Summary

Ketogenic diet has in recent times been popularised as an effective strategy to fight obesity. But, before advising it to patients, doctors must be aware of,

• the mode of action by which weight loss occurs
• the ketogenic 'flu' and other adverse effects
• counterindications and specific clinical considerations

Weight loss via properly tailored diet modification is an option which can seemingly solve the obesity epidemic. A very popular and effective form of dieting that does produce good weight loss results is based on consuming high-fats (55 to 60%), moderate-proteins (30 to 35%), and very-low-carbohydrates (5 to 10%) and this is the hallmark of the ketogenic diet. Used to first treat epilepsy in 1921, the ketogenic diet was in the picture even before the advent of anti-epileptic drugs and was popularly being used to treat epilepsy for almost a decade.

The diet regained its popularity relatively recently as an option that results in rapid and effective weight loss in a short term. Dieting is becoming even more relevant today since obesity is one condition that is rampant and proven to be responsible for significant morbidity and mortality.

Gluconeogenesis and ketogenesis

Once carbohydrate intake reduction (<50 g/day) is experienced, insulin secretion is reduced and catabolism occurs. Glycogen stores are broken down with the result that gluconeogenesis and ketogenesis begins to occur. Glucose production begins in the liver from lactic acid, glycerol, and the amino acids alanine and glutamine. When gluconeogenesis also fails to provide the body with enough glucose and energy, ketone bodies begin to form as an alternate source of energy for the body.

Soon, ketone bodies become the primary source of energy and since glucose levels remain low, insulin production also remains low and hence fat and glucose storage are not stimulated. Fats are broken down into fatty acids at a greater rate due to hormonal changes. They get metabolised to acetoacetate which is then converted to beta-hydroxybutyrate and acetone.

Ketone bodies persist in the body as long as the ketogenic diet is continued, and the body stays in a state of "nutritional ketosis". Nutritional ketosis can be regarded as safe since the concentration level of ketone bodies produced is low and does not alter the blood pH. This is in contrast to the life threatening condition of ketoacidosis in which much higher concentration levels of ketone bodies are formed that alter the pH of the blood making it acidic.

Ketone bodies as energy

Energy produced by ketone bodies is sufficient to meet the demands of the body including that of organs such as heart, muscle tissue, and the kidneys. Moreover since ketone bodies easily cross the blood brain barrier they can provide as an alternative source of energy to the brain. The resting basal metabolic rate (BMR), body mass index (BMI), and body fat percentage are some of the factors that decide the rate of ketone body production.

Ketone bodies can be regarded as "super fuel" since they produce more adenosine triphosphate (ATP) than glucose. Around 100 grams of glucose produces merely 8,700 grams of ATP, whereas 9,400 grams and 10,500 grams of ATP are yielded from 100 grams of acetoacetate and beta-hydroxybutyrate respectively. This ensures that even during a caloric deficit state the body produces fuel efficiently. Ketone bodies are also known to protect from free radical damage by means of their antioxidant properties.

Adverse effects of the ketogenic diet

A ketogenic "flu" is most commonly experienced with symptoms ranging from nausea, vomiting, headache, fatigue, dizziness, insomnia, difficulty in exercise tolerance, and constipation which can occur as mild short term effects lasting between a few days to few weeks.

Rehydration with fluids and electrolytes are beneficial in managing some of these symptoms. The short term benefits of ketogenic diets for up to 2 years are well known but long-term hazards are not very well known. Hepatic steatosis, hypoproteinemia, kidney stones, vitamin and mineral deficiencies are the long term health problems associated with ketogenic diets.

Contraindications and cautions

1. Patients with pancreatitis, liver failure, disorders of fat metabolism, primary carnitine deficiency, carnitine palmitoyltransferase deficiency, carnitine translocase deficiency, porphyrias, or pyruvate kinase deficiency are barred from ever trying the diet.
2. Severe hypoglycemia can occur in diabetes patients on insulin or oral hypoglycemic agents if they do not adjust their dosing appropriately.
3. Although rare, a false positive breath alcohol test can occur in persons on the ketogenic diet since ketones in the blood are sometimes reduced to isopropanol by hepatic alcohol dehydrogenase.

Clinical evidence of weight loss

There is no proof that high fat diets cause obesity or other diseases such as coronary heart disease, diabetes, and cancer. In contrast, high-fat diets with very-low-carbohydrates such as the ketogenic diet have been shown to cause weight loss. Significantly greater weight loss is achieved by lowering carbohydrates in the diet than by lowering fats in the diet. A carbohydrate-restricted diet is better than a low-fat diet for maintaining an individual’s BMR.

It seems that the quality of calories consumed may affect the number of calories burned since the drop in BMR depends on the calorie source, and it drop by more than 400 kcal/day on a low-fat diet when compared to the drop on a very low-carb diet.

Unless the individual following the ketogenic diet is doing a lot of heavy exercise and weight training (in which case 1.5 g/lb body weight protein intake is acceptable), besides limiting carbohydrates, protein intake should be limited to less than 1 g/lb body weight. This prevents gluconeogenesis in the body but does not restrict fat or overall daily calories.

Rapid weight loss of up to 10 lbs in 14 days or less is experienced initially by people that go on the ketogenic diet. Some of this initial loss is water loss, due to ketogenic diets having a diuretic effect but soon after, fat loss is also experienced. Lean body muscle sparing is seen in this diet. Once the nutritional ketosis sets in, hunger pangs settle down and the reduced caloric intake encourages weight loss.

As with any lifestyle changes, compliance with ketogenic diets is low in the long term. The ketogenic diet is significantly superior to any other diet in otherwise healthy people and leads to rapid, intense, sustained weight loss for up to 2 years and it may be started for a minimum of 2 to 3 weeks and continued for 6 months to one year. Renal function monitoring is critical while on the ketogenic diet and the transition back to a standard diet should be slow and gradual.