Radiosensitizers: When Cancer Radiation Fails, These Natural Compounds Change Everything

Learn how curcumin, berberine, and intermittent fasting can overcome radiation resistance + make cancer treatment more effective in this guest post by integrative oncology specialist Dr. Amanda King.

Guest post by Dr. Amanda King.

Find more of Dr. King’s work at her Substack and on her website. Plus, don't miss her live tonight (Wednesday, September 24th) at the next IMA webinar:

“From Stage 4 to Remission: The Power of Integrative Oncology.”

In this webinar, Dr. King introduces Dale—a patient she helped to turn around a terminal diagnosis. Together, they walk through what treatment looked like, what conventional doctors told him, and what changed when he tried a different path. Join us for a powerful reminder that healing is never off the table.

⏰ Showtime: 7:00 PM ET / 4:00 PM PT 🔗 Watch live on: X (Twitter) / Rumble

Our understanding of the importance of integrative oncology is growing. Once dismissed as unscientific or conspiracy, we now have a fast-growing body of peer-reviewed, good data available across this discipline that traditional oncology is finding increasingly difficult to ignore.

When we have a cancer diagnosis, we usually have three or four medical treatment options available to us. Chemotherapy, radiotherapy, immunotherapy, and surgery. Whether we are offered any or all of these treatments depends on the cancer we have, our stage, and hopefully a personal decision about our own treatment, which should always be based on a fully informed choice.

If we choose to receive radiation to kill cancer, our oncology team should advise us about the side effects. While there are many different ways to apply it, radiotherapy always involves exposure to ionizing radiation, which causes serious damage to any tissues that it makes contact with, cancer or not.

An ion is an atom with an electrical charge, which can be positive or negative. Ionizing radiation has to be very powerful since it forces atoms to lose or gain an electron. When damage to the atoms in a cell is severe enough, it damages the DNA of the cell or creates free radicals (ROS), and these often damage the cell irreversibly.

According to the National Cancer Institute, side effects of receiving ionizing radiation can include:

• Sickness

• Vomiting

• Burns

• Blisters

• Skin Changes

• Hair Loss

• Memory Problems

• Fatigue

• Diarrhea

• More Cancer

Why Cancers Can Survive Radiation Treatment

Radiotherapy and chemotherapy both kill rapidly dividing cancer cells. They do this by damaging the cell’s ability to reproduce, in a process called mitosis. This means that cells with high turnover rates are most affected. Since a hallmark of cancer is uncontrolled growth (sustained proliferative signaling), rapidly dividing cancer cells are the most affected by irradiation.

Rapidly dividing healthy tissues are also badly affected, and these include hair, nails, the small intestine, the lining of the gut, and bone marrow.

The rapidly dividing cells are called daughter cells, and these originate from ‘parent’ cells called cancer stem cells. Cancer stem cells are typically radioresistant, meaning that they can resist and recover from the damage of ionizing radiation.

We don’t know fully yet why cancer stem cells (CSCs) are resistant to radiotherapy, but it has been suggested that since ionizing radiation damages DNA and CSCs have in-built excellent repair systems, they can repair radiation damage much faster and survive.

CSCs reside in a hypoxic (without oxygen) environment, and radiation needs oxygen to create ROS (radical oxygen species). This leaves radiation without the right tools to exert its damage.

Cancer stem cells also have different redox/antioxidant mechanisms than non-CSCs. They appear to be able to regulate the levels of oxidative stress much more tightly, which means that when ROS are generated, which would destroy a daughter cell perhaps, the CSC can neutralize the ROS and save itself.

Daughter cells can also develop radioresistance, and in fact it seems obvious how and why they would do that from the perspective of survival of the fittest. The most vulnerable and weakened cancer cells are the most susceptible to radiation, and they succumb first. Those that are left are the strongest, and when they divide, they pass on their ‘stronger genetic material’ to their clones. In fact, daughter cells can develop something called ‘acquired resistance,’ where they ‘learn’ how to survive radiation too. They may stop dividing so rapidly, and they may develop systems of fueling themselves that don’t include exposure to oxygen. They can also develop better ‘redox’ or antioxidant capacity to repair themselves after radiation.

Radiosensitization: How to Make Cancer Vulnerable to Radiation

By identifying how cancer cells might develop radioresistance, we can more precisely target those resistance mechanisms with interventions that weaken cancer’s defenses. Then, we not only knock out cancer’s defense strategy, but we can also further sensitize cancer to the damaging effects of ionizing radiation.

Here’s how:

Curcumin

Curcumin is the active compound in turmeric. Well known as an anti-inflammatory supplement and an ingredient in Asian, African, and Middle Eastern cuisine, it has a distinctive aroma and was even traditionally used as a yellow fabric dye.

As a radiosensitizer, curcumin makes glioblastoma (brain) cancer cells more vulnerable to radiation, and at the same time, it protects regular, healthy cells. It does this by boosting our natural immune response, which goes after the cancer cells, attacking and weakening them and leaving them more sensitive to radiation, whether their environment is hypoxic or not.

We have seen greater efficacy in combination therapies, for example, when curcumin was paired with radiation AND hyperthermia or HBOT—hyperbaric oxygen therapy. We have so much more to learn about combining supplements and therapies for their synergistic effects.

It is interesting that analogues of curcumin, which are essentially pharmacological copies of curcumin but with small alterations, are now being developed, and these are even more effective than regular curcumin. Two compounds called ComA and ComB were used against not only radioresistant but also chemoresistant glioblastoma tumors, and they were found to have ‘enhanced tumor activity’ when compared to regular curcumin. This meant that less of the supplement was needed to have the same effect.

In lung cancer, nano-curcumin was found to work better as a radiosensitizer than regular curcumin, and it was shown to induce apoptosis, the regular cell death that cancers often evade.

The fact that curcumin is both a radiosensitizer to cancer cells and a radioprotector ’of normal, healthy cells makes it particularly interesting since tissue toxicity by radiation limits the amount of radiation that a person can receive. If doses can’t get to high enough amounts due to the toxicity affecting healthy cells, there may be insufficient doses to kill cancer. We can use the protective mechanisms of curcumin, primarily its anti-inflammatory mechanism as a COX inhibitor, to reduce the toxicity of radiation, and this could allow for a higher and more effective dose of radiation treatment.

Berberine

This alkaloid compound is extracted from many different plants and has a formidable array of anti-cancer effects as a standalone supplement. It is most well-known as a blood sugar modulating compound, which means that it brings blood sugar back to normal levels in those who have blood sugar dysregulation, making it an excellent intervention for those with type 2 diabetes. It is also an effective radiosensitizer with a good safety record.

In ovarian cancer, berberine was shown to increase ROS (free radicals) in cancer cells, which caused higher levels of DNA oxidative damage. This weakened the cancer, leaving it more vulnerable to the effects of radiation.

Low-dose berberine was shown to increase cervical cancer sensitivity to radiation in one study, even where hypoxic (low oxygen) conditions were present. Berberine regulated the tumor microenvironment by adjusting levels of HIF1a (hypoxia inducible factor 1 alpha). HIF1a is increased in low oxygen conditions, and higher levels increase angiogenesis, the process where blood vessels are grown towards tumors to allow them the nutrients they need to grow.

Berberine was found to be an effective radiosensitizer in osteosarcoma, a kind of bone cancer. It was shown to inhibit something called Rad51, which is a kind of DNA repair mechanism. Since we know that cancers try to repair themselves after damage to their atoms from radiation, using berberine prevents that repair. When used alongside more radiation to continue to bombard and damage the tumor cell, we can see how that could lead to a much more effective, integrated treatment strategy.

The antioxidant and anti-inflammatory effects of berberine also mean fewer side effects from radiation. This makes berberine also a radioprotective compound, selectively targeting cancer cells while protecting healthy cells.

Intermittent Fasting

Fasting to a daily routine, also called intermittent fasting, and the fasting-mimicking diet (Wei et al., 2017), which is a low-calorie, low-protein, and low-carbohydrate diet intended to mimic fasting, are both shown to effectively sensitize cancer to radiation.

By reducing IGF-1, which is insulin growth factor 1, an anabolic (growth) hormone that looks a lot like insulin, intermittent fasting slows cancer growth.

In pancreatic cancer, fasting helped to repair the gut right quickly before radiation exposure, protecting the rapidly dividing gut cells from damage. In one study, this allowed for higher radiation dosing and more opportunity to kill the cancer present. A mild radiosensitizing effect was also observed.

Several studies have indicated that fasting protects healthy cells in mice, though we do need to remember that these studies often feed mice pro-inflammatory seed oils when they feed them high-fat diets, which is not representative of a healthy keto diet. (Jensen et al., 2013)

Fasting upregulates a pathway in the body called AMPK, which is a catabolic state. AMPK is more protective for us than anabolic (growth states), and it’s the pathway where the body does the cleanup job, repairing damaged DNA and boosting our metabolism. We can’t have both catabolic (AMPK) and anabolic (mTOR) processes on at once; it’s one or the other. We don’t get it both ways. It was found that these metabolic changes induced inflammation and oxidative stress and ultimately sensitized cancer cells to the devastating effects of radiation.

Intermittent fasting should always be done under the guidance of an integrative metabolic oncology nutritionist, who can help you to navigate your diet without unnecessary weight loss or risk of malnutrition.

Dichloroacetate (DCA)

DCA is a drug that forces cancer cells to move away from their preferred method of energy production, which is called glycolysis or the Warburg Effect, usually under anaerobic conditions. (Seyfried et al., 2025) Instead of glycolysis, cancer is forced by DCA to use oxygen for energy production through the batteries of our cells, called the mitochondria, a process known as OXPHOS—oxidative phosphorylation. Thinking back to how cancers can evade radiation damage, we can see how DCA forces cancers to become vulnerable to damage by free radicals (ROS) from radiation. By making the conditions cancer grows in to become more oxygenated, the door is opened for radiation to use the oxygen as a weapon, killing the cancer cells effectively. Radiosensitizing effects have been seen to take place in esophageal and brain cancers through this very mechanism.

DCA inhibits something called PDK, which is pyruvate dehydrogenase kinase. This is an enzyme that opens the door to allow cancer to make energy without oxygen present. When DCA shuts down PDK, the door stays closed, which is why cancers are forced to go through the mitochondria. In cancer the mitochondria is broken, though; this means that more damaging ROS are created when it tries to create energy. To imagine how this looks, think about running a car (mitochondrion) on its last legs and all the smoke (ROS) billowing out of the back. Couple that with cancer needing to grow quickly, the car has to be driven at top speed, and boom, it breaks down, and we have cancer cell death. This radiosensitizing mechanism was seen to happen in breast cancer too.

Questions remain around the safety of DCA, though. Where berberine and curcumin have strong safety records, DCA has a history of side effects, which include asthenia (weakness), reversible toxicity, neuropathy, and an increase in liver enzymes. This means that for some populations, DCA will be contraindicated, reinforcing the need to work with an oncology professional for your personalized protocol when you need support with cancer.

Wrapping Up

We’re only beginning to understand the full potential of radiosensitizers. Each of these compounds—curcumin, berberine, DCA, and even intermittent fasting—offers a unique path to make conventional treatments more effective while minimizing harm to the patient. In Part 2, we’ll go deeper into emerging compounds, protocols, and what it looks like when integrative strategies become the standard, not the exception.

To explore more of Dr. Amanda King’s work, visit her Substack and her website. And stay tuned to IMA as we continue highlighting research and frontline experiences from the most innovative minds in medicine.

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