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Abstracts

ABSTRACTS FOR THE VITAMIN C CONTROVERSY


121. Intake of vitamins A, C, and E and postmenopausal breast cancer.

Am J Epidemiol 1996 Jul 15;144(2):165-74
The Iowa Women's Health Study. Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis 55454-1015, USA.

The association between dietary antioxidant vitamin intake and the risk of breast cancer was examined in a prospective study of 34,387 postmenopausal women in Iowa. Intakes of vitamins A, C, and E and of retinol and carotenoids were assessed in 1986 by mailed semiquantitative food frequency questionnaire. Through December 31, 1992, 879 incident breast cancer cases occurred in this cohort. There was little suggestion that breast cancer risk was associated with differences in intake of these vitamins. For example, from the lowest to highest total vitamin A intake categorized by quintiles, the age-adjusted relative risks of breast cancer were 1.0, 0.95, 1.17, 1.20, and 0.90 (p trend = 0.92). Similarly unremarkable relative risk patterns were seen for the intakes of vitamins C and E and of retinol and carotenoids. These findings were not altered after adjustment for breast cancer risk factors or in analyses confined to women who reported no supplemental vitamin intake. Exclusion of cases that occurred in the first 2 years of follow-up, under the assumption that women may have increased intake of these vitamins in response to preclinical symptoms of breast cancer, did not suggest an inverse association of these vitamins with the risk of breast cancer. Women who reported consuming at least 500 mg/day of supplemental VITAMIN C had a relative risk of breast cancer of 0.79 compared with women who did not take supplemental VITAMIN C, and women who reported consuming more than 10,000 IU/day of vitamin A had a corresponding relative risk of 0.73. However, these relative risks were not statistically significant. These results provide little evidence that intake of these vitamins is associated with breast cancer risk. PMID: 8678048, UI: 96283061


122. Modulation of oxidant stress in vivo in chronic cigarette smokers.

Circulation 1996 Jul 1;94(1):19-25
Reilly M, Delanty N, Lawson JA, FitzGerald GA Center for Experimental Therapeutics, University of Pennsylvania, Philadelphia 19104, USA.

BACKGROUND: Free radical-induced oxidative damage is thought to be involved in the pathogenesis of diseases associated with cigarette smoking. We examined the production of 8-epi-prostaglandin (PG) F2 alpha, a stable product of lipid peroxidation in vivo, and its modulation by aspirin and antioxidant vitamins in chronic cigarette smokers. METHODS AND RESULTS: We performed the following studies: (1) a cross-sectional comparison of smokers and control subjects, (2) an examination of the dose-response relationship, (3) an exploration of the effect of smoking cessation (3 weeks) and nicotine patch supplementation, (4) the effect of aspirin consumption, and (5) the effects of 5 days' dosing with vitamin E (100 and 800 U), VITAMIN C (2 g), and their combination. 8-epi-PGF2 alpha excretion (in pmol/mmol, mean +/- SEM) was 176.5+/-30.6 in heavy smokers, 92.7+/-4.8 (P<.05) in moderate smokers, and 54.1+/-2.7 (P<.005) in nonsmokers. Urinary levels fell from 145.5+/-24.9 to 114.6+/-27.1 (week 2, P<.05) and 112.6+/-24.9 (week 3, P<.05) on cessation of smoking. Aspirin treatment failed to suppress urinary levels of 8-epi-PGF2 alpha despite a significant reduction in urinary 11-dehydro-TxB2 production and suppression of 8-epi-PGF2 alpha and TxB2 in serum. VITAMIN C (pre, 194.6+/-40.9; post, 137.2+/-34.1; P<.05) and a combination of VITAMIN C and E (pre, 171.0+/-39.8; post, 133.5+/-29.6 P<.05) suppressed urinary 8-epi-PGF2 alpha, whereas vitamin E alone had no effect. CONCLUSIONS: Urinary 8-epi-PGF2 alpha may represent a noninvasive, quantitative index of oxidant stress in vivo. Elevated levels of 8-epi-PGF2 alpha in smokers may be modulated by quitting cigarettes and switching to nicotine patches or by antioxidant vitamin therapy. Publication Types: Clinical trial Randomized controlled trial PMID: 8964113, UI: 96266949


123. VITAMIN C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions.

J Infect Dis 1996 Jun;173(6):1502-5
Levy R, Shriker O, Porath A, Riesenberg K, Schlaeffer F Laboratory of Infectious Diseases, Clinical Biochemistry Unit, Ben-Gurion University of the Negev, Beer Sheva, Israel.

The effect of VITAMIN C treatment on 23 patients with a history of recurrent furunculosis with negative nasal cultures was studied. Neutrophil functions (chemotaxis, phagocytosis, or superoxide generation) of 12 patients were significantly lower than those of the matched controls. In this group, treatment with VITAMIN C (1 g/day) caused a dramatic clinical response as well as a significant improvement of neutrophil functions, reaching values similar to those of the controls. Two patients remained VITAMIN C-dependent. In the patients with normal neutrophil functions, VITAMIN C treatment neither affected neutrophil activity nor caused a clinical response. Therefore, patients suffering from recurrent furunculosis with defective neutrophil functions may be treated successfully with VITAMIN C, contributing to both neutrophil function recovery and a dramatic clinical response. Publication Types: Clinical trial PMID: 8648230, UI: 96217755


124. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men.

J Urol 1996 Jun;155(6):1847-51
Curhan GC, Willett WC, Rimm EB, Stampfer MJ Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

PURPOSE: The association between the intake of vitamins C and B6, and kidney stone formation was examined. MATERIALS AND METHODS: We conducted a prospective study of the relationship between the intake of vitamins C and B6 and the risk of symptomatic kidney stones in a cohort of 45,251 men 40 to 75 years old with no history of kidney calculi. Vitamin intake from foods and supplements was assessed using a semiquantitative food frequency questionnaire completed in 1986. RESULTS: During 6 years of followup 751 incident cases of kidney stones were documented. Neither VITAMIN C nor vitamin B6 intake was significantly associated with the risk of stone formation. For VITAMIN C the age-adjusted relative risk for men consuming 1,500 mg. daily or more compared to less than 250 mg. daily was 0.78 (95% confidence interval 0.54 to 1.11). For vitamin B6 the age-adjusted relative risk for men consuming 40 mg. daily or more compared to less than 3 mg. daily was 0.91 (95% confidence interval 0.64 to 1.31). After adjusting for other potential stone risk factors the relative risks did not change significantly. CONCLUSIONS: These data do not support an association between a high daily intake of VITAMIN C or vitamin B6 and the risk of stone formation, even when consumed in large doses. PMID: 8618271, UI: 96212468


125. Effect of allopurinol, sulphasalazine, and VITAMIN C on aspirin induced gastroduodenal injury in human volunteers.

Gut 1996 Apr;38(4):518-24
McAlindon ME, Muller AF, Filipowicz B, Hawkey CJ Division of Gastroenterology, University Hospital, Nottingham.

BACKGROUND--The mechanisms of aspirin induced gastroduodenal injury are not fully understood. Aspirin induces the release of reactive oxygen metabolites in animal models, which may contribute to mucosal injury. AIMS--To investigate the effects of aspirin administered with placebo or antioxidants on gastric mucosal reactive oxygen metabolite release and gastroduodenal injury in human volunteers. SUBJECTS--Fourteen healthy volunteers participated in the study (seven male; mean age 27 years, range 20-40). METHODS--In a double blind, randomised, crossover study, volunteers received aspirin 900 mg twice daily and either placebo, allopurinol 100 mg twice daily, sulphasalazine 1 g twice daily or VITAMIN C 1 g twice daily for three days. Injury was assessed endoscopically and by quantifying mucosal reactive oxygen metabolite release by measuring chemiluminescence before and after each treatment. The effect on prostanoids was determined by measuring ex vivo antral prostaglandin E2 (PGE2) synthesis and serum thromboxane B2 (TXB2). RESULTS--No drug reduced any parameter of gastric injury but VITAMIN C reduced duodenal injury assessed by Lanza score (p < 0.005). Chemiluminescence increased after aspirin both with placebo (p < 0.05) and VITAMIN C (p < 0.05). Post-treatment chemiluminescence was lower in subjects taking allopurinol (p < 0.05) or sulphasalazine (p < 0.005) than in those taking placebo with aspirin. CONCLUSIONS--In this study, aspirin induced gastric injury was associated with reactive oxygen metabolite release. This was reduced by sulphasalazine and allopurinol, although macroscopic injury was not affected. VITAMIN C, however, was shown to have a previously unrecognised protective effect against aspirin induced duodenal injury.


126. [A case-control study for the recognition of nonoccupational risk factors for tumors of the lower urinary tract].

Dtsch Med Wochenschr 1996 Mar 15;121(11):325-30
Jarrar K, Johansson B, Bolm-Audorff U, Woitowitz HJ, Weidner W Urologische Universitatsklinik, Giessen.

OBJECTIVE: A case-control study was performed to assess various nonoccupational factors (smoking, eating and drinking habits, intake of analgesics) that may be aetiological factors in the development of tumours of the lower urinary tract, while vitamins may be protective. PATIENTS AND METHODS: 150 patients (125 men, mean age 66.4 years; 25 women, mean age 68.2 years) with histologically confirmed malignant tumour of bladder or other part of the lower urinary tract and a comparable group of controls, matched for age, sex and home location, were asked in a standardised personal interview about their life-long habits of smoking, eating and drinking, as well as intake of analgesics. RESULTS: Smoking was the greatest risk factor. In men there was a significant positive dose-effect relationship between the number of cigarettes smoked and relative carcinoma risk, compared with nonsmokers, by a factor of 3.68 among those with the highest dosage (> 40 pack-years). Because of the small number of cases this relationship could not be proven in women, but twice as many female tumour patients than controls were smokers (8 vs 4). In men, even after adjusting for smoking, increased coffee consumption increased the risk by a factor of 2 (2-4 cups: odds ratio 2.14 [P < 0.05]; > 5 cups: odds ratio 2.22 [not significant]). An increased beer consumption had no apparent effect on the development of tumours. Findings regarding VITAMIN C were ambiguous. More prolonged and increased intake of phenacetin-containing analgesics in men showed a tendency towards a higher tumour risk. CONCLUSION: Smoking cigarettes is one of the main risk factors for the development of bladder and other lower urinary tract tumours. The influence of other risk factors needs to be elucidated. PMID: 8681721, UI: 96296666 132: Circulation 1996 Mar 15;93(6):1107-13 Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease. Levine GN, Frei B, Koulouris SN, Gerhard MD, Keaney JF Jr, Vita JA Evans Memorial Department of Medicine, Boston University Medical Center, MA 02118, USA. BACKGROUND: In the setting of atherosclerosis, endothelial vasomotor function is abnormal. Increased oxidative stress has been implicated as one potential mechanism for this observation. We therefore hypothesized that an antioxidant, Ascorbic acid, would improve endothelium-dependent arterial dilation in patients with coronary artery disease. METHODS AND RESULTS: Brachial artery endothelium-dependent dilation in response to hyperemia was assessed by high-resolution vascular ultrasound before and 2 hours after oral administration of either 2 g Ascorbic acid or placebo in a total of 46 patients with documented coronary artery disease. Plasma Ascorbic acid concentration increased 2.5-fold 2 hours after treatment (46+/-8 to 114+/-11 micromol/L, P=.001). In the prospectively defined group of patients with an abnormal baseline response (<5% dilation), Ascorbic acid produced marked improvement in dilation (2.0+/-0.6% to 9.7+/-2.0%), whereas placebo had no effect (1.1+/-1.5% to 1.7+/-1.5%, P=.003 for Ascorbic acid versus placebo). Ascorbic acid had no effect on hyperemic flow or arterial dilation to sublingual nitroglycerin. CONCLUSIONS: Ascorbic acid reverses endothelial vasomotor dysfunction in the brachial circulation of patients with coronary artery disease. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in patients with atherosclerosis and that endothelial dysfunction may respond to antioxidant therapy. Publication Types: Clinical trial Controlled clinical trial Comments: Comment in: Circulation 1999 Mar 9;99(9):1272-3


127. A double-blind, placebo-controlled, crossover trial of oral VITAMIN C in erythropoietic protoporphyria.

Photodermatol Photoimmunol Photomed 1996 Feb;12(1):27-30
Boffa MJ, Ead RD, Reed P, Weinkove C Dermatology Centre, University of Manchester School of Medicine, United Kingdom.

There is evidence that reactive oxygen species and free radicals may be involved in the pathogenesis of photosensitivity in erythropoietic protoporphyria (EPP). Considering the well-known antioxidant properties of VITAMIN C, we investigated whether oral supplementation with this vitamin was photoprotective in patients with EPP. Twelve patients with EPP received either oral VITAMIN C 1 g daily or placebo, for 4 weeks, followed by a crossover period of another 4 weeks. Nine patients were already receiving beta carotene at entry and continued this at the same dose throughout the study. Patients compared their sunlight tolerance throughout each of the treatment periods with sunlight tolerance at entry on a 10 cm visual analogue scale; at the end of the study, they were asked to choose which treatment period they felt had been associated with least photosensitivity. Eight patients stated that they were able to tolerate sunshine better during the VITAMIN C period, 2 during the placebo period and 2 noticed no difference between the two periods. This distribution of preferences approached but did not reach statistical significance in favour of VITAMIN C. Visual analogue scores improved by a median of 1.2 cm in the VITAMIN C period. This change too approached but did not reach statistical significance. Although these results do not reach statistical significance, it appears possible that oral VITAMIN C may reduce photosensitivity in some patients with EPP. A larger study is necessary to confirm this impression.


128. Ascorbic acid and total VITAMIN C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation.

Gut 1996 Feb;38(2):171-6
Waring AJ, Drake IM, Schorah CJ, White KL, Lynch DA, Axon AT, Dixon MF Centre for Digestive Diseases, General Infirmary at Leeds, University of Leeds.

Epidemiological evidence suggests that high dietary Ascorbic acid reduces gastric cancer risk. It may do this by either reducing N-nitroso compound formation in gastric juice, or by scavenging reactive oxygen species in gastric mucosa. The aim of this study was to discover if potential Ascorbic acid protection might be increased by supplementation. Thirty two patients were supplemented with Ascorbic acid, 500 mg twice daily for two weeks. Gastric juice, plasma, and upper gastrointestinal biopsy ascorbate concentrations were measured and compared with values in 48 unsupplemented patients. It was found that Ascorbic acid and total VITAMIN C concentrations were considerably higher in biopsy specimens from oesophagus, body, antrum, duodenum, and rectum, compared with values in plasma or gastric juice. Plasma and mucosal concentrations were unaffected by the presence of chronic gastritis but gastric juice concentrations were substantially lower in patients with chronic gastritis than in patients with normal histological assessment (p < 0.01). Patients receiving Ascorbic acid supplements had higher Ascorbic acid concentrations in plasma (p < 0.001), gastric juice (p < 0.001), and at all biopsy sites in the upper gastrointestinal tract (p < 0.05). Gastric juice Ascorbic acid and total VITAMIN C concentrations in gastritic patients, however, were still less after supplementation than in normal subjects (p < 0.01). These data suggest that high Ascorbic acid intake could reduce gastric cancer risk, but its protective effect might be greater if gastritis is treated (for example, by Helicobacter pylori eradication). Publication Types: Clinical trial Controlled clinical trial PMID: 8801192, UI: 96246352


129. The effect of ascorbate and ubiquinone supplementation on plasma and CSF total antioxidant capacity.

Free Radic Biol Med 1996;21(2):211-7
Lonnrot K, Metsa-Ketela T, Molnar G, Ahonen JP, Latvala M, Peltola J, Pietila T, Alho H Department of Biomedical Sciences, University of Tampere, Finland.

Free radicals are thought to be involved in the onset of neuronal disturbances such as Alzheimer's disease, Parkinson's disease, and neuronal ceroid lipofuscinosis. It is also assumed that they play a role in cerebral injury caused by ischemia or trauma. Plasma and cerebrospinal fluid (CSF), Total (peroxyl) Radical-trapping Antioxidant Parameter (TRAP), and the known antioxidant components of TRAP, for instance, Ascorbic acid, uric acid, protein sulfhydryl groups, tocopherol, and ubiquinol were analyzed and the remaining unidentified fragment was calculated in five healthy volunteers before and after 4 weeks of ascorbate and ubiquinone (Q-10) supplementation. In CSF, TRAP was significantly lower than in plasma. The major contributor to plasma's antioxidant capacity was uric acid (UA), whereas in CSF it was Ascorbic acid (AA). In CSF, AA concentrations were four times higher than in plasma. Oral supplementation of AA (500 mg/d first 2 weeks, 1,000 mg/d following 2 weeks) and Q-10 (100 mg/d first 2 weeks, 300 mg/d following 2 weeks) induced a significant increase in plasma AA and Q-10. Surprisingly, in spite of the high lipophilicity of Q-10, its concentration did not change in CSF. The supplementation of AA increased its concentration in CSF by 28% (p < .05). However, the increase in AA did not result in an increase in CSF TRAP. This indicates that AA had lost one-third of its radical trapping capacity as compared to that in plasma. The facts that AA is the highest contributor to CSF TRAP and its effect on TRAP is concentration dependent could indicate that the peroxyl radical-trapping capacity of CSF is buffered by AA


130. [The effect of intravenous Ascorbic acid on urinary 17-hydroxysteroid excretion at an early stage of cerebral stroke].

Neurol Neurochir Pol 1996 Jan-Feb;30(1):49-56
Nadgrodkiewicz K Oddzialu Neurologii Wojewodzkiego Szpitala Zespolonego w Radomiu.

The main symptoms of stroke such as a displacement of intracranial structures, changes in spatial relations, secondary hemorrhagic and ischemic foci, oedema and metabolic disturbances are the cause of the disorders of hypothalamus-hypophysis system leading to increased secretion of corticosteroids including 17-hydroxyketosteroids (17-OHKS). Steroidogenesis in inhibited by high concentrations of Ascorbic acid. Intravenous injections of Ascorbic acid 0.5 g were given to the patients with stroke and their urine was analysed daily to examine the secretion of 17-OHKS. A slight increase in 17-OHKS secretion was found on 1 and 2 days of the disease in patients suffering from TIA and a significant increase in 17-OHKS secretion was detected in patients with cerebral ischaemia (ischemic stroke) and cerebral hemorrhage and persisted for 3-4 days of the illness. One can presume that the disorders of hypothalamus-hypophysis-adrenal system contributes much more to the decrease in 17 OHKS secretion on successive days of stroke than the administration of Ascorbic acid. PMID: 8657350, UI: 96249747.