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

Open Data