What are the indications and risks of a ketogenic diet for patients, particularly those with conditions like epilepsy or type 2 diabetes?

Ketogenic Diet: Indications and Risks

The ketogenic diet is a validated therapeutic option primarily for drug-resistant epilepsy in children, with emerging evidence for metabolic conditions like type 2 diabetes, but should be avoided in patients with or at risk of malnutrition. 1, 2

Primary Indication: Drug-Resistant Epilepsy

Children with Epilepsy

• Use ketogenic diets when seizures persist despite adequate trials of antiepileptic drugs. 2, 3
• Seizure freedom occurs in up to 55% of children on classical 4:1 ketogenic diet at three months, with up to 85% achieving ≥50% seizure reduction. 2
• The diet demonstrates effectiveness comparable to modern antiepileptic drugs for seizure control in short to medium term. 2, 4
• Modified Atkins diet (MAD) may provide similar seizure control benefits with better tolerability—up to 60% of children achieve ≥50% seizure reduction with fewer adverse effects than classical ketogenic diet. 2

Adults with Epilepsy

• Evidence for adults remains limited and uncertain—no adults achieved seizure freedom in available trials. 2
• Modified Atkins diet showed 42.5% of adults achieving seizure reduction at one month, though only 10% maintained this benefit at three months. 2
• Consider ketogenic diets for adults with drug-resistant epilepsy only when surgery is unsuitable and after careful discussion of limited evidence. 2, 4

Emerging Indication: Type 2 Diabetes and Weight Management

Metabolic Benefits

• Low-carbohydrate diets hold no overall advantage for weight loss compared to higher-carbohydrate diets when calories are controlled. 1
• Insulin resistance decreases by 57%, with particularly pronounced improvements in individuals with pre-existing hyperinsulinemia. 5
• Intrahepatic lipid content reduces by approximately 31% in overweight individuals with non-alcoholic fatty liver disease, even with moderate weight loss. 5
• Energy expenditure increases by approximately 52 kcal/day for every 10% decrease in carbohydrate contribution to total energy intake. 5

Diabetes Remission

• The main contributor to HbA1c reduction and diabetes remission is weight loss, irrespective of diet type. 1
• Highest remission rates (up to 75%) occur in people with newly diagnosed diabetes or <2 years duration; much lower rates (20-22%) with longer diabetes duration. 1
• Structured programs with intensive induction phases using total diet replacement are most effective for achieving remission. 1

Absolute Contraindications

Do not use ketogenic diets in the following situations:

• Patients with existing malnutrition or at risk of malnutrition. 1, 5, 6
• Cancer patients who are malnourished—no clinical trials demonstrate benefit, and low palatability may lead to insufficient energy intake and weight loss. 1
• Patients with eating disorders or those unable to maintain adequate energy and protein intake. 7
• Patients taking SGLT2 inhibitors due to metabolic ketoacidosis risk. 1

Significant Risks and Adverse Effects

Nutritional Deficiencies

• Monitor for deficiencies in calcium, vitamin A, thiamine, vitamin C, vitamin D, folate, and pantothenic acid. 6, 7
• Heart failure and neurological problems from thiamine deficiency have been reported. 1
• Reduced intakes of folate, iron, and magnesium are common. 1
• The diet increases risk of insufficient intake of energy, fat, and protein if not meticulously planned. 1, 6

Cardiovascular Concerns

• Elevations in atherogenic lipoproteins, including LDL cholesterol, occur despite weight loss. 6, 7
• Replacing high-carbohydrate foods with red or processed meat increases sodium and long-chain saturated fat intakes, elevating LDL-cholesterol and potentially increasing cardiovascular disease risk. 1
• Baseline and follow-up lipid panels are essential. 7

Metabolic Complications

• Metabolic ketoacidosis is a hazard, particularly with SGLT2 inhibitors. 1
• Blood pressure falls with weight loss; postural hypotension is aggravated during rapid weight loss if diuretic or antihypertensive drugs are taken concurrently. 1
• Hypoglycemia is possible if hypoglycemic drugs are also taken—medication adjustments are mandatory. 1
• High protein intake has been associated with kidney diseases in observational studies. 1
• Extreme fat avoidance provokes cholelithiasis. 1

Gastrointestinal Effects

• Most commonly reported adverse effects are vomiting, constipation, and diarrhea in both children and adults. 2
• Gastrointestinal disturbances are more frequent with 4:1 versus 3:1 ketogenic diet ratios. 2

Tolerability Issues

• High attrition rates suggest many children find the diet difficult to tolerate long-term. 2, 4
• Main reasons for discontinuation include gastrointestinal side effects and dislike for the diet. 2

Essential Monitoring Protocol

Initial Assessment

• Complete baseline metabolic panel, lipid panel, body composition analysis, and micronutrient assessment before starting. 7
• Assess for contraindications including malnutrition risk and eating disorders. 7

Ongoing Monitoring

• Monitor body composition monthly for 3 months, then quarterly, to ensure weight loss comes predominantly from fat rather than muscle. 6, 7
• Monitor lipid panel and metabolic markers at 3 months, then every 6 months. 7
• Monitor micronutrients at 3 months, then as clinically indicated. 7
• Track fluid changes to help patients understand that initial rapid weight loss is primarily water weight due to glycogen depletion. 5, 6

Medication Adjustments

• Account for carbohydrate content in prescription and over-the-counter medications, as overlooked carbohydrates can inhibit ketosis and cause loss of seizure control. 8
• Reduce or discontinue hypoglycemic medications, antihypertensives, and diuretics as needed during rapid weight loss phase. 1

Practical Implementation Algorithm

Step 1: Determine Candidacy

• Primary indication: Drug-resistant epilepsy in children after adequate antiepileptic drug trials. 2, 3
• Secondary consideration: Type 2 diabetes with goal of weight loss and potential remission, particularly if diabetes duration <2 years. 1
• Exclude: Malnutrition, eating disorders, cancer patients with weight loss, concurrent SGLT2 inhibitor use. 1, 7

Step 2: Choose Diet Type

• For epilepsy in children: Start with modified Atkins diet for better tolerability; consider classical 4:1 ketogenic diet if MAD insufficient. 2
• For type 2 diabetes: Any structured program with intensive induction phase; specific macronutrient composition less important than adherence and weight loss. 1

Step 3: Ensure Adequate Protein

• Provide adequate protein intake to support the protein-sparing effect of ketosis and preserve lean body mass. 6
• The diet acts as a "protein sparing modified fast" only when protein intake is sufficient. 5, 6

Step 4: Implement Monitoring Schedule

• Baseline: Metabolic panel, lipids, body composition, micronutrients. 7
• Months 1-3: Monthly body composition. 7
• Month 3: Lipids, metabolic markers, micronutrients. 7
• Ongoing: Quarterly body composition, semi-annual lipids and metabolic markers. 7

Critical Caveats

• Initial rapid weight loss creates false expectations—this is primarily water weight from glycogen depletion, not fat loss. 5, 6
• Skills and empathy of practitioners may overcome diet-specific effects by providing consistent evidence-based support. 1
• Patient preferences, culture, context, and lifestyle demand open conversation and shared decision-making. 1
• For diabetes management, Mediterranean dietary pattern remains first-line for cardiovascular risk reduction. 6
• Ketogenic approaches do not meet criteria for cardiovascular health due to excessive total fat, saturated fat, and severely restricted carbohydrates. 6