Paraxanthine enhances memory and neuroplasticity more than caffeine in rats – PubMed Black Hawk Supplements

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Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, reasoning, response time, and sustained attention; however, no preclinical study has compared the effects of PXN with those of CAF. The aim of this study was to compare the effects of PXN and CAF on memory and related biomarkers in rats. The effects of two different doses of PXN (PXN LOW, PXN HIGH), CAF (CAF HIGH), and a control group on cognition (escape…
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Paraxanthine enhances memory and neuroplasticity more than caffeine in rats - PubMed

Paraxanthine enhances memory and neuroplasticity more than caffeine in rats

Ralf Jäger et al. Exp Brain Res. .

Abstract

Paraxanthine (PXN) is the main metabolite of caffeine (CAF). PXN supplementation has been shown to increase measures of cognition, memory, reasoning, response time, and sustained attention; however, no preclinical study has compared the effects of PXN with those of CAF. The aim of this study was to compare the effects of PXN and CAF on memory and related biomarkers in rats. The effects of two different doses of PXN (PXN LOW, PXN HIGH), CAF (CAF HIGH), and a control group on cognition (escape latency in the Morris water maze test), neurotransmitters (acetylcholine, dopamine, and gamma-aminobutyric acid), and neurochemicals (BDNF, catalase, glutathione, and cyclic GMP) were analyzed from whole brain samples in young (8 weeks old) and aged (16 months old) rats. Compared to the control group, escape latency improved in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.05) in young animals, and in PXN HIGH and CAF HIGH in older animals (P < 0.001). PXN HIGH improved escape latency compared to CAF HIGH in both young (P < 0.001) and old animals (P = 0.003). BDNF levels increased in PXN LOW, PXN HIGH, and CAF HIGH (all P < 0.001), with PXN HIGH increasing BDNF to a greater extent compared to CAF HIGH (P = 0.03). PXN HIGH also significantly increased BDNF levels compared to PXN LOW (P < 0.001). All other neurotransmitters and neurochemicals significantly increased in the PXN HIGH and CAF HIGH groups compared to the control. In conclusion, PXN showed greater improvements in cognition and BDNF levels compared to CAF, further substantiating PXN as a nootropic with greater benefits compared to CAF.

Keywords: BDNF; Caffeine; Cognition; Learning; Nootropics; Paraxanthine.

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Conflict of interest statement

Declarations. Conflict of interest: R.J., M.P., S.D.W. and K.L. are researchers and principals of Ingenious Ingredients, the sponsor of the study, and inventors of numerous patent applications for the use of paraxanthine but have been involved in data collection or analysis. R.J., M.P. and S.D.W. serve on the scientific advisory board and K.L. is the CEO of NNB Nutrition, the manufacturer of the paraxanthine used in this study. S.A. is an employee of Iovate Health Sciences, a distributor of paraxanthine, but has not been involved in data collection or analysis. A.G. is employed by Radiant Research Services Pvt. Ltd., and Radiant Research is a CRO who has received funding from Ingenious Ingredients to conduct this study. G.M.T. provides consulting services, including statistical analysis and dietary supplement formulation, through Tinsley Consulting LLC but has no conflicts of interest related to the use of paraxanthine. M.O. declares no competing interests.

Figures

Fig. 1
Fig. 1

Timeline diagram of the chronological order of manipulations

Fig. 2
Fig. 2

The impact of age and supplementation on BDNF (A), catalase (B), cyclic GMP (C) and β-amyloid (D). Letters that are different indicate significantly different group values based on pairwise comparisons following significant group effects (P < 0.001). P-values: Group all < 0.001; Age all < 0.001; Interaction ≥ 0.59. Data presented as mean ± SD for n = 8 in each group. BDNF, brain-derived neurotrophic factor; CON, control; PXN LOW, low dose paraxanthine; PXN HIGH, high dose paraxanthine; CAF HIGH, high dose caffeine

Fig. 3
Fig. 3

The impact of age and supplementation on (A) acetylcholine, dopamine (B), GABA (C), glutathione (D). Letters that are different indicate significantly different group values based on pairwise comparisons following significant group effects (P < 0.001).*Different from CON within same age group (P ≤ 0.02). #different from PXN LOW within same group (P < 0.001). †YOUNG different from OLD within same treatment group (P < 0.01). P-values: Group all < 0.001; Age all < 0.001; (A–C) Interaction ≥ 0.87, (D) Interaction < 0.001. Data presented as mean ± SD for n = 8 in each group. CON, control; PXN LOW, low dose paraxanthine; PXN HIGH, high dose paraxanthine; CAF HIGH, high dose caffeine

Fig. 4
Fig. 4

The impact of age and supplementation on learning and memory assessed as highlighted by reductions in escape latency. *Different from CON within same age group (P ≤ 0.049). #different from PXN LOW within same age group (P < 0.001). ‡Different from CAF within same age group (P ≤ 0.01). P-values: Group < 0.001; Age < 0.001; Interaction < 0.001. Data presented as mean ± SD for n = 8 in each group. CON, control; PXN LOW, low dose paraxanthine; PXN HIGH, high dose paraxanthine; CAF HIGH, high dose caffeine

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Paraxanthine enhances memory and neuroplasticity more than caffeine in rats – PubMed