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Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.

Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for cervical neoplasia, although infection alone is insufficient to produce disease. Cofactors such as nutritional factors may be necessary for viral progression to neoplasia. Results from previous studies have suggested that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical neoplasia. This study evaluated the role of vitamin A and carotenoids on HPV persistence comparing women with intermittent and persistent infections. As determined by the Hybrid Capture II system, oncogenic HPV infections were assessed at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the risk of persistent HPV infection associated with each tertile of dietary and circulating micronutrients. Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01). These data suggest that vegetable consumption and circulating cis-lycopene may be protective against HPV persistence.

Persistent oncogenic human papillomavirus (HPV) infection is associated with cervical dysplasia. Cofactors, such as nutrient status, may be required for the progression of HPV infection to neoplasia. HPV DNA methylation patterns in vitro have been shown to be associated with viral transcriptional activity. Folate, vitamin B12, vitamin B6, and methionine may function to prevent cervical cancer through their role in DNA methylation. This study was conducted to examine the relationship of dietary intake of folate, vitamin B12, vitamin B6, and methionine, as well as circulating levels of folate and vitamin B12 to HPV persistence. Oncogenic HPV status was determined at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the adjusted odds ratios for persistent HPV infection associated with each tertile of individual nutrient among 201 women with a persistent or intermittent HPV infection. Circulating vitamin B12 levels were inversely associated with HPV persistence (P for trend, 0.037) after adjusting for age, age at first intercourse, marital status, cigarette smoking status, race, and body mass index. In addition, women with circulating levels in the highest tertile (493.2 pg/ml) of vitamin B12 were less likely to have a persistent infection (adjusted odds ratio = 0.4; 95% confidence interval = 0.17-0.96). No significant associations were observed between HPV persistence and dietary intake of folate, vitamin B12, vitamin B6, or methionine from food alone or from food and supplements combined or from circulating folate. These data suggest a role for circulating vitamin B12 in early cervical carcinogenesis.