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Life Extension Magazine

May 9, 2000

National Academy of Sciences References

1. Princess Takamatsu Symp 1985;16:29-40Multiethnic studies of diet, nutrition, and cancer in Hawaii.Kolonel LN, Hankin JH, Nomura AM

Epidemiologic studies of diet and cancer have been facilitated in Hawaii by themultiethnic composition of its population and the consequent heterogeneity indietary intakes. Studies of migrant populations, particularly the Japanese, havefirmly supported the conclusions that environmental factors are of predominantetiologic significance for most major sites of cancer, and that these factorsmay exert their influences at particular periods of life. Recent observations onFilipino migrants reproduce most of the findings in the Japanese, although theydo not show the same abrupt increase in colon cancer rates to the high levelsfound in Caucasians. Data on dietary intakes in these populations supportseveral of the prevailing hypotheses regarding the etiology of certaingastrointestinal and hormone-dependent cancers. Several case-control studies ofdiet and cancer have been completed or are ongoing in Hawaii. Some of these haveincluded comparable studies in Japan, but the findings in Hawaii have generallynot been reproduced in Japan. Weak associations with dietary fat have been foundin Hawaii for breast cancer (particularly in Japanese women) and for prostatecancer (particularly in men greater than or equal to 70 years of age). Vitamin A(especially carotene) has been shown to be inversely associated with lung cancerrisk in men, but positively associated with prostate cancer risk in older men.Vitamin C may be inversely related to bladder cancer risk, but has shown norelationship to lung or prostate cancer risk. These and other findings arediscussed in terms of future needs for epidemiologic research in this field.

2. Br J Cancer 1997;75(1):149-55Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breastcancer risk: a prospective cohort study.Verhoeven DT, Assen N, Goldbohm RA, Dorant E, van 't Veer P, Sturmans F, HermusRJ, van den Brandt PATNO Nutrition and Food Research Institute, Zeist, The Netherlands.

Association between breast cancer risk and the intake of vitamins C and E,retinol, beta (beta)-carotene, dietary fibre, vegetables, fruit and potatoes wasexamined in The Netherlands Cohort Study, for 62,573 women aged 55-69 years.After 4.3 years of follow-up, 650 incident breast cancer cases were identified.After adjusting for traditional risk factors, breast cancer risk was notinfluenced by the intake of beta-carotene, vitamin E, dietary fibre, supplementswith vitamin C, vegetables or potatoes. Fruit consumption showed anon-significant inverse association with breast cancer risk (RR highest/lowestquintile = 0.76, 95% CI 0.54-1.08). A small reduction in risk was also observedwith increasing intake of dietary vitamin C (RR highest/lowest quintile = 0.77,95% CI 0.55-1.08). For retinol, a weak positive association was observed (RRhighest/lowest quintile = 1.24, 95% CI 0.83-1.83). Among subjects with a highintake of polyunsaturated fatty acids (PUFAs), both beta-carotene and vitamin Cintake showed a non-significant inverse association with breast cancer risk(P-trend = 0.15 and 0.16 respectively). Our findings do not suggest a strongrole, if any, for intake of vitamins C and E, beta-carotene, retinol, dietaryfibre, vegetables, fruit and potatoes in the aetiology of breast cancer.

3. Cancer Lett 1996 Jun 5;103(2):183-9Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin,cisplatin, and paclitaxel in human breast carcinoma cells in vitro.Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HWDepartment of Gynecology and Obstetrics, University of Bonn Medical Center,Germany.

Utilizing a microplate ATP bioluminescence assay, two human breast carcinomacell lines, MCF-7 and MDA-MB-231, were tested against doxorubicin (DOX),cisplatin (DDP), and paclitaxel (Tx) alone and in combination with ascorbic acid(Vit C). In both cell lines, Vit C exhibited cytotoxic activity at highconcentrations (i.e. 10(2)-10(3) microM). Both cell lines also were resistant toDOX. MCF-7 was found to be DDP-resistant, MDA-MB-231 was moderately sensitive toDDP. Both cell lines were strongly sensitive to Tx. Vit C both at non-cytotoxic(1 microM) and moderately cytotoxic concentrations (10(2) microM) improved thecytotoxicity of DOX, DDP, and Tx significantly. Combination effects between VitC and DDP or Tx were partly synergistic and partly additive or subadditivewhereas a consistent synergism was found between Vit C and DOX. The mechanismsby which Vit C potentiates the cytostatics studied are yet unclear and should beevaluated further.

4. Nutr Cancer 1996;25(2):173-7Serum carotene, vitamin A, and vitamin C levels in breast cancer and cancer ofthe uterine cervix.Ramaswamy G, Krishnamoorthy LDepartment of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore,India.

Levels of carotene, vitamin A, and vitamin C measured in the serum of patientswith cancer of the breast and uterine cervix were compared with levels inhealthy controls and patients with benign diseases of the breast and cervix.Serum ascorbate levels were significantly lower in patients with benign diseasesof the breast and cervix than in controls. In cancer patients, there was asignificant trend of lower serum vitamin levels with increasing stage of thedisease.

5. Jpn J Cancer Res 1994 Jun;85(6):572-7Diet, serum markers and breast cancer mortality in China.Guo WD, Chow WH, Zheng W, Li JY, Blot WJCancer Institute, Chinese Academy of Medical Sciences, Beijing.

This county-based correlation study examined associations of breast cancermortality with dietary habits and certain serum biochemical markers, utilizingdata collected from an ecological survey in 65 Chinese rural counties.Univariate correlation and multivariate regression analysis showed thatconsumption of animal foods, including eggs, fish and meat, was positivelylinked to county-wide mortality rates of breast cancer in Chinese women. Noclear associations between breast cancer mortality rates and consumption ofgreen vegetables, carrots and fruits were observed in this study. A modestinverse correlation between serum vitamin C levels and breast cancer mortalitywas observed, while selenium levels were positively related to the mortalityrates. Positive correlations for serum ferritin and hemoglobin were found, inagreement with recent reports of an elevated cancer risk with increased bodyiron stores. Limitations of these ecological data preclude causal inferences,but the findings provide clues to breast cancer risk and protective factors in alow incidence area of the world.

6. Nutr Cancer 1993;20(2):167-77Dietary factors and survival from breast cancer.Rohan TE, Hiller JE, McMichael AJNational Cancer Institute of Canada (NCIC) Epidemiology Unit, University ofToronto, Ontario.

The association between self-reported intake of various dietary factors atdiagnosis and survival from breast cancer was studied in a population-basedcohort of breast cancer patients in Adelaide, South Australia. These patientshad been recruited between 1982 and 1984 into a case-control study of diet andincident breast cancer. Of the 451 patients recruited originally, 412 werefollowed for a median interval of 5.5 years. There were decreases in the risk ofdeath from breast cancer ranging from 25 to 40% at all levels of energy andprotein intake above the baseline, whereas for fat intake there was a 40%increase in risk at the uppermost quintile level. There was also some reductionin risk at the upper levels of intake of beta-carotene and vitamin C. However,there were no dose-dependent variations in risk of death by level of intake forany of the dietary factors studied, and most of the variation in risk that wasobserved was relatively insubstantial.

7. Proc Natl Acad Sci U S A 1976 Oct;73(10):3685-9Supplemental ascorbate in the supportive treatment of cancer: Prolongation ofsurvival times in terminal human cancer.Cameron E, Pauling L

Ascorbic acid metabolism is associated with a number of mechanisms known to beinvolved in host resistance to malignant disease. Cancer patients aresignificantly depleted of ascorbic acid, and in our opinion this demonstrablebiochemical characteristic indicates a substantially increased requirement andutilization of this substance to potentiate these various host resistancefactors. The results of a clinical trial are presented in which 100 terminalcancer patients were given supplemental ascorbate as part of their routinemanagement. Their progress is compared to that of 1000 similar patients treatedidentically, but who received no supplemental ascorbate. The mean survival timeis more than 4.2 times as great for the ascorbate subjects (more than 210 days)as for the controls (50 days). Analysis of the survival-time curves indicatesthat deaths occur for about 90% of the ascorbate-treated patients at one-thirdthe rate for the controls and that the other 10% have a much greater survivaltime, averaging more than 20 times that for the controls. The results clearlyindicate that this simple and safe form of medication is of definite value inthe treatment of patients with acvanced cancer.

8. Lepr India 1979 Oct;51(4):511-4Effect of ascorbic acid on blood levels of DDS.Venkatesan K, Bharadwaj VP, Girdhar BK

A study was undertaken to probe into the influence of ascorbic acid on theabsorption and metabolism of administered DDS in leprosy patients. Vit 'C'supplementation did not generally exhibit any effect on blood levels DDS exceptin cases of BB and LL where only 8 hrs DDS values showed a statisticallysignificant increase.

9. Compendium 1994 Jul;15(7):916, 918, 920 passim; quiz 930Vitamin C (ascorbic acid): clinical implications for oral health--a literaturereview.Fontana MOral Health Research Institute, Indianapolis, Indiana, USA.

This article reviews the chemistry, functions, and toxicity of vitamin C, aswell as its food sources, recommended daily allowance, and laboratorybiochemical findings, to help clinicians understand and recognize its systemicand oral deficiency manifestations. An understanding of these topics will helpthe general dentist, periodontist, and oral surgeon appropriately prescribevitamin C for their patients.

10. Int J Vitam Nutr Res 1982;52(3):333-41The effect of ascorbic acid supplementation on periodontal tissue ultrastructurein subjects with progressive periodontitis.Aurer-Kozelj J, Kralj-Klobucar N, Buzina R, Bacic M

In an attempt to determine the optimal daily ascorbic acid requirement, theeffect of different levels of ascorbic acid intake on collagen synthesis wasstudied in a double-blind experimental design. By use of electron microscopy,interproximal gingival tissue sections in subjects consuming between 20 to 35 mgof ascorbic acid daily were examined before and after the administration oftablets containing 70 mg of ascorbic acid. The results showed that practicallyall subjects were affected by progressive periodontitis with marked changes inthe connective tissue of the gingival lamina propria. After six weeks ofsupplementation with ascorbic acid, differences in the shape and activity offibroblasts in the regenerative tissue of lamina propria were observed. This hasresulted in the increased number of collagen bundles in fibroblasts' periphery,increased tonofibril content and an enlarged number of desmosomes betweenadjacent cells. It is concluded that the obtained results, though suggestingthat the optimal daily ascorbic acid intake should be set above the presentlyrecommended 30-50 mg, have to be quantified by a more objective analyticalmethod.