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Abstracts

Abstracts

Adolescence

Ageing

Ageing

Oxidative damage to DNA, proteins and lipids is the greatest contributing factor to ageing, cancer, heart disease, cataracts and cognitive dysfunction. Low vitamin C intake results in a statistically significant higher risk of heart disease mortality and total mortality in the next ten years. Other studies have shown low intakes of the antioxidant nutrients such as vitamin C and carotene increased the risk of developing age-related eye diseases such as cataracts. Large proportions of older individuals have low intakes of antioxidants and blood levels. Individuals with higher dietary intakes of vitamin C or citrus fruit have a lower risk of cancer development.

"Vitamin C, Cancer and Aging", Gladys Block. Age, 1993;16:55-58.

Cataracts

Cataracts

Researchers at Tufts University found that individuals who had higher levels of vitamin C in their blood
had a reduced risk to certain types of cataracts. Individuals need about 800mg/day of vitamin C to
achieve these higher levels.
"Vitamin C Could Cut Cataract Risk", Friend, Tim, USA Today, Life Section, September 18, 1990.

Cataracts affect the majority of people over the age of 75 and their care results in significant health expenditures. There may be due to accumulation of damaged proteins in cataracts with age. It is noted that increased dietary ascorbate (vitamin C) can give protection against solar light-induced damage to the lens proteins and proteases. Epidemiologic evidence supports that higher ascorbate levels are associated with a reduced incidence of certain types of cataracts.

"Oxidant Stress and Cataracts: Experimental Studies", Taylor, A., et al, Journal of The American College of Nutrition, October 199 1;10(5):539/Abstract 21.

Cataracts are the leading cause of blindness worldwide. They occur in almost 50% of individuals over 75 years of age and 15% of those 55 years of age or more. In Canada, a population of 26 million, that accounts for approximately 330,000 cases over the next 5 years. There is strong evidence that oxidative stress due to the accumulation of free radicals (singlet oxygen and hydrogen peroxide) are important in cataract formation. Antioxidants such as vitamin C and E have shown in animal model to be protective against cataract formation. A human study of 112 cataract patients compared to 35 cataract-free controls found that those who consumed less than 3.5 servings of fruit or vegetables per day and had low vitamin C intake had an increased cataract risk.

Those with low vitamin C showed an 11 -fold increased risk of cataracts. Comparing vitamins C and E consumption in a study of 175 cataract cases compared to controls, it was found that those who took regular supplements of vitamins C and E had significantly less risk to cataract formation than those who did not.

"Cataract Prevention: Time For a Clinical Trial?", Robertson, J., McD, DVM, MSc, British Journal of Clinical Practice, November 1990; 44(11):475-476.

A self-reported questionnaire of 175 cataract patients compared to 175 cataract-free individuals found that those who had no cataracts took significantly more supplements with vitamins C and E. These results suggest a 50% reduction in the risk of cataracts. The daily doses of vitamin C were between 300 and 600 mgs and E 400 mg. If 50 to 70 per cent of cataracts could be prevented or postponed by vitamins C and E supplementation, the potential human and economic impact would be extremely significant.

"A Possible Role For Vitamins C and E in Cataract Prevention", Robertson, James, McD, American Journal of Clinical Nutrition, 1991;53:346S-351 S.

Antioxidants' roles in the prevention of macular degeneration are reviewed. Yellow pigments in the eye quench free radicals and singlet oxygen. These pigments are supported by antioxidant enzymes and vitamins E and C. Vitamin C protects vitamin E by regenerating it from its reduced state. In animal models vitamin C supplementation has reduced free radical substances and retinal degeneration. The retina contains a higher concentration of carotenoids and vitamins E and C than other tissues. A higher level of those antioxidant nutrients may be needed to counteract light's damaging effects. Progression of degenerative changes and improvement in some cases has been shown as a result of beta carotene, C and E and selenium in patients with acute macular degeneration and diabetic retinopathy.

"Review: Antioxidant Protection of the Ageing Macula", Gerster, He ' Iga, Age and Ageing, 1991;20:60-
69. (Address: Helga Gerster, Department of Human Nutrition and Health, F. Hoffman-La Roche & Co.,
Ltd., Grensacherstrasse 124, 4002, Basel, Switzerland)

Oxidative damage to DNA, proteins and lipids is the greatest contributing factor to ageing, cancer, heart disease, cataacts and cognitive dysfunction. Low vitamin c intake results in a statistically significant higher risk of heart disease mortality and total mortality in the next ten years. Other studies have shown low intakes of the antioxidant nutrients such as vitamin C and carotene increased the risk of developing age-related eye diseases such as cataracts. Large proportions of 6-Wr individuals have low intakes of antioxidants and blood levels. Individuals with higher dietary intakes of vitamin C or citrus fruit have a lower risk of cancer development.

"Vitamin C, Cancer and Aging", Age, 1993;16:55-58. (Address: Gladys Block, University of California School of Public Health, Department of Social and Administrative Health Sciences, Berkeley, CA 94720, U.S.A.)

Elderly & Vitamin C

Elderly

It is undisputed that both nutritional deficiencies and excesses had a significant impact on immunocompetence and the risk of various diseases. Almost published work emphasizes the reduction in average immune responses in the elderly. There are documented frequent occurrences of subclinical nutritional deficiencies in the aged. Nutritional education supplementation to increase energy intake approximately 500 kilocalories per day and to provide at least the recommended daily allowances of vitamins and trace elements for a period of eight weeks resulted in improved skin test responses, increased T lymphocyte number and enhanced lymphocyte proliferative response to phytohemagglutinin. It has also been found that improvements in diet and nutritional supplementation has enhanced natural killer cell activity, mitogen-induced lymphocyte stimulation response and delayed cutaneous hypersensitivity responses in the elderly and elderly subjects.

Vitamin C supplementation has enhanced lymphocyte proliferate responses in vitro and skin reactivity to tuberculin antigen in vivo.

"Nutrition and Immunity in the Elderly," Chandra, RK, Nutrition Reviews, December 1992;367-371.

Over a 3 year period, this study evaluated 761 noninstitutionalized individuals between 60 and 100 years of age for the relationship between blood pressure and vitamin C intake. The prevalence of elevated blood pressure was approximately across the range of less than 60mg/day intake. This evidence supports the hypothesis that vitamin C and blood pressure are related.

"A Cross-Sectional Study of Vitamin C Intake and Blood Pressure in The Elderly", Jacques, PF. International J of Vitamin and Nutrition Research, 1992;62:252-255.

Vitamin C status was evaluated in 175 free-living, healthy, elderly people between 63 and 81 years of age who were not taking vitamin C supplements. Mean dietary ascorbic acid and serum concentrations were significantly higher for males. To maintain blood serum ascorbic acid levels of 1.0 mg/ 100 ml, 2 mg/kg/d of vitamin C would be needed for females and 3 mg/kg/d for males. Dietary ascorbic acid was the most important predictor of serum concentrations.

"Sex is a Factor in The Levels of Serum Ascorbic Acid in Healthy Elderly Population", Itoh, Riochi, et al, International Journal of Vitamin and Nutrition Research, 1989;59:365-372.

Antioxidants' roles in the prevention of macular degeneration are reviewed, Yellow pigments in the eye quench free radicals and singlet oxygen. These pigments are supported by antioxidant enzymes and vitamins E and C. Vitamin C protects vitamin E by regenerating it from its reduced state. In animal models vitamin C supplementation has reduced free radical substances and retinal degeneration. The retina contains a higher concentration of carotenoids and vitamins E and C than other tissues. A higher level of those antioxidant nutrients may be needed to counteract light's damaging effects. Progression of degenerative changes and improvement in some cases has been shown as a result of beta carotene, C and E and selenium in patients with acute macular degeneration and diabetic retinopathy.

"Review: Antioxidant Protection of the Ageing Macula", Gerster, Helga, Age and Ageing, 1991;20:60-69.

The results of this study of 30 elderly individuals, institutionalized on a long-term basis, suggest that supplementation with physiologic doses of vitamins A, C and E in combination can improve cell mediated immunity. Further studies are needed to see if long-term vitamin supplementation results in reduced morbidity in such patients.

"The Effect of Dietary Supplementation With Vitamins A, C and E on Cell-Mediated Immune Function in Elderly Long-Stay Patients: A Randomized, Controlled Trial", Penn, N.D., et al, Age and Ageing, 1991;20:169-174.

Aids

Aids

This report by a practising clinician who used 50 to 200g per day of vitamin C for the treatment of AIDS patients, notes that vitamin C reduces AIDS to a significant degree. He emphasizes the absolute necessity of massive doses and the avoidance and treatment of opportunistic infection. The success of vitamin C treatment depends of the consistent -administration of enough vitamin C to neutralize free radicals produced by the various disease states.

"Vitamin C in the Treatment of Acquired Immune Deficiency Syndrome (AIDS)", Cathcart, Robert F., III, Medical Hypotheses, 1984; 14:42343 3.

This article reviews the role of glutathione in AIDS. Glutathione is the main intracellular defence against oxidative stress and is decreased in the plasma, lung fluid and T-lymphocytes in individuals with AIDS. Restoring glutathione concentrations will reduce reactive oxygen species, inhibit HIV stimulation by inflammatory cytokines, and block viral production. Replenishment may also restore immune function of T lymphocytes and reduce the cachexia with is often seen in the late stages of AIDS. Vitamin C can also inhibit HIV replication in vitro in synergy with N-acetylcysteine. Two researchers have suggested that antioxidant therapy with N-acetylcysteine and vitamin C have merit given their low toxicity.

"Glutathione Deficiency and Human Immunodeficiency Virus Infection", Stall, Frank, et al, The Lancet, April 11, 1992;339:909-912.

HIV & Vitamin C

HIV

Supplementation with vitamins C and E may reduce oxidative stress in HIV-positive individuals, thereby possibly reducing the viral load, according to this study conducted on 49 HIV patients. Plasma antioxidant micronutrient status, breath pentane output, plasma lipid peroxides, malondialdehyde and viral load were measured at baseline and at 3 months. Those patients taking the vitamins exhibited a reduction in lipid peroxidation, plasma lipid peroxides, and malondialdehyde. There was also a trend towards reduction in viral load. This is worthy of larger clinical trials, especially in HIV-infected persons who cannot afford new combination therapies.

Allard JP; Aghdassi E; Chau J; Tam C; Kovacs CM; Salit IE; Walmsley SL: Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects, AIDS, 1998 Sep 10; 12(13):1653-9

This study found that the continuous presence of ascorbic acid was necessary for HIV suppression. N-acetylcysteine at 10mmol/I cause less than a twofold inhibition of HIV reverse transcriptase activity and had a synergistic effect when tested simultaneously with ascorbic acid. These results support the potent antiviral effects of ascorbic acid and suggest its synergistic effect with certain thiols. Removal of ascorbate resulted in resumption of viral replication. The amount needed to produce this effect is equivalent to about 12g of vitamin C orally. By taking high ascorbate in the plasma to bowel tolerance, one may be able to achieve these high ascorbate levels. Intravenous infusion may be the method of choice to maintain high dose levels in the plasma. Once the system has been saturated with IV vitamin C and bowel tolerance levels of vitamin C have been achieved, the patient could reduce the frequency of IV infusions and maintain a saturated vitamin C state with oral vitamin C.

"Comparative Study of Anti-HIV Activities of Ascorbate and Thiol-Containing Reducing Agents and Chronically HIV Infected Cells", Harakeh, Steve and Jariwalla, Raxit J., American Journal of Clinical Nutrition, 1991;54:123IS-5S.

HIV Infection

HIV Infection

In this review article it is concluded that antioxidants may have a profound effect on the AIDS infection. HIV activity is affected by concentration of antioxidants. Vitamin C and glutathione inhibit replication of HIV. This researcher concludes that the molecular process underlying HIV activation indicates that a cellular transcription factor might be modulated by cellular antioxidant levels.

"Antioxidants Linked to HIV Infection", The Nutrition Report, April 1992; 10(4):29/" Cellular Antioxidant Status in Human Immunodeficiency Virus Replication", Baker, D., Nutrition Reviews, 1992;50:15-17.

HIV Replication

HIV Replication

This study showed that continual exposure of HIV-infected T-cells to vitamin C showed significant
inhibition of viral replication in chronically infected cells and multinucleated giant cell formation in
acutely affected cells. If these findings are confirmed by other work, ascorbate should be used in clinical
trials for AIDS and ARC patients.         r

"Suppression of Human Immunodeficiency Virus Replication by Ascorbate in Chronically and Acutely Infected Cells", Davies, Stephen, MA, BM, Journal of Nutritional Medicine, 1990;1:345346/Pauling, L., et al, Proceedings of The National Academy of Sciences, September 1990 ; 87:7245-7249.

Continuous bathing of HIV infected cells with fresh ascorbate (vitamin C) resulted in inhibition of viral replication. This signifies that vitamin C works on different areas of the HIV lifecycle than does AZT or alph-interferon. The next step will be to establish ascorbate's effect on HIV in human patients. Based on laboratory work at least l2g,day would be necessary to attain minimal levels in blood plasma for HIV suppression. This research was published in the National Academy of Sciences, 1990;87:7245-7249.

"LPI Scientists Find Vitamin C Inhibits AIDS Virus in Cell Culture", Linus Pauling Institute of Science and Medicine Newsletter, Winter, 1990;3(3);1-1,4.

Alcohol & Vitamin C

Alcohol

Thirteen healthy male subjects were evaluated for the ability of ascorbic acid to clear plasma alcohol levels. Long-term vitamin C supplementation resulted in better alcohol clearance. Ascorbic acid may work by functioning as an electron donor and accelerating the conversion of alcohol to its metabolites.

"Effect of Ascorbic Acid on Plasma Alcohol Clearance", Chen, Marianne F., ScD, et al, Journal of The American College of Nutrition, 1990;9(3):185-189.


Allergic Rhinitis

Allergic Rhinitis

Vitamin C has been shown to stimulate nonenzymatic histamine degradation. It appears to accelerate the recovery from histamine airway constriction and produced a significant increase in the PC 15 FEV 1. 2g of vitamin C acutely decreases airway responsiveness to inhaled histamine in subjects with hay fever.

"Effect of Vitamin C on Histamine Bronchial Responsiveness of Patients With Allergic Rhinitis. Bucca, C et al, Annals of Allergy, October 1990;65:311-314.

Alzheimer's Disease & Vitamin C

Alzheimer's Disease

High-dose vitamin E and C supplements may decrease the risk of Alzheimer's Disease (AD), according to this study conducted on 633 people (aged 65 years or more) over a period of 4.3 years. During this time, 91 of the participants developed the criteria for AD. However, none of the 27 vitamin E supplement users had AD, and none of the 23 vitamin C users developed the disease. There was no relation between Alzheimer disease and use of multivitamins. These data suggest that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.

Morris MC; Beckett LA; Scherr PA; Hebert LE; Bennett DA; Field TS; Evans DA: Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease, Alzheimer Dis Assoc Disord, 1998 Sep; 12(3):121-6

Vitamin C levels appear to be decreased in Alzheimer's patients regardless of vitamin C intake, according to this study conducted on several stages of Alzheimer's patients. In the home-living Alzheimer subjects, vitamin C plasma levels decreased in proportion to the severity of the cognitive impairment despite similar vitamin C intakes. The hospitalized Alzheimer subjects had normal vitamin C intakes, but their plasma vitamin C was lower than that of community-living subjects. Institutionalized Alzheimer subjects had normal vitamin C and albumin levels and vitamin C intakes compared with community-dwelling subjects of similar degree of cognitive impairment. These results indicate that plasma vitamin C is lower in AD in proportion to the degree of cognitive impairment and is not explained by lower vitamin C intake.

Rivi`ere S; Birlouez-Aragon I; Nourhash?emi F; Vellas B: Low plasma vitamin C in Alzheimer patients despite an adequate diet, Int J Geriatr Psychiatry, 1998 Nov; 13(11):749-54

Antibiotics

Antibiotics

A recent Harvard study notes that Vitamin C inhibits bacterial resistance to antibiotic therapy and might reduce the dose of antibiotics necessary to effectively suppress bacterial growth

"Vitamin C Enhances Antibiotic Therapy", The Nutrition Report, April, 1992;10(4):3 1/"Decreased Resistance to Antibiotics and Plasmid Loss in Plasmid-Carrying Strains of Staphylococcus Aureus Treated With Ascorbic Acid", Mutation Research, 199 1;264:119-125.

In a study evaluating the relationship between vitamin C intake and mortality in 11,3 84
noninstitutionalized adults aged 25 to 74 years who were nutritionally examined, with follow up, found
there was an inverse relationship between vitamin C intake and the standard mortality ration which was
strong for males and weak for females. The findings were generally consistent with earlier cohort studies
showing a reduced overall mortality associated with increased dietary vitamin C intake. Even if
increased vitamin C per se only has a small beneficial effect, the total population impact would be quite
substantial because of the large variations in vitamin C intake and widespread use of vitamin C
supplements.         1

"Vitamin C Intake and Mortality Among a Sample of the United States Population", Enstrom, James E., Epidemiology, May 1992;3(3):195-202.

500 mg of ascorbic acid given with every 250 mg of tetracycline increased tetracycline blood levels at 2 hours 3 to 15 fold compared to tetracycline administration alone. Vitamin C therapy in conjunction with tetracycline medications may reduce the duration of their use and allow for lower doses of this family of antibiotics to be used thereby reducing potential side effects.

"Adjunctive Ascorbic Acid Administration and Antibiotic Therapy", Freinberg, N. and Lyte, T., Journal of Dental Research, 1957;36: 260-262. "Vitamin C Potentiates Antibiotic Therapy", Gaby, A, Townsend Letter for Doctors, August/September 1990;523

In this study of 9 volunteers, after 2 weeks at a dose of 2g/day blood histamine levels fell by 40 per cent. It is noted that at the 500mg dose, the level of vitamin C achievable by a conscientious diet, there was not a histamine reducing effect.

"Antihistamine Effects and Complications of Supplemental Vitamin C", Johnston, CS et al, J of the American Dietetic Association, August 1992;92(8):988-989.

Antioxidants

Antioxidants

Plasma levels of the antioxidants vitamins A, C and E and carotene were measured in 2974 men over a 2 year period. Out of this group 204 men died of cancer, including 68 with cancer of the bronchus and 37 with gastrointestinal cancer. Overall mortality was associated with low levels of carotene and vitamin C. Stomach cancer patients had lower mean vitamin C and vitamin A levels than survivors. Low vitamin C increased the risk to stomach cancer and gastrointestinal cancer in older subjects. This study was a 12 year follow-up study. This work also encouraged further study in the role of vitamins and the prevention of cancer.

"Plasma Antioxidant Vitamins and Subsequent Cancer Mortality in Twelve-Year Follow-up of the Prospective Basel Study", Stahelin, Hannes B., et al, American Journal of Epidemiology, 1991;133:766-75.

Antioxidants and Cancer Prevention

Antioxidants and Cancer Prevention

There are over 500 naturally occurring carotenoids which are potent antioxidants and immune stimulants. There appears to be a protective effect from cancer with fruit and vegetables which may be rich in antioxidants. Stomach and lung cancer appear to have strong associations with the carotenoids (beta-carotene). Vitamin C is a water soluble antioxidant that scavenges free radicals and reactive oxygen molecules as well as reducing nitrite. It also stimulates immune function. Diet and plasma studies support a protective role of vitamin C in stomach cancer. There also appears in diet studies that vitamin C has a protective role in oral and esophageal cancers. It is not clear whether it is the vitamin C or other constituents in fruits and vegetables that may have the benefit.

"Antioxidant Micronutrients and Cancer Prevention", Dorgan, Joanne F., M.P.H., Ph.D. and Schatzkin, Arthur, M.D., Dr.P.H., Hematology/ Oncology Clinics of North America, February 1991;5(1);43-68.

Antioxidants: malignancies

Antioxidants: malignancies

Recent evidence suggests that beta-carotene and/or vitamin C may reverse or reduce the risk of cervical dysplasia and oral leukoplakia. These two nutrients along with vitamin E may also reduce the risk of atrophic gastritis and/or gastric cancer. Evidence suggests bronchial metaplasia has responded to retinoids, vitamin C, folic acid and vitamin B12. Lung cancer may be prevented by vitamins C, E and beta-carotene.

"Premalignant Lesions: Role of Antioxidant Vitamins Beta-Carotene in Risk Reduction and Prevention of Malignant Transformation", Singh, Vishwa N. and Gaby, Suzanne K., American Journal of Clinical Nutrition, 1991;53:386S-390S.

This is a summary report on the symposium held by the National Cancer Institutes of Health, September 10-12, 1990, on the role of vitamin C as an antioxidant, its enzymatic and immune properties, and its relation to cancer. The results of the conference clearly show that vitamin C has multiple complex biological effects, probably more widespread than any other nutrient. Some of the effects relate to vitamin C's chemical properties and not from its role as a vitamin. Vitamin C's interaction with enzymes is important. Studies were reported on vitamin C's effect as a free radical scavenger. Vitamin C was the most effective of all free radical scavengers tested. Its ability to kill bacteria was reduced in models.. Vitamin C has been shown to suppress chemically induced transformation of cancer cells. This may be due to the redox potential of the cells and the changes in lipid metabolism with ascorbate treatment.

It has also been shown that ascorbate prevents oncogenic transformation of cells infected with certain viruses such as the mouse sarcoma virus. In HIV infection T lymphocytes' reverse transcriptase activity was reduced by more than 99% when cells were bathed in ascorbate. The development of mammary tumors in animal models has been delayed in ascorbate treated animals. The radioprotective effects of ascorbic acid were also shown in animal models. Dr. Block from the National Cancer Institute summarized epidemiologic data on vitamin C and cancer prevention. In 46 reported epidemiologic studies, 33 showed significant protective effects on cancer mortality incidence. Strong epidemiologic evidence for protection was for cancers of the esophagus, larynx, oral cavity and pancreas. Evidence for protection from cancer of the stomach, rectum, lung, breast and uterine-cervix was also present.

Additional scientific studies are needed on ascorbate's biological actions before ascorbate can be used in prevention and treatment of cancer.

"Ascorbic Acid: Biological Functions and Relation to Cancer", Henson, Donald Earl, et al, Journal of The National Cancer Institute, April 17, 1991;83(8):547-550.

Arthritis

Arthritis

Vitamin C prevented and regressed induced arthritis in rats. Since vitamin C levels are significantly reduced in rheumatoid arthritis the authors conclude that vitamin C status needs to be assesses in this condition.

"Vitamin C Influence on Localized Adjuvant Arthritis", Davis, Robert H., Ph.D., et al, Journal of The American Podiatric Medical Association, August 1990;80(8):414-418.



Atherosclerosis

Atherosclerosis

This article starts by saying that there is a common interest among nutritionists, epidemiologists and molecular scientists on the possible preventive role of the antioxidant vitamin C in atherosclerosis. Several researchers have stated that their findings suggest that there is a possible preventive role of the antioxidant vitamin C in atherosclerosis. It may inhibit oxidation of LDLcholesterol, increase HDL, particularly in the elderly. Vitamin C was found to be more powerful than vitamin E as an antioxidant and can help preserve endogenous antioxidants found in LDL itself. Vitamin C is the only antioxidant that completely protected lipoproteins against oxidative damage.

"Vitamin C Seemed to Help Prevent CAD", Strickland, David A., Medical World News, August 1991;11.

LDL Oxidation

LDL Oxidation

Vitamin C can protect LDL by two different mechanisms: 1. Free radical scavenging protects LDL from aqueous oxidants. 2. DHA modifies LDL or decomposition products, thereby increasing the resistance to metal-ion- dependent oxidation. Vitamin C has also been shown to stabilize LDL from oxidation in smokers.

"Ascorbic Acid Oxidation Products (S) Protect Human Low Density Lipoprotein Against Atherogenic Modification," Retsky, Karen L., et al, Journal of Biological Chemistry, January 15, 1993;268(2):13041309.

Reduced levels of plasma vitamin C and beta carotene increase the risk of ischemic heart disease and stroke. The results of this study showed that even though vitamin E was in the normal range, there may be an increased risk of dying from ischemic heart disease when plasma carotene and/or vitamin C levels are low.

"Low Beta-Carotene/Vitamin C Increase Heart Disease Risk", The Nutrition Report, May 1993;11(5):34/"Poor Plasma Status of Carotene and Vitamin C is Associated With Higher Mortality From Ischemic Heart Disease and Stroke", Gey, K., et al, Clinical Investigation, 1993;71:3-6.


Blood lead levels

Blood lead levels

High serum levels of vitamin C are associated with low blood levels of lead, according to this study conducted on 19,578 children and adults. None of those tested had a history of lead poisoning. The study found elevated lead levels in 22 children and 57 adults, and discovered that serum ascorbic acid level was a significant independent continuous predictor of decreased blood lead levels in adults. This data could be significant for the prevention of lead toxicity.

Simon, Joel A. MD; Hudes, Esther S. MD: JAMA, June 1999; 281:2289-2293

Blood Pressure

Blood Pressure

In three different populations the relationship between HDL and plasma ascorbic acid was evaluated, and it was found that In two samples of elderly volunteers HDL levels increased the higher the ascorbic levels in plasma. Except in Caucasian males and those on blood pressure medication, blood pressure dropped in proportion to ascorbic acid content. Vitamin C did not seem to affect HDL cholesterol and blood pressure in smokers.

"Effects of Vitamin C on HDL and Blood Pressure", Jacques, P.F., Journal of The American College of Nutrition, 1990;9(5):554/ Abstract 106.

This study evaluated the antioxidant status and blood pressure in 168 healthy residents of Augusta, Georgia on their usual diets. Plasma concentrations of vitamin C were significantly inversely related to systolic and diastolic blood pressure. The highest and lowest quintiles of vitamin C differed significantly in mean systolic blood pressure and diastolic blood pressure.

"Plasma Ascorbic Acid Concentrations Relate Inversely to Blood Pressure in Human Subjects," Moran, John P., et al, American Journal of Clinical Nutrition, 1993;57:213-7.

Recent evidence suggests that vitamin C deficiency may be a dietary risk factor for cardiovascular disease. In a cross sectional study of 491 males and females 20 to 60 years of age, 696 males and females 60 to 100 years, and 259 male and female Chinese-Americans 69-96 years of age, vitamin C had good correlation with mean HDL levels and was inversely correlated with LDL cholesterol and high blood pressure. Higher vitamin C status is consistently associated with protective levels of the cardiovascular risk factors mentioned.

"Relationship of Vitamin C Status to Cholesterol and Blood Pressure", Jacques, Paul F., Sc.D., Beyond Deficiency: New Views on the Function and Health Effects of Vitamins, New York Academy of Sciences, February 9-12, 1992;19.

The results of this randomized field trial indicated that with vitamin C supplementation there is a 3.7--9.5% higher level of HDL-C, 4.1 % lower level of LDL-C, and a 1.9-5.5% lower level of blood pressure with each 30 umol/l increment of plasma ascorbic acid levels. Deficient plasma ascorbic acid levels may be included as a nutritional risk factor for cardiovascular disease in the near future.

"Effect of Vitamin C on High-Density Lipoprotein Cholesterol and Blood Pressure", Jacques, Paul F., Scl), Journal of the American College of Nutrition, 1992; 11(2):139-144.

Some studies have shown an inverse relationship between vitamin C and blood pressure.

In 2 small intervention trials, vitamin C supplementation has shown a decrease in blood pressure in borderline hypertensive subjects. Some suggest that vitamin C intake is closely correlated with potassium intake, which may be associated with blood pressure lowering effects. In rat models vitamin C has enhanced the ability of tyrosine to decrease blood pressure. Vitamin C levels in spontaneous hypertensive rats are lower than controls.

Supplementation has decreased blood pressure in these spontaneously hypertensive rats. In spontaneously hypertensive rats the myocardium and myocardial membrane show significantly lower vitamin E levels. Vitamin C helps regenerate vitamin E, a lipid antioxidant from its oxidized form. Scurvy is rare in industrialized countries, yet low vitamin C levels are not infrequent.

Vitamin C participates in a large number of enzymatic and nonenzymatic reactions in all tissues, and it is possible that vitamin status could affect blood pressure even though the exact mechanism at present is not known. Further clinical trials are warranted to determine whether vitamin C has a physiologic effect on blood pressure in humans as suggested by epiderniologic data and 2 small intervention trials.

"Vitamin C and Lowering Blood Pressure: Need For Intervention Trials", Hemila, Harri, Journal of Hypertension, 1991;9(11):1076-1077.

In a study of 169 adults it was found that vitamin C levels were inversely related to blood pressure. There was significantly lower blood pressure in the highest versus lowest quintile of plasma vitamin C. It was found that systolic and diastolic blood pressure significantly decreased by 4.21 and 3.32 mmHg from baseline levels in the vitamin C supplemented group.

"Ascorbic Acid Supplements and Blood Pressure -- A Four Week Pilot Study", Feldman, E.B., Beyond Deficiency: New Views on the Function and Health Effects of Vitamins, New York Academy of Sciences, February 9-12, 1992;P-9.

Hypertension

Hypertension

In 20 adults, 1000mg/dayof ascorbic acid was evaluated. Supplementation reduced systolic blood pressure and pulse pressure. It enhances prostacyclin which reduces free radical damage to tissues and increases vasodilation. It can chelate heavy metals. Vitamin C supplementation may have therapeutic value in human hypertensive disease."Blood Pressure and Plasma Lipids During Ascorbic Acid Supplementation in Borderline Hypertensive and Normotensive Adults", Osilesi, Odutola, Ph.D., et al, Nutrition Research, 199 1; 11:405-412.

Bronchial Responsiveness

Bronchial Responsiveness

An increase in bronchial responsiveness is observed in several conditions affecting the airway, such as infections of the upper respiratory tract, atopic rhinitis and exposure to airborne pollutants caused from smoking. Two grams of vitamin C protected against bronchial responsiveness and has been demonstrated for colds, hay fever and exposure to smog.

"Effect of Vitamin C on Transient Increase of Bronchoresponsiveness in Conditions Affecting the Upper Respiratory Airways", Bucca, C., et al, Beyond Deficiency: New Views on The Function and Health Effects of Vitamins, New York Academy of Sciences, February 9-12, 1992.

Bypass Surgery

Bypass Surgery

Twenty-six patients undergoing either coronary bypass surgery or heart valve replacement were given 1.0 gm of ascorbate intravenously about 1.5 hours prior to cardiopulmonary bypass, and an ascorbate containing cardioplegic solution at a concentration of 1.0 mL or placebo. The authors noted that ascorbate use during bypass surgery extends the period in which ischemia can be tolerated prior to reperfusion. Ascorbate may be minimizing myocardial stress during surgery. These findings are in line with the concept of oxygen free radical release during reperfusion which causes myocardial damage.

"A Protective Role For Ascorbate in Induced Ischemic Arrest Associated with Cardiopulmonary Bypass", Eddy, Lynne, et al, Journal of Applied Cardiology, 1990;5:409-414.

Breast Cancer & Vitamin C

Breast Cancer

This article reviewed 12 case-controlled studies of diet and breast cancer. There was a clear positive correlation between breast cancer risk and saturated fat intake in postmenopausal women. There was a protective effect with consumption of fruit and vegetables. Vitamin C had the most significant inverse association with breast cancer in all women including premenopausal women.

"Dietary Factors and The Risk of Breast Cancer: Combined Analysis of 12 Case-Controlled Studies", Howe, Geoffrey R., et al, Journal of The National Cancer Institute, 1990;82:561-569.

Gastric Cancer

Gastric Cancer

In 1016 patients with gastric cancer who were compared to 1,159 patient controls it was found that the risk of gastric cancer was found to rise with increasing consumption of nitrates and protein and to decrease in proportion to intake of ascorbic acid, as well as other antioxidants with vitamin C showing the strongest geographic relationship

"A Case-Controlled Study of Gastric Cancer and Diet in Italy: 11 Association With Nutrients", Buiatti, Eva, et al, International Journal of Cancer, 1990;45:896-901.

Symposium

Symposium

This is a review of a symposium sponsored by the National Cancer Institute on vitamin C entitled, "Ascorbic Acid: Biological Functions and Relation To Cancer" held September 10-12, 1990 at the Lister Hill Auditorium at the National Institutes of Health in Bethesda, Maryland. 40 papers were presented and 130 scientists and doctors were present from all over the world. Dr. Balz Frei from the University of California at Berkeley shared his work showing that no cancer causing chemical reaction (ex. lipid peroxidation) could be detected in human plasma as long as vitamin C was present. Lipid peroxidation would return when vitamin C was gone. Dr. Niki from the University of Tokyo stated that free radicals were destroyed faster by vitamin C than any other antioxidant. Dr. Linus Pauling noted that many animals manufacture the equivalent per body weight of 10,000 mg/d of vitamin C.

He reviewed studies where mice were exposed to carcinogenic ultraviolet light with varying amounts of vitamin C showing reductions and delay in cancerous lesion formation. With increased vitamin C consumption in mice with spontaneous mammary tumors delayed appearance of these tumors occurred. Two different researchers from the Linus Pauling Institute for Science and Medicine in Palo Alto, California, Drs. Raxit J. Jariwalla and Constance S. Tsao, reported on the benefits of vitamin C. Dr. Jariwalla showed that vitamin C in AIDS may inhibit a key viral enzyme needed for viral replication and reduced extracellular levels of p24 core protein. Dr. Tsao showed that vitamin C in conjunction with cupric sulfate had antitumor activity on human mammary tumor fragments implanted in mice. Dr. Joachim Liehr from the University of Texas at Galveston reported that vitamin C inhibited the incidence of kidney tumors induced by estradiol and diethylstilbesterol.

Pretreatment of hamsters with vitamin C protected them against the cancer causing effects of DES injections. In mice models Dr. Poydock showLFd complete inhibition of cancer cell growth with a vitamin C and B 12 combination. Dr. Poydock from the Mercyhurst College Cancer Research Center in Erie, Pennsylvania, who did these studies, gave a case report of a patient with adenocarcinorna of the lung treated intravenously with vitamin C/B 12 and the tumor was reduced significantly after three treatments. Dr. Okunieff from the Radiology Department at Harvard Medical School reported that vitamin C given to laboratory animals just prior to radiation therapy showed a significant reduction in skin damage. A similar effect on bone marrow was also seen. In animals Dr. Okunieff reported that vitamin C necessitated only half as much radiation as those without vitamin C at 40 day survival.

Dr. Gary Meadows, from Washington State University, found that vitamin C supplementation in the drinking water of mice inhibited cancer growth, enhanced the benefit of chemotherapeutic agents, and in combination or by itself increased survival time of tumor bearing mice. Dr. Marcus from Lederle Laboratory in Pearl River, New York found that vitamin C usage was increased with high dose interleukin therapy and suggested that vitamin C should be used as an adjunctive treatment while utilizing interleukin at high dose. Dr. Kan Shimpo from the Institute of Comprehensive Medical Sciences, School of Medicine Fujita Health, University of Japan, found that vitamin C decreased the toxicity of the cancer drug adriamycin. Vitamin C prevented elevation of lipid peroxides from adriamycin administration.

Dr. Jacob from the USDA Western Nutrition Research Center in San Francisco took eight healthy men and put them on a very low vitamin C diet of 5-20 mg/d for 60 days and found levels of fecal mutagens to be increased significantly. Dr. Mark Levine from the Laboratory of Cell Biology and Genetics, reported on NIDDKD a technique for assessing optimal vitamin C status which he calls "in situ kinetics". Dr. Block from the Division of Cancer Prevention and Control at the National Cancer Institute ended the symposium with a review of all the studies that have shown vitamin C having a protective effect in preventing cancer and the sites include the lung, larynx, oral cavity, esophagus, stomach, colon, rectum, pancreas, bladder, cervix, childhood brain tumors, endometrium and breast. Out of 47 studies 34 found vitamin C to have a protective effect from cancer at these sites. The amount of vitamin C that may be protective was stated by Dr. Block to be approximately 380 mg/d.

Those who had the top 25% of vitamin C intake had one-half the cancer risk from those in the bottom 25% of vitamin C intake. A report in the Journal of the National Cancer Institute (1990:82:561569) stated: "Vitamin C had the most consistent and statistically significant inverse association with breast cancer risk ".." If all postmenopausal women in the population modify their saturated fat intake to a level of the lower 1/5th of the population, the current rate of breast cancer would be reduced by 10% in North American women. . ....if all postmenopausal women in the population were to increase fruit and vegetable intake to reach an average daily consumption of vitamin C equaling the level among women in the upper 1/5th of the population the risk of beast cancer ... would be reduced by 16W. Twenty-two of 32 studies showed a cancer protective benefit from increased fruit intake.

It was also noted that blacks on the average have a much lower vitamin C serum level than whites as well as a higher cancer incidence and lower five year cancer survival rate. From these studies it was clear that increased vitamin C intake and fruit consumption are major preventive agents in cancer risk reduction.

"A Major Symposium on Vitamin C Sponsored by The National Cancer Institute", Klein, Morton A., December 1990, pp.7. (Address: Linus Pauling Institute of Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306-2025, U.S.A. 415-327-4064)

This is a summary of abstracts taken from the National Institutes of Health Symposium on vitamin C held September 10-12, 1990. Vitamin C protects plasma lipids against free radical damage from cigarette smoke, neutrophils and other oxidant producing agents. Plasma ascorbate regenerates membrane vitamin E which protects lipids from oxidation. Vitamin C prevented oncogenic transformation of cells infected with the Rous Sarcoma Virus. Vitamin C inhibited HIV replication in T lymphocytes by reducing viral protein production and reducing reverse transcriptase activity. Vitamin C modulates the growth of human leukemic cells. Vitamin C in animal models reduced renal tumors induced by estrogen, spontaneous mammary tumors, and UV-induced tumors. Topical application of ascorbic acid or a lipophilic derivative inhibited tumor promotion. Vitamin C with hydroxocobalamin increased the survival of mice with Ehrlich carcinoma and leukemia.

Vitamin C enhanced levodopa methylester chemotherapy and the survival of tumor bearing mice in conjunction with tumor masses becoming less invasive. Vitamin C enhanced the benefit of radiation therapy. Adriamycin cardiotoxicity was reduced in animals treated with ascorbate. Patients treated with high-dose interleukin 11 and lymphokine-activated killer cells were found to have greatly reduced ascorbate levels. Vitamin C is required for the synthesis of collagen, carnitine, peptidylglycine alpha-amidating monooxygenase and norepinephrine. Vitamin C is a neuromodulator and involved in electron transport. Vitamin C enhances the bioavailability of iron and stimulates acetylcholine receptor expression. Vitamin C regulates chondrocyte function at the epiphyseal growth plates. Vitamin C is found in very high concentrations in human neutrophils. Neutrophils with reduced ascorbate in a guinea pig model have reduced bacteriocidal activity. Complement C1Q was significantly reduced in ascorbate deficient guinea pigs.

Increased fetal mutagens, modified DNA in sperm, and increased oxidative stress are seen in ascorbate depleted humans. Vitamin C requirements in humans may be more appropriately determined by finding optimal enzyme levels that promote optimal enzyme function. There is a consistent and strong amount of epidemiologic evidence for the protective effect of vitamin C in a variety of human tumors.

"Vitamin C: Biological Functions and Relations to Cancer", Henson, Donald Earl, M.D., 1991, Summary of Abstracts.

Cardiovascular Risk

Cardiovascular Risk

Vitamin C supplementation has been shown to lower plasma cholesterol and in certain cases increase HDL cholesterol. In population studies blood pressure has been inversely correlated with vitamin C status. In a recent double-blind, placebo-controlled study in which one gram of ascorbic acid was taken daily for six weeks, a lowering of systolic and pulse pressure was observed. These new findings on blood pressure are encouraging and appear to occur even when vitamin C status is considered normal. The evidence reported here suggests that extra vitamin C is important in hypertensives, smokers, diabetics and elderly men.

"Vitamin C and Cardiovascular Risk Factors", D.L. Trout. American Journal of Clinical Nutrition, 1991;53:322S-325S.

Cholesterol Levels

Cholesterol Levels

Animal studies have consistently found that vitamin C has a substantial effect on cholesterol metabolism. Those with initial high cholesterol levels have had a more significant decrease in cholesterol levels with vitamin C supplementation. There appears to be a reduced absorption of cholesterol from the intestines with vitamin C supplementation. In guinea pig models vitamin C deficiency decreases the rate of catabolism in LDL cholesterol and increases the level of LDL-cholesterol in the plasma. High levels of vitamin C have decreased LDL levels in guinea pigs when fed an atherogenic diet. Vitamin C is a major water soluble antioxidant and may decrease lipid peroxidation directly or indirectly by regenerating vitamin E. In animal models, a vitamin C deficient diet tends to increase triglyceride levels. Vitamin C also participates in the synthesis of carnitine.

In studies in Great Britain the mortality from coronary heart disease and cerebrovascular disease is found to be negatively correlated with the average vitamin C intake. A similar inverse correlation has also been found with coronary artery disease and the amounts of fruits and vegetables eaten. In 16 populations of European countries it was found that low vitamin C levels were more common in regions with higher mortality rates from coronary heart disease. In 22 districts of Scotland, it was found that low vitamin C were the most notable dietary factor associated with mortality from coronary heart disease. The gorilla eats approximately 4 g of vitamin C a day, and the diet of our remote ancestors probably had between .4 and 2g per day.

"Vitamin C and Plasma Cholesterol", Hemila, Harri, Critical Reviews in Food Science and Nutrition, 1992;32(l):33-57.

Copper

Copper Deficiency and Neutropenia

A case report of a 68-year-old female patient who was hospitalized for severe anemia and neutropenia after receiving total parenteral nutrition for over 2.5 years. She was found to have low levels of copper and ceruloplasmin, and the bone marrow showed presence of ringed sideroblasts and vacuolated immature cells.

The patient was initially given .85 mg of copper chloride (which is equivalent to .4 mg of elemental copper) daily for 12 days, followed by 2.5 mg of copper chloride or 1.2 mgs of elemental copper daily for a total of 34 days as a bolus injection. After 2 months her hemoglobin had risen from 6.3 to 10.5 g/dl, and the number of granulocytes from .14 to 4.0 x 109/l. It is noted ceruloplasmin is important for the conversion of iron from its ferris to its ferric, more absorbable, form. Also the low activity of the copper-containing enzyme superoxide dismutase may also cause anemia since copper:zinc SOD contains 60% of the copper in erythrocytes.

Low copper:zinc SOD levels may accelerate the membrane defect because of decreased capacity to prevent superoxide concentrations in the cell membrane. It is believed copper is related closely to the development of granulocytes.

As total parenteral nutrition increases, copper deficiency is reported with increasing frequency. Copper is important in maintaining normal hematopoiesis.

"Anemia and Neutropenia in A Case of Copper Deficiency: Role of Copper in Normal Hematopoiesis", Hirase, Nobuhisa, et al, ACTA Hematologica, 1992;87:195-197.

Diabetes

Diabetes

This study evaluated whether chronic hyperglycemia may result in intracellular deficiency of vitamin C. It was noted that leukocyte ascorbic acid levels tended to be lower in insulin dependent diabetics than in controls or noninsulin dependent diabetic patients. In diabetic patients, plasma ascorbic acid levels were negatively correlated with glycosylated hemoglobin.

"Ascorbic Acid Status in Diabetes Mellitus", Lysy, J., M.D., and Zimmerman, M.D., Nutrition Research, 1992;12:713-720.

Susceptibility to LDL oxidation, relative to vitamin E and vitamin C status, was evaluated in 25 noninsulin dependent diabetics and 22 controls. The authors noted that Vitamin C supplementation may be beneficial in the prevention and management of atherosclerosis in diabetic patients.

"Vitamin C Low in Diabetics", The Nutrition Report, June 1992; 10(6):46/"Effects of Dietary Antioxidants on LDL Oxidation in Noninsulin-Dependent Diabetics", Brazg, R., et al, Clin Res, 1992;40:103A.

Eleven Type 1 diabetics had reduced ascorbic acid content of mononuclear leukocytes by 2 per cent compared to 1 controls even though they had adequate dietary intake.

"Tissue Stores of Ascorbic Acid Reduced in Diabetes", Family Practice News, April 1-14, 1990;20(7):38.

Plasma ascorbic acid levels were measured in 58 diabetic patients, and in 19 patients of this group random urinary ascorbic acid excretion was measured. Plasma ascorbic acid concentrations were significantly lower in diabetics than controls. Vitamin C supplementation may be warranted in diabetic who are poorly controlled.

"Abnormalities of Ascorbic Acid Metabolism in Diabetic Control: Differences Between Diabetic Patients and Diabetic Rats", Yue, D.K., et al, Diabetes Research and Clinical Practice, 1990;9:239-244.

Dietary Factors

Contents:

Food Hypersensitivity
Diet
Dietary fat

Food Hypersensitivity


Most children with atopic dermatitis can be positively diagnosed for a food allergy using a prick skin test. In evaluating 165 patients with atopic dermatitis between 4 months and 21.9 years, 60% had at least 1 positive skin prick test. In doing a total of 266 double-blind, placebo-controlled food challenges 64 patients or 38.7% had a positive challenge. Milk, egg, peanut, soy, wheat, cod fish, catfish and cashew accounted for 89% of the positive challenges.

Burks, A., Wesley, M.D., et al: Atopic Dermatitis and Food Hypersensitivity Reactions, Journal of Pediatrics, 1998;132:132-136

Diet

In atopic dermatitis [AD], not only food consumption, but direct skin-contact too can provoke hypersensitivity reactions. We imitated food immediate-contact hypersensitivity [FICH] to cow's milk, egg, peanut or soy by a skin provocation test (the skin application food test [SAFT].

FICH was observed in:

egg72%
cow's milk 47%
peanut34%



FICH is an important symptom in children with AD and food allergy.

Oranje AP et al., Food immediate-contact hypersensitivity (FICH) and elimination diet in young children with atopic dermatitis. Preliminary results in 107 children. Acta Derm Venereol Suppl (Stockh), 176:1992, 41-4.

Dietary fat

The last two decades have seen an increase in the prevalence of asthma, eczema, and allergic rhinitis in developed countries. This increase has been paralleled by a fall in the consumption of saturated fat and an increase in the amount of polyunsaturated fat in the diet. This is due to a reduction in the consumption of animal fat and an increase in the use of margarine and vegetable oils containing omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid. There is also evidence for a decrease in the consumption of oily fish which contain omega-3 PUFAs, such as eicosapentaenoic acid.

In a number of countries, there are social class and regional differences in the prevalence of allergic disease, which are associated with differences in the consumption of PUFAs. Linoleic acid is a precursor of arachidonic acid, which can be converted to prostaglandin E2 (PGE2), whereas eicosapentaenoic acid inhibits the formation of PGE2. PGE2 acts on T-lymphocytes to reduce the formation of interferon-gamma (IFN-gamma) without affecting the formation of interleukin-4 (IL-4).

This may lead to the development of allergic sensitization, since IL-4 promotes the synthesis of immunoglobulin E (IgE), whereas IFN-gamma has the opposite effect. Changes in the diet may explain the increase in the prevalence of asthma, eczema and allergic rhinitis. The effects of diet may be mediated through an increase in the synthesis of prostaglandin E2 which in turn can promote the formation of immunoglobulin E.

Black PN & Sharpe S: Dietary fat and asthma: is there a connection? Eur Respir J, 10:6-12, 1997 Jan.

Exercise Induced Bronchoconstriction

Exercise Induced Bronchoconstriction

This letter to the editor reports that Vitamin C has been shown to attenuate exercise induced bronchoconstriction and is a stimulator of prostacyclin production.

"Caffeine, Prostacyclin and Exercise Induced Bronchoconstriction", Simon, Joel A., M.D., Chest, April 1991;99(4):1053.

Eye

Eye

It is noted that vitamin C's function in various regions of the eye is not well understood. One important function that is known is its protection against oxidative damage, particularly from photo-induced damage. There is also data suggesting that vitamin C may participate in oxidative modification of lens protein seen with ageing. Vitamin C interacts with selenium and is important in the recycling of vitamin E in these membranes. Vitamin C is in very high concentrations in the eye which supports the argument that one of its major functions is to protect against oxidative damage, particularly against light-induced damage. Vitamin C affects fibronectin and laminin, 2 components of the basal lamina, and synthesis of glycosaminoglycans. Vitamin C may help healing of the cornea. It also affects arachidonic acid metabolism in the iris, ciliary body and cornea. Rat models have shown that ascorbic acid reduces membrane damage from diabetes.

It is believed that vitamin C rids the lens of 02, thereby decreasing the likelihood of oxidative insult. There is a high concentration of ascorbate in the aqueous humor of diurnal animals relative to that of nocturnal animals, which supports its photoprotective role. Vitamin C clearly protects against light induced loss of retinal pigment and epithelium and photoreceptor cells. Ascorbic acid in the lens prevents riboflavin-mediated light-induced damage to the cation pump and decreases photoperoxidation of the membranes. In a guinea pig model, supplementation with vitamin C decreased UV and heat-induced damage to the lens proteins. Injections of ascorbic acid have helped prevent the development of selenite-induced cataracts in rats. Epidemiologic evidence supports the connection between low intakes of ascorbate and certain types of cataracts. Ascorbic acid is low or absent in cataractous lenses.

Increased levels of dehydroascorbate and ascorbate free radicals in human lenses are associated with the progression of senile cataracts. Vitamin C can protect against oxidation by its scavenging of free radicals but it also may be a prooxidant by metal-catalyzed oxidation. In the presence of iron or copper, antioxidant ascorbic acid can become oxidized, forming dehydroascorbate, hydrogen peroxide and reduced metals. The hydrogen peroxide may react with the reduced metal, generating the hydroxyl radical or other oxygen radical species. Increasing levels of copper and iron have been reported in ageing lenses and in cataracts. Vitamin C may be involved in the protein modification that occurs during cataract formation. This does not mean that vitamin C actually causes cataracts; these reactions may occur when the overall oxidative stress of the lens exceeds the capacity of the antioxidant system, there is a change in metal metabolism, or when mechanisms that maintain reduced ascorbic acid are compromised.

"Ascorbic Acid and the Eye", Garland, Donita L., American Journal of Clinical Nutrition, 1991;54:1198S-1202S.

Vitamin C is much higher in the aqueous humor of diurnal animals than nocturnal animals. The eye is susceptible to photooxidative damage from free radicals. Ascorbic acid may protect the eye by scavenging disease free radicals. Vitamin C may be in such high concentrations in the eye compared with other antioxidants because there is so much extracellular fluid and a low protein content.

"Ocular Ascorbate Transport Metabolism", Rose, Richard and Dode, Ann M., Comp. Biochem. Physiol., 1991;108(2):273-285.

Heart Attack Prevention

Heart Attack Prevention

Though gross vitamin C deficiency is essentially unknown, chronic dietary vitamin deficiency is widespread. Heart disease is an early stage of scurvy. Atherosclerosis is caused by the instability of the vessel wall as a consequence of vitamin C deficiency. Pauling believes that high cholesterol or other risk factors in the blood are a risk for heart disease, only if the walls of the artery are weakened by vitamin C deficiency.

"How Vitamin C Can Prevent Heart Attack and Stroke", Linus Pauling Institute For Science and Medicine Newsletter, March 1992;3. (Address: Linus Pauling Institute For Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306, U.S.A.)

Heart Disease

Heart Disease

The authors suggest the potential protective effects of vitamin C, and that marginal vitamin C deficiency may result in increased oxidative and heart tissue damage, resulting in cardiovascular disease.

"Vitamin C Deficiency Might Cause Heart Disease", The Nutrition Report, September 1992; 10(9):67. "Protective Role of Ascorbic Acid Against Lipid Peroxidation and Myocardial Injury", Chakrabarty, S., et al, Molecular and Cell Biochemistry, 1992; 111:41-47.

Recently the First National Health and Nutrition Survey found that men and women with the highest vitamin C intakes, at 50+ mg/day and regular vitamin C containing supplements, had 25 and 45% lower coronary heart disease mortality rates, respectively, than subjects with the lowest vitamin cC intake, which was less than 50mg/day. since known isk factors for coronary heart disease explain approximately 50 to 60% of coronary heart disease incidence, the possibility that antioxidant nurtients (such as vitamin Q cannot be ruled out. the article goes on to describe the qualities of this 'unique antioxidant'.

"Vitamin C and Heart Disease", Simon, Joel, A., The Nutrition Report, August 1992; 10(8):5 8,64.

Vitamin C is important in the conversion of cholesterol to bile salts in animal models, and it has been demonstrated to be important in lipid regulation of the guinea pig, rabbit and rat.

Correlation studies in humans have shown an inverse relationship between vitamin C and cardiovascular disease mortality. In those individuals with high total cholesterol levels greater than 5.2 mmol/l (200 mg/dl) and less than full tissue saturation, increasing vitamin C concentrations may have a mild reducing effect on total cholesterol. Vitamin C appears to promote the production and inhibit the degradation of prostacyclin, which may have beneficial effects in thrombosis and atherogenesis. Vitamin C is also important in the prevention of lipid peroxidation, specifically of LDL cholesterol. Vitamin C is beneficial in the aqueous media and in a number of studies has also shown that it can help regenerate oxidized vitamin E, thereby continuing the inhibition of lipid peroxidation. Those groups which are at high risk for coronary artery disease, including men, the elderly, smokers, diabetics, hypertensives and those taking estrogen-containing contraceptives, have lower plasma vitamin C levels in general.

Even though much of the evidence linking vitamin C to cardiovascular disease is circumstantial when taken in total, there is a suggested association.

"Vitamin C and Cardiovascular Disease: A Review", Simon, Joel A., M.D., M.P.H., The AmericanCollege of Nutrition, 1992; 11(2):107-125.

In 1941 the Canadian cardiologist Dr. Patterson reported that 80% of his heart disease patients had low vitamin C levels. In 1954 Dr. G. Willis showed with angiographic methods that vitamin C supplementation can reduce atherosclerotic plaque in the arteries of patients. In 1970 Dr. Pauling published his book on vitamin C. In the following decade vitamin C consumption in the United States rose 300%; during that same period mortality from heart disease in the U.S. decreased more than 3 0%, and the U.S. became the only country with a significant decrease in mortality from heart disease. In 1989 Dr. Rath and Dr. Pauling discovered that lipoprotein (a) is a surrogate for vitamin C and that optimal vitamin C intake prevents the deposition of lipoprotein (a) in the vascular wall.

In April of 1991 Drs. Pauling and Rath presented their publication, "Solution To The Puzzle of Human Cardiovascular Disease", a scientific paper which explains how vitamin C is the direct and most frequent cause of heart disease, the exact mechanism of how plasma risk factors lead to atherosclerotic plaque in the wall of arteries, why humans beings suffer from heart attacks and stroke but rarely from failure of other organs, and why human beings develop heart disease but not other species that are able to produce their own vitamin C in the body. In 1991 the publication "Solution To The Puzzle of Human Cardiovascular Disease" was distributed to the scientific session of the American Heart Association in Anaheim, California.

In January of 1992 the President of the American Heart Association, Dr. Virgil Brown, encouraged clinical trials using "megadoses" of vitamins. Dr. Pauling congratulated Dr. Brown for his actions and expressed the hope that the American Heart Association will now become a strong partner in the worldwide effort to improve human health through dietary supplementation of vitamins.

"Vitamin C and Heart Disease: A Chronology", Linus Pauling Institute for Science and Medicine Newsletter, March 1992;2. (Address: Linus Pauling Institute for Science and Medicine, 440 Page Mill Road, Palo Alto, CA 94306, U.S.A.)

In a study of 87,000 U.S. female nurses aged 34 to 59 years, with follow-up of 8 years the relative risk of coronary heart disease was .58 in the women with highest vitamin C intake, compared with women with low vitamin C intake. Those consuming a multivitamin had an even greater protective benefit than with vitamin C alone. The authors conclude that increased dietary vitamin C intake may help to reduce the risk of coronary artery disease.

"Vitamin C Reduces Risk For Heart Disease", The Nutrition Report, June 1992; 10(6):43/"A Prospective Study of Vitamin C and the Incidence of Coronary Heart Disease in Women", Manson, J., et al, Circulation, 1992;85:865.

Histamine Release

Histamine Release

Vitamin C enhanced the inhibitory activity of quercitin and myricetin. The augmenting effect of ascorbic acid on flavonoid inhibition of the two pathways of histamine release may be related to the preservation of a particular unoxidized structure of the flavonoid

"Effect of Ascorbic Acid and Flavonoids on Human Basophil Histamine Release", Middleton, E., Jr. and Drzewiecki, G., Journal of Allergy and Clinical Immunology, January 1992;89(1/Part 11):278/536.

Iron Deficiency

Iron Deficiency

Iron fortification of milk in children was only partially successful because of its poor bioavailability in milk. Enrichment of milk with ascorbic acid markedly improved iron bioavailability. This new fortified formula has been used since 1976. It is a powdered, fullfat milk acidified and fortified with 15 mg of ferrous sulfate and 100 mg of ascorbic acid per 100 grain of powder. Enrichment of milk with ascorbic acid markedly improved iron bioavailability in formula milk in this study of 276 infants.

"Prevention of Iron Deficiency By Milk Fortification", Olivares, M., et al, ACTA Pediatr. Scand., 1989;Suppl.361:109-113.

Ischemic Heart Disease and Stroke

Ischemic Heart Disease and Stroke

A study of 2,974 men in which plasma levels of the essential antioxidants vitamins C, E, and beta carotene were evaluated over a period of 12 years. Deaths and their causes were noted. The authors concluded that even at protective levels of plasma vitamins E and A, low levels of beta carotene and vitamin C will independently increase the risk of cardiovascular disease mortality.

"Poor Plasma Status of Carotene and Vitamin C is Associated With Higher Mortality from Ischemic Heart Disease and Stroke: Basal Prospective Study," Gey, K.F., et al, Clin Investig, 1993;71:3-6.

Lipoprotein A

Lipoprotein A

In a paper published in the Proc. Natl. Acad. Sci., 1990;87:6204-07 by Rath and Pauling it is suggested that Vitamin C may lower excessive Lp(a) levels and thereby help prevent and treat cardiovascular disease.

"Research on Heart Disease: An Ongoing Investigation at LPI ", The Linus Pauling Institute of Science and Medicine, Winter, 1990;3(3):3.

LDL Cholesterol

LDL Cholesterol

In all types of oxidizing conditions ascorbic acid completely protected lipids in the plasma and LDL against detectable prooxidative damage by a very highly sensitive assay for lipid peroxidation. Vitamin C proved to be superior to other vatersoluble plasma antioxidants. The authors conclude that in light of any significant adverse health effects of vitamin C in humans and its potential antioxidant activity, vitamin C tissue saturation in humans appears to be desirable.

"Ascorbic Acid Protects Lipids in Human Plasma and LowDensity Lipoprotein Against Oxidative Damage", Frei, Balz, American Journal of Clinical Nutrition, 1991;54:1113S-1 8S

Leukemia

Leukemia

L-ascorbic acid modulated the in vitro growth of leukemic colony-forming cells from bone marrow patients with acute myelocytic leukemia. L-ascorbic acid enhanced the growth of leukemic colon- forming cells in 35 per cent of the patients and suppressed the growth of leukemic colony forming cells in 15 per cent of the patients. This ability of ascorbic acid to enhance or suppress human leukemic cell lines needs to be assessed in vivo.

"Growth Modulation of Human Leukemic, Preleukernic and Myeloma Progenitor Cells by L-Ascorbic Acid", Park, Chan H. and Kalmer, Bruce F., American Journal of Clinical Nutrition, 199 1;54:1241 S-6S.

In mice given two forms of cancer a combination of vitamin B12 and vitamin C increased lifespan compared to controls. Autopsy revealed that there was inhibition of mitosis in the leukemia cells but not in the normal cells. When vitamin B 12 is combined with vitamin C, the cobalt nucleus of B 12 attaches to the carbon on vitamin C, forming cobalt ascorbate which has been shown to have antitumour activity. Vitamin C has important inhibitory effects on cell growth and division.

"Effect of Combined Ascorbic Acid and B-12 on Survival of Mice With Implanted Ehrlich Carcinoma and L 121 OLeukemia", Poydock, M. Eymard, American Journal of Clinical Nutrition, 199 1;54:1261 S-5S.

Liver Damage

Liver Damage

This commentary reports on an abstract entitled, "The Protective Action of Vitamin C Against Experimental Liver Damage," published in 1942 by the FASEB and presented by the author at an FASEB meeting. The author's research, using vitamin C, was derived from his work using ascorbic acid as a reagent. The experiments that help show vitamin C preventing hepatotoxicity were done in dog and guinea pig models. Carbon tetrachloride was used to induce liver damage.

"Vitamin C and Serendipity, 50 Years Ago," Beyer, Karl H., Jr., FASEB Journal, November 1992;6:3316-17.

Lung health

Lung health

People who consume high amounts of vitamin C have a greater lung volume than those who do not, according to this study conducted on 3,085 people in 69 rural Chinese counties. For each 100 mg/day increase in vitamin C, lung volume increased by 22 ml. Significantly, this increase was the same for both smokers and nonsmokers.

Guizhou, Hu PhD; Zhang, Xin: American Journal of Epidemiology, 1998 Nov; 148 (6): 594-9

Optimal Levels

Optimal Levels

This article comments on the fact that scurvy is a clearly defined severe vitamin C deficiency which is usually diagnosed by clinical signs in the advanced stage. Laboratory assessments of vitamin C, especially vitamin C assays, are not capable of detecting subclinical vitamin C deficiency at present.

"Vitamin C: From Scurvy to Ideal Vitamin Balance", Labadie, H., La Presse Medicale, December 7, 1991;20(42):2156-2158.

Oxidative Stress

Oxidative Stress

The buildup of free oxygen radicals can cause many problems, such as high LDL cholesterol levels, endothelial dysfunction, platelet aggregation, and heart failure. The evidence that oxidative stress plays a role in heart failure is largely circumstantial, in that malondialdehyde levels are higher and plasma thiol levels are lower in patients with heart failure. The use of antioxidants in the treatment or prevention of clinical heart failure requires further study. The potential for antioxidant therapy in patients with heart failure is suggested by the demonstration that carvedilol reduces both morbidity and mortality in patients with chronic heart failure.

Hoeschen, Robert J., M.D.: Oxidative Stress and Cardiovascular Disease, Canadian Journal of Cardiology, November 1997;13(11):1021-1025.

Pauling

Pauling

Optimal intake is possibly 100 or more times greater than the RDA. most animal species synthesize their own ascorbate - the average amount being between 3000 and 18000mg/day. There is accumulating evidence that ascorbate supplementation can improve health in a variety of diseases. It is suspected that people with low values of blood ascorbate have weakened blood vessels since ascorbate is important for the synthesis of collagen and elastin which strengthen blood vessel walls. Dr Pauling further states that the presence of cardiovascular disease is in general the result of ascorbate deficiency.

"Vitamin C and Cardiovascular Disease", Pauling, Linus, Ph.D., Medical Sciences Research, 199 1; 19:399-40 1, Proceedings of The National Academy of Sciences, 1974;71:4442-4446/Proceedings of The National Academy of Sciences, 1990;87:6204-6207/9388-9890/1991, Rath and Pauling/Ginter, E., Science, 1973;179:702/Rath et. al, Atherosclerosis, 1989;9:579-592.

Premature Ruptured Membranes

Premature Ruptured Membranes

There was an association between low vitamin C levels and cases with premature ruptured membranes (PRM) in a study of pregnant women. Infections were more frequent in the PRM group when there were low leukocyte vitamin C levels. Of importance was the fact that the lowest value established in this study is far above the vitamin C concentration considered normal. None of the women had clinical signs of vitamin C deficiency, which means there may have been subclinical deficiency.

"Incidence of Premature Rupture of Membranes in Pregnant Women With Low Leukocyte Levels of Vitamin C", Casaneuva, Esther, et al, European Journal of Clinical Nutrition, 1991;45:401-405.

Pressure Sores

Pressure Sores

This is a general overview of an entire approach to the prevention and treatment of pressure sores. In the prevention and treatment of pressure sores malnutrition, vitamin deficiency and anemia need to be corrected. Vitamin c has a significant effect on wound healing and is essential for the formation of collagen. Vitamin C also has a profound effect on the immune system by facilitating leukocyte migration and enhancing resistance to infection. Levels below 170 mg/ds indicate poor nutrition

"Pressure Sores: How To Prevent and Treat Them", Emanuele, Judy Ann, M.D., et al, Postgraduate Medicine, May 15, 1992;91(7):113-118.

Twenty-one elderly patients with femoral neck fractures were evaluated in an orthopedic unit. 48 per cent developed pressure sores. The authors conclude that low leukocyte vitamin C levels may be associated with development of pressure sores.

"Vitamin C Depletion and Pressure Sores in Elderly Patients With Femoral Neck Fracture", Goode, Helen F., et al, British Medical Journal, October 17, 1992;305:925-926.

Prooxidant

Prooxidant

Vitamin C plays a key role as an antioxidant. But vitamin C in the presence of trace amounts of copper 2+, iron +, and oxygen may generate free radicals and thereby cause damage to cellular constituents. The prooxidant capacity of the vitamin is a complex function of its relationship with iron.

"Ascorbic Acid and Oxidative Inactivation of Proteins", Stadtman, Earl R., American Journal of Clinical Nutrition, 1991;54:1125S-8S.

Vitamin C is one of the strongest reducing agents and free radical scavengers. Vitamin C reduces stable oxygen, nitrogen and thyl radicals and acts as a primary defense against aqueous radicals in the blood. Vitamin C can scavenge radicals before they reach membranes, such as erythrocyte membranes and LDL cholesterol. Even though vitamin C cannot scavenge lipophilic radicals within lipid membranes, it can act synergistically with vitamin E, reducing lipid peroxyl radicals within the lipid compartment by reacting with the tocopherol radical and regenerating active vitamin E. Even though vitamin C may act as a prooxidant in vitro in the presence of metals, this effect is unlikely to be important in vivo because metal iron is sequestered and other reductants are present. This is due to the fact that iron is sequestered by proteins such as ferritin, transferrin and lactoferrin, so it may not initiate chain oxidation to any appreciable degree. Urate can prevent the prooxidation of ascorbate.

The autoxidation of vitamin C produces hydrogen peroxide, a potential precursor to hydroxyl or hydroxperoxyl radicals. This rate of autoxidation is usually very small when catalases and peroxidases are present in vivo to reduce hydrogen peroxide to water. The author states that it is unlikely that ascorbic acid acts as a prooxidant in vivo under normal conditions.

"Action of Ascorbic Acid as a Scavenger of Active and Stable Oxygen Radicals", Niki, Etsuo, American Journal of Clinical Nutrition, 1991;54:1119S-24S.

Prutitis & Vitamin C

Prutitis

This study examined a child with an isolated complex III respiratory chain deficiency and global developmental delay who had severe pruritus with elevated plasma bile acid levels. A liver biopsy showed micronodular cirrhosis, and enzymologic evaluation demonstrated an isolated complex III deficiency in both liver and muscle. His pruritus improved and serum bile acid levels decreased after treatment with menadione and vitamin C.

Mowat D; Kirby DM; Kamath KR; Kan A; Thorburn DR; Christodoulou J: Respiratory chain complex in deficiency with pruritus: a novel vitamin responsive clinical feature, J Pediatr, 1999 Mar; 134(3):352-4

US RDA & Vitamin C

US RDA
According to this study, the US recommended daily allowance of vitamin C should be doubled, to 120 mg/day. Researchers point out that the current RDA, 60 mg/day, meets the requirement for scurvy prevention (46 mg/day) but is not adequate for the prevention of cancer and cardiovascular disease. Several other researchers have also recommended a doubling of the RDA, including Dr. Mark Levin of the National Institutes of Health.

Carr, Anitra C. MD; Frei, Balz MD; et al: American Journal of Clinical Nutrition, June 1999; 69:1086-1107

Vitamin C RDA Should Be Raised to 200 mg

According to Dr. Mark Levine of the National Institute of Diabetes and Digestive and Kidney Diseases, the RDA for vitamin C should be raised from 60 mg to 200 mg. At 200 mg, the bioavailability of vitamin C is at 100%. Higher doses result in a lower bioavailability percentage. A daily consumption of 5 servings of fruits and vegetables meets this proposed new RDA, providing 210 to 280 mg of vitamin C. Less than 1 in 10 Americans follows this dietary recommendation.

Jancin, Bruce: Expert Says Vitamin C RDA Should Be Raised to 200 mg, Family Practice News, November 1, 1997;21.

A comprehensive review of the literature indicates that populations with long-term consumption of higher than RDA levels of vitamin C (> or = 60 mg/day) from foods and/or supplements have reduced risks of cancer at several sites, cardiovascular disease, and cataracts.

The safety of higher than RDA intakes of vitamin C is confirmed in studies with up to 10,000 mg of vitamin C consumed daily for up to 3 years.

The health effects of vitamin C supplementation: a review. Bendich-A; Langseth-L. J-Am-Coll-Nutr. 1995 Apr; 14(2): 124-36.

Radiation

Prostate cancer is one of the commonest tumours of adult males. It shows a range of biological behaviour: many tumours are discovered incidentally; others will kill by producing widespread metastatic disease.

Despite the fact that radiation is frequently used in the treatment of a range of pelvic lesions, including adenocarcinoma of the prostate itself, studies on the morphological changes in the normal prostate gland after irradiation are limited.

Patients often suffer from lower urinary tract symptoms such as frequency and dysuria and it is possible that these may be related to prostatic and/or periprostatic injury pelvic following irradiation.

Investigated the prostate glands removed at cystoprostatectomy for transitional cell carcinomas of the bladder which had received radiotherapy pre-operatively. The changes were compared to control prostatic tissue from transurethral resection specimens for benign myoadenomatous hyperplasia.

A range of inflammatory, fibrotic and reactive cytological features, including many of the changes seen in benign hyperplasia, but these were significantly more exaggerated in the post-radiation group. In addition intraprostatic vascular and neural changes were prominent.

Sheaff MT & Baithun SI: Effects of radiation on the normal prostate gland. Histopathology, 1997 Apr, 30:4, 341-8.

Research Benefits

Research Benefits

Vitamin C research is beginning to approach a turning point. Dr. Gladys Block states that "there is no question that the status of vitamin C has changed in a lot of researchers' minds". D

There is a growing body of evidence that vitamin C's antioxidant role may have a beneficial role in chronic diseases such as cancer, heart disease and AIDS. Vitamin C is important in neutralizing the harmful effects of cigarette smoke, smog and their ability to oxidize lipids, proteins and DNA. Though many of the vitamin C studies cited by Dr. Linus Pauling have been criticized, and he has not been able to get a National Cancer Institute (NCI) sponsored trial of vitamin C, he did get the NCI to sponser a symposium which presented international speakers' reports on benefits of vitamin C. The fact is that, when you eat foods containing high amounts of vitamin C, there are lower risks of cancer. The National Cancer Institute has a number of cancer prevention trials under way testing vitamin C and other antioxidants, but results are not available yet. Dr. Pauling has probably been the only one willing to bring up the concept of vitamin C's use as an anticancer drug.

The symposium did suggest that vitamin C may be useful in cancer treatments. Vitamin C may also be very important in preventing LDL oxidation. In commenting about other antioxidants, it has been found that n-acetylcysteine replenishes glutathione and slows HIV production, possibly by inhibiting viral transcription. Vitamin C has been shown to inhibit HIV infection in cultured cells, but it does not appear to work by inhibiting HIV transcription. Vitamin C may help in glutathione deficiency but this remains to be conclusively established. Some researchers have stated that getting into vitamin C research was awkward and sometimes embarrassing, which inhibited many individuals in their pursuit of vitamin C research. The new breed of vitamin C researchers is trying to dissociate themselves from the fringe.

"Vitamin C Gets a Little Respect: Some Researchers Say the Climate in This Controversial Field is Changing as Data Mount on the Role of Antioxidants in Disease and Health. Others Remain Skeptical", Barinaga, Marcia, Science, October 18, 1991;254:374-376.

Safety

Safety

Vitamin C is a potent antioxidant. It regenerates Vitamin E. Reduced levels are associated with higher incidences of heart disease, high blood pressure and cancer. 100mg/day are recommended for smokers. Larger doses of vitamin C such as 1,000mg/day have ameliorated symptoms and shortened duration of colds. 10g/day have been given in the treatment of advanced cancer without toxic side effects. Supplementation is not recommended for patients on hemodialysis. There is no evidence that long-term use of high doses of vitamin C increases the amount required to prevent deficiency scurvy if high dose supplementation is withdrawn. Recent research linking oxygen derived free radicals in the body to cancer, cardiovascular disease and cataract have inspired a resurgence in the interest and supplemental uses of the antioxidant vitamins. High doses of vitamin C appear to be safe.

"Antioxidant and Vitamin Supplementation: How Safe?" Flodin, Nestor W., Ph.D., The Nutrition Report, April 1992;10(4):25,32.

Seasons

Seasons

Vitamin C supplements should be given throughout the year in patients with cardiovascular disease. Cholesterol levels rise in the winter and are inversely related to changes in leukocyte ascorbic acid levels. This seasonal variation in ascorbic acid and cholesterol levels becomes very important in patients with hypercholesterolemia, especially during the winter months

"Seasonal and Climatic Variation in Cholesterol and Vitamin C: Effect of Vitamin C Supplementation", MacRury, S.M., et al, Scottish Medical Journal, 1992;37:049-052.

Skin Cancer

Skin Cancer

A 10% ascorbic acid solution was applied topically to the skin of domestic pigs who were exposed to ultraviolet light. Vitamin C skin levels rose 4 to 40 fold or more with topical vitamin C application. Topical vitamin C, applied 15 to 30 minutes before the ultraviolet light exposure, protected the skin against UVB and UVA damage. Similar applications were beneficial but multiple applications gave even better protection. The authors noted that, after exposure to sunlight, skin levels of vitamin C were significantly reduced and suggest that replenishment of skin vitamin C would be important in preventing sun damage.

"Topical Vitamin C Protects Skin", The Nutrition Report, November 1992;10(11):84/"Topical Vitamin C Protects Porcine Skin From Ultraviolet Radiation-Induced Damage", Darr, D., et al, British Journal of Dermatology, 1992;127:247-253.

Vitamin C is particularly interesting as a topical photoprotectant.The author's research has found beneficial effects of topical vitamin C against moderate levels of UVB and psoralen-UVA damage to animal skin. The use of topical antioxidants as an adjunct to familiar sunscreen productswill afford consumers the option of equivalent skin protection without the significant amounts of chemical sunscreen agents. Vitamin C and antioxidants plus sunscreen may be much better together than either one alone in protecting against UVB damage

"Vitamin C: Topical Skin Protector", Darr, Douglas, Ph.D., The Nutrition Report, July 1992;10(7):49-9, 56.

A new topical vitamin C may prevent sun damage to the skin. This form lasts for approximately 3 days and cannot be washed off. It could be used in conjunction with a traditional sunscreen for maximum protection or used alone and allow vitamin D synthesis to occur. An extension of this research is that topical vitamin C may also help prevent wrinkles, declining collagen synthesis or even skin cancers.

"Vitamin C Eyed for Topical Use as A Skin Preserver: The Compound Appears to Ward Off Sun Damage and the Developer Thinks it May Also Promote Collagen Synthesis", Thomas, Patricia, Medical World News, March 1991;12-13.

Vitamin C is a systemic antioxidant and is also important in collagen synthesis. It also prevents oxidation of plasma lipids. Duke University researchers have developed an aqueous formulation of vitamin C that protects the skin against UV light exposure. with this particular formulation, these researchers can deliver 20 times the amount of vitamin C normally found in the skin. These skin levels can not be delivered by diet alone. They believe that the vitamin's photoprotective effects are the results of its anti-inflammatory properties and not because it is a sunblock. Vitamin C helps protect against sunburn by being an antioxidant. If vitamin C levels are enhanced in the skin then connective tissue breakdown that results in premature ageing, wrinkles, and even skin cancer may be prevented.

"Does Vitamin C Protect Against UVA and UVB?", Patient Care, May 30, 1992;14,17/"Biological Functions in Relation to Cancer", Henson, D.E., et al, Journal of the National Cancer Institute, 1991;83:847-550.

Topical Vitamin C

Topical Vitamin C

Topical vitamin C can help prevent skin damage from ultraviolet light due to its powerful antioxidant capabilities. The vitamin is better than normal sunscreens because it lasts 3 days without being washed off and can prevent sun damage without blocking vitamin D syntheses. Vitamin C inhibits damage from all wavelengths as well.

"Topical Vitamin C Limits Ultraviolet Damage to Skin", Pfeiffer, Naomi, Medical Tribune, September 16, 1991;4.

Smoking/Hip Fracture & Vitamin C

Smoking/Hip Fracture

Smoking increases the risk of hip fracture due to oxidative damage, according to this study conducted on 66,651 women from 40 to 76 years old. Information on diet was obtained by a validated food-frequency questionnaire. Smokers with a low intake of vitamins C and E exhibited a higher risk for hip fracture, suggesting oxidative stress as a factor in bone damage. Smokers who consumed large amounts of vitamins C and E had a reduced risk of hip fracture. The influence of the intake of these two antioxidant vitamins on hip fracture risk was less pronounced in former smokers.

Melhus H; Micha?lsson K; Holmberg L; Wolk A; Ljunghall S: Smoking, antioxidant vitamins, and the risk of hip fracture, J Bone Miner Res, 1999 Jan 14; (1):129-35

Smokers

Smokers

This study evaluated the role of fresh fruit and fruit juice consumption in over 1,500 lifelong nonsmokers and 1,300 current smokers, ages 18 to 69, on ventilatory function. Antioxidants and other actions of vitamin C may protect against pulmonary emphysema or reduce bronchoconstrictor responses to environmental pollutants. This supports the hypothesis of association between infrequent fruit or fruit juic consumption and impaired ventilatory function in adults.

"Ventilatory Function and Winter Fresh Fruit Consumption in a Random Sample of British Adults", Strachan, David P., et al, Thorax, 1991;46:624-629.

The new 100 mg/d RDA for smokers may be too low. A review of over 12,000 adults showed that at the 100 mg/d level of dietary intake more than twice as many smokers as nonsmokers had hypovitaminosis C. In this study 34% of smokers and only 12% of nonsmokers had hypovitaminosis C defined as a serum level of .4 mg/dl. When vitamin C was taken at 200 mg/d the odds ratio dropped to a nonsignificant difference between smokers and nonsmokers. In smokers who are not willing to stop smoking vitamin C supplementation at the 200 mg/d range may be of benefit. Smokers apparently metabolize vitamin C more rapidly. Vitamin C hypovitaminosis is the most frequent nutritional deficiency among smokers.

"Increased RDA for Vitamin C for Smokers May Still be Too Low", Family Practice News, August 1-14, 1990;20(15):29.

Smoking

Cigarette smoking may speed the progression to AIDS in some HIV infected people according to scientists from Harvard and U.C. Berkeley studying 387 HIV-infected men, some who were asymptomatic and some who had ARC. In this 56 month observation period cigarette smokers had twice the likelihood of developing AIDS than nonsmokers. Smokers with HIV infection suffer a more rapid depletion of CD4 cells than do infected nonsmokers. 9154

"Smoking May Hasten AIDS Development", New Scientist, July 7, 1990;15.

Smoking and Cancer

Smoking and Cancer

Decreased intakes of vitamin C were observed in the diets of cigarette smokers in the NHANES II study. In further evaluation of over 17,000 patients by food frequency questionnaires, a downward trend of vitamin C with increasing levels of cigarette smoking was observed. Cigarette smokers consumed less vitamin C than nonsmokers. A variety of studies support the conclusion that smokers have lower intakes of vitamin C.

"Dietary Vitamin C Intake and Cigarette Smoking", Gridley, Gloria, MS, et al, AJPH, December 1990;81(12):1526.

Sperm

Sperm

Research done at the University of California at Berkeley showed that men who reduced their vitamin C intake from 250 mg per day to 5 mg per day doubled the DNA damage in their sperm. When the men increased their vitamin C intake to 60 or 250 mgs a day, the DNA damage dropped. Recently it has been shown that vitamin C supplements improve fertility in male smokers with fertility problems. The author recommends a diet rich in fruit and vegetable consumption. It is not known whether supplementation greater than 250 mg/d has any additional benefit. Vitamin C is normally found in high concentrations in semen. It is believed that vitamin C is needed to protect the DNA of sperm cells from toxic oxygen radicals. Studies have shown that children of male smokers are at greater risk of leukemia and immune system cancer than children of male nonsmokers. Studies have also shown that the number of inherited cancers are more often associated with DNA defects in sperm cells than in eggs.

The relationship could be a significant drop in vitamin C in the semen of men who smoke. The government recommendation of 60 mgs per day, which is the amount found in approximately 1 orange, is probably not enough to protect the sperm of smokers from genetic damage.

"Daily Vitamin C Protects Sperm From Genetic Damage", Medical Tribune, January 16, 1992;23.

Vasodilation

Vasodilation

Patients with coronary heart disease may be able to reverse endothelial vasomotor dysfunction with long-term administration of vitamin C, according to this study, in which 46 patients were randomized to receive a single oral dose of 2 g vitamin C, or placebo. Those patients who took the ascorbic acid had improved flow-mediated dilation of the brachial artery. Researchers said this effect was sustained in patients who took 500 mg/d of ascorbic acid for 30 days. The placebo effected no change in flow-mediated dilation of the brachial artery. The study concludes that ascorbic acid treatment may benefit patients with coronary heart disease.

Vita, Joseph A. MD, et al: Circulation, June 1999; 99:3234-3240

Cancer & Vitamin C

Cancer

While human tumor cells may contain higher than normal amounts of vitamin C, these cancer cells are not capable of directly transporting vitamin C, but must obtain high concentrations of the vitamin through other indirect ways. This study, conducted on mice, proposes that stromal cell oxidation plays a vital role in transporting ascorbic acid to tumor cells. If cells in the tumor stroma oxidize the ascorbic acid, the product - dehydroascorbic acid - can be easily transported throughout the tumor by facilitative glucose transporters (GLUTs). Once inside tumor cells, the dehydroascorbic acid is reduced to vitamin C and retained. Coadministration of superoxide dismutase inhibited the accumulation of vitamin C in tumor cells.

Agus DB, Vera JC, Golde DW: Stromal cell oxidation: a mechanism by which tumors obtain vitamin C, Cancer Res 1999 Sep 15;59(18):4555-8

Nonhormone dependent cancers

The protective effect of vitamin C for nonhormone dependent cancers is strong. Thirty-three out of 46 studies found dietary vitamin C gave significant protection against nonhormone dependent cancers.

"Vitamin C and Cancer Prevention: The Epiderniologic Evidence", Block, Gladys, American Journal of Clinical Nutrition, 1991;53: 2701-282S.

Cervical Dysplasia

CERVICAL DYSPLASIA

In this study 175 healthy Japanese residents, 60 years of age or older, volunteered for evaluation of the correlation between HDL cholesterol and ascorbic acid. It was found that there was a significant positive correlation between serum HDL cholesterol and ascorbic acid in both sexes. There was significant positive correlation between serum HDL cholesterol and ascorbic acid in both sexes. The correlation was still significant after taking into account alcohol consumption, physical activity, smoking serum triglycerides and total cholesterol.

"Serum Ascorbic Acid and HDL Cholesterol iA A Healthy, Elderly Japanese Population", Itoh, Roichi, et al, International Journal of Vitamin and Nutrition Research, 1990;60:360-365.

High plasma and dietary vitamin C have been associated with increased HDL cholesterol, lower blood pressure and lower risk of cardiovascular disease. An evaluation of 316 women and 511 men led the authors to conclude that high dose plasma levels of vitamin C may lower atherosclerotic risk.

"High Plasma Vitamin C Associated With Increased Plasma HDL- and HDL2-Cholesterol", Hallfrisch, J., et al, American Journal of Clinical Nutrition, 1991;53:P-19.

Smoking Cessation & Vitamin C Aerosol

Smoking Cessation and Vitamin C Aerosol

Previous research has shown that substituting the sensory cues of smoking with citric acid aerosol can significantly reduce the cravings for cigarettes and enhance smoking cessation and/or smoking reduction. This study confirmed those findings. It was also found that craving for cigarettes and negative mood were both significantly lower in the fine particle device group.

"Clinical Trials Using Ascorbic Acid Aerosol to Aid Smoking Cessation", Levin, Edward D., et al, Drug and Alcohol Dependence, 1993;33:211-223.

Lead Toxicity

Lead toxicity        

High serum levels of vitamin C may be associated with decreased levels of elevated blood lead, according to this study conducted on children and adults with no history of lead poisoning. Children who had sufficient vitamin C levels had 89% less elevated blood lead levels; in adults the blood lead levels were 65% to 68% lower. The researchers note that further studies may find vitamin C to be helpful in treating lead poisoning.

Simon JA, Hudes ES: Relationship of ascorbic acid to blood lead levels, JAMA 1999 Jun 23-30;281(24):2289-93

Coronary Artery Disease & Vitamin C

Coronary artery disease

Long-term use of vitamin C may reverse symptoms due to coronary artery disease, according to this study in which 46 patients with endothelial vasomotor dysfunction took either ascorbic acid or placebo. According to the results from the vascular ultrasound, the ascorbic acid increased the dilation of the brachial artery and blood flow just two hours after vitamin C was ingested. This effect was sustained throughout a month of vitamin C administration, signifying that long-term use of ascorbic acid may improve the conditions of coronary artery disease.

Gokce N, Keaney JF Jr, Frei B, Holbrook M, Olesiak M, Zachariah BJ, Leeuwenburgh C, Heinecke JW, Vita JA: Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease, Circulation 1999 Jun 29;99(25):3234-40


Dementia and Cognitive Function

Dementia and Cognitive Function

Supplementation with vitamins C and E may help to prevent vascular dementia, improving cognitive function later in life, according to the Honolulu-Asia Aging Study conducted on 3,385 Japanese-American men ages 71 to 93 years. Men who reported taking both vitamin C and vitamin E in the past demonstrated a significant protective effect for vascular dementia and mixed/other dementia, but not for Alzheimer's disease. Cognitive performance was evaluated with the Cognitive Abilities Screening Instrument, and the results were analyzed in a multivariate model controlled for other factors.


Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR: Association of vitamin E and C supplement use with cognitive function and dementia in elderly men, Neurology 2000 Mar 28;54(6):1265-1272

Reflex Sympathetic Dystrophy (RSD)

Reflex sympathetic dystrophy (RSD)

The administration of vitamin C after wrist fracture lowers the risk of reflex sympathetic dystrophy (RSD), according to this study conducted on 123 adults with conservatively-treated risk fractures. The patients received either 500 mg/day vitamin C or placebo for 50 days. After a one-year follow-up period, 15% of the placebo group and 7% of the vitamin C group developed RSD. The authors of the study hypothesize that vitamin C may also be of benefit in treating other forms of trauma.

Zollinger PE, Tuinebreijer WE, Kreis RW, Breederveld RS: Effect of vitamin C on frequency of reflex sympathetic dystrophy in wrist fractures: a randomised trial, Lancet 1999 Dec 11;354(9195):2025-8

Gallbladder disease

Gallbladder disease

Low serum levels of ascorbic acid (vitamin C) may be associated with an increased risk of gallbladder disease in women, according to the Third National Health and Nutrition Examination Survey (1988-1994). A total of 761 women and 235 men reported a history of gallbladder disease. Serum ascorbic acid levels were low among women with gallbladder disease, but not among men. Each 27 micromol/L increase in serum ascorbic acid level was associated with a 13% lower prevalence of gallbladder disease in women.


Simon JA, Hudes ES: Serum ascorbic acid and gallbladder disease prevalence among US adults: the Third National Health and Nutrition Examination Survey (NHANES III), Arch Intern Med 2000 Apr 10;160(7):931-6

Bone Mineral Density (BMD)

Bone Mineral Density

Supplementing with vitamin C during estrogen and calcium therapy may significantly increase bone mineral density (BMD), especially for postmenopausal women, according to this population-based study on 994 women. Subjects completed dietary nutrient assessment questionnaires and BMD levels were determined at the ultradistal and midshaft radii, hip, and lumbar spine. Women who consistently supplemented with vitamin C had BMD levels about 3% higher than non-vitamin C users. Estrogen and calcium supplementation further increased these vitamin C-elevated BMD levels, giving women in this group (calcium/estrogen/vitamin C) the highest BMD values at all sites.

Morton DJ, Barrett-Connor EL, Schneider DL: Vitamin C supplement use and bone mineral density in postmenopausal women, J Bone Miner Res 2001 Jan;16(1):135-40

Obesity and Vasodilation

Obesity and Vasodilation

Vitamin C may help to reduce oxidative stress in the endothelial walls of blood vessels, thereby helping to increase vasodilation, a mechanism that seems to be impaired for obese people. Researchers divided 76 healthy subjects into groups based on body mass index (BMI), then measured endothelium-dependent and independent vasodilation (assessed by increasing doses of acetylcholine and sodium nitroprusside). During the vasodilation measurement, some subjects received infusions of saline and others received vitamin C. Obese people had significantly lower blood flow during saline infusion than did non-obese subjects. Vitamin C infusion dramatically increased blood flow, indicating increased vessel diameter, presumably by reducing oxidative damage to the endothelium.

Perticone F, et al: Obesity and body fat distribution induce endothelial dysfunction by oxidative stress: protective effect of vitamin C, Diabetes 2001 Jan;50(1):159-65

Heroin Withdrawal

Heroin Withdrawal

High doses of oral vitamin C may help to reduce heroin withdrawal syndrome from 56.6% severity to 16.6 or 10% severity, compared to untreated controls. Heroin addict subjects were divided into three groups: inpatients given vitamin C/vitaminE/diazepam/analgesic, outpatients given vitamin C/vitamin E, and inpatients given traditional medication. The two groups receiving vitamin C reported a higher degree of mild withdrawal syndrome (as assessed by DMS-III criteria), in contrast to the high percentage of major withdrawal symptom seen in non-vitamin C subjects. The researchers conclude that vitamin C may help to reduce the severity of heroin withdrawal syndrome.

Evangelou A, et al: Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers, In Vivo 2000 Mar-Apr;14(2):363-6

Tumor Cells

Toxic to Tumor cells

Ascorbate (vitamin C) may be cytotoxic to in vivo tumor cells at clinically suitable concentrations, according to this study performed on an SW620 hollow fibre in vitro solid tumor model. Ascorbate alone and in combination with four other antioxidants, including lipoic acid, vitamin K3, phenyl ascorbate, and doxorubicin, were tested for anti-cancer activity on the tumor model. Treatment with ascorbate caused increased apoptosis in the tumor cells, and in combination with lipoic acid, its anti-cancer effects were enhanced. Anti-proliferative action was also mediated by the phenyl ascorbate and vitamin K3-ascorbate combinations. The ability of doxorubicin to enhance absorbate's apoptotic effects was increased when higher doses of the antioxidant were mixed with absorbate.

Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, Riordan HD: Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours, Br J Cancer 2001 Jun 1;84(11):1544-50

Recommended Dosage for Women

Recommended dosage for women

The Recommended Dietary Allowance of vitamin C, which is 75 mg per day, is based on data for men and should be increased to 90 mg per day for women, according to the authors of this study. Vitamin C doses ranging from 30 to 2,500 mg per day were given to young, healthy women for nearly 200 days. Only daily doses of 100 mg were beyond the linear portion of the sigmoidal curve relating dose and steady-state plasma concentration. Plasma and circulating cells were saturated by the 400 mg/day doses. The results of the study also revealed that vitamin C did not alter endogenous lipid peroxidation in healthy young women since varying doses did not affect plasma and urine F(2)-isoprostanes or urine levels of a major metabolite of F(2)-isoprostanes.
        
Levine M, Wang Y, Padayatty SJ, Morrow J: A new recommended dietary allowance of vitamin C for healthy young women, Proc Natl Acad Sci USA 2001 Aug 14;98(17):9842-9846

Hyperglycemia & Vitamin C

Hyperglycemia

Ascorbic acid deficiency may be countered by vitamin C administration during periods of acute and chronic hyperglycemia, according to this study. Vitamin C preserves endothelial function and slows the progression of atherogenesis in people with abnormal glucose and lipid metabolism. In hyperglycemia, the transport of the oxidized form of vitamin C into cells is inhibited, thus placing the patient at a higher risk of developing atherosclerosis. This is a common problem in patients with diabetes mellitus.
        
Price KD, Price CS, Reynolds RD: Hyperglycemia-induced ascorbic acid deficiency promotes endothelial dysfunction and the development of atherosclerosis, Atherosclerosis 2001 Sep;158(1):1-12

Fruit and Vegetable Intake

Fruit and vegetable intake

The plasma nutrient most affected by the intake of fruits and vegetables may be vitamin C, according to this study on 116 male subjects. The subjects, who ranged in age from 35 to 72 years, gave dietetic information and blood samples to researchers who evaluated the correlation between their diet and their plasma nutrient levels. The subjects were nonsmokers and did not consume vitamin supplements.

After blood levels of vitamin C, beta-carotene, beta-cryptoxanthin, and alpha- and gamma-tocopherol were measured, the results revealed that fruit and vegetable intake most strongly correlated with higher vitamin C blood levels. Since fruits and vegetables have been touted as protectors against heart disease and certain cancers, the relation between their intake and higher levels of vitamin C may indicate that vitamin C contributes to their protective effects.

Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K: Which plasma antioxidants are most related to fruit and vegetable consumption, Am J Epidemiol 2001;154(12): 1113-1118

 


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