Lyoto Machida got an 18 month suspension for taking 7-keto-DHEA, what is that?

As reported yesterday, Lyoto Machida has been suspended for 18 months after disclosing the use of 7-keto-DHEA on a declaration form athletes fill in while giving test samples to USADA agents. USADA released a statement mentioning that 7-keto-DHEA is classed as an ‘anabolic agent,’ which sounds a lot like an anabolic steroid, or something equally powerful. That isn’t the case.

There’s a lot of confusion around 7-keto-DHEA and the similar sounding substance DHEA. Let’s start by clearing that up. The two substances are different and have very different effects on the body. The confusion stems from the fact that 7-keto-DHEA is a metabolite of DHEA.

A metabolite is essentially a byproduct created when your body uses or processes a chemical. When you ingest a substance, your body “metabolizes” it, which means your body causes it to undergo a chemical reaction that changes the substance. Basically, anything you ingest is metabolized into a different form before being excreted.

Before you read any further, remember that DHEA and 7-keto-DHEA are not the same thing and have very different effects.

When a person takes a pill containing DHEA, it is processed by the liver and broken down into several substances, including precursors to testosterone. One of the metabolites it is broken down into is 7-keto-DHEA. It must be noted that 7-keto-DHEA does not increase testosterone or break down into anything that increases testosterone.

The confusion arises because DHEA (but not 7-keto-DHEA) does break down into substances that are known to affect levels of testosterone, estrogen, and other related hormones. I'm going to explain what both DHEA and 7-keto-DHEA do so you're able to easily determine whether someone is talking about DHEA or 7-keto-DHEA based on the benefits they mention.

What does the research say about DHEA?

It should be noted that even DHEA itself is—at best—a mild performance enhancer which has nowhere near the same potency as anabolic steroids, even under best case scenarios. WADA itself appears to believe that there is no evidence that DHEA enhances performance in male athletes.

Studies tend to show that it has little to no effect on total testosterone levels in men, though it does appear to increase free testosterone levels in older men. Free testosterone is the testosterone available to be used by muscles, so increasing the amount of free testosterone could have muscle building benefits in that manner. It does not appear to increase free testosterone levels in young, healthy subjects.

DHEA has been shown to mildly increase muscle mass and strength in elderly people, likely via the increase in free testosterone, and via DHEA metabolites which are known or suspected to have roles in increasing muscle mass and athletic performance, such as androstenedione and IGF-1.

The research on healthy adult men used to weight training found DHEA had no effect on muscle mass or strength. This is likely due to healthy, athletic adults already having sufficient natural DHEA production for their bodies needs.

The results are slightly different in elderly people undergoing an exercise program. In the elderly, DHEA has been shown to increase thigh muscle volume by around 7.6% after four months of training versus an increase of around 3.1% in the group following the same program without taking DHEA. In elderly subjects, it was also shown that DHEA plus exercise is somewhat more effective than exercise alone for increasing strength.

The strength and muscle volume increases seen in some studies on the elderly is likely due to elderly people having decreased DHEA production compared to younger, healthier people, as studies involving healthy people tend to find DHEA supplementation does not increase muscle or strength gains

To sum up, the available research suggests DHEA (not 7-keto-DHEA) may help the elderly gain more muscle mass and strength while following a weight training program, but that DHEA supplementation has no effect, or little effect, on healthy, trained men.

What does the research say about 7-keto-DHEA?

So what does 7-keto-DHEA do? There is a dearth of high-quality studies about the effect of orally ingesting 7-keto-DHEA, but we have a reasonable understanding of what it can and can’t do.

Again, I need to reiterate that while DHEA has been found to increase muscle mass and strength in elderly populations, 7-keto-DHEA has not been shown to increase testosterone levels, either free or total, or any other sex hormone, and there is no evidence that it increases muscle mass or strength in any population in any high-quality study I am aware of, and I looked far and wide.

In fact, one study suggests that when applied transdermally (to the skin via a patch) 7-keto-DHEA actually decreases testosterone and free testosterone levels, though I am unaware of any studies showing the same happens with orally ingested 7-keto-DHEA.

What 7-keto-DHEA does appear to do is reduce body fat and aid in weight loss. Studies tend to find that when combined with a calorie controlled diet and an exercise program, 7-keto-DHEA can potentially increase weight loss and lower body fat compared to control groups who do not take 7-keto-DHEA.

7-keto-DHEA seems to work primarily by increasing the amount of the thyroid hormone Triiodothyronine (t3), which increases a person’s basal metabolic rate. Increasing the basal metabolic rate means your body uses more calories while at rest.

It should be noted that studies showing 7-keto-DHEA promoting weight loss tend to have control groups which lose very little weight. In the previously linked study, the control group on the same diet/exercise program lost around a quarter of a pound per week, while the group using 7-keto-DHEA lost around three-quarters of a pound per week.

Losing under a pound per week on a calorie-controlled diet and exercise program is an underwhelming result. Many diet and exercise programs aim for weight loss of 1-2 pounds per week, which is a perfectly safe and healthy target for weight loss.

For further perspective, a study on people drinking green tea with a high caffeine content on a severely calorie-restricted diet shows an average weight loss of 14.74 lbs over 4 weeks, vs. 11.22 lbs in the low caffeine control groups. A meta-analysis of studies examining the effect of green tea intake with or without any change to diet or exercise found that, on average, green tea alone caused, on average, an increased weight loss of 3 lbs over 12 weeks compared to control groups.

What does that tell us about 7-keto-DHEA? Well, the available research suggests 7-keto-DHEA, when taken as part of a calorie controlled diet with exercise, will on average let a person lose 4 lbs more than the same program without 7-keto-DHEA over 8 weeks.

The meta-analysis of green tea—which is not prohibited— showed green tea will on average, even where diet and exercise isn't changed, let a person lose 3 lbs more than someone not taking green tea.

That means the research suggests 7-keto-DHEA is barely more potent than green tea for weight loss, let alone anywhere near as powerful as other banned performance enhancing drugs.

As a result, you should take claims that 7-keto-DHEA "triples weight loss" with a large pinch of salt. It should also be noted that 7-keto-DHEA is patented for use in weight loss as “7-keto," and many of the studies relating to it appear to be directly or indirectly funded by the 7-keto patent holder. This may mean 7-keto-DHEA is actually less effective than the studies suggest.

To sum up, 7-keto-DHEA may make it somewhat easier to lose weight and body fat, but it does not appear to have any performance enhancing benefits. 7-keto-DHEA also appears to be barely more effective than drinking green tea for weight loss. While 7-keto-DHEA comes under the class of “anabolic agent” on WADA’s prohibited list, it is categorically not an anabolic steroid and has no muscle building action.

Is 7-keto-DHEA a masking agent?

Bear with me here, because this will get a little in-depth, and as I don't know exactly what method USADA use to detect DHEA use I need to discuss a few potential scenarios.

The short answer is that 7-keto-DHEA isn't a masking agent in the way people think of masking agents. You can't take 7-keto-DHEA and then not have another banned substance show up on a test because you took 7-keto-DHEA. It won't clear any banned substances out of your system faster, or allow you to have a negative test for something you're actually taking.

The longer answer is that there are several potential methods to detect exogenous DHEA use, and in some of them 7-keto-DHEA can cause a false positive. That is, taking 7-keto-DHEA can look the same as taking DHEA on certain very specific urine tests. Specifically, tests which only check for levels of 7α and 7β-OH-DHEA in the urine could potentially return a false positive if someone was using 7-keto-DHEA, as 7-keto-DHEA would also increase the amount of these substances in the urine. That could potentially allow an athlete to claim they failed the test because they were taking 7-keto-DHEA and not DHEA.

With that being said, there are other methods and markers available to detect DHEA use and differentiate between DHEA use and 7-keto-DHEA use. I find it unlikely that WADA/USADA are incapable of performing these analyses, especially since WADA technical documents from 2009 apparently already included checks for 16α-OH-androsterone alongside 7β-OH-DHEA, which should differentiate between 7-keto-DHEA use and DHEA use.

I should note that I was unable to find an archive of the 2009 technical document in question to check this for myself, but the source making the claim—The Journal of Analytical Toxicology—is reliable.

I was able to find more recent technical documents from WADA, but they did not contain any significant information on WADA's protocol regarding the detection of DHEA in particular. As a result is is possible—though I consider it unlikely—that USADA/WADA currently rely solely on a urine test for a metabolite which is known to give false positives.

WADA does appear to be funding some research into DHEA, though the existing research suggests DHEA provides no performance enhancing benefit to male athletes. The research aims to confirm whether or not DHEA enhances maximal performance in both men and women. The research also looks to find a "metabolic signature" of DHEA use to allow it to be detected by means of an athlete's biological passport.

If this information has left you wondering exactly how to feel about Lyoto Machida’s 18-month suspension, there will be an editorial on Bloody Elbow tomorrow on that exact topic. Don’t miss it.