Research ArticleChemotherapy-induced immunosuppression is restored by a fermented soybean extract: a proof of concept clinical trial☆
Introduction
Cytotoxicity mediated by natural killer (NK) cells is an important defense mechanism against cancer. Depressed NK cell activity has been shown to be associated with a higher incidence of tumor recurrence or metastasis in many animal models [1], [2], [3]. Natural killer cell activity is significantly reduced in patients with cancers of head and neck, gastric, lung, and breast as compared with healthy individuals [4], [5], [6], [7]. The depressed NK activity is closely associated with a higher tumor stage, poor prognosis, and higher recurrent or metastatic rates [8], [9]. Chemotherapy is generally regarded as an immune suppressant if moderate cytotoxic doses are applied. However, the therapeutic effect from chemotherapy may, in turn, increase immunity due to the partial elimination of suppressive factors from tumor cells. Therefore, immune function has been shown to be affected by chemotherapy in both negative [10] and positive [11], [12] ways. Researchers hope that the combination of chemotherapeutic and immunotherapeutic approaches can be used in cancer treatment for 2 reasons: (1) restore depressed NK activity and (2) enhance immunity synergistically when chemotherapy has a positive effect on immunity [13].
During chemotherapy, the quality of life is often compromised, and poor appetite and fatigue are the most common and distressing problems in patients with cancer [14]. The prevalence of fatigue has been reported to range from 50% to 90% among patients with cancer, and 80% have their daily life affected; in fact, 28% of patients have been precluded from working entirely [15], [16], [17]. Anemia, dehydration, malnutrition, metabolic derangements, anorexia, and infection all have been proposed to be the cause of cancer-related fatigue and poor appetite. Because the etiology and mechanisms underlying fatigue and poor appetite in cancer patients are multifactorial, there is considerable variation in current practice regarding the management of such accompaniments of cancer, including antidepressants, glucocorticoids, psychostimulants, appetite stimulants, and transfusion [18].
ChemoYoung (MicroBio Biotech Comp, Taipei, Taiwan) is a fermented product produced from soymilk with microorganisms such as Lactobacillus acidophilus, L bulgaricus, Bacillus koernchen, Micrococcus lactis, and yeasts. The fermented soup is collected, sterilized, and used as a health food that has been sold in the marketplace for many years. ChemoYoung is a conditioned medium derived from an anaerobic microbial fermented product; it contains natural antibiotics to inhibit other bacterial species from growing but helping normal bacterial flora to grow. ChemoYoung was found to have an immune-modulating effect in both in vitro and in vivo experiments where significant activation of NK cells was observed (unpublished data). There is evidence that ChemoYoung is a potent 15-lipooxygenase enzyme activity inhibitor, and many inflammatory mediators are also inhibited (unpublished data). In vitro studies have demonstrated that the fermented soup has excellent antioxidant activities, such as scavenging of free radicals and inhibition of lipid peroxidation [19].
The primary aim of this study was to evaluate the effect of ChemoYoung on the restoration of NK activity depression during chemotherapy. This is the first dietary supplement trial aimed at boosting NK cell activity during chemotherapy.
Section snippets
Study design
This was a prospective, randomized, open-label, self-control, and crossover comparative study of oral ChemoYoung plus chemotherapy vs chemotherapy alone in patients with a variety of advanced cancers. The patient eligibility criteria were as follows: (1) a histologic- or cytologic-confirmed malignancy; (2) participation in an active chemotherapy program for at least one more cycle with the same regimen; (3) recovery from previous chemotherapy with resolution of all treatment-related toxicities
Patient characteristics
There were 32 patients enrolled in this study. Thirty patients completed the 2 cycles of chemotherapy and all the study parameters. Two patients received only 1 cycle of chemotherapy because of chemotherapy toxicity and refused to receive the second cycle. There were 30 paired data used to compare the study end points and 32 collected data points used for toxicity analysis. Table 1 shows the demographic data and baseline disease characteristics for the intent-to-treat study population. There
Discussion
Cancer patients undergoing chemotherapy often suffer from significant immune dysfunction. However, the negative side of chemotherapy has not attracted the attention of clinical oncologists due to a lack of nontoxic and reliable medications or dietary supplements for immune restoration. There has been no clinical trial reported thus far on how to reduce this side effect. We have demonstrated in this study that NK cell activity may be maintained 3 times higher (13.4% vs 4.5%) by the combination
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The study was partially supported by a Veterans General Hospital 92-365 grant from Veterans General Hospital, Taipei, Taiwan and MicroBio Biotech Comp, Taipei, Taiwan.