Elevated Plasma Vitamin B12 in Patients with Hepatic Glycogen Storage Diseases

Abstract

Background: Hepatic glycogen storage diseases (GSDs) are inborn errors of metabolism affecting the synthesis or breakdown of glycogen in the liver. This study, for the first time, systematically assessed vitamin B12 status in a large cohort of hepatic GSD patients. Methods: Plasma vitamin B12, total plasma homocysteine (tHcy) and methylmalonic acid concentrations were measured in 44 patients with hepatic GSDs and compared to 42 healthy age- and gender-matched controls. Correlations of vitamin B12 status with different disease markers of GSDs (including liver transaminase activities and triglycerides) as well as the vitamin B12 intake were studied. Results: GSD patients had significantly higher plasma vitamin B12 concentrations than healthy controls (p = 0.0002). Plasma vitamin B12 concentration remained elevated in GSD patients irrespective of vitamin B12 intake. Plasma vitamin B12 concentrations correlated negatively with triglyceride levels, whereas no correlations were detected with liver transaminase activities (GOT and GPT) in GSD patients. Merging biomarker data of healthy controls and GSD patients showed a positive correlation between vitamin B12 status and liver function, which suggests complex biomarker associations. A combined analysis of biomarkers permitted a reliable clustering of healthy controls versus GSD patients. Conclusions: Elevated plasma concentration of vitamin B12 (irrespective of B12 intake) is a common finding in patients with hepatic GSD. The negative correlation of plasma vitamin B12 with triglyceride levels suggests an influence of metabolic control on the vitamin B12 status of GSD patients. Elevated vitamin B12 was not correlated with GOT and GPT in our cohort of GSD patients. Merging of data from healthy controls and GSD patients yielded positive correlations between these biomarkers. This apparent dichotomy highlights the intrinsic complexity of biomarker associations and argues against generalizations of liver disease and elevated vitamin B12 in blood. Further studies are needed to determine whether the identified associations are causal or coincidental, and the possible impact of chronically elevated vitamin B12 on GSD.

A cross-sectional study of nutritional status in healthy, young, physically-active German omnivores, vegetarians and vegans reveals adequate vitamin B12 status in supplemented vegans

“…The use of oral supplements corrected for this lack, leading to adequate plasma vitamin A levels in all participants across diets. Importantly, relationships between vitamin B12 and markers of lipid [ 55 , 56 ] and iron metabolism [ 57 ] have been described in independent studies. The molecular mechanisms underlying these associations remains to be investigated.…”

Biomarkers, Biocatalysts, or Pathology Conditions to Evaluate Potential History of Liver Disease such as Cancer

“…[14] For liver pathologies and liver damage such as hepatocellular carcinoma, cirrhosis, and hepatitis, elevated vitamin B 12 concentrations have been reported as another biomarker. [15] The deficiency of biomarkers such as methylmalonyl-CoA mutase or propionyl-CoA carboxylase could cause inborn errors of metabolism. [16] In animal models with liver injury, serum histone levels were reported to be raised significantly.…”

“…The highest prevalence rates of NAFLD are reported in the Middle East (31.8%), and South America (30.4%), and the lowest is in Africa. [15] Insulin resistance and systemic hypertension independently were associated with the advanced forms of NAFLD. [26] There is a link between NAFLD and the risk of colorectal adenomas and cancer, intrahepatic and extrahepatic cholangiocarcinoma, and prostate, gastric, breast, pancreatic, and esophageal cancer.…”

The role of vitamin B12 in viral infections: a comprehensive review of its relationship with the muscle–gut–brain axis and implications for SARS-CoV-2 infection

“…84 , 132 , 133 Flores-Guerrero et al 134 showed that a plasma vitamin B 12 concentration > 455.41 pg/mL was associated with a higher risk of all-cause mortality in 1394 adults (mean age ± SD, 54.6 ± 11.6 years). Excess vitamin B 12 is still controversial, and other authors have used distinct values for high plasma B 12 levels: >950 pg/mL or 701 pmol/L 135 ; > 771 pg/mL 136 ; > 203 pg/mL or > 601 pmol/L. 137 …”