The independent and joint associations of vitamin B12 and methylmalonic acid on the risk of mortality in individuals with metabolic dysfunction-associated steatotic liver disease

Article

Author: Yu, Jing ; Simayi, Rukiya ; Shi, Dan ; Zhao, Yaxuan ; Wang, Peng

PURPOSETo investigate the independent and joint associations of vitamin B12 and methylmalonic acid (MMA) with all-cause, cardiovascular disease (CVD), and cancer mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).METHODSWe included 6797 individuals with MASLD from the U.S. National Health and Nutrition Examination Survey. Serum MMA was measured using gas/liquid chromatography-mass spectrometry. Serum vitamin B12 was measured using commercial kits. The separate and joint associations of dietary intake and serum vitamin B12 (cutoff: 400 pg/mL) and MMA (cutoff: 250 nmol/L) levels with mortality were assessed by Cox proportional hazards regression.RESULTSDuring a median follow-up of 9.3 years, 1604 deaths were documented, including 438 from CVD and 365 from cancer. In MASLD patients, dietary intake and serum vitamin B12 did not associate with mortality, while MMA was associated with a 1.35-fold increased risk of all-cause mortality (P-trend < 0.001). The adjusted hazard ratios for the joint association of vitamin B12 and MMA with all-cause and CVD mortality were 1 in the B12_lowMMA_low group (reference), 1.02 (0.87-1.20) and 1.15 (0.90-1.47) in the B12_highMMA_low group, 1.55 (1.29-1.86) and 1.84 (1.28-2.65) in the B12_lowMMA_high group, and 1.82 (1.49-2.21) and 2.28 (1.40-3.71) in the B12_highMMA_high group, respectively. The joint association was modified by serum folate (P-interaction = 0.001).CONCLUSIONSIn MASLD patients, MMA rather than dietary and serum vitamin B12 was positively associated with all-cause mortality. The joint effect of high levels of MMA and vitamin B12 showed the strongest associations with all-cause and CVD mortality, with a significant interaction with serum folate.

01 Apr 2024·Journal of Pharmaceutical and Biomedical Analysis

A novel automated multi-cycle magnetic solid-phase extraction coupled to LC-MS/MS to study the disorders of six functional B vitamins in patients with gastroenterology and hyperhomocysteinemia

Article

Author: Xu, Yang ; Lu, Youli ; Yuan, Xiangmei ; Liang, Yan ; Yu, Chen ; Li, Jie ; Gu, Yuting ; Jia, Jingying ; Ou, Meixian ; Jiang, Fengli ; Liu, Gangyi ; Yu, Fan ; Yang, Shuangshuang ; Zhang, Meiwei ; Xiao, Can

B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique for determining multiple B vitamins, however, their complexity in real biological matrices makes it hard to achieve satisfactory recovery and accuracy when simultaneous detection. In this study, a novel automated multi-cycle magnetic SPE (MSPE) coupled to the LC-MS/MS method was established using a mixed-mode anion exchange magnetic adsorbent for the simultaneous extraction of six functional B vitamins, including methylmalonic acid, riboflavin, pantothenic acid, 4-pyridoxic acid, folic acid, and 5-methyltetrahydrofolate. After three consecutive MSPE cycles, the recoveries of all analytes were between 51.5% and 89.6%. The method exhibited excellent sensitivity and linearity, with a dynamic range of 200-fold (R > 0.99 for all analytes), exceptional accuracy (ranging between 95.4% and 105.6%) and precision (with RSDs ≤ 6.2%) without significant matrix effects or interferences. Compared to manual SPE method, the automated multi-cycle MSPE method has better feasibility and greater vitamin coverage. It shows a high correlation with the manual method for the detection of 5-methyltetrahydrofolate and folate (R > 0.99). A study of patients from the gastroenterology department showed that those undergoing surgery and those with malignancies may be at risk of folate deficiency. In addition, patients with hyperhomocystinemia had higher levels of methylmalonic acid and lower levels of 5-methyltetrahydrofolate, which correlated with homocysteine levels (R = 0.404 and -0.311, respectively) and showed dose-response relationships. This method is highly automated and cost-effective, with minimal systematic error, making it suitable for the analysis of clinical samples.

30 Jun 2023·Gland surgery

Relationships between serum levels of vitamins and papillary thyroid cancer: a single center case-control study.

Article

Author: Benvenga, Salvatore ; Dionigi, Gianlorenzo ; Sindoni, Alessandro ; Fama, Fausto ; Pino, Antonella ; Kim, Hoon Yub ; Wu, Che Wei ; Sun, Hui ; Mazzeo, Carmelo ; Zhang, Daqi ; Frattini, Francesco

BackgroundVitamins are involved in various human physiological and biochemical mechanisms due to their antioxidant properties and their ability to enhance the immune response. Deficiency of some serum vitamins has been reported to be associated with an increased risk of developing cancer, including thyroid cancer. However, medical literature dealing with cholecalciferol supplementation was not able to show the potential of this intervention in cancer prevention. The aim of this paper is to highlight the association between lower serum vitamins levels and papillary thyroid cancer occurrence.MethodsThis case-control study was conducted between September 2018 and October 2019. Cases were defined as patients with histologically diagnosed papillary thyroid cancer who underwent thyroidectomy were retrospectively recruited and serum levels of various vitamins were assessed by examining their relationships with clinical, pathological and molecular data (n=51). Controls matched on sex and thyroid surgery were randomly selected from the same population (n=49).ResultsIn this study, serum concentrations of vitamins A and E in neoplastic patients were significantly lower than in controls (1.40 vs. 1.78, P<0.003 and 23.9 vs. 29.1, P<0.003, respectively). Serum concentrations of vitamin D and methylmalonic acid were borderline significantly low (15.6 vs. 17.9, P=0.06 and 100.3 vs. 110.4, P=0.055, respectively), while homocysteine was statistically similar in the two groups. Furthermore, serum vitamin levels were compared with the pathological characteristics of cancer patients, and vitamin D concentrations were significantly lower in BRAF-positive than in BRAF-negative neoplastic patients (8.2 vs. 16.0, P=0.021). On the other hand, no significant differences were observed in the correlation between serum levels of vitamins and other pathological characteristics, in particular with regard to lymph node metastases.ConclusionsIn conclusion, albeit with the analysis of a limited sample, this study highlighted the phenomenon that deficiencies in vitamins A and E can be associated with a higher frequency of occurrence of papillary thyroid cancer.

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Indication	Highest Phase	Country/Location	Organization	Date
Methylmalonic Acidemia	Preclinical	IT	GeneSpire SrlStartup	09 May 2024

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