**Background:** Oxidative stress accumulates with age and is linked to dementia and other diseases. Antioxidant supplements, especially combinations, may prevent or slow this damage. Twendee X is a commercial mixed antioxidant containing coenzyme Q10, niacin, l-cystine, ascorbic acid, succinic acid, fumaric acid, l-glutamine, and riboflavin. Prior work showed it prevented conversion from mild cognitive impairment to Alzheimer's disease in humans and reduced protein aggregation in transgenic mice. This study aimed to test Twendee X in a vitamin E-deficient mouse model of chronic oxidative stress.
**Methods:** Three-week-old C57BL/6 mice were fed a vitamin E-deficient diet for 5 months (until 6 months of age). At 6 months, they were divided into two groups: one received Twendee X (40 mg/kg/day) in drinking water for one month, the other received plain water. Behavioral tests (Morris water maze for cognition, rota-rod for coordination) were performed during the final month. After euthanasia at 7 months, cerebral cortex and hippocampus were analyzed by Western blot for BDNF, NGF, TrkB, and TrkA. Serum parameters (total protein, albumin, iron, LDH, triglycerides, LDL, HDL, total cholesterol, free cholesterol, esterified cholesterol, AST, ALT, LDL-C, HDL-C) were measured by an external vendor. Statistical significance was set at p<0.05.
**Key Results:** Body weight did not differ between groups, though food and water intake were significantly higher in some weeks for the Twendee X group. In the Morris water maze, the Twendee X-treated group reached the hidden platform significantly faster on 4 of 5 trial days (except Day 3) compared to untreated vitamin E-deficient mice. The proportion of time spent in the platform quadrant was nominally higher on all days and significantly higher from Day 3 onward. Swimming speed on Day 5 was significantly lower in the Twendee X group (p<0.05). In the rota-rod test, time-to-fall was significantly longer in the Twendee X group (p<0.05), with no negative correlation with body weight. Western blot showed that BDNF and NGF levels in the cerebral cortex were significantly higher in Twendee X-treated mice compared to untreated controls (p<0.05). Hippocampal BDNF, NGF, TrkB, and TrkA did not differ between groups. Serum total protein and iron were significantly lower in the Twendee X group; other serum parameters (including cholesterol and liver enzymes) were not significantly different.
**Clinical Implications:** This study provides preclinical evidence that a one-month course of a mixed antioxidant supplement can improve cognitive function and motor coordination in a mouse model of chronic oxidative stress (vitamin E deficiency). The observed increases in cortical BDNF and NGF suggest a potential neurotrophic mechanism. Because oxidative damage accumulates with age in humans, these findings support the idea that mixed antioxidant supplementation may help preserve brain function even after oxidative stress has begun. However, the study has limitations: it did not measure brain vitamin E levels, blood levels of Twendee X components, or markers of oxidative stress (e.g., lipid peroxides, antioxidant enzyme activities). The specific component(s) responsible for the effects and the optimal dose remain unknown. Further research is needed to confirm these effects in aged models and to compare Twendee X with other antioxidants.