Pyridoxine Deficiency in Human Beings Induced With Desoxypyridoxine 1

Mueller, John F.; Vilter, Richard W.

doi:10.1172/jci102246

Cited by 82 publications

(14 citation statements)

References 22 publications

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“…In the present study of niacin requirement, diets were supplemented with other B vitamins and the lesions which developed can be attributed primarily to niacin deficiency. Cheilosis, angular stomatitis and dermatitis of the nasolabial folds, which have been produced in experimental riboflavin deficiency (23,24) and by the administration of desoxypyridoxine (25), were also observed in the present investigation. The occurrence of these lesions in pellagra has previously been attributed to concomitant riboflavin deficiency.…”

Section: Discussionsupporting

confidence: 73%

Studies of Niacin Requirement in Man. I. Experimental Pellagra in Subjects on Corn Diets Low in Niacin and Tryptophan 1

Goldsmith¹,

Sarett²,

et al. 1952

J. Clin. Invest.

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Early attempts to estimate human niacin requirement were based on calculations of the niacin content of pellagragenic and nonpellagragenic diets (1, 2). It was appreciated that the protein content of the diet was in some way related to niacin requirement. Recent studies showing that the amino acid tryptophan is converted in part to niacin compounds in man (3-5) may explain the above relationship, and also the pellagra preventive effect of foods which are low in niacin but rich in "good" protein.The present experiments were designed to study niacin requirement in man with diets of known tryptophan content. Estimation of minimum tryptophan requirement for nitrogen balance (6) permits formulation of diets containing little excess tryptophan which may be converted to niacin. The discovery of the major metabolites of niacin, namely Nl-methylnicotinamide (N'-Me) and the 6-pyridone of Nl-methylnicotinamide (pyridone), and the development of methods for the measurement of these compounds in urine, now permit more complete studies of niacin metabolism (7-11).Seven subjects were maintained on diets low in niacin and tryptophan for from 40 to 135 days and the urinary excretion of niacin metabolites was determined. Clinical signs of pellagra developed in the three subjects who remained on one of these diets for more than 50 days. METHODSThe seven subjects were white females, 25 to 54 years of age, who were found to be essentially free of organic ',This work was supported by grants from the Nutri- The diet for two complete days was analyzed at intervals for niacin, tryptophan and total nitrogen. The diet for each meal was blended with water in a Waring blendor to give a total volume of 1,000 to 1,500 ml. Aliquots of this material were autoclaved in 1 N sulfuric acid solution for 45 minutes, neutralized and analyzed for niacin microbiologically, using L. arabinosus (12). This organism was also employed for tryptophan analysis using aliquots of the homogenate which had been autoclaved in 5 N sodium hydroxide in the presence of cysteine (13). For these analyses 15 ml. portions of 8 N sodium hydroxide solution were placed in 125 ml. Erlenmeyer flasks and 400 mg. of cysteine and 10 ml. of the blended diet were rapidly added. These were covered at once with beakers and autoclaved for six hours at 1210 C.After neutralization with hydrochloric acid, the solutions were diluted to 100 ml., filtered and analyzed. Under these conditions it is assumed that all tryptophan. liberated from the proteins was racemized and was present as D,L-tryptophan. Although it is possible that some tryptophan in the proteins may have been destroyed by this procedure, L-or D,L-tryptophan added to the samples was not destroyed and treatment of L-or D,L-tryptophan alone with these reagents resulted in 90 to 100% recovery. Analyses of the diets and of individual foods gave reproducible results. Nitrogen was determined by the macro-Kjeldahl method.All urine was collected for 24 hour periods in dark bottles containing 5 ml. of glacial acetic acid and kept in th...

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Section: Discussionsupporting

confidence: 73%

Studies of Niacin Requirement in Man. I. Experimental Pellagra in Subjects on Corn Diets Low in Niacin and Tryptophan 1

Goldsmith¹,

Sarett²,

et al. 1952

J. Clin. Invest.

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“…SAH 30 is a potent competitive inhibitor of HMT ( K = 5-18 micromolar), and SAH is reported to have a higher affi nity for HMT than SAM or histamine [258]. Eosinophilia has been induced in humans treated with desoxypyridoxine [259][260][261][262]. 31 One may now begin to perceive why "pyridoxine is the maturation factor involved in the development of the polymorphonuclear 32 leucocyte" [263].…”

Section: The 'Tryptophan Load Test' Pyridoxaldehydes (As Molecular Mmentioning

confidence: 99%

A heretofore undisclosed crux of Eosinophilia-Myalgia Syndrome: compromised histamine degradation

Smith

Garrett

2005

Inflamm. res.

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In contrast to early epidemiological evidence offering links between eosinophilia-myalgia syndrome (EMS) and microimpurities of L-tryptophan-containing dietary supplements (LTCDS), this account shows why reliance on a finite impurity from one manufacturer is both unnecessary and insufficient to explain the etiology of EMS. Excessive histamine activity has induced blood eosinophilia and myalgia (Greek: mys, muscle + algos, pain). Termination of the multiple actions of histamine is dependent on particular amine oxidases and histamine-N-methyltransferase. Histamine metabolism is rapid when these degradative reactions are operative. The latent effects of incurred histamine can be potentiated and aggravating when these mechanisms are impaired. Overloads of tryptophan supplements cause - among other relevant side-effects - an increased formation of formate and indolyl metabolites, several of which inhibit the degradation of histamine. Moreover, (non-EMS) subjects with hypothalamic-pituitary- adrenal (HPA) axis dysregulation have also manifested greatly increased sensitivities to incurred tryptophan and histamine. A final common pathway for syndromes characterized by eosinophilia with myalgia is now evident.

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“…Accordingly, the symptoms in man have only been derived from the results obtained by administering pyridoxine to patients with clinical manifes¬ tations similar to those of pyridoxine-de¬ ficient animals. However, Mueller (1950) and Vilter (1953) made known the deficient symptoms by giving deoxypridoxine, known as antivitamin of pyridoxine. According to their reports, the symptoms in man are suppression of growth, microcytic hypochromic anemia, increase of xanthine in urine, disturbance of amino acid metabolism, and, as dermatic changes, seborrheic derma¬ titis around the eye, the nasolabial area, and the extremities.…”

Section: Commentmentioning

confidence: 99%