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The relationship between ascorbic acid status and the urinary excretion of hydroxyproline was examined in 11 healthy male subjects fed an ascorbic acid-deficient diet for 14 wk while in a metabolic unit. The diet provided 5 mg ascorbic acid/d and was supplemented with ascorbic acid to give intakes of 65 mg/d (2 wk), 5 mg/d (4 wk), 605 mg/d (3 wk), 5 mg/d (4 wk), and an average 375 mg/d (1 wk). The urinary excretion of hydroxyproline increased by an average of 16% and 30% after the first and second depletion periods, respectively, and decreased to baseline values after supplementation with normal or high doses of vitamin C. Significant (p less than 0.05) inverse correlations were found between urinary hydroxyproline and plasma, red cell, and leukocyte ascorbic acid. These results show that urinary hydroxyproline excretion increases during human vitamin C deficiency but that this effect is not strong enough to provide a reliable marker of mild vitamin C deficiency.

Haematological response and ascorbic acid (AA) status were evaluated in 32 young adult females (age 20-34 years) 8 weeks after supplementation with two levels of AA (50 and 100 mg). Both levels of AA intake produced a similar response marked by significant elevation (p less than 0.01) in Hb concentration, Hct level, RBC count, serum and leucocyte ascorbate concentrations. Ten weeks after withdrawal of the supplements, values for all parameters evaluated decreased significantly (p less than 0.01) to presupplementation levels. Haemoglobin concentration and leucocyte ascorbate remained relatively higher (p less than 0.01) than initial values in subjects who received 100 mg AA. This study showed that AA supplementation improved erythropoietic activity and AA status of our female population. However, the higher dose of AA (100 mg) sustained Hb concentration and tissue ascorbate longer after withdrawal of supplementation.

The ascorbate status and the effect of loading doses of ascorbic acid (1,5 g per day by mouth for 7 days) on the porphyric process were studied in 7 black men with porphyria cutanea tarda symptomatica. It was found that the ascorbate stores were depleted in these patients as judged by serum and leucocyte ascorbate levels. Temporary repletion of the ascorbate stores was effected by the loading doses of ascorbic acid: Serum iron concentrations increased in 6 patients; urinary iron excretion showed small peaks a few days after ascorbic acid therapy commenced; haemoglobin concentration was not affected; excessive amounts of oxalate were excreted in the urine; neither total urinary porphyrin excretion nor the composition of the urinary porphyrins was affected in a way which could be related to ascorbate therapy. Further evidence that ascorbate depletion is not important in the induction of porphyria was found when the ascorbate status of siderotic rats, rendered porphyric by hexachlorobenzene-feeding, was examined. Stores of ascorbate and the oxidative catabolism of ascorbate were not different in the prophyric rats as compared with normal litter mates.

The changes in buffy layer (BL) vitamin C concentration following surgical operations were studied in relation to changes in the leucocyte and platelet counts. It was found that the postoperative fall and subsequent changes in BL vitamin C concentration corresponded to changes in the platelet/leucocyte ratio (PLR) in whole blood and consequently in the buffy layer preparations from which vitamin C concentrations were measured. The results of the study showed that the fall in BL vitamin C measured following operations is an artifact of the method used rather than a demand for vitamin C. It highlights the importance of measuring the PLR, and suggests the need for a differential leucocyte count, when undertaking BL vitamin C analysis.

Plasma cholesterol, plasma and white blood cell ascorbic acid concentrations were estimated in 30 untreated, 32 salbutamol-treated patients with bronchial asthma and in 57 normal controls. Treated and untreated asthmatics had significantly higher plasma cholesterol but lower plasma and white cell ascorbic acid levels than normal controls. A negative correlation was found between white cell ascorbic acid level and plasma cholesterol concentration in both treated and untreated asthmatics. These findings are discussed.

Morning plasma and leucocyte vitamin C concentrations were measured in 178 healthy men aged 17-68 years. In the youngest age group (17-29 years), smokers had significantly lower plasma (P less than 0.01) and leucocyte (P less than 0.001) vitamin C levels than non-smokers. With advancing age plasma and leucocyte vitamin C levels of non-smokers appeared to decline. The lower levels in younger smokers did not significantly alter in the later decades. There was no significant difference between the plasma or leucocyte vitamin C levels of smokers and non-smokers in the decade 60-69 years.

Plasma and buffy-coat vitamin C were estimated in 158 samples from 139 lung-cancer patients, at all stages of the disease. Most samples showed hypovitaminosis C in both estimations: 64% had plasma, and 25% buffy-coat values below the thresholds for incipient clinical scurvy (0.3 mg% and 10 micrograms/10(8) cells respectively). Levels were diet-dependent and could be increased by oral supplements. Levels were low both in tumour-bearing patients and in those clinically free of disease after resection. The latter had particularly low values during the first 6 months, indicating the utilization of vitamin C in surgical repair. The vitamin C content of 13 primary lung tumours was assayed: tumours had a higher vitamin C content (mean 111.6 +/- 55.1 micrograms/g tissue) than normal lung (58.5 +/- 20.4 micrograms/g). Mononuclear cells from normal individuals show a higher vitamin C content than polymorphs, but in lung-cancer patients the expected correlation of buffy-coat vitamin C with the proportion of lymphocytes in peripheral blood was obscured by an inverse correlation in patients with relative lymphocytosis (greater than or equal to 25% lymphocytes), confirmed by an inverse correlation of the proportion of lymphocytes in peripheral blood with mononuclear-cell vitamin C in 14 patients in whom this was measured. These correlations were unaffected by controlling for plasma values, and indicate the utilization of vitamin C in lymphocyte-related anti-tumour mechanisms. Vitamin C is necessary for phagocytosis and for the expression of cell-mediated immunity. In view of the increasing circumstantial evidence that immune mechanisms exert some measure of control on tumour extension and metastasis in man, the effect of supplementation with vitamin C in lung-cancer patients on survival should be tested in a clinical trial.

Vitamin C is an essential nutrient whose protective role in carcinogenesis has been discussed for more than 50 years. Epidemiologic studies suggest that the consumption of vitamin C-rich foods is associated with a lower risk of cancers of the esophagus and stomach. The observation that cancer patients have low leukocyte vitamin C levels led to therapeutic trials the results of which are controversial; the hypothesis that vitamin C acts like a drug must be questioned. On the other hand, ascorbic acid interacts with various tumor-inducing compounds, such as the precursors of N-nitroso compounds, to prevent the formation of tumors. Experiments with animals and cell cultures indicate that ascorbic acid can interfere with the metabolism of tumor promoters. It has also been postulated that ascorbic acid helps to prevent cancer by enhancing cellular immunity. In general, evidence suggests that vitamin C can inhibit the formation of some carcinogens.

The influence of vitamin C on the pharmacokinetics of antipyrine was investigated in eleven elderly men aged 65-74. Antipyrine (15 mg kg-1) was administered intravenously on three separate occasions over a 7-week period: (a) before dietary vitamin C restriction, (b) after approximately 5 weeks of dietary vitamin C restriction, and (c) after 2 weeks of vitamin C supplementation (500 mg orally twice daily). The mean plasma and leucocyte vitamin C levels (+/- S.D.) before vitamin C restriction were 1.26 +/- 0.31 mg dl-1 and 26.6 +/- 6.7 micrograms 10(-8) leucocytes, respectively. These values decreased and then increased significantly following vitamin C restriction and supplementation, respectively. The mean plasma half-life of antipyrine was 10.2 h and the mean plasma clearance was 2.561 h-1 1.73 m-2 before vitamin C restriction. No significant changes in the clearance, volume of distribution, or half-life of antipyrine occurred during the study, indicating that short-term alterations in vitamin C intake do not affect the pharmacokinetics of antipyrine in elderly males.

The status of ascorbic acid was studied at the levels of platelet and leucocyte in 32 cases of iron deficiency anaemia, 35 cases of thalassaemia and 18 normal subjects. It was found that in iron deficiency anaemia, platelet ascorbic acid was significantly higher than normal values indicating tissue excess and came down sharply after treatment with iron. In thalassaemia, associated presumably with iron overload, ascorbic acid status of platelets was definitely lower than normal indicating tissue deficiency. Leucocytic level of ascorbic acid was not as good an index of ascorbic acid status as the platelet level.

A double-blind placebo trial has been undertaken on 199 elderly patients admitted to an "acute" geriatric assessment ward. Clinical and biochemical assessment was made on admission (0) and at 2, 4, 8, 16 and 24 weeks (after admission). Ninety-four patients were supplemented with vitamin C (200 mg per day) and 105 had placebo tablets. Biochemical assessment included estimations of plasma and leucocyte (buffy layer) vitamin C, plasma folate, vitamin B12, cortisol and total white cell count. Plasma and leucocyte vitamin C levels remained low for several weeks in a substantial proportion of the non-supplemented patients, whereas low levels were virtually eliminated in the supplemented group. The results from this study suggest that the leucocyte vitamin C levels may give some indication of prognosis in this category of patients (ie. "acute" geriatric admissions) as evidenced by: i) the significantly higher mortality rate during the trial period of patients who started with low initial leucocyte vitamin C levels compared with those starting with higher levels, despite similar mean initial "severity of illness scores" between the two groups. ii) the marked trend, amongst placebo subjects, for those commencing the study with higher leucocyte vitamin C levels to fare better, in terms of progression to "well", than those starting with low levels. Amongst subjects starting with low leucocyte vitamin C levels, there was a trend for "vitamin C" subjects to have fared better by 8 weeks than "placebo" subjects. This again occurred despite similar mean initial "severity scores" between the two groups. Amongst subjects diagnosed with respiratory infections there was some tendency for supplemented patients to fare better than unsupplemented patients. Low leucocyte vitamin C levels, on admission, appear to be predictive of poor subsequent prognosis in elderly hospitalised patients. Results from this trial suggest that supplementation with a moderate dose of vitamin C may improve this prognosis and larger trials with greater numbers appear to be merited to confirm or deny this hypothesis.

Twenty-seven elderly men aged 69-94 years had tyrosine tolerance tests measured before and after receiving ascorbic acid 1 g daily for four days. There was a significant rise in the fasting and half-hourly mean plasma tyrosine levels after ascorbic acid administration in those subjects with an initial leucocyte ascorbic-acid level (LAA) below 15 micrograms/10(8) w.c.c. The peak of the tyrosine tolerance curve was also advanced following administration of ascorbic acid in those subjects with an initial LAA below 15 micrograms/10(8) w.c.c. A further ten elderly men aged 73-89 years had simultaneous measurements of the circadian rhythms of LAA, plasma cortisol and plasma tyrosine levels before and after receiving ascorbic acid 1 g daily for four days. All ten subjects showed a peak LAA level at 5 p.m. when saturated with vitamin C but there was no significant correlation between plasma cortisol changes and plasma tyrosine changes. Possible explanations for the results are discussed.

Patients undergoing maintenance haemodialysis exhibited at a regular level of ascorbic acid in plasma a decreased concentration of ascorbic acid in leukocytes. Therefore, the ascorbic acid should be administered in a high dosage to patients undergoing chronic haemodialysis, in order to prevent a vitamin-C deficiency in leukocytes.

After briefly mentioning the factors which influence the vitamin C levels in tissues, the findings are reported of an investigation, conducted on 11 volunteers, in which some variations were revealed in vitamin C concentrations in the plasma and in the leukocytes of the subjects examined during a period of one year. The lowest levels were found in the months of March and December.

The vitamin C status of 35 men, over 70 years of age from a residential home has been studied by measuring the plasma and leucocyte vitamin C levels and by assessing the intake of vitamin C. The mean plasma vitamin C level of the group was 16 +/- 15 mumol/l which was significantly lower (P less than 0.005) than that of a similar group of elderly men living alone (26 +/- 20 mumol/l). The mean leucocyte vitamin C levels of the two groups did not differ significantly. Twenty-nine (83 percent) of the institution group had plasma vitamin C levels below 23 mumol/l and 13 men (37 percent) had leucocyte vitamin C levels below 10 microgram/10(8)WBC. The residents who supplemented the institution diet with their own fresh fruit supplies had higher plasma and leucocyte vitamin C levels than the men who did not (P less than 0.01). Some clinical signs possible related to vitamin C deficiency were recorded but these could not later be statistically related to either plasma or leucocyte vitamin C levels. A case is made for vitamin C supplementation of puddings in institutional meals for the elderly.

White-blood counts, polymorph counts, leucocyte ascorbic-acid and plasma ascorbic-acid levels were measured in 91 samples of blood obtained from patients admitted to a geriatric assessment unit. There was a correlation between both white-blood counts and polymorph counts and leucocyte ascorbic-acid levels. There was no correlation between white-blood counts and polymorph counts and plasma ascorbic-acid concentrations. It is suggested that this phenomenon represents migration of ascorbate-rich polymorphs to areas of infection and infarction.

This study sought to determine whether the lingual ascorbic acid test (LAAT) and measurement of salivary ascorbate reflect plasma and leukocyte ascorbate levels during controlled periods of ascorbic acid depletion and supplementation. Eleven healthy non-smoking men, aged 19-28 years, ate a diet that was repeated every seven days and was adequate in all nutrients except ascorbic acid (AA). This basal diet, which provided less than 5 mg of AA per day, was supplemented with 60 mg of AA per day for two weeks, 0 mg (placebo) per day for four weeks, 600 mg per day for three weeks, and 0 mg per day for four weeks. Oral examinations, the lingual ascorbic acid test, and measurement of salivary, plasma, and leukocyte ascorbate concentrations were conducted throughout the study. Ascorbic acid concentrations in plasma and leukocytes responded rapidly to changes in vitamin C intake. LAAT-derived ascorbate values were unrelated to ascorbic acid intake and plasma and leukocyte ascorbate concentrations. Salivary ascorbate levels approached the lower limits of detection of the assay and remained constant throughout the investigation. Oral hygiene was consistently excellent, and no severe mucosal or periodontal changes were observed. It was concluded that lingual ascorbic acid test values and salivary ascorbate levels are not related to changes in ascorbic acid intake and are not consistent with plasma or leukocyte ascorbate concentrations.

In leukocytes a dynamic relationship between the reduced form of ascorbic acid (AA) and its oxidized product dehydro-AA has been described. It is therefore important to know which form of the vitamin predominates when choosing a methodology. The purpose of this study was to find out if the majority of ascorbate in human leukocytes isolated by centrifugation through Percoll is in the reduced AA form by measuring reduced AA by HPLC and comparing the values to those obtained by using the 2,4-dinitrophenylhydrazine (DNPH) method which measures total ascorbate, and quantifying the reduced and oxidized forms of the vitamin in leukocytes using a modification of the DNPH method. There was no significant difference (P greater than .05) between the HPLC and DNPH values for 12 individuals and 87% of the AA was found to be in the reduced form. These results support the assumption that the majority of AA found in a mixed leukocyte population isolated through Percoll is in the reduced form and that both methods can be used for AA measurements.

Leucocyte ascorbic acid (LAA) levels were estimated in 26 Nigerian infants and preschool children with protein energy malnutrition (PEM) in order to ascertain their ascorbic acid status. The children included eight with kwashiorkor, 12 with marasmus and six with marasmic kwashiorkor. The mean (SD) LAA level of 13.7 (8.2) micrograms/10(8) leucocytes in the malnourished children did not vary significantly from the mean level of 14.4 (8.8) micrograms/10(8) leucocytes found in 26 age-matched controls, and the values were unrelated to the presence or absence of megaloblastic change in the 14 bone marrows examined. It was concluded that ascorbic acid deficiency was not prevalent amongst children with PEM in Lagos, and was therefore not usually contributory to the anaemia, megaloblastic changes or other features of the syndrome seen in Nigerian children in Lagos.

A dietary survey using the five day record method was carried out on 35 elderly men living alone in the Christchurch area. The mean calculated intake of vitamin C for these men was 31 mg/day. These dietary intakes of vitamin C were significantly correlated with both plasma vitamin C levels and with leucocyte vitamin C levels. Twelve men (34 percent) with lowered dietary intakes of vitamin C were in the range for asymptomatic scurvy. The mean calculated intake of thiamine was 1.05 mg/day. The mean TPP effect was 12.9 percent (n = 27). Dietary intakes of thiamine showed a significant inverse relationship with TPP effect. Eight subjects (23 percent) who too, less than the Australian dietary allowance had an elevated TPP effect. By both dietary and biochemical methods there was evidence of subclinical vitamin C and thiamine deficiencies in more than a quarter of these men.

1. Serial estimations of plasma (PAA) and leucocyte (LAA) ascorbic acid concentrations were made in geriatric patients in a stable phase of their illness, and compared with a similar ('unstable') group suffering from acute illness. 2. In the 'unstable' group, though PAA levels were unchanged, LAA levels were reduced. 3. The 'follow-up' period of 7-8 d there was much greater variation in both PAA and LAA levels in the 'unstable' group. 4. Acute illness was often accompanied by an increase and then a decrease in LAA levels. Recovery was associated with an increase in LAA levels.

Measurements of ascorbic acid concentration in leukocytes by "high-performance" liquid chromatography (HPLC) provides better nutritional assessment, leading to better management, particularly of presymptomatic and critically ill patients. This procedure includes a simple, reproducible cell-separation technique that requires no more than 2 mL of whole blood. Cell populations are separable with greater than 95% purity and greater than 99% viability. Ascorbic acid is assayed by HPLC. The vitamin can be reproducibly quantified in concentrations as low as 0.1 microgram/mL of cell extract. The chromatographic procedure is very rapid, analysis being completed within 15 min after specimen preparation. The assay is suitable also for urine and protein-free filtrates of plasma and of other biological materials. Reference intervals for plasma, mononuclear leukocytes, and polymorphonuclear leukocytes were established. A preliminary clinical evaluation revealed that hospital patients were at a greater risk of ascorbic acid deficiency than expected.

In dogs, the mean plasma vitamin C concentration was found to be 0.88 mg/100 ml plasma while the mean buffy coat concentration of simultaneous blood aliquots was 42.98 mg/10(8) cells. A significant day-to-day variation was recorded for both parameters.

In a prospective double-blind controlled trial the effect of large doses of ascorbic acid on the healing of pressure-sores has been assessed. 20 surgical patients were studied, the pressure areas being assessed by serial photography and ulcer tracings. The mean ascorbic-acid levels in treated and non-treated groups one month after the start of treatment were 65.6 and 25.8 mug per 10-8 white blood-cells. In the group treated with ascorbic acid there was a mean reduction in pressure-sore area of 84% after one month compared with 42.7% in the placebo group. These findings are statistically significant (P less than 0.005) and suggest that ascorbic acid may accelerate the healing of pressure-sores.

Leucocyte ascorbic acid levels failed to identify six of seven elderly patients shown to be deficient on an oral vitamin C saturation test. Compared to those with a normal saturation test, patients judged deficient had lower levels for triceps skinfold thickness, mean arm muscle circumference and Quetelet's index; there was a significant association with the habit of eating alone, and with a dietary intake of less than 30 mg of ascorbic acid daily (the recommended daily allowance in the U.K.). No significant difference was found in the values for haemoglobin, serum albumin or potassium concentrations between the two groups, and no association shown between a deficient saturation test and smoking, season, sublingual varicosities or an abnormal bleeding time.