High-Dose Thiamine and Cancer Cell Metabolism: Evidence from Experimental Cell-Line Studies

Cancer cell proliferation is closely linked to altered cellular metabolism. One of the most well-known metabolic features of cancer is the Warburg effect, in which tumor cells preferentially generate energy through aerobic glycolysis—converting glucose to lactate even in the presence of oxygen. This metabolic shift allows cancer cells to grow rapidly but also creates a potential therapeutic vulnerability. A 2014 experimental study titled “High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate”, published in Cancer Chemotherapy and Pharmacology, explored whether extremely high doses of thiamine (vitamin B1) could interfere with this metabolic advantage and suppress cancer cell growth.

In this study, researchers Hanberry, Berger, and Zastre investigated the effects of pharmacological doses of thiamine on two aggressive human cancer cell lines: neuroblastoma (SK-N-BE) and pancreatic cancer (Panc-1). These cancer types are known for rapid proliferation and poor clinical outcomes, making them relevant models for exploring novel metabolic interventions. The researchers exposed the cancer cells to very high concentrations of thiamine—far exceeding normal nutritional levels—and monitored changes in growth rate, metabolism, and cell survival.

The results demonstrated a marked reduction in cancer cell proliferation following high-dose thiamine treatment. Both neuroblastoma and pancreatic cancer cells showed significantly slower growth compared with untreated controls. Importantly, this growth suppression was not due to simple toxicity but was linked to a fundamental shift in cellular energy metabolism. The authors observed that high-dose thiamine altered how cancer cells processed glucose, directly targeting the metabolic pathways that support rapid tumor growth.

Mechanistically, the study focused on pyruvate dehydrogenase (PDH), a key mitochondrial enzyme that links glycolysis to oxidative phosphorylation. In many cancer cells, PDH activity is suppressed, diverting pyruvate away from the mitochondria and toward lactate production. This supports the glycolytic phenotype characteristic of the Warburg effect. High-dose thiamine was found to reactivate PDH, effectively forcing cancer cells to shift back toward a more “normal,” oxygen-dependent energy pathway. As a result, treated cancer cells consumed less glucose, produced less lactate, and showed reduced reliance on glycolysis.

This metabolic reprogramming had significant downstream consequences. By restoring mitochondrial oxidative metabolism, high-dose thiamine increased metabolic stress within cancer cells and promoted apoptosis, or programmed cell death. The activation of apoptosis suggests that cancer cells were unable to adapt effectively to the forced metabolic shift, leading to self-destruction rather than continued proliferation. Notably, this mechanism closely resembles the action of dichloroacetate (DCA), a metabolic drug known to activate PDH and reverse the Warburg effect. The authors highlighted this similarity, proposing that thiamine, at sufficiently high doses, may function as a metabolic modulator analogous to DCA.

The implications of these findings are conceptually important. Rather than targeting DNA replication or cell division directly, high-dose thiamine interferes with cancer growth by disrupting the metabolic foundation that tumors rely on. This strategy may be particularly valuable for cancers that are resistant to conventional chemotherapy but remain dependent on altered energy metabolism. However, the authors were careful to emphasize the limitations of their work. The experiments were conducted entirely in vitro, using isolated cancer cell lines, and the thiamine concentrations required to achieve these effects were far above typical dietary or supplemental levels.

In conclusion, the 2014 study published in Cancer Chemotherapy and Pharmacology provides experimental evidence that extremely high-dose thiamine can suppress cancer cell growth by reactivating pyruvate dehydrogenase, reversing the Warburg metabolic phenotype, and promoting apoptosis (Cancer Chemotherapy and Pharmacology, 2014). While these findings do not support clinical use at present, they highlight cancer metabolism as a promising therapeutic target and suggest that thiamine, under specific conditions, may influence tumor biology in ways that warrant further investigation through animal studies and carefully controlled clinical trials.