When a person receives a cancer diagnosis, it is completely natural to want to explore every possible option to improve their chances. Along that path, many patients turn to natural supplements with the hope of strengthening their immune system or even directly fighting the tumor. We are also living in what is known as the “immunotherapy revolution,” where treatments such as Nivolumab have radically changed the approach against various types of cancer. However, combining supplements with immunotherapy is not a simple matter and requires understanding how these compounds interact with the immune system.
Immunotherapy works by activating the body’s own defenses so they can recognize and destroy cancer cells. The problem is that tumors develop multiple strategies to hide from the immune system. They can increase immunosuppressive cells, produce substances such as TGF-β that block immune response, or reduce molecules like MHC class I that allow immune cells to identify the enemy. For this reason, any substance that alters the immune system can influence treatment either positively or negatively.
One of the most discussed products is cannabis. It is common to hear that it “cures cancer,” but scientific evidence does not strongly support that claim. Cannabinoids act on receptors called CB1 and CB2; the latter is found in immune system cells. Some experimental studies have shown that certain cannabis compounds can induce cell death in animal or laboratory models. However, there is also research indicating that they may suppress immune response and increase regulatory cells that, in the context of cancer, could favor the tumor. An observational study suggested that patients who used cannabis while receiving immunotherapy with Nivolumab had a lower response rate than those who did not use it. This does not mean cannabis has no usefulness; in fact, it is very effective for controlling pain, nausea, loss of appetite, and anxiety. But its role appears to be mainly palliative, not curative, and it could interfere with certain immunological treatments.
Another supplement that has drawn attention is silibinin, derived from milk thistle and marketed in some places as Legasil. Silibinin works by inhibiting the STAT3 pathway, a molecular signal associated with tumor-related immunosuppression. By blocking this pathway, it could reduce suppressor cells and decrease TGF-β production. A small study in patients with lung cancer and brain metastases showed striking responses in the brain. However, the number of participants was limited, so larger trials are needed to confirm these findings.
6-gingerol, the active compound in fresh ginger, has also generated interest. It has been observed to inhibit the enzyme arginase and modify the behavior of macrophages, key cells in the immune system. In simple terms, it could help convert macrophages that protect the tumor into macrophages that attack it. This point is relevant because some patients treated with PD-1 inhibitors may develop hyperprogression, a phenomenon in which the tumor grows faster after starting immunotherapy. Although there is still no solid clinical data in humans supporting its standard complementary use, the biological mechanism is promising.
Berberine, a plant extract known for its ability to reduce blood glucose levels, has also been studied in oncology. Some studies suggest it may inhibit cell proliferation, induce apoptosis, and decrease immunosuppressive cytokines such as IL-10 and TGF-β. However, other research points to possible immunosuppressive effects. This apparent contradiction reflects the complexity of the immune system: a substance can have different effects depending on the dose, biological context, or type of cancer.
Selenium is another example where chemical form matters greatly. There are different presentations, such as selenomethionine, which is common in commercial supplements. However, experimental studies have shown that methylseleninic acid may have stronger effects in reducing metastasis and increasing molecules that facilitate tumor recognition by the immune system. The drawback is that this form is not usually easily available. This demonstrates that it is not enough to know “what” supplement to take; it is also crucial to understand “how” it is formulated.
Curcumin, the main active component of turmeric, is probably one of the most widely used supplements among cancer patients. It is attributed anti-inflammatory and immune-modulating properties. Some studies indicate that it may protect T cells from tumor-induced damage and reduce TGF-β production. It may also influence tumor suppressor genes such as p53. However, one of its main challenges is its low bioavailability, meaning the body has difficulty absorbing it in significant amounts.
EGCG, a polyphenol from green tea, has also been investigated for its potential anticancer effects. It has been observed to inhibit the enzyme IDO, which is involved in suppressing immune response, and to affect cancer stem cells. However, at high doses, cases of liver toxicity have been reported, underscoring the importance of not assuming that “natural” means “harmless.”
Sulforaphane, derived from cruciferous vegetables such as broccoli, requires enzymatic activation to exert its effects. It is credited with properties including reducing cancer stem cells and inhibiting factors that allow cancer to escape the immune system. However, some studies warn that it could act as a “double-edged sword,” since under certain circumstances it might negatively affect T cell activation.
Polydatin, a precursor of resveratrol, has been studied for its ability to interfere with tumor glucose metabolism. Tumors consume large amounts of glucose and generate lactic acid, creating an environment that hinders immune system activity. By altering these metabolic pathways, polydatin could reduce proliferation and metastasis, although clinical evidence remains limited.
Figure 1. Natural bioactive compounds may exert pleiotropic effects on tumor biology by interacting with interconnected signaling networks that regulate immune surveillance, cellular metabolism, inflammatory signaling, and redox balance. By influencing pathways involved in immune evasion and microenvironmental adaptation, these agents have the potential to modify the dynamic interplay between cancer cells and host immunity.
Finally, beta-glucans, found in oats, barley, mushrooms, and yeast, bind to immune system receptors and can increase the production of stimulating cytokines. Theoretically, they could transform a “cold tumor,” with little immune infiltration, into a “hot tumor,” more susceptible to immunotherapy. However, there is still no consensus on which source is superior or what the optimal dose should be.
When analyzing all these compounds, one clear conclusion emerges: the immune system is extraordinarily complex. It is not enough to simply “stimulate” it; it must be done in the right way and at the right time. Some supplements could enhance immunotherapy, others could interfere, and many still require rigorous studies to determine their true clinical impact.
For this reason, the decision to incorporate supplements should be made with caution and always in coordination with the medical team. More does not always mean better, and the indiscriminate combination of multiple products can generate unwanted interactions, toxicity, or simply unnecessary expense.
Responsible integration between conventional medicine and natural compounds represents a promising area of research. However, evidence must guide every step. Hope is fundamental in cancer treatment, but it must be accompanied by solid knowledge and informed decision-making.
Main reference:
Williams, J. R. (2019). The immunotherapy revolution the immunotherapy revolution: The best New Hope for saving cancer patients’ lives. Independently Published.
