The Role of Fungus in Cancer

Oftentimes, even the most unlikely-sounding theories can be scientifically validated if you just wait long enough. That certainly rings true for recent headlines declaring fungi and bacteria may be playing a role in the development of certain types of cancer, combined with previous research showing baking soda may be a useful remedy.

In 2011, ScienceBasedMedicine.org shamed Dr. Oz for allowing me on his show,¹ and one of the "reasons" given was that I had at one time published information about a novel hypothesis — the idea that cancer could be caused by common fungi and might be treatable with baking soda.

Two early proponents of this hypothesis were Tullio Simoncini^2,3 and Mark Sircus.⁴ As you might expect, they were unsuccessful in their attempts at getting the conventional medical establishment to take the hypothesis seriously and have been maligned and marginalized for promoting these ideas.

So, mark my surprise when October 3, 2019, The New York Times published an article⁵ titled, "In the Pancreas, Common Fungi May Drive Cancer." The article reported the findings of a study^6,7 published in the October 2019 issue of the prestigious Nature journal. According to this study:⁸

"Bacterial dysbiosis accompanies carcinogenesis in malignancies such as colon and liver cancer, and has recently been implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA). However, the mycobiome has not been clearly implicated in tumorigenesis.

Here we show that fungi migrate from the gut lumen to the pancreas, and that this is implicated in the pathogenesis of PDA. PDA tumors in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue."

Fungal Microbiome May Play a Role in Pancreatic Cancer

More specifically, the mycobiome (the fungal microbiome) found in pancreatic tumors was distinctly different from the mycobiome found in the gut and in normal pancreases.

According to the researchers, PDA tumors had far greater amounts of a common fungal genus called Malassezia. Killing off the mycobiome with an antifungal drug was found to be protective, slowing down the progression of the tumor. As reported by Medical News Today:⁹

"The team found that treating mice with a strong antifungal drug called amphotericin B reduced tumor weight by 20–40%. The treatment also reduced ductal dysplasia, an early stage in the development of pancreatic cancer, by 20–30%.

Antifungal treatment also boosted the anticancer power of gemcitabine, a standard chemotherapy drug, by 15–25% …"

On the other hand, repopulating the tumor with Malassezia accelerated tumor growth, except when Candida, Saccharomyces or Aspergillus genera were used. This suggests Malassezia is the main culprit in this kind of cancer. When other genera were included, tumor growth was much slower.

"We also discovered that ligation of mannose-binding lectin (MBL), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 in the extratumoral compartment … were both protective against tumor growth," the authors note,¹⁰ concluding that:

"Collectively, our work shows that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL."

In summary, the fungi trapped in the pancreas appears to drive tumor growth by activating MBL (mannose-binding lectin), a liver protein that triggers the complement cascade¹¹ — an immune mechanism involved in fighting infections.

The problem is that this mechanism can also promote the growth of cells after the infection has been resolved.^12,13 When MBL activation was inhibited, tumor growth was also inhibited.¹⁴

Microenvironment Is an Important Consideration

As reported by The New York Times,¹⁵ up until very recently, the pancreas was thought to be a sterile organ, which made these findings all the more surprising. The New York Times goes on to state:

"There is increasing scientific consensus that the factors in a tumor's 'microenvironment' are just as important as the genetic factors driving its growth.

'We have to move from thinking about tumor cells alone to thinking of the whole neighborhood that the tumor lives in,' said Dr. Brian Wolpin, a gastrointestinal cancer researcher at the Dana-Farber Cancer Institute in Boston.

The surrounding healthy tissue, immune cells, collagen and other fibers holding the tumor, as well as the blood vessels feeding it all help support or prevent the growth of the cancer.

Microbes are one more factor to consider in the alphabet soup of factors affecting cancer proliferation. The fungal population in the pancreas may be a good biomarker for who's at risk for developing cancer, as well as a potential target for future treatments.

'This is an enormous opportunity for intervention and prevention, which is something we don't really have for pancreatic cancer,' said Dr. Christine Iacobuzio-Donahue, a pancreatic cancer researcher at Memorial Sloan Kettering in New York."

That this research is being taken seriously is evidenced by its widespread media coverage. As reported in an accompanying article in Nature News and Views:¹⁶

"The mycobiome is a historically under-recognized player in human health and disease, but its role in both is essential. Harmless organisms called commensals, including fungi, inhabit mucosal surfaces such as the linings of the gut, nose and mouth, and can activate inflammatory processes as part of the immune system's response to injury or infection …

Moreover, it is becoming apparent that there is a relationship between the gut mycobiome and human cancers, including colorectal and esophageal cancer."

Baking Soda Inhibits Cancer Metastasis

While the featured Nature study did not address the potential use of baking soda (sodium bicarbonate), research¹⁷ published in the journal Cancer Research in 2009 did. According to the abstract:¹⁸

"The external pH of solid tumors is acidic as a consequence of increased metabolism of glucose and poor perfusion. Acid pH has been shown to stimulate tumor cell invasion and metastasis in vitro and in cells before tail vein injection in vivo.

The present study investigates whether inhibition of this tumor acidity will reduce the incidence of in vivo metastases. Here, we show that oral NaHCO3 selectively increased the pH of tumors and reduced the formation of spontaneous metastases in mouse models of metastatic breast cancer.

This treatment regimen was shown to significantly increase the extracellular pH, but not the intracellular pH, of tumors … NaHCO3 therapy also reduced the rate of lymph node involvement, yet did not affect the levels of circulating tumor cells, suggesting that reduced organ metastases were not due to increased intravasation.

In contrast, NaHCO3 therapy significantly reduced the formation of hepatic metastases following intrasplenic injection, suggesting that it did inhibit extravasation and colonization."

The authors point out that the extracellular pH of malignant tumors typically ranges between 6.5 and 6.9, whereas normal tissues have an alkaline pH typically ranging between 7.2 and 7.5.

They also cite previous studies showing solid tumors excrete acid and that the spread of cancer cells is stimulated by acidic conditions in the surrounding tissues. The paper also points out that "acid is a byproduct of glucose metabolism," which ties in with research showing cancer feeds on and is accelerated by a diet high in sugar.

In this experiment, mice injected with cancer cells were given either plain drinking water or water with 200 mmol/L bicarbonate. Calculations suggest the equivalent dose in human terms would be 12.5 grams (0.4 ounces) of bicarbonate per day for an individual weighing 154 pounds or 70 kilos. 

While the bicarbonate therapy had no effect on the rate of growth of the primary tumors, it did significantly reduce the number and size of metastatic tumors in the lungs, intestines and diaphragms, which in turn resulted in improved survival. According to the authors:¹⁹

"In the 30-day experiment, pooled data showed that the bicarbonate-treated mice had a total of 147 metastatic lung lesions, whereas the control group had 326 lung lesions. The average lesion diameters were 4.5 ± 0.12 and 5.2 ± 0.14 mm in the NaHCO3 and control groups, respectively."

Baking Soda Might Not Be as 'Quack' as You Thought

In 2012, Mark "Marty" Pagel Ph.D., associate professor of biomedical engineering at the University of Arizona, was given a $2 million grant to investigate whether drinking baking soda water might help patients with breast cancer.^20,21

Interestingly, while the use of baking soda in the treatment of cancer has been written off as the worst possible type of quackery by skeptics and critics, the University of Arizona Cancer Center has actually been studying its use for nearly two decades. As reported by Cancer Active in 2017:²²

"… in 2003 (Raghunand) they showed how drinking sodium bicarbonate resulted in the alkalization of the area around cancer tumors resulting in a cessation of new metastases²³ …

Further research has shown that sodium bicarbonate had an effect on breast and prostate cancers but had mixed results with other cancers … 2009, Robey et al showed that drinking sodium bicarbonate caused new metastases to stop, whilst injection of Bicarbonate into tumors caused regression of the cancer²⁴ …

Ed: At CANCERactive we have a simple view that is identical to that of American cancer researcher Ralph Moss. This is research every cancer patient should know about. If drinking sodium bicarbonate can restrict cancer metastases then it should be considered as a part of an Integrated Cancer Treatment Programme, especially if it enhances the action of chemotherapy drugs."

While Pagel's team has published a number of studies since then, including one detailing the ways in which extracellular pH can be assessed inside in vivo tumors,^25,26 they've not yet published anything discussing the use of baking soda as an adjunct to breast cancer treatment.

Baking Soda Found to Improve Cancer Treatment

More recently, a study²⁷ published in 2018 concluded the addition of baking soda can improve the effectiveness of conventional cancer treatments. According to these findings, published in the journal Cell, when tissues are acidic, cancer cells can go dormant, thereby allowing them to hide from the treatment. Lead author Chi Dang told WhyY.org:²⁸

"Many of the therapies we have — chemotherapy, targeted therapy — work in cells that are actively functioning and dividing. When you awaken cells from a resting state into an active state, they become more vulnerable to cancer therapy."

This study also found that when pH is low, it disrupts your circadian clock. "Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation," the researchers found.²⁹ Acidification also suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling, and this too plays a role. According to the authors:

"Restoring mTORC1 signaling and the translation it governs rescues clock oscillation. Our findings thus reveal a model in which acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents."

WhyY.org expounds on the findings:³⁰

"'What we've discovered in this study is that there's a very rapid mechanism by which low pH, or acid itself, turns off a key toggle in the cells that controls the cell's ability to make proteins,' Dang said. In other words, it prevents cells from dividing.

As their processes slow down, the cells go into hibernation, making them invisible to cancer treatments. Dang and his team wanted to see if they could reverse that process, and they came up with a simple solution: neutralizing the acid with baking soda.

They tested their theory by adding baking soda to the drinking water of mice that had been grafted with tumors. 'What we found is that the areas that were acidic, now are no longer acidic, and they become more active,' Dang said.

'So this toggle comes back on, so that cells that are at rest can now be reawakened.' That allows chemotherapy and other treatments to find and destroy cancer cells … "

Source: Cell June 28, 2018; 174(1): 72-87

Cancer Prevention and Treatment Options

While I wouldn't say the evidence is anywhere near overwhelming, it's certainly intriguing. Perhaps someday there will be enough evidence to warrant baking soda therapy for the prevention of certain cancers, or as an adjunct to improve the effectiveness of other cancer treatments.

In the meantime, there are many other therapies that have a more solid grounding in science. Among them is the use of nutritional ketosis, which I've written about in:

• "Top Tips to Optimize Your Mitochondrial Health"
• "Why Glucose and Glutamine Restrictions Are Essential in the Treatment of Cancer"
• "Why Cancer Needs To Be Treated as a Metabolic Disease"
• "Metabolically Supported Therapies for the Improvement of Cancer Treatment" and many others

Limiting protein is another strategy that makes a lot of sense, as excessive protein activates mTOR, which plays an important role in cancer development. Other oft-ignored prevention strategies include sun exposure and near-infrared light, which like a ketogenic diet helps structure the water in your cells. This too may be part of the cancer puzzle, according to Dr. Thomas Cowan, author of "Cancer and the New Biology of Water."

Additional guidance when it comes to diagnosis and treatment can also be found in "The Cancer Revolution: A Helpful Program to Reverse and Prevent Cancer," which features Dr. Leigh Erin Connealy, and in my interview with Dr. Nasha Winters, a naturopathic physician who specializes in cancer treatment.

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