FASEB J. 2015 Jul;29(7):2681-9. doi: 10.1096/fj.14-264218.

ω-3 Supplementation increases amyloid-β phagocytosis and resolvin D1 in patients with minor cognitive impairment.

Fiala M1, Halder RC2, Sagong B2, Ross O2, Sayre J2, Porter V2, Bredesen DE2.
  • 1*Department of Surgery and Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA; and Department of Biostatistics, University of California, Los Angeles, School of Public Health, Los Angeles, California, USA fiala@mednet.ucla.edu.
  • 2*Department of Surgery and Department of Neurology, University of California, Los Angeles, School of Medicine, Los Angeles, California, USA; and Department of Biostatistics, University of California, Los Angeles, School of Public Health, Los Angeles, California, USA.

 

Abstract

We investigated the effects of 4-17 month supplementation with ω-3 fatty acids and antioxidants (Smartfish drink; Smartfish AS, Oslo, Norway) in 12 patients with minor cognitive impairment (MCI) [minimental state examination (MMSE) ≥19], 2 patients with pre-MCI (normal MMSE), and 7 patients with Alzheimer disease (AD) (MMSE <19). We measured the phagocytosis of amyloid-β 1-42 (Aβ) by flow cytometry and microscopy, the transcription of inflammatory genes by RT-PCR, the production of resolvin D1 (RvD1) by enzyme immunoassay, and the cognitive status by MMSE. In patients with MCI and pre-MCI, phagocytosis of Aβ by monocytes increased from 530 to 1306 mean fluorescence intensity units (P = 0.016). The increase in patients with AD was not significant (N.S.). The lipidic mediator RvD1, which stimulates Aβ phagocytosis in vitro, increased in macrophages in 80% of patients with MCI and pre-MCI (mean increase 9.95 pg/ml) (N.S.). Transcription of inflammatory genes’ mRNAs was increased in a subgroup of patients with low transcription at baseline, whereas it was not significantly changed in patients with high transcription at baseline. The mean MMSE score of patients with MCI and pre-MCI was 25.9 at baseline and 25.7 after 4-17 months (N.S.). Our study is the first to show significant immune and biochemical effects of ω-3 fatty acids with antioxidants in patients with MCI. Cognitive benefits of ω-3 supplementation in patients with MCI should be tested in a clinical trial.

KEYWORDS: inflammatory genes; minimental state examination; monocyte/macrophages; specialized proresolving mediators; ω-3 fatty acids

PMID: 25805829

 

Supplements:

Our study shows how to prevent or at least slow down cognitive loss in patients with Mild Cognitive Impairment (MCI).  The approach is based on our own immune system, which is, unfortunately, failing in MCI patients. In addition, MCI patients may have an unfavorable  genetic constitution that  complicates the function of the immune system. We are showing that the first step is  personalized medicine: a test of the immune function called phagocytosis (uptake) of amyloid-beta (amyloid-beta is the protein clogging the brain in MCI patients). If the test is abnormal (it is always abnormal in patients with Alzheimer disease and sometime abnormal in MCI patients), it is time to pay attention to prevention, including mental and physical exercise and nutrition. Importantly, our new advice is that omega-3 fatty acids and anti-oxidants improve the immune system against amyloid-beta,  as has been shown in our study. However, not all omega-3 are equal and the success in the study was due to the drink with omega-3 and antioxidants called Smartfish. The research in our laboratory and by others suggests that other immune modulators, such as resveratrol and curcumin, may provide additional benefits for the immune system. Therefore, the state of art in MCI prevention will require personalized care including advice about nutrition, exercise, individual monitoring of the immune system and appropriate nutritional supplementation.

 

 

 

 

 

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