Can High-protein, Very Low-carb Diets Lead to Ketoacidosis in Healthy Subjects?

Nutrition & Metabolism

when it comes to fat loss, a calorie is certainly not a calorie. In fact, it seems to me that calorie

content may not be as predictive of fat loss as is reduced carbohydrate consumption. Similarly, a

recent, well-designed meta-analysis (quantitative statistical analysis that’s applied to separate,

but similar, experiments), published in the American Journal of Clinical Nutrition, concluded that

low- and very low-carbohydrate diets favorably affect body mass and composition, independent of

energy intake, supporting the proposed metabolic advantage of these diets.

However, there have been some concerns that very low-carbohydrate diets may have

some adverse effects, especially in the long term. Recently, a well-known medical journal, The, published two articles blasting high-protein/low-carbohydrate diets. Let’s examine

Lancet

whether the information provided by these articles justifies the horror stories published in the

mainstream media.

When the rate of mobilization of fatty acids from fat tissue is accelerated, as, for example,

during a very low-carbohydrate diet, the liver produces ketone bodies. The liver can’t utilize

ketone bodies and thus, they flow from the liver to extra-hepatic tissues (e.g., brain, muscle) for

use as a fuel. Simply stated, ketone body metabolism by the brain displaces glucose utilization

and thus, spares muscle mass. Dietary ketosis is a harmless physiological state; however, many

healthcare professionals have confused dietary ketosis with diabetic ketoacidosis (an abnormal

condition of increased acidity).

All diabetic patients know that the detection in their urine of ketone bodies is a danger

signal that their diabetes is poorly controlled. In severely uncontrolled diabetes, if the ketone

bodies are produced in massive supranormal quantities, they’re associated with ketoacidosis. In

this life-threatening complication of diabetes mellitus, ketone bodies are produced rapidly, which

overwhelm the body’s acid-base buffering system. However, a very low-carbohydrate diet can’t

lead to dangerous ketoacidosis in healthy subjects (without alcohol or drug abuse), because

ketone bodies have effects on insulin and glucagon secretions that contribute to the control of the

rate of their own formation.

Nevertheless, a case report, published in The Lancet, described a 40-year-old female

patient who was vomiting as often as six times daily and had difficulty breathing after strictly

following the Atkins diet for a month. According to the report, "Our patient denied alcohol use; her

serum osmolar gap was 0, which excludes the presence of unmeasured osmotic agents such as

methanol or ethylene glycol; L-lactate concentration was normal; and salicylate was undetectable.

Serum [blood] was positive for acetone, and ß-hydroxybutyrate [a major ketone body] was high at

390 μg/mL (normal 0ˆ44 μg/mL), consistent with ketoacidosis."

However, it’s my view that the level of ketones in her urine (390 μg/mL) isn’t alarming.

Just to be sure, I contacted Dr. Richard Feinman, a professor of biochemistry at SUNY

Downstate Medical Center and a well-known researcher in the area of carbohydrate-restriction, to

ask his opinion about The Lancet case report. According to Dr. Feinman, "Clinicians here agree

that it was kind of a rash conclusion. The ketones are, in fact, not sufficient to have caused the

acidosis, and while high for most people on the Atkins diet, they are in the ballpark of people who

are in starvation for 10 days (who can live for at least another 20-60 days) and less than half of

the ketoacidosis seen in untreated type 1 diabetes. We are actually using the case with students

to show how to do the calculations correctly. I think the physicians were just not familiar with the

whole problem of ketosis and got carried away. The Atkins diet still has so much baggage in

medical circles that they didn't realize you can't attribute things to diet just on what people tell

you. In any case, she apparently hadn't retained much food at all for three days and was probably

in starvation rather than on any diet. The treatment was actually minimal (mostly rehydration) and

the whole thing was blown way out of proportion. Also, even if the problems were due to the diet,

millions of Americans are on some kind of carbohydrate-restricted diet and nutritionists have been

trying unsuccessfully to find a problem for 30 years. Do you know any drug, or even any weight

loss diet, that has this kind of record?"

In a commentary also published in The Lancet, Drs. Lyn Steffen and Jennifer Nettleton of

the University of Minnesota's School of Public Health blasted low-carbohydrate/high-protein diets

like there’s no tomorrow. These sadly misinformed ladies supposedly hold some sort of doctoral

degrees, yet can’t even perform an appropriate PubMed search. They stated, "These [lowcarb/

high-protein] diets also increase the protein load to the kidneys and alter the acid balance of

the body, which result in loss of minerals from bone stores, thus compromising bone integrity."

This statement is misleading, at best. The best available scientific evidence indicates that

protein-induced changes in kidney function are a normal, adaptative mechanism well within the

functional limits of a healthy kidney. However, protein restriction may benefit patients with chronic

kidney disease. Also, there’s no scientific evidence supporting the notion that a lowcarbohydrate/

high-protein diet leads to loss of minerals from bone stores. Quite the contrary.

Many experimental and clinical studies indicate that a low-protein diet negatively affects bone

health. Furthermore, it’s been demonstrated that proteins enhance IGF-1, a growth factor exerting

positive activity on bone formation. Consequently, high-protein intake is, if anything, protective

against loss of bone minerals.

Don’t get me wrong. MD isn’t advocating for the Atkins diet. We feel a diet containing

moderate amounts of low-glycemic carbohydrates is generally the healthiest way to achieve and

maintain ideal bodyweight. However, we realize one diet approach doesn’t fit all. Identifying

specific needs, goals and the activity level of each individual is the key for success. Thus, we

advocate applying science to all diets, including the Atkins diet. Certainly, diet-related public

warnings should be based on thorough analysis of the scientific literature, not unsubstantiated

fears and misrepresentations.