Whole Body Health Sale

VITAMIN A (RETINOL)



Table of Contents
image Intake of carotenoids and retinol in relation to risk of prostate cancer
image Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer
image Zinc, vitamin A and prostatic cancer
image In vitro studies of human prostatic epithelial cells: Attempts to identify distinguishing features of malignant cells
image Application of molecular epidemiology to lung cancer chemoprevention.
image Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease
image Review: Treatment of primary biliary cirrhosis
image Retinol (Vitamin A) supplements in the elderly
image Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group
image Vitamins and metals: Potential dangers for the human being
image Vitamin A concentration in the liver decreases with age in patients with cystic fibrosis.
image Relationship between liver cirrhosis death rate and nutritional factors in 38 countries
image Retinoids and carcinogenesis
image Retinoids in cancer treatment.
image Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro.
image Linking vitamin A and childhood immunizations
image Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 mo
image Molecular mechanisms of vitamin A action and their relationship to immunity
image Historical overview of nutrition and immunity, with emphasis on vitamin A
image Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey.
image Antioxidant status and lipid peroxidation in hereditary haemochromatosis.
image Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer.
image [The role of platelets in the protective effect of a combination of vitamins A, E, C and P in thrombinemia]
image Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome.
image Nutrient intake and food use in an Ojibwa-Cree community in Northern Ontario assessed by 24h dietary recall
image [Patients with type-II diabetes mellitus and neuropathy have nodeficiency of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folic acid]
image Malnutrition in geriatric patients: diagnostic and prognostic significance of nutritional parameters.
image The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc
image [The effect of vitamin A and Astragalus on the splenic T lymphocyte-CFU of burned mice]
image Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer.
image Critical reappraisal of vitamins and trace minerals in nutritional support of cancer patients.
image Vitamin A, a useful biochemical modulator capable of preventing intestinal damage during methotrexate treatment.
image Hyperthermia, radiation carcinogenesis and the protective potential of vitamin A and N-acetylcysteine
image Immune suppression: therapeutic alterations
image Effects of vitamins A, C, and E on aflatoxin Bsub 1-induced mutagenesis in Salmonella typhimurium TA-98 and TA-100
image Effect of vitamin A supplementation on lectin-induced diarrhoea and bacterial translocation in rats
image Increased translocation of Escherichia coli and development of arthritis in vitamin A-deficient rats
image Gastrointestinal infections in children
image Intestinal malabsorption presenting with night blindness
image Etiology of acute lower respiratory tract infection in children from Alabang, Metro Manila
image Effect of vitamin A in enteral formulae for burned guinea-pigs
image Vitamin A supplementation improves macrophage function and bacterial clearance during experimental salmonella infection
image Inhibition by retinoic acid of multiplication of virulent tubercle bacilli in cultured human macrophages
image Corneal ulceration, measles, and childhood blindness in Tanzania
image Impact of vitamin A supplementation on childhood mortality. A randomised controlled community trial
image Impaired blood clearance of bacteria and phagocytic activity in vitamin A-deficient rats (41999)
image Chronic salmonella septicemia and malabsorption of vitamin A
image Retinol level in patients with psoriasis during treatment with B group vitamins, a bacterial polysaccharide (pyrogenal) and methotrexate (Russian)
image Socioeconomic status and lung cancer incidence in men in The Netherlands: Is there a role for occupational exposure?
image Asthma but not smoking-related airflow limitation is associated with a high fat diet in men: Results from the population study 'Men born in 1914'
image Diminished production of malondialdehyde after carotid artery surgery as a result of vitamin administration
image Effect of supplemental vitamin A on colon anastomotic healing in rats given preoperative irradiation
image Nutritional status and cognitive functioning in a normally aging sample: a 6-y reassessment.
image Antioxidant status of hypercholesterolemic patients treated with LDL apheresis
image Diet and risk of esophageal cancer by histologic type in a low-risk Group
image New agents for cancer chemoprevention
image Metabolism of vitamin A in inflammatory bowel disease
image Vitamin status in patients with inflammatory bowel disease
image Zinc and vitamin A deficiency in patients with Crohn's disease is correlated with activity but not with localization or extent of the disease
image Antioxidants, Helicobacter pylori and stomach cancer in Venezuela.
image Vitamins as therapy in the 1990s
image Association of esophageal cytological abnormalities with vitamin and lipotrope deficiencies in populations at risk for esophageal cancer

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VITAMIN A (RETINOL)

Intake of carotenoids and retinol in relation to risk of prostate cancer Journal of the National Cancer Institute (USA), 1995, 87/23 (1767-1776)

Background: Several human studies have observed a direct association between retinol (vitamin A) intake and risk of prostate cancer; other studies have found either an inverse association or no association of intake of beta- carotene (the major provitamin A) with risk of prostate cancer. Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse. Purpose: We conducted a prospective cohort study to examine the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer. Methods: Using responses to a validated, semiquantitative food-frequency questionnaire mailed to participants in the Health Professionals Follow-up Study in 1986, we assessed dietary intake for a 1-year period for a cohort of 47 894 eligible subjects initially free of diagnosed cancer. Follow-up questionnaires were sent to the entire cohort in 1988, 1990, and 1992. We calculated the relative risk (RR) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level. All P values resulted from two-sided tests. Results: Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage A1 cases, were documented. Intakes of the carotenoids beta-carotene, alpha-carotene, lutein, and beta- cryptoxanthin were not associated with risk of non-stage A1 prostate cancer; only lycopene intake was related to lower risk (age- and energy-adjusted RR = 0.79; 95% confidence interval (CI) = 0.64-0.99 for high versus low quintile of intake; P for trend = .04). Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four-tomato sauce (P for trend = .001), tomatoes (P for trend = .03), and pizza (P for trend = .05), but not strawberries-were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65; 95% CI = 0.44-0.95, for consumption frequency greater than 10 versus less than 1.5 servings per week; P for trend = .01) and advanced (stages C and D) prostate cancers (multivariate RR = 0.47; 95% CI = 0.22-1.00; P for trend = .03). No consistent association was observed for dietary retinol and risk of prostate cancer. Conclusions: These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk. Implications: Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk.



Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer

J. NATL. CANCER INST. (USA), 1990, 82/11 (941-946)

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.



Zinc, vitamin A and prostatic cancer

BR. J. UROL. (ENGLAND), 1983, 55/5 (525-528)

The serum zinc, vitamin A, albumin, copper and retinoid-binding protein content was measured in 27 patients with benign prostatic hyperplasia and 19 patients with carcinoma of the prostate. A significantly lower (P = < 0.05) level of serum zinc was found in the cancer group as well as a significant zinc/vitamin A correlation (P = < 0.05). The possible significance of this in relation to the pathogenesis of carcinoma of the prostate is discussed.



In vitro studies of human prostatic epithelial cells: Attempts to identify distinguishing features of malignant cells

GROWTH FACTORS (United Kingdom), 1989, 1/3 (237-250)

Recent advances in culture techniques have enabled routine establishment and propagation of epithelial cells derived from normal and malignant tissues of the human prostate. Comparative studies of the responses of normal and cancer-derived cell populations to various growth and differentiation factors in vitro were undertaken to examine the possibility that cancer cells might respond differentially. Clonal growth assays in serum-free medium demonstrated that optimal proliferation of normal as well as cancer cell strains was generally dependent on the presence of cholera toxin, epidermal growth factor, pituitary extract, hydrocortisone, insulin and high levels of calcium in the culture medium, and on the use of collagen-coated dishes. Only one cancer strain responded aberrantly to epidermal growth factor and hydrocortisone. Putative differentiation factors (transforming growth factor-beta and vitamin A) inhibited the growth of all normal and cancer strains. The origin of a cancer-derived cell strain that responded similarly to normal strains was verified by positive labeling with a prostate cancer-specific antibody, validating the conclusion from these studies that normal and cancer prostatic epithelial cells are not distinguishable on the basis of responses to the tested factors.



Application of molecular epidemiology to lung cancer chemoprevention.

Mooney LA; Perera FP Columbia University School of Public Health, Division of Environmental Health Sciences, New York, New York 10032, USA. J Cell Biochem Suppl (UNITED STATES) 1996, 25 p63-8

Molecular epidemiology has made great progress in detecting and documenting carcinogenic exposures and host susceptibility factors, in an effort to explain interindividual variation in disease. Interindividual differences in genetic and acquired factors including nutritional status. Eleva ted risk of lung cancer has been associated with polymorphisms of metabolic genes such as CYP1A1 and GSTM1. On the other hand, numerous studies have demonstrated that diets rich in fruits and vegetables are protective against cancer, and have correlated high levels of antioxidants in the blood with decreased risk. As a first step in identifying susceptible individuals, we have assessed the combined effect of genetic factors and nutritional status on DNA adducts in a population of healthy smokers. Plasma retinol, beta-carotene, alpha-tocopherol, and zeaxanthin were inversely correlated with DNA damage, especially in subjects lacking the "protective" GSTM1 gene. Research is ongoing using biomarkers to determine the effect of supplementation with antioxidants/vitamins on DNA damage, especially in population subsets with putative "at risk" genotypes. Information on mechanisms of interactions between exposure, micronutrients, and other susceptibility factors is important in the development of effective practical interventions. (33 Refs.)



Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease

Omenn GS; Goodman GE; Thornquist MD; Balmes J; Cullen MR; Glass A; Keogh JP; Meyskens FL; Valanis B; Williams JH; Barnhart S; Hammar S Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA. N Engl J Med (UNITED STATES) May 2 1996, 334 (18) p1150-5

BACKGROUND. Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of luew cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.



Review: Treatment of primary biliary cirrhosis

Journal of Gastroenterology and Hepatology (Australia),1996, 11/7 (605-609)

Primary biliary cirrhosis (PBC) is a slowly progressive chronic cholestatic disease of the liver thought to be caused by immune destruction of the interlobular bile ducts. One-third of patients are asymptomatic and one-third of these develop symptoms within 5 years. Therapeutic regimens should be directed at the control of symptoms, prevention of complications and specific therapy aimed at controlling progression of the disease. Symptoms may be secondary to cholestasis or due to other associated diseases. The cause of pruritus secondary to cholestasis remains unknown; the anion exchange resin cholestyramine generally brings relief. In patients resistant or intolerant to this therapy, rifampin may be helpful, as well as ultraviolet light without sunblock. Liver transplantation may rarely be the only option for uncontrollable pruritus. Clinical manifestations of keratoconjunctivitis sicca and xerostomia need constant attention to prevent corneal ulcers and dental caries. Preventative therapy includes regular screening for thyroid dysfunction and replacement therapy when necessary and the administration of the fat soluble vitamins A, D and K once hyperbilirubinaemia is present. Osteoporosis is a complication of all cholestatic liver disease. There is no satisfactory preventative therapy. It may be appropriate to give hormone replacement therapy to all post- menopausal women with PBC to reduce osteoporosis. Liver transplantation is the best option for those with fractures. Oesophageal varices may develop early in the course of PBC, non selective beta-blocker therapy should be used as prophylaxis against variceal haemorrhage. The only specific therapy shown to cause both a biochemical and survival benefit in patients with PBC is ursodeoxycholic acid (UDCA). Treatment with UDCA delays progression, but does not result in a cure of this disease. Currently, liver transplantation is the only definitive treatment available for end-stage disease.



Retinol (Vitamin A) supplements in the elderly

Drugs and Aging (New Zealand), 1996, 9/1 (48-59)

Aging is associated with many changes in epithelial tissues, immune function and haematopoiesis-myelopoiesis. There is increasing evidence that retinoids can significantly influence some of these changes. Retinoids may also have anticancer effects and protect against age-associated conditions such as macular degeneration. However, retinol (vitamin A) can be toxic when taken in excess and the elderly may be at particular risk for hypervitaminosis A. Evaluation of elderly people ingesting significantly more or less than the recommended daily intake of retinol requires an understanding of the biology of retinoids and consideration of the relative risks and benefits of supplementation.



Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group

JAMA (UNITED STATES) Nov 9 1994

OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.



Vitamins and metals: Potential dangers for the human being

Schweizerische Medizinische Wochenschrift (Switzerland), 1996, 126/15 (607-611)

Administration of vitamins or metals may cause severe side effects. Retinoids (derivatives of vitamin A) used for the treatment of various skin disorders are teratogenic, hepatotoxic and may induce a substantial increase in serum lipids. A case report demonstrates that vitamin D supplementation in a patient under total parenteral nutrition can cause hypercalcemia. The isolated administration of vitamin B1, without concomitant vitamin B6 and nicotinamide may precipitate potentially life-threatening pellagra encephalopathy. Repeat blood transfusions may produce clinically overt organ hemosiderosis, e.g. cirrhosis of the liver, diabetes mellitus or myocardiopathy. The literature contains reports on a few cases of sarcoma associated with orthopedic metal implants. The controversial issue of the potential dangers of dental amalgams is briefly mentioned.



Vitamin A concentration in the liver decreases with age in patients with cystic fibrosis.

J Pediatr Gastroenterol Nutr (UNITED STATES) Mar 1997, 24 (3) p264-70,

BACKGROUND: Vitamin A deficiency is a common manifestation in cystic fibrosis (CF), but high levels of vitamin A in the liver have also been described. High levels of vitamin A in the liver are toxic, while normal levels might be protective against liver damage. In order to investigate whether liver damage in patients with CF is related to vitamin A content of the liver, vitamin A status was investigated in 15 patients with CF aged 8 to 34 years. METHODS: Liver biopsy was performed on clinical indication and the vitamin A concentration in the liver was determined as retinylpalmitate. Serum levels of retinol and retinol-binding protein were investigated on the morning of the biopsy. Eight patients had morphologic signs of cirrhosis. Eight patients had been on treatment with ursodeoxycholic acid for 1 to 3 years. All but three patients had been on vitamin A supplementation for years. RESULTS: Five patients had serum concentrations of retinol below the reference range and seven patients had decreased serum levels of retinol-binding protein. There was a strong correlation between serum levels of retinol and retinol-binding protein (rs = 0.90, p = 0.01), but no correlations with age, Shwachamn score, or genotype. Six of the patients had vitamin A concentrations in the liver < 40 micrograms/g wet weight, and the concentrations decreased significantly with age (rs = 0.77, p = 0.01), without correlation to clinical score or liver disease. There was no indication of hypervitaminosis, although younger patients had been or were being treated with vitamin A in fat-water emulsion. CONCLUSIONS: Our results indicate that the risk of vitamin a deficiency in cystic fibrosis increases with age. The data do not support the view that patients are at risk for hypervitaminosis by long-term supplementation with vitamin A. No correlation was found between the severity of liver disease and the vitamin A content in the liver.



Relationship between liver cirrhosis death rate and nutritional factors in 38 countries

INT. J. EPIDEMIOL. (United Kingdom), 1988, 17/2 (414-418)

The relationship between liver cirrhosis death rates and certain nutritional factors was studied in 38 countries where mortality statistics were considered to be reliable. A partial correlation analysis showed that several food commodity consumption factors were independently and negatively (p < 0.01) associated with liver cirrhosis death rates after adjustment for alcohol consumption. These factors were total calories, protein, fat, calcium, vitamin A and vitamin B2. The significant association of protein, vitamin A, vitamin B2 and calcium with the cirrhosis death rates is of importance since they were not intercorrelated with alcohol consumption. Further results showed that animal protein was more significantly related to cirrhosis death rates than vegetable protein. However, in view of certain limitations of this study, the findings do not necessarily reflect causal relationships but rather support the consideration by scientists that protein and vitamin deficiency may have certain effects on liver cirrhosis.



Retinoids and carcinogenesis

Biotherapy (Japan), 1997, 11/4 (512-517)

A@ 'Retinoid' is a term which collectively indicates vitamin A (retinol) and its derivatives. In addition to well known functions such as dark adaptation and growth, retinoids have an important role in the regulation of cell differentiation and tissue morphogenesis. Since the impaired cell differentiation directly induces cellular atypia and the abnormal morphogenesis is tightly linked with structural atypia, retinoids are regarded to play a significant role in the inhibition of carcinogenesis in various tissues and organs. Following numerous experimental studies on the effects of retinoids on carcinogenesis, clinical use of retinoids has already been introduced in the treatment of cancer (acute promyelocytic leukemia) as well as in the chemoprevention of carcinogenesis of the head and neck region, breast, liver and uterine cervix. Application of retinoids in clinical oncology, and biochemical and immunological mechanisms of retinoids to suppress carcinogenesis are reviewed in this article.



Retinoids in cancer treatment.

J Clin Pharmacol. 1992 Oct. 32(10). P 868-88

Since initial studies identifying the important role of vitamin A and its derivatives (retinoids) in maintaining the integrity of epithelial tissues, these compounds have served as paradigms for experimental studies exploring the pharmacologic modification of carcinogenesis. Retinoids have clearly been shown to inhibit chemically induced mammary and urothelial carcinogenesis in experimental animals. Prohibitive toxicity of the parent compound, vitamin A, led to a systematic search for synthetic derivatives with an improved therapeutic index. More than 1500 such compounds have been synthesized, many retaining chemopreventive potential, but with less toxicity. Although several anecdotal reports confirming therapeutic benefits of cis-retinoic acid in patients with acute promyelocytic leukemia and myelodysplastic syndromes appeared in the late 1970s and early 1980s, the remarkable studies of Huang and his colleagues in China in 1988 reporting complete remissions in patients with this uncommon variety of acute myelogenous leukemia with the transisomer of retinoic acid (all-trans-retinoic acid) led to a resurgence of interest in the retinoids as differentiating agents for the prevention and therapy of cancer. Furthermore, molecular studies showing DNA rearrangements of the alpha nuclear receptor for retinoic acid located on chromosome 17 in patients with acute promyelocytic leukemia, a disease invariably associated with a translocation between chromosomes 15 and 17, provided a direct connection between an altered nuclear receptor and the development of a human malignancy. The retinoids also may have important beneficial effects in prevention of recurrent malignancies once the primary tumor has been treated, such as in squamous cell carcinoma of the head and neck. Because retinoids appear to be less effective in inducing differentiation in nonpromyelocytic leukemia cells, investigators have conducted a number of studies to exploit potential synergism between retinoids and other differentiating agents or biologic effectors. Differentiation therapy and chemoprevention are attractive alternative approaches to intensive cytotoxic chemotherapy. It is now clear that retinoids represent one class of compounds with which it may be possible to reverse the progression of malignant disease and prevent carcinogenesis.



Vitamin A preserves the cytotoxic activity of adriamycin while counteracting its peroxidative effects in human leukemic cells in vitro.

Biochem Mol Biol Int. 1994 Sep. 34(2). P 329-35

Previous results from our laboratory gave evidence that safe doses of vitamin A were very effective in protecting rats from adriamycin-induced oxidative stress and lethal cardiotoxicity (Tesoriere, L. et al. (1994) J. Pharmacol. Experim. Ther. 269, 430-436). This was an incentive also to evaluate whether or not vitamin A affected the antitumor activity of adriamycin. K562 human erythroleukemia cells were exposed to adriamycin or to adriamycin plus vitamin A. Presence of 2.5 to 15 microM all-trans retinol in the cell culture did not impair the cytotoxicity of adriamycin. Rather, an enhanced cell death was observed when cell colony was exposed to both compounds. Additional assays showed that all-trans retinol counteracted the lipoperoxide formation, assayed as malondialdehyde, induced in cell cultures by the redox cycling activity of adriamycin. These data strongly encourage a new therapeuthical approach with safe doses of vitamin A as an adjuvant in cancer chemotherapy.



Linking vitamin A and childhood immunizations

Journal of Nutritional Immunology (USA), 1996, 4/1-2 (87-109)

Although studies conducted over the last twenty-five years have demonstrated that vitamin A and related retinoids are immune enhancers, the use of vitamin A and related retinoids to enhance responses to immunization has been limited. Numerous animal studies have now demonstrated that vitamin A and related retinoids, when given at or prior to immunization, will enhance antibody responses and cell-mediated immune responses to protein antigens. Recent studies with humans show that vitamin A supplementation enhances the IgG response to tetanus toxoid, and that related retinoids can be used to enhance antibody responses to protein antigens. Vitamin A enhances immune responses to poor immunogens, and this may be relevant to vaccines which are characterized by low seroconversion rates. Although most known adjuvants have too many side effects for human use, vitamin A and related retinoids appear to enhance antibody and cell-mediated immunity without severe side effects. Vitamin A, through its metabolites, acts to modify biological responses through specific nuclear receptors which activate gene transcription. Thus, the mechanism for immune enhancement by vitamin A appears to be different from that of known adjuvants. Vitamin A and related retinoids have potential as a safe and effective means of enhancing immune responses to vaccination antigens.



Effect of early vitamin A supplementation on cell-mediated immunity in infants younger than 6 mo

American Journal of Clinical Nutrition (USA), 1997, 65/1 (144-148)

One hundred twenty infants were randomly as signed to receive either 15 mg vitamin A or placebo with each of three DPT/OPV (diphtheria, pertussis, tetanus/oral polio vaccine) immunizations at monthly intervals. Sixty-two received vitamin A and 58 received placebo. One month after the third supplementation dose, the response to the delayed cutaneous hypersensitivity test (multitest cell-mediated immunity (CMI) skin evaluation) for tetanus, diphtheria, and tuberculin (purified protein derivative, PPD) was the same in the vitamin A and placebo infants. The number of anergic infants was 17 (27%) and 19 (33%) in the vitamin A and placebo groups, respectively. The number of positive tests among well-nourished infants was significantly higher than that in malnourished infants irrespective of supplementation (P < 0.001). Among the infants with adequate serum retinol concentrations (> 0.7 micromol/L) after supplementation, the vitamin A-supplemented infants had a significantly higher proportion of positive CMI tests than the placebo infants (chi-square test: 8.99, P = 0.008). Among the infants with low serum retinol concentrations (< 0.7 micromol/L) after supplementation, vitamin A supplementation had no effect on CMI response. These results indicate that CMI in young infants was positively affected by vitamin A supplementation only in those infants whose vitamin A status was adequate (ie, serum retinol > 0.7 micromol/L) at the time of the CMI test. CMI was consistently better in well-nourished infants irrespective of supplementation.



Molecular mechanisms of vitamin A action and their relationship to immunity

Journal of Nutritional Immunology (USA), 1996, 4/1-2 (35-45)

This paper addresses the molecular mechanisms by which vitamin A (retinol) could influence the immune system, and the relationships of these mechanisms to the better known mechanisms in which retinol affects other non-immune biological phenomena, such as epithelial cell differentiation, embryogenesis, and organ development. In many tissues, the sequential molecular actions of the retinoids have been well defined. However, major questions remain about the action of retinoids on lymphocytes. Much evidence indicates an important role for vitamin A molecules (called retinoids) in the function of both the cellular and the humoral arms of the immune system. Attention should also be paid to the nuclear retinoic acid receptors (RAR) in various cells. These protein receptors are similar to those which bind steroids, thyroid hormones, and vitamin D. The nuclear retinoic acid receptors, and another analogous receptor family initially called 'orphan receptor' now designated 'nuclear RXR receptors,' together with other described cellular binding proteins, appear to be involved in regulating, as well as transmitting, the effects of the retinoids on the molecular machinery of various body cells, including the lymphocytes.



Historical overview of nutrition and immunity, with emphasis on vitamin A

Journal of Nutritional Immunology (USA), 1996, 4/1-2 (1-16)

In retrospect, the foundations for Nutritional Immunology emerged in the early 1800s with the finding that severe malnutrition would lead to thymic atrophy, and for most of that century, all evidence for a relationship between malnutrition and the immune system was based on anatomical findings. With the discovery of vitamins, it became evident that single essential nutrients each played an important role in host resistance. During the 1920s and 1930s, vitamin A became known as the 'anti-infective' vitamin, and the first attempts were made to use vitamin A therapeutically during infectious illnesses. With the gradual emergence of knowledge about the details of immune system functions, malnutrition was found to depress humoral immunity (by reducing the production of antibodies to vaccines), cell mediated;immunity (by inducing anergy to skin tests), and allergic symptoms. But the first systematic studies of immunonutritional interrelationships in laboratory animals were initiated in 1947 by Abraham E. Axelrod and his students. Human studies followed soon thereafter, and by the late 1970s the field of nutritional immunology was well established. The importance of vitamin A in reducing the morbidity and mortality caused by measles and other infectious illnesses has now re-emerged. The potential importance of correcting vitamin A deficiency, as a practical and inexpensive public health strategy to reduce childhood mortality in the Third World, is being tested in many locations, with The Johns Hopkins School of Hygiene and Public Health playing an important role.



Factors associated with age-related macular degeneration. An analysis of data from the first National Health and Nutrition Examination Survey.

Am J Epidemiol (UNITED STATES) Oct 1988, 128 (4) p700-10

Data from the first National Health and Nutrition Examination Survey collected between 1971 and 1972 were used to determine what factors are associated with the prevalence of age-related macular degeneration. The study was limited to those who were at least 45 years old at the time of the ophthalmology examination. Stratified analysis, adjusting for age, showed that education, systolic blood pressure, past history of hypertension, cerebrovascular disease, and refractive error were all associated with macular degeneration. With the exception of education, these factors remained statistically significant when simultaneously entered into a logistic regression model. The frequency of consumption of fruits and vegetables rich in vitamins A and C suggested a negative association with the prevalence of macular degeneration after stratified adjustment for age. In a logistic regression analysis, adjusting for demographic and medical factors, the inverse association of vitamin C with age-related macular degeneration was no longer present. The frequency of consumption of fruits and vegetables rich in vitamin A remained negatively correlated with age-related macular degeneration even after adjustment for demographic and medical factors.



Antioxidant status and lipid peroxidation in hereditary haemochromatosis.

Free Radic Biol Med (UNITED STATES) Mar 1994, 16 (3)

Hereditary haemochromatosis is characterised by iron overload that may lead to tissue damage. Free iron is a potent promoter of hydroxyl radical formation that can cause increased lipid peroxidation and depletion of chain-breaking antioxidants. We have therefore assessed lipid peroxidation and antioxidant status in 15 subjects with hereditary haemochromatosis and age/sex matched controls. Subjects with haemochromatosis had increased serum iron (24.8 (19.1-30.5) vs. 17.8 (16.1-19.5) mumol/l, p = 0.021) and % saturation (51.8 (42.0-61.6) vs. 38.1 (32.8-44.0), p = 0.025). Thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were increased in haemochromatosis (0.59 (0.48-0.70) vs. 0.46 (0.21-0.71) mumol/l, p = 0.045), and there were decreased levels of the chain-breaking antioxidants alpha-tocopherol (5.91 (5.17-6.60) vs. 7.24 (6.49-7.80) mumol/mmol cholesterol, p = 0.001), ascorbate (51.3 (33.7-69.0) vs. 89.1 (65.3-112.9), p = 0.013), and retinol (1.78 (1.46-2.10) vs. 2.46 (2.22-2.70) mumol/l, p = 0.001). Patients with hereditary haemochromatosis have reduced levels of antioxidant vitamins, and nutritional antioxidant supplementation may represent a novel approach to preventing tissue damage. However, the use of vitamin C may be deleterious in this setting as ascorbate can have prooxidant effects in the presence of iron overload.



Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high incidence of oral and esophageal cancer.

Ann Epidemiol. 1993 May. 3(3). P 225-34

This intervention trial carried out in Uzbekistan (former USSR) in an area with a high incidence of oral and esophageal cancer involved random allocation of 532 men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one of four arms in a double-blind, two-by-two factorial design, with active arms defined by the administration of (a) riboflavin; (b) a combination of retinol, beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene was 40 mg/d. Men in the trial were followed for 20 months after randomization. The aim of the trial was to determine whether treatment with these vitamins or their combination could affect the prevalence of oral leukoplakia and/or protect against progression of oral leukoplakia and esophagitis, conditions considered to be precursors of cancer of the mouth and esophagus. A significant decrease in the prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95% confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect of vitamin supplementation was seen when the changes in chronic esophagitis were compared in the four different treatment groups, although the risk of progression of chronic esophagitis was lower in the subjects allocated to receive retinol, beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary analysis not based on the randomized design revealed a decrease in the prevalence of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20 months of treatment. Risk of progression of chronic esophagitis was also lower in men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95% CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels, respectively. A decrease in risk, also statistically not significant, was observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These results were based on levels of vitamins in blood drawn after 20 months of treatment.



[The role of platelets in the protective effect of a combination of vitamins A, E, C and P in thrombinemia]

Gematol Transfuziol (RUSSIA) Sep-Oct 1995, 40 (5) p9-11

White rat experiments have shown that combination of vitamins A, E, C and P diminishes thrombin-induced thrombocytopenia and low platelet aggregation. This is explained by limited activation of free radical processes initiated by thrombin in plasma, red cells and platelets. It was found that thrombin ability to activate lipid peroxidation is not related to coagulatory transformation of fibrinogen, but is rather due to a direct contact of the enzyme with platelets. A protective effect of vitamins-antioxidants in thrombinemia is likely to rest on their ability to restrict activation of free radical oxidation in platelets



Vitamin A and carotene values of institutionalized mentally retarded subjects with and without Down's syndrome.

Journal of Mental Deficiency Research 1977 Mar Vol 21(1) 63-74

Assessed vitamin A and carotene values of 44 3-34 yr old Down's syndrome, 56 3-35 yr old non-Down's syndrome mentally retarded, and 40 normal 1-25 yr old Ss. Dietary and environmental uniformity was maintained by utilizing Down's and non-Down's Ss residing in the same institution. Results show that Down's Ss showed vitamin A values that were significantly higher than those of the non-Down's retarded Ss and similar to those of the normal Ss. Carotene values were similar in the Down's and non-Down's retarded groups, but were significantly higher than those of the normal Ss. This difference in carotene is seen as reflecting in part the high level of carotenoid products in the institutional diet. Carotene/vitamin A ratio values are reported, and the possibility that relatively high ratio values reflected a decreased efficiency in converting carotene to vitamin A is discussed. It is suggested that Down's Ss may suffer some impairment in the utilization of vitamin A at its site of action.