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Table 6
Safety of Immunomodulatory Polysaccharide Products Following Oral Intake
Category	Source	Test group	Test	Design	Results	Equivalent human dose*	Reference

Arabino-galactans	Argemone mexicana (arabinogalactan protein)	Pregnant rats	Develop-mental toxicity	250, 500, or 1,00 mg/kg, gestational days 5-19	No developmental toxicity: NOAEL = 1 g/kg	68 g	[151]

		♀ and ♂ rats	Fertility	250, 500, or 1,00 mg/kg, 1 month	No effects on reproduction: NOAEL = 1 g/kg

Fucoidans	Undaria pinnatifida	Rats	Subchronic toxicity	1.35 g/kg, 1 month	No evidence of toxicity	91.8 g	[152]

Galacto-mannans	Cyamopsis tetragonolobus	Adolescent and adult ♂ rats	Subchronic and chronic toxicity	8% of diet, 6-67 weeks	No evidence of toxicity	8% of diet	[153]

		Rats	Acute toxicity	One 7.06 g/kg dose: observed 2 weeks	LD₅₀= 7.06 g/kg	480 g	[96]

			Subchronic and chronic toxicity	1, 2, 4, 7.5 or 15% of diet, 3 months	All doses ↓ ♀ BW; 7.5-15% ↓ ♂ BW; 15% ↓ bone marrow cellularity; ↓ kidney and liver weights	1-15% of diet

		19 adults with hypercholesterol-emia		18 g/day, 1 year	Short-term gastric bloating/loose stools, in 8 subjects, resolved in 7-10 days; 2 withdrew because of diarrhea. No toxicity for 13 subjects completing study	18 g	[154]

		16 Type II diabetics		26.4-39.6 g/day, 6 months	No effects on hematologic, hepatic, or renal function	39.9 g	[155]

		18 Type II diabetics		30 g/day, 4 months		30 g

	Cyamopsis tetragonolobus (partially hydrolyzed guar gum)	Mice & rats	Acute toxicity	One 6 g/kg dose; observed 2 weeks	LD₅₀> 6 g/kg	>408 g	[156]

		Rats	Subchronic toxicity	0.2, 1.0 or 5% of diet, 13 weeks	No evidence of toxicity	5% of diet

				0.5 or 2.5 g/kg, 1 month	NOAEL > 2.5 g/kg	>170 g	[157]

		S. typhimurium	Mutagenicity	Ames test	Not mutagenic	NA

Glucans	Agaricus subrufescens (aqueous extract)	Rats	Subchronic toxicity	0.63, 1.25, 2.5 or 5% of diet, 3 months	NOAEL = 5% of diet	5% of diet	[158]

		3 women with advanced cancers	Case reports	Specific identity of products, doses, and durations of intake unknown	Severe hepatotoxicity; two patients died	NA	[97]

	Agaricus subrufescens (freeze dried powder)	24 normal adults and 24 adults with liver problems	Subchronic toxicity	3 g, 4 months	No evidence of toxicity	3 g	[159]

	Ganoderma lucidum (supplement)	Elderly woman	Case report	1 year G. lucidum (and another unidentified product, initiated one month previous)	Elevated liver enzymes and liver tissue damage	NA	[98]

	Grifola frondosa (powder)	Rats	Acute toxicity	One 2 g/kg dose	No evidence of toxicity	136 g	[160]

	Lentinula edodes (powder)	10 adults	Safety	4 g/day for 10 weeks; repeated 3-6 months later	50% of subjects experienced blood eosinophilia, ↑ eosinophil granule proteins in serum and stool, ↑GI symptoms	4 g	[99]

	Lentinula edodes (SME)	Nude mice	Safety	10% of diet days 1-18, 33-50	No adverse events	10% of diet	[80]

		61 men with prostate cancer		0.1 g/kg, 6 months	No adverse events	6.8 g

	Lentinus lepideus (PG101)	Female mice	Subchronic toxicity	0.5 g/kg, 24 days	No evidence of toxicity	34 g	[92]

	Phellinus linteus (crude extract)	Rats	Acute toxicity	One 5 g/kg dose; observed 2 weeks	LD₅₀> 5 g/kg	349 g	[161]

	Pleurotus ostreatus (aqueous extract)	Mice	Acute toxicity	One 3 g/kg dose; observed 1 day	LD₅₀> 3 g/kg	>204.g	[100]

			Subacute toxicity	319 mg/kg, 1 month	Hemorrhages in intestine, liver, lung, kidney; inflammation and microabscesses in liver	21.7 g

	Saccharomyces cerevisiae (particulate glucan [WGP])	Rats	Acute toxicity	One 2 g/kg, observed 2 weeks	LD₅₀> 2 g/kg	>136 g	[144]

			Subchronic toxicity	2, 33.3 or 100 mg/kg, 3 months	NOAEL = 100 mg/kg	6.80 g

Heteroglycans	Trametes versicolor (PSP)	Rats	Subchronic toxicity	1.5, 3.0 or 6.0 mg/kg, 2 months	No evidence of toxicity	408 mg	[162]

		Rats & monkeys	Subchronic and chronic toxicity	100-200X equivalent human dose, 6 months	No evidence of toxicity	NA

	Trametes versicolor (PSK)	Humans with colon cancer	Safety	3 g/day, up to 7 years	No significant adverse events	3 g	[57]

		Humans with colorectal cancer		3 g/day, 2 years		3 g	[58]

Mannans	Aloe vera gel	Dogs	Acute toxicity	Fed one 32 g/kg; observed 2 weeks	LD50 > 32 g/kg	>2,176 g	Bill Pine, personal communi-cation

		Rats		One 21.5 g/kg; observed 2 weeks	LD50 > 10 g/kg	>680 g

*150 lb adult
Ramberg et al. Nutrition Journal 2010 9:54 doi:10.1186/1475-2891-9-54

Table 6