Natural Vitamins and Novel Synthetic Antioxidants Targeting Mitochondria in Cognitive Health: A Scoping Review of In Vivo Evidence.

Squillace A, Fernando MG, Sullivan K, Kiat H, Martins RN

Antioxidants (Basel, Switzerland)7 Jan 2026Cited by 1 (Europe PMC)

PMID41596136PMCIDPMC12837595DOI10.3390/antiox15010078PepBankPUB-41596136

Summary

Mitochondrial dysfunction and oxidative stress are crucial contributors to the pathogenesis of Alzheimer's disease (AD) and dementia exhibiting cognitive decline at the early stage of neurodegeneration. Natural vitamin antioxidants (NVAs) and novel mitochondria-targeted antioxidants (MTAs) are proposed as potential therapeutics though conclusive evidence is lacking. Objectives were to examine in vivo evidence on NVAs and MTAs for preventing and/or treating cognitive decline leading to dementia, to identify the most promising antioxidants, and highlight translational gaps. Methods followed PRISMA-ScR guidelines. MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia. A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria. NVAs (Vitamin A, B, C, E) demonstrated mixed efficacy in reducing oxidative stress and improving cognitive outcomes, with Vitamin E showing the most consistent neuroprotective effects. MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology. Both NVAs and MTAs improved biomarker profiles and cognitive outcomes in vivo animal models of AD and dementia, but MTAs showed more robust and consistent efficacy by directly targeting mitochondrial pathways. Given the favourable safety profiles of MTAs in other clinical conditions, early-phase human trials in dementia and AD are warranted to evaluate their long-term cognitive benefits.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In in vivo animal models of Alzheimer's disease and dementia, pooled mitochondria-targeted antioxidants (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics.
In plain wordsIn animal models of Alzheimer's disease, a group of mitochondria-targeted antioxidants, including SS31, improved how mitochondria behave.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMitochondrial dynamics
Study
animaln: not reported in source
in vivo models of Alzheimer's disease and dementia
Outcome group
Mitochondrial function · Nervous system and cognition
Source sentences
Summary
MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology.
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia.
Summary · context
A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-4159613601
02AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In in vivo animal models of Alzheimer's disease and dementia, pooled mitochondria-targeted antioxidants (MitoQ, MitoTEMPO, SS31, SkQ1) improved cognitive performance.
In plain wordsIn animal models of Alzheimer's disease, a group of mitochondria-targeted antioxidants, including SS31, improved cognitive performance.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseCognitive performance
Study
animaln: not reported in source
in vivo models of Alzheimer's disease and dementia
Outcome group
Cognition and memory · Nervous system and cognition
Source sentences
Summary
MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology.
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia.
Summary · context
A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-4159613602
03AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In in vivo animal models of Alzheimer's disease and dementia, pooled mitochondria-targeted antioxidants (MitoQ, MitoTEMPO, SS31, SkQ1) reduced dementia-related pathology.
In plain wordsIn animal models of Alzheimer's disease, a group of mitochondria-targeted antioxidants, including SS31, reduced signs of dementia-related disease.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseDementia-related pathology
Study
animaln: not reported in source
in vivo models of Alzheimer's disease and dementia
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology.
2 context sentences(design, population, supporting numbers)
Summary · context
MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia.
Summary · context
A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-4159613603

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 10:21 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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