The Vitamins: Fundamental aspects in nutrition and health (3rd Edition)
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It was included in the original mix, but at a level well below what turned out to be its requirement. The second factor was a previously unknown amino acid, which they identified as 2-aminohydroxybutanoic acid and named threonine When it was included in the amino acid mix the rats grew well so that this was a most important finding. Starting in , Rose set out to extend the study to human adults. This involved preparing much larger quantities of amino acids, and then careful control of the energy intakes of volunteers and measurement of their nitrogen balance.
All of this took time and the findings will be considered in Part 4. Meanwhile, the availability of isotopes had allowed a new approach to studying the fate and distribution of nutrients in the body. In Rudolf Schoenheimer and his colleagues at Columbia University reported results from feeding rats for three days a physiological dose of l -leucine, doubly labeled with N 15 and deuterium replacing hydrogen in the side chain. It was assumed that this was the consequence of transamination reactions. Schoenheimer thought at this time of protein molecules opening to release one amino acid molecule at a time into the blood stream before reattaching a replacement.
In any case, it appeared that most synthesis of body proteins must be coming from recycled amino acids rather than from newly digested dietary protein.
The first workers with purified diets felt that they could meet their animals' mineral requirements by giving them the residual ash from combustion of an apparently satisfactory food such as milk or dog biscuits. Then when the problems of supplying vitamins and amino acids had been solved they could begin to study individual mineral requirements.
One early finding, already quoted, was that rats would become rachitic if either the calcium or phosphorus content of the diet was greatly increased in the absence of vitamin D or irradiation. The development by of analytical procedures using emission spectroscopy allowed the detection of trace elements in foods. Thus, it was found that cow's milk contained strontium and vanadium in addition to the previously detected iron, copper, zinc and manganese, as well as larger quantities of calcium, magnesium, potassium, sodium and phosphorus Chlorine and iodine had been found using other procedures.
At Wisconsin copper had already been found to be required for the production of hemoglobin in rats fed purified diets Then in a deficiency of copper was found to be responsible for a characteristic sickness occurring in cattle in parts of Florida In the same year McCollum's group reported results with young rats fed a purified diet designed to be as low as possible in manganese content. They grew normally, but the males were sterile with testicular degeneration, and the females would breed when mated with normal males, but were unable to suckle their young Magnesium was known to be present in both bones and soft tissues of animals but it proved difficult to obtain a deficiency condition in rats.
Finally, by feeding rats a diet that after careful purification contained only 1. In contrast, grass-fed cattle would sometimes develop tetany that responded to dosing with magnesium salts even when the level in their blood appeared normal It also proved possible to produce zinc deficiency with a highly purified diet on which rats showed slow growth and loss of hair However, no evidence of zinc deficiency being a practical problem was seen in the period under review.
In contrast, serious problems affecting cattle and sheep in parts of Australia were recognized in as being due to cobalt deficiency without its having first been produced experimentally in laboratory animals The special function of cobalt in ruminant nutrition would only be worked out in a later period. The importance of iron in the prevention of microcytic anemia in human subjects was previously discussed 2.
Interestingly, iron deficiency had been much less of a problem in traditional animal husbandry, in large part because animals had access to soil which is rich in iron. However, when sows began to be brought indoors in the s for farrowing, the piglets had a higher death rate. This was found to be the result of anemia and workers in Scotland prevented it by adding iron salts to the sows' feed It was thought that the piglets obtained additional iron from contamination with her feed and feces rather than from any additional iron appearing in the sow's milk and this was confirmed in Wisconsin In Robert McCance and Elsie Widdowson, working in London at that time, published a classic paper arguing that contrary to current opinion, humans had little or no ability to excrete iron, and that there must therefore be a mechanism that regulated its absorption according to need This was confirmed by work with dogs using radioactive iron when it became available from the Berkeley cyclotron.
It was interesting that absorption did not increase immediately after dogs had been bled to induce anemia, but only seven days later when body iron stores had been exhausted as a consequence of increased synthesis of red cells As previously stated, the old idea that goiter was caused by deficiency of iodine became discredited in the 's as a result of toxic overdosing 1.
However, it gradually became recognized that iodine was concentrated in the thyroid gland and that the enlarged thyroid in goiter had a low iodine content The first thyroid hormone, thyroxine was also found to contain iodine in its molecule Old observations that the incidence of goiter did not seem to parallel the deficiency of iodine in local water and food supplies had made many enquirers believe that other factors must also be at work. In workers at Johns Hopkins discovered that rabbits fed mainly cabbage and being used for a study of infections had developed goiters Deliberate studies with rats then showed that most Brassica plants and also unprocessed soybeans had goitrogenic activity that responded to higher intakes of iodide , However, feeding Brassica seeds resulted in goiters that were reversed with thyroxine but not with iodine In David Marine organized a large-scale trial of iodine supplementation of schoolgirls in an area of Ohio where the disease was endemic The results of reexamination of these subjects six months after their first treatment are summarized in Table 3.
Longer periods of treatment produced more complete freedom from the problem with no evidence of harm. After this iodized salt began to be produced in many parts of the world with government encouragement. Results from the reexamination of the thyroids of schoolgirls in Akron, Ohio 6 mo after dosing with 2. Fluoride ions were recognized in the s as being toxic for livestock in areas where fluoride-rich ash was scattered as a result of mining or smoke from the manufacture of aluminum, with animals becoming stiff and lame and without appetite In the same period it was realized that mottling of the enamel of human teeth in particular areas was associated with a relatively high fluorine content of the local water supply It was then appreciated that at the other extreme children growing up where the water was low in fluoride had more dental caries.
This was accepted only with great reluctance, and the fluoridation of water supplies low in fluoride was delayed for several years Clive McCay had learned of this work while with Lafayette Mendel on a postdoctoral fellowship. Mendel had told him that a younger man was needed to pursue such long-term work. McCay, who had moved to a faculty position at Cornell in , decided to take it on. However, they also had to report that when the heating failed in the animal room it was only the skinny ones that succumbed! In addition to the advances in scientific knowledge in this period, there were important advances in its practical application.
Distributing iodized salt, as already mentioned, significantly reduced the incidence of goiter.
But there can be difficulties; for example, fortifying foods with iron salts may result in rancidity and destruction of vitamin A. Solving such technical problems can be as demanding as the original discoveries of nutrients, but is outside the scope of these articles as is the work of developing standards for the level of individual nutrients in adequate diets and also the evaluation of nutritional status in different population groups.
We are certainly indebted to them for their findings, but did they leave anything still to be discovered? That is what will have to be considered in Part 4. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide.
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The Benefits of B-Vitamins
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Rickets and vitamin D. Experimental scurvy. Beriberi and vitamin B.
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Pellagra in the United States. Folic acid. Other B vitamins. The fat-soluble vitamins. Essential fatty acids. Proteins and amino acids.
Mineral elements. Diet restriction and life span. Oxford Academic. Google Scholar. Cite Citation. Permissions Icon Permissions. The vitamin era In Casimir Funk wrote that the antiberiberi factor, because of the different conditions under which it could be extracted from rice polishings and then precipitated, must be an organic base and therefore contain an amine group. Rats and mice fed purified diets Previously most work started with a diet that had been found in practice to be associated with a particular disease, and this type of work was to continue with important results that we shall consider shortly.
McCollum To begin with I will follow the progress in the field through the work of McCollum and his volunteer assistant Marguerite Davis at the Wisconsin Agricultural Experiment Station attached to the University of Wisconsin; they were certainly leading the pack in the early years McCollum's first trials It had been speculated at this time that animals needed to be supplied with phosphorus in the form of nucleic acids. Open in new tab Download slide. TABLE 1. Open in new tab. TABLE 2. TABLE 3. Search ADS.
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