Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies

Abstract

<jats:p>Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.</jats:p>

Vitamin B12 Induces Hepatic Fatty Infiltration through Altered Fatty Acid Metabolism

“…Accumulation of lipid droplets underlies and defines the state of steatosis in the liver [35], therefore implying that our observation of low B12 induced accumulation of lipids in HepG2, may be associated with the pathogenesis of hepatic steatosis. This supports the clinical observation which showed that serum B12 negatively associated with serum triglyceride and VLDL levels in Indian subjects [17,36]. In an animal model, severe B12 deficiency was associated with higher serum triglyceride levels which resulted in adverse pregnancy outcome [37].…”

“…Compared to the liver, the contribution of adipose tissue to the circulating levels of lipids is considerably lower [16]. Therefore, if the effects of B12 are similar in hepatocytes, this may explain the association observed between low B12 and dyslipidaemia in humans [17] and the causal association observed in animal models [17].…”

Current Nanocarrier Strategies Improve Vitamin B12 Pharmacokinetics, Ameliorate Patients’ Lives, and Reduce Costs

“…Authors highlight that children born from pregnant women that presented VitB12 deficiency have more frequently developed excess fat accumulation and thus a higher risk factor for insulin resistance, type 2 diabetes, and/or cardiovascular disease in adulthood. This evidence strongly suggests an involvement for VitB12 on epigenetic mechanisms although there are very few association studies currently available [ 20 ]. As mentioned, in some cases, VitB12 deficiency can be asymptomatic in the onset phase with no obvious symptoms but can cause devastating effects.…”

Low Serum Vitamin B12 Levels Are Associated with Adverse Lipid Profiles in Apparently Healthy Young Saudi Women

“…Observational studies have shown an inverse association between vitamin B12 intake and metabolic disorders, including body mass index (BMI) [17], insulin resistance [18], type 2 diabetes mellitus (T2DM) [19], adverse lipid profile [20], and cardiovascular diseases (CVDs) [21][22][23]. Animal studies suggest that maternal low B12 levels may be causally linked to adverse lipid profiles in offspring [21]. In addition, vitamin B12 deficiency among pregnant women has been associated with gestational diabetes mellitus [24] and impaired cardiometabolic health of offspring [25].…”