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May 9, 2000

National Academy of Sciences References

51. Arch Ophthalmol 1978 Nov;96(11):2069-72Ascorbate therapy in impaired neutrophil and monocyte chemotaxis. With atopy,hyperimmunoglobulinemia E, and recurrent infection.Foster CS, Goetzl EJ

A Candida albicans corneal ulcer developed in a 24-year-old man with a historyof eczema, asthma, and multiple bacterial infections since childhood. Theinfection responded well to oral flucytosine (12 g/day for 15 days) and topicalamphotericin B. Positive laboratory findings included eosinophilla,hyperimmunoglobulinemia E, and impaired neutrophil and monocyte spontaneousmigration and chemotactic responses. Ascorbic acid corrected the monocyte defectin vitro and in vivo, but had no effect on neutrophil function.

52. Dermatologica 1980;160(2):106-12Repeated staphylococcal pyoderma in two siblings with defective neutrophilbacterial killing.Rebora A, Crovato F, Dallegri F, Patrone F

2 children with undue susceptibility to skin infections and isolated defectiveneutrophil bacterial killing are described. Since the NBT-reducing capabilitiesof granulocytes were normal, a mild form of chronic granulomatous disease wasexcluded. Ascorbic acid was effective in delaying and eventually suppressinginfectious episodes.

53. Med Microbiol Immunol (Berl) 1982;171(2):113-22Disorders of neutrophil function in children with recurrent pyogenic infections.Patrone F, Dallegri F, Bonvini E, Minervini F, Sacchetti C

Ten patients with neutrophil dysfunctions and recurrent pyogenic infections,mainly of the skin middle-ear, and respiratory tract, are described. The mostfrequently affected functions were chemotaxis and bacterial killing.Pharmacologic restoration of functional defects was tried in all cases.Levamisole was given in two cases and ascorbic acid in the other eight cases.During a follow up of at least 18 months, seven patients showed a completerestoration of neutrophil function and a long-lasting clinical remission. One ofthe two patients with Chronic Granulomatous Disease has been free frominfections for 1 year, despite persistent neutrophil dysfunction, while theother did not display consistent clinical improvement. Another patient, who wasgiven ascorbic acid for a short period only due to non compliance, showedneither laboratory nor clinical improvement.

54. Acta Vitaminol Enzymol 1982;4(1-2):163-8Effects of ascorbic acid on neutrophil function. Studies on normal and chronicgranulomatous disease neutrophils.Patrone F, Dallegri F, Bonvini E, Minervini F, Sacchetti C

Ascorbic acid is able to stimulate neutrophil oxidative metabolism in normalneutrophils, as well as other several functions of these cells, either in thenormal state or in the defective one. In the present study, we have investigatedthe effects of ascorbic acid on the hexose monophosphate shunt (HMPS) and on thebactericidal activity of neutrophils from Chronic Granulomatous Disease (CGD)patients. Furthermore, we have investigated the effects of ascorbic acid on theantibody dependent cell cytotoxicity (ADCC) of normal neutrophils. Ascorbic acidin vitro was able to significantly improve both HMPS activity and bacterialkilling of CGD neutrophils. Its prolonged administration to such patients led toconsistent clinical improvement, possibly related to the enhancement ofchemotaxis, although the effects on HMPS and bacterial killing seen in vitrocould not be confirmed. Ascorbic acid was also able to interfere with neutrophilADCC with different results depending on its concentration and the experimentalconditions.

55. Br J Dermatol 1980 Jan;102(1):49-56Neutrophil dysfunction and repeated infections: influence of levamisole andascorbic acid.Rebora A, Dallegri F, Patrone F

Neutrophil function was studied in several patients with recurrent infections,mainly of the skin. Twelve patients showed impairment of neutrophil functions,either chemotaxis or bacterial killing and phagocytosis. Levamisole was given infour cases: improvement of neutrophil function and long-lasting clinicalremission occurred in three of them, whilst in the fourth the drug was nottolerated. Ascorbic acid was administered to three other patients, withsatisfactory improvement of neutrophil function and long-lasting clinicalremission.

56. Can J Physiol Pharmacol 1998 Apr;76(4):373-80Immune function in aged women is improved by ingestion of vitamins C and la Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel JDepartamento de Biologia Animal II (Fisiologia Animal), Facultad de CienciasBiologicas, Universidad Complutense, Madrid, Spain.

We have investigated the effects of supplementation of the diet with theantioxidant vitamins C and E on several functions of the immune response of agedwomen. Ten healthy women and 20 women (72 6 years old) suffering twodiseases often associated with age (10 with major depression disorders, MDD, and10 with coronary heart disease, CHD) were administered 1 g of vitamin C and 200mg of vitamin E daily for 16 weeks. Blood samples were collected before andafter treatment for measurement of several immunological functions, namelyproliferative response of lymphocytes to the mitogen phytohemagglutinin (20mg/L) and phagocytic functions of polymorphonuclear (PMN) neutrophils, i.e.,adherence to vascular endothelium, chemotaxis, phagocytosis of latex beads, andsuperoxide anion production. In addition, we also determined the levels of serumcortisol and lipid peroxides. Intake of vitamins resulted in a significantincrease in the lymphoproliferative capacity and in the phagocytic functions ofPMN neutrophils as well as in a significant decrease of serum levels of lipidperoxides and cortisol, both in the healthy aged women and in the aged womenwith MDD or CHD. These findings suggest an important role of antioxidantsupplementation in the improvement of immune function in aged females as well asin the prevention and treatment of specific diseases associated with age thatare quite prevalent in the developed countries.

57. Int J Dermatol 1993 Nov;32(11):832-4Successful treatment of a patient with recurrent furunculosis by vitamin C:improvement of clinical course and of impaired neutrophil functions.Levy R, Schlaeffer FLaboratory of Infectious Diseases, Soroka Medical Center of Kupat Holim, BeerSheva, Israel.

BACKGROUND. Neutrophils play a critical role in host defense against a varietyof microbial pathogens. There is much information to suggest a role for vitaminC in the physiology of neutrophils. Thus, the effects of vitamin C treatmentwere studied in a patient with a history of recurrent furunculosis who showedaltered neutrophil functions. METHODS. Superoxide generation was measured bycytochrome C reduction. Phagocytosis of opsonized zymosan by neutrophils andchemotaxis on agarose plates were determined. RESULTS. Chemotaxis, phagocytosis,and superoxide generation of the patient's neutrophils were significantly lowerthan those of the matched control. Treatment with vitamin C (500 mg/day) for 30days caused a dramatic clinical response and a significant improvement of allthree neutrophil functions to values similar to those of the controls.CONCLUSIONS. We suggest that the patient described here had a temporary defectin neutrophil functions. The treatment with vitamin C probably preventedneutrophil oxidation, thus contributing to recovery of neutrophil function andarrest of furunculosis.

58. Am J Clin Nutr 1981 Sep;34(9):1906-11Ascorbate-mediated stimulation of neutrophil motility and lymphocytetransformation by inhibition of the peroxidase/H2O2/halide system in vitro andin vivo.Anderson R

Neutrophil migration, postphagocytic hexose-monophosphate shunt activity andmyeloperoxidase-mediated iodination of ingested Candida albicans and lymphocytemitogen-induced transformation were assessed in six normal volunteers before and1 h after a single intravenous injection of 1 g ascorbate. Increased neutrophilmotility was observed which was associated with decreasedmyeloperoxidase-mediated iodination of C. albicans and a slight increase inhexose-monophosphate shunt activity. Lymphocyte transformation was alsoincreased. Alterations in these activities were related to serum ascorbatelevels. To investigate the relationship of ascorbate-mediated increasedneutrophil motility and lymphocyte transformation to decreased peroxidaseactivity neutrophils and lymphocytes from normal individuals were exposed to thehorseradish peroxidase/H2O2/sodium iodide system in the presence and absence ofascorbate and tested for migratory and proliferative responses respectively.Exposure to the horseradish peroxidase/H2O2/halide system caused inhibition ofneutrophil motility and lymphocyte responsiveness to mitogens. However,inclusion of ascorbate protected both the neutrophils and lymphocytes from theinhibitory effects of the horseradish peroxidase/H2O2/halide system.

59. Exp Gerontol 1999 Aug;34(5):675-85Effects in vitro of several antioxidants on the natural killer function of aging mice.Ferrandez MD, Correa R, Del Rio M, De la Fuente MDepartment of Animal Physiology, Faculty of Biological Sciences, ComplutenseUniversity of Madrid, Spain.

The aim of the present work is to study the change with aging in the effect invitro of several antioxidants: thiazolidine-4-carboxylic acid or thioproline,N-acetylcysteine (NAC), ascorbic acid (AA), and alpha-tocopherol (vitamin E, VE)on the natural killer (NK) activity in mononuclear cells from axillary nodes,spleen, thymus and peritoneal leukocytes from BALB/c male mice. Young (82weeks), adult (242 weeks). mature (482 weeks), and old (722 weeks)animals were studied. A nonradioactive cytotoxic assay with cells from themurine lymphoma YAC-1 as target cells and a relation effector cells/target cellsof 10/1 were used. The concentrations of the different antioxidants were: 1 mMfor thioproline and N-acetylcysteine and 5 microM for ascorbic acid andalpha-tocopherol, which induced a maximum effect in our previous dose-responseexperiments. The results show that, in general, the above antioxidants cause anenhancement of the NK activity at all ages studied, this stimulation beinghigher with thioproline and N-acetylcysteine than with ascorbic acid andalpha-tocopherol. The effects were similar for the three lymphoid organs and theperitoneum. This stimulation of the NK activity by antioxidants is an importantfavorable response, especially in old mice, in which age results in a decreasein NK function and, therefore, in a higher incidence of neoplasia.

60. Immunopharmacol Immunotoxicol 1997 Aug;19(3):291-312Enhancement of natural killer cell activity and T and B cell function bybuffered vitamin C in patients exposed to toxic chemicals: the role of proteinkinase-C.Heuser G, Vojdani ANeuromed & Neurotox Associates, Thousand Oaks, CA 91361, USA.

After exposure to many toxic chemicals, NK function can be decreasedsignificantly. Weeks or months later, natural killer (NK) function can reboundto normal levels in some and can be suppressed for prolonged periods of time inother patients. In view of this, we decided to study the effect of bufferedvitamin C on NK, T and B cell function in patients who had been exposed to toxicchemicals. After the first blood draw, 55 patients immediately ingestedgranulated buffered vitamin C in water at a dosage of 60 mg/Kg body weight.Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T andB cell function. Vitamin C in high oral dose was capable of enhancing NKactivity up to ten-fold in 78% of patients. Lymphocyte blastogenic responses toT and B cell mitogens were restored to the normal level after vitamin C usage.Signal transduction enzyme protein kinase C (PKC) appeared to be involved in themechanism of induction of NK activity by vitamin C. We conclude that immunefunctional abnormalities can be restored after toxic chemical exposure by oralusage of vitamin C.