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Cited by 18Alzheimer's disease research and treatmentsFatty Acid Research and HealthDementia and Cognitive Impairment Research

Immunotherapy of Mild Cognitive Impairment by ω -3 Supplementation: Why Are Amyloid-β Antibodies and ω -3 Not Working in Clinical Trials?

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Fiala, Milan, Restrepo, Lucas, Pellegrini, Matteo·2018·Journal of Alzheimer’s Disease
DOI 10.3233/jad-170579PMC PMC5870008
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Abstract

This article reviews the basic tenets of a clinical approach to effective immunotherapy of Alzheimer’s disease (AD) in patients with mild cognitive impairment (MCI). Although one randomized controlled study in early MCI patients by fish-derived omega-3 fatty acids ( ω-3) showed slowing of disease progression, large clinical trials with different products have failed to show cognitive effects. Macrophages of healthy subjects phagocytize and degrade amyloid-β 1 - 42 (Aβ) in the brain tissues, whereas macrophages of patients with AD and MCI are functionally defective. ω-3 and ω-3-derived specialized proresolving mediators (SPMs), such as resolvin D1, have powerful biochemical and immunological effects, which may repair the functions of MCI patients’ macrophages in the brain’s clearance of Aβ. Unfortunately, ω-3 products on the market have a variable quality. Nutritional supplementation with a combination drink called Smartfish with an emulsion of ω-3 and other fatty acids, antioxidants, 1,25-dihydroxy vitamin D3, and resveratrol improved the innate immune system of MCI patients by modulation of macrophage type to the pro-phagocytic M1-M2 type with an effective unfolded protein response against endoplasmic reticulum stress. Some MCI patients maintained their initial cognitive status for three years on Smartfish supplementation. Future randomized clinical trials should investigate the immune effects of ω-3, 1,25-dihydroxy vitamin D3, and SPMs on macrophage type, function, and biochemistry in parallel with cognitive effects.

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  • Diverse outcomes of ω-3 PUFA trials may result from variable quality of ω-3 PUFA supplements on the market.

    “These diverse outcomes may be resulted from the variable quality of ω-3 PUFA supplements on the market553; larger and more rigorous clinical trials on the effect of ω-3 PUFA in AD treatment are needed in the future.”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [553]

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Cited by

Sorted by citations

Authors
Fiala, M., Restrepo, L., & Pellegrini, M.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Fiala, Milan
ORCID
Venue
Journal of Alzheimer’s Disease
Publisher
SAGE Publications
Published
2017-10-30
Volume
62
Issue
3
Pages
1013-1022
ISSN
  • 1387-2877 (ISSN-L)
  • 1875-8908
DOI
10.3233/jad-170579
PMC
PMC5870008
OpenAlex
W2767025329
Cited by
18
References
1
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 3 · 2020: 6 · 2018: 1
FWCI
0.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
Funders
National Cancer Institute (P50CA211015)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
mild cognitive impairment, Alzheimer's disease
MeSH terms
Animals, Clinical Trials as Topic, Humans, Immunotherapy, Fatty Acids, Omega-3, Dietary Supplements, Cognitive Dysfunction

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