Abstract

Depressed activity of natural killer (NK) cells is often associated with a higher incidence of infection and tumor recurrence. Despite evidence that NK cell activity is depressed after chemotherapy, there have been no clinical trials reporting the amelioration of this side effect. ChemoYoung, a fermented soybean extract, has been shown to activate NK cells in vivo. We conducted a randomized clinical trial to examine the effect of ChemoYoung on the restoration of NK cell activity during chemotherapy. Thirty-two patients were recruited for a self-controlled, randomized, crossover chemotherapy program with 2 consecutive, identical dose intensity chemotherapy cycles, with or without the oral intake of ChemoYoung during each cycle of chemotherapy. Patients were administered ChemoYoung (MicroBio Biotech Comp, Taipei, Taiwan) for 21 days during chemotherapy. The NK cell activity, T4/T8 ratio, NK cell number, and serum interleukin (IL) 2 level on day 21 of each cycle were compared. The mean white blood cell nadir, T4/T8 (%), NK number (%), and IL-2 serum level (ng/mL) of the combined group vs the chemotherapy-alone group were 3096/μL vs 2404/μL, 35.3/15.2 vs 29.2/13.7, 19% vs 17%, and 3.2 vs 2.0, respectively (all P > .1). However, the NK activity was 13.4 ± 10.3 for the combined treatment group and 4.5 ± 3.2 for the chemotherapy-alone group (P = .001). Natural killer cell activities were significantly reduced in patients who received chemotherapy without the adjuvant use of ChemoYoung. A trend to a better quality of life was also noted as assessed using the instrument of the European Organization for Research and Treatment of Cancer core questionnaire.

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.

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