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Article ; Online: Noncanonical function of folate through folate receptor 1 during neural tube formation.

Balashova, Olga A / Panoutsopoulos, Alexios A / Visina, Olesya / Selhub, Jacob / Knoepfler, Paul S / Borodinsky, Laura N

Nature communications

2024 Volume 15, Issue 1, Page(s) 1642

Abstract: Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that ... ...

Abstract	Folate supplementation reduces the occurrence of neural tube defects (NTDs), birth defects consisting in the failure of the neural tube to form and close. The mechanisms underlying NTDs and their prevention by folate remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. FOLR1 knockdown in neural organoids and in Xenopus laevis embryos leads to NTDs that are rescued by pteroate, a folate precursor that is unable to participate in metabolism. We demonstrate that FOLR1 interacts with and opposes the function of CD2-associated protein, molecule essential for apical endocytosis and turnover of C-cadherin in neural plate cells. In addition, folates increase Ca
MeSH term(s)	Humans ; Folic Acid/metabolism ; Neural Tube/metabolism ; Folate Receptor 1/genetics ; Folate Receptor 1/metabolism ; Neural Tube Defects/genetics ; Neural Tube Defects/metabolism ; Neural Plate/metabolism
Chemical Substances	Folic Acid (935E97BOY8) ; Folate Receptor 1 ; FOLR1 protein, human
Language	English
Publishing date	2024-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-45775-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Non-canonical function of folate/folate receptor 1 during neural tube formation.

Balashova, Olga A / Panoutsopoulos, Alexios A / Visina, Olesya / Selhub, Jacob / Knoepfler, Paul S / Borodinsky, Laura N

bioRxiv : the preprint server for biology

2023

Abstract: Folate supplementation reduces the occurrence of neural tube defects, one of the most common and serious birth defects, consisting in the failure of the neural tube to form and close early in pregnancy. The mechanisms underlying neural tube defects and ... ...

Abstract	Folate supplementation reduces the occurrence of neural tube defects, one of the most common and serious birth defects, consisting in the failure of the neural tube to form and close early in pregnancy. The mechanisms underlying neural tube defects and folate action during neural tube formation remain unclear. Here we show that folate receptor 1 (FOLR1) is necessary for the formation of neural tube-like structures in human-cell derived neural organoids. Knockdown of FOLR1 in human neural organoids as well as in the
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.19.549718
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Article ; Online: Interaction between excess folate and low vitamin B12 status.

Paul, Ligi / Selhub, Jacob

Molecular aspects of medicine

2017 Volume 53, Page(s) 43–47

Abstract: Current epidemiological evidence suggests that an imbalance of high folate status and low vitamin B12 status is associated with negative health outcomes in older adults and children. Such an imbalance during pregnancy also predisposes women to diabetes ... ...

Abstract	Current epidemiological evidence suggests that an imbalance of high folate status and low vitamin B12 status is associated with negative health outcomes in older adults and children. Such an imbalance during pregnancy also predisposes women to diabetes and their offspring to insulin resistance and adiposity and low birthweight. In older adults, vitamin B12 status can remain low despite adequate intake due to age-related decline in vitamin B12 absorption. Pregnant women are exposed to folic acid at varying doses depending on the prenatal care prescribed in different countries. This review summarizes the current knowledge on the interaction between folate and vitamin B12 and the associated health outcomes.
MeSH term(s)	Animals ; Biomarkers/metabolism ; Female ; Folic Acid/metabolism ; Humans ; Pregnancy ; Vitamin B 12/metabolism ; Vitamin B 12 Deficiency/metabolism
Chemical Substances	Biomarkers ; Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article ; Review ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	197640-0
ISSN	1872-9452 ; 0098-2997
ISSN (online)	1872-9452
ISSN	0098-2997
DOI	10.1016/j.mam.2016.11.004
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Article ; Online: Sulfur amino acids and atherosclerosis: a role for excess dietary methionine.

Selhub, Jacob / Troen, Aron M

Annals of the New York Academy of Sciences

2016 Volume 1363, Page(s) 18–25

Abstract: The homocysteine theory of arteriosclerosis received credence when it was shown that after a methionine load, circulating homocysteine-cysteine concentrations were higher in cardiovascular disease patients than in healthy controls. Subsequent studies ... ...

Abstract	The homocysteine theory of arteriosclerosis received credence when it was shown that after a methionine load, circulating homocysteine-cysteine concentrations were higher in cardiovascular disease patients than in healthy controls. Subsequent studies showing associations between homocysteine and coronary artery disease, stroke and cognitive impairment, relied on small increases in homocysteine concentration unlike the very high homocysteine seen in the rare genetic disorders that lead to homocystinuria and much higher homocysteine levels. Subsequent studies in cell culture, animals, and humans showed that a variety of cardiovascular adverse effects of "high homocysteine" introduced either as a nonphysiological bolus or as a methionine load led to high homocysteine. We fed apolipoprotein E-deficient mice diets designed to achieve three conditions: (1) high methionine intake with normal blood homocysteine, (2) high methionine intake with B vitamin deficiency and hyperhomocysteinemia, and (3) normal methionine intake with both B vitamin deficiency and hyperhomocysteinemia. We found that the mice fed methionine-rich diets had significant atheromatous pathology in the aortic arch even with normal plasma homocysteine levels. Mice fed B vitamin-deficient diets developed severe hyperhomocysteinemia but without any increase in vascular pathology. Our findings suggest that even moderate increases in methionine intake are atherogenic in susceptible mice while high plasma homocysteine is not.
MeSH term(s)	Amino Acids, Sulfur/blood ; Amino Acids, Sulfur/metabolism ; Animals ; Apolipoproteins E/deficiency ; Atherosclerosis/blood ; Atherosclerosis/etiology ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Biomarkers ; Blood Chemical Analysis ; Diet ; Disease Models, Animal ; Homocysteine/blood ; Homocysteine/metabolism ; Metabolic Networks and Pathways ; Methionine/blood ; Methionine/metabolism ; Mice ; Mice, Knockout ; Plaque, Atherosclerotic/pathology ; Time Factors
Chemical Substances	Amino Acids, Sulfur ; Apolipoproteins E ; Biomarkers ; Homocysteine (0LVT1QZ0BA) ; Methionine (AE28F7PNPL)
Language	English
Publishing date	2016-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	211003-9
ISSN	1749-6632 ; 0077-8923
ISSN (online)	1749-6632
ISSN	0077-8923
DOI	10.1111/nyas.12962
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Article ; Online: Excessive folic acid intake and relation to adverse health outcome.

Selhub, Jacob / Rosenberg, Irwin H

Biochimie

2016 Volume 126, Page(s) 71–78

Abstract: The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. ... ...

Abstract	The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that "high folic acid intake has not reliably been shown to be associated with negative healeffects". In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999-2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young. Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that excessive intake of folic acid is not always safe in certain populations of different age and ethnical/genetic background.
MeSH term(s)	Aging/genetics ; Aging/immunology ; Aging/pathology ; Base Sequence ; Breast Neoplasms/chemically induced ; Breast Neoplasms/genetics ; Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Female ; Folic Acid/adverse effects ; Folic Acid/therapeutic use ; Humans ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Neoplasm Proteins/genetics ; Neoplasm Proteins/immunology ; Polymorphism, Genetic ; Sequence Deletion ; Tetrahydrofolate Dehydrogenase/genetics ; Tetrahydrofolate Dehydrogenase/immunology
Chemical Substances	Neoplasm Proteins ; Folic Acid (935E97BOY8) ; Tetrahydrofolate Dehydrogenase (EC 1.5.1.3)
Language	English
Publishing date	2016-07
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	120345-9
ISSN	1638-6183 ; 0300-9084
ISSN (online)	1638-6183
ISSN	0300-9084
DOI	10.1016/j.biochi.2016.04.010
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Article ; Online: Perspective: The High-Folate-Low-Vitamin B-12 Interaction Is a Novel Cause of Vitamin B-12 Depletion with a Specific Etiology-A Hypothesis.

Selhub, Jacob / Miller, Joshua W / Troen, Aron M / Mason, Joel B / Jacques, Paul F

Advances in nutrition (Bethesda, Md.)

2021 Volume 13, Issue 1, Page(s) 16–33

Abstract: Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vitamin B-12 deficiency has many identifiable causes, including autoimmune and other gastrointestinal malabsorption disorders, dietary deficiency, and ... ...

Abstract	Vitamin B-12 is a water-soluble vitamin that plays important roles in intermediary metabolism. Vitamin B-12 deficiency has many identifiable causes, including autoimmune and other gastrointestinal malabsorption disorders, dietary deficiency, and congenital defects in genes that are involved in vitamin B-12 trafficking and functions. Another putative cause of vitamin B-12 deficiency is the high-folate-low vitamin B-12 interaction, first suspected as the cause for observed relapse and exacerbation of the neurological symptoms in patients with pernicious anemia who were prescribed high oral doses of folic acid. We propose that this interaction is real and represents a novel cause of vitamin B-12 depletion with specific etiology. We hypothesize that excessive intake of folic acid depletes serum holotranscobalamin (holoTC), thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues. This effect is specific for holoTC and does not affect holohaptocorrin, the inert form of serum vitamin B-12. Depletion of holoTC by folic acid in individuals with already low vitamin B-12 status further compromises the availability of vitamin B-12 coenzymes to their respective enzymes, and consequently a more pronounced state of biochemical deficiency. This hypothesis is drawn from evidence of observational and intervention studies of vitamin B-12-deficient patients and epidemiological cohorts. The evidence also suggests that, in a depleted state, vitamin B-12 is diverted to the hematopoietic system or the kidney. This most likely reflects a selective response of tissues expressing folate receptors with high affinity for unmetabolized folic acid (UMFA; e.g., hematopoietic progenitors and renal tubules) compared with those tissues (e.g., liver) that only express the reduced folate carrier, which is universally expressed but has poor affinity for UMFA. The biochemical and physiological mechanisms underlying this interaction require elucidation to clarify its potential public health significance.
MeSH term(s)	Folic Acid ; Homocysteine ; Humans ; Malnutrition ; Vitamin B 12 ; Vitamin B 12 Deficiency ; Vitamins
Chemical Substances	Vitamins ; Homocysteine (0LVT1QZ0BA) ; Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2583634-1
ISSN	2156-5376 ; 2156-5376
ISSN (online)	2156-5376
ISSN	2156-5376
DOI	10.1093/advances/nmab106
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Article: Public health significance of elevated homocysteine.

Selhub, Jacob

Food and nutrition bulletin

2008 Volume 29, Issue 2 Suppl, Page(s) S116–25

Abstract: Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. ... ...

Abstract	Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/mortality ; Dementia/blood ; Dementia/epidemiology ; Diet ; Female ; Folic Acid/administration & dosage ; Folic Acid/blood ; Fractures, Bone ; Homocysteine/blood ; Humans ; Hyperhomocysteinemia/complications ; Hyperhomocysteinemia/prevention & control ; Male ; Middle Aged ; Neural Tube Defects/blood ; Neural Tube Defects/epidemiology ; Neural Tube Defects/etiology ; Pregnancy ; Public Health ; Risk Factors ; Vitamin B 12/administration & dosage ; Vitamin B 12/blood ; Vitamin B 6/administration & dosage ; Vitamin B 6/blood
Chemical Substances	Homocysteine (0LVT1QZ0BA) ; Vitamin B 6 (8059-24-3) ; Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2008-06
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	449173-7
ISSN	0379-5721
ISSN	0379-5721
DOI	10.1177/15648265080292S116
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Article: Excessive folic acid intake and relation to adverse health outcome

Selhub, Jacob / Rosenberg, Irwin H

Biochimie. 2016 July, v. 126

2016

Abstract	The recent increase in the intake of folic acid by the general public through fortified foods and supplements, has raised safety concern based on early reports of adverse health outcome in elderly with low B12 status who took high doses of folic acid. These safety concerns are contrary to the 2015 WHO statement that “high folic acid intake has not reliably been shown to be associated with negative healeffects”. In the folic acid post-fortification era, we have shown that in elderly participants in NHANES 1999–2002, high plasma folate level is associated with exacerbation of both clinical (anemia and cognitive impairment) and biochemical (high MMA and high Hcy plasma levels) signs of vitamin B12 deficiency. Adverse clinical outcomes in association with high folate intake were also seen among elderly with low plasma B12 levels from the Framingham Original Cohort and in a study from Australia which combined three elderly cohorts. Relation between high folate and adverse biochemical outcomes were also seen in the Sacramento Area Latino Study on Aging (High Hcy, high MMA and lower TC2) and at an outpatient clinic at Yale University where high folate is associated with higher MMA in the elderly but not in the young.Potential detrimental effects of high folic acid intake may not be limited to the elderly nor to those with B12 deficiency. A study from India linked maternal high RBC folate to increased insulin resistance in offspring. Our study suggested that excessive folic acid intake is associated with lower natural killer cells activity in elderly women. In a recent study we found that the risk for unilateral retinoblastoma in offspring is 4 fold higher in women that are homozygotes for the 19 bp deletion in the DHFR gene and took folic acid supplement during pregnancy. In the elderly this polymorphism is associated with lower memory and executive scores, both being significantly worse in those with high plasma folate. These and other data strongly imply that excessive intake of folic acid is not always safe in certain populations of different age and ethnical/genetic background.
Keywords	Latinos ; National Health and Nutrition Examination Survey ; World Health Organization ; anemia ; central nervous system diseases ; cohort studies ; elderly ; erythrocytes ; folic acid ; fortified foods ; genes ; genetic background ; homozygosity ; insulin resistance ; memory ; natural killer cells ; pregnancy ; progeny ; risk ; vitamin B12 ; women ; Australia ; India
Language	English
Dates of publication	2016-07
Size	p. 71-78.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	120345-9
ISSN	0300-9084
ISSN	0300-9084
DOI	10.1016/j.biochi.2016.04.010
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Article: The many facets of hyperhomocysteinemia: studies from the Framingham cohorts.

Selhub, Jacob

The Journal of nutrition

2006 Volume 136, Issue 6 Suppl, Page(s) 1726S–1730S

Abstract: Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5'-phosphate, the B-6 coenzyme. Data from several ... ...

Abstract	Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of 2 pathways: remethylation, which requires folic acid and B-12 coenzymes, and transsulfuration, which requires pyridoxal-5'-phosphate, the B-6 coenzyme. Data from several studies suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies we have shown that plasma total homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B-6 as well as vitamin B-12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid artery stenosis of at least 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and CVD mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. This multitude of relationships between elevated plasma total homocysteine and diseases that afflict the elderly point to the existence of a common denominator that may be responsible for these diseases. Whether this denominator is homocysteine itself or whether homocysteine is merely a marker remains to be determined.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/epidemiology ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/mortality ; Carotid Stenosis/etiology ; Cohort Studies ; Dementia/epidemiology ; Diet ; Female ; Folic Acid/administration & dosage ; Folic Acid/blood ; Fractures, Bone ; Heart Failure/epidemiology ; Homocysteine/blood ; Humans ; Hyperhomocysteinemia/complications ; Male ; Massachusetts ; Middle Aged ; Risk Factors ; Stroke/epidemiology ; Vascular Diseases/etiology ; Vitamin B 12/administration & dosage ; Vitamin B 12/blood ; Vitamin B 6/administration & dosage ; Vitamin B 6/blood
Chemical Substances	Homocysteine (0LVT1QZ0BA) ; Vitamin B 6 (8059-24-3) ; Folic Acid (935E97BOY8) ; Vitamin B 12 (P6YC3EG204)
Language	English
Publishing date	2006-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	218373-0
ISSN	1541-6100 ; 0022-3166
ISSN (online)	1541-6100
ISSN	0022-3166
DOI	10.1093/jn/136.6.1726S
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Article ; Online: Adverse effects related to methotrexate polyglutamate levels: adjudicated results from the cardiovascular inflammation reduction trial.

Xu, Chang / Selhub, Jacob / Jacques, Paul / Paynter, Nina P / MacFadyen, Jean G / Glynn, Robert J / Ridker, Paul M / Solomon, Daniel H

Rheumatology (Oxford, England)

2021 Volume 60, Issue 6, Page(s) 2963–2968

Abstract: Objectives: Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) ...

Abstract	Objectives: Methotrexate is widely used at low dosages (LD-MTX) for non-oncologic indications and is associated with a variety of adverse effects (AEs). We sought to determine whether concentrations of the active metabolite, MTX polyglutamates (MTX-PGs) 1-5, correlate with AEs. Method: We examined data from the LD-MTX arm of the randomized double-blind Cardiovascular Inflammation Reduction Trial (CIRT). All AEs were blindly adjudicated and monitoring laboratories were tested centrally. The MTX-PGs 1-5 were assessed in one reference laboratory using liquid chromatography-tandem mass spectrometry. Based on prior literature, MTX-PGs 3-5 were chosen as the exposure of interest and quartiles of MTX-PGs 3-5 were assessed for their relationship with all AEs and each pre-specified category of AE using adjusted Cox proportional hazards regression. Results: Of the 2391 subjects randomized to LD-MTX, MTX-PG levels were available for 1319 subjects (median dosage 16.1 mg/week) from the 8 month visit. We followed these subjects for a median of 2.2 years [interquartile range (IQR) 1.5-2.9]. Higher MTX-PG3-5 levels were related to an increased risk of anaemia [compared with quartile 1 (Q1); hazard ratio (HR) for Q4 1.27 (95% CI 0.98, 1.65), P for trend = 0.05] and a decreased risk of thrombocytopenia [HR for Q4 0.52 (95% CI 0.32, 0.84), P for trend = 0.05]. MTX-PG3-5 levels >134 nmol/l were associated with an increased risk of liver abnormalities [HR 1.36 (95% CI 1.08, 1.72)]. Conclusions: Higher MTX- PG3-5 levels were modestly associated with LD-MTX AEs, including anaemia and liver function abnormalities, but a reduced risk of thrombocytopenia and haemorrhage. Clinical trial registration: NCT01594333.
MeSH term(s)	Aged ; Antirheumatic Agents/adverse effects ; Cardiovascular Diseases/prevention & control ; Double-Blind Method ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Male ; Methotrexate/adverse effects ; Methotrexate/analogs & derivatives ; Middle Aged ; Polyglutamic Acid/adverse effects ; Polyglutamic Acid/analogs & derivatives
Chemical Substances	Antirheumatic Agents ; Polyglutamic Acid (25513-46-6) ; methotrexate polyglutamate (82334-40-5) ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1464822-2
ISSN	1462-0332 ; 1462-0324
ISSN (online)	1462-0332
ISSN	1462-0324
DOI	10.1093/rheumatology/keaa650
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