EFFECT OF DEFICIENCY IN ANIMALS 



7. EFFECT OF NICOTINIC ACID DEFICIENCY IN ANI2V1ALS 



It has already been stated (page 211) that, in the original experi- 

 ments on the cause of pellagra, rats and chickens did not respond 

 with characteristic deficiency symptoms when maintained on a nico- 

 tinic acid-deficient diet ; the symptoms observed were in fact due to 

 a deficiency of other vitamins. The diets used in these early experi- 

 ments presumably contained tryptophan and, as is now known, rats 

 do not require nicotinic acid if tryptophan is available, being able to 

 convert it into nicotinic acid (page 241). Moreover, in some animals 

 nicotinic acid may be provided by intestinal bacteria,^ although rats 

 were not rendered nicotinic acid-deficient by administration of sulpha- 

 guanidine ; ^ in these experiments, however, tryptophan was probably 

 present in the diet. 



Rats 



Nicotinic acid deficiency can be induced in rats by feeding a diet 

 substantially free from both nicotinic acid and tryptophan. ^ Growth 

 is suppressed and the nicotinic acid content of the tissues is diminished. 

 Under normal circumstances nicotinamide does not promote growth in 

 the rat, but actually inhibits it.* This adverse effect is attributed to 

 the conversion of nicotinamide into N^-methylnicotinamide by methy- 

 lation. This results in a smaller number of methyl groups than usual 

 being available for essential metabolic processes. The administration 

 of methionine or of choline plus homocystine prevented the inhibition 

 of growth by nicotinamide, but choline, betaine, homocystine or cystine 

 alone had no effect. Nicotinic acid behaved differently from nicotin- 

 amide ; it had no adverse effect on growth but caused fatty livers. 

 These were prevented by methionine, choline or betaine, but were 

 aggravated by cystine or homocystine. The apparent trigonelline 

 excretion was greater after feeding nicotinamide than after feeding 

 nicotinic acid, and was increased by administration of methionine or 

 choline. 



Horses ^ and cows,^ like rats, were able to synthesise all the nico- 

 tinic acid they required. 



Dogs 



The dog is the animal that most clearly demonstrates the effects 

 of nicotinic acid deficiency. The most striking symptom is the appear- 

 ance of the tongue, which becomes very dark in colour ; hence the 

 name applied to this condition — canine blacktongue. It was the 

 onset of this symptom that Goldberger and his colleagues used as a 

 test in their pioneer work on pellagra (see page 212). Dogs suffering 



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