Fatigue and Endurance
A study in mice using a forced swim test noted that the polysaccharide content of Panax Ginseng may offer benefits to endurance via reducing fatigue, as administration of polysaccharides at 50, 100, and 200mg/kg bodyweight for 15 days noted that 1 hour after the last dose that only 200mg/kg bodyweight significantly improved performance. When the neutral polysaccharide fragment (40, 100, 160, and 200mg/kg) were compared against the acidic polysaccharide fragment, it was found that all doses of the acidic polysaccharides significantly improved performance and were the active ingredients (although the highest dose only of neutral polysaccharides also showed benefit). The acid fragment was more effective at enhancing circulating glucose, suppressing circulating TGs, and increased SOD expression relative to both the neutral fragment and supplemented control.
Another study using 1, 10, and 100mg/kg in mice (10% Ginsenosides) failed to demonstrate a statistically significant improvement in forced swim time after 7 days of supplementation in mice (although trended towards significance).
One study using 2g of Panax Ginseng 60% ethanolic extract in endurance trained athletes (minimum 2 years’ experience with 5 hours exercise weekly) for 6 weeks failed to notice any significant changes in testosterone, cortisol, or their ratio associated with Panax Ginseng. (Life Sci. 2001)
A study on 30 male endurance runners failed to establish any altered immune cell count or receptor (CD3+, CD4+, CD8+, CD20+) expression after 6 weeks of having 2g of 60% ethanolic extract of Panax Ginseng alongside their running regimens.
One study done in mice who were primed to be either cold (lower caloric intake, cold water swimming until fatigue) or feel warm (excess of dietary protein) noted that the addition the Panax Ginseng root was able to confer a warming effect on both groups, as assessed by less time spent on a warming pad located near the mice.
Ginseng is one of few herbs that has traditionally been used as an appetite stimulant for anorexia (appetite-loss) and cancer-related cachexia to stimulate appetite alongside the vertical root of Astragalus Membranaceus. Studies looking into the appetite enhancing effect of Panax Ginseng are lacking, with a study which injected isolated Ginsenoside Rb1 and found no influence on appetite per se, but a prevention of heat and surgery induced reduction of appetite; in accordance with traditional claims. One other rat study merely measuring food intake as an outcome parameter noted increases of 37.7% and 50% in normal chow and high-fat chow with 3% Red Ginseng, respectively, without significant differences in weight gain observed with the added calories (which was attributed to decreasing fat absorption from the diet, due to in vitro lipase testing and fecal analysis). This study used male Balb/c mice 8 weeks of age with no health abnormalities.
Ginsenoside-enriched fragments of Panax Ginseng at 12.5-25mg/kg (relatively low dose to anti-obesity doses) appear to somewhat attenuate radiation-induced pica (appetite for non-food products) in rats and the berries may have the same effect at a slightly higher dose of 50-150mg/kg. (Emendable, 2005)
Actual studies done on the subject matter note a reduction in food intake in obese mice possibly secondary to regulation of NPY in the hypothalamus (possibly secondary to IL-1b modulation (Kim JH, 2005), using an isolated Ginsenoside mixture at 200mg/kg bodyweight and suppressing intake by 12.4-21.2% that also affected lean mice over 3 weeks. Another study using Panax Ginseng berries found that 150mg/kg bodyweight was able to suppress food intake by 16% of the control group in diet-induced obese mice, and this was demonstrated to not occur with isolated ginsenoside Re at 20mg/kg bodyweight; this study tested lean mice, but did not report food intake alterations, food intake suppression may be more related to Rb1( Eutou,1988) or protopanaxadiols in general, including Rb1-3 and Ra1-3 (amongst others) which have been shown to reduce food intake by 16.3% in high-fat fed mice given 50mg/kg.
It is possible that Red Ginseng ginsenosides (also applies to Panax Ginseng in general) may help regulate abnormal feeding patterns with no influence on normal feeding patterns, but surprisingly little research has been done on appetite stimulation for which Ginseng is traditionally said to do. No human studies directed to answer this topic either, but potent and acute suppression of intake is seen in obese mice that overeat with mixed results in lean mice
A study in young healthy adults using 200 or 400mg acutely noted increased reaction time associated with 400mg, but not 200mg, 2.5 hours after ingestion. Interestingly, 200mg led to slightly but significantly slower reaction times on the first day of tested, which may have been secondary to an induction of calmness. (Reay JL, 2010). These improvements in reaction time have been replicated with 400mg of 4% Ginsenoside extract (G115) in regards to spatial reaction time at the same time after ingestion, but only when combined with Ginkgo Biloba did they reach statistical significance at 4 hours post ingestion for simple reaction time. A third test measuring reaction time noted some significant improvements, but most results were statistically insignificance; the results of this test may be secondary to anti-fatigue. The addition of Ginseng to Ginkgo appears to improve the parameters related to accuracy, and the ‘relaxing’ reports of Ginseng may reduce frequency of errors in cognitive tests. (Kennedy,2002)
Another study by the same researchers tested 200mg and 400mg of G115 in healthy young adults found improved performance on the serial sevens subtraction task, a test for intellectual efficiency. Lesser inconsistent benefits were achieved on serial threes and on a reduction of errors in serial 3s, but little benefit was seen in reduction of errors in serial sevens.
Alertness and relaxation specifically have also been noted with a Ginseng multi-nutrient combination supplement when taken over a period of 12 weeks, when compared to baseline values.
Panax ginseng might improve reaction speed and accuracy, but by currently unknown mechanisms and relative potency to other herbs; it doesn’t reach statistical significance all the time, so it may be unreliable as well.
Many of the general cognitive benefits may be secondary to the anti-fatigue effects of Ginsenosides and Polysaccharides, paired with persistence causing differences from the fatigued placebo
Depression, Anxiety, Stress
In mice, 100mg/kg of the acidic polysaccharide fragment of Ginseng was able to decrease depressive symptoms in mice while improving social interactions and reducing aggression. 200mg/kg appeared to not be significantly effective on these parameters. Anti-depressive effects have been noted in mice given Ginsenosides as well, suggesting both main components of Ginseng are active regarding depression. (Dang H,2009)
Red Ginseng also appears to be effective, with either hydrolysis of Red Ginseng or acetate fermentation (fermented Korean Red Ginseng) being significantly more effective at exerting anti-depressive effects in mice relative to normal Red Ginseng.
In regards to stress, a possible mechanism may be altering genetic transcription of some enzymes.  This study used pure saponin extracts in vitro at 10ug/mL and orally to rats at 200mg/kg noted that the mRNA levels of Tyrosine Hydroxylase and dopamine β-hydroxylase that was increased with stimuli was attenuated with Ginseng by 35.6 and 48.2% in adrenal glands (induced by stress) and 57.2% and 48.9% in neurons (induced by nicotine), respectively. (Kim Y,2010)
Memory and Learning
When looking at Ginsenoside Rb1 in isolation, it appears to be responsible for enhanced learning rats in the hippocampus. It can enhance NGF-induced neurite growth in the ganglia of chicks, and when fed orally to rats at 2mg/kg daily for 30 days showed a decrease in acquisition phase of learning, suggesting that the enhanced memory seen later was secondary to better learning. (Liu L,2011). This latter study failed to note any significant influence on motivation despite the enhanced learning, and after 30 days there was no significant difference in immunostaining of the hippocampus suggesting that no significant neurogenesis occurred.
In studies assessing learning deficits (cognitive decline) associated with toxins or aging, Ginseng appears to be somewhat effective at reducing the rate of learning deficits.
Oral administration of the Korean Red Ginseng compound Ginsenoside Rg3 has shown protective effects against cerebral ischemia-induced injury in animals, and in transient focal cerebral ischemia where 5, 10, and 20mg/kg Rg3 was given in feed found that 10mg/kg was as effective as 1mg/kg active control Nimodipine in reducing the cognitive deficit induced by ischemia, and 20mg/kg appeared to be more protective but not significantly so.(He B,2012)The percentage of infarct volume in the hippocampus was reduced to a similar degree in both 20mg/kg and Nimodipine, at about 20.1+/-2.8%, suggesting the potential to improve mitochondrial activity after brain injury with Rg3; and other measures of neurodegradation (TUNEL positive cells, Calpain-1 or Capsase-3 positive cells) were equally reduced by 10-20mg/kg Rg3 and Nimopidine. The mechanism by which Ginseng may protect from Ischemia can be through deregulating the expected sequence of hypoxia, as the incubation of ginsenosides from Korean Red Ginseng (KRG) appear to reduce the activity of a protein (Hypoxia-Inducible factor-1; HIF1) on the nucleus at the post-transcriptional level, but incubation with ginsenosides appears to actually increase HIF1 activity despite lesser actions.( Choi YJ, 2011) This appears to be since HIF1 needs to bind to the nuclear factor ARNT to induce its effects, and incubation with Korean Red Ginesng prevents this.
One study in humans assessing Panax Ginseng ingestion at either 200mg or 400mg acutely in healthy young adults noted that 200mg was able to reduce a fall in mood associated with prolonged (4 hour) psychological testing and 400mg induced a state of calmness. (Reay JL, 2010) There were no significantly different effects when comparing the first dose against the 8th consecutive daily dose, suggesting no tolerance nor build-up effect.
Another study replicated this reduction of fatigue with 200mg of the G115 extract (4% Ginsenosides) where a 10-minute neural test was performed, followed by 50 minutes’ rest, and then the same test 6 times in immediate succession. 400mg was still effective, but less so than 200mg.
A study done in humans assessing blood flow to the brain after Ginseng ingestion in healthy persons where 200mg G115 extract noted significantly reduced P300 latency (not amplitude) in all five tested cerebral lobes (main four, but left and right temporal tested independently) with significantly reduced beta and theta waveband power (in mV2/Hz) while alpha was reduced only in the frontal lobe, where beta and theta were more potent. No significant differences were seen between placebo and Ginseng in regards to CNV data, and the above differences were seen with eyes closed, with no significant differences on any parameter with eyes open.
A systemic review of Cerebrovascular effects of Ginseng only found two studies, the aforementioned study and one other that is not indexed online. (Lee,2011) The aforementioned study was rated high quality on the Jadad scale, with the other of low quality; their combination constituted moderate evidence, but both showed similar results.
Mood and Quality of Life
One study using 200 and 400mg Panax Ginseng found increased calmness in a relatively dose-dependent manner after acute ingestion in healthy adults. (Reay, 2010) These same doses and product were used in another trial on young adults over a period of 60 days in another trial, which failed to note any significant changes in any mood parameter measured. Interesting, a study conducted over a period of 8 weeks with a measurement at the 4-week marker found significant improvements in mental health and function as well as social function (assessed by the Short Form-36 Health Survey v.2) at 4 weeks, but the benefits associated with 200mg Ginseng became not significantly different than placebo at 8 weeks. (Ellis ,2002) One of the studies on mood and cognition that measured reactions to the initial dose and reactions to the 8th dose (when a once daily dose was taken) found that some parameters were less potent than baseline, but none of these trends of attenuation reached statistical significance.
It is possible that the mood improving effects of Panax are short-lived, either somewhere between 1-4 weeks before it starts to lose efficacy or perhaps slightly longer. That being said, acute usage of Panax does appear to improve subjective wellbeing and mood in otherwise healthy persons according to some evidence
Another study using a lower dose of 100mg or 200mg found that, over the course of 8 weeks, mood was improved in type II diabetics; this may be secondary to a bettering of the glycemic profile. A study using Ginseng in menopause failed to note global relief of menopausal symptoms but did note significant improvements in depression, well-being, and subjective ratings of ‘health’ over a period of 16 weeks.
One study that used a Ginseng multi-nutrient formulation that noted statistically significant improvements across the board on alertness and relaxation (placebo and ginseng both improved, significantly better effects in ginseng though) noted that when the results were controlled for only the persons in the lowest quintile of scores on the Visual Analogue Scale at baseline (a psychometric test) that there were also significant improvements in depressive scores and vitality, giving some evidence that the effects of Panax may be more pronounced in those more deviant from ‘normal’ baseline values.
The above may be overridden when it comes to persons who are not ‘healthy young adults’, where improvements in healthy may vicariously increase mood over a longer period of time.
Interestingly, an increase in quality of life is seen with multivitamins containing 40mg Panax Ginseng (as G115 extract) more-so than using standard multivitamins without the Ginseng, suggesting low dose Panax Ginseng may be valuable to add into a multivitamin formulation. Ginseng also appeared to abrogate an increase in diastolic blood pressure seen in the multivitamin group (for unknown reasons) and attenuated weight gain. This study was comparative with no placebo control, and thus the improvements seen in both groups could be attributed to placebo. Panax Ginseng has been investigated as part of a multivitamin formulation at 100mg as well, and a reduced occurrence of the flu as well as increased libido were both statistically significant between groups (overall sample size of 114) alongside the increase in subjective wellbeing, although the control group used pure placebo rather than a multivitamin without ginseng.
Benefits with Ginseng-containing multinutrient formulations are not always present, with trends towards improvement that are not statistically significant being seen and sometimes benefits only seen with the subject’s dietary habits are deemed as ‘poor’.
Ginseng might be a useful addition to multivitamin formulations when it comes to improving mood due to having some bioactivity at low doses (40-100mg), but its inclusion in multivitamin formulations is not completely reliable and valid with studies showing benefits as well as no significant benefits. It is plausible it may improve mood more than placebo in persons with worse baseline parameters of health than persons with better baseline parameters
A study in rats undergoing morphine withdrawal found that when wild ginseng (50, 100, 200mg/kg bodyweight) or cultivated Panax Ginseng (500mg/kg bodyweight) was injected alongside the morphine, that subsequent withdrawal (over 72 hours) showed significantly less pro-anxiety and depressive effects in the 200mg/kg group (with the other three groups trending towards less anxiety and depression, but not reaching significance).(Lee B,2011) These effects correlated with CFY and NPY immunoreactivity in the brain, suggesting that Wild Ginseng can act to normalize corticotrophin-releasing factor (CFY) and neuropeptide Y (NPY). Due to increased immunoreactivity of these molecules also being seen in nicotine dependence, (Slawecki,2005) it is plausible that Ginseng may interact with nicotine withdrawal.
Ginseng has been reported before as being a ‘vaccine adjuvant’, being able to amplify the efficacy of vaccines when Ginseng is in circulation when the vaccine is administered. (Hu S, 2003) It appears to be further synergistical with aluminum hydroxide. Coad ministration of ginseng extracts alongside the antigen appears to improve the immune antibody response. When administered as the G115 extract (4% Ginsenosides) in a 100mg dose to humans, it appears that G115 has the ability to reduce the occurrence of the flu when G115 is taken for 12 weeks and the vaccination is applied at week 4. (Scaglione,1996) This human study noted that the addition of Ginseng brought the rate of flu occurrence down to 35.7% of the control group with no clinically relevant side effects recorded over 12 weeks.
In a study using the polysaccharide of Panax Ginseng (Ginsan) in isolation, 100mg/kg injection once a day for two days prior to infection with an antigen resulted in significantly (3-4 fold) higher levels of IgG1 and IgG2, as well as secretory IgA (up to 2-fold) when compared to mice who did not receive Ginsan before infection. The observed effects are thought to be through enhanced CCL3 expression in Peyer’s patches, which influences dendritic cell migration (Sozzani,1997) and may positively influence antigen presentation to immune cells; this theory came from Coad ministration of COX inhibitors both reducing the increased CCL3 expression as well as reducing the beneficial observed effects of Panax Ginseng, although the tested COX inhibitor (aspirin) did not negatively influence immunity per se.
Coingestion of Panax Ginseng alongside an antigen (vaccinations) appears to augment the immune response to the antigen, and may work synergistically with vaccinations by being an immunostimulant during this time
Additionally, Red ginseng polysaccharides have been demonstrated to increase Natural Killer (NK) Cell activity (Du XF,2008) which seems to also apply to the polysaccharide Ginsan (not exclusive to Red Ginseng). When fed orally to rats, an increase in Natural Killer Cell activity is seen with Panax Ginseng.(Liou CJ,2006) When 100mg G115 (4% Ginsenosides) is administered to humans for 12 weeks, measurements at 8-12 weeks note a doubling of Natural Killer Cell activity relative to control. This increase in Natural Killer Cells has been failed to be noted with 2g of a 60% ethanolic extract over 6 weeks in athletes, however.
Panax Ginseng administration causes a drop in blood glucose in healthy persons while increasing cognition, although no significant correlations appear to exist between the two. When Panax Ginseng is consumed alongside 25g glucose, there do not appear to be any additive or synergistic effects of the combination while both, in isolation, can improve cognitive function in healthy adults. (Xie JY,2002).
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- The Serial Sevens Subtraction Test.