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Life Extension Magazine




May 9, 2000

 

National Academy of Sciences References


141. Biomed Biochim Acta 1991;50(3):265-72
Effect of ascorbic acid on hydroxyl radical generation by chemical, enzymatic and cellular systems. Importance for antioxidant prevention of pulmonary emphysema.
Nowak D, Piasecka G, Antczak A, Pietras T
Department of Pneumonology and Allergology, Medical Academy, Lodz, Poland.

The ability of ascorbic acid (AA) (25 to 500 microM) to increase OH production
by a chemical (Fe(2+)-EDTA-H2O2), an enzymatic (xanthine-xanthine
oxidase-Fe(2+)-EDTA) and a cellular system (3.10(6) human polymorphonuclear
leukocytes (PMNL) or murine peritoneal macrophages (PM) activated with 7.2 ng
PMA/ml) was studied. At all concentrations used AA strongly enhanced OH
generation by the chemical and the enzymatic systems. However, the maximal
increase of about 14-fold was found for incomplete chemical system (10 microM
Fe(2+)-20 microM EDTA) and 500 microM AA. In the case of
phorbol-myristate-acetate-activated-PMNL and macrophages, the moderate increase
in OH formation was only caused by low AA concentrations. At 50 microM AA, the
OH formation was 112 +/- 3 and 117 +/- 4% of control, respectively. Higher AA
concentrations had no influence or even decreased OH formation by phagocytes. It
is suggested that administration of AA will not significantly enhance OH
generation from pulmonary phagocytes and could be useful for prevention of the
oxidant-mediated lung injury related to inflammation.

142. J Pharm Sci 1990 Oct;79(10):913-5
Oxidation kinetics of an antiasthmatic,
2-[(4-hydroxyphenyl)amino]-5-methoxybenzenemethanol, and stabilization with ascorbic acid.
Yu AB, Portmann GA
Pharmaceutical Sciences, Sterling Drug, Inc., Rensselaer, NY 12144.

A novel antiasthmatic, 2-[(4-hydroxyphenyl)amino]-5-methoxybenzenemethanol (1),
oxidizes to the corresponding iminoquinone in aqueous solutions. The reaction
was monitored by a paired-ion reversed-phase HPLC method. The oxidation rate was
highly dependent on the solution pH, with a large rate increase occurring above
pH 6.1. In nonaqueous solution, the oxidation reaction was significantly slower.
Ascorbic acid protects 1 from oxidation. The aqueous solution of the decomposed
product is reduced to 1 in the presence of ascorbic acid.

143. S Afr Med J 1983 Apr 23;63(17):649-52
Ascorbic acid in bronchial asthma.
Anderson R, Hay I, van Wyk HA, Theron A

Sixteen White children with bronchial asthma were divided into two groups; one
received standard anti-asthma chemoprophylaxis (SAC) and the other SAC
supplemented with 1 g ascorbic acid (Redoxon) given as a single daily dose for a
6-month period. In 10 patients the effects of ascorbic acid on exercise-induced
bronchoconstriction (EIB) were assessed by comparing the pre-ascorbic acid
results with those obtained 2 1/2 hours after the intravenous injection of 1 g
ascorbic acid. Immunological investigations performed on the two groups were
assessment of polymorphonuclear leucocyte (PMNL) motility, phagocytosis and
nitroblue tetrazolium reduction and measurement of secretory IgA, serum
immunoglobulin and total haemolytic complement levels and levels of the
components C3 and C4, alpha 1-antitrypsin, antistreptolysin O (ASO), C-reactive
protein and antibodies to certain respiratory viruses. These investigations were
performed before and 1, 3 and 6 months after the commencement of therapy. Radio-allergosorbent testing for sensitivity to four common allergens was
carried out at the outset and after 6 months of therapy. Injection of ascorbic
acid had no detectable effects on the degree of EIB. Slight but not significant
immunological changes were observed in the SAC group over the 6-month study
period. However, in the SAC plus ascorbic acid group significantly improved PMNL
motility and decreased ASO levels and reduced (although not to a significant
extent) IgE levels and titres of antibodies to the respiratory viruses were
observed.

144. Am Rev Respir Dis 1983 Feb;127(2):143-7
Effect of ascorbic acid on response to methacholine challenge in asthmatic subjects.
Mohsenin V, Dubois AB, Douglas JS

We studied the effect of ascorbic acid in 14 mild asthmatic subjects. The effect
of ascorbic acid (1.0 g orally) was assessed by the changes in concentration of
methacholine required to decrease the specific airway conductance by 40% (pD40).
Ascorbic acid increased pD40 from control values of 9.38 1.97 mg/ml mean SEM) to 12.59 mg/ml 2.52 (p less than 0.05). Administration of 50 mg of
indomethacin, orally, reversed the effect of ascorbic acid. Indomethacin alone
had no effect on the mean pD40. The results suggest that ascorbic acid exerts
its effect via alteration of arachidonic acid metabolism.

145. Plucne Bolesti 1991 Jan-Jun;43(1-2):94-7
[Effect of vitamin C on exercise-induced bronchoconstriction].
[Article in Serbo-Croatian (Roman)]
Miric M, Haxhiu MA
Institut za klinicku fiziologiju, Medicinski fakultet, Pristina.

The effect of vitamin C on exercise-induced airway constriction was studied.
Pretreatment with ascorbic acid prevented the significant alteration in airway
geometry induced by exercise asthmatic patients. These results suggest that
vitamin C deficiency might augment airway responses to exercise and other
bronchospasmogenic factors, and treatment with vitamin C may decrease airway
hyperresponsiveness.

146. S Afr Med J 1980 Dec 13;58(24):974-7
The effect of ascorbate on cellular humoral immunity in asthmatic children.
Anderson R, Hay I, van Wyk H, Oosthuizen R, Theron A

Ten White children with bronchial asthma and exercise-induced
bronchoconstriction were assessed immunologically before and 1, 3 and 6 months
after the commencement of standard therapy supplemented with ascorbate 1 g/d.
The tests of cellular immune function were neutrophil chemotaxis, phagocytosis
and resting and stimulated nitroblue tetrazolium reduction, and lymphocyte
mitogen-induced transformation. Humoral functions measured were secretory IgA,
serum immunoglobulins, alpha 1-antitrypsin, C3, C4 and total haemolytic
complement, antistreptolysin O (ASO) and C-reactive protein.
Radio-allergosorbent testing to the common allergens Cynodon dactylon (grass),
Dermatophagoides pteronyssinus (mite), house dust and cat epithelium was
performed on each child before and 3 and 6 months after treatment. Two children
had depressed neutrophil motility, 4 had depressed lymphocyte transformation,
and 7 had elevated levels of ASO. These functions normalized after 6 months of
ascorbate-supplemented therapy. Serum total IgE levels but not specific IgE
levels were likewise reduced after 6 months of therapy. Reduced levels of serum
alpha 1-antitrypsin were observed in 2 children, and remained unchanged
throughout the study.

147. Trop Geogr Med 1980 Jun;32(2):132-7
High dose ascorbic acid in Nigerian asthmatics.
Anah CO, Jarike LN, Baig HA

Forty-one asthmatic patients in remission were randomly allocated to two
treatment groups in a double-blind trial. One group took 1 g, of ascorbic acid
as one effervescent tablet once daily and the second group took a matching
placebo. The asthmatics were selected from those attending the Asthma Clinic.
One criterion for selection was the increase in exacerbation during the rainy
season. These exacerbations were precipitated by respiratory infection. After 14
weeks, an assessment of the severity and rate of attacks showed that those on
ascorbic acid suffered less severe and less frequent attacks of asthma during
the study period. Plasma ascorbic acid astimations showed a significant rise in
the level in those taking ascorbic acid over those on placebo. (P < 0.01).
Cessation of ascorbic acid in the group taking it increased attack rates. It is
concluded that high dose ascorbic acid is probably a good prophylaxis in some
bronchial asthmatics.

148. Am J Epidemiol 1998 Jul 1;148(1):45-50
Cohort study of vitamin C intake and cognitive impairment.
Paleologos M, Cumming RG, Lazarus R
Department of Public Health and Community Medicine, Faculty of Medicine,
University of Sydney, New South Wales, Australia.

To test the hypothesis that vitamin C protects against cognitive impairment, the
authors conducted a cohort study (n=117) in a retirement community in Sydney,
Australia. Vitamin C intake was assessed at baseline (1991) with a
semiquantitative food frequency questionnaire, and cognitive function was
assessed 4 years later (1995). After adjustment for age, sex, smoking,
education, total energy intake, and use of psychotropic medications, consumption
of vitamin C supplements was associated with a lower prevalence of more severe
cognitive impairment (based on scores on the Mini-Mental State Examination;
adjusted odds ratio=0.39, 95% confidence interval 0.18-0.84). There were no
associations between vitamin C intake and scores on tests of verbal and category
fluency. This study suggests that vitamin C might protect against cognitive
impairment.

149. Am J Clin Nutr 2000 May;71(5):1194-200
Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes.
Lenton KJ, Therriault H, Cantin AM, Fulop T, Payette H, Wagner JR
Centre de Recherche, Institut Universitaire de Geriatrie de Sherbrooke,
Sherbrooke, Canada, and Unite de Recherche Pulmonaire, Centre de Sante de l'Estrie, Fleurimont, Canada.

BACKGROUND: Endogenous reactive oxygen species appear to contribute to aging and
cancer and dietary antioxidants, present in fruit and vegetables, counteract
these effects. OBJECTIVE: The objective was to examine the association between
intracellular glutathione, ascorbate (vitamin C), and alpha-tocopherol (vitamin
E) in human lymphocytes. DESIGN: The study group consisted of 240 healthy
nonsmoking volunteers with an approximately equal number of male and female
subjects subdivided into 3 age groups: 18-39, 40-59, and >/=60 y). Glutathione,
glutathione disulfide, ascorbate, and alpha-tocopherol were measured in
lymphocytes by HPLC. RESULTS: The average concentration of antioxidants in
lymphocytes was 27 8 nmol/mg protein for glutathione, 21 8 nmol/mg
protein for ascorbate, and 0.4 0.2 nmol/mg protein for alpha-tocopherol.
There was a strong positive correlation between glutathione and ascorbate (r =
0.62, P < 0.001). No correlation was observed for glutathione and ascorbate with
alpha-tocopherol. The concentration of glutathione in lymphocytes was inversely
correlated with age (r = -0.19, P < 0.01), as was that of ascorbate (r = -0.22,
P < 0.01), with 10-20% lower values in elderly than in young and elderly
subjects. The concentrations of glutathione in lymphocytes were as much as 25%
higher and those of ascorbate were as much as 38% higher during the summer than
during the winter. The seasonal variation of ascorbate in lymphocytes was
described by a linear function for age and a periodic sine function for season.
CONCLUSION: Glutathione and ascorbate are directly correlated in human
lymphocytes.

150. J Pediatr 1994 Feb;124(2):229-33
Effect of ascorbate or N-acetylcysteine treatment in a patient with hereditary glutathione synthetase deficiency.
Jain A, Buist NR, Kennaway NG, Powell BR, Auld PA, Martensson J
Department of Internal Medicine, Greenwich Hospital/Yale University School of Medicine, CT 06830-4697.

A 45-month-old girl with 5-oxoprolinuria (pyroglutamic aciduria), hemolysis, and
marked glutathione depletion caused by deficiency of glutathione synthetase was
followed before and during treatment with ascorbate or N-acetylcysteine. High
doses of ascorbate (0.7 mmol/kg per day) or N-acetylcysteine (6 mmol/kg per day)
were given for 1 to 2 weeks without any obvious deleterious side effects.
Ascorbate markedly increased lymphocyte (4-fold) and plasma (8-fold) levels of
glutathione. N-Acetylcysteine also increased lymphocyte (3.5-fold) and plasma
(6-fold) levels of glutathione. After these treatments were discontinued,
lymphocyte and plasma glutathione levels decreased rapidly to pretreatment
levels. Ascorbate treatment was extended for 1 year, and lymphocyte (4-fold) and
plasma (2- to 5-fold) glutathione levels remained elevated above baseline. In
parallel, the hematocrit increased from 25.4% to 32.6%, and the reticulocyte
count decreased from 11% to 4%. The results demonstrate that ascorbate and
N-acetylcysteine can decrease erythrocyte turnover in patients with hereditary
glutathione deficiency by increasing glutathione levels.

 



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