Vitamin Deficiencies and Alzheimer's Disease: Evidence and Implications for Supplementation

Mariya Timotey Miteva^1,2Davide Laurenti³Roberto Mattioli³Daniel Di Risola^3*Alessia Mariano³Luciana Mosca³

• ¹Istituto di Farmacologia Traslazionale Consiglio Nazionale delle Ricerche, Rome, Italy
• ²Universita degli Studi di Roma La Sapienza Dipartimento di Sanita Pubblica e Malattie Infettive, Rome, Italy
• ³Universita degli Studi di Roma La Sapienza Dipartimento di Scienze Biochimiche A Rossi Fanelli, Rome, Italy

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by beta-amyloid (Aβ) deposition, hyperphosphorylation of tau protein (pTau), mitochondrial impairment and neuroinflammation. Several risk factors, such as aging, genetics, cardiovascular diseases (CVD) and lifestyle, concur to the onset of the disease. Among modifiable risk factors, micronutrient intake has gained attention for its potential role in preventing or slowing down disease progression. In this narrative review, we summarize current evidence linking vitamin deficiencies to the onset and progression of AD. We analyze evidence for fat-soluble (A, D, E, K) and water-soluble vitamins (C and B-complex, both canonical B1–B12 and non-canonical forms such as B13, B15, and B17). We then analyze individual and combinational vitamin supplementation in AD patients as the primary focus, with additional data derived from animal and cellular studies where human data are limited. As final result, Particular attention is given to the B6, B9, and B12 vitamins, which have demonstrated promising effects in clinical trial. Interestingly, some beneficial effects have also been observed in the prodromal stage of AD when these vitamins are combined with antioxidant compounds such as vitamin C and, vitamin E, and selenium. Given the multifactorial nature of AD, targeting isolated vitamin deficiencies may not be sufficient. Future research should focus on long-term clinical trials (at least Codice campo modificato two years), particularly exploring combinations of vitamins and antioxidants, to achieve meaningful therapeutic effects. Future research should focus on replicating the most promising findings to date, particularly those involving supplementation in the form of vitamins cocktails. To ensure clinical relevance, such trials should be designed with a duration of at least two years. This review is intended as a point of support for future clinical trials in the treatment of AD from a nutritional point of view.