MINERALS 617 



nicotinamide, ascorbic acid, and thiamine rather effective in preventing 

 anemia in monkeys on the Goldberger diet. 



Summarizing, one may say that, with the possible exception of 

 pyridoxine, pantothenic acid, and perhaps fractions of the anti- 

 pernicious anemia principle, none of these substances exert a direct 

 influence on the synthesis of hemoglobin in the bone marrow. 



3.3.3. Minerals. There is a large literature on the effect of metals 

 on hemopoiesis. We can only quote a few of these papers and refer 

 the reader to the reviews of Schultze (2^76), of McCance and Widdow- 

 son (1799), of Maynard and Loosli (1891) and of Elvehjem (678). 



Copper. In 1928, Hart, Steenbock, Waddell, and Elvehjem (lUO) 

 bund that rats on a milk diet developed an anemia which was not 

 abolished by addition of iron, although this element was absorbed 

 and stored in liver and spleen. Only when small amounts of copper 

 were added to the diet did hemoglobin formation become possible. 

 A rat requires 0.3 mg. iron and 0.01 mg. copper per day. In spite of 

 findings to the contrary, it can now be considered as proved that 

 small_amounts of copper are needed for the synthesis of hemoglobin 

 in the mammalian body (cf. 21Jf, 2015, 2180,21^81); this also holds for 

 man (4^0,679,1378), although there is little evidence that copper 

 deficiency is important in the etiology of microcytic anemia in the 

 adult. 



The erythrocytes in the anemia of copper deficiency are only slightly 

 hypochromic, and copper has occasionally been observed to produce a marked 

 rise in erythrocyte numbers with little increase of the hemoglobin concen- 

 tration in the blood. This has led several workers to assume that copper is 

 necessary for cytopoiesis rather than for hemopoiesis. The effect on hemo- 

 globin formation is certainly of greater importance (cf. the discussion by 

 Schultze, 2^7^, as well as 25i8Q). Copper has little effect on the absorption 

 of iron {681,11^30,2520), but affects iron mobilization from the stores (Elveh- 

 jem and Sherman, Q81\ Sachs and co-workers, 21i.0d\ Copp and Greenberg, 

 1^89). Copper produces the typical reticulocyte response only in the presence 

 of iron (2479). Cunningham (518) observed that copper decreases the inor- 

 ganic iron content of the liver, while leaving its hematin iron content prac- 

 tically unaltered. He assumed that copper stimulates the synthesis of 

 "hemochromogen" precursors of hemoglobin in the liver, but such an explana- 

 tion is not acceptable in view of the fact that plasma iron is nonhematin 

 iron and there is no evidence for a transport of preformed hematin from the 

 liver to the bone marrow. In fact, his results are satisfactorily explained by 

 mobilization of nonhematin iron from the liver by the action of copper. 



In spite of the fact that the liver contains far more copper than the 

 bone marrow, it appears more likely that it is within the latter that 



