What does the evidence show?
What does the evidence show?
There are, in the usual theoretical framework, three levels of training hell. First you’ve got functional overreaching, in which you temporarily push your body beyond what it can really handle—think of an intense week-long training camp, for example—but you then pull back in time and get a rebound effect that supercharges your fitness. Then there’s non-functional overreaching, in which you don’t pull back in time and end up with dead legs and a serious case of the blahs that takes days or weeks to recover from.
And then, beyond that, there’s the terrible specter of full-blown overtraining. No one really understands exactly why it happens, how to predict it, or what to do about it, other than lie in a dark room for months cursing the fates.
Figuring out how to reap the benefits of functional overreaching without tipping over the edge is one of the great challenges of training. That’s what gives a new study from researchers in Belgium its kick. There’s been a bunch of research and interest in the idea of ketone drinks as an endurance booster (as I described in the magazine last year). Ketones are a form of emergency fuel produced in your body when you’re starving or very low on carbohydrate energy, which have only become available in drink form in the past few years. The new research suggests we might have had it backwards all this time: the real magic isn’t what ketones do for you during exercise; it’s what they do afterwards.
The research comes from a Belgian group at KU Leuven led by Peter Hespel, a sports science researcher who works with (among many other pro-sports groups) the QuickStep pro cycling team and the UPlace-BMC pro triathlon team. He and his colleagues put 18 volunteers through a three-week cycling ordeal that involved 10 or 11 workouts per week, specifically designed to push the subjects into non-functional overreaching by the third week. The goal was to put the volunteers through something comparable to what a Tour de France rider experiences.
Half the riders were given ketone ester drinks from HVMN, which is the drink I wrote about last year (ketone esters are a chemical formulation that, by some accounts at least, are more easily processed by your body than other versions like ketone salts). There’s plenty of debate about different kinds of ketone drinks: salts versus esters, doses, palatability, and so on. On Twitter, Hespel made the point that his results only apply to the specific drink he tested. With that point in mind, it’s worth noting that the study was funded by Research Fund Flanders, the Belgian equivalent of something like the National Institutes of Health; the authors declare no competing interests; and they specifically note that the drinks used in the study were purchased from TdeltaS, the Oxford-based company that helped developed the ketone ester now licensed to HVMN. That’s no small detail, because HVMN sells three 25-gram bottles of its drink for $99—and the subjects were drinking up to three bottles per day: one after each workout and one before bed.
The control group, meanwhile, was drinking a medium-chain triglyceride drink spiked with “bitter sucrose octaacetate” to make it taste like crap, or at least like the famously unappetizing ketone drink. Both drinks were tinted with red colorant, and the study was double-blinded, meaning that neither the subjects nor the scientists supervising the study knew who was getting which drink. At the end of the study, only 5 out of 9 subjects in each group correctly guessed what they’d been drinking—more or less what you’d expect by chance, meaning that the blinding was successful.
I’m emphasizing all these methodological details because I approach any new miracle supplement or biohacking research with a huge load of skepticism. To me, the word biohacking is basically a synonym for the exhaustive pursuit of negligible or non-existent gains backed by shoddy research and often at the expense of far more powerful and obvious hacks like, say, getting a good night’s sleep and a reasonable amount of exercise. These experimental details don’t guarantee that the results are bulletproof, but they’re a good start.
So what happened? In brief: the ketone group was able to sustain a higher level of training in the last week of the study, they had less pronounced physiological signs of overtraining, and they performed better in a time trial. Specifically, even though they were all assigned the same basic training sessions, the ketone riders were able to push harder, accumulating a third-week training load that was 15 percent higher than the control group. Midway through that week, they did a two-hour ride that consisted of 90 minutes at a steady pace followed by a 30-minute all-out time trial. The ketone group’s power output was 15 percent higher in that time trial.
One of the classic signs of overtraining is a reduction in heart rate, reflecting a shift in the balance between your sympathetic and parasympathetic nervous systems. By the third week, both groups did indeed see reductions in their resting heart rate, their submaximal heart rate at a given level of exertion, and their maximal heart rate. But the reduction in the ketone group was significantly less (black circles are ketones, white circles are control):
Perhaps the most telling difference between the two groups was in what they ate. Other than a post-workout protein-carbohydrate recovery drink, the subjects were free to eat whatever they wanted to. Initially, both groups were averaging about 3,500 calories per day. But as the training load ramped up from week to week, the groups diverged. The control group kept eating roughly the same amount, resulting in a daily caloric deficit of about 800 calories by the third week. The ketone group, meanwhile, ramped up its intake, averaging 4,200 calories in the final week and remaining roughly in caloric balance.
The researchers also measured a bunch of different appetite hormones, and one of them—something called growth differentiation factor 15 (GDF15)—looked to be the smoking gun. GDF15 is apparently a relatively recent addition to the list of appetite hormones; the researchers describe it as a “stress-induced hormone that is involved in appetite regulation by decreasing food intake.” As the control group accumulated fatigue, their GDF15 levels climbed, which is perhaps why they failed to eat enough to match their energy burn. The ketone group, meanwhile, had lower levels. Here’s what that looked like:
As an aside, the researchers propose that GDF15 may be a useful biomarker to diagnose overtraining before it gets too serious. That’s an interesting idea, and one that I’m sure they’re pursuing in further studies, because an overtraining predictor would be very useful.
That said, it’s tempting to wonder whether the biggest difference between the two groups was simply that one ate more than the other. The researchers argue against this, pointing out that there were differences in overreaching symptoms (heart rates, stress hormones, GDF15) before significant differences in dietary intake occurred. I can’t really judge that from the data presented, since we only see weekly averages. I’m not ready to rule out the possibility that caloric intake is the biggest factor here, and that ketones somehow encourage people to keep eating in the face of major training stress. Perhaps future research will make that clearer.
There’s more in the study—glycogen levels, nighttime levels of adrenaline, and so on—but I think those are the key points. How practical is it to imagine taking a $33 bottle of ketones after every workout and before every bedtime? For me, not so much. (Have I mentioned recently that you should buy my book?) For pro cyclists, maybe it is. There’s an interesting article (in Dutch) in which Peter Hespel gives some context about the study, with plenty of speculation about the possible use of ketones by QuickStep riders. Other teams obviously know about ketones, but they may not have as much information about its value for recovery rather than direct performance boost. “I can imagine that quite a few athletes are currently using it incorrectly or certainly not in the most optimal way,” Hespel (according to Google Translate) says.
In fact, he goes on to say, taking ketones immediately before a workout or race may actually have a negative effect. There’s been speculation that ketone use could inhibit high-intensity sprint ability. The new study did include weekly tests that involved a 90-second sprint. There were no significant differences between the ketone and control group—but that doesn’t really reveal anything, because the subjects were only taking their ketones after the testing, not before.
So what’s the final takeaway? I’m not sure at this point. But if you’re going to make eyebrow-raising claims about performance enhancement, this is the sort of rigorous and independent research you need to back it up. Here’s hoping there’s more to come.
My new book, Endure: Mind, Body, and the Curiously Elastic Limits of Human Performance, with a foreword by Malcolm Gladwell, is now available. For more, join me on Twitter and Facebook, and sign up for the Sweat Science email newsletter.