Vitamin C, neutrophil function, and upper respiratory tract infection risk in distance runners: the missing link.
Division of Physical Education, University of the Witwatersrand, Johannesburg, South Africa.
Exerc Immunol Rev (UNITED STATES) 1997, 3 p32-5
Moderate submaximal exercise results in neutrophilia and enhanced phagocytic and oxidative capacity of neutrophils. It has been hypothesized, however, that during intensive exercise and periods of intensive training this pro-oxidative effect becomes suppressive. Vitamin C is widely recognized for its antioxidant function in extracellular fluid, and it has been shown to neutralize O2-, HOCl, and .OH and to attenuate the suppression of phagocytic function. Clinical manifestation of reduced neutrophil function following participation in ultramarathon races has, however, not been observed. Although neutrophils constitute 50-60% of leukocytes and although they are the first line of defense to bacteriological invasion, postrace episodes of upper respiratory tract infection (URTI) are not correlated with a decrement in the function of this individual parameter of immune function. The efficacy of Vitamin C supplements in reducing the incidence of postrace URTI symptoms, therefore, cannot be fully explained at this stage. (99 Refs.)
Vitamin C intake and susceptibility to the common cold.
Department of Public Health, University of Helsinki, Finland.
Br J Nutr (ENGLAND) Jan 1997, 77 (1) p59-72
Although the role of vitamin C in common cold incidence had been studied extensively, the level of vitamin C intake has not been unequivocally shown to affect the incidence of colds. In the present study the six largest vitamin C supplementation (> or = 1 g/d) studies, including over 5000 episodes in all, have been analysed, and it is shown that common cold incidence is not reduced in the vitamin C-supplemented groups compared with the placebo groups (pooled rate ratio (RR) 0.99; 95% CI 0.93, 1.04). Consequently these six major studies give no evidence that high-dose vitamin C supplementation decreases common cold incidence in ordinary people. Nevertheless, the analysis was continued with the hypothesis that vitamin C intake may affect common cold susceptibility in specific groups of people. It was assumed that the potential effect of supplementation might be most conspicuous in subjects with low dietary vitamin C intake. The average vitamin C intake has been rather low in the UK and plasma vitamin C concentrations are in general lower in males than in females. In four studies with British females vitamin C supplementation had no marked effect on common cold incidence (pooled RR 0.95; 95% CI 0.86, 1.04). However, in four studies with British male schoolchildren and students a statistically highly significant reduction in common cold incidence was found in groups supplemented with vitamin C (pooled RR 0.70; 95% CI 0.60, 0.81). Thus, these studies with British males indicate that vitamin C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people and is not very large.
Ascorbic acid and atherosclerotic cardiovascular disease.
Lynch SM; Gaziano JM; Frei B
Whitaker Cardiovascular Institute, Boston University School of Medicine, Massachusetts 02118-2394, USA.
Subcell Biochem (ENGLAND) 1996, 25 p331-67
In this chapter, we have briefly reviewed the current scientific knowledge of the role of vitamin C in the prevention of atherosclerosis and its associated clinical manifestations. There is good evidence from animal studies that vitamin C can slow the progression of experimental atherosclerosis. Most of these studies, however, were done either in guinea pigs, using ascorbic acid depletion, or in cholesterol-fed rabbits, using ascorbic acid supplementation. Both animal models have limitations, as guinea pigs are not a well-established (nor well-studied) model of atherosclerosis, and rabbits develop atherosclerosis at high serum beta-VLDL cholesterol levels, and in addition can synthesize ascorbic acid. In contrast, humans develop atherosclerosis spontaneously and readily at moderately elevated serum LDL cholesterol levels and have lost the ability to synthesize ascorbic acid. Thus, the animal studies discussed, although quite promising and suggestive of an anti-atherogenic effect of ascorbic acid, need to be expanded to primates before more definitive conclusions can be drawn. Similar to the animal data, the current evidence from epidemiological studies on the role of vitamin C in the prevention of CVD is inconclusive, with some studies showing a very strong correlation between increased vitamin C intake and incidence of CVD events and other studies showing no correlation at all. Studies on CVD risk factors indicate that vitamin C may moderately decrease total serum cholesterol levels, increase HDL levels, and exert a hypotensive effect. These findings are particularly intriguing and should be pursued vigorously in basic research studies to elucidate biological mechanisms. In addition, it appears that large placebo-controlled, double-blind, randomized trials of vitamin C supplementation (without simultaneous supplementation with vitamin E) in populations with a wide range of vitamin C body levels are needed in order to confirm or refute a role for vitamin C in the prevention of CVD. Unfortunately, no such trials are currently being conducted. The possible mechanisms by which ascorbic acid may affect the development of atherosclerosis and the onset of acute coronary events include effects on arterial wall integrity related to biosynthesis of collagen and GAGs, altered cholesterol metabolile acids, and effects on triglyceride levels via modulation of lipoprotein lipase activity. A particularly intriguing possible mechanism for the anti-atherogenic effect of vitamin C is prevention of atherogenic, oxidative modification of LDL. Numerous in vitro studies have demonstrated that ascorbic acid strongly inhibits LDL oxidation by a variety of mechanisms. The potential effects of ascorbic acid on platelet function and EDRF metabolism are particularly intriguing, as they might have widespread consequences for the prevention of atherosclerotic lesion development as well as acute clinical events. Thus, both metabolic and antioxidant functions may contribute to the possible reduction of CVD risk by vitamin C. (165 Refs.)
Ascorbic acid protects against male infertility in a teleost fish.
Dabrowski K; Ciereszko A
School of Natural Resources, The Ohio State University, Columbus 43210, USA.
Experientia (SWITZERLAND) Feb 15 1996, 52 (2) p97-100
An animal unable to synthesize ascorbic acid uniquely mimicks human and non-human primates. Therefore, in this study we used the rainbow trout, a teleost fish, as the model animal to study the importance of dietary ascorbic acid on the fertilizing ability of sperm. A high concentration of ascorbic acid in semen plays a key role in maintaining the genetic integrity of sperm cells, by preventing oxidative damage to sperm DNA. This study will show that the concentration of ascorbic acid in seminal plasma reflects the dietary intake of vitamin C. The concentration of ascorbic acid in seminal plasma of fish declined significantly in groups fed either an ascorbate-free diet (from 4.74 +/- 0.9 to 0.16 +/- 0.08 microgram ml-1) or an ascorbate-rich diet (from 37.9 +/- 4.7 to 17.7 +/- 3.2 microgram ml-1) during the spermiation season. The relationship between ascorbate status and fertility was studied in six groups of fish fed graded levels of ascorbic acid, which spermiated over a 150-day-period. Sperm from individual males was used to fertilize several batches of eggs. When the seminal plasma ascorbate concentration decreased to 7.3 microgram ml-1 a significant decrease of fertilization rate and the hatching rate of embryos resulted. This is the first evidence that dietary ascorbate level directly affected sperm quality and influenced male fertility in a scurvy-prone vertebrate.
Oxidatively modified LDL and atherosclerosis: an evolving plausible scenario.
Jialal I; Fuller CJ
Center for Human Nutrition, University of Texas--Southwestern Medical Center, Dallas 75235-9052, USA.
Crit Rev Food Sci Nutr (UNITED STATES) Apr 1996, 36 (4) p341-55
Much evidence has accumulated that implicates the oxidative modification of low-density lipoprotein (LDL) in the early stages of atherogenesis. The , they have nutrients alpha-tocopherol, ascorbic acid, and betacarotene been shown to increase the resistance of LDL to oxidation when given to animals and humans. Because plasma levels of these nutrients can be increased by dietary supplementation with minimal side effects, they may show promise in the prevention of coronary artery disease. (115 Refs.)
In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals
USA Neurochemistry International (United Kingdom), 1995, 26/5 (527-535)
The kinetics of oxidation of endogenous antioxidants such as vitamins C and E and thiols as well as membrane cholesterol in isolated rat brain mitochondria were studied. Oxidation was induced by incubating the mitochondria at 37degreeC with the free radical generators 2,2' azobis (2'-amidinopropane) dihydrochloride (ABAPH) and 2,2' azobis (2,4-dimethyl) valeronitrile (ABDVN) which undergo thermal decomposition to yield free radicals. An approximate order for the in vitro ease of oxidation was. ascorbate >> alpha-tocopherol > sulfhydryls >> cholesterol. However, small amounts of ascorbate were present in the mitochondria when alpha-tocopherol and sulfhydryl compounds were getting oxidized. This observation is different from those with more homogeneous biological substrates like blood plasma or serum. The order of oxidation of the various compounds is a function of not only the redox potentials but also the (a) concentrations of the oxidized and reduced species, (b) compartmentation of the compounds and (c) enzymatic and nonenzymatic systems for the repair or regeneration of the individual antioxidants. Even though ascorbate levels are quite low within mitochondria this nutrient may play a major role as a first line of defense against oxidative stress. The lipid-soluble ABDVN was much more potent in oxidizing membrane alpha-tocopherol and thiols than the water-soluble ABAPH. With both free radical generators the rate of oxidation of the antioxidants consisted of two phases. The initial phase, that is more rapid, may represent a pool of antioxidant that is involved in immediate antioxidant protection of the organelle with the slower compartment being responsible for replenishing the faster pool whenever needed. The observation that one antioxidant (e.g. vitamin E) is oxidized prior to the total depletion of a more easily oxidized compound (vitamin C) suggests that antioxidants of different structures and redox potentials can function simultaneously in biological systems. Many degenerative brain diseases such as Parkinson's disease have been associated with oxidative damage. Therefore, it is possible that novel synthetic antioxidants may find therapeutic use in these conditions by providing additional antioxidant protection and/or enhancing the activities of endogenous antioxidants.
Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group
JAMA (UNITED STATES) Nov 9 1994
OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.
Antioxidant status and neovascular age-related macular degeneration
ARCH. OPHTHALMOL. (USA), 1993, 111/1 (104-109)
We evaluated the hypothesis that higher serum levels of micronutrients with antioxidant capabilities may be associated with a decreased risk of neovascular age-related macular degeneration by comparing serum levels of carotenoids, vitamins C and E, and selenium in 421 patients with neovascular age-related macular degeneration and 615 controls. Subjects were classified by blood level of the micronutrient (low, medium, and high). Persons with carotenoid levels in the medium and high groups, compared with those in the low group, had markedly reduced risks of neovascular age-related macular degeneration, with levels of risk reduced to one half and one third, respectively. Although no statistically significant protective effect was found for vitamin C or E or selenium individually, an antioxidant index that combined all four micronutrient measurements showed statistically significant reductions of risk with increasing levels of the index. Although these results suggest that higher blood levels of micronutrients with antioxidant potential, in particular, carotenoids, may be associated with a decreased risk of the most visually disabling form of age-related macular degeneration, it would be premature to translate these findings into nutritional recommendations.
Antioxidant defenses in metal-induced liver damage
Seminars in Liver Disease (USA), 1996, 16/1 (39-46)
Recent investigations have begun to define more clearly the cellular and molecular roles of oxidant stress in mediating the liver injury and fibrosis of metal storage diseases. Because of a variety of perturbations in antioxidant homeostasis in iron and copper overload, restoring the antioxidant balance to normal, or even exceeding normal levels of selected antioxidants, may provide additional protection against liver injury and prevent the progression to fibrosis and cirrhosis. Inasmuch as GSH levels appear to be elevated in livers of experimentally iron-overloaded animals, attempts to increase this antioxidant should perhaps be limited to copper overload conditions in which hepatic GSH is low. Vitamin C (ascorbate) supplementation should probably be avoided in all metal overload states because of its potentiation of radical generation by transition metals. The safety of beta-carotene in alocholic liver disease has been questioned. Therefore, until more is known about its toxicity in metal overload, beta- carotene may not be an ideal antioxidant for clinical trials. Vitamin E and related compounds, therefore, appear to be the most reasonable antioxidants to test in metal overload states at this time. In the near future, the results of controlled clinical trials of the use of antioxidants in these and other liver disorders will hopefully provide clearer guidelines for their safety and possible use.
Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. II. Synergism with combined chemotherapy action.
Anticancer Res. 1993 Jan-Feb. 13(1). P 103-6
The growth inhibitory effects of a combined application of sodium ascorbate (Vitamin C) and 2-methyl-1,4-naphthoquinone (Vitamin K3) together with various chemotherapeutic agents has been examined on in vitro cultured human endometrial adenocarcinoma (AN3CA) cells. Combined vitamin treatment and chemotherapy in well defined conditions of cell confluence and at the dose levels applied result in a synergistic effect on growth inhibition. The combined vitamins when reaching their own synergistic cytotoxicity levels frequently obscure the additional synergistic effects attributable to the chemotherapeutic agents. Apart from the specific cytotoxic characteristics of the chemotherapeutic drugs examined, the formation of reactive oxygen radicals during treatment, possibly accentuated by less defined secondary mechanisms, appears essentially responsible for the observed stimulated cytotoxicity.
Recent knowledge concerning the biochemistry and significance of ascorbic acid
Z Gesamte Inn Med (GERMANY, EAST) Jan 15 1984, 39 (2) p21-7
The ascorbic acid plays an important part by activation of hydroxylation reactions in various biosyntheses, such as in that of tropocollagen, bile acids and carnitine. It also considerably participates in the detoxication of compounds by hydroxylation and in the maintenance of the cytochrome P 450 contents in the liver. A sufficient supply is of importance for the absorption and accumulation of iron as well as for the efficiency of the immune system. After application of 14C-labelled ascorbic acid the compound is retained mainly in the brain, the salivary glands, the adrenal glands, the testes and in the eye lens. The largest contents of ascorbic acid lies in the pituitary gland, in the adrenal glands and in the eye lens. The need of ascorbic acid varies in man in dependence upon the state of development and the loads between 30 and 60 mg/die. In great smokers, after operations and traumas as well as when infections are present the intake of 100 to 200 mg a day are recommended. When more 1 g a day are taken the utilization decreases, the decomposition and the excretion, respectively, increase. A dose of more than 2 g a day inhibits the phagocytosis activity of leucocytes. (53 Refs.)
Anti-Aging News, January 1982 Vo.2, No. 1 pg 6-7
Cysteine is a strong reducing agent (it can prevent oxidation of some other substances). In fact, it has been found that too much cysteine in a cell culture medium can inactivate the hormone insulin contained in the medium. The insulin molecule contains three disulfide bonds, at least one of which can be reduced by cysteine. When this happens, the insulin molecule can no longer maintain the proper shape to function normally in stimulating the metabolism of sugar. In hypoglycemia attacks, there is too much insulin and too little sugar in the blood stream. Cysteine can inactivate insulin, thereby allowing the sugar level to begin to rise again. We and others have used the combination of vitamins B1, C, and cysteine to successfully abort severe attacks of hypoglycemia. A reasonable dose for a healthy adult is 5 grams of C, 1 gram of B1, and 1 gram cysteine. Although cysteine is a nutrient, it s use on a long-term basis should be considered experimental. Start with a low dose (250 milligrams per day) and work your way up. Always use at least three times as much vitamin C as cysteine. Be sure to consult with your physician and have regular clinical tests of basic body functions, especially liver and kidney. Diabetics should not use cysteine supplements due to its anti-insulin effects.
Prevention of cerebrovascular insults
Schweiz Med Wochenschr (SWITZERLAND) Nov 12 1994, 124 (45) p1995-2004
Cerebrovascular infarction is the third leading cause of mortality following coronary heart disease and malignancies. WHO studies show that more than half of patients admitted for cerebrovascular infarction were not treated for hypertension. The risk factors for coronary heart disease and cerebrovascular infarction are not identical. Patients with systolic and diastolic hypertension, atrial fibrillation, stenosis of the carotid artery, and smoking, have a significantly elevated risk for cerebrovascular accidents. Hypercholesterolemia and diabetes are less important risk factors. Risk factors amendable by adequate nutritional intake are low supply of carotene and vitamin C. Homocysteineemia appears to be a risk factor that may be influenced by appropriate nutrition. Antihypertensive therapy is the most important primary and secondary preventive measure. No smoking and adequate dietary intake are also important. Primary prevention with low dose salicylic acid (ASA) is recommended in the presence of additional cardiovascular risk factors. The benefit of low dose anticoagulant therapy in atrial fibrillation without symptoms is not fully established. In subjects with atrial fibrillation with cerebrovascular events anticoagulants are superior to ASA. Surgical treatment of significant stenosis of the carotid artery is indicated. In secondary prevention of thromboembolic events, low dose ASA is recommended. A valuable alternative in case of side effects is available in ticlopidine. (58 Refs.)
A double-blind, placebo-controlled parallel trial of vitamin C treatment in elderly patients with hypertension.
Gerontology (SWITZERLAND) 1994, 40 (5) p268-72
We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
The decline in stroke mortality. An epidemiologic perspective
Ann Epidemiol (UNITED STATES) Sep 1993, 3 (5) p571-5
The evidence that treatment of hypertension prevents stroke is incontrovertible. Several observations, however, suggest that improvements in the prevalence of antihypertensive treatment cannot explain all of the recent decline in stroke mortality. Changes in nutritional patterns may explain some of the observed decline. Prospective studies have demonstrated conclusively an independent, increasing risk of hemorrhagic, but not thrombotic, stroke at higher levels of alcohol use. Stroke mortality is associated inversely with fat and protein intake. Dietary sodium has been linked to stroke in ecologic studies but not in prospective studies. Ecologic studies have suggested that foods high in vitamin C and potassium protect against stroke; an inverse association of potassium intake with fatal stroke has been demonstrated in cohort studies. Two studies in humans also suggest a protective effect of serum selenium against subsequent stroke. Determination of the influence of nutrients on stroke incidence offers tantalizing opportunities for future research and possibly, intervention.
Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey.
Am J Epidemiol (UNITED STATES) Oct 1988, 128 (4) p700-10
Data from the first National Health and Nutrition Examination Survey collected between 1971 and 1972 were used to determine what factors are associated with the prevalence of age-related macular degeneration. The study was limited to those who were at least 45 years old at the time of the ophthalmology examination. Stratified analysis, adjusting for age, showed that education, systolic blood pressure, past history of hypertension, cerebrovascular disease, and refractive error were all associated with macular degeneration. With the exception of education, these factors remained statistically significant when simultaneously entered into a logistic regression model. The frequency of consumption of fruits and vegetables rich in vitamins A and C suggested a negative association with the prevalence of macular degeneration after stratified adjustment for age. In a logistic regression analysis, adjusting for demographic and medical factors, the inverse association of vitamin C with age-related macular degeneration was no longer present. The frequency of consumption of fruits and vegetables rich in vitamin A remained negatively correlated with age-related macular degeneration even after adjustment for demographic and medical factors.
Vitamin C deficiency and low linolenate intake associated with elevated blood pressure
J Hypertens Suppl (ENGLAND) Dec 1987, 5 (5) pS521-4
We investigated the association of dietary fatty acids and plasma antioxidative vitamins with blood pressure in 722 eastern Finnish men aged 54 years, examined in the Kuopio Ischaemic Heart Disease Risk Factor Study in 1984-1986, who had no known hypertension nor any cerebrovascular disease. Allowing for the major anthropometric, dietary, medical and psychological determinants of blood pressure in a multivariate regression analysis, plasma ascorbic acid concentration had a moderate, independent inverse association (P less than 0.0001) and the estimated dietary intake of linolenic acid an inverse (P = 0.026) independent association with mean resting blood pressure. The marked elevation of blood pressure at the lowest levels of plasma vitamin C concentration supports the hypothesis of the role of antioxidants in the aetiology of hypertension.
Nutrition and the elderly: a general overview.
J Am Coll Nutr (UNITED STATES) 1984, 3 (4) p341-50
Throughout adult life, there is progressive alteration in body composition and tissue function. There is loss of lean body mass, notably by muscle, with a gain in body fat. We do not know whether nutritional factors affect these gross changes. In the case of loss of bone density (osteoporosis), however, there is evidence that the process is retarded by raising the intake of calcium and by exercise. Aging also adversely affects tissue function at the level of the whole organ and tissue as well as at the cellular and subcellular level. Animal models show similar age-related changes, and demonstrate further that alterations in nutrient intake or exercise can alter the rate of loss of tissue and cellular function. In addition to the effects of adult aging on tissue function, certain chronic diseases and disabilities are related to aging. These conditions include atherosclerosis, hypertension, coronary thrombosis, cancer, etc. Both human epidemiological studies and animal experiments on aging suggest strongly that nutrition plays a role in the onset and development of these conditions. There is a need for more accurate assessments of the nutrient needs of people over 65 years of age. A few selected nutrients are discussed. Studies of energy intake during adult life show a progressive reduction with increasing age, due mainly to reduced physical activity. Vitamin C levels in the white blood cells of elderly women can be half those of young adults; these respond to supplementary vitamin C without evidence of clinical benefit. Nitrogen balance studies suggest that the allowance of protein for older adults is not less than for young. Finally, surveys of elderly in whole populations and in selected groups show that, by the nutritional standards of young adults, there may exist a significant amount of malnutrition in people as they grow old, though we do not know whether this affects rate of loss of tissue function with age.
Vitamin C status and blood pressure.
J Hypertens (ENGLAND) Apr 1996, 14 (4) p503-8
OBJECTIVE: To examine the cross-sectional relationship between blood pressure and plasma vitamin C. DESIGN: A cross-sectional analysis. SETTING: A population-based study. SUBJECTS: The subjects were 835 men and 1025 women aged 45-75 years registered with general practices in Norfolk. INTERVENTIONS: Completion of health and lifestyle questionnaire and attendance for a health check. MAIN OUTCOME MEASURES: Diastolic blood pressure (DBP), systolic blood pressure (SBP) and plasma vitamin C level. RESULTS: The mean SBP was 135.8 +/- 18.5 mmHg (mean +/- SD) and the mean DBP was 82.5 +/- 11.3 mmHg. The mean plasma vitamin C level was 52.6 +/- 19.7 mumol/l. The plasma vitamin C level was negatively correlated both with SBP and with DBP. These correlations persisted after adjustment for age, sex and body mass index. Adjusting for other confounders including cigarette smoking, physical activity and alcohol intake did not alter the observed association. Exclusion of subjects taking vitamin supplements and those with known hypertension did not affect the results. The differences in SBP and in DBP for a 50 mumol/l difference in vitamin C, estimated using linear regression, were -3.6 and -2.6 mmHg, respectively. CONCLUSIONS: The plasma vitamin C level may be a marker of other factors; nevertheless, these results are consistent with other published work indicating that a high intake of vitamin C from food confers protection against raised blood pressure and strokes.
[Relation between vitamin C consumption and risk of ischemic heart disease]
Vopr Pitan (USSR) Nov-Dec 1983
Interrelation was studied between vitamin C consumption and the prevalence of coronary heart disease and some risk factors in a non-organized male population in Kiev. A reverse relationship was established between vitamin C consumption, the prevalence of coronary heart disease and some risk factors, such as arterial hypertension, hyperlipoproteinemia and overweight.
Increased uptake and accumulation of vitamin C in human immunodeficiency virus 1-infected hematopoietic cell lines
Journal of Biological Chemistry (USA), 1997, 272/9 (5814-5820)
Vitamin C (ascorbic acid) is required for normal host defense and functions importantly in cellular redox systems. To define the interrelationship between human immunodeficiency virus (HIV) infection and vitamin C flux at the cellular level, we analyzed vitamin C uptake and its effects on virus production and cellular proliferation in HIV-infected and uninfected human lymphoid, myeloid, and mononuclear phagocyte cell lines. Chronic or acute infection of these cell lines by HIV-1 led to increased expression of glucose transporter 1, associated with increased transport and accumulation of vitamin C. Infected cells also showed increased transport of glucose analogs. Exposure to vitamin C had a complex effect on cell proliferation and viral production. Low concentrations of vitamin C increased or decreased cell proliferation depending on the cell line and either had no effect or caused increased viral production. Exposure to high concentrations of vitamin C preferentially decreased the proliferation and survival of the HIV-infected cells and caused decreased viral production. These findings indicate that HIV infection in lymphocytic, monocytic, and myeloid cell lines leads to increased expression of glucose transporter 1 and consequent increased cellular vitamin C uptake. High concentrations of vitamin C were preferentially toxic to HIV-infected host defense cell lines in vitro.
Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells.
Am J Clin Nutr (UNITED STATES) Dec 1991, 54 (6 Suppl) p1231S-1235S
To elucidate the action of vitamin C on pathogenic human retroviruses, we investigated and compared the effects of noncytoxic concentrations of ascorbic acid (AA), its calcium salt (Ca-ascorbate), and two thiol-based reducing agents [glutathione (GSH) and N-acetyl-L-cysteine (NAC)] against human immunodeficiency virus (HIV)-1 replication in chronically infected T lymphocytes. Ca-ascorbate reduced extracellular HIV reverse transcriptase (RT) activity by about the same magnitude as the equivalent dose of AA. Long-term experiments showed that continuous presence of ascorbate was necessary for HIV suppression. NAC (10 mmol/L) caused less than twofold inhibition of HIV RT and conferred a synergistic effect (approximately eightfold inhibition) when tested simultaneously with AA (0.426 mmol/L). In contrast, nonesterified GSH (less than or equal to 1.838 mmol/L) had no effect on RT concentrations and did not potentiate the anti-HIV effect of AA. These results further support the potent antiviral activity of ascorbate and suggest its therapeutic value in controlling HIV infection in combination with thiols.
Antioxidant status and lipid peroxidation in patients infected with HIV
CHEM.-BIOL. INTERACT. (Ireland), 1994, 91/2-3 (165-180)
Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cystein or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.
Antioxidant activity of vitamin C in iron-overloaded human plasma
Journal of Biological Chemistry (USA), 1997, 272/25 (15656-15660)
Vitamin C (ascorbic acid, AA) can act as an antioxidant or a pro- oxidant in vitro, depending on the absence or the presence, respectively, of redox-active metal ions. Some adults with iron-overload and some premature infants have potentially redox-active, bleomycin-detectable iron (BDI) in their plasma. Thus, it has been hypothesized that the combination of AA and BDI causes oxidative damage in vivo. We found that plasma of preterm infants contains high levels of AA and F2-isoprostanes, stable lipid peroxidation end products. However, F2-isoprostane levels were not different between those infants with BDI (138 plus or minus 51 pg/ml, n = 19) and those without (126 plus or minus 41 pg/ml, n = 10), and the same was true for protein carbonyls, a marker of protein oxidation (0.77 plus or minus 0.31 and 0.68 plus or minus 0.13 nmol/mg protein, respectively). Incubation of BDI-containing plasma from preterm infants did not result in detectable lipid hydroperoxide formation (less than or equal to10 nM cholesteryl ester hydroperoxides) as long as AA concentrations remained high. Furthermore, when excess iron was added to adult plasma, BDI became detectable, and endogenous AA was rapidly oxidized. Despite this apparent interaction between excess iron and endogenous AA, there was no detectable lipid peroxidation as long as AA was present at >10% of its initial concentration. Finally, when iron was added to plasma devoid of AA, lipid hydroperoxides were formed immediately, whereas endogenous and exogenous AA delayed the onset of iron-induced lipid peroxidation in a dose-dependent manner. These findings demonstrate that in iron-overloaded plasma, AA acts an antioxidant toward lipids. Furthermore, our data do not support the hypothesis that the combination of high plasma concentrations of AA and BDI, or BDI alone, causes oxidative damage to lipids and proteins in vivo.
Antioxidant status and lipid peroxidation in hereditary haemochromatosis.
Free Radic Biol Med (UNITED STATES) Mar 1994, 16 (3)
Hereditary haemochromatosis is characterised by iron overload that may lead to tissue damage. Free iron is a potent promoter of hydroxyl radical formation that can cause increased lipid peroxidation and depletion of chain-breaking antioxidants. We have therefore assessed lipid peroxidation and antioxidant status in 15 subjects with hereditary haemochromatosis and age/sex matched controls. Subjects with haemochromatosis had increased serum iron (24.8 (19.1-30.5) vs. 17.8 (16.1-19.5) mumol/l, p = 0.021) and % saturation (51.8 (42.0-61.6) vs. 38.1 (32.8-44.0), p = 0.025). Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were increased in haemochromatosis (0.59 (0.48-0.70) vs. 0.46 (0.21-0.71) mumol/l, p = 0.045), and there were decreased levels of the chain-breaking antioxidants alpha-tocopherol (5.91 (5.17-6.60) vs. 7.24 (6.49-7.80) mumol/mmol cholesterol, p = 0.001), ascorbate (51.3 (33.7-69.0) vs. 89.1 (65.3-112.9), p = 0.013), and retinol (1.78 (1.46-2.10) vs. 2.46 (2.22-2.70) mumol/l, p = 0.001). Patients with hereditary haemochromatosis have reduced levels of antioxidant vitamins, and nutritional antioxidant supplementation may represent a novel approach to preventing tissue damage. However, the use of vitamin C may be deleterious in this setting as ascorbate can have prooxidant effects in the presence of iron overload.
Ascorbic acid prevents the dose-dependent inhibitory effects of polyphenols and phytates on nonheme-iron absorption.
Am J Clin Nutr (UNITED STATES) Feb 1991, 53 (2)
The effects of maize-bran phytate and of a polyphenol (tannic acid) on iron absorption from a white-bread meal were tested in 199 subjects. The phytate content was varied by adding different concentrations of phytate-free and ordinary maize bran. Iron absorption decreased progressively when maize bran containing increasing amounts of phytate phosphorous (phytate P) (from 10 to 58 mg) was given. The inhibitory effect was overcome by 30 mg ascorbic acid. The inhibitory effects of tannic acid (from 12 to 55 mg) were also dose dependent. Studies suggested that greater than or equal to 50 mg ascorbic acid would be required to overcome the inhibitory effects on iron absorption of any meal containing greater than 100 mg tannic acid. Our findings indicate that it may be possible to predict the bioavailability of iron in a diet if due account is taken of the relative content in the diet of the major promoters and inhibitors of iron absorption.
Dietary supplementation with orange and carrot juice in cigarette smokers lowers oxidation products in copper-oxidized low-density lipoproteins
Journal of the American Dietetic Association (USA), 1995, 95/6 (671-675)
Objective: Our objective was to evaluate the effect of daily supplementation with foods high in vitamin C and beta carotene on plasma vitamin levels and oxidation of low-density lipoprotein (LDL) in cigarette smokers. Subjects: Fifteen normolipidemic male cigarette smokers who did not usually take vitamin supplements were recruited into the study. Interventions: Throughout the study, subjects consumed a diet rich in polyunsaturated fatty acids, which provided 36% of energy as fat: 18% from meat, dairy products, vegetable oils, and fat spreads and 18% from walnuts (68 g/day). Subjects consumed a vitamin-free drink daily for 3 weeks; then for 3 weeks they consumed daily supplements of orange juice (145 mg vitamin C) and carrot juice (16 mg beta carotene). Results: Vitamin-rich food supplements raised plasma levels of ascorbic acid (1.6-fold; P<.01) and beta carotene (2.6-fold; P<.01). Malondialdehyde, one end product of oxidation, was lower in copper-oxidized LDL after vitamin supplementation (meanplus or minusstandard error=65.7plus or minus2.0 and 57.5plus or minus2.9 micromol/g LDL protein before and after supplementation, respectively; P<.01). Rate of LDL oxidation and lag time before the onset of LDL oxidation were not affected by antioxidant supplementation. Conclusions: In habitual cigarette smokers, antioxidant vitamins, which can be feasibly provided from food, partly protected LDL from oxidation despite a diet rich in polyunsaturated fatty acids.
Vitamin C, oral scurvy and periodontal disease.
S Afr Med J (SOUTH AFRICA) May 26 1984, 65 (21)
Scurvy and periodontitis both manifest gingival bleeding but constitute separate entities. Defective collagen in scurvy reflects many symptoms emanating from deficient vitamin C physiology. The various periodontal diseases are caused by oral plaque micro-organisms, the body's reaction to which is strongly influenced by inadequate functioning of leucocytes and monocytes. Although certain infections and systemic diseases cause gingival bleeding, avitaminosis C does not cause commonly encountered periodontal disease, but will aggravate established periodontitis. Vitamin C should not be used for prophylaxis or cure of periodontitis in healthy well-nourished individuals. A patient with bleeding gingivae warrants referral to oral medicine and periodontics specialists for examination and treatment. (64 Refs.)
Diabetes and periodontal diseases. Possible role of vitamin c deficiency: an hypothesis.
J Periodontol (UNITED STATES) May 1981, 52 (5) p251-4
An hypothesis is proposed relating the possible role of vitamin deficiency as an etiologic factor contributing to periodontal disease in diabetes. The hypothesis is based upon the following: (1) transport of ascorbate across cell membranes may be impaired by glucose, but facilitated by insulin; (2) glucose utilization is significantly accelerated by sublethal concentrations of endotoxin; (3) endotoxin-induced histamine sensitivity of tissue is enhanced by ascorbic deficiency; and (4) ascorbic acid deficiency alters mucosal barrier function. The interrelationship of these factors is discussed.
The value of the dehydroepiandrosterone-annexed vitamin C infusion treatment in the clinical control of chronic fatigue syndrome (CFS). II. Characterization of CFS patients with special reference to their response to a new vitamin C infusion treatment.
In Vivo (GREECE) Nov-Dec 1996, 10 (6) p585-96
This study is a counterpart of the pilot study on the clinical management of chronic fatigue syndrome (CFS) by the combined use of the old (annex-free) and the new (dehydro-epiandrosterone- annexed) vitamin C infusion treatments with and without oral intake of erythromycin and chloramphenicol. We were motivated to start this clinical study by 2 reasons: i) we have made a success in the clinical management of autoimmune disease and allergy by use of the old megadose vitamin C infusion treatment, and we therefore took up CFS as a good candidate for vitamin C infusion treatment; ii) In 1995, we received a total of 313 chronic pneumonia patients whose clinical course showed a good fitness to the criteria of CFS. We assessed the nature of the disease by investigating theclinicoepidemiological aspect of our patients on the one hand and the response of the disease to both the old and new vitamin C infusion treatments with and without the use of 2 antibiotics on the other hand. Results are summarized as follows: a) the analysis of the medical records of our outpatients revealed that chronic type pneumonia epidemic in Nagoya Japan, with its onset of January 1995, showed no sign of its extinction by the end of May 1996. The patient population contained no patients under 15 years of age, and showed a distinct female predominance in the patient number (207 females versus 106 males). In 1995, we also experienced a simple cold epidemic with its onset of January 1995 (162 males and 224 females). The majority of simple cold patients were under 25 years of age in both sexes. b) A chronic type pneumonia patient was distinguished from a simple cold patient in 2 respects: firstly the former required prolonged medical care (over 1 month) resulting in an incomplete cure and return to medical care upon the recurrence of disease, whereas the latter required short-term medical care (mostly within 1 week) ending up with complete cure. Secondly, the former required the long term use of 2 antibiotics (erythromycin and chloramphenicol) together with regular practice of the old and new vitamin C infusion treatments for disease control, whereas the latter recovered from the disease after the short time use of a set of conventional cold remedies. c) The clinical manifestations of our chronic pneumonia patients showed good fitness to the criteria of CFS. d) CFS wasdistinguished from autoimmune disease-allergy complex by the method of clinical control: the former required the long-term use of 2 antibiotics together with regular practice of the old and new vitamin C infusion treatments, whereas the latter was controllable by the single use of the old vitamin C infusion treatment. e) The combined use of the old and new vitamin C infusion treatments rather than the single use of the old vitamin C infusion treatment was more effective for the control of CFS-a finding which suggests that deficient activities of both endogenous glucocorticoid and endogenous androgen in a CFS patient are somehow related to the genesis and further development of CFS. f) Evidence was available to indicate that the sole use of the new vitamin C infusion treatment may induce a state of gonadal steroid excess together with various other problems in the recipient. The maintenance of a good balance between the old vitamin C infusion set (glucocorticoid-inducer) and the new vitamin C infusion set (inducer of both glucocorticoid and gonadal steroids) in their use was of prime importance for the successful control of CFS. g) The historical significance of CFS epidemic in 1995, and in Nagoya-Japan, is discussed in the light of the new infection concept.
Epidemiology of coagulation factors, inhibitors and activation markers: The Third Glasgow MONICA Survey. II. Relationships to cardiovascular risk factors and prevalent cardiovascular disease.
Woodward M; Lowe GD; Rumley A; Tunstall-Pedoe H; Philippou H; Lane DA; Morrison CE
Department of Applied Statistics, University of Reading.
Br J Haematol (ENGLAND) Jun 1997, 97 (4) p785-97
Coagulation factor activity (fibrinogen, VII, VIII and IX), coagulation inhibitor activity (antithrombin, protein C, protein S), and coagulation activation markers (prothrombin fragment F1, 2; thrombin-antithrombin complexes) were measured in 746 men and 816 women aged 25-74 years, randomly sampled from the north Glasgow population in the Third MONICA Survey. After age-adjustment, significant associations with cardiovascular risk factors were observed. Serum cholesterol and triglyceride were associated with increases in factors VII and IX, as well as antithrombin, protein C and protein S; and with increased fibrinogen and factor VIII in women. Apart from factor VIII (related to blood pressure in men, but not in women), similar associations were observed for blood pressure and body mass index. Smoking status and/or smoking markers were related to fibrinogen, factor IX, antithrombin and protein S. Alcohol intake was related to protein S, and inversely to fibrinogen and antithrombin in men. Low social class was associated with fibrinogen, factor VIII, factor IX, and with antithrombin, protein S, and low protein C in men. Serum vitamin C was associated inversely with coagulation factors and coagulation inhibitors. The only associations of activation markers were with low serum vitamin C, and with alcohol consumption and low social class in men. Prevalent cardiovascular disease was associated only with fibrinogen. These associations of coagulation factors and inhibitors with cardiovascular risk factors are plausibly relevant to thrombotic risk in cardiovascular disease. In general, 'worse' values of risk factors are associated with increased plasma levels of both coagulation factors and inhibitors, without significant increase in coagulation activation markers. However, the association of lower serum vitamin C with increased coagulation activation markers is of potential therapeutic interest.
Vitamin C blocks inflammatory platelet-activating factor mimetics created by cigarette smoking
Lehr H.-A.; Weyrich A.S.; Saetzler R.K.; Jurek A.; Arfors K.E.; Zimmerman G.A.; Prescott S.M.; McIntyre T.M.
T.M. McIntyre, CVRTI, Building 500, University of Utah, Salt Lake City, UT 84112 USA
Journal of Clinical Investigation (USA), 1997, 99/10 (2358-2364)
Cigarette smoking within minutes induces leukocyte adhesion to the vascular wall and formation of intravascular leukocyte-platelet aggregates. We find this is inhibited by platelet-activating factor (PAF) receptor antagonists, and correlates with the accumulation of PAF-like mediators in the blood of cigarette smoke-exposed hamsters. These mediators were PAF-like lipids, formed by nonenzymatic oxidative modification of existing phospholipids, that were distinct from biosynthetic PAF. These PAF-like lipids induced isolated human monocytes and platelets to aggregate, which greatly increased their secretion of IL-8 and macrophage inflammatory protein-1alpha. Both events were blocked by a PAF receptor antagonist. Similarly, blocking the PAF receptor in vivo blocked smoke-induced leukocyte aggregation and pavementing along the vascular wall. Dietary supplementation with the antioxidant vitamin C prevented the accumulation of PAF-like lipids, and it prevented cigarette smoke-induced leukocyte adhesion to the vascular wall and formation of leukocyte-platelet aggregates. This is the first in vivo demonstration of inflammatory phospholipid oxidation products and it suggests a molecular mechanism coupling cigarette smoke with rapid inflammatory changes. Inhibition of PAF-like lipid formation and their intravascular sequela by vitamin C suggests a simple dietary means to reduce smoking-related cardiovascular disease.
Dietary vitamin C, beta-carotene and 30-year risk of stroke: Results from the western electric study.
Daviglus M.L.; Orencia A.J.; Dyer A.R.; Liu K.; Morris D.K.; Persky V.; Chavez N.; Goldberg J.; Drum M.; Shekelle R.B.; Stamler J.
Neuroepidemiology (Switzerland), 1997, 16/2 (69-77)
The relations of dietary antioxidants vitamin C and beta-carotene to 30-year risk of stroke incidence and mortality were investigated prospectively in the Chicago Western Electric Study among 1,843 middle-aged men who remained free of cardiovascular disease through their second examination. Stroke mortality was ascertained from death certificates, and nonfatal stroke from records of the Health Care Financing Administration. During 46,102 person-years of follow-up, 222 strokes occurred; 76 of them were fatal. After adjustment for age, systolic blood pressure, cigarette smoking, body mass index, serum cholesterol, total energy intake, alcohol consumption, and diabetes, relative risks (and 95% confidence intervals) for nonfatal and fatal strokes (n = 222) in highest versus lowest quartiles of dietary beta-carotene and vitamin C intake were 0.84 (0.57-1.24) and 0.71 (0.47-1.05), respectively. Generally similar results were observed for fatal strokes (n = 76). Although there was a modest decrease in risk of stroke with higher intake of beta-carotene and vitamin-C intake, these data do not provide definitive evidence that high intake of antioxidant vitamins decreases risk of stroke.