Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.
Darr D Dunston S Faust H Pinnell S. Acta Derm Venereol (1996 Jul) 76(4):264-8
Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection. Melatonin Suppresses UV-Induced Erythema
Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Populations for Epidemiologic Studies of the Elderly
Losonczy KG; Harris TB; Havlik RJ Epidemiology, Demography and Biometry Program, National Institute on Aging, Bethesda, MD 20892-9205, USA. email@example.com Am J Clin Nutr (UNITED STATES) Aug 1996, 64 (2) p190-6,
We examined vitamin E and vitamin C supplement use in relation to mortality risk and whether vitamin C enhanced the effects of vitamin E in 11,178 persons aged 67-105 y who participated in the Established Populations for Epidemiologic Studies of the Elderly in 1984-1993. Participants were asked to report all nonprescription drugs currently used, including vitamin supplements. Persons were defined as users of these supplements if they reported individual vitamin E and/or vitamin C use, not part of a multivitamin. During the follow-up period there were 3490 deaths. Use of vitamin E reduced the risk of all-cause mortality [relative risk (RR) = 0.66; 95% CI: 0.53, 0.83] and risk of coronary disease mortality (RR = 0.53; 95% CI: 0.34, 0.84). Use of vitamin E at two points in time was also associated with reduced risk of total mortality compared with that in persons who did not use any vitamin supplements. Effects were strongest for coronary heart disease mortality (RR = 0.37; 95% CI: 0.15, 0.90). The RR for cancer mortality was 0.41 (95% CI: 0.15, 1.08). Simultaneous use of vitamins E and C was associated with a lower risk of total mortality (RR = 0.58; 95% CI: 0.42, 0.79) and coronary mortality (RR = 0.47; 95% CI: 0.25, 0.87). Adjustment for alcohol use, smoking history, aspirin use, and medical conditions did not substantially alter these findings. These findings are consistent with those for younger persons and suggest protective effects of vitamin E supplements in the elderly.
Carotenoids, vitamins C and E, and mortality in an elderly population
Sahyoun NR; Jacques PF; Russell RM Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Am J Epidemiol (U.S.) Sep 1 1996, 144 (5) p501-11,
In 1981-1984, the nutritional status of 747 noninstitutionalized Massachusetts residents aged 60 years and over was assessed. Nine to 12 years later, the vital status of these subjects was determined. The data of a subset of 725 community-dwelling volunteers was used to examine associations between mortality and the nutrient antioxidants (carotenoids and vitamins C and E) in plasma, diet, and supplements. Results indicated that subjects with plasma vitamin C levels in the middle and high quintiles had a lower overall mortality (relative risk (RR) = 0.64, 95% confidence interval (CI) 0.44-0.94 and RR = 0.54, 95% CI 0.32-0.90, respectively) than those in the lowest quintile even after adjustment for potential confounders. These associations were largely due to reduced mortality from heart disease. Subjects in the highest quintile of total intake of vitamin C also had a significantly lower risk of overall mortality (RR = 0.55, 95% CI 0.32-0.93) and mortality from heart disease (RR = 0.38, 95% CI 0.19-0.75) than did those in the lowest quintile after potential confounders were controlled for. Intake of vegetables was inversely associated with overall mortality (p for trend = 0.003) and mortality from heart disease (p for trend = 0.04). No other significant associations were observed. In conclusion, the results indicate that high intakes and plasma levels of vitamin C and frequent consumption of vegetables may be protective against early mortality and mortality from heart disease.
Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction
Herbaczynska-Cedro K; K+osiewicz-Wasek B; Cedro K; Wasek W; Panczenko-Kresowska B; Wartanowicz M Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland Eur Heart J (ENGLAND) Aug 1995, 16 (8) p1044-9,
Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL). The present study, performed in patients with acute MI aimed (1) to investigate the effect of vitamin C and E supplementation upon neutrophil OFR production and serum lipid peroxides, (2) to evaluate serum levels of vitamins C and E in the course of MI. Forty-five patients with acute MI were randomized to receive either conventional treatment only (control, n=22). All measurements were performed on the 1st and 14th day. Neutrophil OFR production assayed by CL decreased significantly in VIT patients (Wilcoxon test for paired data P<0.01, Chi square test P<0.01). In the control group, changes in OFR production were not significant. Serum lipid peroxides (measured as TBARS) increased in controls (P<0.05), but remained stable in VIT patients. Mean (+/-SE) serum ascorbic acid and tocopherol on the 1st day were 0.43 +/- 0.18% and 3.25 +/- 1.32 microM.M(-1) cholesterol, respectively, in all patients. On the 14th day in non-supplemented patients mean tocopherol was unchanged, whereas ascorbic acid increased significantly (0.63 +/- 0.24 mg%, P<0.01) suggesting that a low basal level was associated at least in part with the acute phase of the disease. An expected increase in serum vitamin levels occurred in VIT patients. In conclusion, supplementation with vitamins C and E suppresses neutrophil OFR production and lowers the marker of lipid peroxidation in patients with MI.
Effect of vitamin E, vitamin C and beta-carotene on LDL oxidation and atherosclerosis
Jialal I; Fuller CJ Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas 75235-9052, USA. Can J Cardiol (CANADA) Oct 1995, 11 Suppl G p97G-103G,
OBJECTIVE: The oxidative modification of low density lipoprotein (LDL) may be an early step in atherogenesis. Furthermore, evidence of oxidized LDL has been found in vivo. The most persuasive evidence shows that supplementation of some animal models with antioxidants slows atherosclerosis. The purpose of this review is to examine the roles that vitamin E, vitamin C and beta-carotene may play in reducing LDL oxidation.
DATA SOURCES: English language articles published since 1980, particularly from groups active in this field of research. STUDY LECTION: In vitro, animal, and human studies on antioxidants, LDL oxidation, and atherosclerosis were selected. DATA SYNTHESIS: Vitamin E has shown the most consistent effects with regard to LDL oxidation. Beta-carotene appears to have only a mild or no effect on oxidizability. Ascorbate, although it is not lipophilic, can also reduce LDL oxidative susceptibility. CONCLUSIONS: LDL oxidizability can be reduced by antioxidant nutrients. However, more research is needed to establish their utility in the prevention of coronary artery disease. (97 Refs.) x?
Effect of intake of exogenous vitamins C, E and beta-carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes
Mekinova D; Chorvathova V; Volkovova K; Staruchova M; Grancicova E; Klvanova J; Ondreicka R Research Institute of Nutrition, Bratislava, Slovak Republic Nahrung (GERMANY) 1995, 39 (4) p257-61,
We studied the effect of supplementation with vitamins C, E and beta-carotene (PARABION, produced by Syndipharma) on antioxidative status in kidneys of male Wistar rats with diabetes induced by intravenous application of streptozotocin (45 mg.kg-1 of body weight). The animals received subtherapeutic doses of Insulin Interdep (6 U.kg-1 of body weight). A significant decrease of malondialdehyde (MDA), reduced (GSH) and oxidized (GSSG) glutathione and reduction of the activities of Se-glutathione peroxidase (Se-GSH-PX, EC. 22.214.171.124.) and glutathione S-transferase (GST, EC. 126.96.36.199.) were observed in kidneys of diabetic rats treated with these vitamins. On the contrary, the activity of CuZn-superoxide dismutase (CuZn-SOD, EC. 188.8.131.52) and the level of vitamin C (vit. C) increased significantly. No changes were observed for vitamin E (vit. E), beta-carotene and catalase (CAT, EC. 184.108.40.206). Supplementation with vitamins C, E and beta-carotene resulted in an improvement of antioxidative status of kidneys of rats with streptozotocin-induced diabetes.
Serial coronary angiographic evidence that antioxidant vitamin intake reduces progression of coronary artery atherosclerosis
Hodis HN; Mack WJ; LaBree L; Cashin-Hemphill L; Sevanian A; Johnson R; Azen SP Atherosclerosis Research Unit, University of Southern California School of Medicine, Los Angeles 90033, USA. JAMA (UNITED STATES) Jun 21 1995, 273 (23) p1849-54,
OBJECTIVE-To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease.
DESIGN-A subgroup analysis of the on-trial antioxidant vitamin intake database acquired in the Cholesterol Lowering Atherosclerosis Study, a randomized, placebo-controlled, serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression. SETTING-Community- and university-based cardiac catheterization laboratories.
SUBJECTS-A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery. INTERVENTION-Supplementary and dietary vitamin E and C intake (nonrandomized) in association with cholesterol-lowering diet and either colestipol-niacin or placebo (randomized)
OUTCOME-Change per subject in the percentage of vessel diameter obstructed because of stenosis (%S) determined by quantitative coronary giography after 2 years of randomized therapy on all lesions, mild/moderate lesions (< 50%S), and severe lesions (> or = 50%S).
RESULTS-Overall, subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions (P = .04) and for mild/moderate lesions (P = .01). Within the drug group, benefit of supplementary vitamin E intake was found for all lesions (P = .02) and mild/moderate lesions (P = .01). Within the placebo group, benefit of supplementary vitamin E intake was not found. No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E, use of multivitamins, or increased dietary intake of vitamin E or vitamin C.
CONCLUSIONS-These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression. Verification from carefully designed, randomized, serial arterial imaging end point trials is needed.
The excretion of large vitamin C loads in young and elderly subjects: an ascorbic acid tolerance test
Neale RJ; Lim H; Turner J; Freeman C; Kemm JR Department of Applied Biochemistry and Food Science, University of Nottingham, Loughborough Age Ageing (ENGLAND) Jan 1988, 17 (1) p35-41,
An ascorbic acid tolerance test is described for assessing vitamin C status. The test is simple to administer and suitable for elderly patients. It involves giving an oral load of 1 g ascorbic acid in water and then measuring urinary excretion of vitamin C over the next 6h. The excretion pattern at dosing has been studied in ten young subjects. The result of the ascorbic acid tolerance test in these young subjects was significantly different after supplementation with 1g ascorbic acid daily for 1 month. Two series of elderly patients were also studied with the ascorbic acid tolerance test. They had low initial plasma ascorbic acid levels and much less vitamin C was excreted in the urine after dosing. Seven of these elderly patients were then supplemented with 1g ascorbic acid for 1 month. After supplementation the initial plasma levels and their response to the ascorbic acid tolerance test became similar to that seen in younger subjects.
Effect of dietary vitamin C on compression injury of the spinal cord in a rat mutant unable to synthesize ascorbic acid and its correlation with that of vitamin E
Spinal Cord (United Kingdom), 1996, 34/4 (234-238)
The roles of vitamines after spinal cord injury were investigated by evaluating the effects of dietary vitamin C on experimental spinal cord injury in a mutant strain of Wistar rats unable to synthesize ascorbic acid (ODS rats). Two groups of ODS rats were given vitamin C-deficient or vitamin C-supplemented diet for 1 week before injury. Motor disturbance induced by spinal cord injury was found to be greater in the vitamin C-deficient group. Histologically, the area of bleeding in the spinal cord was also greater in the vitamin C-deficient group. The levels of ascorbic acid and alpha-tocopherol in the spinal cord tissue and serum decreased during and after compression injury of the spinal cord. The decrease of alpha-tocopherol was similar in the two groups. However, the decrease of ascorbic acid was greater in the vitamin C-supplemented group. These results indicated that their protective effects against spinal cord injury are through scavenging water-soluble free radicals by vitamin C and lipid-soluble by vitamin E, and the effects of these vitamins were suggested to be independent.Cerebral astrocytes transport ascorbic acid and dehydroascorbic acid through distinct mechanisms regulated by cyclic AMP.
J Neurochem (UNITED STATES) Jun 1997, 68 (6) p2378-85
Cerebral ischemia and trauma lead to rapid increases in cerebral concentrations of cyclic AMP and dehydroascorbic acid (DHAA; oxidized vitamin C), depletion of intracellular ascorbic acid (AA; reduced vitamin C), and formation of reactive astrocytes. We investigated astrocytic transport of AA and DHAA and the effects of cyclic AMP on these transport systems. Primary cultures of astrocytes accumulated millimolar concentrations of intracellular AA when incubated in medium containing either AA or DHAA. AA uptake was Na+-dependent and inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), whereas DHAA uptake was Na+-independent and DIDS-insensitive. DHAA uptake was inhibited by cytochalasin B, D-glucose, and glucose analogues specific for facilitative hexose transporters. Once inside the cells, DHAA was reduced to AA. DHAA reduction greatly decreased astrocytic glutathione concentration. However, experiments with astrocytes that had been previously depleted of glutathione showed that DHAA reduction does not require physiological concentrations of glutathione. Astrocyte cultures were treated with a permeant analogue of cyclic AMP or forskolin, an activator of adenylyl cyclase, to induce cellular differentiation and thus provide in vitro models of reactive astrocytes. Cyclic AMP stimulated uptake of AA, DHAA, and 2-deoxyglucose. The effects of cyclic AMP required at least 12 h and were inhibited by cycloheximide, consistent with a requirement for de novo protein synthesis. Uptake and reduction of DHAA by astrocytes may be a recycling pathway that contributes to brain AA homeostasis. These results also indicate a role for cyclic AMP in accelerating the clearance and detoxification of DHAA in the brain.
Osmotic swelling stimulates ascorbate efflux from cerebral astrocytes.
J Neurochem (UNITED STATES) Mar 1996, 66 (3) p1227-33
Ascorbate (reduced vitamin C) is an important enzyme cofactor, neuromodulator, and antioxidant that is stored at millimolar concentrations in the cytosol of cerebral astrocytes. Because these cells swell during hyponatremia, cerebral ischemia,sport of ascorbate. Ascorbate efflux from primary cultures of rat astrocytes was rapidly (within 1 min) increased by incubation in hypotonic medium. Efflux also increased when astrocytes, which had been adapted to a hypertonic environment, were swollen by transfer to isotonic medium. Swelling-induced ascorbates efflux was inhibited by the anion-transport inhibitors 4,4'-diisothiocyanostilbene-2,2 '-disulfonic acid (DIDS) and 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS). The pathway that mediates ascorbate efflux was found to be selective because a larger anion, 2',7'-bis(carboxyethyl)-5-(or -6)-carboxyfluorescein (BCECF), was retained in the swollen astrocytes. Na(+)-dependent ascorbate uptake into astrocytes was inhibited slightly during the first minute of hypotonic stress, indicating that the sodium ascorbate cotransporter does not mediate swelling-induced efflux. Cell concentration of authentic ascorbate was measured by HPLC with electrochemical detection. When astrocytes were incubated in ascorbate-free medium, hypotonicity decreased cell ascorbate concentration by 50% within 3 min. When astrocytes were incubated in ascorbate-supplemented hypotonic medium, intracellular ascorbate concentration was restored within 10 min because uptake remained effective. Many pathological conditions cause brain cell swelling and formation of reactive oxygen species. Ascorbate release during during astrocytic swelling may contribute to cellular osmoregulation in the short-term and the scavenging of reactive oxygen species.
Effect of allopurinol, sulphasalazine, and vitamin C on aspirin induced gastroduodenal injury in human volunteers
United Kingdom Gut (United Kingdom), 1996, 38/4 (518-524
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 l 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.
Hemodynamic effects of delayed initiation of antioxidant therapy (beginning two hours after burn) in extensive third-degree burns
Journal of Burn Care and Rehabilitation (USA), 1995, 16/6 (610-615)
The hemodynamic effects of the delayed initiation of antioxidant therapy with high-dose vitamin C were studied in 12 guinea pigs with third-degree burns over 70% of their body surface area. All animals were resuscitated with Ringer's lactate solution (RE) according to the Parkland formula (4 ml/kg/% burn during the first 24 hours) from one-half to 2 hours after burn, and the infusion rate was reduced thereafter to 23% of that of the Parkland formula. The vitamin C group (n = 6) received RL with vitamin C (14 mg/kg/hr), and the control group (n = 6) received RE only. The 24-hour fluid intake for each group was 32.5% of the Parkland formula volume. Burn wound edema in the vitamin C group was significantly less than that in the control group. The vitamin C group maintained adequate hemodynamic stability as determined with hematocrit and cardiac output values, but the control group did not. Even though the initiation of the vitamin C administration is delayed until 2 hours after burn, the hourly infusion rate of the resuscitation fluid can be reduced to 25% once it is started. Thus antioxidant therapy with adjuvant vitamin C administration may be applicable to the clinical setting in which a patient with burns arrives at the burn care facility a few hours after the burn injury occurred.
Vitamin C and pressure sores
Journal of Dermatological Treatment (United Kingdom), 1995, 6/3
This review describes 50 years of studies on the relationship between vitamin C and wound healing. Several early studies in animals reported a clear link between vitamin C depletion and impaired wound healing, shown later to be due to an effect on collagen synthesis. Further clinical studies found that supplementary vitamin C improves wound healing even in apparently vitamin C-replete individuals. Associations between vitamin C and pressure sore development, and healing of pre-existing pressure sores have been described, suggesting a therapeutic role for vitamin C supplementation. However, this would be complementary to current nursing and skin care strategies in patients with, or at risk of developing, pressure sores, such as those elderly patients admitted with femoral neck fractures, or paraplegic subjects.
Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model
ANN. PLAST. SURG. (USA), 1994, 33/6 (620-623)
Free radicals have been implicated in the cause of ischemia-reperfusion injury. Various agents have been used in an attempt to reduce ischemia-reperfusion injury pharmacologically, including free radical scavengers. Vitamin C (ascorbic acid), a well-known free radical scavenger, has not, to the best of our knowledge, been evaluated in this respect. Previous work at our institution has shown that vitamin C decreases capillary permeability, thus significantly reducing fluid resuscitation requirements in postburn cases. Because this is due in part to the scavenging effect of vitamin C on free radicals, we investigated the role, if any, of vitamin C on ischemia-reperfusion injury in a rat epigastric island skin flap model. Twenty-four adult Sprague-Dawley rats were divided into control and vitamin C groups. Superficial epigastric island skin flaps measuring 6.0 x 3.5 cm were raised. Pedicles were isolated and occluded with microvascular clamps for 6 hours. The flaps were then sutured back to their beds over Steri-Drape barriers. Fifteen minutes before reperfusion, the control group flaps were perfused via femoral artery cannulation with normal saline (2.5 ml/kg). The vitamin C- treated group was perfused in a similar fashion with 2.5 ml/kg of a vitamin C/normal saline solution (27 mg/ml). The animals were observed for 7 days, and the percentage of flap survival was determined using a paper template technique. The vitamin C-treated group demonstrated a significantly higher percentage of flap survival than did the control group (25.8% mean vs. 7.5% mean, p < 0.025). In this animal model, vitamin C reduced or limited reperfusion injury after 6 hours of ischemia. Its presumed mechanisms of free radical reduction and its relative safety make vitamin C a promising area of investigation in future animal studies as well as in human studies examining reperfusion injury.
An experimental study on the protection against reperfusion myocardial ischemia by using large doses of vitamin C
CHIN. J. CARDIOL. (China), 1994, 22/1 (52-54+80)
To obtain the practical measure for the ischemia-reperfusion injury, we developed an open chest pig model (occlusion for 1 hour and reperfusion for 2 hours). Vitamin C (Vit C 0.2 g/kg) was intravenously given within five minutes to 8 pigs and 12 pigs received only saline as control. The results showed that there were no differences in the hemodynamic parameters, but the release of the creatine kinase isoenzyme after the reperfusion was significantly decreased in the vit C group (P < 0.05-0.01), and the ratio of the infarct area and the risk area was 30.2% in the vit C group and 49.2% in controls respectively (P < 0.05). Furthermore, the content of myocardial malondialdehyde was significantly decreased in the vit C group. In order to observe the protective effect of vitamin C we also developed an open chest rabbit model. After four-hour reperfusion, vit C group had less severe bleeding and milder damage to the capillary endothelium than that of control group. On the rabbit model, the myocardial free radicals were directly measured with the electron resonance spectrograph after one half hour reperfusion (P < 0.05). It was found that the free radical content was significantly elevated in the control group (P < 0.05), vit C could inhibit such elevation (P < 0.01). So it was evident that the protection of vit C was directly related to scavenging the free radicals.
Vitamins as radioprotectors in vivo. I. Protection by vitamin C against internal radionuclides in mouse testes: Implications to the mechanism of damage caused by the auger effect
USA RADIAT. RES. (USA), 1994, 137/3 (394-399)
The potential of vitamin C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of vitamin C (1.5 microg in 3 microl saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an alpha-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations.
Experimental studies on the treatment of frostbite in rats
INDIAN J. MED. RES. SECT. B BIOMED. RES. OTHER THAN INFECT. DIS. (India), 1993, 98/AUG. (178-184)
The effect of treatment by high dose of vitamin C, rapid rewarming by 37degreeC water alone and with vitamin C, rapid rewarming by 37degreeC decoction of Indian black tea alone and with vitamin C for experimentally produced frostbite was evaluated in 6 groups (25 each) of rats. Frostbite was produced experimentally in the hind limbs by exposing the animals at -15degreeC for 1h using the harness technique. The degree of injury was assessed and classified on the basis of tissue necrosis at the end of 15 days. Administration of high dose of vitamin C for prolonged period and rapid rewarming at 37degreeC water bath immediately after cold exposure apparently reduced the tissue damage. High dose of vitamin C therapy preceded by rapid rewarming in plain water showed additional benefit. Rapid rewarming in decoction of Indian tea resulted in identical beneficial effect. The degree of tissue preservation was highest with rapid rewarming in tea decoction followed by high dose of vitamin C.
The effects of high-dose vitamin C therapy on postburn lipid peroxidation
USA J. BURN CARE REHABIL. (USA), 1993, 14/6 (624-629)
The effects of vitamin C treatment (14 mg/kg/hr) on postburn lipid peroxidation were evaluated in 12 dogs. A lymph duct above the ankle was cannulated bilaterally. Hourly lymph flow rates, plasma and lymph total protein concentrations, and plasma and lymph malondialdehyde concentrations were measured before the burn injury and for 24 hours after the burn injury. Four groups were employed: nonburn without treatment, nonburn with vitamin C treatment, burn without treatment, and burn with vitamin C treatment. The nonburn groups showed no significant differences in lymph flow rates, total protein flux, or lymph malondialdehyde level. In the burn groups the postburn hourly lymph flow rate increased by 850% without treatment and by 500% with vitamin C treatment, whereas the postburn hourly total protein flux increased by fiftyfold and twentyfold, respectively. There was a significant reduction in the postburn lymph malondialdehyde level in the group treated with vitamin C as compared with the nontreatment group. We conclude that high-dose vitamin C administration diminishes early postburn lipid peroxidation and reduces microvascular leakage of fluid and protein.
Vitamin C as a radioprotector against iodine-131 in vivo
J. NUCL. MED. (USA), 1993, 34/4 (637-640)
The capacity of vitamin C (ascorbic acid) to mitigate radiation damage resulting from the tissue-incorporated radionuclide 131I is examined. Spermatogenesis in mice is the experimental model and spermhead survival is the biological endpoint. When a small nontoxic amount of vitamin C was injected, followed by a similar injection of 131I, the 37% spermhead survival dose (D37) increased by a factor of 2.2 compared with the D37 in animals receiving only the radionuclide. Similar radioprotection was also observed when the animals were maintained on a diet enriched with 1% vitamin C (by weight). These results suggest that vitamin C may play an important role as a radioprotector against accidental or medical radiation exposures, especially when radionuclides are incorporated in the body and deliver the dose in a chronic fashion.
Effects of high-dose vitamin C administration on postburn microvascular fluid and protein flux
REHABIL. (USA), 1992, 13/5 (560-566)
The effects of vitamin C treatment (14 mg/kg/hr) on burn injury were evaluated in the hind paws of 12 mongrel dogs. A lymph duct above one hind paw of each dog was cannulated. Hourly lymph flow rates (QL) and plasma and lymph total protein concentrations were measured before the burn injury and for 6 hours after the burn injury. Data from 24 paws were divided into four groups: nonburn without treatment, nonburn with treatment, burn without treatment, and burn with treatment. The nonburn groups showed no significant differences in QL or in total protein flux. In the burn groups the postburn hourly QL increased by sevenfold in the nontreatment group and only by threefold in the treatment group, whereas the postburn hourly total protein flux increased by fifteenfold and fivefold, respectively. We conclude that administration of high-dose vitamin C reduces early postburn microvascular leakage of fluid and protein.
Ascorbate treatment prevents accumulation of phagosomes in RPE in light damage
INVEST. OPHTHALMOL. VISUAL SCI. (USA), 1992, 33/10 (2814-2821)
In dark-reared albino rats, exposure to 2 or 3 hr of intense light interrupted by 2 hr dark periods resulted in extensive degeneration of photoreceptor cells and degeneration of the retinal pigment epithelium (RPE). Ascorbate (ie, vitamin C) administration prior to light exposure protected photoreceptors and the RPE from light damage. In the present study, ascorbate-treated and untreated rats were exposed to various cycles of intermittent light. Immediately after this light exposure, phagosome frequency in the RPE was morphologically evaluated in comparable 50 microm sections. In untreated rats, exposure to 2 or 3 hr of intermittent light resulted in a five- to sixfold increase in phagosome density compared to unexposed controls. In contrast, no increase in phagosome density was observed in ascorbate-treated rats. In these animals, under all lighting regimens, phagosome levels remained essentially identical to those in rats not exposed to light. After a single nondamaging light exposure, phagosome density remained at the level of dark controls in ascorbate-treated and untreated rats. These results indicate that phagosome frequency may serve as an index for light damage and that the protective effect of ascorbate may be linked to its capacity to prevent rod outer segment shedding and phagocytosis under intense light conditions.
Topical vitamin C protects porcine skin from ultraviolet radiation-induced damage
BR. J. DERMATOL. (United Kingdom), 1992, 127/3 (247-253)
Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.
The synergism of gamma-interferon and tumor necrosis factor in whole body hyperthermia with vitamin C to control toxicity
MED. HYPOTHESES (United Kingdom), 1992, 38/3 (257-258)
In a previous paper, the synergism of gamma-interferon and tumor necrosis factor was considered with whole body hyperthermia. Because of the toxic effect of TNF due to oxygen radicals, it is suggested that vitamin C be added.
Vitamin C supplementation in the patient with burns and renal failure
J. BURN CARE REHABIL. (USA), 1992, 13/3 (378-380)
Vitamin C supplementation is an important component of nutritional management in patients with burns. To supply appropriate vitamin C therapy, complications such as renal failure must be considered. An understanding of current vitamin regimens and potential metabolic sequelae can assist the practitioner in providing safe and therapeutic vitamin C doses.
High-dose vitamin C therapy for extensive deep dermal burns
USA BURNS (United Kingdom), 1992, 18/2 (127-131)
We studied the haemodynamic effects of antioxidant therapy with high-dose vitamin C administration (170 mg/kg/24h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with vitamin C; and group 3 with 25 per cent of the Parkland formula without vitamin C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of vitamin C. With adjuvant high-dose vitamin C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.
Metabolic and immune effects of enteral ascorbic acid after burn trauma
BURNS (United Kingdom), 1992, 18/2 (92-97)
A burned guinea-pig model (30 per cent BSA) was used to study the effect of vitamin C on immune and metabolic responses following burn trauma. Thirty-six guinea-pigs received identical enteral diets (175 kcal/kg) except for the amount of vitamin C. Groups I, II, III and IV were given formulae delivering no vitamin C (1 RDA) 15 mg/kg/day 75 mg/kg/day or 375 mg/kg/day respectively. Resistance to infection was evaluated by injecting each animal with 0.1 ml of 1 x 109 Staph. aureus 502A subcutaneously on day 10. On day 14, Staph. aureus abscesses were excised and the numbers of viable colonies were determined. Results showed no statistical differences between groups in the clearance of Staph. aureus. From days 2 to 12, animals in groups I, II and III had body weights of approximately 97 per cent of preburn body weight. Animals in group IV however, had a body weight gain, 102 per cent of preburn body weight on day 12. Animals in group IV also had significantly lower metabolic rates on day 12 as compared to the animals in the other groups. These results suggest that large amounts of vitamin C have beneficial effects on the maintenance of body weight and metabolic rate following burn trauma.
Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose vitamin C
J. BURN CARE REHABIL. (USA), 1991, 12/6 (525-532)
The effects of high-dose vitamin C therapy (170 mg, 340 mg, and 680 mg/kg/day) were evaluated in 70% body surface area third-degree burns in guinea pigs that were resuscitated with 1 ml/kg/%burn Ringer's lactate solution. The water content measurements of the burned skin at 24 hours after burn injury in the vitamin C-treated groups were significantly lower than those of the control group (1 ml/kg/%burn) and those of the standard resuscitation group (4 ml/kg/%burn). The cardiac outputs in the group that received 340 mg vitamin C were significantly higher than those of the control group but not significantly different than those of the standard therapy group at 2 hours after burn injury and thereafter. In comparison with the regimen of 340 mg vitamin C, the regimen of 680 mg vitamin C was no more beneficial, and the regimen of 170 mg was less effective. With administration of adjuvant high-dose vitamin C, we were able to reduce the total 24-hour resuscitation volume from 4 ml/kg/%burn to 1 ml/kg/%burn, while a comparable cardiac output was maintained.
Nutritional considerations for the burned patient
SURG. CLIN. NORTH AM. (USA), 1987, 67/2 (109-131)
The metabolic response to injury is one of marked catabolic hormonal predominance resulting in hypermetabolism and protein wasting. Energy expenditure increases with increasing severity of injury, but reaches a maximum of twice resting energy expenditure when 50 percent TBSA is burned. We agree with the nutritional recommendations of the group at the Boston Shriner's Burn Institute and the Massachusetts General Hospital. These include providing calories at twice the resting energy expenditure, as predicted by the Harris-Benedict equations, for patients with greater than 30 percent BSAB; protein is provided at 2.5 gm per kg per day based on ideal body weight. It is important to recognize that these are optimal goals, but their attainment must be governed by safety considerations for the patient. It is probably safe to supplement intake with a multivitamin and vitamin C, as well as zinc, but our understanding of micronutrient therapy for stressed patients is rudimentary.
Ascorbic acid metabolism in trauma
INDIAN J. MED. RES. (INDIA), 1982, 75/5 (748-751)
In major trauma such as severe head injury, burns or lacerated injury, there was a precipitous fall in plasma ascorbic acid level accompanied by a significant rise in blood dehydroascorbate level. However, this change was temporary and normal vitamin C status was regained after recovery from the stress condition. A similar alteration in plasma ascorbate level was also found after major surgery. This alteration in ascorbic acid status was not due to lack of reduction of dehydroascorbic acid to ascorbic acid but due to a high turnover of ascorbic acid in trauma. Supplementation of ascorbic acid in trauma resulted in a temporary increase in the plasma ascorbic acid level.
Multiple pathologic fractures in osteogenesis imperfecta
ORTHOPADE (GERMANY, WEST), 1982, 11/3 (101-108)
The authors survey the current orthopedic possibilities in treating multiple fractures in osteogenesis imperfecta. Also the general influence of vitamin C treatment is discussed.
Determination of ascorbic acid in human vitreous humor by high-performance liquid chromatography with UV detection
Current Eye Research (United Kingdom), 1997, 16/6 (589-594)
Purpose. Ascorbic acid (AA) accumulates in vitreous at a concentration several times higher than in plasma. It has been suggested that AA may serve as an antioxidant that protects ocular tissues from free radical attack. There are many reports about the concentration of AA in ocular tissues. However, AA in adult human vitreous humor has not been determined. We measured concentrations of AA from pathologic human vitreous samples and compared the results. Methods. AA was measured by high-performance liquid chromatography (HPLC) with UV detection. Human vitreous humor was collected from patients undergoing pars plana vitrectomy. Results. AA was quantified in vitreous humor of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), macular hole (MH), idiopathic premacular fibrosis (PMF), and Terson syndrome (Terson). The concentrations of AA were 120.9 plus or minus 36.3 microg/ml (mean plus or minus SD), 129.8 plus or minus 36.6, 311.5 plus or minus 126.7, 446.9 plus or minus 154.2 and 406.0 plus or minus 22.0, respectively. There was no significant difference between the PDR and the PVR groups (unpaired t-test). Patients with PDR and PVR showed significantly lower concentrations of AA than those with MH. Conclusions. These findings suggest that increased oxidative stress may be produced in the ocular tissues of eyes with PDR and PVR, and AA appears to be consumed (oxidized) in performing its protective role.
Erythrocyte and plasma antioxidant ASMATIQUE DANS LE DIABETE DE TYPE I
Presse Medicale (France), 1996, 25/5 (188-192)
Objectives: Some biologic parameters involved in cell defence against oxygen radicals (plasmatic vitamins C and E, erythrocyte glutathione peroxidase, glutathione reductase and superoxide dismutase) were measured in single blood samples from 119 diabetic infants, adolescents and young adults. Methods: Data were studied in relation to residual insulin secretion determined by C peptide, level of metabolic control appreciated by glycosylated haemoglobin, lipid abnormalities and subclinical complications (retinopathy, neuropathy and nephropathy). Results: There was no change in antioxidant parameters with insulin secretion. Patients with poor glycaemic control and high plasma lipids had higher levels of plasma vitamin E. Patients with nephropathy had lower plasma vitamin C levels and those with neuropathy showed lower erythrocyte glutathione peroxidase activity. Plasma vitamin C concentrations and erythrocyte glutathione reductase activities were negatively correlated with the age of the patients and the duration of the disease. Conclusion: Higher transport capacity of vitamin E probably explains the elevated levels of vitamin E observed in patients with high lipid levels and long lasting illness. The lower levels of vitamin C in the presence of nephropathy may be due to an increased renal excretion of this vitamin. The reduction of glutathione peroxidase, glutathione reductase activities and vitamin C levels confirms the existence of an oxidative stress in type 1 diabetes.
The regional distribution of vitamins E and C in mature and premature human retinas
INVEST. OPHTHALMOL. VISUAL SCI. (USA), 1988, 29/1 (22-26)
Vitamin E is used to ameliorate retinopathy of prematurity, but little is known about baseline vitamin E levels in retinas of premature infants or the effect of vitamin E supplementation on these levels. Vitamin E and C levels were measured in mature retinas (1 month to 73 years) and in retinas of premature infants (22 to 33 weeks of gestation). The infants fell into two groups: (1) those who survived <12 hr and received no vitamin E, and (2) those who survived >4 days and received vitamin E supplementation. Premature infants are born with 5 to 12 percent the vitamin E levels found in mature retinas. Vitamin E levels in vascular and avascular retina of premature infants increased with gestation. Infants born >27 weeks gestation and surviving at least 4 days with vitamin E supplementation demonstrated markedly elevated vitamin E levels in vascular and avascular retina when compared to supplemented infants <27 weeks gestation. Premature infants possessed 35-50% higher levels of retinal vitamin C than those found in mature retinas. These data demonstrate that premature infants are born with relatively low levels of retinal vitamin E, particularly in the avascular region, but contain an abundance of retinal vitamin C. These data further suggest that vitamin E supplementation results in a rapid increase in retinal vitamin E levels, particularly in infants >27 weeks gestational age.
Effects of dietary vitamin C and E supplementation on the copper mediated oxidation of HDL and on HDL mediated cholesterol efflux.
Rifici VA; Khachadurian AK
Department of Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick 08903-0019, USA.
Atherosclerosis (IRELAND) Nov 15 1996, 127 (1) p19-26
Copper mediated oxidative modification of high density lipoprotein (HDL) diminishes its capacity to promote cholesterol efflux from cells in culture. In the present study, HDL was isolated from eight subjects before and after a 10 day administration of the antioxidant vitamins C and E. After incubation HDL (1.25 mg protein/ml) with 10 microM copper for 0-4 h or with 0-20 microM copper for 4 h, thiobarbituric acid reactive substances (TBARS) production was significantly decreased following vitamin administration suggesting that the vitamins decreased the susceptibility of HDL to oxidation. However, two other assays of lipoprotein oxidation, trinitrobenzene sulfonic acid reactivity and conjugated diene formation, did not show a consistent effect of vitamin administration. To study cholesterol efflux, J774 macrophages were labeled with 3H cholesterol (0.1 microCi/ml, 50 micrograms/ml) and incubated with HDL or oxidized HDL (100 micrograms protein/ml) for 24 h. HDL isolated before vitamins and oxidized in vitro was 39% less effective in mediating efflux compared to unmodified HDL, while HDL isolated after vitamins and oxidized was 22% less effective (before vs. after vitamins, P < 0.015). HDL oxidation determined by measuring TBARS production correlated with decreased cholesterol efflux (r = 0.37, P < 0.050). These data suggest that oxidation of HDL interferes with its role in reverse cholesterol transport and that antioxidant vitamins have a protective effect.
Possible prevention of postangioplasty restenosis by ascorbic acid.
Tomoda H; Yoshitake M; Morimoto K; Aoki N
Department of Cardiology, Tokai University, Kanagawa, Japan.
Am J Cardiol (UNITED STATES) Dec 1 1996, 78 (11) p1284-6
In this preliminary study to assess the possibility of using ascorbic acid to prevent post-percutaneous transluminal coronary angiography (PTCA) restenosis, the incidence of restenosis was significantly less in 50 patients receiving 500 mg/day of oral ascorbic acid than idant, appeared to be possibly effective in attenuating post-PTCA restenosis.
Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants.
Darr D; Dunston S; Faust H; Pinnell S
North Carolina Biotechnology Center, Raleigh, N.C., USA.
Acta Derm Venereol (NORWAY) Jul 1996, 76 (4) p264-8,
Considerable interest has been recently generated concerning the use of natural compounds, anti-oxidants in particular, in photoprotection. Two of the best known anti-oxidants are vitamins C and E, both of which have been shown to be somewhat effective in different models of photodamage. Very little has been reported, however, on the effectiveness of a combination of the two (known to be biologically the more relevant situation); nor have there been detailed studies on the ability of these antioxidants to augment commercial sunscreen protection against UV damage. We report that (in swine skin) vitamin C is capable of additive protection against acute UVB damage (sunburn cell formation) when combined with a UVB sunscreen. A combination of both vitamins E and C provided very good protection from a UVB insult, the bulk of the protection attributable to vitamin E. However, vitamin C is significantly better than vitamin E at protecting against a UVA-mediated phototoxic insult in this animal model, while the combination is only slightly more effective than vitamin C alone. When vitamin C or a combination of vitamin C and E is formulated with a commercial UVA sunscreen (oxybenzone), an apparently greater than additive protection is noted against the phototoxic damage. These results confirm the utility of anti-oxidants as photoprotectants but suggest the importance of combining the compounds with known sunscreens to maximize photoprotection.
Prevention of dopamine-induced cell death by thiol antioxidants: possible implications for treatment of Parkinson's disease.
Offen D; Ziv I; Sternin H; Melamed E; Hochman A
Department of Neurology, Beilinson Medical Center, Petah-Tiqva, Israel.
Exp Neurol (UNITED STATES) Sep 1996, 141 (1) p32-9
We have recently shown that dopamine (DA) can trigger apoptosis, an active program of cellular self-destruction, in various neuronal cultures and proposed that inappropriate activation of apoptosis by DA and or its oxidation products may initiate nigral cell loss in Parkinson's disease (PD). Since DA toxicity may be mediated via generation of oxygen-free radical species, we examined whether DA-induced cell death in PC12 cells may be inhibited by antioxidants. We have found that the thiol containing compounds, reduced glutathione (GSH), N-acetyl-cysteine (NAC), and dithiothreitol (DTT) were markedly protective, while vitamins C and E had lesser or no effect. The thiol antioxidants and vitamin C but not vitamin E, prevented dopamine autooxidation and production of dopamine-melanin. Their protective effect has also manifested by inhibiting DA-induced apoptosis; DNA fragmentation was prevented as was shown histochemically by the in situ end-labeled DNA technique (TUNEL). Intracellular GSH and other thiols constitute an important natural defense against oxidative stress. We have found that depletion of cellular GSH by the addition of phoron, a substrate of glutathione transferase, and buthionine sulfoximine (BSO), an inhibitor of gamma-glutamyl transpeptidase, significantly enhanced DA toxicity. Cotreatment with NAC rescued the cells from the toxic effect of BSO+DA, and phoron+ DA, while addition of GSH provided only partial protection from BSO+DA toxicity. Our data indicate that the thiol family antioxidants, but not vitamins C and E, are highly effective in rescuing cells from DA-induced apoptosis. Further study of the mechanisms underlying the unique protective capacity of thiol antioxidants may lead to the development of new neuroprotective therapeutic strategies for PD.
Vitamin C intake and cardiovascular disease risk factors in persons with non-insulin-dependent diabetes mellitus. From the Insulin Resistance Atherosclerosis Study and the San Luis Valley Diabetes Study.
Mayer-Davis EJ; Monaco JH; Marshall JA; Rushing J; Juhaeri
epartment of Public Health Sciences, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1063, USA.
Prev Med (UNITED STATES) May-Jun 1997, 26 (3) p277-83
BACKGROUND: Persons with non-insulin-dependent diabetes mellitus (NIDDM) are at increased risk for cardiovascular disease, partly due to concomitant worsening of traditional risk factors including dyslipidemia and hypertension. Based on evidence from small, controlled clinical trials, we hypothesized that increased intake of vitamin C would be associated with improved cardiovascular disease (CVD) risk factor status among community-dwelling persons with NIDDM. METHODS: In separate but parallel statistical analyses, hypotheses were evaluated among persons with NIDDM confirmed by WHO criteria from the Insulin Resistance Atherosclerosis Study (IRAS, n = 520) and from the San Luis Valley Diabetes Study (SLVDS, n = 422). For IRAS, diet and vitamin supplement use was assessed by food frequency interview and for SLVDS, by 24-hr dietary recall interview. RESULTS: Mean vitamin C intake (mg/day) was 275 for IRAS and 133 for SLVDS, including supplements. In cross-sectional regression models from each data set, vitamin C intake was not associated with systolic or diastolic blood pressure nor with HDL-C, LDL-C, or triglycerides (P values > 0.10; adjusted for calories, demographic and lifestyle variables, obesity, diabetes duration, and medications). In prospective analyses including 285 SLVDS participants, baseline vitamin C intake was not related to any of these CVD risk factors measured an average of 4 years later nor to change in CVD risk factor status during the follow-up period. CONCLUSIONS: We conclude that, across a wide range of intake, vitamin C does not appear to be associated with improved CVD risk factor status among community-dwelling persons with diabetes.
Vitamin C and cardiovascular disease: a systematic review.
Ness AR; Powles JW; Khaw KT
Institute of Public Health, University Forvie Site, Cambridge, UK.
J Cardiovasc Risk (ENGLAND) Dec 1996, 3 (6) p513-21
BACKGROUND: Laboratory studies suggest that antioxidants, such as Vitamin C, are important inhibitors of atherosclerotic lesions. Most epidemiological reviews have considered all antioxidants together. This review seeks to clarify the current state of knowledge specifically concerned with vitamin C. METHODS: All ecological studies, case-control studies, prospective studies and trials in humans that examined the association between vitamin C intake or blood levels of vitamin C and cardiovascular disease were included. Relevant references were located search for articles published from 1966 to 1996, by an EMBASE search for articles published from 1980 to 1996, by searching personal bibliographies, books and reviews and from citations in located articles. RESULTS: For coronary heart disease four of seven ecological studies, one of four case-control studies and three of 12 cohort studies found a significant protective association with vitamin C intake or status. For strokes two of two ecological studies, none of one case-control study and two of seven cohort studies found a significant protective association. For total circulatory disease, two of three cohort studies reported a significant protective association. CONCLUSIONS: The evidence, albeit limited, is consistent with vitamin C having protective effect against stroke whereas the evidence that vitamin C is protective against coronary heart disease is less consistent. The lack of an association for coronary heart disease could be explained in terms of there being a true lack of effect, dietary measurement error, a threshold effect, and effect of seasonal variations in intake, an interaction with other dietary constituents or a relatively short duration of follow-up. (63 Refs.)