Lithium is a naturally occurring element used primarily as a mood stabilizer for the long-term management of bipolar disorder. Patients often remain on this medication for decades due to its effectiveness in reducing the severity and frequency of mood episodes. Because of this prolonged exposure, there is understandable public interest regarding potential long-term risks, particularly the possibility of the drug increasing cancer risk. This article examines the current scientific evidence to provide a clear understanding of the established safety profile and the specific concerns surrounding lithium and cancer incidence.
Established Non-Carcinogenic Safety Profile
Long-term lithium therapy affects two main organ systems: the thyroid gland and the kidneys. Lithium can interfere with the thyroid gland’s ability to produce hormones, commonly leading to hypothyroidism, or an underactive thyroid.
The kidneys are also affected by lithium’s impact on water balance and concentration. Many patients experience nephrogenic diabetes insipidus, where the kidneys are unable to properly concentrate urine, leading to increased thirst and frequent urination.
Over many years, lithium exposure can result in chronic changes in the kidney tissue, such as interstitial fibrosis, which may contribute to a decrease in overall kidney function. These effects necessitate regular blood testing to measure thyroid function and estimated glomerular filtration rate (eGFR) to assess kidney health.
Population Studies on Cancer Incidence
Large-scale epidemiological research assesses the link between lithium use and overall cancer risk. Multiple population-based cohort studies comparing cancer incidence rates in patients on long-term lithium therapy against control groups generally find that lithium does not appear to increase the overall risk of cancer mortality or incidence. Some studies even suggest a reduced risk for overall cancer in lithium-treated patients compared to those with bipolar disorder not taking lithium.
The interpretation is nuanced, as individuals with bipolar disorder not treated with lithium often show a higher baseline rate of cancer compared to the general population. When comparing lithium-treated patients to the general population, the rates are often similar. This suggests that lithium may normalize the elevated cancer risk associated with the underlying psychiatric illness itself.
A recent large-scale study investigating environmental lithium exposure in drinking water found that higher concentrations were associated with a lower risk for several types of cancer. This protective association was observed across malignancies, including breast, prostate, and colorectal cancer. Although these environmental exposure levels are much lower than therapeutic doses, the data supports the perspective that lithium is generally not a systemic carcinogen.
Cellular Pathways and Growth Regulation
The rationale for investigating a cancer link stems from lithium’s mechanism of action at the cellular level. Lithium acts as a direct inhibitor of Glycogen Synthase Kinase-3 beta (GSK-3β), an enzyme regulating cell proliferation, programmed cell death (apoptosis), and the Wnt signaling pathway.
Inhibition of GSK-3β stabilizes \(\beta\)-catenin, a key effector of the Wnt pathway. Because the Wnt pathway is frequently overactive in many human cancers and promotes cell survival and growth, this mechanism theoretically raises concern about lithium encouraging tumor development.
However, lithium’s effects are not uniformly pro-cancerous. In laboratory settings, some studies show that lithium can exhibit anti-cancer properties, particularly at high concentrations, by disrupting cellular metabolism and inducing cell cycle arrest in certain cancer cell lines. Lithium’s dual ability to influence both pro-growth and anti-growth pathways explains the continued scientific interest and contradictory results from in vitro experiments.
Thyroid and Renal Cancer Surveillance
Despite reassuring data on overall cancer incidence, specific concerns remain regarding the thyroid and the kidneys. Some case reports describe the occurrence of papillary thyroid carcinoma and renal cell carcinoma in patients on lithium for extended periods. However, the risk is considered small, and large studies have not consistently confirmed a statistically significant increase in the incidence of these specific tumors compared to control groups.
The possibility of surveillance bias complicates the interpretation of data concerning these organ-specific cancers. Patients taking lithium undergo frequent monitoring of thyroid and kidney function, often including imaging or blood tests. This intense surveillance means that small, slow-growing tumors are more likely to be detected earlier in lithium users than in the general population.
The standard of care for patients on long-term lithium includes proactive surveillance. Clinicians routinely monitor serum creatinine and estimated glomerular filtration rate (eGFR) for kidney function and thyroid-stimulating hormone (TSH) levels for thyroid function. This regular monitoring allows for the early detection of any structural changes, such as nodules or masses, ensuring prompt treatment.