A systematic review and meta-analysis of cognitive and behavioral tests in rodents treated with different doses of D-ribose

Background: D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents.

Methods: The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed.

Results: A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: –0.80; 95% CI: –1.14, –0.46; p < 0.00001), percentage of distance traversed in the target quadrant (SMD: –1.20; 95% CI: –1.47, –0.92; p < 0.00001), percentage of time spent in the target quadrant (SMD: –0.93; 95% CI: –1.18, –0.68; p < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; p = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; p < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; p = 0.02). Subsequently, subgroup analysis for the dose of D-ribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses.

Conclusion: D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment.