Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status

Mark Lucock, Zoe Yates, Lyndell Boyd, Charlotte Naylor, Jeong-Hwa Choi, Xiaowei Ng, Virginia Skinner, Ron Wai, Jeremy Kho, Sa Tang, Paul Roach, Martin Veysey

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: Folate-related nutrient–nutrient and nutrient–gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status.
Methods: Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C.
Results: When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH3-H4-PteGlun correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH3-H4-PteGluninteract synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This ‘natural’ nutrient–nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH3-H4-PteGlun act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173).
Conclusions: 5CH3-H4-PteGlun assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.
Original languageEnglish
Pages (from-to)569-582
Number of pages14
JournalEuropean Journal of Nutrition
Volume52
Issue number2
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Folic Acid
Ascorbic Acid
Food
Genes
Erythropoiesis
Immunoassay
Methionine
Nucleic Acids
Single Nucleotide Polymorphism

Cite this

Lucock, M., Yates, Z., Boyd, L., Naylor, C., Choi, J-H., Ng, X., ... Veysey, M. (2013). Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status. European Journal of Nutrition, 52(2), 569-582. https://doi.org/10.1007/s00394-012-0359-8
Lucock, Mark ; Yates, Zoe ; Boyd, Lyndell ; Naylor, Charlotte ; Choi, Jeong-Hwa ; Ng, Xiaowei ; Skinner, Virginia ; Wai, Ron ; Kho, Jeremy ; Tang, Sa ; Roach, Paul ; Veysey, Martin. / Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status. In: European Journal of Nutrition. 2013 ; Vol. 52, No. 2. pp. 569-582.
@article{b12aaadc464846e2a43322c33f1ce039,
title = "Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status",
abstract = "Purpose: Folate-related nutrient–nutrient and nutrient–gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status.Methods: Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C.Results: When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH3-H4-PteGlun correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH3-H4-PteGluninteract synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This ‘natural’ nutrient–nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH3-H4-PteGlun act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173).Conclusions: 5CH3-H4-PteGlun assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.",
author = "Mark Lucock and Zoe Yates and Lyndell Boyd and Charlotte Naylor and Jeong-Hwa Choi and Xiaowei Ng and Virginia Skinner and Ron Wai and Jeremy Kho and Sa Tang and Paul Roach and Martin Veysey",
year = "2013",
doi = "10.1007/s00394-012-0359-8",
language = "English",
volume = "52",
pages = "569--582",
journal = "European Journal of Nutrition",
issn = "0044-264X",
publisher = "Springer",
number = "2",

}

Lucock, M, Yates, Z, Boyd, L, Naylor, C, Choi, J-H, Ng, X, Skinner, V, Wai, R, Kho, J, Tang, S, Roach, P & Veysey, M 2013, 'Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status', European Journal of Nutrition, vol. 52, no. 2, pp. 569-582. https://doi.org/10.1007/s00394-012-0359-8

Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status. / Lucock, Mark; Yates, Zoe; Boyd, Lyndell; Naylor, Charlotte; Choi, Jeong-Hwa; Ng, Xiaowei; Skinner, Virginia; Wai, Ron; Kho, Jeremy; Tang, Sa; Roach, Paul; Veysey, Martin.

In: European Journal of Nutrition, Vol. 52, No. 2, 2013, p. 569-582.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Vitamin C-related nutrient-nutrient and nutrient-gene interactions that modify folate status

AU - Lucock, Mark

AU - Yates, Zoe

AU - Boyd, Lyndell

AU - Naylor, Charlotte

AU - Choi, Jeong-Hwa

AU - Ng, Xiaowei

AU - Skinner, Virginia

AU - Wai, Ron

AU - Kho, Jeremy

AU - Tang, Sa

AU - Roach, Paul

AU - Veysey, Martin

PY - 2013

Y1 - 2013

N2 - Purpose: Folate-related nutrient–nutrient and nutrient–gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status.Methods: Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C.Results: When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH3-H4-PteGlun correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH3-H4-PteGluninteract synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This ‘natural’ nutrient–nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH3-H4-PteGlun act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173).Conclusions: 5CH3-H4-PteGlun assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.

AB - Purpose: Folate-related nutrient–nutrient and nutrient–gene interactions modify disease risk; we therefore examined synergistic relationships between dietary folic acid, vitamin C and variant folate genes with respect to red cell folate status.Methods: Two hundred and twelve subjects were examined using chemiluminescent immunoassay, PCR and food frequency questionnaire to determine red cell and serum folate, 14 folate gene polymorphisms, dietary folate (natural and synthetic) and vitamin C.Results: When examined independently, synthetic PteGlu correlates best with red cell folate at higher levels of intake (p = 0.0102), while natural 5CH3-H4-PteGlun correlates best with red cell folate at lower levels of intake (p = 0.0035). However, dietary vitamin C and 5CH3-H4-PteGluninteract synergistically to correlate with red cell folate at higher levels of intake (p = 0.0005). No interaction between dietary vitamin C and PteGlu was observed. This ‘natural’ nutrient–nutrient interaction may provide an alternative to synthetic PteGlu supplementation that is now linked to adverse phenomena/health outcomes. On its own, vitamin C also correlates with red cell folate (p = 0.0150) and is strongly influenced by genetic variation in TS, MTHFR and MSR, genes critical for DNA and methionine biosynthesis that underpin erythropoiesis. Similarly, dietary vitamin C and 5CH3-H4-PteGlun act synergistically to modify red cell folate status according to variation in folate genes: of note, heterozygosity for 2R3R-TS (p = 0.0181), SHMT (p = 0.0046) and all three MTHFR SNPs (p = 0.0023, 0.0015 and 0.0239 for G1793A, C677T and A1298C variants, respectively) promote a significant association with red cell folate. Again, all these genes are critical for nucleic acid biosynthesis. Folate variants with the strongest independent effect on folate status were C677T-MTHFR (p = 0.0004) and G1793A-MTHFR (p = 0.0173).Conclusions: 5CH3-H4-PteGlun assimilation and variant folate gene expression products may be critically dependent on dietary vitamin C.

U2 - 10.1007/s00394-012-0359-8

DO - 10.1007/s00394-012-0359-8

M3 - Article

VL - 52

SP - 569

EP - 582

JO - European Journal of Nutrition

JF - European Journal of Nutrition

SN - 0044-264X

IS - 2

ER -