Neuropsychiatric Manifestations Due to Lack of Vitamin B5, B7, C, D, Iron, Magnesium, Zinc and Homocysteine. A Drug Management and Comprehensive Review
Author(s): Sandisiwe Kema1, Lourdes de Fatima Ibanez Valdes2, Sibi Joseph2, Humberto Foyaca Sibat2*
Abstract
Introduction: The role of certain micronutrients, including zinc, iron, vitamins A, D, C and B12, among others, in synergistically and individually ensuring the proper functioning of our complex immune network has become increasingly evident. Recently, some authors have established that ageing and insufficient plasma levels of water-soluble vitamins are both associated with immune decline and chronic inflammation. Therefore, a proper diet and supplementation with vitamins B1 –B12 and vitamin C will counteract these ageing-related immune alterations by supporting immune cell metabolism and reducing susceptibility to infections.
Methods: This review examines the neuropsychiatric manifestations of nutritional deficiencies. PubMed/Medline and Cochrane review databases were searched using the term and Boolean operators: (“nutritional deficiency” OR vitamin deficiency OR mineral deficiency) AND (“neuropsychiatric” OR psychiatric OR cognitive OR depression OR psychosis OR dementia OR anxiety). The search covered publications from January 2020 to June 2026. Studies were eligible for inclusion if they were peer-reviewed articles, systematic reviews, narrative reviews, or original research articles. Articles not available in English, duplicate publications, and studies not primarily focused on FND were excluded. The systematic review performed in this study followed the guidelines recommended by PRISMA (2020 statement).
Results: A total of 924 records were identified through the database search with the search terms. 214 Duplicates were removed. Remaining records underwent title and abstract screening, and 397 were excluded. Articles were excluded if they were not focused on neuropsychiatry, not nutritional deficiency-related or did not meet study eligibility. 149 full-text articles were sought for full-text retrieval. 52 records were further excluded because the full text could not be accessed, and 18 were excluded because they could not be fully translated into English. Ultimately, 94 studies were included for this review.
Conclusion: Nutritional deficiencies may manifest as neuropsychiatric symptoms. Pathophysiology is multifactorial, including impairment to cerebral energy metabolism, disruption of monoamine neurotransmitte synthesis, glutamatergic excitotoxicity through NMDA receptor dysregulation, oxidative stress and loss of antioxidant defence, neuroinflammation, and compromised myelination. Neuropsychiatric symptoms may precede the somatic and systemic manifestations associated with nutritional deficiency. In many cases, these neuropsychiatric features are incorrectly attributed to primary psychiatric disorders. Severe and life-threatening neuropsychiatric syndromes may be missed, leading to increased morbidity and mortality.