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Life Extension Magazine

May 9, 2000

National Academy of Sciences References

71. Free Radic Biol Med 2000 Feb 1;28(3):428-36Vitamin C prevents the acute atherogenic effects of passive smoking.Valkonen MM, Kuusi TDepartment of Medicine, University of Helsinki, Helsinki, Finland.

During passive smoking the body is attacked by an excess of free radicals inducing oxidative stress. In nonsmoking subjects even a short period of passive smoking breaks down serum antioxidant defense (TRAP) and accelerates lipid peroxidation leading to accumulation of their low-density lipoprotein (LDL) cholesterol in cultured human macrophages. We now studied whether these acute proatherogenic effects of secondhand smoke could be prevented by an effective free radical scavenger, vitamin C. Blood samples were collected from nonsmoking subjects (n = 10) as they were consecutively exposed to normal air or cigarette smoke during four separate days. During the last 2 d, a single dose of vitamin C (3 g) was given, which doubled its plasma concentration. Vitamin C did not influence the plasma antioxidant defense or the resistance of LDL to oxidation in normal air, but prevented the smoke-induced decrease in plasma TRAP (p <.001), the decrease in the resistance of LDL to oxidation (p <.05), and the accelerated formation of serum thiobarbituric acid reactive substances (TBARS) (p <.05) otherwise observed 1.5 h after the beginning of passive smoking. Vitamin C protected nonsmoking subjects against the harmful effects of free radicals during exposure to secondhand smoke.

72. Microvasc Res 1999 Nov;58(3):305-11A single high dose of vitamin C counteracts the acute negative effect on microcirculation induced by smoking a cigarette.Zhang J, Ying X, Lu Q, Kallner A, Xiu RJ, Henriksson P, Bjorkhem IKarolinska Institutet, Huddinge University Hospital, Huddinge, SE-141 86, Sweden.

Cigarette smoking is associated with marked acute changes in microcirculation including reduced blood flow. We tested the hypothesis that the reduced blood flow velocity is due to the imbalance between prooxidants and antioxidants that occurs as a consequence of smoking and that it can be reduced by an antioxidant. The effect of smoking a single cigarette on nail-fold microcirculation was analyzed in 24 healthy subjects with varying smoking habits. Vital capillary microscopy was used and the blood cell flow velocity in the capillaries was evaluated before and 1-30 min after smoking. Smoking induced a marked decrease in microcirculatory blood flow in 23 of the 24 subjects (40-50% decrease 1-5 min after smoking). This change was reduced by more than 50% in the same subjects after intake of 2 g of vitamin C 2 h before smoking (P < 0.0001 by ANOVA test) with smokers responding similarly to nonsmokers in these experiments. Intake of 1 g of vitamin C had no significant effect on the smoking-induced changes in most of the subjects tested (n = 11). Pretreatment with aspirin had little or no effect on the response to smoking (n = 9). Our results show that treatment with a single high dose of vitamin C can reduce and in some individuals even completely abolish the negative acute effect on microcirculation induced by smoking a single cigarette. This effect of vitamin C is not likely to be mediated by the cyclooxygenase system.

73. Jpn J Physiol 1999 Apr;49(2):159-67Effect of vitamin C and E in modulating peripheral vascular response to local cold stimulus in man at high altitude.Purkayastha SS, Sharma RP, Ilavazhagan G, Sridharan K, Ranganathan S, Selvamurthy WDefence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India.

At high altitude (HA), cold stress is aggravated by hypoxia, perhaps due to the increased formation of free radicals which trigger oxidative stress. This may be one of the contributing factors for adverse effects including disturbances in microcirculation and capillary permeability resulting in decreased peripheral blood flow. This leads to altered cold-induced-vasodilatation (CIVD) response on exposure to HA. The present study was conducted on 40 male volunteers (4 groups of 10 each) to evaluate the utility of supplementation of vitamin C (500 mg/d)and vitamin E (400 mg/d) singly, as well as in combination, in modulating peripheral vascular response by assessing CIVD response under local cold stimulus both at Delhi (200 m) and at HA (3,700 m). On exposure to 3,700 m, decreased CIVD response was observed in all the groups. The responses were better in vitamin supplemented groups, in general, as compared to the placebo group. The best CIVD response was seen in the vitamin C (singly)-treated group. Administration of vitamin C and E together did not result in any additional benefit. Facilitation of CIVD response due to supplementation of vitamin C may be attributed to its (a) antioxidant effect, and (b) major physiological functions of increased metabolism and thermogenic properties, facilitation of collagen synthesis, restoration of intercellular substances and better maintenance of the rheological status of the blood. Hence, vitamin C is effective for improving peripheral blood flow and thereby reduces the incidence of cold injuries during acclimatization or outdoor duties at HA.

74. Am J Cardiol 1996 Feb 1;77(4):237-41Effects of antioxidant vitamins C and E on signal-averaged electrocardiogram in acute myocardial infarction.Chamiec T, Herbaczynska-Cedro K, Ceremuzynski LDepartment of Cardiology, Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.

Experimental studies indicate that oxygen-free radicals contribute to ischemic myocardial damage and affect electric properties of cellular membranes. We hypothesize that an association exists between an oxygen-free radical-induced component of myocardial ischemic injury and altered electric function that underlies the genesis of ventricular late potentials in the course of myocardial infarction. If so, antioxidant vitamins C and E may prevent alterations in the signal-averaged electrocardiogram (SAECG). To test this hypothesis, weinvestigated the effect of supplementation with vitamins C and E on the indices of the SAECG in patients with acute myocardial infarction (AMI). Sixty-one patients with AMI were randomized to receive conventional treatment and vitamins C and E, each 600 mg/day, orally for 14 days (supplemented group, n = 33) or conventional treatment only (control group, n = 28). SAECG was recorded on days 1 or 2 and between days 9 and 13 (mean 10). Serum ascorbic acid, tocopherol, plasma lipid peroxides, and oxygen-free radical production by isolated leukocytes were measured on days 1 or 2 and between days 12 and 14. In thecontrol group, SAECG showed an increase in mean QRS and low-amplitude ( < 40 microV) signal durations, from 99 +/- 10 to 111 +/- 13 ms (p < 0.001) and from 31 +/- 8 to 38 +/- 10 ms (p < 0.001), respectively, and a decrease in the root-mean-square voltage of the last 40 ms of the QRS complex, from 36 +/- 25 to 21 +/- 11 microV (p < 0.002). In vitamin-supplemented patients, all these indices remained unchanged. Oxygen-free radical production by isolated leukocytes was decreased compared with that in controls (p < 0.02). Supplementation was confirmed by elevation of serum ascorbic acid and tocopherol. Results support the hypothesis that in patients with AMI, oxygen-free radical-induced cellular damage contributes to alterations in electric function of the heart as seen on the SAECG.

75. J Am Coll Nutr 1996 Apr;15(2):154-8Ascorbic acid induces a favorable lipoprotein profile in women.Gatto LM, Hallen GK, Brown AJ, Samman S Department of Biochemistry, University of Sydney, NSW, Australia.

OBJECTIVES: The aim of this study was to determine the effect of Ascorbic acid (AA) supplements on plasma lipids and lipoproteins in healthy, young women. METHODS: Ten women were recruited to participate in a randomized double-blind cross-over trial and supplemented with 1000 mg AA daily for 4 weeks, followed by placebo, and vice versa. RESULTS: Plasma AA concentrations were significantly higher at 2 weeks (p < 0.0001) and at 4 weeks (p < 0.001), compared with baseline. Plasma AA levels appeared to peak after 2 weeks of supplementation. Plasma concentrations of LDL-C were found to be 16% lower at 4 weeks compared with baseline (p < 0.05) and although HDL-C levels did not change significantly with AA supplementation, the change in HDL-C was positively associated with the change in plasma AA (p < 0.05). Significant decreases were observed in the total cholesterol (TC) to HDL-C at 2 weeks and LDL-C to HDL-C ratios at 2 and 4 weeks supplementation (p < 0.05). CONCLUSIONS: Our findings agree with those from epidemiological studies and suggest that increases in AA intake may favorably alter the lipoprotein profile in young women.

76. Am J Cardiol 1996 Feb 1;77(4):232-6Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian experiment of infarct survival-3).Singh RB, Niaz MA, Rastogi SS, Rastogi S Heart Research Laboratory, Medical Hospital and Research Centre, Moradabad, India.

In a randomized, double-blind, placebo-controlled trial, the effects of combined treatment with the antioxidant vitamins A (50,000 IU/day), VITAMIN C (1,000 mg/day), vitamin E (400 mg/day), and beta-carotene (25 mg/day) were compared for 28 days in 63 (intervention group) and 62 (placebo group) patients with suspected acute myocardial infarction. After treatment with antioxidants, the mean infarct size (creatine kinase and creatine kinase-MB gram equivalents) was significantly less in the antioxidant group than in the placebo group. Serum glutamic-oxaloacetic transaminase decreased by 45.6 IU/dl in the antioxidant group versus 25.8 IU/dl in the placebo group (p < 0.02). Cardiac enzyme lactate dehydrogenase increased slightly (88.6 IU/dl) in the antioxidant group compared with that in the placebo group (166.5 IU/dl) (p < 0.01). QRS score in the electrocardiogram was significantly less in the antioxidant than in the placebo group. The following levels increased in the antioxidant group versus the placebo group, respectively: plasma levels of vitamin E increased by 8.8 and 2.2 mumol/L (p < 0.01), VITAMIN C increased by 12.6 and 4.2 mumol/L (p < 0.01), beta-carotene increased by 0.28 and 0.06 mumol/L (p < 0.01), and vitamin A increased by 0.36 and 0.12 mumol/L (p < 0.01). Serum lipid peroxides decreased by 1.22 pmol/ml in antioxidant versus 0.22 pmol/ml in the placebo group (p < 0.01). Angina pectoris, total arrhythmias, and poor left ventricular function occurred less often in the antioxidant group. Cardiac end points were significantly less in the antioxidant group (20.6% vs 30.6%, respectively). These results suggest that combined treatment with antioxidant vitamins A, E, C, and beta-carotene in patients with recent acute myocardial infarction may be protective against cardiac necrosis and oxidative stress, and could be beneficial in preventing complications and cardiac event rate in such patients.

77. Ann Med Interne (Paris) 1994;145(1):13-9Effect of VITAMIN C on lipoproteins in healthy adults.Munoz JA, Garcia C, Quilez JL, Andugar MA Department of Internal Medicine, Hospital General y Universitario, Murcia, Spain.

BACKGROUND: It has been suggested that VITAMIN C can modify the composition of lipoproteins in healthy subjects. OBJECTIVE: To determine the possible modification of lipid levels in the presence of VITAMIN C, and the effect of various doses on lipid levels. DESIGN: This is a sequential open clinical trial, where the same individuals are used as their own controls, and where the same observer at random administers 1 or 2 g of oral VITAMIN C during a month, followed by a further month without treatment. PATIENTS: 124 healthy volunteers of both sexes, between 17 and 74 years of age, whose lifestyle was not modified during the study. MEASUREMENT: At the beginning of the study a determination was made of lipid levels, risk factors such as age, physical activity, tobacco and alcohol use, weight and arterial pressure; at the end of the first month during VITAMIN C therapy, and again at the end of the second month without therapy, lipid levels were determined, namely, TG, TC, HDL-C, HDL2-C, HDL3-C, LDL-C, ApoA1, ApoB and Lp(a). RESULTS: After one month of treatment with 2 grams of VITAMIN C, a significant decrease of ApoB was observed, namely, 5.5% in females and 8% in males (p = 0.019). VITAMIN C treatment shows the following differential data: a negative correlation of Lp(a) with HDL3-C, in both sexes; in males, the positive correlation of age with LDL-C and the negative correlation of tobacco with HDL-C disappear, positive correlations appear between physical activity and HDL-C, between tobacco and LDL-C, between weight and ApoB, between SBP and TG, and between DBP and ApoB; in females, the positive correlation between weight and TG, and the negative correlation between weight and HDL-C both disappear, negative correlations appear between physical activity and both TC and ApoB, between weight and HDL3-C, a positive correlation appears between DBP and HDL2-C. Compared to non-drinkers, in males who consume less than 50 grams of alcohol daily, VITAMIN C produces a significant decrease in DHL3-C, while the significant increase in Lp(a) disappears. CONCLUSIONS: From the results in the follow-up of this group of healthy individuals, it can be deduced that VITAMIN C produces a decrease in ApoB in both sexes where 2 g are administered daily. When the risk factors are correlated, the results vary substantially, particularly with reference to the sex of the individuals. Women benefit much more than men from VITAMIN C therapy, especially when physical activity, weight and diastolic blood pressure are considered. Compared to non-drinkers, male drinkers demonstrate a decrease in HDL3-C, and the significant increase in Lp(a) disappears.

78. Am J Cardiol 1996 Dec 1;78(11):1284-6Possible prevention of postangioplasty restenosis by Ascorbic acid.Tomoda H, Yoshitake M, Morimoto K, Aoki N Department of Cardiology, Tokai University, Kanagawa, Japan.

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 in 51 control patients. Thus, Ascorbic acid, a potent natural antioxidant, appeared to be possibly effective in attenuating post-PTCA restenosis.

79. Int J Cardiol 1995 Mar 3;48(3):235-7Mortality and clinical course of patients with acute myocardial infarction treated with streptokinase and antioxidants: mannitol and Ascorbic acid.Laskowski H, Minczykowski A, Wysocki H Department of Cardiology, Regional Hospital, Leszno, Poland.

There is increasing evidence that free radical scavengers limit reperfusion injury in animal experiments. We randomly administered 250 ml 20% mannitol infusion and 10.0 g Ascorbic acid infusion, potent free radical scavengers to 42 patients with acute myocardial infarction receiving streptokinase. A control group of 42 patients received only standard fibrinolytic therapy. We found that additional antioxidant treatment with Ascorbic acid and mannitol decreased the number of some complications of acute myocardial infarction.

80. Ann Nutr Metab 1995;39(4):217-23Magnesium and Ascorbic acid supplementation in diabetes mellitus.Eriksson J, Kohvakka A Malmi Municipal Hospital, Helsinki, Finland.

The effect of magnesium (Mg) and Ascorbic acid (AA) supplementation on metabolic control was assessed in 56 outpatient diabetics. A 90-day run-in period was followed by two 90-day treatment periods, during which Mg (600 mg/day) and AA (2 g/day) were administered in a randomized double-blind cross-over fashion. A decrease in systolic and diastolic blood pressure (132 +/- 3 vs. 138 +/- 4 and 77 +/- 2 vs. 82 +/- 2 mm Hg; p < 0.05) was observed in insulin-dependent diabetes mellitus subjects during Mg supplementation. No beneficial effect of Mg supplementation was observed on glycemic control, lipids or blood pressure in non-insulin-dependent diabetes mellitus (NIDDM) subjects. AA supplementation improved glycemic control among NIDDM subjects and both fasting blood glucose (9.1 +/- 0.5 vs. 10.1 +/- 0.6 mmol/l; p < 0.05) and HbA1c (8.5 +/- 0.3 vs. 9.3 +/- 0.3%; p < 0.05) improved. Beneficial effects of AA supplementation on cholesterol (5.9 +/- 0.2 vs. 6.2 +/- 0.2 mmol/l; p < 0.05) and triglycerides (2.2 +/- 0.2 vs. 2.5 +/- 0.2; p < 0.05) were also observed in NIDDM subjects. The results suggest that high-dose AA supplementation may have a beneficial effect in NIDDM subjects on both glycemic control and blood lipids.