THE BETAINES AND THE VITAMINES 191 



Trigonelline is the betaine of nicotinic acid and, therefore, unlike the 

 betaines heretofore considered, is not obtainable from any amino-acid 

 cleavage-product of proteins. Its constitution is as follows: 



/ CH \ 



\ 



HC C.CO 



HC CH 



I 

 CH 3 



it is devoid of any obvious physiological action, but is of especial 

 interest because in the first place of its wide distribution in a variety 

 of vegetable tissues and in the second place because Nicotinic Acid, 

 from which it is derived by methylation, occurs in the polishings from 

 rice. 



In various parts of the Orient, but particularly Japan and the 

 Philippines, where rice constitutes a very large proportion of the 

 dietary, the introduction of milling methods which involve stripping 

 off the pericarp, or "polishing" of rice has led to the widespread occur- 

 rence of a disease known as Beri-Beri, the ravages of which were par- 

 ticularly prominent in the Japanese army during the Russo-Japanese 

 War. The disease is evidenced by general lassitude accompanied by 

 anesthesia in certain areas of the skin, edema of the ankles and face, 

 partial paralysis of the leg-muscles and, toward the termination of the 

 disease, distress in breathing. These symptoms are traceable to a 

 widespread peripheral neuritis, beginning in the nerve-fibers most 

 remote from the central nervous system and travelling centripetally. 

 The mortality is very high. It was pointed out by Eijkman in 1897 

 that beri-beri could be prevented by eating unpolished rice with the 

 pericarp intact, and that it could furthermore be cured by the adminis- 

 tration of rice-polishings ("rice-bran"). He discovered that a very 

 similar disease, involving peripheral polyneuritis and ultimate death, 

 could be induced artificially in pigeons by feeding them exclusively upon 

 polished rice. The inference was plain that a preventive and curative 

 substance is present in the pericarp of rice. 



The nature of this substance has been extensively investigated by 

 C. Funk and many others. Funk has succeeded in isolating a curative 

 crystalline substance from Yeast which is exceedingly potent, as little 

 as two milligrammes restoring the power of movement within three 

 hours to pigeons which have been completely paralysed by a diet of 

 polished rice. Curative substances are also found in a variety of other 

 foodstuffs and in animal tissues. They are soluble in water and in 

 alcohol, but insoluble, or sparingly soluble in ether. An active curative 

 substance is invariably found to yield a blue color when mixed with 

 Folin and Macallum's "Uric Acid Reagent," which is a solution of 

 sodium phosphotungstate containing a specified proportion of phos- 



