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Omega-3 paused Alzheimer's decline - RCT Sept 2021


Comments on the study by Dr. Rhonda Patrick

"The intervention study involved 33 people who had been diagnosed with Alzheimer’s disease. Approximately half of the participants took a supplement providing 2.3 grams of omega-3 fatty acids daily for six months; the other half took a placebo. All participants took the Mini Mental State Examination (MMSE), a widely accepted measure of memory and cognitive function, before and after the intervention. The study investigators collected cerebrospinal fluid samples before and after the intervention to measure several biomarkers associated with neurodegenerative diseases and inflammation, including amyloid beta proteins, tau, interleukin 6, chitinase-3-like protein 1 (YKL-40), and neurofilament light (NfL). YKL-40 is associated with neuroinflammation, and NfL is associated with damage to the axons of nerves in brain white matter.

The MMSE scores of the participants who took the omega-3 fatty acid supplements remained stable over the six-month intervention, decreasing by only 0.06 points, but the scores of those who took the placebo decreased by 2.0 points. The two groups' biomarkers were similar at the beginning of the intervention, but YKL-40 and NfL increased slightly in the group that received the omega-3 fatty acid supplement, indicating a possible increase in neurodegeneration and inflammatory responses. However, the increase in the two biomarkers did not correlate with the participants' MMSE scores.

Effects of Peroral Omega-3 Fatty Acid Supplementation on Cerebrospinal Fluid Biomarkers in Patients with Alzheimer’s Disease: A Randomized Controlled Trial—The OmegAD Study

: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2021 DOI: 10.3233/JAD-210007
Authors: Tofiq, Avina | Zetterberg, Henrikb; c; d; e | Blennow, Kajb; c | Basun, Hansf; g; h | Cederholm, Tommyi; j | Eriksdotter, Mariaj; k | Faxén-Irving, Gerdk | Hjorth, Erikl | Jernerén, Fredrikm | Schultzberg, Mariannel | Wahlund, Lars-Olofj; k | Palmblad, Jann | Freund-Levi, Yvonnek; o; p; q; r; *
Correspondence to: Yvonne Freund-Levi, MD, PhD, Associate Professor, School of Medicine Örebro University and Dep of NVS Karolinska Institutet, Stockholm, Sweden. E-mail: yvonne.freund at oru.se.

Background:Studies have suggested a connection between a decrease in the levels of polyunsaturated fatty acids (PUFAs) and Alzheimer’s disease (AD). We aimed to assess the effect of supplementation with omega-3 fatty acids (n-3 FAs) on biomarkers analyzed in the cerebrospinal fluid (CSF) of patients diagnosed with AD.

Objective:To investigate the effects of daily supplementation with 2.3 g of PUFAs in AD patients on the biomarkers in CSF described below. We also explored the possible correlation between these biomarkers and the performance in the cognitive test Mini-Mental State Examination (MMSE).

Methods:Thirty-three patients diagnosed with AD were randomized to either treatment with a daily intake of 2.3 g of n-3 FAs (n  =  18) or placebo (n  =  15). CSF samples were collected at baseline and after six months of treatment, and the following biomarkers were analyzed: Aβ 38, Aβ 40, Aβ 42, t-tau, p-tau, neurofilament light (NfL), chitinase-3-like protein 1 (YKL-40), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), soluble IL-1 receptor type II (sIL-1RII), and IL-6. Results:There were no significant differences between the groups concerning the level of the different biomarkers in the CSF at baseline. Within the treatment group, there was a small but significant increase in both YKL-40 (p = 0.04) and NfL (p = 0.03), while the other CSF biomarkers remained stable.

Conclusion:Supplementation with n-3 FAs had a statistically significant effect on NfL and YKL-40, resulting in an increase of both biomarkers, indicating a possible increase of inflammatory response and axonal damage. This increase in biomarkers did not correlate with MMSE score.


Cognition and Omega-3 items in VitaminDWiki


Reasons why Omega-3 sometimes does not help Alzheimer's

Why Alzheimer’s studies using Omega-3 have mixed results – quality, dose size, Omega-6, genes, etc. March 2018 starts with

  1. Quality of the Omega-3
       contaminants as well as the source - fish liver, salmon brain, krill, and plant
  2. Dose size used (200 mg is unlikely to be as good as 2000 mg)
  3. Larger dose size needed for a heavier person
       Omega-3 index would determine that
  4. Larger dose size needed if much of the Omega-3 is fighting other inflammation
       Omega-3 index would determine that
  5. The Omega-6 in the body can block the benefits of Omega-3
       Omega-3 index would determine that
  6. Genes - Alzheimers APoE4 gene limits DHA
       additional genes may limit Omega-3, Magnesium, and Vitamin D
  7. Fraction of Omega-3 EPA and DHA
  8. The Omega-3 Index is a proven measure of Omega-3 for the blood - but is rarely used in trials
       Suspect that Omega-3 benefit is only seen in those who were previously deficient
       Wonder if the Omega-3 index is a good proxy measure for Omega-3 in the brain
  9. Omega-3 might be less bio-available in those with poor guts/gallbladder surgery
       Omega-3 index would determine that
  10. Omega-3 might not help all three forms of Alzheimer's
    See book End of Alzheimer's - Bredesen

Inflammation and Omega-3 items in VitaminDWiki


Alzheimers-Cognition in VitaminDWiki

Alzheimers-Cognition - Overview starts with


Omega-3 in VitaminDWiki

Vitamin D and Omega-3 category starts with

345 Omega-3 items in category Omega-3 and Vitamin D separately & together help with: Autism (9 studies), Depression (24 studies), Cardiovascular (29 studies), Cognition (45 studies), Pregnancy (33 studies), Infant (23 studies), Obesity (12 studies), Mortality (5 studies), Breast Cancer (5 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), etc

   See also - Overview: Omega-3 many benefits include helping vitamin D


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