Sugar substitutes Increased interest in controlling body weight, coupled with wide publicity about the effects on health of consuming refined sugars, have resulted in widespread use of sugar substitutes by many Canadians. Although there are clear pressures to increase the use of sugar substitutes, public attitudes towards such products are in part also conditioned by more general concerns about chemical additives in food. These concerns stem from the cancer phobia so prevalent in North America, the growing distrust of science and technology, and the expanding ability of scientists to detect and evaluate subtle or delayed effects of chemicals on health. Saccharin has been used as a sugar substitute for more than three quarters of a century, following its accidental discovery in 1879 by Constantin Fahlberg, a graduate student in Ira Remsen's laboratory at Johns Hopkins University in Baltimore, Maryland. Had Fahlberg been more fastidious in his personal habits the discovery of saccharin's sweetening powers might well have been delayed. In the course of investigations on the oxidation of toluenesulfonamide he spilled on his fingers some of a compound he was working with. He noted the sweet taste of the bread he ate with his meal that night and traced the sweetness to the chemical now known as saccharin. Saccharin's potential as a sweetening agent was quickly recognized and the substance was soon used as a substitute for sugar in candies and bakery products. Almost at once controversy arose regarding its safety;
the passage of time has done little to reduce the furore. Although Theodore Roosevelt considered that "anybody who says saccharin is injurious to health is an idiot",1 during the presidency of his successor, W. Howard Taft, saccharin was banned in the United States from use in soft drinks and foods. A shortage of sugar in World War I led to its reintroduction, but it was used little until the late 1 950s, when sugar substitutes began to be used in foods designated for special diets. By 1970 the consumption of saccharin in Canada and the United States had risen to more than 2.5 million kg annually, as compared with less than 15 000 kg in 1953. In 1976 approximately 70% of the saccharin used in Canada and the United States was in so-called "diet" soft drinks, 13% was in dietetic foods and 12% was in table-top sweeteners. Given the continued controversy about its use, it is not surprising that saccharin has been extensively tested for safety. At least 13 long-term studies in rats, hamsters and mice have been conducted in such countries as Canada, Germany, Japan, the Netherlands, the United Kingdom and the United States.2 All but three were one-generation studies, none of which showed saccharin to be unsafe. However, in all three two-generation studies an increased incidence of bladder tumours was found in second-generation male rodents given large amounts of saccharin.' In 1977, following evaluation of the results of a two-generation study on rats conducted by the health protection
branch of Health and Welfare Canada,4 saccharin was banned from use in foods sold in Canada. However, it continues to be available in pharmacies, alone or in combination with cyclamates, for persons with diabetes or other reasons for restricting their intake of sugar. Although the use of large amounts of saccharin in studies with animals has been disputed by some, both the office of technology assessment (a branch of the United States Congress)5 and the United States National Academy of Sciences (NAS)' have concluded that saccharin is carcinogenic for rats, albeit with low potency. In addition to acting by itself, saccharin promotes the effects of other carcinogens in rats. It thus acts as both an initiator and a promoter of cancer. The NAS committee concluded that, although results obtained from valid studies with animals can, in principle, be extrapolated to humans, it is impossible at this time to estimate with confidence the risk to humans of saccharin consumption. The committee also noted that available reports of epidemiologic studies do not provide clear evidence to support or refute an association between bladder cancer in males and the use of saccharin. The NAS committee called attention to the increasing use of saccharin by children under 10 years of age in the United States: approximately one third of American children in this age group now regularly consume products containing saccharin. Much of the controversy surrounding regulatory decisions on saccharin use has revolved around the pur-
CMA JOURNAL/MARCH 17, 1979/VOL. 120 633
ported benefits in the treatment of diabetes, hypertriglyceridemia and excessive body weight, and in the prevention of dental caries. It is clear that many persons who have diabetes or are attempting to control their body weight perceive saccharin-containing foods and beverages to be beneficial. However, the reality of such presumed benefits is far from clear. In fact, the NAS committee found "no studies that permit objective assessment of the asserted health benefits of saccharin use". It is unclear, for instance, whether ingested saccharin replaces a significant amount of sugar, or whether its use simply leads to a shift in the pattern of food intake, with no change in the total energy intake. In the face of a lack of objective evidence of benefits from saccharin use, the long latent period for production of bladder tumours, the recently recognized role of saccharin as a promoter of cancer, and the fact that, with unrestricted marketing, young children are consuming more and more saccharin, a conservative attitude towards the use of this sugar substitute seems amply warranted. Sodium and calcium cyclamate have also been used extensively as sugar substitutes. The sweetness of sodium cyclamate was discovered by Audrieth and Sveda6 in 1937. By the mid-l 960s the use of cyclamates as sugar substitutes, primarily in "diet" soft drinks, had reached major proportions in Canada and the United States. However, in 1969 the use of cyclamates was substantially curtailed in Canada and was banned in many other countries because of evidence that suggested a link between cyclamate ingestion and bladder cancer in rats. Since then, several well designed and carefully conducted studies on the safety of the use of cyclamates have failed to demonstrate that cyclamate or its principal metabolite, cyclohexylamine, is carcinogenic in animals.7 It is interesting, however, that since 1969 evidence from various laboratories has shown that cyclohexylamine produces testicular atrophy in rats. On the basis of the "no-effect" level in the
rat, the acceptable daily intake, throughout life, of cyclamates for humans can be calculated to be approximately 8 mg/kg of body weight. The acceptable daily intake is not sufficiently high to permit the reintroduction of cyclamates in foods, but their use in table-top sweeteners or as sweetening agents in drugs seems warranted and is now permitted in Canada. At present there is considerable interest in yet another sugar substitute - aspartame. Although aspartame is a dipeptide ester and hence not a totally non-nutritive sweetener, it is a potential replacement for saccharin and cyclamates in at least some foods. This compound, which is approximately 180 times sweeter than sucrose, has not yet been approved for marketing in Canada. Regulatory authorities in the United States have questioned the authenticity of data provided by the manufacturer of aspartame for various other products. Although these allegations have vigorously been denied by the manufacturer, a thorough, independent assessment of the authenticity of the data supporting a request to market aspartame has been completed under the auspices of the Universities Associated for Research and Training in Pathology in Bethesda, Maryland. It seems prudent to delay a final decision on the acceptability of aspartame for marketing until an assessment of the review is complete. Finally, the five-carbon sugar alcohol known as xylitol, which is found in many edible fruits and vegetables, is used as a sweetening agent in Canada, but only in chewing gum. Although all of the data are not yet available for evaluation, results of recent studies in rats in a commercial laboratory in the United Kingdom suggest a significant increase in the occurrence of benign adrenal tumours, such as pheochromocytoma, in rats given 20% xylitol in the diet.8 The relevance of these findings to the safety of the consumption of xylitol by humans is not yet clear. In what may have been an over-reaction to data of unknown relevance, the National Institute of Dental
634 CMA JOURNAL/MARCH 17, 1979/VOL. 120
Health in the United States cancelled a study with children that was intended to determine whether xylitol helps prevent tooth decay. In Canada no action has been taken to discontinue the use of xylitol in chewing gum and, in the light of the available evidence, none seems warranted. The public must consider the risks and benefits associated with the use of sugar substitutes. Many people want such products. It is an ineluctable fact that such decision-making must be carried out in the face of less than ideal amounts of sound information on risks and benefits. Furthermore, the evaluation of available data, much of which lies at the very margin of scientific experience, is undeniably difficult. Thus, it is not easy to provide consumers with the information needed to permit them to make informed judgements about risks and benefits associated with the use of sugar substitutes. Furthermore, there are limitations to the doctrine that all consumers will make wise choices if information is made available to them. There are various options, ranging from a ban on selected sweeteners, to elimination of sugar substitutes from certain popular foods, to restriction on outlets of sale, to warning labels or other educational efforts, and, perhaps, to unrestricted marketing. In the absence of objective data on benefits, and in the light of available knowledge on the safety of currently marketed sugar substitutes, a conservative attitude towards their use seems warranted, especially for women of childbearing age, children and adolescents. A.B. MoRRIsoN, PH D
Assistant deputy minister Health protection branch Health and Welfare Canada Ottawa, Ont.
References 1. Influence of Saccharin on the Nutrition and Health of Man, rep no 94, US Dept of Agriculture, Washington, 1911 2. ZIENTY FB: Saccharin, in Symposium: Sweeteners, INGLETr GE (ed), Am Publ, Westport, Conn, 1974, p 141 3. Saccharin: Technical Assessment of Risks and Benefits, part 3, rep no 1, National Research Council/National Academy of Sciences, Washington, 1978, pp 20-21
* Atromid-S (clofI brate) Indications ATRQMID-S is indicated as an adjunct to diet and other measures for the reduction of elevated plasma lipids. Contraindications Pregnancy; lactation; hypersensitivity to ATROMID-S; clinically significant hepatic or renal dysfunction. Warnings Caution should be exercised when oral anticoag ulants are given in conjunction with A ROMID-S. The dosage of the anticoagulant should be reduced, usually by one-half (depending on the individual case), to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the levels have been stabilized. ATROMID-S may displace other acidic drugs, such as phenyton and tolbutamide, from binding sites on plasma proteins. In diabetics on sulfonylurea type drugs, ATROMID-S may potentiate hypoglycemia. The safety of this drug in children has not yet been established. Precautions Patients with a history of jaundice or hepatic disease should be treated cautiously. Frequent liver function tests should be performed since the drug may produce functional liver abnormalities, which are usually reversible. If these tests are persistently abnormal, the drug should be discontinued. Complete blood counts should be carried out periodically because anemia, and more frequently, leukopenia have been reported in patients on ATROMID-S. Patients with low serum albumin levels should be treated cautiously. High levels of unbound drug may cause myalgia and raised creatine phosphokinase serum levels. This "flu like" syndrome, which usually disappears when the dose is reduced, has also been observed. Adverse Reactions Nausea may occur in 5% of patients. Less common effects are vomiting, loose stools, dyspepsia, flatulence, and abdominal distress. Headache, dizziness, fatigue, weakness, skin rash, urticaria, pruritus, stomatitis are reported occasionally. A slight transient rise in SGOT and/or SGPT has been observed in some patients without evidence of hepatotoxicity. A few cases of increased BSP retention have been reported. Muscle cramping, aching or weakness have also been reported. A Product Monograph is available on request Dosage and administration For adults only-two capsules (1 g) twice daily with meals. Availability No.3243-Each capsule contains 500 mg clofibrate in bottles of 100 and 1000.
Ayerst .
AYER5T LABORATORIES Division of Ayerst, McKenna & Harrison Limited Montreal. canada Made in canada by arrangement with Imperial chemical PAAB Industries, Limited. Reg'd
4. ARNOLD
DL,
CHARBONNEAU
SM.
MOODIE CA, et al: Long-term toxicity study with orthotoluenesulfonamide and saccharin (abstr 78). Presented at the 15th annual meeting of the Society of Toxicology, Toronto, Mar 28-30, 1977 5. Cancer Testing Technology and Saccharin, office of technology assessment, US Congress, Washington, 1977
6. AUDRIETH LF, SVEDA M: Preparation and properties of some N-substituted sulfamic acids. J Org Cliem 9: 89, 1944 7. Evaluation of certain food additives. WHO Tech Rep Ser 557: 1974 8. Evaluation of certain food additives. WHO Tech Rep 5cr 631: 1978
Ciguatera poisoning - snowbirds beware Seafood fans who frequent the sunbelt areas of our continent should be aware of the increasing dangers of ciguatera poisoning. The reef fish of subtropical waters in North America consume algae that may contain a deadly heat-stable neurotoxin.'3 (These algae have recently been identified as a new species of dinoflagellate - a free-swimming unicellular organism that enters the food chain at a very early microscopic level.4) Over many months the neurotoxin accumulates in the tissues of the fish, much as mercury accumulates in the tissues of fish in our northern climes. This heat-stable, fatsoluble neurotoxin is particularly potent in large fish and is not destroyed by any amount of cooking. Black-fin grouper, amberjack and barracuda are particularly dangerous, although occasionally many other reef fish have been found to contain the toxin. However, shellfish and deep-water fish such as wahoo, mackerel and tuna do not contain the toxin. No fish in temperate Canadian waters are affected. In humans severe gastroenteritis develops 4 or 5 hours after consumption of toxic fish, and diarrhea may persist for many days. During recovery the patient becomes aware of a substantial sensitivity to cold, especially in the fingers and feet. To walk on a cool, tiled floor may be intolerable; to hold one's hand under cold water may be extremely painful. Even the air from air-conditioning units may be intolerable and painful to the nostrils and trachea. Aches in the
joints, jaws and muscles are very common during the recovery period (C. Deichman: personal communication, 1978), becoming somewhat intermittent and then more severe with exacerbations of cold intolerance. Full recovery may take 9 months or more; the intolerance to cold and paresthesia are the last symptoms to subside. The diagnosis of ciguatera poisoning is confirmed by feeding a specimen of the toxic fish to laboratory animals. Radioimmunoassay of the specimen has also been used with some success.5 Intraperitoneal injection of an extract into mice is a very sensitive test, and consumption of the fish by cats and dogs will produce classical neurologic changes followed by rapid death.1 Local commercial fishermen have several fascinating, although erroneous, methods of determining whether a fish has been affected by a toxin: a lone fish, separated from the rest of the school, should not be touched; if ants are repelled by the fish, it is considered dangerous to eat; if a turtle refuses to eat the fish, it is considered dangerous for humans to eat; if a thin slice of fish does not show the effect of a rainbow when held up to the sun, the fish is dangerous to eat; if a silver spoon is placed in the cooking pot, it will tarnish if the fish is toxic. The overall mortality associated with ciguatera poisoning is between 7% and 20%; respiratory paralysis, profound bradycardia and convulsions precede death. The distribution
CMA JOURNAL/MARCH 17, 1979/VOL. 120 637
the passage of time has done little to reduce the furore. Although Theodore Roosevelt considered that "anybody who says saccharin is injurious to health is an idiot",1 during the presidency of his successor, W. Howard Taft, saccharin was banned in the United States from use in soft drinks and foods. A shortage of sugar in World War I led to its reintroduction, but it was used little until the late 1 950s, when sugar substitutes began to be used in foods designated for special diets. By 1970 the consumption of saccharin in Canada and the United States had risen to more than 2.5 million kg annually, as compared with less than 15 000 kg in 1953. In 1976 approximately 70% of the saccharin used in Canada and the United States was in so-called "diet" soft drinks, 13% was in dietetic foods and 12% was in table-top sweeteners. Given the continued controversy about its use, it is not surprising that saccharin has been extensively tested for safety. At least 13 long-term studies in rats, hamsters and mice have been conducted in such countries as Canada, Germany, Japan, the Netherlands, the United Kingdom and the United States.2 All but three were one-generation studies, none of which showed saccharin to be unsafe. However, in all three two-generation studies an increased incidence of bladder tumours was found in second-generation male rodents given large amounts of saccharin.' In 1977, following evaluation of the results of a two-generation study on rats conducted by the health protection
branch of Health and Welfare Canada,4 saccharin was banned from use in foods sold in Canada. However, it continues to be available in pharmacies, alone or in combination with cyclamates, for persons with diabetes or other reasons for restricting their intake of sugar. Although the use of large amounts of saccharin in studies with animals has been disputed by some, both the office of technology assessment (a branch of the United States Congress)5 and the United States National Academy of Sciences (NAS)' have concluded that saccharin is carcinogenic for rats, albeit with low potency. In addition to acting by itself, saccharin promotes the effects of other carcinogens in rats. It thus acts as both an initiator and a promoter of cancer. The NAS committee concluded that, although results obtained from valid studies with animals can, in principle, be extrapolated to humans, it is impossible at this time to estimate with confidence the risk to humans of saccharin consumption. The committee also noted that available reports of epidemiologic studies do not provide clear evidence to support or refute an association between bladder cancer in males and the use of saccharin. The NAS committee called attention to the increasing use of saccharin by children under 10 years of age in the United States: approximately one third of American children in this age group now regularly consume products containing saccharin. Much of the controversy surrounding regulatory decisions on saccharin use has revolved around the pur-
CMA JOURNAL/MARCH 17, 1979/VOL. 120 633
ported benefits in the treatment of diabetes, hypertriglyceridemia and excessive body weight, and in the prevention of dental caries. It is clear that many persons who have diabetes or are attempting to control their body weight perceive saccharin-containing foods and beverages to be beneficial. However, the reality of such presumed benefits is far from clear. In fact, the NAS committee found "no studies that permit objective assessment of the asserted health benefits of saccharin use". It is unclear, for instance, whether ingested saccharin replaces a significant amount of sugar, or whether its use simply leads to a shift in the pattern of food intake, with no change in the total energy intake. In the face of a lack of objective evidence of benefits from saccharin use, the long latent period for production of bladder tumours, the recently recognized role of saccharin as a promoter of cancer, and the fact that, with unrestricted marketing, young children are consuming more and more saccharin, a conservative attitude towards the use of this sugar substitute seems amply warranted. Sodium and calcium cyclamate have also been used extensively as sugar substitutes. The sweetness of sodium cyclamate was discovered by Audrieth and Sveda6 in 1937. By the mid-l 960s the use of cyclamates as sugar substitutes, primarily in "diet" soft drinks, had reached major proportions in Canada and the United States. However, in 1969 the use of cyclamates was substantially curtailed in Canada and was banned in many other countries because of evidence that suggested a link between cyclamate ingestion and bladder cancer in rats. Since then, several well designed and carefully conducted studies on the safety of the use of cyclamates have failed to demonstrate that cyclamate or its principal metabolite, cyclohexylamine, is carcinogenic in animals.7 It is interesting, however, that since 1969 evidence from various laboratories has shown that cyclohexylamine produces testicular atrophy in rats. On the basis of the "no-effect" level in the
rat, the acceptable daily intake, throughout life, of cyclamates for humans can be calculated to be approximately 8 mg/kg of body weight. The acceptable daily intake is not sufficiently high to permit the reintroduction of cyclamates in foods, but their use in table-top sweeteners or as sweetening agents in drugs seems warranted and is now permitted in Canada. At present there is considerable interest in yet another sugar substitute - aspartame. Although aspartame is a dipeptide ester and hence not a totally non-nutritive sweetener, it is a potential replacement for saccharin and cyclamates in at least some foods. This compound, which is approximately 180 times sweeter than sucrose, has not yet been approved for marketing in Canada. Regulatory authorities in the United States have questioned the authenticity of data provided by the manufacturer of aspartame for various other products. Although these allegations have vigorously been denied by the manufacturer, a thorough, independent assessment of the authenticity of the data supporting a request to market aspartame has been completed under the auspices of the Universities Associated for Research and Training in Pathology in Bethesda, Maryland. It seems prudent to delay a final decision on the acceptability of aspartame for marketing until an assessment of the review is complete. Finally, the five-carbon sugar alcohol known as xylitol, which is found in many edible fruits and vegetables, is used as a sweetening agent in Canada, but only in chewing gum. Although all of the data are not yet available for evaluation, results of recent studies in rats in a commercial laboratory in the United Kingdom suggest a significant increase in the occurrence of benign adrenal tumours, such as pheochromocytoma, in rats given 20% xylitol in the diet.8 The relevance of these findings to the safety of the consumption of xylitol by humans is not yet clear. In what may have been an over-reaction to data of unknown relevance, the National Institute of Dental
634 CMA JOURNAL/MARCH 17, 1979/VOL. 120
Health in the United States cancelled a study with children that was intended to determine whether xylitol helps prevent tooth decay. In Canada no action has been taken to discontinue the use of xylitol in chewing gum and, in the light of the available evidence, none seems warranted. The public must consider the risks and benefits associated with the use of sugar substitutes. Many people want such products. It is an ineluctable fact that such decision-making must be carried out in the face of less than ideal amounts of sound information on risks and benefits. Furthermore, the evaluation of available data, much of which lies at the very margin of scientific experience, is undeniably difficult. Thus, it is not easy to provide consumers with the information needed to permit them to make informed judgements about risks and benefits associated with the use of sugar substitutes. Furthermore, there are limitations to the doctrine that all consumers will make wise choices if information is made available to them. There are various options, ranging from a ban on selected sweeteners, to elimination of sugar substitutes from certain popular foods, to restriction on outlets of sale, to warning labels or other educational efforts, and, perhaps, to unrestricted marketing. In the absence of objective data on benefits, and in the light of available knowledge on the safety of currently marketed sugar substitutes, a conservative attitude towards their use seems warranted, especially for women of childbearing age, children and adolescents. A.B. MoRRIsoN, PH D
Assistant deputy minister Health protection branch Health and Welfare Canada Ottawa, Ont.
References 1. Influence of Saccharin on the Nutrition and Health of Man, rep no 94, US Dept of Agriculture, Washington, 1911 2. ZIENTY FB: Saccharin, in Symposium: Sweeteners, INGLETr GE (ed), Am Publ, Westport, Conn, 1974, p 141 3. Saccharin: Technical Assessment of Risks and Benefits, part 3, rep no 1, National Research Council/National Academy of Sciences, Washington, 1978, pp 20-21
* Atromid-S (clofI brate) Indications ATRQMID-S is indicated as an adjunct to diet and other measures for the reduction of elevated plasma lipids. Contraindications Pregnancy; lactation; hypersensitivity to ATROMID-S; clinically significant hepatic or renal dysfunction. Warnings Caution should be exercised when oral anticoag ulants are given in conjunction with A ROMID-S. The dosage of the anticoagulant should be reduced, usually by one-half (depending on the individual case), to maintain the prothrombin time at the desired level to prevent bleeding complications. Frequent prothrombin determinations are advisable until it has been definitely determined that the levels have been stabilized. ATROMID-S may displace other acidic drugs, such as phenyton and tolbutamide, from binding sites on plasma proteins. In diabetics on sulfonylurea type drugs, ATROMID-S may potentiate hypoglycemia. The safety of this drug in children has not yet been established. Precautions Patients with a history of jaundice or hepatic disease should be treated cautiously. Frequent liver function tests should be performed since the drug may produce functional liver abnormalities, which are usually reversible. If these tests are persistently abnormal, the drug should be discontinued. Complete blood counts should be carried out periodically because anemia, and more frequently, leukopenia have been reported in patients on ATROMID-S. Patients with low serum albumin levels should be treated cautiously. High levels of unbound drug may cause myalgia and raised creatine phosphokinase serum levels. This "flu like" syndrome, which usually disappears when the dose is reduced, has also been observed. Adverse Reactions Nausea may occur in 5% of patients. Less common effects are vomiting, loose stools, dyspepsia, flatulence, and abdominal distress. Headache, dizziness, fatigue, weakness, skin rash, urticaria, pruritus, stomatitis are reported occasionally. A slight transient rise in SGOT and/or SGPT has been observed in some patients without evidence of hepatotoxicity. A few cases of increased BSP retention have been reported. Muscle cramping, aching or weakness have also been reported. A Product Monograph is available on request Dosage and administration For adults only-two capsules (1 g) twice daily with meals. Availability No.3243-Each capsule contains 500 mg clofibrate in bottles of 100 and 1000.
Ayerst .
AYER5T LABORATORIES Division of Ayerst, McKenna & Harrison Limited Montreal. canada Made in canada by arrangement with Imperial chemical PAAB Industries, Limited. Reg'd
4. ARNOLD
DL,
CHARBONNEAU
SM.
MOODIE CA, et al: Long-term toxicity study with orthotoluenesulfonamide and saccharin (abstr 78). Presented at the 15th annual meeting of the Society of Toxicology, Toronto, Mar 28-30, 1977 5. Cancer Testing Technology and Saccharin, office of technology assessment, US Congress, Washington, 1977
6. AUDRIETH LF, SVEDA M: Preparation and properties of some N-substituted sulfamic acids. J Org Cliem 9: 89, 1944 7. Evaluation of certain food additives. WHO Tech Rep Ser 557: 1974 8. Evaluation of certain food additives. WHO Tech Rep 5cr 631: 1978
Ciguatera poisoning - snowbirds beware Seafood fans who frequent the sunbelt areas of our continent should be aware of the increasing dangers of ciguatera poisoning. The reef fish of subtropical waters in North America consume algae that may contain a deadly heat-stable neurotoxin.'3 (These algae have recently been identified as a new species of dinoflagellate - a free-swimming unicellular organism that enters the food chain at a very early microscopic level.4) Over many months the neurotoxin accumulates in the tissues of the fish, much as mercury accumulates in the tissues of fish in our northern climes. This heat-stable, fatsoluble neurotoxin is particularly potent in large fish and is not destroyed by any amount of cooking. Black-fin grouper, amberjack and barracuda are particularly dangerous, although occasionally many other reef fish have been found to contain the toxin. However, shellfish and deep-water fish such as wahoo, mackerel and tuna do not contain the toxin. No fish in temperate Canadian waters are affected. In humans severe gastroenteritis develops 4 or 5 hours after consumption of toxic fish, and diarrhea may persist for many days. During recovery the patient becomes aware of a substantial sensitivity to cold, especially in the fingers and feet. To walk on a cool, tiled floor may be intolerable; to hold one's hand under cold water may be extremely painful. Even the air from air-conditioning units may be intolerable and painful to the nostrils and trachea. Aches in the
joints, jaws and muscles are very common during the recovery period (C. Deichman: personal communication, 1978), becoming somewhat intermittent and then more severe with exacerbations of cold intolerance. Full recovery may take 9 months or more; the intolerance to cold and paresthesia are the last symptoms to subside. The diagnosis of ciguatera poisoning is confirmed by feeding a specimen of the toxic fish to laboratory animals. Radioimmunoassay of the specimen has also been used with some success.5 Intraperitoneal injection of an extract into mice is a very sensitive test, and consumption of the fish by cats and dogs will produce classical neurologic changes followed by rapid death.1 Local commercial fishermen have several fascinating, although erroneous, methods of determining whether a fish has been affected by a toxin: a lone fish, separated from the rest of the school, should not be touched; if ants are repelled by the fish, it is considered dangerous to eat; if a turtle refuses to eat the fish, it is considered dangerous for humans to eat; if a thin slice of fish does not show the effect of a rainbow when held up to the sun, the fish is dangerous to eat; if a silver spoon is placed in the cooking pot, it will tarnish if the fish is toxic. The overall mortality associated with ciguatera poisoning is between 7% and 20%; respiratory paralysis, profound bradycardia and convulsions precede death. The distribution
CMA JOURNAL/MARCH 17, 1979/VOL. 120 637
