X. PHARMACOLOGY 377 



Ihreshold is 1.4 mg. %)'•- This threshold falls as the state of deficiency 

 progresses. There is always some vitamin cleared even when the tissues 

 are severely depleted. Under these circumstances less than 5 % of a test 

 intravenous dose of 100 mg. will appear in the urine in 3 hours, whereas, 

 when this dose is given to a person whose tissues are saturated, more than 

 50 % will appear in the urine in 3 hours. 



Ascorbic acid also appears in the stool, but not more than 6 to 10 mg. is 

 excreted by this route in 24 hours even when large doses are fed.* Diarrhea 

 increases excretion by the fecal route. 



Ascorbic acid is found in greatest concentration in tissues of high meta- 

 bolic activity. It is highest in the retina, and occurs in decreasing concentra- 

 tion m the following tissues; pituitary gland, corpus luteum, adrenal cortex, 

 young thymus, liver, brain, testes, ovaries, spleen, thyi'oid, pancreas, sali- 

 vary glands, lungs, kidney, intestinal wall, heart muscle, spinal fluid, white 

 blood cells, erythrocytes, and plasma.^ 



Physical stress such as occurs during surgical operations or following 

 severe burns or shock of any type induces a precipitous fall in the plasma 

 ascorbic acid level and in the amount excreted in the urine A\ith or A\ithout 

 a load or tolerance test.^* ^ Massive doses of ascorbic acid given orally or 

 parenterally can restore the plasma level temporarily to normal. Normal 

 levels can be maintained only by high dosage with the vitamin until the 

 stress is temmiated. Ascorbic acid seems to be diverted from the plasma 

 and urine to the tissue or to storage depots. IMany other plasma constituents 

 including iron and the B complex vitamin react in the same way during 

 stress, and the fact that plasma levels are low does not necessarily indicate 

 that there is a deficiency of the substance, nor that more of the substance 

 is being utilized and therefore is required in much larger amounts than 

 usual. In the case of ascorbic acid such low levels do not mean that wounds 

 ■will not heal unless high plasma levels are maintained by massive dosage, 

 although the surgical literature implies that such is the case. Serum iron 

 levels fall when the adrenals are stimulated by ACTH but so far this 

 parallelism has not been demonstrated for ascorbic acid and much more 

 investigation is needed before the function of ascorbic acid during stress 

 will be clarified. 



1 E. P. Ralli and S. Sherry, Medicine 20, 251 (1941). 



2 J. M. Faulkner and F. H. L. Taylor, J. Clin. Invest. 17, 69 (1938). 



3 A. F. Abt and C. J. Farmer, The Vitamins, p. 411. American Medical Association, 

 1939. 



*M. Yavorsky, P. Almaden, and C. G. King, J. Biol. Chem. 106, 525 (1934). 



« C. C. Lund, S. M. Levenson, R. W. Green, R. W. Paige, P. E. Robinson, M. A. 



Adams, A. H. McDonald, F. H. L. Taylor, and R. E. Johnson, Arch. Surg. 55, 



557 (1947). 

 « C. C. Lund and J. H. Crandon, J. Atn. Med. Assoc. 116, 663 (1941). 



