What are the Side Effects of Ketosis?

Ketosis is a result of change in the body’s energy source from carbohydrate to fat. In humans, carbohydrate is the primary source of energy. Once the carbohydrate storage in the body (glycogen) is completely used by the body and low insulin secretion is seen, the body undergoes metabolic changes. The metabolic changes include production of glucose in the liver from lactic acid, glycerol, amino acids and glutamine (gluconeogenesis). As the glucose level further drops, fat is broken into fatty acids (ketogenesis) in the form of ketone bodies. Ketone bodies serve as an alternate form of energy source, this metabolic state is known as ketosis.⁽¹⁾

Ketosis is a normal mechanism in humans which is generally seen during fasting, breastfeeding and after exercise. Ketones serve as an additional source of energy to the brain after glucose. During fasting, ketone bodies act as an alternate to glucose which is important for preventing muscle destruction during glucose synthesis. Ketogenic diet is intake of 55% to 60% fat, 30% to 35% protein and 5% to 10% carbohydrates. This diet forces the liver to produce ketone bodies into the circulation, and this is known as nutritional ketosis.^(1,2)

As this diet is continued, the body will adapt to ketone bodies as a primary source of energy for the body, this adaptation is called as Keto-adaptation. The keto-adaptation has many benefits such as properties of anti-inflammation, anti-oxidative properties, preventing fatigue after exercise and preventing organ damage. Nutrititional ketosis was first introduced for treating epilepsy in the year 1921 by Russel Wilder. It provided the required anti-epileptic agents for the treatment of epilepsy. It was also used for weight loss, obesity, bipolar illness, and infantile spasms.⁽³⁾ However, too much of ketone on the body can have side effects. Let us look at the different side effects that can happen due to excess ketones in the body.

Nutritional ketosis has lot of benefits such as weight loss, to enhance memory and cognition, for treatment of type 2 diabetes. It also acts as an adjuvant therapy for cancer and neurological disorders.

However, excess of ketones in the body can have its own impact. Let us look at the side effects of ketosis such as short-term and long-term effects.

Side effects of following a ketogenic diet and the mechanism of ketosis are seen as early as first few days to few weeks. The symptoms are referred as “keto-flu”. The short term symptoms are:

• Gastrointestinal discomfort such as nausea, vomiting, diarrhea
• Headache
• Fatigue (tiredness)
• Reduced exercise tolerance
• Constipation
• Hypoglycaemia (low blood sugar)
• Insomnia. (sleep disorder)^(1,4)

Severe Hepatic Steatosis as a Long-term Side Effect of Ketosis: In this condition, there is excess fat stored in the liver which on a prolonged period can lead to metabolic dysfunction in liver, inflammation and non-alcoholic fatty liver disease.⁽⁵⁾

• Hypoprotenemia: In nutritional ketosis, there is reduced intake of protein which causes deficiency and can lead to hypoprotenemia.⁽⁶⁾
• Cardiomyopathy as a Long-term Side Effect of Ketosis: In ketosis, there is deficiency of selenium (mineral), which causes impairment in myocardial function, prolonged QT interval in ECG. This can lead to selenium-deficiency cardiomyopathy.⁽⁷⁾
• Mineral Deficiencies: Studies show that there are marked decrease in the minerals in the body such as copper, zinc and selenium during ketosis.⁽⁸⁾
• Increased Risk of Kidney Stones: In ketosis, one can experience hypercalciuria (excess calcium in the urine), there is increased calcium exertion by the kidney this increases the stone formation.⁽⁹⁾
• Dyslipidemia as a Long-term Side Effect of Ketosis: Studies show marked increase in the cholesterol and triglycerides levels during the ketosis stage which increases the chances of getting heart problems such as atherosclerosis.⁽¹⁰⁾
• Metabolic Acidosis as a Long-term Side Effect of Ketosis: Metabolic acidosis is caused due to lack of glucose. It is a life-threatening condition if not treated, as it is associated with organ failure such as the respiratory system and cardiovascular system.⁽¹¹⁾

The management of the adverse effects of ketosis needs to be conservative and through medical management. These include:

The symptoms of keto flu i.e., nausea, vomiting, hypoglycaemia can be managed with adequate fluid and electrolyte intake.

Decreasing the quantity of long-chain triglycerides (LCT) or medium chain triglycerides (MCT) and increasing the meal frequency helps in improving the ketosis related diet tolerance.

Changing the fat source and increasing oils and decreasing saturated fat can reduce the cholesterol level. Intake of omega-fatty acids and changing the protein source can also help in decreasing the cholesterol level.

Taking supplements of zinc, calcium, selenium, vitamin D and oral alkalis can reduce nutritional deficiencies, decreases selenium related heart problems and also the kidney stone formation.

Taking medications such as H2 blockers or proton pump inhibitors can prevent gastro-intestinal dysmotility and gastroesophageal reflux.

High-fibre rich food intake such as vegetables and fruits can be recommended for treating constipation. Constipation can also be managed by using more oils than saturated fats and use of non-absorbable fibers.

Metabolic acidosis can be managed by monitoring protein intake, increasing the intake of alkaline mineral-rich, and low carbohydrate green vegetables.^(1,12,13)

Ketosis is used as an alternative therapy to treat conditions such as epilepsy in paediatric patients, diabetes, obesity, endocrine disorders, Alzheimer’s disease, neurodegenerative disorders. It is proved to be safe to be followed for long period of time. Even though there are side- effects due to ketosis, it can be managed conservatively and through medical management. It requires a strict medical supervision to identify and manage the side effects at the earliest.

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