Several types of cancer can cause folic acid deficiency, either by draining the body’s folate stores, interfering with absorption, or both. The cancers most commonly linked to folate depletion include blood cancers like leukemia and myeloproliferative disorders, gastrointestinal cancers that damage the digestive tract, and fast-growing solid tumors that consume folate to fuel their rapid cell division. Cancer treatments, particularly certain chemotherapy drugs, can also create a functional folate deficiency even when dietary intake is adequate.
Blood Cancers and Bone Marrow Disorders
Myeloproliferative disorders, a group of conditions where the bone marrow overproduces blood cells, are among the strongest cancer-related drivers of folate deficiency. The connection is straightforward: the massive increase in cell production burns through folate reserves faster than the body can replenish them. Folate is essential for making new DNA every time a cell divides, and when millions of abnormal blood cells are being churned out in the bone marrow, the demand for folate skyrockets.
Research published in Case Reports in Hematology found a high incidence of folate deficiency in patients with myeloproliferative disorders, with the deficiency likely driven by the sheer burden of proliferating cells. This folate depletion also causes a secondary problem: it allows a compound called homocysteine to accumulate in the blood, which raises the risk of blood clots, an already common complication in these patients. Leukemias and lymphomas can trigger similar dynamics, with rapidly multiplying cancer cells essentially outcompeting healthy tissues for the body’s limited folate supply.
Cancers That Disrupt the Digestive Tract
Your body absorbs folate primarily through the lining of the small intestine. Any cancer that damages or removes part of this system can lead to deficiency through malabsorption. Stomach cancer is a prime example, especially when treatment involves partial or total removal of the stomach. After a gastrectomy, food moves through the digestive system differently, and the body’s ability to break down and absorb nutrients, including folate, is significantly impaired.
Cancers of the small intestine, pancreas, and colon can cause similar problems. A tumor growing in the intestinal wall may physically block absorption, while pancreatic cancer can reduce the digestive enzymes needed to process nutrients properly. Colon cancer can also contribute, particularly when the disease or its surgical treatment shortens the length of functional intestine. In all these cases, the deficiency isn’t caused by eating too little folate. It’s caused by the body’s inability to extract and use the folate that’s there.
How Tumors Compete for Folate
Beyond blood cancers and digestive cancers, many solid tumors actively pull folate out of the bloodstream to support their own growth. Cancer cells divide far more frequently than normal cells, and folate is a critical ingredient in the biochemical reactions that make this possible. The folate cycle sustains the metabolic reactions needed for DNA synthesis, so any tissue growing at an abnormal rate will consume disproportionate amounts.
Some tumors take this a step further by overproducing a protein on their surface called the folate receptor. In healthy tissue, this receptor appears only in a few specific locations, like the kidneys, lungs, and placenta, and sits on parts of the cell that don’t directly contact the bloodstream. But in cancer, these receptors spread across the entire surface of the tumor cell, giving it far greater access to circulating folate. Ovarian, uterine, and certain brain cancers overexpress this receptor in the majority of cases. It also appears at elevated levels in a variable percentage of lung, kidney, breast, and colon cancers. The result is that the tumor siphons folate away from healthy tissues that need it.
Chemotherapy as a Cause
Some of the most widely used cancer treatments deliberately target the folate pathway to starve tumors of the raw materials they need to grow. Methotrexate, for example, works by blocking an enzyme that converts folate into its active form inside cells. This effectively creates a folate deficiency at the cellular level, which is exactly the point: without usable folate, cancer cells can’t replicate their DNA and divide.
The problem is that this mechanism isn’t selective. Healthy cells, particularly fast-dividing ones in the bone marrow, gut lining, and mouth, also lose access to folate. This is why methotrexate commonly causes side effects like mouth sores, low blood counts, and digestive issues. Research from the American Association for Cancer Research showed that methotrexate reduces intracellular folate concentration and disrupts related metabolic processes, including changes to DNA chemistry that go beyond simple folate depletion. Other chemotherapy drugs in the antifolate class work through similar mechanisms and carry the same risk.
Recognizing Folate Deficiency
Folate deficiency develops gradually, and its early signs often overlap with the fatigue and malaise that cancer patients already experience, making it easy to miss. The hallmark is a type of anemia where red blood cells are abnormally large because they can’t divide properly without adequate folate. This shows up as persistent fatigue, weakness, shortness of breath, and pale skin. Other symptoms include a sore or swollen tongue, mouth ulcers, difficulty concentrating, and irritability.
In cancer patients, these symptoms frequently get attributed to the cancer itself or to treatment side effects, so deficiency can go undetected. A blood test measuring serum folate levels is the standard diagnostic tool, with levels below 4.0 ng/mL generally considered deficient. Red blood cell folate is sometimes measured as well, since it reflects longer-term folate status rather than what you ate in the past few days.
The Complicated Role of Supplementation
Correcting folate deficiency in someone with cancer isn’t as simple as taking a supplement, because folate has a dual relationship with cancer. In healthy tissue, adequate folate protects DNA and may help prevent tumors from forming in the first place. But once cancer is established, supplemental folic acid may actually promote tumor growth by giving cancer cells the very nutrient they need to keep dividing.
A large umbrella review published in BMJ Open found that folic acid supplements may inhibit cancer development in normal tissues while promoting it in tissues where early cancerous changes already exist. The data was particularly striking for advanced tumors: elevated circulating folate was associated with roughly double the odds of advanced-stage tumor progression. The review recommended that folic acid supplements be used cautiously in individuals with pre-existing cancerous or precancerous lesions.
This creates a genuine clinical tension. A cancer patient with folate deficiency needs correction to prevent anemia and maintain quality of life, but overshooting that correction could theoretically benefit the tumor. In practice, this means folate levels in cancer patients are typically monitored carefully, and supplementation is tailored to bring levels back to normal range without pushing them excessively high.