# Differential Safety and Lipid Control Efficacy of β‐1,3/1,6‐Glucan Oligosaccharides and Polysaccharides Derived From Ophiocordyceps dipterigena BCC 2073 in Healthy Volunteers

## TL;DR

A 12-week study found that β-glucan oligosaccharides safely lower cholesterol in healthy people, with fewer side effects than polysaccharides.

## Contribution

This study is the first to compare the long-term safety and lipid-lowering efficacy of β-glucan oligosaccharides versus polysaccharides in humans.

## Key findings

- β-glucan oligosaccharides significantly reduced total cholesterol and LDL levels compared to placebo.
- Polysaccharides caused mild gastrointestinal side effects like constipation and loose stools.
- Both forms of β-glucan were safe with no serious adverse events observed over 12 weeks.

## Abstract

β‐1,3/1,6‐glucan is an immune‐modulating functional ingredient. To enhance solubility, β‐1,3/1,6‐glucan oligosaccharides were developed from polysaccharides through gamma‐irradiation. Nevertheless, whether their safety and efficacy profiles are different remains unclear. Our previous study identified 2000 mg/day as the maximum short‐term tolerable dose of Ophiocordyceps dipterigena BCC2073‐derived β‐1,3/1,6‐glucan oligosaccharides and polysaccharides. However, the long‐term safety of this dosage was unknown. This randomized, blinded, placebo‐controlled trial was conducted to evaluate their safety over 12 weeks. Ninety‐six healthy participants were randomly assigned to receive 2000 mg daily of either β‐glucans oligosaccharides, β‐glucans polysaccharides, or placebo capsules (n = 32 each group). Adverse symptoms, changes in body weight, defecation, hematological, and biochemical parameters, vital signs, and heart function were assessed using subject diaries, interviews, blood and urine tests, and electrocardiograms. No serious adverse events or changes in body weight, liver or renal function, complete blood counts, blood glucose levels, urinalysis, or electrocardiogram were observed in any of the groups. Notably, supplementation with β‐glucan oligosaccharides, but not polysaccharides, resulted in significant reductions in total cholesterol and LDL levels compared to the control group. Only the polysaccharides group had significant positive (easier defecation) and negative (constipation, loose stools) defecation‐related symptoms. The negative symptoms (found in 3%–19% of participants) were mild. These findings indicate that daily supplementation with 2000 mg of β‐1,3/1,6‐glucan oligosaccharides or polysaccharides for 12 weeks is safe in healthy individuals. The oligosaccharides demonstrated superior lipid‐lowering efficacy with fewer adverse events compared to the polysaccharides. Possible defecation‐related side effects of β‐1,3/1,6‐glucan polysaccharides should be considered.

Trial Registration: Thai Clinical Trial Registry: TCTR20240622005

This randomized, blinded, placebo‐controlled trial uncovers the novel findings that daily supplementation with 2000 mg of β‐1,3/1,6‐glucan oligosaccharides or polysaccharides for 12 weeks is safe in healthy individuals. The oligosaccharides demonstrated superior lipid‐lowering efficacy with fewer adverse events than the polysaccharides. Possible defecation‐related side effects should be a concern for β‐1,3/1,6‐glucan polysaccharides.