Urinary ascorbate

The glucose oxidase method (used in the dipsticks and by many automated analyzers) can show a false positive result in some species (e.g, dog, mouse) with high urinary ascorbate levels or in urine contaminated with hypochlorite (bleach) used as a disinfectant (Finco 1997 Loeb and Quimby 1999). 

Urinary excretion of ascorbate fails to undetectably low levels in deficiency therefore, very low excretion will indicate deficiency. However, no guidelines for the interpretation of urinary ascorbate have been established, and basal urinary excretion of ascorbate is rarely used in the assessment of status. During depletion/repletion studies, urinary excretion increases before tissue saturation has been achieved (Sauberlich, 1975). 

Zinc and Ascorbic Acid Metabolism and Excretion. Iron has an oxidizing effect on ascorbic acid, reducing its urinary excretion therefore, Keltz et al. (61) questioned whether zinc would show a similar effect. Human subjects were fed a diet containing either 11.5 or 19.5 mg of zinc/d for 7-d balance periods. Daily ascorbic acid intake was 100 mg. Consistent with the findings from iron-loaded Africans, the higher zinc intake caused a significant 30% decrease in urinary ascorbate excretion. No explanation for the zinc-related reduction in ascorbic acid beyond the analogy with the iron-loaded individuals is readily available. 

Kato N, Mochizuki S, Kawai K, et al. 1982a. Effect of dietary level of sulfur-containing amino acids on liver drug-metabolizing enzymes, serum cholesterol and urinary ascorbic acid in rats fed PCB. J Nutr 112 848-854. 

At the conclusion of the Medical Research Council study, saturation tests were done on the subjects with long histories of accurately known ascorbic acid intakes. More than three daily test doses (10 mg/kg body weight) were necessary before a sharp rise occurred in urinary ascorbic acid excretion of subjects who had been receiving 20 mg/day or less, but again no distinction could be made in this way between the deficient and the protected individuals receiving the lower amounts. 

Poon, R., 1. Chu, P. Lecavalier, A. Bergman, and D. C. Villeneuve. 1994. Urinary ascorbic acid—HPLC determination and application as a noninvasive marker of hepatic response. Journal of Biochemical Toxicology 9 297-304. 

Fewer studies have been made with man and they have, of necessity, been confined to the influence of dietary flavonoid supplements on blood and urinary ascorbic acid. A weakness of such studies is that the diet of most subjects contains a substantial amount of flavonoid material — even when obvious sources such as citrus fruits are excluded from the diet. This makes difficult the inclusion of a control group and also reduces the significance of additional flavonoid supplements. Nevertheless, there is some evidence that flavonoids may modify the absorption—retention—stability of ascorbic acid in man. 

Early literature demonstrated that the administration of various drugs to rats stimulated ascorbic acid synthesis, as evidenced by the dramatic increases in urinary ascorbate (Longenecker et al., 1940) and the doubling of body pools (Conney et al., 1961). Drug-induced ascorbate synthesis appeared to proceed through the glu-... 

RECOMMENDED DAILY ALLOWANCE OF VITAMIN C. Many studies have been conducted to determine the human vitamin C requirements. Consideration has been given to the effect of age, environment, physical exertion, infections, and fevers. Also, various measurements for determining the adequacy of vitamin C have been devised, including (1) the daily intake of vitamin C necessary to prevent the symptoms of scurvy (2) the amount of vitamin C required to saturate whole blood, blood plasma, white blood cells, or body tissue and (3) the intake of vitamin C necessary to maintain blood and urinary ascorbic acid levels within normal range. The results of these studies vary widely. 

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

The nurse measures the fluid intake and output, especially when the primary health care provider orders an increase in fluid intake or when a kidney infection is being treated. The primary health care provider may also order daily urinary pH levels when methenamine or nitrofurantoin is administered. These drugs work best in acid urine failure of the urine to remain acidic may require administration of a urinary acidifier, such as ascorbic acid. 

Fig. 10 Urinary excretion of riboflavin (A, B) and ascorbic acid (C, D) in humans as a function of oral dose. Graphs A and C illustrate the nonlinear dependence of absorption on dose, which is suggestive of a saturable specialized absorption process. Graphs B and D represent an alternative graph of the same data and illustrate the reduced absorption efficiency as the dose increases. (Graphs A and C based on data in Ref. 39 and graphs B and D based on data in Ref. 40.)...

Chromium compounds interact synergistically or antagonistically with many chemicals. For example, potassium dichromate administered by subcutaneous injection potentiated the effects of mercuric chloride, citrinin, and hexachloro-1,3-butadiene on rat kidneys (USPHS 1993). Chromium effects were lessened by ascorbic acid and Vitamin E, and N-acetyl cysteine was effective in increasing urinary excretion of chromium in rats (USPHS 1993)... 

The bone becomes depleted of calcium salts when the urine is acidic over a relatively long period. This was shown by Goto (17) who fed rabbits large doses of hydrochloric acid. He then showed that urinary calcium loss occurred in concert with a marked reduction in mass of the skeletal system, and also that the total non-fat dry weight of bone decreased,implying a loss of bone matrix. A dose-dependent, dietary acid induced loss of labelled calcium from rat bone has been reported by Thorn and his coworkers (18). They demonstrated that in response to graded doses of ascorbic acid, cells in tissue culture, and bones in whole animals fed such doses were depleted of the labelled calcium. 

Earlier animal work showed similar results in terms of urinary acid production from dietary precursors that could be converted into acid before excretion. However, most investigators used salts rather than foods containing the anion or its precursor. The addition of acid, in the form of hydrochloric, sulfuric, or ammonium chloride, acid phosphate salts, or ascorbate resulted in enhanced urinary acidity and concomitant calcium excretion. For example, in the detailed study of bone salt metabolism, Barzel and Jowsey (19) showed that the rat fed supplementary ammonium chloride subsequently lost more calcium, and developed markedly demineralized fat-free bone mass. 

Drugs that may affect aspirin include activated charcoal, ammonium chloride, ascorbic acid or methionine, antacids and urinary alkalinizers, carbonic anhydrase inhibitors, corticosteroids, and nizatidine. Drugs that may be affected by aspirin include alcohol, ACE inhibitors, anticoagulants (oral), beta-adrenergic blockers, heparin, loop diuretics, methotrexate, nitroglycerin, NSAIDs, probenecid and sulfinpyrazone, spironolactone, sulfonylureas and exogenous insulin, and valproic acid. 

B. Proteus species produce urease (A) that produces ammonia and urea, alkalizing urine. Urine requires acidification for effective therapy. Hippuric (B), mandelic, or ascorbic acids or methionine are urinary acidifying agents. The normal acidic urinary environment is disturbed by recurrent Proteus in-... 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

Methenamine mandelate is a salt of mandelic acid and methenamine and both of these possess property of urinary antiseptic. It is rapidly absorbed in gastrointestinal tract and excreted unchanged in urine, where it broken down in acidic pH (< 5) of urine and formaldehyde is released, which inhibits most of the bacteria. It is administered with sodium biphosphate, mandelic acid or ascorbic acid to keep the urinary pH below 6. Its use is restricted to chronic, resistant type of UTI. 

Methenamine mandelate, 1 g four times daily, or methen-amine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to suppress, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4-12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites. 

Ascorbic acid is the main endogenous precursor of oxalic acid and in healthy persons up to 30% of urinary oxalate can originate from ascorbate. Ascorbate is extremely unstable in neutral and alkaline solutions and degrades to oxalate nonenzymatically [6]. Acidification to pH 1-2 is required to prevent deposition of insoluble Ca-oxalate. 

Cohen SM, Garland EM, Cano M, St. John MK, Khachab M, Wehner JM, Arnold LL. 1995. Effects of sodium ascorbate, sodium saccharin and ammonium chloride on the male rat urinary bladder. Carcinogenesis 16 2743-2750. 

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