Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial

Jéssica Vanessa De Carvalho Lisboa,Darlene Camati Persuhn,Mussara Gomes Cavalcante Alves Monteiro,Robson Cavalcante Veras,Ronei Marcos De Moraes,Marina Ramalho Ribeiro,Alcides Da Silva Diniz,Rayner Anderson Ferreira Do Nascimento,Maria José De Carvalho Costa,Flávia Emília Leite De Lima Ferreira,Maria Da Conceição Rodrigues Gonçalves,Naila Francis Paulo De Oliveira,Carla Patrícia Novaes Dos Santos Fechine,Aléssio Tony Cavalcanti De Almeida,Rafaella Cristhine Pordeus Luna,Keylha Querino De Farias Lima,Alexandre Silva ,Eliseu Verly ,Roberto Teixeira De Lima ,Renally Bezerra Wanderley E Lima

doi:10.3390/nu12020361

Abstract

Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism associated with body fat accumulation could possibly trigger an inflammatory process by elevating homocysteine levels and increasing cytokine production, causing several diseases. This study aimed to evaluate the effects of food intervention, and not folate supplements, on the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in overweight and obese women with the MTHFR C677T polymorphism. A randomized, double-blind eight-week clinical trial of 48 overweight and obese women was conducted. Participants were randomly assigned into two groups. They received 300 g of vegetables daily for eight weeks containing different doses of folate: 95 µg/day for Group 1 and 191 µg/day for Group 2. MTHFR C677T polymorphism genotyping was assessed by digestion with HinfI enzyme and on 12% polyacrylamide gels. Anthropometric measurements, 24-h dietary recall, and biochemical analysis (blood folic acid, vitamin B12, homocysteine (Hcy), TNF-α, IL-1β, and IL-6) were determined at the beginning and end of the study. Group 2 had a significant increase in folate intake (p < 0.001) and plasma folic acid (p < 0.05) for individuals with the cytosine–cytosine (CC), cytosine–thymine (CT), and thymine–thymine (TT) genotypes. However, only individuals with the TT genotype presented reduced levels of Hcy, TNF-α, IL-6, and IL-1β (p < 0.001). Group 1 showed significant differences in folate consumption (p < 0.001) and folic acid levels (p < 0.05) for individuals with the CT and TT genotypes. Food intervention with folate from vegetables increased folic acid levels and reduced interleukins, TNF-α, and Hcy levels, mainly for individuals with the TT genotype.

Highlights

Women with an unbalanced diet in calories could have an excessive accumulation of body fat, especially in the abdominal circumference, and an elevated body mass index (BMI)
As for groups 1 and 2, it was observed that both of them presented reduced values of habitual folate intake according to the estimated average requirement (EAR) (400 mcg/day)
Many studies have shown that an intervention with enriched folic acid diet resulted in positive health effects in adults with hyperhomocysteinemia and low folic acid levels carrying the Methylenetetrahydrofolate reductase (MTHFR) C677T

Summary

Introduction

Women with an unbalanced diet in calories could have an excessive accumulation of body fat, especially in the abdominal circumference, and an elevated body mass index (BMI) This nutritional status of overweight and obesity generates systemic subclinical inflammation from the adipose tissue. In this situation, nuclear factor kappa-light-chain-enhancer (NF-κB) of the active B cell pathway increases cytokine synthesis. Nuclear factor kappa-light-chain-enhancer (NF-κB) of the active B cell pathway increases cytokine synthesis This inflammation increases the production of reactive oxygen species (ROS), triggering oxidative stress, and as a consequence, there is a higher production of cytokines, creating a vicious cycle. A metabolite derived from folate metabolism, may be increased in the presence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism [1,2,3]

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