# Vitamin deficiencies and Alzheimer’s disease: evidence and implications for supplementation

**Authors:** Mariya Timotey Miteva, Davide Laurenti, Roberto Mattioli, Daniel Di Risola, Alessia Mariano, Luciana Mosca

PMC · DOI: 10.3389/fnut.2026.1676497 · Frontiers in Nutrition · 2026-02-13

## TL;DR

This review explores how vitamin deficiencies may contribute to Alzheimer’s disease and suggests that vitamin supplementation could help slow its progression.

## Contribution

The paper highlights the potential of B6, B9, and B12 vitamins combined with antioxidants in slowing Alzheimer’s progression.

## Key findings

- B6, B9, and B12 vitamins showed promising effects in clinical trials for Alzheimer’s.
- Combining these vitamins with antioxidants like vitamin C and E showed benefits in the early stages of Alzheimer’s.
- Long-term clinical trials are needed to explore vitamin and antioxidant combinations for effective treatment.

## Abstract

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 when human data are limited. As final result, B6, B9, and B12 vitamins have demonstrated promising effects in clinical trials. Interestingly, some beneficial effects have also been observed in the prodromal stage of AD when these vitamins were combined with antioxidant compounds such as vitamin C and vitamin E. 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 2 years), particularly exploring combinations of vitamins and antioxidants, to achieve meaningful therapeutic effects. This review is intended as a point of support for future clinical trials in the treatment of AD from a nutritional point of view.

## Linked entities

- **Chemicals:** vitamin A (PubChem CID 445354), vitamin E (PubChem CID 14985), vitamin K (PubChem CID 5280483), vitamin C (PubChem CID 54670067), vitamin B6 (PubChem CID 1054), vitamin B9 (PubChem CID 135398658), vitamin B12 (PubChem CID 73415824), vitamin B13 (PubChem CID 967), vitamin B15 (PubChem CID 45934203), vitamin B17 (PubChem CID 5484354)
- **Diseases:** Alzheimer’s disease (MONDO:0004975)

## Full-text entities

- **Genes:** Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, PROS1 (protein S) [NCBI Gene 5627] {aka PROS, PS21, PS22, PS23, PS24, PS25}, PEMT (phosphatidylethanolamine N-methyltransferase) [NCBI Gene 10400] {aka PEAMT, PEMPT, PEMT2, PLMT}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TAS2R62P (taste 2 receptor member 62, pseudogene) [NCBI Gene 338399] {aka PS1, T2R62, TAS2R62}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Ache (acetylcholinesterase) [NCBI Gene 83817], Casp1 (caspase 1) [NCBI Gene 25166] {aka Ice, Il1bc, p45}, VDR (vitamin D receptor) [NCBI Gene 7421] {aka NR1I1, PPP1R163}, GAS6 (growth arrest specific 6) [NCBI Gene 2621] {aka AXLLG, AXSF}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Slc24a2 (solute carrier family 24 (sodium/potassium/calcium exchanger), member 2) [NCBI Gene 76376] {aka 2810021B17Rik, 6330417K15Rik, Nckx2}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Becn1 (beclin 1, autophagy related) [NCBI Gene 56208] {aka Atg6}, Slc23a2 (solute carrier family 23 (nucleobase transporters), member 2) [NCBI Gene 54338] {aka NBTL1, SVCT2, Slc23a1, YSPL2, YSPL3, mKIAA0238}, TH (tyrosine hydroxylase) [NCBI Gene 7054] {aka DYT14, DYT5b, TYH}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, TKT (transketolase) [NCBI Gene 7086] {aka HEL-S-48, HEL107, SDDHD, TK, TKT1}, Lep (leptin) [NCBI Gene 16846] {aka ob, obese}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Casp9 (caspase 9) [NCBI Gene 58918] {aka Apaf3, Casp-9-CTD, Casp9_v1, Ice-Lap6, Mch6}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, Map1lc3a (microtubule-associated protein 1 light chain 3 alpha) [NCBI Gene 66734] {aka 1010001H21Rik, 4922501H04Rik, LC3, LC3a}, BACE1 (beta-secretase 1) [NCBI Gene 23621] {aka ASP2, BACE, HSPC104}, NDUFB3 (NADH:ubiquinone oxidoreductase subunit B3) [NCBI Gene 4709] {aka B12, CI-B12, MC1DN25}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Chat (choline O-acetyltransferase) [NCBI Gene 12647] {aka B230380D24Rik, CHOACTase}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Ttpa (tocopherol (alpha) transfer protein) [NCBI Gene 50500] {aka alpha-TTP}, DBH (dopamine beta-hydroxylase) [NCBI Gene 1621] {aka DBM, ORTHYP1}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Hsp86-ps2 (heat shock protein 86, pseudogene 2) [NCBI Gene 111042] {aka 86kDa, Hsp86-3, Hsp90}, Nup62 (nucleoporin 62) [NCBI Gene 18226] {aka D7Ertd649e, Nupc1, p62}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Pla2g4a (phospholipase A2, group IVA (cytosolic, calcium-dependent)) [NCBI Gene 18783] {aka Pla2g4, cPLA2, cPLA2-alpha, cPLA2alpha}, CAT (catalase) [NCBI Gene 847], Bche (butyrylcholinesterase) [NCBI Gene 65036], Gdnf (glial cell line derived neurotrophic factor) [NCBI Gene 14573] {aka ATF}, Gas6 (growth arrest specific 6) [NCBI Gene 58935], Ide (insulin degrading enzyme) [NCBI Gene 15925] {aka 1300012G03Rik, 4833415K22Rik}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Nos1 (nitric oxide synthase 1, neuronal) [NCBI Gene 18125] {aka 2310005C01Rik, N-NOS, NC-NOS, NO, NOS, NOS-I}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Bace1 (beta-site APP cleaving enzyme 1) [NCBI Gene 23821] {aka ASP2, Bace}, MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) [NCBI Gene 4548] {aka HMAG, MS, cblG}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Bace1 (beta-secretase 1) [NCBI Gene 29392] {aka Bace}, OCM (oncomodulin) [NCBI Gene 654231] {aka OCM1, OM, ONCM}, Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Ghrl (ghrelin) [NCBI Gene 58991] {aka 2210006E23Rik, Ghr, MTLRP, MTLRPAP, m46}, App (amyloid beta precursor protein) [NCBI Gene 54226] {aka Abeta}, Rars1 (arginyl-tRNA synthetase 1) [NCBI Gene 104458] {aka 2610011N19Rik, 2610037E21Rik, Rars}, Casp3 (caspase 3) [NCBI Gene 25402] {aka CPP32-beta, Lice, Yama}, Cdk5 (cyclin dependent kinase 5) [NCBI Gene 12568] {aka Crk6}
- **Diseases:** neuropathological process (MESH:D001308), neurodegeneration (MESH:D019636), inflammation (MESH:D007249), mitochondrial damage (MESH:D028361), tube (MESH:D005184), bone fracture (MESH:D050723), vitamin B5 deficiency (MESH:C567102), diabetes (MESH:D003920), cerebral ischemia (MESH:D002545), cancer (MESH:D009369), AD (MESH:D000544), MCI (MESH:D060825), brain atrophy (MESH:C566985), reduced (MESH:D001523), neural dysfunction (MESH:D015441), neurotoxicity (MESH:D020258), neuroinflammation (MESH:D000090862), atrophy (MESH:D001284), BBB (MESH:C536830), NAD+ deficiency (MESH:D016111), Riboflavin (MESH:D012257), vitamin D deficiency (MESH:D014808), a decrease in motor skills (MESH:D019957), Vitamin B12 deficiency (MESH:D014806), neurological dysfunction (MESH:D009461), seizure (MESH:D012640), metabolic defects (MESH:D008659), synaptic degeneration (MESH:D012183), frailty (MESH:D000073496), TDP (MESH:D013832), Vitamin E (MESH:D014811), perturbations (MESH:C536875), nerve damage (MESH:D000080902), brain injuries (MESH:D001930), vascular dementias (MESH:D015140), malnutrition (MESH:D044342), cerebral infarct (MESH:D002544), infections (MESH:D007239), CVD (MESH:D002318), osteoporosis (MESH:D010024), insulin resistance (MESH:D007333), cytotoxicity (MESH:D064420), VAD (MESH:D014802), vitamin K deficiency (MESH:D014813), hypovitaminosis of B1 (MESH:C566196), vitamin C deficiency (MESH:D001206), axon degeneration (MESH:D009410), dementia (MESH:D003704), amyloid (MESH:C000718787), low (MESH:D009800), glutamate (MESH:C537425), vitamin B2 deficiency (MESH:C536943), loss of appetite (MESH:D001068), hyperoxaluria type I. (MESH:C536414), necrosis (MESH:D009336), intestinal diseases (MESH:D007410), amnesia (MESH:D000647), synaptic dysfunction (MESH:C536122), memory deficits (MESH:D008569), motor dysfunctions (MESH:D000068079)
- **Chemicals:** 3-O-methyl DCI (MESH:C021730), Vitamin D (MESH:D014807), 2-methyl-1,4-naphthoquinone (MESH:D024483), metal (MESH:D008670), fat (MESH:D005223), methionine (MESH:D008715), choline alfoscerate (MESH:D005997), zinc (MESH:D015032), pyridoxine (MESH:D011736), Pangamic acid (MESH:C105565), sugar (MESH:D000073893), 24S-HC (MESH:C044563), phosphate (MESH:D010710), Choline (MESH:D002794), Orotate (MESH:D009963), Vitamin E (MESH:D014810), delta-tocotrienol (MESH:C082097), omega-3 fatty acid (MESH:D015525), lipid peroxide (MESH:D008054), Epi (MESH:D004837), ADP (MESH:D000244), vitamin K2 (MESH:D024482), gluconic acid (MESH:C030691), Vitamin B3 (MESH:D009536), lovastatin (MESH:D008148), E (MESH:D004540), phospholipid (MESH:D010743), Water (MESH:D014867), B12 (MESH:C034730), AGE (MESH:D017127), S-adenosylmethionine (MESH:D012436), ACh (MESH:D000109), DIPA (MESH:C001002), Vitamin A (MESH:D014801), TMT (MESH:C040533), nucleotides (MESH:D009711), paeoniflorin (MESH:C015423), acetyl-CoA (MESH:D000105), glycogen (MESH:D006003), isoflurane (MESH:D007530), iron (MESH:D007501), copper (MESH:D003300), Vitamin B4 (MESH:D000225), Vitamin C (MESH:D001205), magnesium orotate (MESH:C104468), glutamate (MESH:D018698), uridine nucleotides (MESH:D014500), isoprostane (MESH:D028421), GABA (MESH:D005680), Biotin (MESH:D001710), NE (MESH:D009638), pentoses (MESH:D010429), glycine (MESH:D005998), C, E (MESH:D002563), TDP (MESH:D013835), pyrimidine (MESH:C030986), UDP (MESH:D014530), SAH (MESH:D012435), retinyl esters (MESH:D000084562), cholesterol (MESH:D002784)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Caenorhabditis elegans (species) [taxon 6239], C. elegans [taxon 328850], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Drosophila melanogaster (fruit fly, species) [taxon 7227]
- **Mutations:** rs7946, D for 3-4
- **Cell lines:** CVCL_5G94 — Homo sapiens (Human), Down syndrome, Finite cell line (CVCL_LM91), PC-12 — Mus musculus (Mouse), Hybridoma (CVCL_J992), C6 — Rattus norvegicus (Rat), Rat malignant glioma, Cancer cell line (CVCL_0194), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), SH-SY5Y — Homo sapiens (Human), Neuroblastoma, Cancer cell line (CVCL_0019)

## Full text

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## Figures

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## References

266 references — full list in the complete paper: https://tomesphere.com/paper/PMC12947704/full.md

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Source: https://tomesphere.com/paper/PMC12947704