Preliminary Evidence Shows That Folic Acid Fortification of the Food Supply Is Associated with Higher Methotrexate Dosing in Patients with Rheumatoid Arthritis

Arabelovic, Senada; Sam, Gina; Dallal, Gerard E.; Jacques, Paul F.; Selhub, Jacob; Rosenberg, Irwin H.; Roubenoff, Ronenn

doi:10.1080/07315724.2007.10719635

Cited by 30 publications

(13 citation statements)

References 4 publications

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“…Folic acid fortification in foods has been associated with requirement for higher MTX dose in a small study of patients with RA. 55 However, in Sweden, there is no obligatory fortification of food. Results from our study, performed in a country where there is no obligatory fortification, suggest that dietary folate intake before starting with MTX and/or other DMARDs did not associate with inferior EULAR response.…”

Section: Discussionmentioning

confidence: 99%

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study

et al. 2017

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BackgroundDietary intake of vitamin D and omega-3 fatty acids (FA) may be associated with superior response to antirheumatic treatments. In addition, dietary folate intake may be associated with worse response to methotrexate (MTX). The aim of this study was to investigate the association between dietary vitamin D, omega-3 FA, folate and treatment results of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA).MethodsThis prospective study was based on data from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, and included 727 patients with early RA from 10 hospitals in Sweden. Data on dietary vitamin D, omega-3 FA and folate intake based on food frequency questionnaires were linked with data on European League Against Rheumatism (EULAR) response after 3 months of DMARD treatment. Associations between vitamin D, omega-3 FA, folate and EULAR response were analysed with logistic regression adjusted for potential confounders.ResultsThe majority of patients (89.9%) were initially treated with MTX monotherapy and more than half (56.9%) with glucocorticoids. Vitamin D and omega-3 FA were associated with good EULAR response (OR 1.80 (95% CI 1.14 to 2.83) and OR 1.60 (95% CI 1.02 to 2.53), respectively). Folate was not significantly associated with EULAR response (OR 1.20 (95% CI 0.75 to 1.91)). Similar results were seen in a subgroup of patients who were initially treated with MTX monotherapy at baseline.ConclusionsHigher intake of dietary vitamin D and omega-3 FA during the year preceding DMARD initiation may be associated with better treatment results in patients with early RA. Dietary folate intake was not associated with worse or better response to treatment, especially to MTX. Our results suggest that some nutrients may be associated with enhanced treatment results of DMARDs.

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Section: Discussionmentioning

confidence: 99%

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study

et al. 2017

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“…Apart from MTX, the activity of the TS inhibitor pemetrexed and the lipophilic DHFR inhibitor TMQ were also found to be influenced by alterations in intracellular folate status, while other drugs (e.g. BGC9331 and GW1843) retained potent activity regardless of folate status (22,40,41). Consistently, such a profile was also observed in Figure 4, revealing that addition of leucovorin rescued activated T cells from apoptosis induced by MTX, TMQ, raltitrexed, pemetrexed and, to some extent PT523, whereas the efficacy of PT644, BGC9331, and GW1843 was not influenced by this reduced folate.…”

Section: Discussionmentioning

confidence: 98%

“…The widespread application of folate supplementation to RA patients (39), along with folate food fortification programmes in the past decade, has resulted in markedly higher plasma folate levels in RA patient populations (40), which could confer diminished efficacy of MTX. Apart from MTX, the activity of the TS inhibitor pemetrexed and the lipophilic DHFR inhibitor TMQ were also found to be influenced by alterations in intracellular folate status, while other drugs (e.g.…”

Section: Discussionmentioning

confidence: 99%

Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients

Heijden

Assaraf

Gerards

et al. 2013

Scandinavian Journal of Rheumatology

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“…Arabelovic and his colleagues computed MTX doses per patient per year ( 139 ). They compared the overall mean MTX doses before and after 1998 (when mandatory folic acid fortification was instituted) for thirty-six rheumatoid arthritis subjects in the US.…”

Section: The Controversy Of Potential Adverse Effects Of Excess Folicmentioning

confidence: 99%

Contemporary Issues Surrounding Folic Acid Fortification Initiatives

Choi

Yates

Veysey

et al. 2014

JFN

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The impact of folate on health and disease, particularly pregnancy complications and congenital malformations, has been extensively studied. Mandatory folic acid fortification therefore has been implemented in multiple countries, resulting in a reduction in the occurrence of neural tube defects. However, emerging evidence suggests increased folate intake may also be associated with unexpected adverse effects. This literature review focuses on contemporary issues of concern, and possible underlying mechanisms as well as giving consideration the future direction of mandatory folic acid fortification. Folate fortification has been associated with the presence of unmetabolized folic acid (PteGlu) in blood, masking of vitamin B12 deficiency, increased dosage for anti-cancer medication, photo-catalysis of PteGlu leading to potential genotoxicity, and a role in the pathoaetiology of colorectal cancer. Increased folate intake has also been associated with twin birth and insulin resistance in offspring, and altered epigenetic mechanisms of inheritance. Although limited data exists to elucidate potential mechanisms underlying these issues, elevated blood folate level due to the excess use of PteGlu without consideration of an individual’s specific phenotypic traits (e.g. genetic background and undiagnosed disease) may be relevant. Additionally, the accumulation of unmetabolized PteGlu may lead to inhibition of dihydrofolate reductase and other enzymes. Concerns notwithstanding, folic acid fortification has achieved enormous advances in public health. It therefore seems prudent to target and carefully monitor high risk groups, and to conduct well focused further research to better understand and to minimize any risk of mandatory folic acid fortification.

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Preliminary Evidence Shows That Folic Acid Fortification of the Food Supply Is Associated with Higher Methotrexate Dosing in Patients with Rheumatoid Arthritis

Abstract: This preliminary study suggests that folic acid supplementation may contribute to higher MTX dosing in patients with RA.

Cited by 30 publications

References 4 publications

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study

Are dietary vitamin D, omega-3 fatty acids and folate associated with treatment results in patients with early rheumatoid arthritis? Data from a Swedish population-based prospective study

Methotrexate analogues display enhanced inhibition of TNF-α production in whole blood from RA patients

Contemporary Issues Surrounding Folic Acid Fortification Initiatives

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