Effect of Cordyceps Militaris Beverage on the Immune Response

Study Overview
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Brief Summary
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This study developed functional beverages from the submerged fermentation of Cordyceps militaris (FCM) and aimed to investigate the potential of FCM in male and female healthy volunteers in Phayao province, Thailand. To provide essential information for the development of healthy drink products.

Detailed Description
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Healthy Thai males and females aged 25-60 were recruited at the School of Medical Sciences, University of Phayao, in 2022. Written informed consent was obtained from all research participants. A total of 40 participants were randomly assigned to one of the study groups (10 subjects each). Inclusion Criteria : Male and female adult participants aged 25-60 during the screening test. No history of hypersensitivity or idiosyncratic reactions to drugs or herbal products. Willing to participate in the project throughout the research program. Exclusion Criteria : Participants diagnosed with immune-mediated disease, nervous system disorders, cardiovascular disease, or liver or kidney disease. Participants diagnosed with chronic health problems such as hypertension, diabetes, or renal failure, etc. A body mass index (BMI) greater than 29.9 or less than 18 kg/m2. Participants who were pregnant or lactating or intended to become pregnant during the trial period. Participants who, within two weeks, ingested a drug or functional food that may affect the immunomodulatory effect of the test product. Participants who had an alanine transaminase (ALT) or aspartate transaminase (AST) plasma level more than three times the guideline of the organization. Laboratory research has been conducted to confirm the eligibility of research participants, including hematology, serum biochemistry, blood coagulation, and urinalysis. The participants who met the inclusion requirements were randomized into experimental groups. Twenty random numbers were generated using Statistical Package for the Social Sciences (SPSS) 26.0. Digits 1st-10th of each gender were numbered as the FCM group, and the remaining digits, 11th-20th of each gender, were numbered as the placebo group. All researchers, participants, and related medical staff were blinded to the intervention assignments throughout the study.

Official Title
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A Randomized Controlled Clinical Trial of Cordyceps Militaris Beverage on the Immune Response

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Functional beverages from the submerged fermentation of Cordyceps militaris
* Other: Fruit juice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adult participants aged 25-60 during the screening test. No history of hypersensitivity or idiosyncratic reactions to drugs or herbal products. Willing to participate in the project throughout the research program. Exclusion Criteria: Participants diagnosed with immune-mediated disease, nervous system disorders, cardiovascular disease, or liver or kidney disease. Participants diagnosed with chronic health problems such as hypertension, diabetes, or renal failure, etc. A body mass index (BMI) greater than 29.9 or less than 18 kg/m2. Participants who were pregnant or lactating or intended to become pregnant during the trial period. Participants who, within two weeks, ingested a drug or functional food that may affect the immunomodulatory effect of the test product Participants who had an alanine transaminase (ALT) or aspartate transaminase (AST) plasma level more than three times the guideline of the organization.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Male or female received a single oral dose of functional beverages from submerged fermentation of Cordyceps militaris (FCM) or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Male received functional beverages<br>Male received single oral dose of functional beverages from submerged fermentation of Cordyceps militaris (FCM) | Dietary Supplement: Functional beverages from the submerged fermentation of Cordyceps militaris<br>* The Cordyceps militaris submerged fermentation in fruit juice.<br>* Other names: FCM;|
| Placebo Comparator: Male received placebo<br>Male received placebo | Other: Fruit juice<br>* Fruit juice is used as a placebo.<br>* Other names: Placebo;|
| Experimental: Female received functional beverages<br>Female received single oral dose of functional beverages from submerged fermentation of Cordyceps militaris (FCM) | Dietary Supplement: Functional beverages from the submerged fermentation of Cordyceps militaris<br>* The Cordyceps militaris submerged fermentation in fruit juice.<br>* Other names: FCM;|
| Placebo Comparator: Female received placebo<br>Female received placebo | Other: Fruit juice<br>* Fruit juice is used as a placebo.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from the baseline on physical examination (Height) | The first visit was conducted within one week after screening. Every 15 days after taking the test substance, the subjects were examined for height (Centimeter). | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the physical examination (Weight) | The first visit was conducted within one week after screening. Every 15 days after taking the test substance, the subjects were examined for weight (Kilogram). | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the physical examination (Blood pressure) | The first visit was conducted within one week after screening. Every 15 days after taking the test substance, the subjects were examined for blood pressure using an automatic blood pressure monitor (mmHg). | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the physical examination (oxygen saturation) | The first visit was conducted within one week after screening. Every 15 days after taking the test substance, the subjects were examined for oxygen saturation using a fingertip pulse oximeter (%). | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the physical examination (adverse reactions) | The first visit was conducted within one week after screening. Every 15 days after taking the test substance, the subjects were examined for adverse reactions (Questionnaire). | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the immune response (NK cells) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in natural killer cells (NK cells), measurement by using flow cytometry-based assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the cluster of differentiation (CD) antigens | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in cluster of differentiation (CD) antigens Cluster of differentiation 3 (CD3) Cluster of differentiation 4 (CD4) Cluster of differentiation 8 (CD8) B-lymphocyte antigen CD19 (CD19) Measurement by using flow cytometry-based assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the immunoglobulins | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in immunoglobulins Immunoglobulin A (IgA) Immunoglobulin G (IgG) Immunoglobulin M (IgM) Measurement by using flow cytometry-based assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the inflammatory cytokines | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in inflammatory markers Tumor necrosis factor alpha (TNF-α) Interleukin 1 beta (IL-1β) Interleukin 6 (IL-6) Measurement by using ELISA assay. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the safety parameters (Complete blood count (CBC)) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in complete blood count (CBC), measurement by using colorimetric assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the safety parameters (Fasting blood glucose) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in fasting blood glucose, measurement by using colorimetric assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the safety parameters (Plasma lipids) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in safety parameters Triglyceride Total cholesterol Measurement by using colorimetric assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the safety parameters (Renal function) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in safety parameters Creatinine Total protein Measurement by using colorimetric assays. | At 0, 4 and 8 weeks after end of the intervention | 
| Change from the baseline on the safety parameters (Liver function) | Blood samples (10 ml for each time point) were collected at 0, 30, and 60 days. The fasting blood samples were collected into plain and ethylenediamine tetraacetic acid (EDTA) tubes and delivered to the laboratory within 2 hours of collection. This experiment examined the changes in safety parameters Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Measurement by using colorimetric assays. | At 0, 4 and 8 weeks after end of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cordyceps militaris, Healthy subjects, NK cell, Cytokine, Immunomodulation