Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites.

Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986-1989) that included comparable numbers of Black men and White men aged 40-79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites.

Serum retinyl esters are not associated with biochemical markers of liver dysfunction in adult participants in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994.

BACKGROUND: Serum retinyl ester concentrations are elevated in hypervitaminosis A. It was suggested that retinyl esters >10% of total serum vitamin A indicate potential hypervitaminosis, but this cutoff was derived from small clinical samples that may not be representative of the general population. OBJECTIVE: We sought to examine the distribution of serum retinyl ester concentrations and associations between retinyl ester concentrations and biochemical markers of liver dysfunction in a nationally representative sample. DESIGN: We assessed the associations between serum retinyl ester concentrations and 5 biochemical indexes of liver dysfunction by using multivariate linear and multiple logistic regression techniques and controlling for age, sex, use of supplements containing vitamin A, alcohol consumption, smoking status, and use of exogenous estrogens in 6547 adults aged > or =18 y in the third National Health and Nutrition Examination Survey (NHANES III), 1988--1994. RESULTS: Thirty-seven percent of the sample had serum retinyl ester concentrations >10% of total serum vitamin A and 10% of the sample had serum retinyl esters >15% of total vitamin A. We found no associations between serum retinyl ester concentrations and 1) concentrations of any biochemical variable (multiple linear regression) or 2) risk of having biochemical variables above the reference range (multiple logistic regression). We did not find a serum retinyl ester value with statistically significant sensitivity and specificity for predicting increases in biochemical indexes of liver dysfunction. CONCLUSIONS: The prevalence of serum retinyl ester concentrations >10% of the total vitamin A concentration in the NHANES III sample was substantially higher than expected but elevated retinyl ester concentrations were not associated with abnormal liver function.

Serum retinol distributions in residents of the United States: third National Health and Nutrition Examination Survey, 1988-1994.

BACKGROUND: Inadequate vitamin A status has been a potential nutritional problem for some segments of the US population, particularly children and the poor. OBJECTIVE: We evaluated serum retinol concentration by using population-representative data from 16058 participants aged 4 to >/=90 y in the third National Health and Nutrition Examination Survey, 1988-1994. DESIGN: We used multivariate regression to examine the simultaneous associations of sociodemographic, biologic, and behavioral factors with serum retinol concentration. RESULTS: In children, serum retinol concentrations were greater with greater age, body mass index, serum lipids, and the use of supplements containing vitamin A. In adults, male sex, serum lipids, alcohol consumption, and age were positively associated with serum retinol concentration in most racial/ethnic strata. Household income was not associated with serum retinol concentration in children; associations were inconsistent in adults. The prevalence of serum retinol <0.70 micromol/L was very low in all strata; the prevalence of serum retinol <1.05 micromol/L was 16.7-33.9% in children aged 4-8 y and 3.6-14.2% in children aged 9-13 y, depending on sex and racial/ethnic group. The prevalence of serum retinol<1.05 micromol/L was higher in non-Hispanic black and Mexican American children than in non-Hispanic white children; these differences remained significant (P < 0.0001) after covariates were controlled for. Among adults, nonwhite women were significantly (P < 0.0001) more likely than white women to have serum retinol <1.05 micromol/L after covariates were controlled for. CONCLUSIONS: Clinically low serum retinol concentration is uncommon in US residents aged > or = 4 y, although racial/ethnic and socioeconomic differences in serum retinol concentration still exist.

NIST micronutrients measurement quality assurance program: characterizing individual participant measurement performance over time.

The mission of the Micronutrients Measurement Quality Assurance Program (M2QAP) at the National Institute of Standards and Technology is enhanced interlaboratory measurement comparability for fat-soluble vitamin-related measurands in human serum. We recently described improved tools for evaluating individual participant measurement performance in single interlaboratory comparison exercises; we here apply and extend these tools to the evaluation of participant performance over the entire 15-year history of the M2QAP. We describe and illustrate a set of interconnected graphical reporting tools for identifying long-term trends and single-exercise events. We document and discuss recurrent patterns we observe in the measurement performance characteristics for M2QAP participants. The graphical analysis techniques utilized may be applicable to other interlaboratory comparison programs.

Micronutrients Measurement Quality Assurance Program: helping participants use interlaboratory comparison exercise results to improve their long-term measurement performance.

Over the past decade, the Micronutrients Measurement Quality Assurance Program (M2QAP) at the National Institute of Standards and Technology (NIST) has administered nearly 40 interlaboratory comparison exercises devoted to fat-soluble vitamin-related analytes in human serum. While M2QAP studies have been used to help certify reference materials and to document the performance of analytical systems, the primary focus of the M2QAP has been, and remains, the improvement of among-participant measurement comparability for target analytes. Recent analysis of historical measurement performance indicated the most efficient mechanism for further improving measurement comparability among participants is the improvement of long-term (months to years) comparability within each laboratory. The summary reports for the M2QAP studies are being redesigned to provide more chemist-friendly analyses of participant performance, dissecting systematic and random components of measurement incomparability as functions of analyte level and time. This report documents the semantic and graphical tools developed to help interlaboratory-comparison-exercise participants interpret their own measurement performance.

Effect of hemolysis on serum retinol as assessed by direct fluorometry.

To assess the effect of hemolysis on serum retinol concentrations determined by direct fluorometry, we assayed 196 blood samples from children 6-72-mo of age with various grades of hemolysis for serum retinol by both fluorescence and HPLC. Mean serum retinol concentrations determined by HPLC did not differ significantly according to hemolysis grade; however, fluorometric values did. Additionally, serum retinol concentrations obtained from HPLC and those obtained from direct fluorometry were significantly different in samples with severe hemolysis. Multivariate-regression analysis showed that hemolysis grade was a significant predictor of the difference in mean serum retinol values determined by the two methods. Although severe hemolysis interfered with determinations of serum retinol by direct fluorometry, this method is still a viable choice for field studies of vitamin A status.

Serum carotenoid concentrations and their reproducibility in children in Belize.

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood sample 2 wk after the first collection from a subset of children (n = 23) who consumed their habitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26% and 24% of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoxanthin, constituted 51% of median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentration indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrations determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-carotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggests both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or = 2 wk without significant bias.

Serum carotenoid concentrations and their reproducibility in children in Belize

Suggestions that carotenoid-containing foods are beneficial in maintaining health have led to several studies of circulating carotenoid concentrations of adults. Because few data are available for children, we report serum carotenoid concentrations of 493 children in Belize. Carotenoid concentrations were determined as part of a survey of vitamin A status of children, most between 65 and 89 mo of age. Reproducibility was tested by collecting a second blood samples 2 wk after the first collection from a subset of children (n = 23) who consumed their habiitual diet with no treatment during the interim. Predominant serum carotenoids were lutein/zeaxanthin and beta-carotene, which accounted for 26 percent and 24 percent of median total carotenoids, respectively. The three provitamin A carotenoids, alpha- and beta-carotene and beta-cryptoaxnthin, constituted 51 percent od median total carotenoid concentrations. Partial correlations of each carotenoid with fasting retinol concentrations indicated that beta-carotene had the highest correlation. Concordance correlation coefficients (rc) for fasting carotenoid concentrati9ons determined 2 wk apart were > or = 0.89 for lycopene, beta-cryptoxanthin, and alpha- and beta-catotene. The rc for lutein/zeaxanthin and total carotenoids was lower, 0.59 and 0.68, respectively, because of higher lutein/zeaxanthin concentrations at the second sampling than at the first. The reproducibility of the concentrations suggest both that individuals have characteristic profiles and that serum carotenoid concentrations can be measured randomly over > or =2 wk without significant bias. (au)

Comparison of methods of assessing vitamin A status in children.

OBJECTIVE: A study of children (2-8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed. METHODS: The three methods of assessing vit A status were: RDR test, fasting serum retinol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined. RESULTS: Inadequate vit A status was indicated for 17% of subjects by the RDR test (14% cutoff), for 24% by fasting serum retinol concentration (< 0.87 mumol/L), and for 49% by "abnormal" CIC score. Retinyl esters constituted 24% of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regression tree analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of 0-hour retinyl ester concentration. CONCLUSION: The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for vit A deficiency. Increased concentrations of retinyl esters at 5 hours compared to those at 0 hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of 0-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect the RDR test.

Reproducibility of relative dose response (RDR) test and serum retinol and retinyl ester concentrations in children after a 2-week interval.

OBJECTIVE: Reproducibility of the relative dose response test (RDR), a test designed to measure vitamin A status, was tested in 23 Belizean children, 5-8 years after 2-week interval during which no treatment was given. METHODS: As required for the RDR test, serum retinol concentrations were determined before and 5 hours after an oral dose of vitamin A. An RDR score > 14% was used as the criterion of inadequate vitamin A status. The HPLC method used to measure serum retinol concentrations also determined the concentrations of four retinyl esters. RESULTS: The RDR test was reproducible for 17 of 23 subjects: 3 scored > 14% on both tests; 14, < 14% on both. Six subjects scored > 14% on only one test. The concordance correlation coefficient (rc) for the percent change in the two tests was 0.24; for fasting serum retinol concentration, rc = 0.81. For retinyl palmitate and stearate, the esters present in highest concentrations at 5 hours, concordance correlation coefficients were 0.75 and 0.59, respectively. CONCLUSION: The failure of the RDR test to classify 26% of the subjects reproducibly reduces the usefulness of the test. In addition, the reproducibility of the retinyl ester concentrations in serum 5 hours after the retinyl palmitate dose and the relatively high concentrations in some subjects suggests that some individuals may not metabolize sufficient retinol in 5 hours to cause a maximal increase in serum retinol, resulting in an underestimation of deficiency in a population in which the RDR test is used.

Comparison of methods of assessing vitamin A status in children

A study of children (2 - 8 years; n = 613) in Belize, Central America, was conducted to determine what proportion of the children might be at risk of vitamin A (vit A) deficiency. The data provide an opportunity to compare results of three methods of assessing vit A status in a population which was not severely malnourished. Serum retinyl ester concentrations were also determined; their relevance to one of the tests, the relative dose response (RDR) test, is discussed. METHODS: The three methods of assessing vit A status were: RDR test, fasting serum rintol concentration, and conjunctival impression cytology (CIC). Retinol-binding protein (RBP), serum retinyl esters and serum zinc concentrations were also determined. RESULTS: Inadequate vit A status was indicated for 17 percent of subjects by the RDR test (14 percent cutoff), for 24 percent by fasting serum retinol concentration (< 0.87 mumol/L), and for 49 prcent by abnormal. CIC score. Retinyl esters constituted 24 percent of serum retinoids at the time (5 hours after a retinyl palmitate dose) at which the second blood sample is taken for the RDR test. Regresssion trees analyses (CART) indicated ethnicity was a predictor of RDR score; ethnicity, stunting and age were predictors of fasting serum retinol concentration; ethnicity and stunting were predictors of O-hour retinyl ester concentration. CONCLUSION: The three indices of vit A status did not identify the same individuals nor indicate the same percentage of the population to be at risk for hours compared to those at O hours suggest that insufficient retinol may have been taken up by the liver at 5 hours to release all accumulated retinol-binding protein (RBP) in deficient individuals; prevalence of vit A deficiency might therefore be underestimated by the RDR test. The selection of ethnicity as a predictor of RDR score and of O-hour retinol and retinyl ester concentrations suggests that factors other than vit A status affect vit A metabolism and may affect the RDR test.(AU)

Vitamin A therapy for children with respiratory syncytial virus infection: a multicenter trial in the United States.

BACKGROUND: High dose vitamin A therapy is effective in reducing morbidity and mortality associated with measles infection. Children with acute respiratory syncytial virus (RSV) infection have low serum vitamin A concentrations. METHODS: We performed a multicenter, randomized, placebo-controlled trial of high dose vitamin A therapy among 239 children 1 month to 6 years of age to determine whether high dose vitamin A therapy would reduce morbidity associated with RSV infection. RESULTS: There were no differences between the vitamin A and placebo recipients for most clinical outcomes; however, vitamin A recipients had-longer hospital stays than placebo recipients (5.0 days vs. 4.4 days, P = 0.01) after enrollment. This effect was significant for children who were older than 1 year (who also had received the highest doses of vitamin A), particularly among those at low risk for complications of RSV infection and those enrolled during the second study season. Serum retinol levels at enrollment were inversely correlated with severity of illness. CONCLUSIONS: We found no evidence of a beneficial effect of vitamin A for the treatment of RSV infection in children in the United States. There may be groups of children for which vitamin A has an adverse effect, resulting in longer hospital stays.

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND: Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS: To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS: There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS: If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.

Effect of smoking on serum nutrient concentrations in African-American women.

The relationship between current cigarette smoking and serum concentrations of vitamins C, E, and A, and of five carotenoids in human serum were examined in 91 low-income, African-American women. General linear models were used to adjust geometric mean serum concentrations of micronutrients for age, dietary and supplement intakes, total energy intake, alcohol intake, medication use, body mass index, and serum concentrations of cholesterol and triglycerides. Among smokers, serum concentrations of alpha-carotene, beta-carotene, cryptoxanthin, and lycopene averaged only 71-79% of the concentrations among nonsmokers. Mean serum concentrations of vitamins C and E and lutein/zeaxanthin were only slightly lower among smokers relative to nonsmokers, and current smokers had higher serum concentrations of vitamin A. Among current smokers, mean serum concentrations of all five carotenoids decreased with an increase in the amount smoked. The negative effect of smoking on serum concentrations of antioxidant carotenoids may pose a serious health risk in low-income populations already at higher risk for many chronic diseases.

Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection.

We describe the use of HPLC with multiwavelength detection to measure retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, beta-carotene, and the linoleate, oleate, palmitate, and stearate esters of retinol in a single 200-microL serum sample. The method is sensitive enough to detect individual retinyl esters in fasting serum from a nonhyperlipidemic population and requires only 12 min for each sample. Serum concentration ranges and means are reported for retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and the sum of the retinyl esters from serum analyses of 3480 participants from several different studies.

Measles severity and serum retinol (vitamin A) concentration among children in the United States.

BACKGROUND: Studies in developing countries have shown that children with measles have low serum retinol concentrations and that lower retinol levels are associated with measles-related mortality. Vitamin A therapy has been shown to reduce mortality among African children with acute measles. OBJECTIVES: To determine whether serum retinol concentration is low among children with measles in the United States and to determine whether retinol concentration is associated with illness severity. SETTING: Pediatric referral hospital and clinic in Milwaukee, WI, during the measles outbreak of 1989-1990. PATIENTS: One hundred fourteen patients < or = 5 years of age evaluated for serologically confirmed measles with serum obtained within 5 days following rash onset. METHODS: Serum retinol concentration was determined by high-performance liquid chromatography. Clinical data were collected by hospital record review. A modified Pediatric Risk of Mortality (PRISM) score was used to assess physiologic instability as a measure of illness severity. RESULTS: Retinol concentrations ranged from 0.25 to 1.18 mumol/L (median 0.58 mumol/L); 82 (72%) patients had low retinol concentration (< or = 0.70 mumol/L). Median retinol concentrations were lower among hospitalized patients (0.56 vs 0.70, P = .006) and patients with pneumonia (0.52 vs 0.64, P = .02) but higher among children with otitis media (0.63 vs 0.54, P = .01). Higher modified PRISM scores, reflecting greater physiologic instability, were associated with lower retinol concentration (beta coefficient -.0147, P = .025). In multivariate analysis, higher modified PRISM scores were associated with lower retinol concentration (beta coefficient -.0144, P = .025) even after controlling for hospitalization, presence of complications, race, age, receipt of Aid to Families With Dependent Children, gender, and interval from rash onset until serum was collected. CONCLUSIONS: Among these children with measles in an urban United States community, retinol concentrations were depressed, and the degree of depression was associated with illness severity. Vitamin A therapy should be considered for children with measles in the United States who require hospitalization.

Role of nutritional status and weight loss in HIV seroconversion among Rwandan women.

To investigate nutritional status and heterosexual human immunodeficiency virus (HIV) transmission, we performed a nested case-control study of sexually active, adult women in Kigali, Rwanda. Forty-five women who seroconverted during the 24-month study period were compared to 74 women who remained seronegative throughout the study. Seroconvertors and nonseroconvertors did not differ in preseroconversion serum levels of vitamin A, carotenoids, vitamin E, selenium, albumin, ferritin, or cholesterol. Weight loss, however, was a significant predictor of eventual HIV seroconversion. Subsequent seroconvertors lost an average of 1.5 kg during the first 6 months of the study compared with a 1.0-kg gain (p = 0.001) for nonconvertors. Nine of 27 (33%) seroconvertors, compared with one of 44 (2%) controls, lost at least 5 kg in the 6-month period beginning 1 year before their seroconversion (odds ratio, 21.5, 95% confidence interval 4.1-112). The association between weight loss and seroconversion was independent of other potential risk factors such as socioeconomic status, pregnancy, and genital ulcer disease. In addition to these findings for measured weight loss during follow-up, reported weight loss before enrollment was also a risk factor for subsequent seroconversion. Additional studies of heterosexual HIV transmission are needed to determine whether or not weight loss is causally related to susceptibility for HIV infection.

Vitamin A levels and severity of measles. New York City.

Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. Vitamin A levels of children with measles have not been studied in developed countries. We therefore measured vitamin A levels in 89 children with measles younger than 2 years and in a reference group in New York City, NY. Vitamin A levels in children with measles ranged from 0.42 to 3.0 mumol/L; 20 (22%) were low. Children with low levels were more likely to have fever at a temperature of 40 degrees C or higher (68% vs 44%), to have fever for 7 days or more (54% vs 23%), and to be hospitalized (55% vs 30%). Children with low vitamin A levels had lower measles-specific antibody levels. No child in the reference group had a low vitamin A level. Our data show that many children younger than 2 years in New York City have low vitamin A levels when ill with measles, and that such children seem to have lower measles-specific antibody levels and increased morbidity. Clinicians may wish to consider vitamin A therapy for children younger than 2 years with severe measles. Additional studies of vitamin A in measles and other infectious diseases, and in vaccine efficacy trials, should be done.