APOE-04 Alzheimer’s progression slowed up by Omega-3 – RCT Aug 2024

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ω-3 PUFA for Secondary Prevention of White Matter Lesions and Neuronal Integrity Breakdown in Older Adults

A Randomized Clinical Trial
JAMA Netw Open. 2024;7(8):e2426872. doi:10.1001/jamanetworkopen.2024.26872
Lynne H. Shinto, ND, MPH1; Charles F. Murchison, PhD1,2; Lisa C. Silbert, MD, MCR1,3; et alHiroko H. Dodge, PhD1,4; David Lahna, MS1; William Rooney, PhD5; Jeffrey Kaye, MD1,3; Joseph F. Quinn, MD1,3,6; Gene L. Bowman, ND, MPH1,7

Key Points

• Question Does ω-3 polyunsaturated fatty acid treatment reduce cerebral white matter lesion (WML) accumulation and neuronal integrity breakdown among older adults?
• Findings In this randomized clinical trial of 102 participants, ω-3 treatment failed to significantly reduce WML progression and neuronal integrity breakdown among all participants; however, apolipoprotein E ε4 allele (APOE*E4) carriers who received ω-3 had significant reductions in neuronal integrity breakdown over 3 years.
• Meaning Although ω-3 treatment failed to reach significant reduction in WML progression and neuronal integrity breakdown among all participants at risk for dementia, the findings suggest that APOE*E4 carriers may benefit from ω-3 treatment.
• Importance Older adults with lower intake and tissue levels of long-chain ω-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) have more brain white matter lesions (WMLs), an association suggesting that small-vessel ischemic disease, a major contributor to the development of dementia, including Alzheimer disease, may be preventable through ω-3 treatment.

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Objective To determine whether ω-3 treatment reduces WML accumulation in older adults without dementia harboring WMLs and with suboptimal ω-3 status.

Design, Setting, and Participants This quadruple-blinded, placebo-controlled, randomized clinical trial with treatment stratification by apolipoprotein E ε4 allele (APOE*E4) carrier status used linear mixed-effects models to estimate mean annual change between groups. The study was conducted at Oregon Health & Science University, a major academic medical center in the Pacific Northwest, from May 2014 to final participant visit in September 2019. Data analysis concluded in July 2022. Participants were adults without dementia aged 75 years and older with WMLs greater than or equal to 5 cm3 and plasma ω-3 PUFA less than 5.5 weight percentage of total.

Intervention Three-year treatment with 1.65 g of ω-3 PUFA (975 mg of EPA and 650 mg of DHA) vs a soybean oil placebo matched for taste, smell, and appearance.

Main Outcomes and Measures The primary outcome was annual WML progression measured using magnetic resonance imaging. Secondary outcomes included diffusion tensor imaging of fractional anisotropy (DTI-FA), representing neuronal integrity breakdown.

Results A total of 102 participants (62 women [60.8%]; mean age, 81 years [range, 75-96 years]) were equally randomized, 51 per treatment group. Although the ω-3 group had less annual WML accumulation than the placebo group, the difference was not statistically significant (1.19 cm3 [95% CI, 0.64-1.74 cm3] vs 1.34 cm3 [95% CI, 0.80-1.88 cm3]; P = .30). Similarly, the ω-3 group had less annual DTI-FA decline than the placebo group, but the difference was not statistically significant (−0.0014 mm2/s [95% CI, −0.0027 to 0.0002 mm2/s] vs −0.0027 mm2/s [95% CI, −0.0041 to −0.0014 mm2/s]; P = .07). Among APOE*E4 carriers, the annual DTI-FA decline was significantly lower in the group treated with ω-3 than the placebo group (−0.0016 mm2/s [95% CI, −0.0032 to 0.0020 mm2/s] vs −0.0047 mm2/s [95% CI, −0.0067 to −0.0025 mm2/s]; P = .04). Adverse events were similar between treatment groups.

Conclusions and Relevance In this 3-year randomized clinical trial, ω-3 treatment was safe and well-tolerated but failed to reach significant reductions in WML accumulation or neuronal integrity breakdown among all participants, which may be attributable to sample size limitations. However, neuronal integrity breakdown was reduced by ω-3 treatment in APOE*E4 carriers, suggesting that this treatment may be beneficial for this specific group.
 Download the PDF from VitaminDWiki

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Expect far more success If 1) Reduce Omega-6 intake 2) Use Omega-3 emulsion 3) Add Vitamin D

• Omega-6 blocks the ability of the body to adsorb Omega-3
• Omega-3 emulsions are about 3X more bio-available
  • Very few RCTs do either one as of 2024

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VitaminDWiki - 52 studies in both categories Omega-3 and Cognitive

This list is automatically updated

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VitaminDWiki – Overview Alzheimer's-Cognition and Vitamin D contains:

• FACT: Cognitive decline is 19X more likely if low vitamin D
• FACT: Dementia is associated with low vitamin D levels.
• FACT: Alzheimer’s Dementia 2.3X more likely in elderly if low vitamin D – Dec 2022
• FACT: Dementia is associated with low vitamin D - many studies
• FACT: Alzheimer's Disease is 4X less likely if high vitamin D
• FACT: Every single risk factor listed for Alzheimer's Disease is also a risk factor for low vitamin D levels
• FACT: Elderly cognition gets worse as the elderly vitamin D levels get even lower (while in senior homes)
• OBSERVATION: Reports of increased vitamin D levels result in improved cognition
• OBSERVATION: Alzheimer’s patients 3X more likely to have a malfunctioning vitamin D receptor gene – 2012
• OBSERVATION: Alzheimer's Disease has been seen to halt when vitamin D was added.
• OBSERVATION: Alzheimer’s is associated with all 7 of the genes which restrict vitamin D
• OBSERVATION: 39 vitamin D and Alz. or Cognition intervention trials as of Sept 2018
• OBSERVATION: 2 Meta-analysis in 2012 agreed that Alzheimer's Disease. associated with low vitamin D
• OBSERVATION: 50X increase in Alzheimer's while decrease in vitamin D
• OBSERVATION: Vitamin D reduces Alzheimer’s disease in 11 ways
• OBSERVATION: Alzheimer’s cognition improved by 4,000 IU of vitamin D
• OBSERVATION: Plaque removed in mice by equiv. of 14,000 IU daily
• OBSERVATION: DDT (which decreases Vit D) increases risk of Alzheimer's by up to 3.8X
• OBSERVATION: 2% of people have 2 copies of the poor gene reference: Alz Org
• OBSERVATION: Genes do not change rapidly enough to account for the huge increase in incidence
• OBSERVATION: End of Alzheimer's videos, transcripts and many studies protocol has been very successful
  • It adjusts Vitamin D, B-12, Iron, Omega-3, food, etc, and can now be done at home. $75/month.
• FACT: Vitamin D is extremely low cost and has very very few side effects
• CONCLUSION: Everyone concerned about cognitive decline or Alzheimer's Disease should take vitamin D
• PREDICTION MET: By 2024 Omega-3 and high dose Vitamin D will be found to reverse Alzheimer's in humans
  There are 13+ Alzheimer’s meta-analyses in VitaminDWiki
  There are 97+ Alzheimer’s studies in VitaminDWiki
  Dementia is associated with low vitamin D - many studies 50+ studies
  16+ studies in both categories Cognitive and Omega-3

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VitaminDWiki - Omega-3 helps many health problems

409 Omega-3 items in category Omega-3 helps with: Autism (7 studies), Depression (28 studies), Cardiovascular (34 studies), Cognition (52 studies), Pregnancy (44 studies), Infant (34 studies), Obesity (14 studies), Mortality (7 studies), Breast Cancer (5 studies), Smoking, Sleep, Stroke, Longevity, Trauma (12 studies), Inflammation (18 studies), Multiple Sclerosis (9 studies), VIRUS (12 studies), etc
CIlck here for details

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VitaminDWiki - Overview: Omega-3 many benefits include helping vitamin D

(409) items in category Omega-3 and Vitamin D

• Omega-3 reduces risk of COVID-19 - many studies
• Cardiovascular problems reduced by Omega-3 - many studies
• Omega-3 helps muscles - many studies
• Omega 3 increases vitamin D in the blood – many studies
• Omega-3 index - many studies
• Omega-6 blocks Omega-3 etc. -many studies
• Omega-6 increase may have increased the risk of many diseases - Jan 2022
• Preterm birth decreased by Omega-3, etc. - many studies
• Omega-3 reduces many psychiatric disorders – 2 reviews 2016
• ADHD, Autism, Early Psychosis and Omega-3 – review Dec 2017
• Schizophrenia relapses reduced 3X by Omega-3 – RCT Mar 2015
• Typical pregnancy is now 39 weeks – Omega-3 and Vitamin D might restore it to full 40 weeks
• Omega-3 supplementation during pregnancy reduce early preterm births (save 1500 USD per child) – Aug 2016
• Infants getting 1 g of Omega-3 for 12 weeks got better brains – RCT March 2017
• Omega-3 conference and 12 publications – Nov 2014
• Vitamin D Cofactors in a nutshell by VitaminDWiki
• For every Omega-3 dollar there is a 84 dollar savings in Cardiovascular costs - Foster and Sullivan April 2016
• Overweight women on caloric restriction diet got 3X benefits from 8 weeks of Omega-3 – RCT Dec 2015
• 2.7 fewer days in hospital after surgery if had taken Omega-3 (19 RCT) – meta-analysis – June 2017
• Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
• Omega-7 - in addition to Omega-3
• Consuming more monounsaturated fat increased vitamin D – Aug 2011 has the following
  WikiPedia Good (more vitamin D into bloodstream)= much more BLUE than Green

Almonds and macadamia nuts are examples of good foods to take with vitamin D