by Craig Weatherby
Brain tissue samples from Alzheimer's patients show markedly low levels of DHA… the omega-3 fatty acid essential to brain health and other body functions.
And several, albeit not all, epidemiological and clinical studies suggest that higher intake of DHA reduces the risk of dementia in elderly adults (Crawford MA et al. 2009).
Animal experiments support this notion and indicate that omega-3 DHA might help deter or ameliorate dementia by promoting survival of brain cells (Bazan NG et al. 2006; Green KN et al. 2007; Lukiw W et al. 2008).
People can either get DHA by eating seafood and fish oil, or they can make it from a non-functional omega-3 fat (ALA) found in leafy greens, walnuts, canola oil, and flaxseed.
Now, UC Irvine researchers report that the documented DHA-deficiency in the brains of Alzheimer's patients may be due to a genetic quirk that impairs their livers’ ability to make DHA from ALA.
UC Irvine team makes landmark discovery
Until now, there’s been no known cause for the low DHA levels found in Alzheimer's patients.
Previous studies have shown that most brain DHA is made in the liver, thanks to a protein that catalyzes the last metabolic step needed to convert plant-source ALA into DHA.
When the UCI group examined liver tissue from Alzheimer's patients, they found a genetic defect that prevents the protein from being created in sufficient quantities … thereby crippling the liver’s ability to make DHA.
Non-Alzheimer's livers did not have this defect, said co-author Daniele Piomelli, who led the research along with UCI pharmacologist Giuseppe Astarita.
According to lead author Daniele Piomelli, “We all know Alzheimer's is a brain disease, but our findings—which were totally unexpected—show that a problem with liver fat metabolism can make people more vulnerable” (UCI 2010).
Dr. Piomelli hypothesized that this findings also suggests a possible reason why clinical trials in which Alzheimer’s patients are given omega-3s have had mixed results.
Patients’ cognitive capacities linked closely to brain DHA levels
Dr. Astarita described another key discovery by the UCI team, which affirms previous findings:
“Additionally, we found that the greater the amount of Alzheimer's-related cognitive problems experienced in life by the patients, the lower were their liver DHA levels. So we do see a connection” (UCI 2010).
And Dr. Piomelli noted that the results point to new diagnostic and dietary approaches to Alzheimer’s.
He speculated that blood-fat tests might identify persons at higher risk, and that omega-3 supplements containing a more easily absorbed form of DHA may benefit early-stage patients.
This idea suggests that trials should be conducted to test krill oil, whose omega-3s come in the phospholipid form that predominates in human cell membranes.
Compared with the forms that predominate in fish and fish oils, phospholipid-form omega-3s appears to be absorbed more efficiently … probably because they take fewer metabolic steps to reach consumers’ cell membranes.
Findings should lead to future progress
The UCI team’s findings may lead to new prevention and treatment tactics.
And as Dr. Piomelli said, their discovery may not produce miracles, but could prove important:
“Our research isn't advocating that liver metabolism is a key to Alzheimer’s. The factors causing the disease are many and complex, but we feel this is another piece in the Alzheimer's puzzle” (UCI 2010).
This oddly overlooked (by the media) study deserves more attention—and funding for follow-up research.
Astarita G, Jung K-M, Berchtold NC, Nguyen VQ, Gillen DL, et al. (2010) Deficient Liver Biosynthesis of Docosahexaenoic Acid Correlates with Cognitive Impairment in Alzheimer's Disease. PLoS ONE 5(9): e12538. doi:10.1371/journal.pone.0012538
Bazan NG (2006) Cell survival matters: docosahexaenoic acid signaling, neuroprotection and photoreceptors. Trends Neurosci 29: 263–271.
Calon F, Lim GP, Yang F, Morihara T, Teter B, et al. (2004) Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 43: 633–645.
Crawford MA, Bazinet RP, Sinclair AJ (2009) Fat intake and CNS functioning: ageing and disease. Ann Nutr Metab 55: 202–228.
Green KN, Martinez-Coria H, Khashwji H, Hall EB, Yurko-Mauro KA, et al. (2007) Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci 27: 4385–4395.
Lim GP, Calon F, Morihara T, Yang F, Teter B, et al. (2005) A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 25: 3032–3040.
Lukiw W, Bazan N (2008) Docosahexaenoic acid and the aging brain. J Nutr 138: 2510–2514.
University of California - Irvine (UCI). Liver defect likely cause of DHA deficiency in Alzheimer's patients, UCI study finds. Sept. 8, 2010. Accessed at http://today.uci.edu/news/2010/09/nr_dha_100908.php