propensities to form sex hormones, Dr. Lardy initiated a program assaying the derivatives of DHEA. The activity of 150 of these metabolites was monitored by measuring the induction of two thermogenic enzymes, mitochondrial glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme. The results of this landmark study were published in 1998. The study showed that 7-oxo DHEA was 2.5 times more active than DHEA at inducing the activity of these thermogenic enzymes. More importantly, Dr. Lardy discovered that in contrast to DHEA, the 7-oxo DHEA metabolite was not convertible to compounds with estrogenic or androgenic activity. Based on these results, the 7-oxo DHEA metabolite was chosen for further study as a weight loss ingredient.

Increased Metabolism

In 2004, a clinical study involving 45 subjects was performed to evaluate the effect of 7-Oxo-DHEA on resting metabolic rate (RMR). The results revealed that administration of 7-Oxo DHEA  to overweight adults in conjunction with a calorie restricted diet effectively reversed the decline in resting metabolic rate (RMR) normally associated with dieting. 7-Oxo DHEA plus a restricted calorie diet demonstrated an increase in RMR by 1.4% above baseline levels versus a 3.9% decrease in RMR in the restricted calorie diet only group. Therefore, the addition of 7-Oxo DHEA  to a restricted calorie diet produced a statistically significant 5.4% increase in daily RMR when compared to only a calorie restricted diet.

Most weight loss programs are designed to manipulate diet and appetite, but there is a growing rationale to support efforts to increase energy expenditure (RMR) as a tool to enhance the results of a weight loss program. 7-Oxo DHEA  achieves this thermogenic effect by directly up-regulating the activity of fat burning enzymes rather than through the use of stimulants. Thus, with the addition of 7-Oxo DHEA , dieters attempting any weight loss program can enjoy more success, and more quickly achieve their weight loss goals.

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The Science Behind Enhancing Thermogenesis

Thermogenesis is a term which describes the creation of heat in mammals. Heat is a form of energy produced when the food we eat is metabolized in the cells of our body. Chemical energy, in the form of adenosine triphosphate (ATP) is also produced in this reaction and is the body’s biologically useful energy. ATP is the “energy currency” of the cell and is used to drive all energy requiring reactions including the synthesis of proteins,
Carbohydrates and fats. It also causes muscles to contract and nerves to conduct.

ATP, while a good energy packet, is not a good fuel storage molecule, as it is used quickly after being formed. Better storage forms of energy are glycogen and triglycerides. Glycogen is broken down to glucose and triglycerides are broken down to fatty acids, both of which are readily utilized for energy. Of importance, is that any food not utilized for energy is subsequently stored for use later, and mostly as fat since it is the most efficient energy storage form at 9 kcal/gm. The synthesis of triglycerides requires glycerol (from carbohydrates), fatty acids and energy from ATP.

The production of energy from glucose and fatty acids occurs at the cellular level with glycolysis (glucose metabolism) occurring in the cytosol of the cell and fatty acid oxidation in the mitochondria of the cell. The mitochondria is often considered the “powerhouse” of the cell, and most cells involved with fatty acid metabolism are in the liver. Acetyl CoA, an essential substrate for energy production, is an end product of both glycolysis and fatty acid metabolism. The enzyme required for the oxidation of fatty acids to acetyl CoA is fatty acyl CoA oxidase.

Acetyl CoA, as a substrate in the Krebs cycle, produces NADH, NADPH and FADH2, which are reducing agents that supply hydrogen atoms or electrons in chemical reactions and are used for ATP production in the mitochondria via a process called oxidative phosphorylation. The oxidation of fatty acids also produces NADH and FADH2. Each molecule of NADH produces 3 ATP’s within the confines of the mitochondria. NADH is also produced in the cytosol (outside of the mitochondria) but needs to be transported into the mitochondria in order to be converted to energy. This transport mechanism is called the “glycerol-3-phosphate shuttle” and requires the enzyme glycerol-3-phosphate dehydrogenase to catalyze the reaction. This “shuttle” requires energy and the end result is that cytosolic NADH is only able to produce 2 ATP’s per mole and the rest of the energy is released as heat. This is therefore a more “thermogenic” utilization of NADH (the reaction produces less ATP and more heat, also called “futile cycling”).

For the purpose of this discussion we will also include the reaction which converts malic acid (a Krebs cycle intermediate) to pyruvate and NADPH. This conversion occurs in the cytosol and requires an enzyme called malic enzyme. This reaction is important since it not only produces cytosolic NADPH but also produces heat.

Compounds with thermogenic activity are substances which foster the production of heat relative to the production of ATP. Very often, these compounds have the ability to enhance the activity of certain enzymes which drive these thermogenic reactions. The quintessential thermogenic compound is the thyroid hormone, thyroxin (T4). Thyroxin has the ability to “uncouple” oxidative phosphorylation (less ATP production and more heat production) by enhancing the activity of glycerol-3-phosphate dehydrogenase and malic enzyme.

Research by Lardy and others has shown that 7-oxo DHEA is able to enhance the activity of three thermogenic enzymes: glycerol-3-phosphate dehydrogenase, malic enzyme and fatty acyl CoA oxidase.

Glycerol-3-phosphate dehydrogenase

The activation of glycerol-3-phosphate dehydrogenase results in an up-regulation
of the glycerol-3-phosphate shuttle. This, in turn, favors the conversion of cytosolic NADH to a pathway of less ATP production and more heat production.

Malic Enzyme

The activation of malic enzyme results in the conversion of malic acid to pyruvate
and NADPH in the cytosol. This results in an excess of NADPH in the cytosol, which is subsequently transported into the mitochondria there it is converted to ATP and heat. This is a thermogenic effect since more heat is produced relative to ATP production due to the cytosolic origin of the reaction.

Fatty Acyl CoA Oxidase

Lastly, the activation of fatty acyl CoA oxidase results in an enhancement of fatty acid breakdown.This reaction results in the production of acetyl CoA, NADH and FADH2. This drives the cell to utilize fatty acids for energy, which in turn promotes the breakdown of triglycerides, the body’s fat storage moiety. The acetyl CoA, NADH and FADH2 produced in this reaction are subsequently converted to ATP and heat, and at a faster rate than normally expected. The end result is an increased production of heat considering the inefficiency of the reaction.

All three of these enzyme activations drive energy producing substrates in a direction of less efficient ATP production relative to heat production. This is the biological definition of thermogenesis. In addition, they promote the utilization of fat stores for energy and heat production. Hence, 7-Oxo DHEA ’s ability to enhance thermogenesis and through that mechanism, accelerate the utilization of fat stores for heat production.