Heo J-H, Lee S-T, Chu K, et al. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol. 2008;15: 865-868.

In studies of animals and healthy humans, ginseng exhibits cognition-enhancing properties. However, according to these authors from Seoul Medical Center and Seoul National University Hospital in Korea, no direct evidence is available to suggest that ginseng therapy can improve cognitive function in patients with Alzheimer's disease. The authors conducted an open-label pilot study to analyze the effects of Korean red ginseng (KRG; Panax ginseng) on the cognitive function of such patients.

Red ginseng is produced by steaming raw ginseng. It is reported to be more pharmacologically active, and it is widely held that the observed enhanced biological activities of red ginseng likely result from the production of deglycosylated ginsenosides formed during the steaming process from raw white ginseng root.¹ The active constituent of KRG is ginsenosides, which, in this study, is claimed to account for 8.54% of the herb. [Editor's Note: This value seems unusually high and is probably reflective of the common commercial practice of using rootlets, which are cheaper and higher in ginsenoside content. It is interesting to note that a recent study with steam-processed KRG claimed that ginsenosides Rg3 and Rg5 attained levels of 39% and 19%, respectively, of total ginsenosides, whereas this study indicates less than 3% of Rg3 and none of Rg5; Rg3 and Rg5 are widely regarded as the main principles responsible for the enhanced bioactivity of red ginseng over white.] Several animal studies have shown that ginsenosides such as Rb1 and Rg1 prevent scopolamine-induced memory deficits² and that ginsenosides Rb1 and M1 (from extensively deglycosylated protopanaxadiols), improve amyloid-induced amnesia in mice.^3,4

To be included in this study, patients had to be older than 50 years and have a baseline Mini-Mental State Examination (MMSE) score of 10 to 26. Patients were excluded if they had a history of psychiatric disorder, seizure disorder, or a medical condition that would hinder study completion; or if they had cognitive impairment because of stroke, hypoxic brain damage, cerebral neoplasia, infection, or medications such as antidepressants or psychoactive drugs.

The study was approved by the Institutional Review Board of Seoul National University Hospital. Intergroup comparisons of changes in Alzheimer's Disease Assessment Scale (ADAS) and MMSE scores were performed by using the Student's t test. The frequencies of side effects and withdrawal from the study were compared by using Fisher's exact test. All P values are two-tailed, and statistical significance was accepted for P values <0.05.

Sixty-one patients, aged 50 to 80 years, who were diagnosed with probable Alzheimer's disease according to the Neurologic and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, were enrolled in the study. No further details of patient recruitment are given. All patients had been treated with either donepezil (5-10 mg/day), galantamine (16-24 mg/day), memantine (20 mg/day), or rivastigmine (6-12 mg/day) for at least 6 months before the study. Antidementia drugs were continued during the study period.

The patients were randomly assigned to 1 of 3 treatment groups:

*Low-dose KRG (4.5 g/day) (n=15),

*High-dose KRG (9 g/day) (n=15), or

*Control (n=31).

KRG (total powder capsule, 6-year-old root, Korea Ginseng Corporation, Korea) was administered as adjunctive therapy for 12 weeks. Details of the KRG administration were not given.

No differences were reported among the 3 groups in baseline characteristics, including age; gender; scores on the ADAS-cognitive subscale, ADAS-noncognitive subscale, MMSE, and Clinical Dementia Rating (CDR); and composition of conventional antidementia drugs. Cognitive functioning was assessed using the ADAS, the Korean version of the MMSE, and the CDR scale before and 12 weeks after administration of KRG.

After 12 weeks, patients in the KRG groups showed trends toward improvement on the ADAS-cognitive subscale (P=0.057) and CDR (P=0.037) when compared with those in the control group. The improvements were significant in the patients treated with 9 g of KRG: the mean change in ADAS-cognitive score for the patients treated with 9 g of KRG was -4.02 ± 12.27, and for those in the control group, -0.43 ± 5.92. Similarly, the changes in CDR score between the patients treated with 9 kg of KRG (-0.69 ± 0.90) (P=0.0007) and those in the control group (-0.07 ± 0.49) (P=0.006) were significant.

No significant differences were reported in ADAS-noncognitive subscale and MMSE scores among the 2 KRG groups and the control. No significant difference in adverse events was found among the 3 treatment groups. 

According to the authors, this study was limited by its short duration and small number of patients. Also, because the study was not blinded, the possibility of a placebo effect cannot be ruled out. The exact cerebral locations affected by ginseng remain unknown because this study did not use a detailed neuropsychological test to assess specific brain regions.

KRG did, however, show "good efficacy for the treatment of Alzheimer's disease; further studies with larger samples of patients and a longer efficacy trial should be conducted to confirm the efficacy of KRG," say the authors.

-Shari Henson

References

¹Baek NI, Kim DS, Lee YH, Park JD, Lee CB, Kim SI. Ginsenoside Rh4, a genuine dammarane glycoside from Korean red ginseng. Planta Med. 1996;62:86-87.

²Benishin CG, Lee R, Wang LCH, Liu HJ. Effects of ginsenoside Rb1 on central cholinergic metabolism. Pharmacol. 1991;42:223-229.

³Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K. Ab(25-35)-induced memory impairment, axonal atrophy, and synaptic loss are ameliorated by M1, a metabolit of protopanaxadiol-type saponins. Neuropsychoparmacol. 2004;29:860-868.

⁴Kim J-H, Park C, Lee S-J. Effects of sun ginseng on subjective quality of life in cancer patients: A double-blind, placebo-controlled pilot trial. J Clin Pharm Ther. 2006 ;31:331-334.

Editor's Note: Many of these authors have also written another article on ginseng's use in Alzheimer's disease which will appear in a later HerbClip bin. (Lee S-T, Chu K, Sim JY, Heo J-H, Kim M. Panax ginseng enhances cognitive performance in Alzheimer [sic] disease. Alzheimer Dis Assoc Disord. 2008 July/September;22(3):222-226.)

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