High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations

Obeid, Rima

doi:10.3390/nu14214476

Cited by 19 publications

(8 citation statements)

References 64 publications

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“…Interestingly, high vitamin B12 was noted in one-fifth of PDAC patients in our cohort. The cause of elevated vitamin B12 remains unknown, but it is described as a poor prognostic factor in patients with advanced cancer [ 28 , 29 ]. Folate concentration was significantly lower in the palliative than in the adjuvant group but remained within the normal range and should not have clinical implications.…”

Section: Discussionmentioning

confidence: 99%

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis

Osmola,

Gierej,

Mleczko-Sanecka

et al. 2023

Current Oncology

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Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% (n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% (n = 5) of patients. Furthermore, 8.7% (n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl’s Prussian blue to detect iron deposits on available tumor samples (n = 56). ZIP14 expression was significantly higher in less advanced tumors (p = 0.01) and correlated with mitochondrial mass (p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl’s Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.

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Section: Discussionmentioning

confidence: 99%

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis

Osmola,

Gierej,

Mleczko-Sanecka

et al. 2023

Current Oncology

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“…Some researchers propose that it may act as a predisposing factor for Alzheimer's disease [173]. Additionally, it is associated with various other neurological conditions including Wernicke's encephalopathy, subacute combined degeneration of the spinal cord, and peripheral neuropathy [174].…”

Section: Long-distance Consequences Of Vitamin B12 Deficiencymentioning

confidence: 99%

“…Recently, MMA was also found to promote metastasis in colon tumor models [183]. However, the direct effect of vitamin B12 deficiency on cancer onset, prognosis, and progression remains unresolved due to many inconsistent studies [173][174][175][176][177][178].…”

Section: Long-distance Consequences Of Vitamin B12 Deficiencymentioning

confidence: 99%

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes

Mucha,

Kus,

Cysewski

et al. 2024

Preprint

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The water-soluble vitamin - vitamin B12, also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its de-ficiency can lead to hematological and neurological disorders, however the manifestation of these clinical outcomes is relatively late. It leads to difficulties in its early diagnosis, often resulting in the development of hidden subclinical cobalamin deficiency. Prolonged lack of vitamin B12 con-dition may have severe consequences including increased morbidity to neurological and cardio-vascular diseases. Beyond inadequate dietary intake, vitamin B12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabo-lism. Despite nearly 70 years of knowledge since its isolation and characterization, there are still gaps in understanding its metabolic pathways. Thus, this review aims to gather current knowledge about the crucial proteins necessary to efficiently process vitamin B12 in humans, presenting it as a multi-protein mediated network. Based on these findings, we also highlight new potential methods for supporting the evaluation of the risk of epidemiological consequences of vitamin B12 deficiency or clinical warnings of increased risk of vitamin B12 deficiency based on already testing targeting specific moonlighting proteins engaged in vitamin B12 metabolic path-ways.

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“…High concentrations of vitamin B12 may be due to underreporting supplement use, autoimmune disorders interfering with the B12 assay, or underlying renal or liver diseases. In addition, some malignancies cause high circulating levels of vitamin B12 and may thereby impact the interpretation of this marker in the context of diagnosing vitamin B12 deficiency [92]. In this case, the concentrations of methylmalonic acid or homocysteine can provide clues on intracellular vitamin B12 status.…”

Section: Delphi Consensusmentioning

confidence: 99%

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus

Obeid,

Andrès,

Češka

et al. 2024

JCM

Self Cite

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Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

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High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations

Cited by 19 publications

References 64 publications

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis

Vitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes

Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus

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