The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial

• Published in: The Journal of nutrition, health & aging health & aging, 2024-08, Vol.28 (8), p.100287, Article 100287
• Main Authors: Baltic, Sonja, Nedeljkovic, David, Todorovic, Nikola, Ranisavljev, Marijana, Korovljev, Darinka, Cvejic, Jelena, Ostojic, Jelena, LeBaron, Tyler W., Timmcke, Judi, Stajer, Valdemar, Ostojic, Sergej M.
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers - blood; Brain - drug effects; Brain - metabolism; Brain-Derived Neurotrophic Factor - blood; Brain-Derived Neurotrophic Factor - metabolism; Cerebral oxygenation; Cognition; Cognition - drug effects; Cognitive Dysfunction; Dietary Supplements; Dihydrogen; Double-Blind Method; Female; Humans; Male; Mitochondria - drug effects; Mitochondria - metabolism; PQQ Cofactor - pharmacology; Pyrroloquinoline quinone
• ISSN: 1279-7707; 1760-4788; 1760-4788
• DOI: 10.1016/j.jnha.2024.100287

To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman’s 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation saturation exhibited a significant increase following the administration of the dihydrogen-PQQ mixture, from 48.4 ± 7.2% at baseline to 52.8 ± 6.6% at 6-week post-administration (P = 0.005). In addition, brain N-acetyl aspartate levels significantly increased at seven out of thirteen locations post-intervention in participants receiving the mixture (P ≤ 0.05). Despite