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

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

doi:10.3390/nu12020361

Cited by 24 publications

(17 citation statements)

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“…The MTHFR thermolabile variant encoded by the MTHFR 677 CT/TT genotypes leads to impaired homocysteine (Hcy) metabolism and elevated plasma Hcy levels, which has been associated with some metabolic diseases when coupled with insufficient dietary folate intake [10,11,54]. In particular, its association with accumulation of body and liver fat and increased risk of obesity have been explained by a possible mechanism in which elevated Hcy levels trigger an inflammatory process and increased production of cytokines, a metabolic feature that may cause insulin resistance, that later has been improved by a folate-rich diet [55]. Herein, the regionalized GENOMEX diet provided an adequate folate intake even higher than that usually consumed by individuals, and because the T allele was one of the most frequent among study subjects, it is plausible that the beneficial metabolic response was more evident compared to the other polymorphisms.…”

Section: Discussionmentioning

confidence: 99%

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases

et al. 2020

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Obesity-related chronic diseases (CD) are highly prevalent in Mexicans who show moderate to high frequencies of diet-related adaptive gene (DRAG) polymorphisms and recent shifts in traditional dietary habits and lifestyles. This study first evaluated the effects of a regionalized genome-based Mexican (GENOMEX) diet on anthropometric and biochemical parameters and, subsequently their relationship with the genetic profile of DRAG polymorphisms in subjects with metabolic risk factors for obesity-related CD. Thirty-seven eligible subjects underwent a 24-week dietary intervention with a GENOMEX diet. The DRAG polymorphisms were determined by an allelic discrimination real-time assay to evaluate their association with the clinical response to diet. The GENOMEX diet significantly improved anthropometric parameters such as total weight, body mass index, waist circumference, and body fat percentage, with an average weight loss of 6.6% (5.3 ± 5.3 kg). The frequency of subjects with insulin resistance, hypertriglyceridemia and elevated VLDL-c (48.5% vs. 24.2%, p = 0.041; 45.5% vs. 12.1%, p = 0.003; and 39.4% vs. 15.2%, p = 0.027, baseline vs. 24-weeks, respectively) was reduced. A more significant favorable effect in HOMA-IR and insulin was observed in MTHFR 677T adaptive allele carriers, but no other DRAG polymorphism was associated with clinical changes. The GENOMEX diet improved the metabolic risk factors for obesity-related CD. The recommendation and habitual consumption of a traditional Mexican diet based on knowledge of the population's genetic and cultural history may be effective in preventing current obesity-related CD.Abstract: Obesity-related chronic diseases (CD) are highly prevalent in Mexicans who show moderate to high frequencies of diet-related adaptive gene (DRAG) polymorphisms and recent shifts in traditional dietary habits and lifestyles. This study first evaluated the effects of a regionalized genome-based Mexican (GENOMEX) diet on anthropometric and biochemical parameters and, subsequently their relationship with the genetic profile of DRAG polymorphisms in subjects with metabolic risk factors for obesity-related CD. Thirty-seven eligible subjects underwent a 24-week dietary intervention with a GENOMEX diet. The DRAG polymorphisms were determined by an allelic discrimination real-time assay to evaluate their association with the clinical response to diet. The GENOMEX diet significantly improved anthropometric parameters such as total weight, body mass index, waist circumference, and body fat percentage, with an average weight loss of 6.6% (5.3 ± 5.3 kg). The frequency of subjects with insulin resistance, hypertriglyceridemia and elevated VLDL-c (48.5% vs. 24.2%, p = 0.041; 45.5% vs. 12.1%, p = 0.003; and 39.4% vs. 15.2%, p = 0.027, baseline vs. 24-weeks, respectively) was reduced. A more significant favorable effect in HOMA-IR and insulin was observed in MTHFR 677T adaptive allele carriers, but no other DRAG polymorphism was associated with clinical changes. The GENOMEX diet improved the metabolic risk ...

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Section: Discussionmentioning

confidence: 99%

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases

et al. 2020

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“…We additionally reviewed a number of studies reporting the levels of TNF-α across the different genotypes for other variants associated with different genes related with obesity and metabolic disorders [ 137 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ] ( Table S8 ). We also found a very high genotype intra-subgroup variability (CV% >40% in most cases), highly variable levels (0.11–90 pg/mL) in the homozygous reference subgroups, and small and mostly (NS) differences across the genotypes except for some specific SNPs.…”

Section: The Influence Of Genetic Variants On Tnf-α Levelsmentioning

confidence: 99%

An Exploratory Critical Review on TNF-α as a Potential Inflammatory Biomarker Responsive to Dietary Intervention with Bioactive Foods and Derived Products

Quarta

Massaro

Carluccio

et al. 2022

Foods

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This review collects and critically examines data on the levels of tumour necrosis factor-alpha (TNF-α) in lean, overweight and obese subjects, and the effects of intervention with different foods and food products containing bioactive constituents in overweight/obese individuals. We additionally explore the influence of different single nucleotide polymorphisms (SNPs) on TNF-α levels and compare the response to food products with that to some anti-obesity drugs. Our aim was to provide an overview of the variability, consistency, and magnitude of the reported effects of dietary factors on TNF-α, and to envisage the reliability of measuring changes in the levels of this cytokine as a biomarker responsive to food intervention in association with the reduction in body weight. Regarding the circulating levels of TNF-α, we report: (i) a large intra-group variability, with most coefficients of variation (CV%) values being ³30% and, in many cases, >100%; (ii) a large between-studies variability, with baseline TNF-α values ranging from <1.0 up to several hundred pg/mL; (iii) highly variable effects of the different dietary approaches with both statistically significant and not significant decreases or increases of the protein, and the absolute effect size varying from <0.1 pg/mL up to ≈50 pg/mL. Within this scenario of variability, it was not possible to discern clear differentiating limits in TNF-α between lean, overweight, and obese individuals or a distinct downregulatory effect on this cytokine by any of the different dietary approaches reviewed, i.e., polyunsaturated fatty acids (PUFAs), Vitamin-D (VitD), mixed (micro)nutrients, (poly)phenols or other phytochemicals. Further, there was not a clear relationship between the TNF-α responses and body weight changes. We found similarities between dietary and pharmacological treatments in terms of variability and limited evidence of the TNF-α response. Different factors that contribute to this variability are discussed and some specific recommendations are proposed to reinforce the need to improve future studies looking at this cytokine as a potential biomarker of response to dietary approaches.

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“…Reduction of neurotransmitter levels due to inflammation is also thought to contribute to the development of syndromal symptoms of depression ( 14 ). Of note, higher dietary folate intake in obese/overweight women with the MTHFR C677T polymorphism, an indicator of elevated homocysteine levels and inflammation, has also been shown to reduce levels of inflammatory biomarkers, indicating that folate may play a role in the reduction of inflammation in the obese population ( 5 ).…”

Section: Inflammation and Depressionmentioning

confidence: 99%

“…Papakostas et al ( 1 ) first demonstrated that depressed patients with elevated body mass index (BMI) and inflammatory biomarkers responded particularly well to adjunctive LMF treatment. In subsequent years, additional data demonstrated the impact of elevated BMI and inflammation on depression and antidepressant response ( 2 , 3 ), as well as the potential for LMF to be an effective adjunctive treatment in this population ( 4 , 5 ). Because of the current interest on the effect of BMI and inflammation on major depressive disorder (MDD), these data will be revisited to provide additional context, potentially opening the door for additional investigation in this area.…”

Section: Introductionmentioning

confidence: 99%

L-Methylfolate in Antidepressant Non-responders: The Impact of Body Weight and Inflammation

Macaluso

2022

Front. Psychiatry

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This summary provides context for the role of L-methylfolate (LMF) in treating antidepressant non-responders. Bidirectional relationships have been observed between obesity and/or inflammation and depression. Studies have shown an increased prevalence of depression among patients with elevated body mass index and/or chronic inflammation and an increased risk of becoming obese and experiencing chronic inflammation in those with depression. These relationships can negatively affect the pathophysiology of depression. Elevated cytokine levels have been found to be among the factors that correlate with poor antidepressant treatment responsiveness. Low baseline neurotransmitter levels (e.g., serotonin) can also be associated with reduced effectiveness of commonly used antidepressants [e.g., selective serotonin reuptake inhibitors (SSRIs)]. LMF is an approved nutritional adjunctive antidepressant therapy that increases central neurotransmitter levels and thereby improves the effectiveness of antidepressant therapy. LMF can increase clinical response when used adjunctively in patients with major depressive disorder (MDD) and who are SSRI-resistant. In 2 randomized controlled trials, the pooled results showed increased response rates (32.3 vs. 14.6%; P = 0.04) as measured by a ≥50% reduction or final score ≤ 7 on the Hamilton Depression Rating Scale (HAM-D) and greater mean HAM-D reductions (−5.6 vs. −3.0; P = 0.05) when LMF was added to an SSRI compared with an SSRI plus placebo. Additionally, LMF has demonstrated effectiveness in real-world studies, with 67.9% of patients responding to therapy, using the 9-item Patient Health Questionnaire (P < 0.001). Post-hoc analyses found that patients with inflammation and/or obesity responded better to adjunctive LMF therapy compared with the overall sample (mean HAM-D reduction: −2.74 vs. +0.99).

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

Cited by 24 publications

References 72 publications

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases

A Regionalized Genome-Based Mexican Diet Improves Anthropometric and Metabolic Parameters in Subjects at Risk for Obesity-Related Chronic Diseases

An Exploratory Critical Review on TNF-α as a Potential Inflammatory Biomarker Responsive to Dietary Intervention with Bioactive Foods and Derived Products

L-Methylfolate in Antidepressant Non-responders: The Impact of Body Weight and Inflammation

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