Vitamin C: Fact and fiction. The human studies (in vivo)!!

**Big_r** · 11-08-2005, 11:32 PM

CONTENT:
-Vitamine C in exercise.
The majority of studies show a positive effect from vit C on exercise.
-Vitamin C and the immune system
The majority of studies show a positive effect from vit C (sometimes in synergy with other substances/antioxidants on the immune system)
-Vitamin C and the liver
Vitamine C only or combined with vit E may be beneficial for treating various forms of liver stress.
-Vitamin C and the heart.
The majority of studies show no- or a minor significant positive effect from vit C on CHD, but vit C may be of value for some specific heart problems.
-Other interesting studies
-Side effects
No side effects from vitamin C (except for possible gastrointestinal upset) are reported in doses up to 2 (possibly 4) g. There is no clear establishment of vit C as a possible risk factor for calcium oxalate stones. Furthermore vit C does not show pro-oxidant effects (at least in doses up to 5 g) in human in vivo studies.
Vitamin E supplementation in doses higher than those used in multivitamine pills may have a negative impact on vascular disorders.
Vitamin A should be avoided by people with liver disorders.
Vitamin supplementation by pregant women is discouraged.

VITAMIN C IN EXERCISE

A)Studies showing an adverse effect from vit C on exercise (1x).
B)Studies showing no effect from vit C on exercise (4x).
C)Studies showing a positive effect from vit C on exercise (6x).
D)Studies showing an adverse effect from vit C + other antioxidants on exercise (1x).
E)Studies showing no effect from vit C + other antioxidants on exercise (3x).
F)Studies showing a positive effect from vitamine C + other antioxidants on exercise (8x).

A)Studies showing an adverse effect from vit C on exercise:

Influence of vitamin C supplementation on oxidative and salivary IgA changes following an ultramarathon. = probably the same study as:
Influence of vitamin C supplementation on oxidative and immune changes after an ultramarathon.
500 mg vit C supplemented 3 times/day for 7 weeks prior to an ultramarathon in 15 subjects. During the race, runners received 1 l/h carbohydrate beverages (60 g/l) with vitamin C (150 mg/l) or without in a double-blinded fashion.
No significant correlations were found between post-race plasma vitamin C, oxidative, and saliva measures, except for a positive correlation between post-race serum cortisol and serum vitamin C (r=0.50, P=0.006) (Note from author: there was no difference in serum cortisol during the marathon after 32 km between the vit C and placebo group > http://jap.physiology.org/cgi/conten...l/92/5/1970/T3) (A502).

B)Studies showing no effect from vit C on exercise:

Vitamin C supplementation does not alter the immune response to 2.5 hours of running.
1000 mg vit C for 8 days in experienced marathon runners had no significant effect on cortisol and catecholamines; leukocyte subsets; interleukin-6; natural killer cell activity; lymphocyte proliferation as induced by concanavalin A, phytohemagglutinin, and pokeweed mitogen; and granulocyte ****ocytosis and activated oxidative burst (A509).

Prolonged vitamin C supplementation and recovery from eccentric exercise.
200 mg vit C 2x/day for 14 days before (and 3 d after) 30 min. downhill running does not decrease muscle soreness and muscle damage (creatine kinase activity and myoglobin concentration), and interleukin-6 concentrations (A517).

Post-exercise vitamin C supplementation and recovery from demanding exercise.
200 mg vit C following an unaccustomed bout of exercise, followed by an additional 200 mg later that day + 2x/day for the following 2 days did not improve recovery. Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation (A519).

Muscle soreness and damage parameters after prolonged intermittent shuttle-running following acute vitamin C supplementation.
Nine habitually active males consumed 1 g vit C 2 h before a 90 min intermittent shuttle-running test, and on another occasion consumed an identical placebo.
Muscle soreness, and markers of both muscle damage (creatine kinase and aspartate aminotransferase) and lipid peroxidation (malondialdehyde) were elevated to an equal extent after exercise in placebo and supplemented trials (A524).

**Big_r** · 11-08-2005, 11:33 PM

C)Studies showing a positive effect from vit C on exercise:

Prolonged vitamin C supplementation and recovery from demanding exercise.
200 mg vit C 2 x/day 14 days prior to a 90 min. unaccustomed shuttle run in 8 subjects: Post-exercise serum creatine kinase activities and myoglobin concentrations were unaffected by supplementation. However, vitamin C supplementation had modest beneficial effects on muscle soreness, muscle function, and plasma concentrations of malondialdehyde. Furthermore, although plasma interleukin-6 increased immediately after exercise in both groups, values in the VC group were lower than in the P group 2 hours after exercise (p < .05) (A504).

Vitamin C supplementation attenuates the increases in circulating cortisol, adrenaline and anti-inflammatory polypeptides following ultramarathon running.
The study demonstrates an attenuation, albeit transient, of both the adrenal stress hormone and anti-inflammatory polypeptide response to prolonged exercise in runners who supplemented with 1500 mg vitamin C per day when compared to < or = 500 mg per day (for 7 days before the race)(A505).

Attenuation of increase in circulating cortisol and enhancement of the acute phase protein response in vitamin C-supplemented ultramarathoners.
500 mg vit C 2 x/day for 7 days in 10 ultramarathon athletes significantly increased C-reactive protein and decreased cortisol by 30% post race (A507).

Influence of vitamin C supplementation on cytokine changes following an ultramarathon.
500 mg vit C (10 subjects) or 1500 mg (12 subjects) for 7 days before an ultramarathon: Cortisol increased in all groups immediately after the race but significantly less in the vit C-1500 group. Runners experienced strong increases in concentrations of plasma IL-6, IL-10, IL-1RA, and IL-8. These increases were attenuated in runners ingesting 1500 mg but not 500 mg vitamin C (A508).

An effect of ascorbic acid on delayed-onset muscle soreness.
Delayed-onset muscle soreness following strenuous use of the posterior calf muscles was studied to determine if ascorbic acid might have an effect on the appearance of this familiar pain. A double-blind, randomized, crossover study compared the soreness in subjects taking ascorbic acid against those taking a lactose placebo. Visual analog scales were used in conjunction with a variety of pain-challenging methods, and the results indicated a significant difference between experimental and placebo groups at the height of soreness. Typical soreness abatement scores of 25-44% were observed. A sample size of 19, lack of an untreated control group as well as the singular nature of the exercise and its intensity were considered limitations of the study (A529).

Exercise-induced endotoxemia: the effect of ascorbic acid supplementation.
Strenuous short-term aerobic exercise results in significant increases in plasma LPS levels (endotoxemia) together with increases in markers of oxidative stress. Supplementation with ascorbic acid (1000 mg), however, abolished the increase in LPS and nitrite but led to a significant increase in the ascorbate radical in plasma (A539).

D)Studies showing an adverse effect from vit C + other antioxidants on exercise

Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise.
There has been no investigation to determine if the widely used over-the-counter, water-soluble antioxidants vitamin C and N-acetyl-cysteine (NAC) could act as pro-oxidants in humans during inflammatory conditions. We induced an acute-phase inflammatory response by an eccentric arm muscle injury. The inflammation was characterized by edema, swelling, pain, and increases in plasma inflammatory indicators, myeloperoxidase and interleukin-6. Immediately following the injury, subjects consumed a placebo or vitamin C (12.5 mg/kg body weight) and NAC (10 mg/kg body weight) for 7 d.
Lactate dehydrogenase, creatine kinase, lipid hydroperoxides and 8-Iso-PGF2alpha were elevated to a greater extent in the vitamin C and NAC group.
This acute human inflammatory model strongly suggests that vitamin C and NAC supplementation immediately post-injury, transiently increases tissue damage and oxidative stress (A522).

**BringnIt** · 11-08-2005, 11:34 PM

http://www.fasebj.org/cgi/content/full/13/9/1007

**Big_r** · 11-08-2005, 11:35 PM

E)Studies showing no effect from vit C + other antioxidants on exercise:

Effect of Vitamin C and E supplementation on biochemical and ultrastructural indices of muscle damage after a 21 km run.
Vitamin C and E supplementation (500 or 1000 mg or IU per day) for four weeks does not reduce either biochemical or ultrastructural indices of muscle damage in experienced runners after a half marathon(A520).

Effect of vitamin supplementation on cytokine response and on muscle damage after strenuous exercise.
Twenty male recreational runners randomly received either antioxidants (500 mg of vitamin C and 400 mg of vitamin E) or placebo for 14 days before and 7 days after a 5% downhill 90-min treadmill run. The two groups showed identical exercise-induced changes in cytokine, muscle enzyme, and lymphocyte subpopulations. The plasma level of interleukin (IL)-6 and IL-1 receptor antagonist increased 20- and 3-fold after exercise. The plasma level of creatine kinase was increased sixfold the day after exercise(A523).

No effect of antioxidant supplementation in triathletes on maximal oxygen uptake, 31P-NMRS detected muscle energy metabolism and muscle fatigue.
Seven male triathletes received daily oral antioxidant supplementation in capsule form including 100 mg coenzyme Q10 (CoQ10), 600 mg ascorbic acid and 270 mg alpha-tocopherol or placebo over a 6-week interval.
The results demonstrate no effect of antioxidative vitamin supplementation on maximal oxygen uptake, muscle energy metabolism or muscle fatigue in triathletes (A525).

F)Studies showing a positive effect from vitamine C + other antioxidants on exercise:

Supplementation with vitamins C and E inhibits the release of interleukin-6 from contracting human skeletal muscle
Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 (IL-6).
Supplementation of vitamins C (500 mg/d) and E (400 i.u./d) for 28 days to 7 healthy men attenuated the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from the contracting skeletal muscle per se. Plasma interleukin-1 receptor antagonist (IL-1ra), C-reactive protein and cortisol levels all increased after the exercise in Control, but not in Treatment (A501).

Effects of alpha-tocopherol, beta-carotene and ascorbic acid on oxidative, hormonal and enzymatic exercise stress markers in habitual training activity of professional basketball players.
600 mg alpha-tocopherol, 1000 mg vit C, and 32 mg beta-carotene for 35 days in 13 professional basketball players decreases plasma lipid peroxides by 27.7%. A significant decrease of lactate dehydrogenase serum activity was observed during the 24 h recuperation time. During this time the anabolic/catabolic balance increased about 29.8% in the antioxidant supplemented group, although this increase did not reach statistical significance (A506).

Effects of dietary supplementation with vitamins C and E on muscle function during and after eccentric contractions in humans.
500 mg of vitamin C and 1,200 IU of alpha-tocopherol/day for 37 days in 12 volunteers: After 30 days of treatment, volunteers performed 300 maximal eccentric contractions of the knee extensor muscles of one leg.
Prior supplementation with dietary antioxidants ameliorates muscle functional decrements subsequent to eccentric muscle contraction. Both groups experienced similar significant muscle soreness and swelling after exercise (A515).

Effects of antioxidant therapy in women exposed to eccentric exercise.
18 women randomized to antioxidants or placebo before a bout of eccentric exercise: Antioxidants attenuated the creatine kinase activity and muscle soreness responst to the EE, with little impact on maximal isometric force and range of motion (A516).

Antioxidant supplementation preserves antioxidant response in physical training and low antioxidant intake.
An antioxidant mixture (Se 150 microg, retinyl acetate mg, ascorbic acid 120 mg, alpha-tocopheryl succinate 20 mg) for 7 thriathletes (10 control subjects) in a controlled double blind study alleviated muscle damage during 4 weeks of overloaded training followed by 4 weeks of normal training. The effects of the antioxidant mixture were observed for doses that can be provided by a diversified and well-balanced diet (A518).

Lipid peroxidation and antioxidative vitamins under extreme endurance stress.
A randomized and placebo-controlled study on 24 trained long-distance runners substituted with alpha-tocopherol (400 I.U. d-1) and vit C (200 mg d-1) during 4.5 weeks prior to a marathon race.
The increase of CK serum concentration is remarkably lower in the supplemented group compared with the placebo group (P < 0.01) (A526).

Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults.
21 men reveived 800 IU dl-alpha-tocopherol or placebo for 48 days before a bout of eccentric exercise in a double blind protocol.
The alterations in fatty acid composition, vitamin E, and lipid conjugated dienes in muscle and in urinary lipid peroxides in controls after eccentric exercise are consistent with the concept that vitamin E provides protection against exercise-induced oxidative injury (A527).

Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise.
24 physically young subjects ingested either placebo (n=8), Vit E (400 mg; n=8) or vit C (400 mg; n=8) for 21 days prior to and for 7 days after performing 60 min of box-stepping exercise.
Compared to the placebo group no significant changes in MVC were observed immediately post-exercise, though recovery of MVC in the first 24 h post-exercise was greater in the group supplemented with vitamin C. The decrease in 20/50 Hz ratio of tetanic tension was significantly less (P < 0.05) post-exercise and in the initial phase of recovery in subjects supplemented with vitamin C but not with vitamin E. These data suggest that prior vitamin C supplementation may exert a protective effect against eccentric exercise-induced muscle damage (A528).

**Big_r** · 11-08-2005, 11:36 PM

VITAMIN C AND THE IMMUNE SYSTEM

A)Vitamin C only
B)Positive synergistic actions between vit C + other antioxidants
A combination of vitamin C + E seems to:
1)Improve immune function in aged women.
2)Inhibit lipoperoxidation (2 studies).
3)Have some preventive effect on an experimental influenza virus infection in mice.
A combination of vitamin C + phytoestrogens seems to:
Show stronger antioxidant activity on LDL oxidation in vitro (2 studies).
A combination of vitamin C + citrus extract seems to:
Increase the lag time of lipoprotein oxidation in vitro and in vivo.
A combination of vitamin C + 17 beta-estradiol seems to:
Inhibit LDL oxidation.
A combination of vitamin C, E, beta carotene and penicillin seems to:
Decrease immunological abnormalities more effectively.
C)Negative synergistic effects
Adding vitamin E to vitamine C seems to:
Show an adverse effect on respiratory tract infections in elderly.
Vitamin C seems to:
Be able to reduce the action of some medicines.

A)Vitamin C only:

Relation of serum ascorbic acid to Helicobacter pylori serology in US adults: the Third National Health and Nutrition Examination Survey.
Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82-0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12-0.79, p < 0.05).
Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites (A315).

Correlation between Helicobacter pylori infection and vitamin C levels in whole blood, plasma, and gastric juice, and the pH of gastric juice in Korean children.
During a 5-year period, multiple gastric antral biopsies were taken from 452 children who underwent gastroduodenoscopy.
Vitamin C levels in whole blood, plasma, and gastric juice exhibited significant negative correlation with the age of patients, the histologic density of H. pylori, the degree of active and chronic gastritis, and the severity of H. pylori infection (A316).

**Big_r** · 11-08-2005, 11:37 PM

B)Positive synergistic actions between vit C + other antioxidants:

Immune function in aged women is improved by ingestion of vitamins C and E.
30 women (10 healthy, 10 with major depression disorders, and 10 with coronary heart disease were administered 1 g vit C and 200 mg vit E/day for 16 weeks.
Intake of vitamins resulted in a significant increase in the lymphoproliferative capacity and in the ****ocytic functions of PMN neutrophils as well as in a significant decrease of serum levels of lipid peroxides and cortisol, both in the healthy aged women and in the aged women with MDD or CHD. These findings suggest an important role of antioxidant supplementation in the improvement of immune function in aged females as well as in the prevention and treatment of specific diseases associated with age that are quite prevalent in the developed countries (A301).

Inhibitory capacity of human serum on induced micro****l lipoperoxidation.
Ten volunteers were supplemented with 400 mg of vitamin E and 1 g of vitamin C/daily for 2 weeks. Their serum inhibitory capacity increased in 12% (p < 0.05). The serum inhibitory capacity for micro****l lipoperoxidation is described herein, and we propose its utilization as an index to determine the individual nonspecific antioxidative defenses against free radical injury and lipoperoxidation in relation to exposure to air pollutants, tobacco smoke, and several acute and chronic diseases, including the hypoxia-reperfusion phenomena (A309).

[Experimental and clinical assessment of antioxidant efficacy of multicomponent antioxidant medication]
The study was made of kinetic parameters of copper-initiated free radical oxidation (FRO) of low density lipoproteins (HDLP) in human blood plasm, antioxidant potential of rat liver and myocardium, the level of FRO products in HDLP and activity of glutathione peroxidase in erythrocytes of 31 males aged 40-64 years with coronary heart disease (CHD).
An antioxidant action of the combinations alpha-tocopherol+ascorbic acid and alpha-tocopherol+beta-carotin was much more potent than that of each of the component alone.
A complex of antioxidant vitamins and selenium given to CHD patients for 2 months, sharply reduced the amount of FRO primary and secondary products in blood plasm LDLP in growing activity of erythrocytic selenium-containing glutathione peroxidase (A310).

Effect of vitamin E and vitamin C combination on experimental influenza virus infection.
Male mice (ICR), infected with influenza virus A/2/68/(H3N2) (1.5 of LD(50)), were administered single once-daily doses of vitamin E (60 mg/kg b.w.) and vitamin C (80 mg/kg b.w.) intraperitoneally (3 days before virus inoculation).
The preventive effect of vitamin E was stronger than the effect of vitamin C, but the combination (vitamin E + C) had the strongest effect. The superior protective effect of the combination is probably due to vitamin C's repairing effect on vitamin E's tocopheroxyl radical (A318).

Soy and alfalfa phytoestrogen extracts become potent low-density lipoprotein antioxidants in the presence of acerola cherry extract.
Copper-mediated LDL oxidation was inhibited in the presence of soy and alfalfa extracts, and this effect was further enhanced in the presence of acerola cherry extract, which is rich in ascorbic acid. Male rabbit aortic endothelial cells pretreated with soy extract were resistant to the toxic effects of high levels of LDL and LDL(-), and a lesser, but significant protection, was also afforded by alfalfa extract. Cell-mediated oxidation of LDL, measured by LDL(-) formation, was inhibited in the presence of soy extract but not alfalfa extract. However, in the presence of acerola cherry extract, both soy and alfalfa extracts potently inhibited the formation of LDL(-). These findings show that acerola cherry extract can enhance the antioxidant activity of soy and alfalfa extracts in a variety of LDL oxidation systems. The protective effect of these extracts is attributed to the presence of flavonoids in soy and alfalfa extracts and ascorbic acid in acerola cherry extract, which may act synergistically as antioxidants (A305).

Synergistic inhibition of LDL oxidation by phytoestrogens and ascorbic acid.
Increasing levels of genistein, daidzein, and equol inhibited LDL oxidation, and this inhibitory effect was further enhanced in the presence of ascorbic acid. The synergism exhibited by these compounds is of clinical importance to phytoestrogen therapy since the efficacy of phytoestrogens as effective antioxidants is evident at concentration well within the range found in the plasma of subjects consuming soy products (A307).

In Vitro and In Vivo Lipoprotein Antioxidant Effect of a Citrus Extract and Ascorbic Acid on Normal and Hypercholesterolemic Human Subjects.
In a double-blind, placebo-controlled study with 26 normal and hypercholesterolemic subjects, the citrus extract and vitamin C, but not vitamin C or vitamin E alone, significantly lowered triglycerides. The combination of citrus extract and vitamin C increased the lag time of lipoprotein oxidation, compared with vitamin C alone or a placebo, and was a significantly better antioxidant than vitamin E. These results and other published studies are highly suggestive of in vitro and in vivo antioxidant synergism between citrus extract and vitamin C (A306).

Ascorbic acid enhances 17 beta-estradiol-mediated inhibition of oxidized low density lipoprotein formation.
The enhanced activity of E(2) in the presence of ascorbate indicates that the antioxidant and antiatherosclerosis activity of E(2) may occur at concentrations within the physiological range (A308).

Immunological response to antioxidant vitamin supplementation in rural Bangladeshi school children with group A streptococcal infection.
Treatment by antioxidant vitamins (beta carotene, alpha tocopherol and ascorbic acid) plus penicillin is more effective in decreasing immunological abnormalities in GABHS infected children then penicillin alone (A314).

Antioxidant activity of dietary fruits, vegetables, and commercial frozen fruit pulps.
Fruits, vegetables, and commercial frozen pulps (FP) consumed in the Brazilian diet were analyzed for antioxidant activities using two different methods, one that determines the inhibition of copper-induced peroxidation of liposome and another based on the inhibition of the co-oxidation of linoleic acid and beta-carotene.
Some samples showed pro-oxidant activity in the liposome system coincident with a low antioxidant activity in the beta-carotene system. There was no relationship between total phenolics content, vitamin C, and antioxidant activity, suggesting that the antioxidant activity is a result of a combination of different compounds having synergic and antagonistic effects (A311).

**Big_r** · 11-08-2005, 11:39 PM

Treatment of chronic hepatitis C virus infection via antioxidants: results of a phase I clinical trial]
Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks.
A combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted (A312).

Antioxidant vitamins improves hemoglobin level in children with group a beta hemolytic streptococcal infection.
Hemoglobin level increases after antioxidant vitamin supplementation (8 weeks) in 606 children suffering from group A beta hemolytic streptococcal infection (A317).

C)Negative synergistic effect:

Vitamin C and E supplements to lansoprazole-amoxicillin-metronidazole triple therapy may reduce the eradication rate of metronidazole-susceptible Helicobacter pylori infection.
Adding vitamin C and E (250 mg + 200 mg, 2x/day) to triple therapy (lansoprazole, amoxicillin, metronidazole) cannot improve the H. pylori eradication rate and gastric inflammation. For patients with metronidazole susceptible strain infection, adding these vitamins may even reduce the eradication rate of triple therapy (A319).

Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial.
Neither daily multivitamin-mineral supplementation at physiological dose nor 200 mg of vitamin E showed a favorable effect on incidence and severity of acute respiratory tract infections in well-nourished noninstitutionalized elderly individuals. Instead we observed adverse effects of vitamin E on illness severity (A320).

**Big_r** · 11-08-2005, 11:40 PM

VITAMIN C AND THE LIVER

A)Vitamin C only
4 Studies showing a positive effect of vit C during liver stress.
B)Vitamin C + E
3 Studies showing a positive effect from combined vit C + E on liver stress.
B)Vitamin C + other antioxidants
3 Studies showing a positive effect from various antioxidants on the liver.
2 Studies showing no (positive nor negative) effect from mixed antioxidants on the liver.

A)Vitamin C only:

Vasoconstrictor hyporeactivity can be reversed by antioxidants in patients with advanced alcoholic cirrhosis of the liver and ascites.
Nine patients with liver cirrhosis Child-Pugh grade C and nine healthy age-matched volunteers.
In patients with cirrhosis, the reactivity to norepinephrine and angiotensin II was markedly reduced (p < .05 vs. controls). Coadministration of vitamin C completely restored the potency of vasoconstrictors to that in controls but had no effect in healthy subjects (A401).

Estimation of the functional reserve of the human liver by urinary D-glucaric acid excretion after vitamin C administration.
The excretion of D-glucaric acid in the urine (uGA) correlates with the total liver content of hepatic cytochrome P-450, the metabolism of which depends on adenosine triphosphate (ATP) being produced by intrahepatic cellular mitochondria. Five cases of compensated liver cirrhosis group with less than 0.4 mg/kg/min of the maximum removal rate of indocyanine green (ICGR max), and 5 cases with normal hepatic function (control group), were monitored for uGA before and after P-450 activation induced by administration of 1 g of vitamin-C. Before vitamin-C administration, no differences in uGA excretion were observed comparing the cirrhosis with the control group. After administration of vitamin-C, the excretion of uGA was significantly lower in the cirrhosis group. The measurement of uGA is considered to represent vitamin-C induced activation by P-450, and is a new method for evaluation of the functional reserve of the liver (A414).

Antioxidant levels in peripheral blood, disease activity and fibrotic stage in chronic hepatitis C.
Glutathione was an independent negative predictor of portal/periportal inflammation (P = 0.02) and fibrosis (P = 0.01). Vitamin C was an independent negative predictor of fibrosis stage (P = 0.02). Antioxidant intake was associated with higher vitamin C (P < 0.0001) and vitamin E (P = 0.005) levels, but not glutathione.
Whole blood glutathione and plasma vitamin C are negatively associated with hepatic portal/periportal inflammation and fibrosis stage in chronic hepatitis C (A402).

Supplementation of antioxidants prevents oxidative stress during a deep saturation dive.
A deep saturation dive (400 msw) decreases cholesterase activity, being highly suggestive of liver dysfunction.
600 mg of vitamin C, 150 mg of alpha-tocopherol, and 600 mg of tea catechins per day appeared to prevent a hepatic disturbance (A403).

**Big_r** · 11-08-2005, 11:41 PM

B)Vitamin C + E

Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis.
1000 iu vit E + 1000 mg vit C/day for 6 months in 45 patients with nonalcoholic steatohepatitis did not show any significant side effects.
Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment (A405).

Antioxidant capacity in Fasciola hepatica patients before and after treatment with triclabendazole alone or in combination with ascorbic acid (vitamin C) and tocofersolan (vitamin E).
Vitamin C (1000 mg/day) and vitamin E (600 mg/day) for 2 months in fasciola hepatica patients significantly improves of SOD and GPX activities and in lipid peroxide levels triclabendazole treatment(A408).

[Antioxidants in the treatment of cholelithiasis patients]
Complex administration of ascorbic acid and alpha-tocopherol was shown to improve the liver function in 157 patients operated upon for cholelithiasis (A411).

C)(Vitamin C +) other antioxidants:

[Antioxidants in liver protection]
Combined antioxidant treatment is more favourable compared with monotherapy, because antioxidants have scavenger-, compartment- and tissue-specificity and they regenerate each other directly, too. Beside their antioxidant property they may also directly regulate many important processes, e.g. cell cycle. We have some favourable results with regard combined antioxidant therapy of liver disease of different etiology (A404).

Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States.
We analyzed the associations of serum iron measures and antioxidant concentrations with abnormal serum alanine transaminase (ALT) activity in a large, national, population-based study (13,605 adult participants). The risk for apparent liver injury was associated with increased iron and decreased antioxidants, particularly carotenoids (A406).

**Big_r** · 11-08-2005, 11:42 PM

..

Oral antioxidant supplementation for fatigue associated with primary biliary cirrhosis: results of a multicentre, randomized, placebo-controlled, cross-over trial.
We have previously reported, in an uncontrolled trial, an improvement in fatigue scores in patients with primary biliary cirrhosis given oral antioxidant supplementation. We now present data from a controlled trial.
Antioxidant supplementation (vitamins A, C and E, selenium, methionine and ubiquinone) for 12 weeks in 61 patients with primary biliary cirrhosis-associated fatigue does not show any significant changes in fatigue. Neither medication was associated with improvement in any other symptoms related to primary biliary cirrhosis. Adverse effects were more common during active therapy and were mild and self-limiting (A407).

[The role of alpha-tocopherol and retinol in correcting disorders of lipid peroxidation in patients with malignant liver neoplasms]
Treatment with alpha-tocoferol (600 mg), retinol (100,000 MU) and ascorbic acid (1.5 g) for 7 days before surgery was found to significantly reduce dialdehyde level in the liver. Also, the catalase level increased. Treatment with alpha-tocoferol and retinol resulted in their selective accumulation in the liver. No changes in lipid peroxidation or accumulation of alpha-tocoferol in tumor were recorded. Purulent and septic complications were 1.6 times less frequent after preoperative antioxidant treatment than in controls. It is recommended that said antioxidant treatment should be used to correct lipid peroxidation and to improve the effectiveness of therapy of liver cancer (A412).

The effect of antioxidant supplementation on a serum marker of free radical activity and abnormal serum biochemistry in alcoholic patients admitted for detoxification.
Alcoholics admitted for detoxification were entered into a double blind placebo controlled trial of oral supplementation with an antioxidant cocktail (vitamin E, beta carotene, vitamin C and selenium). There was no effect of this supplementation on the rate of resolution of a serum marker of free radical activity and abnormal serum biochemistry (A413).

**Big_r** · 11-08-2005, 11:43 PM

VITAMINE C AND THE HEART

Sorry, vitamine C does not seem to have a significant positive effect on CHD, but it may be beneficial for some specific heart problems.

A)Studies showing no benefit (nor adverse effect) from vit C on the heart.
B)Studies showing a positive effect from vit C on the heart.
C)Studies showing no beneficial (nor adverse) effect from vit C + other antioxidants on the heart
D)Studies showing a positive effect from vitamine C + other antioxidants on the heart

A)Studies showing no benefit (nor adverse effect) from vit C on the heart:

Vitamin C is not associated with coronary heart disease risk once life course socioeconomic position is taken into account: prospective findings from the British Women's Heart and Health Study.
4286 british women (60-79 years) were followed up for 4 years:
Full adjustment for life course socioeconomic position, adult risk factors, leg length and forced expiratory volume in one second resulted in a hazard ratio of 0.95 (95% CI 0.85 to 1.05). A stratified analysis found that the hazard ratio among those with 0-4 adverse indicators was 0.89 (95% CI 0.76 to 1.02) and among those with 5-10 adverse indicators it was 0.95 (95% CI 0.83 to 1.09).
When life course socioeconomic position was taken into account, either in multivariable models or by stratified analysis, there was no association between vitamin C and CHD (A203).

Cardiovascular effects of oral Supplementation of vitamin C, E and folic acid in young healthy males.
An antioxidant mix (1000 mg vit C, 800 mg vit E, and 10 mg folate) for healthy men (n=14) or placebo (n=17) shows a significant decrease (p = 0.03) in systolic blood pressure in the experimental group. No statistically significant changes were observed within other cardiovascular variables of the experimental group, but possible beneficial decreases in diastolic blood pressure and increases in arterial compliance after 12 weeks of vitamin supplementation were indicated. In conclusion, beneficial effects of antioxidants and folate were observed probably because the supplementation was used by young healthy subjects under carefully controlled conditions (A209).

Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men.
The adverse changes in large elastic artery compliance and central BP with aging in healthy men are not 1). mediated by ascorbic acid-sensitive oxidative stress (infusion experiments) and 2). affected by short-term, moderate daily ascorbic acid (vitamin C) supplementation (A213).

Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure.
Acute intravenous (2g), but not chronic oral, vitamin C (4g/day for 4 weeks) improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects (A219).

**Big_r** · 11-08-2005, 11:44 PM

..

Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality.
During a follow-up of 5.5 years in 83 639 male physicians residing in the United States who had no history of CVD or cancer, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality.
For vitamin E use, the relative risks (RRs) were 0.92 (95% confidence interval [CI], 0.70-1.21) for total CVD mortality and 0.88 (95% CI, 0.61-1.27) for CHD mortality; for use of vitamin C, the RRs were 0.88 (95% CI, 0.70-1.12) for total CVD mortality and 0.86 (95% CI, 0.63-1.18) for CHD mortality; and for use of multivitamin supplements, the RRs were 1.07 (95% CI, 0.91-1.25) for total CVD mortality and 1.02 (95% CI, 0.83-1.25) for CHD mortality (A222).

Vitamin C and the risk of acute myocardial infarction.
A low plasma concentration of vitamin C was not associated with an increased risk of acute myocardial infarction (AMI). The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response (A243).

Effects of a 'healthy' diet and of acute and long-term vitamin C on vascular function in healthy older subjects.
A 'Mediterranean-type' diet rich in vitamin C improves vascular function. Neither acute intra-arterial nor sustained administration of oral vitamin C (1 g/day for 6 weeks) improves vascular function in healthy older subjects (A245).

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.
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).
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).
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 (A247).

**Big_r** · 11-08-2005, 11:46 PM

B)Studies showing a positive effect from vit C on the heart:

Improvement of sympathetic response to exercise by oral administration of ascorbic acid in patients after myocardial infarction.
2 g vit C before exercise improved exercise capacity through enhancement of the heart rate and norepinephrine response to exercise in 21 male patients after myocardial infarction (A202).

Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation.
Vitamin C reduces the early recurrence rates after cardioversion of persistent arterial fibrillation and attenuates the associated low-level inflammation (A204).

Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease, ischemic, and dilated cardiomyopathy.
Endothelial dysfunction has been described in patients with coronary artery disease (CAD) or chronic heart failure (CHF). Vitamin C administration leads to an improvement of endothelial function by reducing elevated levels of reactive oxygen species.
Acute vitamin C administration restored peripheral endothelial function in patients with CAD to normal values, whereas endothelial function remained attenuated in CHF, in particular in patients with DCM. These results suggest that in patients with CHF, factors other than oxidative stress (eg, cytokines) contribute to the pathologic endothelial function (A216).

Vitamin C and risk of coronary heart disease in women.
85,118 female nurses were followed up for 16 years for the development of incident CHD (nonfatal myocardial infarction and fatal CHD).
We observed a modest significant inverse association between total intake of vitamin C and risk of CHD (relative risk [RR] = 0.73; 95% confidence interval [CI] 0.57 to 0.94). Among women who did not use vitamin C supplements or multivitamins, the association between intake of vitamin C from diet alone and incidence of CHD was weak and not significant (RR = 0.86; 95% CI 0.59 to 1.26) (A217).

Influence of vitamin C on baroreflex sensitivity in chronic heart failure.
Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF-dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF-related endothelial damage.
Acute administration of vitamin C at high doses improves baroreflex sensitivity and vagal sinus modulation in patients with CHF (A218).

Vitamin C preserves endothelial function in patients with coronary heart disease after a high-fat meal.
The postprandial state after a high-fat meal is critical in atherogenesis, as it induces endothelial dysfunction through an oxidative stress mechanism. Vitamin C treatment has a promising benefit for patients with CHD (A224).

**Big_r** · 11-08-2005, 11:47 PM

..

Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria.
Vitamin C ameliorates endothelial dysfunction in patients with homocystinuria, independent of changes in homocysteine concentration and should therefore be considered as an additional adjunct to therapy to reduce the potential long-term risk of atherothrombotic disease (A225).

Vitamin C inhibits endothelial cell apoptosis in congestive heart failure.
To assess EC protection by vitamin C in CHF patients, we prospectively randomized CHF patients in a double-blind trial to vitamin C treatment versus placebo. Vitamin C administration to CHF patients markedly reduced plasma levels of circulating apoptotic microparticles to 32+/-8% of baseline levels, whereas placebo had no effect (87+/-14%, P<0.005). In addition, vitamin C administration suppressed the proapoptotic activity on EC of the serum of CHF patients (P<0.001). CONCLUSIONS: Administration of vitamin C to CHF patients suppresses EC apoptosis in vivo, which might contribute to the established functional benefit of vitamin C supplementation on endothelial function (A228).

Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. European Prospective Investigation into Cancer and Nutrition.
We prospectively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes, and to cardiovascular disease, ischaemic heart disease, and cancer in 19 496 men and women aged 45-79 years.
Plasma ascorbic acid concentration was inversely related to mortality from all-causes, and from cardiovascular disease, and ischaemic heart disease in men and women. Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile (p<0.0001). The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations. 20 micromol/L rise in plasma ascorbic acid concentration, equivalent to about 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality (p<0.0001).
Ascorbic acid was inversely related to cancer mortality in men but not women (A231).

Comparison of antioxidant efficacy of vitamin E, vitamin C, vitamin A and fruits in coronary heart disease: a controlled trial.
A randomized controlled trial in 175 patients with CHD: Lipid peroxide levels decreased significantly in all the treatment groups (p < 0.01). This decrease was the highest in Group II (vitamin E; -36.4 +/- 17.7%) as compared to Group III (vitamin C -19.8 -/+ 10.8%); Group IV (vitamin A -5.4 +/- 17%) and Group V (fruits -13.1 +/- 12.0%).
All the antioxidant vitamins and fruits significantly decrease lipid peroxide levels and oxidant load in CHD patients. However, fruits are the best choice as they also favourably modify the lipid profile (A232).

Acute methionine loading does not alter arterial stiffness in humans.
8 healthy men were studied on 3 occasions in a double blind, double dummy, randomized order.
These data reinforce evidence that vitamin C (2 g single ingestion) reduces arterial stiffness but do not indicate any important interaction with oral methionine (A234).

Neutrophil superoxide anion--generating capacity, endothelial function and oxidative stress in chronic heart failure: effects of short- and long-term vitamin C therapy.
Oxidative stress is increased in ischemic and nonischemic chronic heart failure, and neutrophils may be an important cause. Vitamin C reduces oxidative stress, increases flow-mediated dilation and, when given long term, decreases neutrophil O2- generation, but the lack of a correlation between changes in endothelial function and oxidative stress with vitamin C implies possible additional non-antioxidant benefits of vitamin C (A236).

**Big_r** · 11-08-2005, 11:48 PM

..

Serum vitamin C concentration was inversely associated with subsequent 20-year incidence of stroke in a Japanese rural community. The Shibata study.
Strong inverse associations were observed between serum vitamin C concentration and all stroke (sex- and age-adjusted hazard ratios were 0.93, 0.72, and 0.59, respectively, for the second, third, and fourth quartiles compared with the first quartile; P for trend=0.002) (A238).

Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina: possible role of reactive oxygen species.
Vitamin C improves both endothelial function and insulin sensitivity in patients with coronary spastic angina (A242).

**Big_r** · 11-08-2005, 11:49 PM

C)Studies showing no beneficial (nor adverse) effect from vit C + other antioxidants on the heart:

MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial.
20,536 UK adults (aged 40-80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg beta-carotene daily) or matching placebo for 5 years.
There were no significant differences in all-cause mortality (1446 [14.1%] vitamin-allocated vs 1389 [13.5%] placebo-allocated), or in deaths due to vascular (878 [8.6%] vs 840 [8.2%]) or non-vascular (568 [5.5%] vs 549 [5.3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10.4%] vs 1047 [10.2%]), non-fatal or fatal stroke (511 [5.0%] vs 518 [5.0%]), or coronary or non-coronary revascularisation (1058 [10.3%] vs 1086 [10.6%]). For the first occurrence of any of these "major vascular events", there were no material differences either overall (2306 [22.5%] vs 2312 [22.5%]; event rate ratio 1.00 [95% CI 0.94-1.06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause (A223).

The MRC/BHF Heart Protection Study: preliminary results.
The Heart Protection Study (HPS), with over 20,500 subjects, is the largest trial of statin therapy ever conducted.
It is a prospective double blind randomised controlled trial with a 2 x 2 factorial design investigating prolonged use (>5 years) of simvastatin 40 mg and a cocktail of antioxidant vitamins (650 mg vitamin E, 250 mg vitamin C and 20 mg beta-carotene). The HPS specifically included patients with high risk for coronary heart disease (CHD).
Simvastatin 40 mg treatment showed benefit across all patient groups regardless of age, gender or baseline cholesterol value and proved safe and well tolerated.
Preliminary results of the HPS are negative for the antioxidant vitamin cocktail but provide reassurance that vitamins do no harm (A227).

Effects of long-term daily low-dose supplementation with antioxidant vitamins and minerals on structure and function of large arteries.
Antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta carotene, 100 microg selenium, and 20 mg zinc) or placebo and followed-up over an average of 7.2+/-0.3 years for 1162 subjects suggest no beneficial effects on carotid atherosclerosis and arterial stiffness (A244).

D)Studies showing a positive effect from vitamine C + other antioxidants on the heart:

Combined vitamin C and E supplementation retards early progression of arteriosclerosis in heart transplant patients.
Supplementation with vitamins C and E retarded the progression of coronary arteriosclerosis during the early stage following cardiac transplantation (A221).

**Big_r** · 11-08-2005, 11:50 PM

OTHER INTERESTING STUDIES

A randomized controlled trial of high dose ascorbic acid for reduction of blood pressure, cortisol, and subjective responses to psychological stress.
Response to acute psychological stress in 60 healthy subjects supplemented 1000 mg sustained release vit C 3 x/day for 14 days: The ascorbic acid group had less systolic blood pressure (an increase of 23 versus 31 mmHg), diastolic blood pressure, and subjective stress responses to the TSST; and also had faster salivary cortisol recovery (but not smaller overall cortisol response). Cortisol response to 1 microg ACTH, and reported side-effects during the trial did not differ between groups (A503).

[Role of vitamin C on adrenocortical effects of etomidate]
A 1 g vit C infusion at induction of anaesthesia decreases cortisol levels (47.6 +/- 9% in vs 76.5 +/- 33%, p less than 0.05) (A510).

Strategies for Healthy Weight Loss: From Vitamin C to the Glycemic Response
Vitamin C status is inversely related to body mass. Individuals with adequate vitamin C status oxidize 30% more fat during a moderate exercise bout than individuals with low vitamin C status; thus, vitamin C depleted individuals may be more resistant to fat mass loss (A530).

A double blind placebo controlled trial of ascorbic acid in obesity.
A double blind placebo controlled trial of ascorbic acid was carried out in 41 severely obese subjects. 38 patients completed the 6 week trial. 19 received 3g of ascorbic acid per day, 19 received placebo. The weight loss during the trial was small in both groups but was significantly greater in the ascorbic acid treated group (A531).

[Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals]
1 g vit C or placebo for 4 weeks in 16 obese males in a randomized double-blind clinical trial id not modify the lipid profile nor insulin sensitivity (A532).

Insulin sensitivity and intake of vitamins E and C in African American, Hispanic, and non-Hispanic white men and women: the Insulin Resistance and Atherosclerosis Study (IRAS).
These cross-sectional analyses (1151 women) do not support the hypothesis of improved SI with increased intake of vitamins E and C (A533).

N-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid.
We measured levels of N-nitrosodimethylamine (NDMA) in peripheral blood from 13 fasting male patients, 30-74 years old, who had chronic renal failure, and in five healthy control subjects (four males and one female) 31-50 years old. In the patients, we found significant (P less than .01) levels of NDMA (mean +/- SD; 201 +/- 111 ng/kg of blood), which is known to be carcinogenic in animals.
In five of six patients, pretreatment with oral ascorbic acid resulted in a blunting, but not statistically significant, effect on maximum blood NDMA levels after consumption of ethanol. Mean levels were 340 +/- 100 ng/kg before treatment with ascorbic acid and 237 +/- 127 ng/kg during treatment (A534).

**Big_r** · 11-08-2005, 11:52 PM

..

Inhibitory effect of ascorbic acid (vitamin C) on cortisol secretion following adrenal stimulation in children.
On the 5th day of AA administration (1 g/day) the mean cortisol values after ACTH were significantly lower than the corresponding values in group A (p less than 0.02), or the post-ACTH values in group B observed on the 1st experimental day, i.e., before AA administration (p less than 0.001). On the other hand, AA administration had no significant effect on the fasting plasma cortisol values. These data suggest that AA excess following adrenal stimulation with ACTH exerts an inhibitory effect on cortisol secretion and consequently it may be of no benefit in conditions of stress (A535).

Vitamin C supplementation and respiratory infections: a systematic review.
For this systematic review, we identified seven trials with military personnel, three trials with students in crowded lodgings, and two trials with marathon runners. Eight of these trials were double blind and placebo controlled and seven were randomized. Five small trials found a statistically significant 45 to 91% reduction in common cold incidence in the vitamin C group. These trials were short and the participants were under heavy exertion during the trial. Furthermore, three other trials found a statistically significant 80 to 100% reduction in the incidence of pneumonia in the vitamin C group (A536).

Vitamin C for preventing and treating the common cold.
This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004).
The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms (A537).

[Antioxidant treatment with N-acetylcysteine and vitamin C in patients with chronic bronchitis]
N-acetylcysteine (NAC) (600 mg), Vitamin C (500 mg) and the NAC/ Vitamin C-combination (in a randomized, double-blinded, placebo controlled trial) did neither enhance antioxidant protection in the blood nor is it of any clinical benefit in chronic bronchitis. Possible reasons may be a lack of antioxidant deficiency in these patients and negative feedback mechanisms of the glutathione-system (A538).

**Big_r** · 11-08-2005, 11:53 PM

SIDE EFFECTS

Vitamin C and Vitamin E for Alzheimer's Disease (December).
Mega-trial results suggest that vitamin E doses >/=400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted (A801).

Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements.
Vitamin A should be avoided in women who may become pregnant, in those with liver disease, and in people who drink heavily. Relationships have been found between vitamin A and reduced bone mineral density, and beta-carotene and increased risk of lung cancer in smoking males. Vitamin E and Ginkgo biloba have anticoagulant and anti-platelet effects respectively, and high doses are contraindicated in those being treated for vascular disorders (A802).

Vitamin C in health and disease.
High intakes of the vitamin are generally well tolerated, however, a Tolerable Upper Level (TUL) was recently set at 2 g based on gastrointestinal upset that sometimes accompanies excessive dosages (A803).

Vitamins E and C are safe across a broad range of intakes.
Numerous studies of vitamin C supplementation have provided no pattern of evidence to support concerns about safety other than occasional gastrointestinal upset or mild diarrhea resulting from the osmotic effects of unabsorbed quantities of vitamin C. Evidence of bleeding effects and other potential adverse effects of high vitamin E intakes in humans is not convincing. Evidence of adverse effects of vitamin C that result from its effects on iron absorption and metabolism has not been confirmed in clinical trials. Thus, we conclude from clinical trial evidence that vitamin E supplements appear safe for most adults in amounts </=1600 IU (1073 mg RRR-alpha-tocopherol or the molar equivalent of its esters) and that vitamin C supplements of </=2000 mg/d are safe for most adults (A804).

Safety of antioxidant vitamins.
Approximately 10 to 15 cases of vitamin A toxic reactions are reported per year in the United States, usually at doses greater than 100,000 IU/d. No adverse effects have been reported for beta-carotene. The frequency of vitamin E toxic reactions is not well delineated, but case reports are few at dosages less than 3200 mg/d. Ascorbic acid toxic reactions are rare at dosages less than 4 g/d. Despite a lack of clinical trial data, it seems that antioxidant vitamins are safe, although prudence might dictate their avoidance by women of childbearing potential, persons with liver disease or renal dysfunction (A805).

Antioxidant intake in pregnancy in relation to wheeze and eczema in the first two years of life.
In the children's second year, maternal vitamin E intake during pregnancy was negatively associated with wheeze in the absence of a "cold" (p for trend 0.010) and, in children whose mothers were atopic, there was a negative association between maternal vitamin E intake and childhood eczema (p for trend 0.024). Maternal vitamin C intake during pregnancy was positively associated with "ever wheeze" and eczema during the children's second year (A807).

[Vitamin C and stone risk. Review of the literature]
Vitamin C has been incriminated as a possible risk factor for calcium oxalate stones due to its enzymatic conversion into oxalate. However, this lithogenic role has never been clearly established. Studies evaluating the effect of ascorbic acid on lithogenesis have reported contradictory results. Ascorbic acid has also been extensively used as an urine acidifier for the treatment of chronic or recurrent urinary tract infection. Once again, the data of the literature are contradictory (A808).

New evidence for antioxidant properties of vitamin C.
This study was designed to examine the effect of 500 to 5,000 mg of ascorbic acid on DNA adducts, natural killer (NK) cell activity, programmed cell death, and cell cycle analysis of human peripheral blood leukocytes. According to our hypothesis, if ascorbic acid is a pro-oxidant, doses between 500 and 5,000 mg should enhance DNA adduct formation, decrease immune function, change the cell cycle progression, and increase the rate of apoptosis.
500, 1000 or 5000 mg vit C for 2 weeks in 15 healthy volunteers resulted in no statistically meaningful changes in the level of 8-hydroxyguanosine, increased NK cytotoxic activity, a reduced percentage of cells undergoing apoptosis, and switched cell cycle phases from S and G2/M to G0/G1.
Ascorbic acid is an antioxidant and that doses up to 5,000 mg neither induce mutagenic lesions nor have negative effects on NK cell activity, apoptosis, or cell cycle (A809).

**Big_r** · 11-08-2005, 11:54 PM

**Big_r** · 11-08-2005, 11:55 PM

**Big_r** · 11-08-2005, 11:57 PM

THE END for now.

More will be added in due time!!!!

(When i feel like it

)

**DejaBlue55** · 11-09-2005, 12:13 AM

WOW!!

Great thread. Haven't read through it yet, but I will soon. Thanks BigR.

**McBurly** · 11-09-2005, 12:19 AM

I can't even fathom how long this must have taken you...

**tek.** · 11-09-2005, 01:42 AM

reps

**cowboyathlete** · 11-09-2005, 04:56 AM

This is also a good reminder that sometimes we are so focused on the expensive and hard to find supplements that we forget the importance of something as inexpensive and widely available as vitamin C.

**Tim_G** · 11-09-2005, 05:22 AM

much appreciated....repped and bookmarked...

**Bane** · 11-09-2005, 08:09 AM

Nice post man!

**pu12en12g** · 11-13-2005, 05:41 AM

Great thread

**DrGonzo** · 11-13-2005, 12:13 PM

Heres a good question:
We know that vitamin C is good for the immune system ( amongst many other things) but does that mean that taking more will work even better? I'm a firm believer that your body uses what it needs and pisses out the rest.

Thread: Vitamin C: Fact and fiction. The human studies (in vivo)!!

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