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The FDA recently issued an alert warning of significant safety risks associated with cesium chloride (CsCl). CsCl is a mineral salt promoted by naturopathic “doctors” and “integrative” medicine practitioners as an alternative treatment for cancer, despite the lack of evidence of safety and efficacy in treating cancer or any other disease. In another chilling example of the harm so-called “complementary medicine” causes cancer patients, dangers cited by the FDA include death, QT prolongation (“a dangerous abnormality that can impair the heart’s ability to maintain a normal rhythm”), arrhythmias, cardiac arrest, low potassium, seizures, and fainting.

The FDA also announced that it would take regulatory action, such as issuing a warning letter, seizure of product, seeking a court injunction, or criminal prosecution, against any pharmacy or health care practitioner compounding a drug containing cesium chloride. Until the announcement, CsCl was on a list of substances, called “Category 1”, that could be used in compounding without fear of regulatory action, pending further review of the substance by the FDA. The FDA has now moved CsCl to what is known as the “Category 2” list, substances that are effectively banned from use in compounding because of significant safety risks.

The FDA took this action in response to a Citizen Petition filed by Public Citizen in December of 2017, and only then on the heels of a lawsuit filed by Public Citizen last month. The suit chastised the agency for sitting on its hands for two years after the FDA’s own reviewers determined that cesium chloride had not been shown to be effective for “the prevention or treatment of any form of cancer,” presented “serious safety concerns”, and is “not safe for human use”.

Given these grave concerns, how did cesium chloride ever get on the Category 1 list in the first place, enabling healthcare practitioners to use it as a bogus cancer treatment by either compounding it themselves, or having a pharmacy compound it, and injecting it into patients? Because the American Association of Naturopathic Physicians, the Alliance for Natural Health, the Integrative Medicine Consortium, and McGuff Compounding Pharmacy Services, citing a quack cancer treatment “theory” and cherry-picked evidence of safety, nominated it for Category 1. The FDA decided that this was “sufficient supporting information” for the FDA to refrain from taking any action against its use pending further review.

Before we return to this little rogues’ gallery and their successful efforts to fend off the FDA from banning their bogus cancer treatment, it’s helpful to understand a bit about compounding and how it is regulated.

Compounding 101

A licensed pharmacist or physician can legally combine ingredients to create a medication tailored to the needs of an individual patient. This is called “compounding.” Compounded drug products, when prescribed and produced appropriately, can, according to the FDA, serve an important role for patients whose clinical needs cannot be met by an FDA-approved drug product. However, precisely because they are not FDA-approved, compounded drugs have not undergone premarket review for safety, effectiveness, and quality, nor are pharmacists and healthcare practitioners who engage in traditional compounding required to comply with current good manufacturing practices.

In 2012, an outbreak of fungal meningitis due to contaminated injectable drug products shipped by a compounding pharmacy to patients and health care practitioners across the country resulted in 60 deaths and 750 cases of infection. In response, both Congress and the FDA took steps to clean up the compounding industry’s act.

As part of this effort, the FDA announced it would develop a list of approved substances (called the “503A list,” or “503A bulks list,” named after the section in the FD&C Act authorizing it) that could be legally used in compounding and that the agency would take nominations for inclusion on that list. (Substances that are already the subject of an USP or National Formulary monograph or are a component of an FDA-approved drug can be used in compounding without further review.) However, pending a more extensive review for inclusion on the FDA’s final approved 503A list, the agency divided nominated substances into three categories:

Category 1: substances nominated with sufficient supporting information to permit FDA to evaluate them.

Category 2: substances nominated with sufficient information for evaluation, but which pose “significant safety risks related to [their] use in compounding.”

Category 3: substances nominated without sufficient supporting information.

The FDA said it would forego any regulatory action against Category 1 substances, essentially allowing their use unless and until they fail to make the FDA’s final cut. Category 2 and 3 substances cannot currently be used in compounding, although they are still technically eligible for the 503A list.

Naturally, if you will, the FDA’s action was met with some consternation among naturopaths, who like to whip up concoctions of unproven remedies and inject their patients with them, sometimes with disastrous results. The turmeric injection that killed Jade Erick was a compounded remedy for eczema injected by her California-licensed naturopathic doctor.

In 2014, in response to the FDA’s new compounding regulatory scheme, the American Association of Naturopathic Physicians nominated favorites like Artemesia, Boswellia, calcium EDTA, Echinacea, DHEA, DMPS, DMSA, co-enzyme Q10, and germanium, along with cesium chloride, for FDA-approved use in compounding. It also wanted to dump the entire Homeopathic Pharmacopoeia of the United States and the USP Dietary Supplements Compendium on the approved list, even though the law specifically limits compendia to the USP or National Formulary.

The AANP complained bitterly that the FDA was requiring evidence – imagine that! – which busy naturopathic clinicians could not be bothered to supply, a tacit admission that naturopaths were using these substances without sufficient proof of safety and efficacy. The AANP also pontificated as to how the conventional medical system had failed the typical naturopathic patient (whose “immune systems are often depleted”), but, because naturopaths

are trained to find the underlying cause of a patient’s condition rather than focusing solely on symptomatic treatment, [they expertly prescribe and administer] safely compounded medications – including nutritional, herbal, and homeopathic remedies [which] prove efficacious to meet their needs every day in doctors’ offices across the country.

So, these substances are efficacious, according to the AANP, they just couldn’t tell the FDA how they came to that conclusion.

Germanium ended up on the FDA’s Category 2 list. Other naturopathic favorites are on the list of substances nominated without adequate support (Category 3) and therefore cannot legally be used in compounding. These include Coenzyme Q10, ginger root powder, ginkgo biloba standardized extract, nux vomica extract, and colloidal silver.

Cesium chloride

With that background, let’s turn to cesium chloride and its appearance on the FDA’s Category 1 list. As noted, CsCl was nominated by the AANP, joined in its efforts by representatives from the fringes of medicine: A group calling itself the “Integrative Medicine Consortium,” which includes a couple of Pseudomedical Pseudoprofessional Organizations that have appeared on SBM ’s radar before – the American Academy of Environmental Medicine and the American College for the Advancement in Medicine – as well as the AANP and the International College of Integrative Medicine. The Integrative Medicine Consortium was also speaking on behalf of the Academy of Integrative Health and Medicine, whose mostly online “fellowship” program allows one to sit for the American Board of Integrative Medicine exam and become board-certified in the dubious specialty known as “integrative medicine“. The Alliance for Natural Health, a faux “grassroots” organization that advocates for the protection of quackery and against vaccination and fluoridation, and McGuff Compounding Pharmacy, whose self-interest in the subject should be obvious, rounded out the list of organizations nominating CsCl.

Supporters wanted to be able to compound up to 500 mg/mL in a multiple dose vial for injection for use in the treatment of cancer. (To access documents in support of their nomination, see Tab A, at p. 38, of this FDA Briefing Document.) In support of their nomination of CsCl as an effective treatment for cancer, they claimed:

Cesium chloride 500 mg/ml has been helpful and useful in combination with other natural substances in treating individuals with numerous types of cancers, by a presumed alkalinizing effect. Cancer has been found to thrive in a low-pH environment, and to be hindered in a high pH environment. It has been known for decades that a thriving cancer cell produces an acidic micro-environment, and a weak cancer cell does not. (Jahde and Rajewsky, “Tumorselective modification of cellular microenvironment in vivo: effect of glucose infusion on the pH in normal and malignant rat tissues.” Cancer Research. 1982 Apr 42(4): 1505-12). This is known to be due to cancer’s product, lactic acid. However, it is also known that acidic fluid holds less oxygen than alkaline fluid. Thus the acidic, deoxygenated water in the cancer microenvironment is conducive to anaerobic metabolism, which is the default metabolism of cancer cells. Thus an alkaline agent that can be delivered to that intracellular and extracellular microenvironment indirectly has a selectively suppressive effect on cancer cells.

Wow! It’s pH woo déjà vu: “Dr.” Robert Young’s pH Miracle Living and the alkaline diet, all rolled into one and delivered via injection. Or, as the Memorial Sloan Kettering Cancer Center put it, more politely,

Supporters claim that cesium neutralizes the toxic material produced by tumor cells and prevents them from dividing. There is no scientific evidence to support these claims.

And this, from the nominators of CsCl:

Cesium chloride has a history of use among various professions in integrative medicine in the U.S., and many hundreds of patients have been helped by cesium chloride in their fight against cancer.

Of course, “a history of use among various professions in integrative medicine” is meaningless as far as evidence of safety and effectiveness is concerned. Homeopathy, which is demonstrably worthless as a treatment for anything, also has “a history of use among various professions in integrative medicine.” There is absolutely no reliable evidence that “many hundreds of patients have been helped” and none is cited.

Finally, these outrageous statements,

No existing drug matches the advantages of cesium chloride against cancer: the evident ability to enter the cancer cell together with the pH rise, as well as the high remission rate and lack of observed side effects at therapeutic dose. Generally safe and non-toxic substances such as cesium chloride are a viable alternative . . . No approved drug product exists that addresses the condition of cancer adequately. Conventional cytotoxic chemotherapy drugs are generally very poorly tolerated, having life threatening side effects, and a high mortality rate. With a realistic assessment of their odds, there are patients who choose to avoid chemotherapy, and have opted instead for alternatives, including cesium chloride.

As for safety, they ignored published animal studies and human safety data and minimized the few adverse events (e.g., “anecdotes on the internet”) they did recognize in their nomination.

For undisclosed reasons, the FDA found that CsCl was nominated “with sufficient information for evaluation” and placed in Category 1, pending further review.

Subsequently, in May, 2016, FDA’s expert reviewers recommended against adding cesium chloride to the 503A list substances approved for use in compounding, in part because of “serious safety concerns related to [its] use.” The reviewers cited animal studies showing CsCl caused ventricular tachycardia and other heart risks, decreased motor activity, autonomic disturbance, diarrhea, and developmental issues in offspring. Thus, “the toxicity profile of cesium chloride in animal studies weighs against its inclusion on the 503A list.” (Their report starts at p. 60 of the FDA Briefing Document.)

As for human risks, the reviewers concluded:

The limited information available about the safety of cesium chloride gives rise to significant concern about its use in compounding. The evidence of cesium chloride causing hypokalemia [low potassium levels], seizures, QT prolongation, and cardiac arrhythmias is particularly concerning.

Possibly as a rejoinder to the AANP’s swipe at chemotherapy drugs, the reviewers noted:

There are numerous FDA-approved agents that have demonstrated safety and efficacy for the treatment of patients with various cancers.

Speaking of efficacy,

Cesium chloride has not been shown to be efficacious for the prevention or treatment of any form of cancer. . . evidence of clinical benefit from cesium in human cancer is limited to one case series published in 1984 by Sartori [cited by the AANP et al.]. That case series has major flaws including its uncontrolled nature, retrospective design and probable case selection bias. Therefore, the results cannot be considered reliable.

The reviewers also noted:

In addition, use of cesium chloride may cause a patient to delay the use of treatments that have been found to be safe and effective for treating cancer.

Thus, the reviewers concluded that cesium chloride is not a suitable substance for the 503A list.

In June, 2016, the FDA’s Pharmacy Compounding Advisory Committee considered the nomination of CsCl to the 503A list and recommended, based on the reviewers’ concerns as well as their own, by a unanimous vote of 11-0, that the FDA should not place CsCL on the list. (Transcript here, see p. 75.) As one committee member, a pharmacology professor, said:

So even if you state the point that the efficacy is not demonstrated, it has a major safety issue, and safe doses have not been established, forget the fact that we know nothing about effective doses.

The Committee’s recommendation awaits final FDA action.

The only problem was, even in light of the FDA’s own damning review, CsCl remained on the Category 1 list, meaning nothing was stopping naturopathic doctors and integrative physicians from plugging their patients with CsCl. This prompted Public Citizen to file its Citizen Petition in December of last year, asking the FDA (1) to immediately add cesium chloride to the Category 2 list of substances that raise significant safety risks, thereby effectively prohibiting it use for the time being, and (2) to promulgate a rule excluding CsCl from the 503A list, thereby permanently prohibiting its use.

The FDA did nothing until suit was filed against it in federal district court by Public Citizen in July, seeking to compel the agency to act on its Petition. Within hours, the FDA granted the Petition in part, issued its alert warning “of significant safety risks associated with cesium chloride” and moved CsCl to Category 2. In addition to the data discussed in the Pharmacy Compounding Advisory Committee’s 2016 recommendation, the FDA conducted a comprehensive review and found three more published cases of adverse events related to cesium chloride describing “life-threatening neurologic and cardiac toxicity”. The agency declined, however, to promulgate a rule excluding CsCl from the 503A list, although it said it will make a final determination at some point.

On the same day suit was filed, Public Citizen filed another Citizen Petition asking the FDA to immediately remove dietary supplements containing CsCl from the market. The Petition is based on the same safety risks and lack of efficacy recognized by the FDA and the promotion of CsCl-containing dietary supplements in the treatment of cancer. The FDA has yet to respond.

It’s hard to imagine that cesium chloride will make it onto the final 503A list of substances approved for compounding in the treatment of cancer given the Pharmacy Compounding Advisory Committee’s recommendation. For now, its use in compounding risks regulatory action, including a criminal complaint, by the FDA. Of course, unless the FDA acts to ban it as a dietary supplement ingredient as well, it will remain available and its promotion as a quack cancer treatment will continue.

FDA inaction aside, what this whole episode should demonstrate to everyone (including state legislators and medical boards) is the absolute disregard for evidence of safety and effectiveness on the part of naturopathic “doctors” and integrative physicians and their “professional” organizations. Not only did they cherry-pick the published literature on safety, which alone should disqualify cesium chloride’s use, they credulously promoted a highly dubious mechanism of action and questionable case reports as evidence of efficacy, all the while complaining that they had to provide the FDA with evidence in the first place. I realize that the naturopaths may not have known better, given their substandard education and training. As for the integrative physicians, I’ll chalk it up to their “specialty’s” penchant for mendacity and colluding (if I may use that word) with naturopathic “oncologists“.