The effect of plasmalogen precursor supplementation on blood catalase and malondialdehyde levels in cognitively impaired persons. (31st December 2021) - Goodenowe, Dayan B.
Abstract: Background: Malondialdehyde (MDA) is a metabolic byproduct of lipid peroxidation that is elevated in in the serum of Alzheimer's patients. Catalase (CAT) enzymatically and plasmalogens (PLS) biochemically react with and neutralize hydrogen peroxide. 1‐O‐alkyl‐2, 3‐diacylglycerol (ADG) PLS precursors containing docosahexaenoic acid (DHA) at the sn‐2 position have been shown to increase blood PLS and to be neuroprotective in animal models of neurodegeneration. The goal of this study was to evaluate the effect of dietary DHA‐ADG supplementation on PLS and MDA levels and CAT activity in the serum of cognitively impaired persons. Method: Twenty‐two persons (11M/11F), aged 37‐84 (average = 69) with mild to moderate cognitive impairment [CDR: 14(0.5); 4(1); 4(2)] were administered DHA‐ADG [1.0ml/day for 30 days; 2.0ml/day for 60 days; 4.0ml for 30 days, followed by a 30‐day wash‐out period]. Serum PLS, MDA, and CAT were measured at baseline and the end of each month. Result: Blood DHA‐PLS were elevated two‐fold by month 3 (2.06, 95% CI=1.64‐2.48) and remained elevated during treatment. Serum DHA‐PLS levels were positively correlated with CAT activity (R=0.32, p=2.7e‐03) and negatively correlated with MDA levels (r=0.41, p=9.3e‐05). Increased DHA‐PLS levels from baseline correlated with decreased MDA levels (r=0.42, p=6.4e‐05), but not increased CAT (r=0.02, p=0.9e‐01). DHA‐ADG supplementation significantly elevated CAT activity in persons with baseline CAT activity less than the average and significantly decreased MDA levels in persons with baseline MDA levels above the average to levels equivalent to the top and bottom 50%, respectively (p<0.05). MDA levels and CAT activity were negatively correlated (r=0.26, p=1.4e‐02). Conclusion: DHA‐ADG was effective at elevating blood DHA‐PLS, reducing MDA in persons with high baseline MDA levels and increasing CAT activity in persons with low baseline CAT activity at the dosages studied. Although total serum DHA‐PLS were correlated with both MDA and CAT, DHA‐PLS elevation from baseline was only correlated with decreased MDA levels from baseline suggesting that the increased CAT effect of DHA‐PLS elevation was due to its MDA lowering effect. These observations are consistent with the known biochemical effects of PLS on peroxide neutralization and provide further mechanistic evidence regarding the protective effects of high blood PLS levels.