Are Protein Supplements Sabotaging Your Ketogenic Diet?

By Dan Gwartney, M.D.

There is a really obnoxious commercial that tries to convince recipients of structured payment settlements that they deserve it all immediately – “I want it now!” Philosopher and cartoon character Homer Simpson defined American character in asking “Do you want the job done right or do you want it done fast?” Wife Marge Simpson responds, “Well, like all Americans, fast.”

This is the appeal of the ketogenic diet; people have reported losing 20 pounds or more in a matter of a week or two. Popularized as the induction phase of the Atkins diet, ketogenic diets have actually been a clinical tool for decades, though not as one might think. The history of ketogenic diets in medical practice originates with the condition of epilepsy.1

Are Protein Supplements Sabotaging Your Ketogenic Diet?


Epilepsy is also known as seizure disorder, and is diagnosed when a person has two or more seizures without apparent cause. Known causes of seizure that are not epilepsy include low blood sugar, alcohol withdrawal, certain drugs, etc. Epileptic seizures may be the result of a malformed brain pathway, trauma, family traits, genetic, or unknown reasons. Currently, there is no cure for epilepsy. At best, medications and lifestyle programming offer varying degrees of control. In addition to medication, epileptics have to avoid triggering events (flashing lights, hyperventilation, etc.). A treatment method initially reported back in the 1920s, forgotten with the introduction of anti-convulsant medications, has regained popularity in the last two decades— ketogenic diets.

As one might imagine, the need for strictly adhering to a ketogenic diet is more critical to an epileptic than a casual dieter. Thus, the dietary and macronutrient protocols in this setting are very strict and concise. Epileptic patients who respond to the ketogenic diet tend to see a rapid increase in seizure frequency and severity if they fail to maintain ketone production due to a dietary lapse. For these patients, the goal is not weight loss but maintaining ketosis to protect against injury or worse. Interestingly, the modified Atkins diet (less than 10 grams carbohydrate daily for children, less than 15 for adults) appears to be similarly effective.2


Most dieters have fallen into the “low-carb” trap when considering ketogenic diets. The appeal to the bodybuilder, beyond the rapid weight/fat loss, is the theoretical protection of lean mass/muscle against protein breakdown. In the muscle and other tissue, a build-up of ketones signals pathways that inhibit further protein breakdown and may stimulate anabolic processes. Further, the ketones can be used as a source of energy (ATP production); this is a critical source of energy for the brain when blood sugar is below what is normally available and stored sugar (glycogen) has been depleted.3 It is important to understand the conditions necessary for ketone production to begin, and equally important to understand what conditions cause ketone production to end.

Ketones are formed primarily in the liver; they are metabolites of long chain fatty acids and certain amino acids created during periods when immediate and near-immediate energy stores are insufficient to meet demand. Typically, active tissues, such as skeletal muscle, use ATP for immediate energy which is quickly regenerated by phosphocreatine. When ATP is used up, it becomes ADP waiting for an energy source to “recharge” it back to ATP. This can come from phosphocreatine; the anaerobic calorie burning of sugar (glucose); or the aerobic calorie burning of sugar, fatty acids, or amino acids. When the ADP:ATP ratio gets higher than normal, fatty acid consumption pathways get activated to promote the breakdown of stored or absorbed fatty acids.

When glucose is readily available from circulating glucose (released by the liver or from a meal) or from the storage form called glycogen (present primarily in skeletal muscle and the liver), sugar metabolism accounts for the majority of calories burned for energy (ATP production) at rest and during intense exercise. During low-intensity exercise, fat may account for the majority of calories burned.

Ketogenesis and Insulin

When glucose is available, the main end products of energy production are carbon dioxide and water derived from the oxidative metabolism of glucose. Ketones accumulate in significant quantities when only fats and ketogenic amino acids are used as substrates (fuel) for oxidative metabolism, and insulin concentration is at a physiologic minimum. The process of generating ketones is called ketogenesis. Ketogensis is ongoing, as there is always a degree of fatty acid metabolism happening, but ketones do not accumulate unless they are being produced at a higher rate than they are cleared (used for energy production).

In order for ketogenesis to progress to a measurable degree, it must not be inhibited by insulin, available glucose (stored or circulating) must be minimal or absent, and the substrates (fatty acids and ketogenic amino acids) must be present in sufficient concentration. Ketogenesis is impeded (slowed or halted) by an influx of glucose or an insulin spike. When most foods are consumed, insulin is released in two phases— a rapid spike and a prolonged surge, depending upon insulinemic agents in the meal (primarily starches and sugars, but also many proteins (especially whey protein) and amino acids).4,5

The first spike suppresses gluconeogenesis (the production of glucose from certain amino acids and glycerol) and readies the liver to accept and store any glucose from the meal or from circulation.6 Insulin also affects the adipocytes (fat cells), reducing the release of stored fat, reducing the availability of fatty acids for calorie-burning or ketone production.7

The Ketogenic Ratio

Looking at the clinical ketogenic diets used in the treatment of epilepsy, one is immediately struck by the macronutrient ratio, which is very different from what athletes typically consume on “low-carb” diets. Ketogenic diets prescribed to minimize and protect against epilepsy are extremely high in fat, not protein. Author Lyle McDonald, well known to many in the bodybuilding and nutritional industry, refers to a 1980 article offering a formula for establishing a “ketotic:anti-ketotic ratio” or K:A.8 To reliably establish and maintain a state of ketosis, it is stated that meals must maintain a K:A ratio of 1.5 or greater.

The IKetogenic Ratio

One might note that by weight (grams), fat needs to be four times that of protein and carbohydrate combined. While many athletes and dieters are capable of reducing carbohydrate intake to 20 grams per day or less (equivalent to the modified Atkins diet), they often resort to high-protein supplements and meals to replace the carbohydrate calories, with only minimal increases in dietary fat. While this may reduce the amplitude (height or power) of the insulin surge and fasting insulin concentration, it is not sufficient to induce dietary ketogenesis.

A recent study compared three days of starvation to a high-fat/high-protein/low-carbohydrate diet (HPLC), as well as a normal mixed diet as a control diet (NPNC).9 Starvation resulted in a reduction in circulating glucose, fatty acids, and an increase in the relative stores of fat in skeletal muscle. Blood glucose was maintained as well on a HPLC diet as it was on a NPNC diet. The authors concluded that increased availability of protein from the diet increased glucose availability and at least reduced if not prevented the release of stored fat from fat cells.

Recall that though some amino acids do convert to ketones, most are readily converted to glucose in the right metabolic conditions. The body is readily able to convert gluconeogenic amino acids to glucose, impeding the need for and rate of ketogenesis. This can be checked individually by using keto-stix or a similar dipstick to check the urine for ketones. Though a crude measure, if one is truly in pronounced ketosis, it should register positive.


Fat is nearly always avoided, as it is calorie dense and traditional lore states that eating fat causes fatness. However, this is challenged by the results of ketogenic diets, such as the induction phase of Atkins, and the results of a recent study completed at East Carolina University.10 The authors demonstrated healthy overweight/obese men had a greater rate of lipolysis (breakdown and release of stored fat) from subcutaneous abdominal fat cells (the ones you can pinch above your belt line) consuming a high-fat diet rather than a balanced diet. Of course, the released fatty acids would still need to be burned for energy production, else they will be re-absorbed into fat cells for a zero-gain effect. This can be accomplished by moderate aerobic exercise or maintaining a hypocaloric intake (eating fewer calories than burned during the day).

Are Protein Supplements Sabotaging Your Ketogenic Diet?


There remains a question then: how much protein can be consumed and allow a person to maintain ketosis? If the data from rodent studies are reliable, the answer appears to be no more than 20 percent (by weight) in a low-carbohydrate setting.11 When fed a diet that was 75 percent fat/10 percent protein/2 percent carbohydrates (the rest was the stuff that gets labeled as “ash” or other products), rats developed a significant ketosis, but this was diminished when the protein content of the diet increased by as little as 5 percent. By the time the protein content reached 30 percent, the rats were no longer in ketosis. Regardless, rats lost about the same amount of bodyweight, due primarily to a loss of lean mass. Obviously, this would be disastrous for a bodybuilder or athlete.

The protein restriction needed to induce and maintain ketosis accounts for one reason that Lyle McDonald does not advocate ketogenic dieting. The other reason is that the fat loss effect of low-carbohydrate diets does not appear to be dependent upon the production or presence of ketones.12

Perhaps the most telling study is the one recently published in the journal Metabolism, the study comparing starvation to a high-protein/low-carbohydrate diet and a control diet.

The percentage (by calorie) of protein was absurdly high, compared to most research diets, being 63 percent protein (35 percent fat and 2 percent carbohydrate). Yet, is that so different from what many bodybuilders following a “ketogenic” diet might consume? The goal of most athletes and bodybuilders is to consume at least 1 gram of protein in a non-ketotic state, and two to five times that in the catabolic environment of ketosis.

Even 1 gram per pound for a 200-pound bodybuilder is 800 calories, or approximately 30 percent of maintenance calories. Double that, substituting protein calories for fat, and you have about the same as this study. Considering that much of the protein is sourced through whey protein powders or milk protein drinks, the fat content is much lower than whole food which would be preferentially high in fat calories.


Ironically, it may be the anabolic-androgen steroid (AAS) using athlete who may be able to tolerate a true ketogenic diet. Though most think of AAS for their anabolic properties, remember that a great deal of AAS use in clinical practice and history entails the anti-catabolic properties of the hormones, and prevention of muscle wasting.13 Also, the shift toward an anabolic state would increase the non-oxidative amino acid disposal (using amino acids for tissue building, not calorie burning), allowing for a greater protein intake.14 This effect to be enhanced when growth hormone is present.

For the drug-free bodybuilder, the data is somewhat conflicting. Hypocaloric dieting, especially in a physically stressful setting, will greatly reduce testosterone concentration.15 When adequate calories are consumed, a low-carbohydrate (not necessarily ketogenic) diet will maintain testosterone concentration.16 Yet, when calorie intake is relatively low, it has been shown that carbohydrate intake of 30 percent or greater enhances testosterone response to exercise.17 If mass retention or gain is part of one’s goals, low-carbohydrate dieting seems counterproductive.

Wrapping Up

What does this tell us in the end? First, it may be folly for a drug-free athlete to attempt a ketogenic diet if he is supplementing with protein (especially whey protein, which spikes insulin) or even consuming a large amount of food-based protein. Second, it is not recommended by many experts, such as Lyle McDonald, for weight loss and especially not for athletes. Third, those still wishing to pursue ketogenic dieting need to restrict not only carbohydrates, but also protein and total calories. Remember, even the glycerol backbone of fat (triglycerides) can provide a source of sugar via gluconeogenesis.

The struggles with ketogenic diets are expressed in a human way in a recent news article, “Epilepsy’s Big Fat Miracle” printed in The New York Times (available online).18 Those wishing to understand what a lifetime adherence to the diet means may find it enlightening.

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