expert opinion

Using marine omega-3s to revitalize brain function in the elderly via restoration of mitochondrial function

October 1, 2015

file

Professor Gunter Eckert, Nutritional Neuroscience Research Group, Goethe University, Frankfurt, Germany

Ageing is the primary risk factor for the development of Alzheimer’s Disease. One of the pathological hallmarks of the condition is the formation of amyloid plaques that contain beta-amyloid proteins. These beta-amyloid proteins are derived from transmembrane amyloid precursor protein (APP). Marine omega-3 fatty acids are able to increase the fluidity of cell membranes. This fluidity has an important role in the modulation of APP processing (1). Professor Eckert has found that dysfunction of mitochondria has a key role in brain ageing and development of AD. Increased APP processing protects against mitochondrial dysfunction.

The key marine omega-3 fatty acids are docosahexaenoic acid (DHA) and eicospentaenoic acid (EPA). Both produce a series of important metabolites important for good cell health, but DHA specifically is incorporated into the cell membrane of neural tissue. A recent study of the distribution of omega-3 fatty acids in the bodies of rats showed that the brain and testes contained a total of 12% and 15.6%, respectively, of the total DHA (2).

Using rats, Professor Eckert’s team demonstrated that supplementation with fish oil for three weeks could restore the mitochondrial function lost as the rats age i.e., respiration rates and ATP production were increased (3). They were also able to show using isolated cell membrane fractions that the fish oil was also able to partially improve membrane fluidity. Finally, they noted increases in the anti-apoptotic protein Bcl-2 and neuroprotection D1 (NPD1), a powerful neuroprotective metabolite of DHA produced by lipoxygenase oxidation (4).

In 2014, Witte et al. (5) conducted a double blinded clinical trial on a small cohort (n=65) of health elderly people aged between 50 to 75 years with an intervention of 2.2g fish oil per day for 26 weeks to determine if there was an improvement in cognition. They found significant benefits in cognition and also beneficial effect to the structure of the brain, namely white matter microstructural integrity and grey matter volume in the temporal, parietal and limbic areas.

A recent meta-analysis (6) showed that DHA alone, or in combination with EPA, was associated with improved episodic memory in adults with mild memory complaints. Specifically, episodic memory was significantly improved with a daily intervention of 1g or more day of DHA and EPA.

Professor Eckert’s team (1) concluded that “our findings provide new mechanisms underlying the neuroprotective actions of polyunsaturated fatty acids and underscore the impact of fish oil as a promising nutraceutical to delay age-related cerebral alterations”.

References

  1. Eckert GP, Chang S, Eckmann J et al., “Liposome-incorporated DHA increases neuronal survival by enhancing non-amyloidogenic APP processing” Biochim. Byophys. Acta 2011, 1808: 236-243”.
  2. Salem NM, Lin YH, Moriguchi T, Lim SY, Salem N & Hibbeln JR; “Distribution of omega-6 and omega-3 polyunsaturated fatty acids in the whole rat body and 25 compartments”; Prostaglandins, Leukotrienes and Essential Fatty Acids 2015; 100: 13–20.
  3. Afshordel S, Hagl S, Werner D1, Röhner N2, Kögel D, Bazan NG, and Eckert GP, “Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging-impact of Bcl-2 and NPD-1 like metabolites”, Prostaglandins Leukot Essent Fatty Acids. 2015 Jan;92:23–31. doi: 10.1016/j.plefa.2014.05.008. Epub 2014 Jun 9.
  4. Bazan NG, Musto AE, Knott EJ; “Endogenous signalling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity”, Mol. Neurobiol. 2011, 44: 216–222.
  5. Witte AV, Kerti L, Hermannstädter HM, Fiebach JB, Schreiber SJ, Schuchardt JP, Hahn A & Flöel A; ”Long-chain omega-3 fatty acids improve brain function and structure in older adults”; Cereb Cortex. 2014 Nov;24(11):3059–68.
  6. Yurko-Mauro K, Alexander DD & Van Elswyk ME, “Docosahexaenoic Acid and Adult Memory: A Systematic Review and Meta-Analysis”; PLoS ONE 2015; 10(3): e0120391. Doi10.1371/journal.pone.0120391.