Quick Study Analysis: Omega-6 fats cause Alzheimer's disease?
More evidence of an effect in humans.
(Snowden et al., 2017) is an interesting study, for two reasons.
They find an association between Ω-6 fats an Alzheimer's in a fairly neutral analysis.
The association they find is an inverse association. They don't assume that less Ω-6 in the diet is the problem, but that 'dysregulation' of some sort is.
(It would be absurd to think that 'less' Ω-6 could be causal in Alzheimer's in the US.)
"The main molecules that were different were six small fats, such as omegas, which were different everywhere in the brain.
"The number of people in the study was small, but the results suggest a role of fats in dementia." (Snowden et al., 2017)
I've often talked about lower Ω-6 indicating progression in the disease process (in ARDS, T2DM, and CVD), and here again we see such a phenomenon.
The authors conjecture that it's the Ω-6 metabolites that are driving the process, but seem unaware (they don't mention it) that non-enzymatic metabolites might be involved, and have been shown to be involved in humans.
“Lipid peroxidation (4-HNE generation) and H2O2 production were significantly higher (p = 0.004 and 0.0001 respectively) in AD patients compared to controls, and this was accompanied by lower ATP production in AD (p = 0.0009).” (Bose et al., 2024)
“The present study demonstrates a direct cause-and-effect correlation between oxidative stress and altered amyloid-β production, and provides a molecular mechanism by which naturally occurring product of lipid peroxidation [4-HNE] may trigger generation of toxic amyloid-β42 species.” (Arimon et al., 2015)
For the 'no evidence in humans' crowd, this is another tear in their already-shredded argument.
For the rest of us, this is another compelling reason to fix your diet before the damage become irreversible.
References
Arimon, M., Takeda, S., Post, K. L., Svirsky, S., Hyman, B. T., & Berezovska, O. (2015). Oxidative Stress and Lipid Peroxidation Are Upstream of Amyloid Pathology. Neurobiology of Disease, 84, 109–119. https://doi.org/10.1016/j.nbd.2015.06.013
Bose, C., Kshirsagar, S., Vijayan, M., Kumar, S., Singh, S. P., Hindle, A., & Reddy, P. H. (2024). The Role of RLIP76 in Oxidative Stress and Mitochondrial Dysfunction: Evidence Based on Autopsy Brains from Alzheimer’s Disease Patients. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1870(2), 166932. https://doi.org/10.1016/j.bbadis.2023.166932
Snowden, S. G., Ebshiana, A. A., Hye, A., An, Y., Pletnikova, O., O’Brien, R., Troncoso, J., Legido-Quigley, C., & Thambisetty, M. (2017). Association Between Fatty Acid Metabolism in the Brain and Alzheimer Disease Neuropathology and Cognitive Performance: A Nontargeted Metabolomic Study. PLOS Medicine, 14(3), e1002266. https://doi.org/10.1371/journal.pmed.1002266