Ginseng and Ganoderma lucidum (G. lucidum) are two herbal remedies that have been widely used to proactively promote health, vitality, and longevity in Asia [10], [11], [12]. In recent years, ginseng use has gained popularity in Western countries. For instance, ginseng has been included in the Pharmacopoeias of Germany, Austria, and the United Kingdom [13]; in the United States, ginseng has been ranked as the fourth top-selling herbal medicine [14]. However, evidence-based information on the association between ginseng use and QOL is inconsistent and limited, particularly among patients with cancer [13], [15], [16]. G. lucidum is a popular medicinal mushroom. Besides being used for promoting health, it is also used for prevention or treatment of a variety of diseases, including cancer [12]. We have found that G. lucidum is one of the most commonly used herbs among Chinese breast cancer survivors [17]. Several in vitro studies have reported that G. lucidum has anti-cancer properties [12], [18], [19], [20]. However, to date, no clinical or epidemiological studies have described the influence of G. lucidum use after cancer diagnosis on clinical outcomes or survivor’s QOL.

Demographic, lifestyle, and medical characteristics of all participants and by ginseng or G. lucidum use at the baseline interview are presented in Table 1. The mean age at diagnosis was 53.8 years (±10.0 SD). At baseline, ginseng users, compared with non-users, were older and were more likely to take vitamins and other supplements, have a higher comorbidity index, be regular cigarette smokers, have undergone tamoxifen treatment, and report a better overall QOL at study enrollment, but were less likely to use G. lucidum or other TCM, be post-menopausal, or to have undergone mastectomy or chemotherapy. Compared with non-users of G. lucidum, G. lucidum users were younger and were more likely to use vitamins and TCM, have better education and higher income, be married, be post-menopausal, have menopausal symptoms, have a lower comorbidity index, regularly participate in exercise, have received chemotherapy and radiotherapy, and were less likely to be regular cigarette smokers.

We found no overall associations between ginseng use during the three time periods we assessed and total QOL score or scores for the physical, psychological, social, or material well-being domains measured at the 36-month follow-up (Table 2). Subdomain analysis showed that a lower score for daily living capability and a higher score for community services was associated with ginseng use at the baseline survey, a higher score for body/self-image was associated with ginseng use assessed at 18-month survey, and a lower score for the financial situation subdomain was associated with ginseng use assessed at the 36-month survey.

G. lucidum use at the 6- and 36-month surveys was not significantly associated with total QOL or psychological well-being at the 36-month follow-up (Table 3). However, we observed significant associations with higher scores for social well-being and material well-being and with a lower score for physical well-being. Specifically, G. lucidum users had higher scores for self-image, social support, interpersonal relationships, housing situation, and community services, but lower scores for sleep and energy, physical discomfort, and eating function.

We also evaluated associations of pattern of use, average frequency of use, and cumulative number of times of use of ginseng or G. lucidum since cancer diagnosis with QOL at the 36-month survey (Table 4). In general, there were no significant differences in total or subscale QOL scores between participants who never used ginseng regularly and those who ever used ginseng regularly after cancer diagnosis. We found that ginseng users in the “consistent” group, compared with never-users, had a lower score for physical well-being, which reached borderline statistical significance (adjusted mean difference: −0.71; 95% CI: −2.49, 0.07). A borderline significant association between higher frequency of ginseng use (>11.6 times/month) and low physical well-being was also observed (adjusted mean difference: −0.92 (95% CI: −1.90, 0.05).

Higher frequency (≥31.8 times/month) of G. lucidum use after diagnosis was related to higher total QOL scores (P for trend =0.05) and higher social well-being scores (P for trend <0.0001). A higher cumulative number of times (>360 times) of G. lucidum use after diagnosis was positively associated with social well-being (P for trend <0.0001; adjusted mean difference: 1.52; 95% CI: 0.81, 2.23) and inversely associated with physical well-being (P for trend =0.0003; adjusted mean difference: −1.49; 95% CI: −2.30, −0.68). These associations were predominantly observed among “pick-up” users and “consistent” users (Table 4).

Further analyses stratified by baseline QOL showed that the associations between regular ginseng/G. lucidum use and QOL at the 36-month follow-up were not modified by baseline QOL total score (interaction term test: all P >0.05) (Table 5). Similarly, we found no interaction of comorbidity, radiotherapy, or ER/PR status with regular use of ginseng or G. lucidum among the study participants (data not shown).

Ginseng has been used to maintain natural energy, increase physical and psychomotor performance, and improve mood and general health [13]. There are several types of ginseng, including Asian ginseng (Panax ginseng) and American ginseng (P. quinquefolius); the major active constituents are ginsenosides. Over 80% of our study population used American ginseng. In vitro experiments and in vivo animal studies have reported that ginsenosides have a variety of beneficial effects, including immunodulatory, anti-stress, anti-fatigue, and anti-carcinogenic effects [30], [31], [32]. However, in human studies, findings on the effects of ginseng on health-related QOL are mixed [13], [15], [16]. A systematic review by Vogler et al. summarized several randomized clinical trials and found contradictory results for ginseng ability to improve physical performance and immune function [16]. Coleman et al. reviewed 9 clinical trials and concluded that improvement in overall health-related QOL cannot be attributed to P. ginseng, although various facets of QOL had improved [13].

There is a paucity of data from epidemiological studies regarding the effects of ginseng use on QOL among cancer patients. Our previous studies have shown that ginseng use, particularly current use at the fourth year post-diagnosis, was positively associated with QOL scores, with the strongest effects in the psychological and social well-being domains [15]. In the present study, however, we found no significant positive associations between post-diagnosis ginseng use and survivors’ QOL at the 36-month follow-up. There are several potential reasons for this discrepancy. First, the design of previous studies differed from the present study, which is a prospective survival study specifically designed to investigate post-diagnostic lifestyle and CAM use and collected relevant information at multiple, pre-determined time points (6, 18, and 36 months after cancer diagnosis). Our previous study was an ad hoc follow-up of breast cancer patients enrolled in a case-control study, for which exposure data were collected at one time point after cancer diagnosis (approximately 48 months). Second, the prevalence of ginseng use among breast cancer survivors was substantially lower in the current study compared with the previous study, which may have obscured the association between ginseng use and breast cancer survivors’ QOL. In the previous study, 62.8% of women with breast cancer reported post-diagnosis ginseng use, and 30.6% were current users. In the present study, 14.2% of participants were ginseng users at baseline and 10.9% were ginseng users at the 36-month follow-up. In addition, the timing of the QOL assessment also differed between our two studies. In our earlier study, QOL was assessed only once at the fourth year post-diagnosis, while in the present study, QOL was assessed at 6 and 36 months post-diagnosis and the association of QOL at the 36-month survey with ginseng use was adjusted for the baseline QOL score.

G. lucidum was the most popular herbal remedy used by our study participants [17]. The prevalence of use among women with breast cancer increased during the decade prior to the current study’s recruitment period from 18.9% among breast cancer cases enrolled in our case-control study (1996–1998) [33] to 58.4% (2002–2006) [17]. In the present study, 58% of participants reported G. lucidum use at the 36-month survey. To date, over one hundred species of oxygenated triterpenes have been isolated from G. lucidum. G. lucidum has been reported to have many biological activities, such as histamine release-inhibitory action, immunomodulatory activity, antitumor cytokines acting on inhibition of leukemic-cell growth, and differentiation inducing activity [10]. In vitro experiments have shown that G. lucidum can inhibit proliferation, invasive behavior, and growth of tumor cells, and induce tumor cell apoptosis [12], [18], [19], [20], [34], [35]. However, no study has reported on the effects of G. lucidum use on clinical outcomes and/or QOL among breast cancer survivors. In the present study, we found that G. lucidum use after breast cancer diagnosis was associated with a higher score for social well-being, but a lower score for physical well-being. As a result, the overall QOL score was not significantly associated with G. lucidum use. The underlying mechanisms for these associations are unclear. The improvement of social well-being may reflect better financial and social support, while the reduced physical well-being score may suggest that either G. lucidum use negatively influenced patients’ physical well-being or patients with low physical well-being were more likely to seek G. lucidum as complementary treatment. Given the popularity of G. lucidum use among women with breast cancer, more studies should be conducted to clarify its effects on breast cancer survivors’ QOL.

Our study has several strengths. It is the first population-based, longitudinal, prospective study with a large enough sample size to investigate relationships between the use of ginseng and G. lucidum after diagnosis and QOL among breast cancer survivors. Multiple assessments improved the quality of both the exposure and outcome information. Selection bias was largely minimized due to the high response and follow-up rates. The detailed data on socio-demographic, lifestyle, and known clinical prognostic factors that we collected allowed a detailed adjustment for potential confounding factors. However, several limitations of our study should also be noted. First, information about pre-diagnosis use of ginseng and G. lucidum was not available; thus, we were unable to evaluate the influence of pre-diagnosis ginseng and G. lucidum use on QOL. Second, the brand of ginseng and G. lucidum products and specific dosages used may affect their effectiveness, but our study did not collect this information. Third, although sexual functioning is an important component of QOL, we were not able to evaluate its association with ginseng and G. lucidum use, because of the very small number of participants who reported being sexually active, which is likely due to the fact that the subject of “sexual functioning” is considered to be very private in Eastern cultures.