Advantages of a Ketogenic Diet
  • Superior fat loss
  • Better appetite control
  • Increased uncoupling proteins stimulated in muscle and fat
  • Lowers cardiovascular risk by reducing insulin, triglycerides, etc.
  • Ketogenic diets may be cardioprotective
Disadvantages of a Ketogenic Diet
  • Insulin is a potent anti-catabolic hormone.
  • Low-carb diets are currently being used to reduce prostate cancer via reducing IGF-1.
  • Ketogenic diets promote acidosis in muscle (reduced Ph), which can increase muscle tissue proteolysis.
  • Ketogenic diets turn on genes for catabolism. (SEE AMPK section).
  • Reduced exercise intensity
  • Carbs suppress cortisol
  • Lowers SHBG (i.e., lowers free testosterone)
Why Ketogenic Diets May Not Be Conducive for Muscle Anabolism

During the Pre-competition Diet

Many people on the message boards were asking, “Where is your proof that you need carbs to build muscle?” There are two studies that lead one to speculate that training in a glycogen-depleted state leads to impaired genes for muscle hypertrophy. This study does not prove that being in a glycogen-depleted state all the time may not be healthy for muscle anabolism.

The study was published in the Journal of Applied Physiology and reported that performing resistance training in a glycogen-depleted state results in impaired genes for muscle hypertrophy.1 The study follows a 2005 study in which researchers from the Human Performance Lab in Indiana reported that a glycogen-depletion diet blunts the expression of the muscle protein Akt. Akt, or protein kinase B (PKB), is an important molecule in cellular signaling. Akt is also able to induce protein synthesis pathways and is therefore a key signaling protein in the cellular pathways that lead to skeletal muscle hypertrophy and general tissue growth.

Akt is regulated in response to a wide variety of growth factors, including insulin and more recently has been associated with rapid activation in response to exercise in human skeletal muscle. In the study, they didn’t use rats or cell cultures; they used resistance-trained athletes. (The athletes had trained for almost 8 years, using resistance exercise and had exceptional leg press strength). Resistance-trained males performed resistance exercise in the glycogen-depleted state or with adequate glycogen stores. The next day the subjects returned to the weight room and completed 1-legged leg presses (8 sets of 5 repetitions ~80 percent of a 1 RM) with one leg that was glycogen-depleted while the other leg was not. Muscle biopsies were taken before exercise, immediately after and three hours after recovery.

When they examined the muscle biopsies, the researchers found that depleted muscle glycogen concentrations reduced the gene expression of muscle hypertrophy genes. Some of the more disturbing findings were that resting levels of genes involved in muscle hypertrophy (Myogenin and IGF-1) were lower in the glycogen-depleted muscle.2 Akt expression was similar in both groups before and immediately after exercise (after 10 minutes of recovery in the high carbohydrate trial). The Akt/mTOR regulates muscle hypertrophy and is downregulated during muscle atrophy. Akt phosphorylation increased 1.5-fold after resistance exercise with glycogen. During the low glycogen trial after exercise, Akt remained unchanged.2The study concluded that commencing resistance exercise with depleted muscle glycogen does not enhance the activity of genes implicated in promoting hypertrophy. This is the stance that Steve Blechman took on the message boards; low-to-moderate carb diets are better for losing fat and maintaining an anabolic state than a low-carb ketogenic diet. The study raises awareness that low-carb ketogenic diets may not be conducive for putting on muscle mass.
For a look at a brief overview of the study, download a free copy of the National Strength and Conditioning Association’s Performance Training Journal and go to page 5. The article is titled, “Is Muscle Glycogen A Concern For Athletes Who Want To Stimulate Muscle Hypertrophy?” by Gregory Haff, Ph.D.

The AMPK Connection

AMPK is activated during states of energy stress such as hypoxia, glucose starvation and restores the energy-depleted status by concomitantly inhibiting anabolic and stimulating catabolic pathways.11-13 Protein synthesis, a major consumer of ATP in mammalian cells, is inhibited upon AMPK activation.14 Protein synthesis as mentioned previously is inhibited by increased levels of AMPK.10 Furthermore, the degree of AMPK activation during sub-maximal exercise was also shown to be dependent on the fuel status of the contracting musculature, with AMPK activity elevated to a greater extent in muscle with glycogen depletion compared with high glycogen levels.15 A new study released this month in the Journal of Applied Physiology reported that low levels of glycogen caused an increase in levels of AMPK. They examined athletes (not resistance trained, but endurance athletes) and assigned them to high fat/low carb/high protein diets. The subjects were prescribed a high-fat (4.6 g/kg/bw, 68 percent of energy), low-CHO (2.5 g/kg/day, 17 percent of energy) diet. High carbohydrate was used as a comparison. CHO was an isoenergetic diet providing 10.3 g/kg/day-70 percent of energy from CHO and 1.0 g/kg/day, 18 percent of energy from fat. Protein content was maintained at 2.3 g/kg/day during both trials and diets were constructed to maximize, or at least match, absorbable energy. After 5 days of a high fat/lo-carb diet, levels of AMPK were higher than those on the carbohydrate-rich diet. This is valuable data, but does not prove that carbs play a role in the regulation of muscle mass.

All Anabolic Reactions Occur in a Hydrated Cell

Many of the research studies investigating ketogenic diets have reported that dehydration is a common adverse event that occurs with low-carb diets. Cells that experience decreased hydration have impaired anabolic reactions. There is evidence that cellular hydration is an important factor in controlling cellular protein turnover, while protein synthesis and degradation are affected in opposite directions by cell shrinking and that an increase in cellular hydration (swelling) acts as an anabolic agent, whereas cell shrinkage is catabolic.16 Additionally, subsequent studies on the effects of cell volume on protein synthesis have reported similar findings. The results strongly suggest that cell volume is an important cellular signal for the control of protein synthesis in general.17 Being on a ketogenic diet naturally disposes you to dehydration and as mentioned previously, training in a dehydrated state also blunts testosterone levels.18

Ketogenic Diets and Exercise Intensity

Resistance exercise is intermittent in nature so typically, resistance exercise does not result in significant reductions in muscle glycogen. Some of the respondents in the debate say that they feel they can train harder on ketogenic diets. The literature suggests that reduced muscle glycogen is associated with muscle weakness,3 decreased isokinetic force production,4 and reduced isokinetic strength.5 The only athletes who have been shown to benefit from low-carb diets are endurance athletes training at low intensity, which enhances fat oxidation. Some members in the debate reported having increased strength gains on a ketogenic diet— remember that resistance training at low reps (5 reps are less) is dependent on the ATP-PC system. However, high intensity training using resistance exercise (10-12 reps, multiple sets, with short rest periods) can result in depletion in muscle glycogen.6,7 In a review article written in the Journal of Strength and Conditioning Research titled “Carbohydrate Supplementation and Resistance Training,” the author makes several points about the benefits of carbohydrates and resistance exercise.

Spiking insulin occasionally can increase elevations in GH later in the day through hypoglycemia by insulin. Therefore, occasional carbohydrate spikes lead to increases in GH that may enhance hypertrophy induced by resistance exercise. For example, a study reported that the supplements which promote the greatest insulin spike post-exercise lead to significantly higher GH levels 5-6 hours later. In the study, the supplements that contained carbohydrates and/or carbohydrates/protein caused this spike.8 So occasionally spiking insulin with a carbohydrate may be good for muscle.

The author also concluded in the review article that, “Current research strongly suggests that resistance training, especially using large-muscle mass free-weight exercises performed with high training volumes with moderate loads, is partially dependent upon muscle glycogen stores. The amount of glycogen used in these exercises also appears to be related to the total amount of work accomplished and the duration of the resistance-training bout. The ingestion of liquid carbohydrate may serve to promote a faster recovery, which may enhance subsequent exercise and training sessions.9
The bottom line is that there is no universal diet that works for everyone. My graduate professor always told me to remain objective. Each year at major conferences such as Experimental Biology, National Strength and Conditioning Association, and American College of Sports Medicine, scientists present research from their laboratories and at the end of each session, there are other scientists who question the validity of their ideas and research. In the scientific community, being skeptical stimulates thought and leads to other questions and keeps the scientific community pursuing more answers.

Based on the literature, it seems that carbs, although not essential to the human diet, are needed for muscle anabolism, as indicated by certain genes being blunted during glycogen-depleted states. I am not recommending a high carbohydrate diet, but I am also not recommending a low-carb ketogenic diet. I personally believe that occasional increases in carbohydrates and insulin are necessary to hold on to muscle while losing fat during the pre-competition diet. Based on the literature, training in a glycogen-depleted state adversely affects genes for muscle anabolism. No one has looked at changing the fat ratios either; no study has ever looked at zero-carb diets while using healthy fats (mono and omega-3s).

Unfortunately, there will probably never be a study performed for bodybuilders dieting for competition and muscle growth. We can only make conclusions based on peer-reviewed research articles; there is no one shoe that fits everyone. Only through trial and error can you find out exactly how many carbs you need and how frequently they should be consumed.

Key Points:

· Ketogenic diets are great for enhancing fat loss, but may cause more muscle loss.
· Training in a glycogen-depleted state resulted in reduced genes for muscle hypertrophy.
· Weight training performance is limited by low muscle glycogen levels.
· Low glycogen turns on AMPK which is a molecular component of a functional signaling pathway that allows skeletal muscle cells to sense and react to nutrient availability. Interestingly, age-related atrophy and decreased growth capacity is specific to fast-twitch skeletal muscle. When muscle biopsies are performed, AMPK is elevated with age in resting muscle; additionally elevated AMPK activity would correspond with atrophy in growth in fast-twitch muscle.
· Ketogenic diets promote acidosis in muscle (reduced Ph), which can increase muscle tissue proteolysis.

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  15. Steinberg GR, Watt MJ, McGee SL, Chan S, Hargreaves M, Febbraio MA, Stapleton D, Kemp BE. Reduced glycogen availability is associated with increased AMPKalpha2 activity, nuclear AMPKalpha2 protein abundance, and GLUT4 mRNA expression in contracting human skeletal muscle. Appl Physiol Nutr Metab. 2006 Jun;31(3):302-12.
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