Dr Paul Clayton 2010


Back in 1997, an epidemiological study found that increased fish consumption was linked to a lower risk of Alzheimer’s Disease (AD) (Grant ’97).

Then in 2005, a pre-clinical study showed that a diet rich in the poly-unsaturated omega-3 fatty
acids slowed the progression of Alzheimer’s type brain pathology in an aged
mouse model (Lim et al ’05).

Three years later, a relatively small prospective clinical trial found that small doses of omega-3s led to some improvements in patients with mild cognitive impairment, although not with Alzheimer’s Disease (Chiu et al ’08).

This boosted sales of fish oil supplements, and triggered another, larger trial which has just been published – with disappointing results.

According to this study, daily supplements of docosahexaenoic acid (DHA), one of the two omega-3s in
fish oil, did not reduce cognitive decline in patients with mild-to-moderate Alzheimer’s disease (Quinn et al ’10, Yaffe ’10).

Here is a prime example of more damn-fool research, using concepts and trial designs more suited to testing drugs than nutritional interventions. The truth is that the biochemical imbalances that have been identified in AD are far too many, and too complex, to be amenable to single, simple input solutions such as a DHA supplement. They are, however, amenable to diet, which contains thousands of different compounds, many of which are known to interact with brain chemistry.

At Columbia University, Professor Nicholas Scarmeas has been studying the relationship between
diet and AD for many years. He has published a series of papers that show, unequivocally, that
the risk of developing this cruel disease is diminished by the consuming a Mediterranean
diet (ie Gu et al ’10). This is a diet that contains high levels of a range of bioactive compounds, including the anti-inflammatory flavonoids – which are also strongly linked to a reduced risk of AD (ie Dai et al ’06), and have plausible mechanisms of action (ie Fernandez et al ’10,
Jonova et al ’10)

The current anti-AD drugs are fairly useless, and have a range of adverse effects. If you want to protect yourself or a loved one against AD, the logical way forwards is not drugs, or pharma-style single compound supplements, but by dietary improvement and/or a comprehensive, broad
spectrum micro- and phytonutritional support programme. These should contain omega-3s (all of them, not just DHA), which after all play a key role in neuronal defence mechanisms (ie Palacios-Pelaez et al ’10); but they must also contain flavonoids and a wide range of antioxidants.

The inclusion of anti-oxidants is critical; omega-3 supplements taken alone, without
antioxidants, are oxidised in the body producing toxic and pro-inflammatory lipid oxidation
products which shorten life span in pre-clinical models (ie Tsuduki et al ’10); and actually exacerbate Alzheimer’s (Liu et al ’08)!!

No wonder the big Quinn trial failed.

REFERENCES

Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, Stewart R, Huang SY. The effects of omega-3 fatty acids monotherapy in Alzheimer’s disease and mild cognitive impairment: a preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Aug 1;32(6):1538-44

Dai Q, Borenstein AR, Wu Y, Jackson JC, Larson EB. Fruit and vegetable juices and Alzheimer’s disease: the Kame Project. Am J Med 2006 Sep;119(9):751-9.

Fernandez JW, Rezai-Zadeh K, Obregon D, Tan J. EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP. FEBS Lett. 2010 Oct 8;584(19):4259-67

Grant WB. Dietary links to Alzheimer’s disease. Alzheimer Dis Rev 1997;2:42-55.

Gu Y, Luchsinger JA, Stern Y, Scarmeas N. Mediterranean Diet, Inflammatory and Metabolic Biomarkers, and Risk of Alzheimer’s Disease. J Alzheimers Dis. 2010 Aug 30. [Epub ahead of print]

Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem. 2010 Dec;345(1-2):91-104

Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, Cole GM. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005 Mar 23;25(12):3032-40

Liu L, Komatsu H, Murray IV, Axelsen PH. Promotion of amyloid beta protein misfolding and fibrillogenesis by a lipid oxidation product. J Mol Biol. 2008 Apr 4;377(4):1236-50

Palacios-Pelaez R, Lukiw WJ, Bazan NG. Omega-3 essential fatty acids modulate initiation and progression of neurodegenerative disease. Mol Neurobiol. 2010 Jun;41(2-3):367-74

Quinn JF, Raman R, Thomas RGH, Yurko-Mauro K, et al. Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial. JAMA 2010, 304 (17), 1903-1911

Tsuduki T, Honma T, Nakagawa K, Ikeda I, Miyazawa T. Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice. Nutrition. 2010 Jul 10. [Epub ahead of print]

Yaffe K. Treatment of Alzheimer Disease and Prognosis of Dementia. JAMA 2010, 304 (17), 1952-1953: editorial