Folate intake in North America has drastically increased over the past decade due to folic acid fortification and widespread supplemental use. The role of folate in breast cancer is highly controversial and the effects of folic acid supplementation on breast cancer patients are currently unknown. An animal study was performed to determine the effects of folic acid supplementation on the progression of the mammary tumors in the DMBA-carcinogen model. Folic acid supplementation was associated with more rapid sentinel tumor progression and with higher sentinel tumor weight, volume, and area, although no clear dose-responsive relationship was observed. Folic acid supplementation was associated with an increased expression of proapoptotic protein PARP and decreased expression of proliferation protein PCNA. These data suggest that folic acid supplementation may promote the progression of established mammary tumors. Whether or not folic acid supplementation may adversely affect the outcome of patients with breast cancer warrants further studies.

Folate blood levels in North America have dramatically increased over the past decade owing to folic acid (FA) fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer (CRC) patients use vitamin supplements containing FA while receiving chemotherapy whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of human colon cancer cells to 5FU, the cornerstone of CRC treatment, using a xenograft model. FA supplementation was associated with a non-dose dependent decrease in chemosensitivity, where mice receiving 8 mg FA did not respond to 5FU and had greater tumor growth with treatment, compared to 2 (control) or 25 mg FA. Results of this study pose concern given the drastically increased intake of FA, particularly among recently diagnosed CRC patients, and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate underlying mechanisms.

It is highly recommended for women to take multivitamin/mineral supplements during the periconceptional and prenatal periods. Studies have confirmed that taking prenatal multivitamins prevents maternal iron deficiency anemia, and reduces the risk for neural tube defects (NTDs). To date, research aimed at optimizing the use of multivitamins before and during pregnancy has been minimal. My thesis focused on two challenges of periconceptional and prenatal multivitamin supplementation. The first challenge was gastrointestinal (GI) adverse events such as nausea and constipation which may be attributed to iron content and tablet size. Pregnant women are highly susceptible to GI adverse events since 80% experience nausea and vomiting of pregnancy. A prospective, randomized, controlled, open-label study was conducted to investigate whether a low-iron, small-tablet prenatal multivitamin can reduce GI adverse events, and improve supplement tolerability and adherence, relative to a high-iron, small-tablet prenatal multivitamin. We determined that low iron dose did not produce a significant difference, while small tablet size could be considered an important factor. Moreover, our results confirmed that adherence was poor in pregnant women. We were prompted to identify determinants which could predict adherence to prenatal multivitamins. Our retrospective study determined that predictors of adherence are rooted in women’s prior experiences with multivitamin use. The second challenge we addressed was achieving adequate blood folate concentrations for prevention of NTDs. If adherence is poor, standard dosing of 0.4-1 mg folic acid may not produce the blood folate concentrations needed in women prior to conception. We investigated the pharmacokinetics of 5 mg folic acid. Our prospective, parallel, open-labeled study, comparing a single dose of 5 mg to 1.1 mg folic acid, confirmed that folic acid follows linear (proportional) pharmacokinetics. However, our prospective, randomized, controlled, open-labeled, multiple-dose study determined that repeated use of folic acid at these 2 doses followed non-linear pharmacokinetics. Nevertheless, our data confirmed that 5 mg folic acid can produce higher blood folate concentrations, with a faster rate, which can counter the effect of poor adherence. In conclusion, optimal use of prenatal multivitamins requires improvements in supplement tolerability, adherence, and pharmacokinetics which depend on supplement formulations, and individualized assessment and counseling.

BAKGRUND: Folsyra och järn är två viktiga ämnen som under graviditeten har olika betydelser dels för mamman och dels för fostret. Brister på dessa ämnen kan således leda till skador av olika slag och därför rekommenderas ofta kosttillskott till gravida kvinnor. Kvinnornas matvanor kan påverka om de får i sig tillräcklig mängd av dessa ämnen. SYFTE: Syftet med denna studie var att se hur gravida förhåller sig till att ha en hälsosam kost under graviditeten samt inställningen till kosttillskott med järn och folsyra. Studien syftade till att undersöka eventuella hinder samt se användningen av järn och folsyra. METOD: Studien är av kvantitativ typ med en enkät som inför denna undersökning har modifierats, Health and Taste Attitude Scale. Enkäten består av 7 frågor och 21 påståenden varav 6 st är från HTAS och resterande tillagda. Deltagarna kommer från ett internetforum "Min Bebis" där enkäten skickades ut som ett personligt meddelande till 151 st, varav 44 st kom att delta. En beskrivande analys gjordes med medelvärde och standardavvikelse. RESULTAT: Denna studie hade en majoritet av blivande förstagångsföräldrar och visade på att fler gravida kvinnor tar kosttillskott med järn än folsyra. Det verkar finnas en bristande konsumtion på livsmedel rika på folsyra och järn däribland blodpudding, frukter och fullkornsprodukter. I resultatet framkommer att de flesta inte har tagit tillskott av folsyra innan graviditet. De gravida verkar ha en måttlig inställning till att äta hälsosamt under sin graviditet. / BACKGROUND: Folic acid and iron are two important substances during pregnancy which have different meanings for the mother and the child. Deficiencies of these substances can lead to damage, and therefore often recommended supplements to pregnant. Women´s diet can affect whether they get enough of those substances. AIM: The aim of this study was to see how the pregnancy is related to having a healthy diet and attitudes to food supplements with iron and folic. The study aimed to investigate possible barriers and ensure the use of iron and folic acid. METHOD: This study is quantitative using a questionnaire developed for this study. The questionnaire contained part of the Health and Taste Attitude Scale. The items were partly modified to suit the aim of the study. The questionnaire was send as a message to 151 pregnant women in the internet forum "MinBebis" and 44 were participating. RESULTS: Respondents in this study were mainly prospective first-time parents and the results showed that more pregnant women take supplements with iron than folic acid. There seems to be a low consumption of foods rich in folic acid and iron, example fruit and whole grains. The majority did not take supplements of folic before pregnancy. The pregnant women seem to have a moderate approach to eating healthy during their pregnancy.

Thesis (Ph.D.)--Virginia Commonwealth University, 2009. / Prepared for: Dept. of Pharmacology and Toxicology. Title from title-page of electronic thesis. Bibliography: leaves 266-287.

Thesis (Ph. D.)--Mississippi State University. Department of Chemistry. / Title from title screen. Includes bibliographical references.

published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Pathology / Master / Master of Medical Sciences

No description available.

MTHFD is a folate-dependent trifunctional protein comprised of three activities: N$ sp5$,N$ sp{10}$-methylenetetrahydrofolate dehydrogenase, N$ sp5$,N$ sp{10}$-methenyltetrahydrofolate cyclohydrolase and N$ sp{10}$-formyltetrahydrofolate synthetase. The enzymes catalyse the sequential interconversion of tetrahydrofolate derivatives required for purine, methionine and thymidylate synthesis. A Chinese hamster ovary cell line, reported to have reduced cyclohydrolase activity, was studied to characterize the nature of its mutation. / Enzymatic assays showed reduced activities of all three enzymes. Immunoblotting and immunoprecipitation of radiolabelled cell extracts indicated that the gene product was greatly reduced or absent in the mutant. Southern analysis showed no differences between normal and mutant cells, indicating that the defect was not due to a major gene rearrangement. RNA analysis, by Northern blotting and by RNA amplification using the polymerase chain reaction, showed that a mRNA for MTHFD of normal size was present in mutant cells. These results suggest that the mutation is post-transcriptional and that it disrupts the synthesis of MTHFD.