Histidine-containing dipeptide supplementation improves delayed recall: a systematic review and meta-analysis

Context: Histidine-containing dipeptides (carnosine, anserine, beta-alanine and others) are found in human muscle tissue and other organs like the brain. Data in rodents and humans indicate that administration of exogenous carnosine improved cognitive performance. However, RCTs results vary. Objectives: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of histidine-containing dipeptide (HCD) supplementation on cognitive performance in humans to assess its utility as a cognitive stabiliser. Data sources: OVID Medline, Medline, EBM Reviews, Embase, and Cumulative Index to Nursing and Allied Health Literature databases from 1/1/1965 to 1/6/2022 for all RCT of HCDs were searched. Data extraction: 2653 abstracts were screened, identifying 94 full-text articles which were assessed for eligibility. Ten articles reporting the use of HCD supplementation were meta-analysed. Data analysis: The random effects model has been applied using the DerSimonian-Laird method. HCD treatment significantly increased performance on Wechsler Memory Scale (WMS) -2 Delayed recall (Weighted mean difference (WMD) (95% CI (CI)) = 1.5 (0.6, 2.5), P < .01). Treatment with HCDs had no effect on Alzheimer's Disease Assessment Scale-Cognitive (WMD (95% CI) = -0.2 (-1.1, 0.7), P = .65, I-2 = 0%), Mini-Mental State Examination (WMD (95% CI) = 0.7 (-0.2, 1.5), P = .14, I-2 = 42%), The Wechsler Adult Intelligence Scale (WAIS) Digit span Backward (WMD (95% CI) = 0.1 (-0.3, 0.5), P = .51, I-2 = 0%), WAIS digit span Forward (WMD (95% CI) = 0.0 (-0.3, 0.4), P = .85, I-2 = 33%) and the WMS-1 Immediate recall (WMD (95% CI) = .7 (-.2, 1.5), P = .11, I-2 = 0%). The effect on delayed recall remained in subgroup meta-analysis performed on studies of patients without mild cognitive impairment (MCI), and in those without MCI where average age in the study was above 65. Conclusion: HCD, supplementation improved scores on the Delayed recall examination, a neuropsychological test affected early in Alzheimer's disease. Further studies are needed in people with early cognitive impairment with longer follow-up duration and standardization of carnosine doses to delineate the true effect.