The Dynamics of Folic Acid Metabolism in an Adult Given a Small Tracer Dose of 14C-Folic Acid

Clifford, Andrew J.; Arjomand, Ali; Dueker, Stephen R.; Schneider, Philip D.; Buchholz, Bruce A.; Vogel, John S.

doi:10.1007/978-1-4899-1959-5_15

Cited by 55 publications

(65 citation statements)

References 17 publications

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“…As shown by others (Krumdieck et al, 1978;Clifford et al, 1998), the results indicate that folic acid bioavailability in the young adults is nearly complete, but variation of the estimate existed due to small sample size in each subgroup. The elimination constant in our study is higher than reported in radioactive folic acid studies conducted in two healthy adults (Krumdieck et al, 1978;Clifford et al, 1998). Exchange with hydrogen of the deuterium in the folic acid tracer may result in underestimation of the 5-methylTHF enrichment (Gregory & Quinlivan, 2002).…”

Section: Discussionsupporting

confidence: 53%

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

et al. 2005

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Objectives: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. Design: A randomized, double-blind intervention study. Subjects: A total of 12 young (o30 y) and 12 middle-aged (Z50 y) healthy volunteers were recruited. Methods: Volunteers were randomized to receive daily supplementation with 400 mg folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [ 2 H 2 ]folic acid test doses using isotope kinetics in plasma. Results: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P ¼ 0.03) and after (P ¼ 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P ¼ 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young ( þ 50%; P ¼ 0.05) but not in the middle-aged ( þ 18%; P ¼ 0.5) adults. Conclusions: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults.

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Section: Discussionsupporting

confidence: 53%

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

et al. 2005

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“…Folic acid is an essential nutrient that functions within the cell to carry one-carbon groups for methylation reactions and for nucleic acid synthesis (13). Several mechanisms have evolved for uptake of folate in eukaryotic cells.…”

Section: Clinical Relevancementioning

confidence: 99%

Molecular Imaging of Folate Receptor β–Positive Macrophages during Acute Lung Inflammation

Han

Zaynagetdinov

Yull³

et al. 2015

Am J Respir Cell Mol Biol

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Characterization of markers that identify activated macrophages could advance understanding of inflammatory lung diseases and facilitate development of novel methodologies for monitoring disease activity. We investigated whether folate receptor b (FRb) expression could be used to identify and quantify activated macrophages in the lungs during acute inflammation induced by Escherichia coli LPS. We found that FRb expression was markedly increased in lung macrophages at 48 hours after intratracheal LPS. In vivo molecular imaging with a fluorescent probe (cyanine 5 polyethylene glycol folate) showed that the fluorescence signal over the chest peaked at 48 hours after intratracheal LPS and was markedly attenuated after depletion of macrophages. Using flow cytometry, we identified the cells responsible for uptake of cyanine 5-conjugated folate as FRb 1 interstitial macrophages and pulmonary monocytes, which coexpressed markers associated with an M1 proinflammatory macrophage phenotype. These findings were confirmed using a second model of acute lung inflammation generated by inducible transgenic expression of an NF-kB activator in airway epithelium.Using CC chemokine receptor 2-deficient mice, we found that FRb 1 macrophage/monocyte recruitment was dependent on the monocyte chemotactic protein-1/CC chemokine receptor 2 pathway. Together, our results demonstrate that folate-based molecular imaging can be used as a noninvasive approach to detect classically activated monocytes/macrophages recruited to the lungs during acute inflammation.

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“…Folic acid (FA,folate,vitamin B 9 ) is an essential nutrient required by all living cells for proper metabolic maintenance of 1-carbon pathways as well as for nucleotide biosynthesis (Clifford et al, 1998). Hence, acquisition of folates is extremely important for maintaining the viability of both normal and proliferating (e.g., cancer) cells.…”

mentioning

confidence: 99%

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

Leamon

Reddy²,

Dorton³

et al. 2008

J Pharmacol Exp Ther

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Herein, we present a detailed analysis on the effects of feeding laboratory mice both high and low folic acid (folate)-containing diets as related to associated changes in serum and red blood cell (RBC) folate levels, tissue-derived folate receptor levels, and the ability of folate-drug conjugates to bind and effectuate activity against folate receptor (FR)-positive tumor xenografts. Our data show that serum and RBC folate concentrations sharply drop immediately after mice are switched to low folate diets; however, both parameters reach steady-state, "humanlike" levels after 6 weeks. Interestingly, tissue-related folate binding capacities were also lowered during the dietary modulation period, whereas the net uptake of a radiolabeled folate conjugate was simultaneously increased 2.6-and 5-fold in FR-positive kidney and tumor tissue, respectively. Finally, the performances of several clinically and preclinically relevant folate-drug conjugates were evaluated against tumors in mice that were fed high or low folate diets. Except when administered at a dose level 6-fold less than that required to saturate endogenous FRs, no significant loss of antitumor activity was observed. From these findings, we conclude that lowering the dietary intake of folates in mice has little impact on the biological activity of repetitively dosed folate-targeted agents but that low folate diet regimens will reduce serum and RBC folate levels down to levels that more closely approximate the normal human ranges.

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The Dynamics of Folic Acid Metabolism in an Adult Given a Small Tracer Dose of 14C-Folic Acid

Cited by 55 publications

References 17 publications

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults

Molecular Imaging of Folate Receptor β–Positive Macrophages during Acute Lung Inflammation

Impact of High and Low Folate Diets on Tissue Folate Receptor Levels and Antitumor Responses Toward Folate-Drug Conjugates

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