Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis

Ulloque-Badaracco, Juan R.; Hernandez-Bustamante, Enrique A.; Alarcon-Braga, Esteban A.; Al-kassab-Córdova, Ali; Cabrera-Guzmán, Juan C.; Herrera-Añazco, Percy; Benites-Zapata, Vicente A.

doi:10.3389/fendo.2023.1221259

Cited by 10 publications

(3 citation statements)

References 111 publications

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“…Additionally, the ameliorating effect of vitamin B12 on metabolic disorders may also contribute to lower odds of ischemic stroke. A meta-analysis revealed an inverse association between higher vitamin B12 levels and metabolic syndrome (OR = 0.87; 95% CI: 0.81–0.93; p < 0.01) [ 35 ]. Animal studies have shown that low vitamin B12 levels lead to lipid accumulation in adipocytes, inhibit β-oxidation of fatty acids and lipolysis in hepatic tissues, thus triggering dyslipidemia in mice [ 36 , 37 ].…”

Section: Discussionmentioning

confidence: 99%

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study

Zhou,

Wang,

et al. 2024

Nutr J

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Purpose This study aimed to identify and quantify the association and investigate whether serum vitamin B12 alone or vitamin B12 combined with folate and plasma total homocysteine (tHcy) levels could be used to predict the risk of acute ischemic stroke. Materials and methods This retrospective case-control study was conducted in the Department of Neurology, First Affiliated Hospital of Chongqing Medical University. It included 259 inpatients experiencing their first-ever acute ischemic stroke and 259 age-matched, sex-matched healthy controls. Patients were categorized into groups based on the etiology of their stroke: large-artery atherosclerosis (LAAS, n = 126), cardio embolism (CEI, n = 35), small vessel disease (SVD, n = 89), stroke of other determined etiology (ODE, n = 5), and stroke of undetermined etiology (UDE, n = 4). The associations of serum vitamin B12, folate, and plasma tHcy levels with the risk of ischemic stroke were evaluated using multivariable logistic regression analysis. Receiver operator characteristic (ROC) curves were used to assess the diagnostic power of vitamin B12, folate, and tHcy levels for ischemic stroke. Results Serum vitamin B12 and folate levels were significantly lower in ischemic stroke patients compared to controls, while plasma tHcy levels were significantly higher. The first quartile of serum vitamin B12 levels was significantly associated with an increased risk of LAAS (aOR = 2.289, 95% CI = 1.098–4.770), SVD (aOR = 4.471, 95% CI = 1.110–4.945) and overall ischemic stroke (aOR = 3.216, 95% CI = 1.733–5.966). Similarly, the first quartile of serum folate levels was associated with an increased risk of LAAS (aOR = 3.480, 95% CI = 1.954–6.449), CEI (aOR = 2.809, 95% CI = 1.073–4.991), SVD (aOR = 5.376, 95% CI = 1.708–6.924), and overall ischemic stroke (aOR = 3.381, 95% CI = 1.535–7.449). The fourth quartile of tHcy levels was also significantly associated with an increased risk of LAAS (aOR = 2.946, 95% CI = 1.008–5.148), CEI (aOR = 2.212, 95% CI = 1.247–5.946), SVD (aOR = 2.957, 95% CI = 1.324–6.054), and overall ischemic stroke (aOR = 2.233, 95% CI = 1.586–4.592). For predicting different types of ischemic stroke, vitamin B12 alone demonstrated the best diagnostic value for SVD, evidenced by a sensitivity of 71.0% and negative predictive value of 90.3%, along with the highest positive likelihood ratio (+ LR) for SVD. Vitamin B12 + tHcy + folate are valuable in predicting different types of ischemic stroke, with the most significant effect observed in SVD, followed by LAAS, and the weakest predictive effect in CEI. Additionally, vitamin B12 alone in combination with other indicators, such as folate alone, tHcy alone, and folate + tHcy could reduce negative likelihood ratio (-LR) and improve + LR. Conclusions Vitamin B12 was an independent risk factor for acute ischemic stroke. The risk calculation model constructed with vitamin B12 + tHcy + folate had the greatest diagnostic value for SVD.

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Section: Discussionmentioning

confidence: 99%

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study

Zhou,

Wang,

et al. 2024

Nutr J

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“…Similarly, Ulloque-Badaracco et al . ( Ulloque-Badaracco et al, 2023 ) identified a significant correlation between elevated Hcy levels and MetS. You et al .…”

Section: Potential Mechanisms Linking Nnmt To Metsmentioning

confidence: 98%

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

Sun,

Zhu,

et al. 2024

Front. Pharmacol.

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Metabolic syndrome (MetS) represents a constellation of metabolic abnormalities, typified by obesity, hypertension, hyperglycemia, and hyperlipidemia. It stems from intricate dysregulations in metabolic pathways governing energy and substrate metabolism. While comprehending the precise etiological mechanisms of MetS remains challenging, evidence underscores the pivotal roles of aberrations in lipid metabolism and insulin resistance (IR) in its pathogenesis. Notably, nicotinamide N-methyltransferase (NNMT) has recently surfaced as a promising therapeutic target for addressing MetS. Single nucleotide variants in the NNMT gene are significantly correlated with disturbances in energy metabolism, obesity, type 2 diabetes (T2D), hyperlipidemia, and hypertension. Elevated NNMT gene expression is notably observed in the liver and white adipose tissue (WAT) of individuals with diabetic mice, obesity, and rats afflicted with MetS. Knockdown of NNMT elicits heightened energy expenditure in adipose and hepatic tissues, mitigates lipid accumulation, and enhances insulin sensitivity. NNMT catalyzes the methylation of nicotinamide (NAM) using S-adenosyl-methionine (SAM) as the donor methyl group, resulting in the formation of S-adenosyl-l-homocysteine (SAH) and methylnicotinamide (MNAM). This enzymatic process results in the depletion of NAM, a precursor of nicotinamide adenine dinucleotide (NAD+), and the generation of SAH, a precursor of homocysteine (Hcy). Consequently, this cascade leads to reduced NAD+ levels and elevated Hcy levels, implicating NNMT in the pathogenesis of MetS. Moreover, experimental studies employing RNA interference (RNAi) strategies and small molecule inhibitors targeting NNMT have underscored its potential as a therapeutic target for preventing or treating MetS-related diseases. Nonetheless, the precise mechanistic underpinnings remain elusive, and as of yet, clinical trials focusing on NNMT have not been documented. Therefore, further investigations are warranted to elucidate the intricate roles of NNMT in MetS and to develop targeted therapeutic interventions.

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“…This includes examining the frequency of food consumption across different groups, assessing the extent of deficiencies in individuals with ASD, and exploring their dietary preferences. Additionally, aside from inflammatory factors, elevated blood homocysteine levels have been linked to various neurological and mental disorders, including autism [ 17 , 18 ].. Homocysteine is an amino acid involved in methylation reactions and the metabolism of folate and vitamin B12 [ 19 ]. It can have neurotoxic effects, impacting neuronal function, neurotransmitter synthesis, and oxidative stress levels [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Serum interleukin-17 A and homocysteine levels in children with autism

Li,

Dang,

Yan

2024

BMC Neurosci

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Background Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) and the severity of ASD symptoms in children. Methods In this study, 50 children diagnosed with ASD comprised the observation group, while 50 healthy children constituted the control group. Serum levels of IL-17 A, Hcy, folate, and vitamin B12 were compared between the study group and control group, as well as among children with different degrees of ASD severity. The correlation between the Childhood Autism Rating Scale (CARS) score and serum levels of IL-17 A, Hcy, folate, and vitamin B12 was examined. Additionally, the relationship between serum IL-17 A and Hcy levels and their association with the severity ASD were explored. Results Compared to the control group, the observation group demonstrated elevated serum Hcy and IL-17 A levels alongside decreased folate and vitamin B12 levels. Individuals with severe ASD exhibited higher Hcy and IL-17 A levels but lower folate and vitamin B12 levels compared to those with mild to moderate ASD. The CARS score showed negative correlations with serum folate and vitamin B12 levels and positive correlations with serum IL-17 A and Hcy levels in ASD patients. Additionally, serum Hcy and IL-17 A levels were correlated with ASD severity. Conclusion Children diagnosed with ASD presented with reduced serum vitamin B12 levels and increased levels of Hcy, potentially contributing to the onset and severity of ASD.

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Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis

Cited by 10 publications

References 111 publications

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study

Serum levels of vitamin B12 combined with folate and plasma total homocysteine predict ischemic stroke disease: a retrospective case-control study

Nicotinamide N-methyltransferase (NNMT): a novel therapeutic target for metabolic syndrome

Serum interleukin-17 A and homocysteine levels in children with autism

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