Elsevier

Nutrition Research

Volume 27, Issue 11, November 2007, Pages 679-684
Nutrition Research

Research Article
Chemotherapy-induced immunosuppression is restored by a fermented soybean extract: a proof of concept clinical trial

https://doi.org/10.1016/j.nutres.2007.09.001Get rights and content

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.

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

References (36)

  • A.V. LeFever et al.

    Phenotype and function of natural killer cells in patients with bronchogenic carcinoma

    Cancer Res

    (1991)
  • S. Cunningham-Rundles et al.

    Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women

    J Natl Cancer Inst

    (1981)
  • J. Harris et al.

    The effect of immunosuppressive chemotherapy on immune function in patients with malignant disease

    Cancer

    (1976)
  • M. Okamoto et al.

    cis-Diamminedichloroplatinum and 5-fluorouracil are potent inducers of the cytokines and natural killer cell activity in vivo and in vitro

    Cancer Immunol Immunother

    (1998)
  • T. Kiyohara et al.

    Induction of lymphokine-activated killer-like cells by cancer chemotherapy

    J Exp Med

    (1988)
  • L.H. Li et al.

    Relationship between modulation of natural killer cell activity and antitumor activity of bropirimine when used in combination with various types of chemotherapeutic drugs

    Cancer Res

    (1987)
  • C. Miaskowski et al.

    Update on the assessment and management of cancer-related fatigue

    Princ Pract Support Oncol Updates

    (1998)
  • N.J. Vogelzang et al.

    Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition

    Semin Hematol

    (1997)
  • Cited by (15)

    • Diadzein ameliorates 5-fluorouracil-induced intestinal mucositis by suppressing oxidative stress and inflammatory mediators in rodents

      2019, European Journal of Pharmacology
      Citation Excerpt :

      Diadzein pretreatment remarkably reversed this leukopenia associated with chemotherapy. These results are comparable with previous studies that reported diadzein has successfully reversed chemotherapy-induced immunosuppression (Tsang et al., 2007). Key findings of the present study provide significant evidence of the ameliorative potential of diadzein against intestinal mucositis associated with 5-FU administration.

    • Recent research process of fermented plant extract: A review

      2017, Trends in Food Science and Technology
      Citation Excerpt :

      The mice in the VFFL 66.6 ml/kg group exhibited significantly extended survival rates compared with the mice in the control group, concluding that VFFL possesses anti-tumor properties. Tsang et al.(Tsang et al., 2007). found that ChemoYoung, a fermented soybean extract from Taiwan, China, could re store chemotherapy-induced immunosuppression.

    • Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer

      2014, Nutrition Research
      Citation Excerpt :

      Based on the properties of the ingredients [12-17], MB-6 is marketed as a dietary supplement to promote longevity. Furthermore, the active ingredients of MB-6 (fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin) have been shown to have biological activity in a number of pathologic conditions [7,10,18-21]. Preliminary pharmacologic studies have suggested that MB-6 suppresses the growth of human colon adenocarcinoma grade II cell line human colon cancer cells and that green tea extract and curcumin play a major role in this tumor-suppressive activity (unpublished data).

    • Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats

      2011, Pharmacology Biochemistry and Behavior
      Citation Excerpt :

      Monocyte populations have been suggested to be expanded in vivo following cytotoxic antineoplastic therapy which may contribute to T-cell immunosuppression by the production of suppressive factors inhibiting T-cell function (Ageitos et al., 1999; Mackall, 2000). Granulocytopenia following chemotherapeutic regimens increased risk of bacterial, viral, and fungal infections (Tsang et al., 2007). Grant et al. (1991) previously elicited myelo- and immune-suppressive functions of ADR.

    View all citing articles on Scopus

    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.

    View full text