The herbal root extract ginseng has been used for centuries to treat mental and physical ailments, and promote longevity, thanks to its high content of flavonoids, other phenolic compounds, essential oils, vitamins, and ginsenosides including Rb1, Re, Rd, and F11.
American ginseng (Panax quinquefolius) provides a particularly rich source of these ginsenoside types when compared to other ginseng varieties.
Emerging research suggests that supplementation with P. quinquefolius may elicit cognitive enhancement effects. Several studies have investigated the benefits of Naturex SA's standardised American ginseng supplement Cereboost, although only acute benefits have been investigated to date. What's more, there is currently limited in vitro and in vivo research investigating possible mechanisms of action for observed improvements to mood and cognition, according to the authors of the current study.
This double blind, placebo controlled clinical trial therefore aimed to investigate the acute, chronic, and acute-on-chronic benefits of 200 mg Cereboost in healthy young adults (aged 18–40 years).
For the in vivo study (Experiment 1) 61 healthy participants, aged 18–40 years (15 males), were recruited from the University of Reading. Participants were randomised to receive either 200 mg Cereboost treatment or a placebo.
During the first test visit, mood and cognitive testing was performed at baseline (session 1), then 2 h, 4 h and 6 h following acute supplementation (sessions 2, 3, and 4, respectively). Participants then took supplements daily (1 capsule each morning with their breakfast) for a 2-week chronic intervention period, followed by a second test visit where mood and cognitive testing was repeated at baseline (session 5), then 2 h, 4 h, and 6 h following acute-on-chronic supplementation (sessions 6, 7, and 8).
Cognitive domains assessed included attention, working memory (provides for the temporary storage and manipulation of information that is necessary for complex cognitive tasks), episodic memory (the ability to recall and mentally reexperience specific episodes from one's personal past), and mood.
To investigate whether Cereboost might impact gut microbiota, a concurrent in vitro study was performed (Experiment 2). The Simulator of the Human Intestinal Microbial Ecosystem (SHIME) technology platform was used to model changes in the human microbiome, using a faecal sample obtained from a healthy young adult donor, and following the same daily dosing with 200 mg Cereboost with weekly microbial sampling for up to 21 days.
It was hypothesized that the composition of the gut microbiota would be beneficially affected, resulting in a greater abundance of SCFA microbial metabolites.
Consistent with previous findings, the results suggest Cereboost improved working memory and attention during the immediate postprandial period; effects that were amplified following two weeks’ treatment (acute-on-chronic) compared to acute testing alone. Chronic supplementation improved cognition on an acetylcholine-sensitive attention task and improved mental fatigue and self-assurance aspects of mood.
The parallel in vitro study revealed significantly increased acetate, propionate, and butyrate levels in simulated proximal and distal colon regions, linked with observed increases in Akkermansia muciniphila and Lactobacillus.
The authors conclude: "This study confirmed the promising effects of Cereboost on cognitive function. Acute benefits to working memory and executive function were further improved following a two-week period of daily supplementation. Daily supplementation with Cereboost also benefitted performance accuracy, mood and mental fatigue. Results from the concurrent in vitro study suggest a possible mechanism of action, via changes to the gut microbiome, potentially underlying the observed improvements to cognitive function. Chronic improvements to RVIP task performance also suggest that acetylcholine pathways of neurotransmission may be implicated. Further studies will be required to fully unravel the mechanisms involved."
A notable observation from the current study was a lack of acute improvements to mood, and a lack of acute or chronic episodic memory benefits.
The report notes: "Therefore, it appears possible that P. quinquefolius may not facilitate broad improvements to mood at the dose used in the current study. Here, no changes to positive affect, negative affect or mental fatigue were observed during the immediate post-prandial period, although benefits to mental fatigue and self-assurance were subsequently observed after daily treatment for 14 days.
"A more sensitive episodic memory task such as Reys Auditory Verbal Learning Task (RAVLT) may be better suited to the investigation of acute memory changes, rather than the simplified task used here. Daily supplementation over a two-week period also failed to elicit an episodic memory effect in the current study. Short-term (working) memory effects were observed for the Corsi task during this time frame. However, benefits to long-term memory may require an extended supplementation period."
Mechanisms of action
There are several possible underlying mechanisms of action that could explain the cognitive and mood changes that were observed in the current study following treatment with Cereboost. For example, acetylcholine plays an important role in the modulation of cognition and affect, and acetylcholine-related pathways of neurotransmission are already known to be impacted by P.quinquefolius. The chronic mood and fatigue effects observed here may therefore be due to facilitation of acetylcholine neurotransmission. Indeed, caffeine and other natural extracts are known to promote benefits to mental fatigue, through inhibition of acetylcholine esterase.
With respect to cognition, Rapid visual information processing (RVIP) was previously reported to be an acetylcholine-sensitive task following observed increases and decreases in task performance after treatment with an acetylcholine agonist (scopolamine) and an acetylcholine antagonist (nicotine), respectively. In the current study, chronic treatment with Cereboost seems to provide a beneficial effect on the RVIP task, thereby suggesting an acetylcholine-related mechanism of action for long-term cognitive improvements.
Emerging evidence suggests that the gut microbiome may impact cognitive function and mood, in part due to the facilitation of effective digestion and metabolism of bioactive compounds in food. Indeed, during the present in vitro study using a donor sample from a young adult of similar demographic to the cognitive participants, significant increases in SCFA levels and Akkermansia muciniphila abundance, and a clear trend towards increased Lactobacillus levels, were observed across three weeks of Cereboost supplementation. These improvements to the gut microbiome model provide a potential mechanism of action for improvements to cognitive function by facilitating not only the absorption and metabolism of bioactive compounds present in American ginseng, but potentially also the absorption of beneficial bioactive compounds found in habitually consumed foods.
It has been suggested that the gut microbiota play an important role in the bidirectional interactions between the central and the enteric nervous system, thereby likely affecting cognitive function. In the current in vitro study, Cereboost has demonstrated a prebiotic effect resulting in increased metabolite production as well as modulation of the microbial community composition. Therefore, it can be hypothesised that microbial modulation might be involved in the observed cognitive improvements following Cereboost supplementation.
These changes to gut microbiome were observed in vitro, rather than in the cognitive study participants, and so the current report states it will be critical for future research to provide an in vivo link between changes in gut microbiota and cognitive changes in the same host. A further limitation in the current study is that participants were predominantly female, while the faecal donor was male, so future studies should seek to confirm the cognitive and gut microbiota effects of Cereboost in a representative sample of both males and females.
Source: European Journal of Nutrition
Bell, L., Whyte, A., Duysburgh, C. et al.
"A randomized, placebo-controlled trial investigating the acute and chronic benefits of American Ginseng (Cereboost) on mood and cognition in healthy young adults, including in vitro investigation of gut microbiota changes as a possible mechanism of action"