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Life Extension Magazine

Vitamin C

May 2013

Supplementation of ascorbic acid and alpha-tocopherol is useful to preventing bone loss linked to oxidative stress in elderly.

OBJECTIVE: To determine the effect of ascorbic acid and alpha-tocopherol on oxidative stress and bone mineral density (BMD) in elderly people. DESIGN: A double-blind, controlled clinical assay was carried out in a sample of 90 elderly subjects divided into three age-paired random groups with 30 subjects in each group. Group Tx0 received placebo, group Tx1 received 500 mg of ascorbic acid and 400 IU of alpha-tocopherol, whereas group Tx2 received 1,000 mg of ascorbic acid and 400 IU of alpha-tocopherol, for a 12-month period. MEASUREMENTS: We measured thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), superoxide dismutase (SOD), and glutation peroxidase (GPx); BMD was obtained on DXA of hip and spine before and after the 12-month treatment period with supplementation of vitamins C and E. RESULTS: We found a positive correlation between hip-BMD and SOD (r = 0.298, p < 0.05) and GPx (r = 0.214, p < 0.05). Also, a significantly lower decrease of LPO (p < 0.05) was observed as linked with hip bone loss in the Tx2 group than in the Tx0 group. CONCLUSIONS: Our findings suggest that that administration of 1,000 mg of ascorbic acid together with 400 IU of alpha-tocopherol could be useful in preventing or aiding in the treatment of age-related osteoporosis.

J Nutr Health Aging. 2010 Jun;14(6):467-72

Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries.

A concentration-function approach to vitamin C (ascorbate) has yielded new physiology and pharmacology discoveries. To determine the range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted. They showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal reabsorption. A 4th mechanism, rate of utilization, may be important in disease. With ingested amounts found in foods, vitamin C plasma concentrations do not exceed 100 µmol/L. Even with supplementation approaching maximally tolerated doses, ascorbate plasma concentrations are always <250 µmol/L and frequently <150 µmol/L. By contrast, when ascorbate is i.v. injected, tight control is bypassed until excess ascorbate is eliminated by glomerular filtration and renal excretion. With i.v. infusion, pharmacologic ascorbate concentrations of 25-30 mmol/L are safely achieved. Pharmacologic ascorbate can act as a pro-drug for hydrogen peroxide (H(2)O(2)) formation, which can lead to extracellular fluid at concentrations as high as 200 µmol/L. Pharmacologic ascorbate can elicit cytotoxicity toward cancer cells and slow the growth of tumors in experimental murine models. The effects of pharmacologic ascorbate should be further studied in diseases, such as cancer and infections, which may respond to generation of reactive oxygen species via H(2)O(2).

Adv Nutr. 2011 Mar;2(2):78-88

Dihydroquercetin: More than just an impurity?

Dihydroquercetin (taxifolin) is a potent flavonoid found in onions, French maritime bark, milk thistle, tamarind seeds and commercially available semi-synthetic monoHER marketed as Venoruton. This review focuses on the therapeutic promise of dihydroquercetin in major disease states such as cancer, cardiovascular disease and liver disease by reviewing the proposed mechanism(s) of action, including the activation of the antioxidant response element (ARE) and detoxifying phase II enzymes, inhibition of cytochrome P(450) and fatty acid synthase in carcinogenesis. TNF-alpha and NF-ĸB dependent transcription in hepatitis C infections, the scavenging effect of myeloperoxidase (MPO) derived reactive nitrogen species and subsequent effects on cholesterol biosynthesis as well as the effects on apob/apoA-I, HMG-CoA reductase and apoptosis are reviewed. The stereochemistry and pro-oxidant effect of dihydroquercetin are also considered. Although the majority of research on dihydroquercetin to date has focused on the identification of molecular targets in vitro, this review will bring together evidence of the potency and mode of action of dihydroquercetin and will propose a role for the therapeutic potential of flavonoid antioxidants.

Eur J Pharmacol. 2012 Jun 5;684(1-3):19-26

Vitamin C and E consumption and coronary heart disease in men.

Atherosclerotic cardiovascular diseases (CVD) are a major source of mortality and morbidity in general population. Oxidative modification of low density lipoprotein (LDL) represent the most important determinant factor in the development and progression of atherosclerotic lesions. Oxidative damage and the production of free radicals (FRs) in the endothelium are some of the main factors involved in the pathogenesis of the atherosclerotic process which causes CVD. Appropriate nutritional practices are of central importance in managing risk and treatment of CVD; indeed, many current guidelines contain nutritional recommendations to reduce the risk of these diseases. In observational studies vitamin C and E, the most prevalent natural antioxidant vitamins, have suggested that supplemental users have lower rate of coronary events. Despite these data, several large randomized controlled trials (RCTs) have failed to confirm the benefits for vitamin C and E in cardiovascular (CV) prevention. The aim of this review is to examine the studies published in literature which report the effect of supplementation with antioxidant vitamins (C,E) in the primary and secondary prevention of CVD in men due to atherosclerotic process.

Front Biosci (Elite Ed). 2012 Jan 1;4:373-80

Plasma vitamin C predicts incident heart failure in men and women in European Prospective Investigation into Cancer.

BACKGROUND: Fruit and vegetable intake has been associated with lower risk for cardiovascular risk factors and disease, but data on heart failure are sparse and inconsistent. The association of plasma vitamin C, a biomarker reflecting fruit and vegetable intake, with heart failure has not been studied. METHODS: We examined the prospective association of plasma vitamin C concentrations with incident fatal and nonfatal heart failure events in apparently healthy 9,187 men and 11,112 women aged 39 to 79 years participating in the “European Prospective Investigation into Cancer and Nutrition” study in Norfolk. RESULTS: The risk of heart failure decreased with increasing plasma vitamin C; the hazard ratios comparing each quartile with the lowest were 0.76 (95% CI 0.65-0.88), 0.70 (95% CI 0.60-0.81), and 0.62 (95% CI 0.53-0.74) in age- and sex-adjusted analyses (P for trend <.0001). Every 20 µmol/L increase in plasma vitamin C concentration (1 SD) was associated with a 9% relative reduction in risk of heart failure after adjustment for age, sex, smoking, alcohol consumption, physical activity, occupational social class, educational level, systolic blood pressure, diabetes, cholesterol concentration, and body mass index, with similar result if adjusting for interim coronary heart disease. CONCLUSIONS: Plasma vitamin C, a biomarker reflecting fruit and vegetable intake, was inversely associated with the risk of heart failure in this healthy population. This observation should be regarded as hypothesis generating for further prospective trials aimed at examining the effect of a diet rich in fruit and vegetables for prevention of heart failure.

Am Heart J.2011 Aug;162(2):246-53.

Association between plasma vitamin C concentrations and blood pressure in the European prospective investigation into cancer-Norfolk population-based study.

The effect of fruit and vegetable consumption and blood pressure is unclear. A population-based cross-sectional study was conducted in 20,926 men and women aged 40 to 79 years participating in the European Prospective Investigation Into Cancer-Norfolk who completed a health questionnaire and attended a clinic from 1993 to 1997. The relationship between plasma vitamin C concentrations, as an indicator of fruit and vegetable intake, and systolic BP was examined. The magnitude of their association was assessed using dichotomized values of high (≥140 mm Hg) and low (<140 mm Hg) systolic blood pressure. A total of 20,926 participants (46% men; mean [SD] 58.5 years [9.2 years]) were included after excluding participants with any missing data for variables of interest. People with high vitamin C concentrations had lower clinic blood pressure. The likelihood of having high blood pressure was 22% lower (odds ratio: 0.78 [95% CI: 0.71 to 0.86]) for those who were in the top quartiles of plasma vitamin C levels compared with the bottom quartiles after adjusting for age, sex, body mass index, cholesterol, prevalent medical conditions, smoking, physical activity, alcohol consumption, social class, education, use of vitamin C-containing supplement, and antihypertensive medication. Sex-specific analysis, as well as repeated analysis after exclusion of people who used vitamin C-containing supplements or who were taking antihypertensive medication, did not alter the results. There appears to be a strong association between vitamin C concentrations, an indicator of fruit and vegetable consumption, and a lower level of blood pressure. This may provide further evidence for health benefits of dietary patterns with higher fruit and vegetable consumption.

Hypertension. 2011 Sep;58(3):372-9

Effect of acute administration of vitamin C on muscle sympathetic activity, cardiac sympathovagal balance, and baroreflex sensitivity in hypertensive patients.

BACKGROUND: Essential hypertension is characterized by both increased oxidative stress and sympathetic traffic. Experimental studies have shown that reactive oxygen species can modulate autonomic activity. OBJECTIVE: The aim of this study was to determine whether acute administration of the antioxidant vitamin C modifies sympathetic nerve activity in essential hypertension. DESIGN: Thirty-two untreated patients with essential hypertension and 20 normotensive subjects received vitamin C (3 g intravenously in 5 min) or vehicle. Heart rate, noninvasive beat-to-beat blood pressure, and muscle sympathetic nerve activity (microneurography) were monitored at baseline and up to 20 min after the infusion. Spectral analysis of RR interval variability and spontaneous baroreflex sensitivity were also computed. RESULTS: Vitamin C infusion significantly lowered blood pressure in hypertensive patients but not in normotensive subjects (maximal changes in systolic blood pressure: -4.9 ± 10.1 compared with -0.7 ± 4.0 mm Hg, respectively; P < 0.05). Moreover, muscle sympathetic nerve activity was significantly reduced after vitamin C infusion in hypertensive patients (from 53.3 ± 12.2 to 47.4 ± 11.5 bursts/100 heart beats; P < 0.01) but not in healthy subjects (from 42.0 ± 10.1 to 42.7 ± 11.8 bursts/100 heart beats; NS). On the contrary, in 16 hypertensive patients, sodium nitroprusside in equidepressor doses induced a significant increase in muscle sympathetic nerve activity compared with vitamin C (+10.0 ± 6.9 bursts/100 heart beats). Sympathovagal balance and spontaneous baroreflex sensitivity were restored during vitamin C infusion in hypertensive subjects. CONCLUSIONS: These results indicate that acute administration of vitamin C is able to reduce cardiovascular adrenergic drive in hypertensive patients, which suggests that oxidative stress is involved in the regulation of sympathetic activity in essential hypertension.

Am J Clin Nutr. 2012 Aug;96(2):302-8

Effect of vitamin C supplementation on postprandial oxidative stress and lipid profile in type 2 diabetic patients.

Diabetes mellitus is one of the most wide spread endocrine disorders and an important developing health problem in the world. Cardiovascular disease is a common complication of type 2 diabetes. Several risk factors for coronary heart disease cosegregate in type 2 diabetes, including hyperglycemia, hyperlipaemia, increases production of free radical and decrease in antioxidant defense system. In this study we evaluated the effect of vitamin C supplementation on fasting and postprandial oxidative stress and lipid profile in type 2 diabetic patients. 30 patients with type 2 diabetes from Nader Kazemi Clinic, Shiraz, Iran were randomly divided into 2 groups; vitamin C treatment group (1,000 mg d(-1)) and placebo group from May to September 2010. Fasting and postprandial lipid profile and Malondialdehyde (MDA) level were measured at the beginning of the study and after six weeks of supplementation. Data analysis was carried out using Mann-Whitney U test with p < 0.05 being significant by SPSS software version 16. The result of the study showed a significantly decrease in fasting (p = 0.006) and postprandial MDA (p < 0.001) in vitamin C group compare to placebo group but not in lipid profile. This study suggests that vitamin C supplementation can decrease fasting and postprandial oxidative stress and may prevent diabetes complication.

Pak J Biol Sci. 2011 Oct 1;14(19):900-4

Vitamin-C as anti-Helicobacter pylori agent: More prophylactic than curative- Critical review.

Potential of nonantibiotic therapies for treatment of Helicobacter pylori-related acid peptic disease remains underexplored. Several clinical studies have shown that higher prevalence of H. pylori infection is associated with low Vitamin C (Vit C) level in serum and gastric juice. However, there is no consensus regarding the usefulness of Vit C supplementation in the management of H. pylori infection. Surveying the existing literature we conclude that high concentration of Vit C in gastric juice might inactivate H. pylori urease, the key enzyme for the pathogen’s survival and colonization into acidic stomach. Once infection established, urease is not very important for its survival. The role of Vit-C as anti-H. pylori agent in peptic ulcer diseases appears to be preventive rather than curative. Rather than supplementing high dose of Vit C along with conventional triple therapy, it is preferable to complete the conventional therapy and thereafter start Vit C supplementation for extended period which would prevent reinfection in susceptible individuals, provided the patients are not achlorhydric. Further studies are required to prove the role of Vit C in susceptible population.

Indian J Pharmacol.2011 Nov;43(6):624-7

Vitamin C prevents hypogonadal bone loss.

Epidemiologic studies correlate low vitamin C intake with bone loss. The genetic deletion of enzymes involved in de novo vitamin C synthesis in mice, likewise, causes severe osteoporosis. However, very few studies have evaluated a protective role of this dietary supplement on the skeleton. Here, we show that the ingestion of vitamin C prevents the low-turnover bone loss following ovariectomy in mice. We show that this prevention in areal bone mineral density and micro-CT parameters results from the stimulation of bone formation, demonstrable in vivo by histomorphometry, bone marker measurements, and quantitative PCR. Notably, the reductions in the bone formation rate, plasma osteocalcin levels, and ex vivo osteoblast gene expression 8 weeks post-ovariectomy are all returned to levels of sham-operated controls. The study establishes vitamin C as a skeletal anabolic agent.

PLoS One. 2012;7(10):e47058