Hallucinations and Vitamin B12 Deficiency: A Systematic Review.

introductionVitamin B12 deficiency is primarily associated with pernicious anaemia, polyneuropathy, and spinal-cord disease, but publications on its association with hallucinations are on the rise.

methodsI carried out a systematic literature search on these hallucinations in PubMed, PsycINFO, and Google Scholar, up until July 1, 2023.

resultsThe search yielded 50 case studies published between 1960 and 2023. The hallucinations described therein are predominantly visual and/or auditory in nature, with 20% being specified as complex, compound, or panoramic. They are often described in the context of vitamin B12-related neuropsychiatric conditions such as dementia, delirium, epilepsy, psychotic disorder, schizoaffective disorder, bipolar disorder, depressive disorder, catatonia, or obsessive-compulsive disorder. In the context of such disorders, they tend to appear first and also often appear to be the first to disappear with cobalamin treatment. Within an average of 2 months, full amelioration was thus obtained in 75% of the cases and partial amelioration in the remaining 25%. Remarkably, a quarter of the cases involved therapy-resistant hallucinations that fully resolved under cobalamin monotherapy, while other neuropsychiatric manifestations of vitamin B12 deficiency disappeared in 60% of the treated cases. Only 32% of the cases involved comorbid pernicious anaemia. This suggests that two separate or diverging pathways exist for perceptual and haematological symptoms of vitamin B12 deficiency.

conclusionIn the light of the high prevalence rate of vitamin B12 deficiency in the general population, the findings here presented should be interpreted with great caution. Nonetheless, they offer cues for further research and experimental application in clinical practice. This may be especially relevant in light of the recent increase in the popularity of vegetarianism and the recreational use of nitrous oxide (laughing gas), which are both risk factors for vitamin B12 deficiency.