FRI FOOD SAFETY REVIEWS TOXINS FROM CYANOBACTERIA M. Ellin Doyle Food Research Institute University of Wisconsin–Madison Madison WI 53706 Contents34B Microcystins...................................................................................................................................2 Beta-methylamino-L-alanine (BMAA)..........................................................................................3 Paralytic Shellfish Poisoning (PSP) Toxins ...................................................................................3 Anatoxin-a .....................................................................................................................................3 References......................................................................................................................................4 Appendix — FRI Briefing, May 1998: Toxins from Algae/Cyanobacteria (includes Pfiesteria) Cyanobacteria (previously called blue green algae) are strain-specific and is influenced by environmental ancient single-celled organisms, widely distributed in factors. These toxins include: aquatic environments, soil, and other moist surfaces Microcystins: heat stable, cyclic heptapep- and can survive in very inhospitable environments such tides that are toxic to liver cells and promote as hot springs and the arctic tundra. Some species growth of some tumors partner with fungi to form lichens, and others engage Beta-methylamino-L-alanine (BMAA): in symbiotic relationships with higher plants. Cyano- a neurotoxin, possibly associated with bacteria in lakes are often overlooked until their amyotrophic lateral sclerosis and populations grow rapidly, forming blooms that cover Alzheimer’s Disease large areas of the surface of lakes. Increased light and warm temperatures of spring and summer and high Paralytic shellfish poisoning toxins: nutrient levels, particularly phosphorus in runoff from neurotoxins that block sodium channels in agricultural operations and lawn fertilizers, are known neurons and calcium and potassium to stimulate growth of cyanobacteria. channels in cardiac cells Many cyanobacteria produce toxic compounds, Anatoxin-a: neurotoxin that inhibits acetyl- presumably for self-defense. Toxin production is cholinesterase Corresponding author: M. Ellin Doyle, Ph.D., [email protected] August 2011 http://fri.wisc.edu/docs/pdf/FRI_Brief_CyanobacteriaToxins_Aug2011.pdf Food Research Institute, University of Wisconsin–Madison 2 FRI FOOD SAFETY REVIEW: Toxins from Cyanbobacteria Intake of contaminated drinking water or food is ment, most microcystins are also eliminated along with the main route of human exposure to cyanotoxins. the cyanobacterial cells. Toxins released from damaged Humans may be exposed to these toxins by intentional cells can be neutralized by oxidation with chlorine or consumption of cyanobacteria. In some traditional ozone (18). Several drinking water treatment processes communities in Asia and South America, globular and biodegradation by certain bacteria can significantly colonies of Nostoc commune are harvested from lakes decrease microcystin levels in water (11;24;42). or rice paddies and are eaten alone or in soups or stews Humans may also be exposed to microcystins by (21;36). There have also been numerous reports of eating animals that have themselves consumed cyano- healthy compounds in cyanobacteria, and extracts of bacteria or cyanotoxins in water. Analyses for micro- cyanobacteria have become popular as dietary supple- cystins in muscle tissue of several species of fish ments (8;33). Cyanotoxins may also be present in revealed that walleye (23.9 µg/kg wet weight), white drinking water derived from surface water sources and bass (18.3 µg/kg wet weight), and smallmouth bass in food, particularly fish and shellfish that have con- (13.4 µg/kg wet weight) in Lake Erie and alewives sumed cyanobacteria. Exposure also occurs from aero- (25.9 µg/kg wet weight) and northern pike (10.2 µg/kg sols from lakes with cyanobacterial blooms and during wet weight) in Lake Ontario contained the highest recreational activities in such lakes (43). Risks to average levels. The highest level detected in any fish human health from different routes of cyanotoxin from these lakes was 43.6 µg/kg wet weight. Fish in exposure were reviewed with a discussion of both some lakes in Uganda have much higher microcystin acute, short term effects and chronic, long term effects concentrations. In tropical climates, cyanobacterial (1;14). Another recent review discussed inactivation blooms can occur year round and people are likely at and removal of cyanotoxins during drinking water greater risk because of constant, chronic exposure to treatment (42). An earlier FRI article on microcystins microcystin in drinking water and fish (34). Cooking and a toxic alga, Pfiesteria, is appended to this review. fish in the microwave or in boiling water decreases microcystin levels by 36–59% (17). Microcystins also accumulate in crayfish (40) and Microcystins blue crabs (15). Generally higher levels are detected in Microcystins are heat-stable, water-soluble, cyclic the intestine and hepatopancreas than in muscle tissue. peptides, containing 7 amino acids, that are produced Highest concentration of microcystin determined in by some strains of several genera of cyanobacteria: blue crab muscle from Louisiana was 105 µg/kg wet Microcystis, Anabaena, Nostoc, and Oscillatoria. Over weight. Shellfish (clams, oysters, mussels) are filter 70 varieties of microcystins have been described. feeders and may consume cyanobacteria and concen- These toxins are usually contained within living cells trate cyanotoxins up to 107 times the level found in but are released when cells die or are lysed by water ambient water. High concentrations of microcystins treatments, such as copper sulfate. Microcystin synthe- may be present in the water of eutrophic freshwater sis appears to peak at high cell concentrations, and total rivers that empty into the ocean and nearby marine microcystin concentrations of several mg/L have been shellfish may become contaminated. This has been reported in some scum samples (18;44). documented along the California coast where micro- Microcystins irreversibly inhibit serine/threonine cystin-poisoned sea otters have been observed (27). phosphatase enzymes, causing liver and kidney dam- There have been concerns that some foods that are age. Acute liver failure resulting in 56 deaths occurred not produced in aquatic environments might harbor in Brazil in 1996 when water containing microcystin microcystins. Providing drinking water containing was used for hemodialysis (20). Although some toxigenic Microcystis (105 cells/ml) to beef cattle for a research reports indicate that microcystins may have month did not cause liver dysfunction nor high levels carcinogenic effects, IARC reviewed these studies and of microcystin in liver tissue (30). Microcystins also concluded that available data indicate that these toxins did not accumulate to high levels in milk from dairy should be classified as possible carcinogens for humans cows that consumed Microcystis-contaminated water and other animals (18;46). (31). Microcystins in irrigation water do adhere to plant WHO has set a provisional tolerable daily intake surfaces in the field, with highest concentrations found of 0.04 µg microcystin/kg body weight and a recom- in the roots. If highly contaminated water must be used mended guideline limit of 1 µg/L in drinking water. for irrigation, toxin levels in plants should be moni- Microcystins have been detected in drinking water tored (14;28). samples from many countries, but toxin levels are usu- Cyanobacteria ingested directly as food supple- ally well below the guideline and acute oral doses are ments may contain microcystins. Research published in unlikely to occur. However, some communities con- 2000 reported that microcystins were detected in 85 of suming inadequately treated surface waters may be 87 commercial supplements tested and 63 samples chronically exposed to elevated microcystin levels contained >1 µg/g, the regulatory limit (16). Since then (34). When particles are removed during water treat- supplement producers have tested their products more Corresponding author: M. Ellin Doyle, Ph.D., [email protected] August 2011 http://fri.wisc.edu/docs/pdf/FRI_Brief_CyanobacteriaToxins_Aug2011.pdf Food Research Institute, University of Wisconsin–Madison FRI FOOD SAFETY REVIEW: Toxins from Cyanobacteria 3 frequently. Nevertheless, a 2008 paper reported that produced by other genera of cyanobacteria (9) and has 94% of cyanobacterial supplements tested in China been detected worldwide in lakes with algal blooms, contained 2–163 ng microcystin/g (19). Some non- including New Hampshire (7), Florida (6), The Nether- toxigenic cyanobacteria (Nostoc commune and lands (13), the Baltic Sea (22), and also in cyanobacte- Spirulina plantensis) are now cultivated in artificial rial crusts in the deserts of Qatar (10). BMAA has been ponds for use in supplements and these strains do not detected in fish muscle tissue, shrimp, crabs, and appear to have toxic effects in cell culture and animal cyanobacteria used as food and supplements tests (45). However, cyanobacteria do not generally (6;22;29;38). grow in pure cultures, and some supplements labeled Some studies have reported that brain tissue from as containing Spirulina were found to also contain patients who died of Alzheimer’s Disease, amyotrophic Microcystis and microcystin (37). lateral sclerosis,