Adverse events and tolerability of ketogenic diets – a systematic literature analysis

BACKGROUND: Ketogenic diets (KDs) are becoming increasingly popular in the treatment of various diseases, not just pharmacoresistant epilepsy. Despite the growing use of this dietary approach and its economic rationale, a systematic overview of the associated adverse events remains conspicuously absent. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines in the electronic database PubMed. Prospective interventional studies documenting adverse events associated with ketogenic diets published between 2019 and 2024 were included. The recorded adverse events were categorized according to CTCAE criteria and analyzed based on frequency and diversity by diet type. RESULTS: A total of 36 studies involving 42 ketogenic interventions (classic KD, modified Atkins diet, MCT-based KD, LGIT) were evaluated. The included studies covered a wide range of age groups and conditions. At least one adverse event was documented in 43% of the participants (0-89%, 0.91 ± 0.71 adverse events per person). The most prevalent adverse events were gastrointestinal (40%), followed by neurological (17%), and metabolic and nutritional (12%) disorders. Constipation (24%) was the most commonly reported individual adverse event. A higher rate and severity of adverse events was observed in patients following stricter diets. The tolerability of the intervention was influenced by several factors, including age, the presence of underlying diseases, and the duration of the intervention. CONCLUSIONS: The analysis indicates that adverse events frequently occur alongside KD and encompass a broad spectrum, with gastrointestinal complaints predominating. However, the significance of the findings is limited by the heterogeneity of dietary regimens, the lack of standardization, and the occasional inadequate documentation of adverse events. In clinical practice, it is recommended that adverse events are recorded systematically and monitored regularly.