There have been many reports of research on cognitive functional improvement in the fields of medicine, psychology, and exercise physiology. The aging population and the medical issues that accompany aging have raised concerns about cognitive function improvement. And it is hoped that prevention may be achieved via specific dietary changes; there have been promising reports on the effectiveness of docosahexaenoic acid,(27)
and acetic acid bacteria(31)
in retarding cognitive function loss.
Ax is a strong anti-oxidant. Nakagawa et al.(32)
reported the anti-oxidant effect of Ax-Hp on phospholipid peroxidation in human erythrocytes. Iwabayashi et al.(33)
reported that Ax-Hp increases the biological anti-oxidants potential (BAP) in human. It is clear that the anti-oxidant activity of Ax-Hp is effective in human and animal studies. This study lets expect that Ax-Hp reduces oxidisation in the brain, leading to improved scores in tests of cognitive function.
Flavonoids are strong natural anti-oxidants like Ax, and they were thought to improve age-related cognitive decline. Youdim et al.(34)
reported on the neuroprotective effects of dietary flavonoids in vivo
. Pipingas et al.(30)
reported that flavonoid-rich P. radiata
bark extract improved cognitive function in tests of immediate recognition and spatial working memory. It is thought that the brain and nervous oxidisation are improved by the anti-oxidant activity of flavonoids, as is the case with Ax-Hp.
We performed a preliminary clinical trial of Ax-Hp and cognitive function improvement in 10 healthy men between 50 to 69 years of age, who complained of age-related forgetfulness. We reported that the response time of 5 CogHealth tasks was significantly improved (p<0.05) and that the amplitude of P300 brain waves, which are related to cognitive function, tended to increase (p<0.1) after 12 weeks of Ax-Hp treatment.
This randomised double-blind placebo-controlled study was performed to validate the beneficial effects of Ax-Hp on cognitive function in human subjects. Based on the results of the preliminary study, the high dosage was set at 12 mg/day, and 6 mg/day was set as the low dosage in order to confirm the presence of a dose response. The administration period was set to 12 weeks as in the preliminary study. Brain function was assessed with the CogHealth test and GMLT, both of which can perform objective measures in a large number of subjects.
We failed to show a significant difference between groups in the CogHealth test. No differences were observed at any of the assessments (4, 8, or 12 weeks). In addition, there were no differences between the high-dosage, low-dosage, and placebo groups in the reaction time and accuracy of the task-switching test. However, we observed significant improvements in the high-dose group in the response time for 1 task and in the accuracy of 1 task, and improvement trends was observed in 3 tasks. We conclude that these significant differences and trends are indicative of the Ax-induced improvement in cognitive function.
GMLT also revealed no significant differences between groups. The total duration did not change between groups or over time. However, total error improved significantly by 4 weeks in the low-dosage and high-dosage groups in contrast to the placebo group, which showed significant improvement only at 12 weeks. These results also suggest the Ax-induced improvement in cognitive function.
Although improvements in the CogHealth test were observed only with a dose of 12 mg/day, GMLT scores were improved at 6 mg/day. This difference may be because the methods of measuring cognitive performance differ. The GMLT includes a test of spatial working memory that is highly sensitive, can be used to measure age-related reductions in cognitive function, and can detect the effect of a supplement or remedy. Further verification is required.
Although the tests employed by Pipingas et al.(30)
differ from the tests used in this study, immediate recognition is evaluated by the CogHealth test and spatial working memory is evaluated by the GMLT. The combination of these tasks may be useful to verify other supplements or remedies.
The CogHealth test revealed improvements in cognitive function with 12 mg/day Ax-Hp for 12 weeks. This supports the results of our preliminary clinical study. In particular, the improvement in response time, which is a measure of short-term memory, and in the accuracy of the ’delayed recall’ task was remarkable. Moreover, total errors in the GMLT, which is also associated with memory, showed significant improvement with 6 and 12 mg/day Ax-Hp.
However, significant differences between groups were not observed, possibly due to the small sample size. Moreover, the average age may have been too young to observe age-related cognitive decline. We plan to investigate this issue further.
We observed no adverse effects to express any concerns regarding the safety of Ax-Hp.