by Loren Bertocci, Ph.D

Over the last few years, several masters-aged friends of mine have asked me about ketogenic diets and, usually, both the question and answer were brief. But recently, one of them asked me a more complicated question, one that solicited what I knew about the effect of a ketogenic diet on muscle growth, exercise performance, and inflammation. I want to be clear about one thing – what follows has nothing to do with how any reader might decide to manage their own diet. This is merely an article that results from several masters-aged friends, and more recently one particular masters-aged friend of mine and me.

Although there is an enormous amount of well-documented information on both the dietary components required for muscle growth, as well as the relative uses of fuel by exercising muscle, I did not know anything about any interactions between this kind of a diet and inflammation. So, I did what I always do in such situations, did a search of the scientific literature, specifically on the listings from the National Library of Medicine (aka “PubMed”).

First, let’s consider what is known about diet and muscle growth. For purposes of this article, let’s make the simplifying assumption that the athlete is actually training properly to increase muscle strength. What follows is a paraphrasing of my answer to my masters-aged friend who has a body weight of roughly 85 kgs (185 lbs). Adding muscle is one of the most difficult things you can try to do. After a strength training session, the mTOR (mechanistic Target Of Rapamycin) gene is stimulated to begin the process of building contractile proteins. However, even after it is stimulated, it cannot actually activate muscle protein growth unless it senses two things: (1) that you are in an overall positive caloric balance and (2) you have an adequate supply of protein, in particular an adequate supply of leucine (one of the amino acids).

Fat contains no protein. Consuming 200g of fat (what my friend indicated had been recommended to him) means that you are consuming almost 2000 kcals per day solely from fat. If you want to gain muscle, at a masters (40+) age, you should be consuming more than 2g of protein per kilogram body weight per day. This is another (roughly) 650 kcals. So, together, you have consumed 2,650 kcals without having consumed even one gram of carbohydrate. Why does this matter? It matters because when a muscle cell is presented with a wide array of fuels, it uses all of them, although the ratio of fuel use is a function of exercise intensity. The lower the exercise intensity, the higher the ratio of fat used. The higher the exercise intensity, the higher the ratio of carbohydrate used. When your carbohydrate stores are inadequate, it is unavoidable that you will catabolize your muscle proteins to make the carbohydrates you need to do intense exercise. This will cause a net loss of muscle protein. The only carbohydrate your muscle uses is glycogen. If there is enough glycogen, you will use what you have. If you do not have enough glycogen, it is replenished from two sources: (1) glucose released from the liver and (2) conversion of protein to glucose.

If your diet does not contain enough carbohydrate, it will inevitably lead to muscle glycogen depletion. As a response to intense (and nothing is more intense than heavy lifting) exercise, glycogen depleted muscle will (1) be work capacity limited; (2) not grow contractile proteins; and (3) trigger overall whole-body protein breakdown. My friend asked me this summary question: “As a masters athlete will a Keto based diet do more harm than good?” My answer was simple: “there are no benefits – there is only harm.” Not only is this kind of a diet unsupported by legitimate biochemical or biomedical research, it is something that no legitimate physician would ever prescribe.”

In a follow-up email, he asked for some elaboration on the muscle fuel question. In particular, he made reference to a term I see far too often: “fuel switching.” What this term means is that there is some magical sensor inside of skeletal muscle cells that “switches” between its use of carbohydrate, fat, and protein, via some equally magical process. Naturally, there are no legitimate data that support the existence of either such a magical sensor or magical process. What really occurs is much more simple and easy to understand. Skeletal muscle can only use two fuels: carbohydrate and fat. At low power outputs, all of the ATP required to do muscular work can be made solely from the oxidation of fats. As exercise intensity increases, so does the obligation to oxidize carbohydrates. At the highest exercise intensities, close to 100% of the fuel used by muscle must be carbohydrate. It is important to note that there is no such thing as “fuel switching.” At all times, both fat and carbohydrate are being oxidized. The only thing that changes is their ratio of oxidation, and, when graphed, this change is a smooth curve with no discontinuities.

So what about protein? Can it be used as a muscle fuel? The answer is simple and it is “no, it cannot.” Muscle cells can catabolize protein, via the process of removing the amino (–NH3) group from an individual amino acid. After this process (called a deamination), the cell is left with a carbohydrate that can be oxidized. So, any time your muscle cells are required to do intense exercise, if there is not enough glycogen available, they breakdown their own proteins, deaminate those amino acids, and oxidize the resultant carbohydrate backbone to generate the carbohydrates required to generate the large amounts of energy required for intense exercise.

The final part of his question was about the ketogenic diet and inflammation, the part of this topic about which I knew nothing. So, I did a search and found the following:

  • There were only 67 publications listed that contained both the word “ketogenic” and “inflammation;”
  • Of those 67, there were only 4 that reported any evidence of attenuation of inflammation and a ketogenic diet. All of these were in rodents that had some sort of artificial inflammatory stimulus imposed by the investigators;
  • Of the remaining 63, there was one study done on human exercise. They reported no evidence of any improvement in endurance capacity and a ketogenic diet;
  • The remaining 62 papers focused on any relationship between a ketogenic diet and one or more well-known diseases. None of these are relevant to this article.

What was most striking to me was that there were only 67 publications listed. The NLM is a world-wide index of biomedical research. A single journal can often contain 67 different articles. There are 1,000s, perhaps 10,000s, of journals that can contain this kind of research. Some of these journals have been in existence for more than 100 years. Given the reality that biomedical scientists can only advance their careers via the publication of research results, if there were any reason to suspect that there actually was a relationship between a ketogenic diet and inflammation, 100s, perhaps 1,000s of biomedical scientists would have redirected their research to address this, and it would not be difficult to find 10,000s of publications on this topic. That this has not occurred supports only one simple conclusion – a ketogenic diet does not attenuate inflammation in any useful manner.

So, from a practical perspective, what does this all mean to the athlete or coach? Although there are all sorts of good reasons for an athlete to make any individual dietary choice, there is simply no legitimate evidence to support the value of a ketogenic diet as a way to grow muscle, to augment exercise performance, or to attenuate exercise-induced inflammation.

Dr. Loren Bertocci
Following his undergraduate career at Stanford University, Dr. Loren Bertocci earned his PhD in Biochemistry/Biophysics with a specialization in skeletal muscle mitochondria and has dedicated his career to studying the role of mitochondria in secondary metabolism (skeletal muscle). The outcome of his 20+ years of research at UT Southwestern Medical School is the creation of a product that triggers mitochondrial biogenesis to reduce the effects of the aging process.
Dr. Bertocci’s publication record is world-class, including 26 papers in peer-reviewed journals. He has been awarded (as Principal Investigator, Co-Principal Investigator, or Collaborating Investigator) more than $3 million in grants from the American Heart Association, the Department of Defense, the Department of Veterans Affairs, the Muscular Dystrophy Association, NASA, and the National Institutes of Health. With athletic backgrounds swimming, water polo, triathlon and track, Dr. Bertocci is also an accomplished Crossfit athlete and recently earned a Bronze Medal in Olympic Weightlifting at the 2015 Pan Am Masters Championships. He is currently training to qualify for the World Weightlifting Championships in the 65+ category.
Dr. Bertocci is Director of Science at Pangea Biomedical, which produces supplements designed for the specific needs of athletes over 40.