Comparative effectiveness of a prenatal medical food to prenatal vitamins on hemoglobin levels and adverse outcomes: a retrospective analysis.

BACKGROUND: The role of folate in pregnancy is well established, with most prenatal vitamins (PNVs) on the market containing at least 800 µg of folic acid. Folic acid must be converted in the body to L-methylfolate, the natural and biologically active form of folate. The role of vitamin B(12) in pregnancy is less characterized, and most PNV formulations contain only 0 to 12 µg. The present study was undertaken to evaluate whether taking a prenatal medical food containing L-methylfolate and much higher doses of vitamin B(12) results in higher hemoglobin levels and thus, a lower incidence of anemia during pregnancy. OBJECTIVE: The objective of this exploratory study was to evaluate the effects of the prenatal medical food versus standard PNVs on hemoglobin levels and adverse outcomes throughout pregnancy. METHODS: For this retrospective analysis, we reviewed the charts of female patients taking either a prenatal medical food or standard PNV during pregnancy. Hemoglobin levels measured at initiation of prenatal care, end of second trimester, and delivery were recorded. Patients who had received additional iron supplementation, beyond that contained in the prenatal medical food or PNV they were taking and before anemia screening at the end of the second trimester, were excluded from the study. Fisher exact test, χ(2) test, student t test, and ANOVA were used to evaluate differences between the treatment groups. RESULTS: Data were analyzed from 112 charts: 58 patients (51.8%) were taking the prenatal medical food; 54 patients (48.2%) were taking standard PNVs. Mean (SD) age at first prenatal visit was 27 (4.6) years in the medical food group and 28.8 (3.5) years in the PNV group (P = 0.024). Mean (SD) body mass indices were 29.1 (6.5) and 31.7 (8.9) in the medical food and PNV groups, respectively (P = NS). In the medical food group, 35 women (60.3%) were white/Caucasian, 17 (29.3%) were African American, and 6 (10.4%) were of other races. In the PNV group, 24 women (44.4%) were white/Caucasian, 25 (46.3%) were African American, and 5 (9.3%) were of other races. However, race was not significantly different between the two groups. At end of second trimester and at delivery, mean (SD) hemoglobin levels were higher in the prenatal medical food group (11.8 [1.1] g/dL and 11.8 [1.3] g/dL, respectively) than in the PNV group (11.3 [1.2] g/dL and 10.7 [1.2] g/dL, respectively) (P = 0.011 and P = 0.001, respectively). Significantly fewer cases of anemia were reported at end of second trimester in the prenatal medical food group than in the PNV group (39.7% vs 74.1%; P = 0.001). CONCLUSIONS: In the present study, supplementation with a prenatal medical food containing L-methylfolate and high-dose vitamin B(12) may maintain hemoglobin levels and decrease rates of anemia in pregnancy more effectively than standard prenatal vitamins; however, prospective, controlled studies are warranted. ClinicalTrials.gov identifier: NCT01193192.

Annurca apple polyphenols have potent demethylating activity and can reactivate silenced tumor suppressor genes in colorectal cancer cells.

The CpG island methylator phenotype is characterized by DNA hypermethylation in the promoters of tumor suppressor genes with silencing of transcription. Hypermethylation of the promoter of hMLH1 and subsequent microsatellite instability occurs in approximately 12% of sporadic colorectal cancers (CRC). Annurca apple, a variety of southern Italy, is rich in polyphenols that are associated with anticancer properties. Populations in southern Italy have lower incidences of CRC than elsewhere in the western world. We evaluated the mechanisms of putative anticancer effects of Annurca polyphenol extract (APE) in in vitro models of CRC. We extracted polyphenols from Annurca apples and treated RKO, SW48, and SW480 cells with APE and assessed the cell viability, apoptosis, and cell cycle. DNA methylation of selected tumor suppressor genes was evaluated after treatment with APE and was compared with the synthetic demethylating agent 5-aza-2'deoxycytidine (5-aza-2dC). DNA methyltransferase (DNMT)-1 and -3b levels were evaluated. Decreased cell viability and induction of apoptosis was evident after treatment. We found no significant changes in cell cycle dynamics. We observed significant increases of p53 protein expression in RKO after treatment. APE treatment strongly reduced DNA methylation in the promoters of hMLH1, p14(ARF), and p16(INK4a) with consequent restoration of normal expression. These effects were qualitatively comparable with those obtained with 5-aza-2dC. We observed a significant reduction in expression of DNMT proteins after treatment without changes in messenger RNA. In conclusion, APE have potent demethylating activity through the inhibition of DNMT proteins. The lack of toxicity in Annurca extracts makes them excellent candidates for the chemoprevention of CRC.