I’ve been blogging for well over 14 years now. So you’d think (or at least I do much of the time) that over all those years I’ve covered pretty much every form of dubious cancer treatment there is. Sadly, every so often reality disabuses me of this notion. Over the weekend, I was perusing what I like to call my Folder of Woo, basically a folder of links to potential blogging topics, when I noticed something called the NORI Protocol. I forgot when I had come across it the first time, but obviously I had meant to write about it sometime or another. After all, it was in my Folder of Woo! Given how much I write, though, I couldn’t remember if I had ever covered it. A quick search of both my blogs disabused me of this notion. There was one hit here, but only because someone mentioned the NORI Protocol in the comments. Damn, I thought. How could I have failed to write about this one, given that it shows up all over the place?

So it’s time to take a more in-depth look at the NORI Protocol.

NORI Protocol: Red flags for quackery galore

So what is the NORI Protocol? Basically, it’s a high-fruit diet coupled with selenium supplementation It helps to know what “NORI” stands for, and it stands for the Nutritional Oncology Research Institute, home of the NORI Protocol. If you visit the website, the main page of NORI regales visitors with this description of the “institute”:

NORI is an independent research organization that has developed non-conventional methods for cancer treatment that do not rely on toxic drugs, surgery, or radiation. Cancer patients who choose to avoid conventional therapies or who have exhausted all other options may wish to explore this revolutionary and unique approach to cancer treatment and management offered exclusively by NORI. The NORI program is designed to be the most cost-effective alternative cancer treatment available. NORI represents the future in treating cancer in a safely and holistically, in the most health-promoting, effective, and scientifically sound manner possible.

So. Many. Red. Flags. And all of them right on the entry page. There’s the quack trope about cancer treatment that “does not rely on toxid drugs, surgery, or radiation.” There’s the statement about using this treatment instead of conventional therapies. There’s the claim that NORI is the “future of treating cancer in a safely and holistically, in the most health-promoting, effective, and scientifically sound manner possible,” whatever that means.

Then there’s this:

NORI is an organization focused on research and development of nutritionally based, nontoxic, drug-free cancer treatment methods. NORI has created a unique treatment protocol that may be utilized along with conventional therapies, or utilized alone for the treatment of nearly any form and stage of cancer. The NORI protocol is based on a specialized plant-based diet as a foundation while administering safe and effective natural compounds that selectively kill cancer cells. The NORI protocol has been proven effective for a wide array of cancers at all stages.

I love it when alternative medicine sellers claim that their treatment has been “proven effective for a wide array of cancers at all stages.” Whenever I see that, I ask: Where’s the beef? Where’s the science? Where are the randomized controlled clinical trials? As you will soon see, there is, to put it kindly, a paucity of these things supporting the NORI Protocol, although if you look at NORI’s page on its protocol, you’ll see lots of cherry picked studies, most in vitro, with only a phase I and phase II trial, the latter of which was not randomized. (Phase I trials by definition are not randomized.) You’ll also see lots of testimonials. I’ll discuss these later, with one exception, this testimonial from Amy H. in Los Angeles:

I was diagnosed with DCIS, stage 0, breast cancer in January of 2014. A surgeon wanted to give me a mastectomy and flap, and felt no other way would ensure my survival, or an attractive appearance. Shell shocked, I chose to treat it with a Naturopath, who guided me to healthier living on all levels. While I felt the results of that, I had developed a growth. I was told that it was a biopsy scar, but in late 2016 it grew significantly. I suspected it was not scar but tumor and started researching more about cancer, which made me doubt the effectiveness of what I was doing to heal. Sure enough, I went for an ultrasound and was told I had stage 4 breast cancer. Through a series of events I was told about the NORI Protocol and put into contact with Mark Simon. He presented what sounded to me like a very clear understanding of cancer and how to treat it. I had been facing unavailable doctors and practitioners, and he was available and supportive, and put me on a path that honored my instincts, calmed my fears, and made me feel like an active participant in my healing. While new to the protocol, I feel hopeful and aptly guided.

This testimonial is horrifying on so many levels, and I can’t believe that any hawker of an alternative dietary cure for cancer would include a testimonial like this. Those of you who’ve read this blog for a long time know that I’ve often questioned whether we overdiagnose and overtreat DCIS. However, that doesn’t mean that DCIS is benign, only that, because we don’t know which DCIS lesions will go on to turn into invasive cancer, we feel obligated to treat them all. However, as a breast surgeon, I can read between the lines here. If the surgeon seeing Amy H. recommended a mastectomy, that means that the DCIS took up so much of the breast that breast conserving surgery was not possible. That’s high risk DCIS. It’s therefore not surprising that Amy’s DCIS progressed to invasive cancer. (It might well already have been invasive at the time of diagnosis.) As for having stage 4 cancer, it’s not clear to me how that could be diagnosed with just an ultrasound, unless maybe she had metastases in her liver that could be evaluated by ultrasound. Be that as it may, this testimonial shows a woman with high risk DCIS refusing standard-of-care treatment, seeing her cancer progress under the care of a naturopathic quack (even watching a mass grow and attributing it to scar tissue from her previous biopsy!), and then choosing another dubious treatment, with no outcome other than “hope” and being “aptly” guided being listed.

Time to discuss the NORI approach in more detail. First, let’s look at its creator, Mark Simon. Then we’ll look at the protocol itself, which involves a high fruit diet to “starve” cancer cells of the amino acid methionine, which, it is claims, sensitizes cells to selenium. Of course, it can’t be just any selenium. It has to be a special form of selenium. Nothing else will work.

Mark Simon: “Nutritional oncology expert”?

Perhaps the best introduction I could find to Mark Simon is this 2015 interview with Chris Wark of Chris Beat Cancer fame. As I’ve described, Mr. Wark has the typical anecdote in which he misattributes his cure to the wrong treatment. Basically, he had stage 3 colon cancer, underwent surgery, but refused the recommended standard-of-care chemotherapy afterward. As is all too often the case, he sought out all manner of quackery, and when he did well he attributed his good outcome to the quackery, not to the surgery that removed his cancer. Now he runs a website and an alternative cancer cure Internet business in which he sells books and “coaching,” and uses all manner of dubious testimonials to hawk his wares. It’s a perfect match.

We learn from this interview that Mark Simon that he had been interested in alternative medicine for a long time, but details on his actual professional background are maddeningly vague. We’re told that he has a background in neuroscience and biomedical engineering, which is nice, but finding out what that background actually is wasn’t too easy. It took a fair amount of Googling to lead me to pages like this one, where I learned that Simon’s credentials include being a “health coach” and having a Clinical Nutrition Certificate from Natural Healing Institute. His LinkedIn profile only shows his positions at NORI dating back to 2011, when he founded NORI. Elsewhere, on Facebook Gene Fuss posted on The Truth About Cancer page that Simon “is trained in Neuroscience and Biomedical Engineering and nutrition, and has been a vegan for 32 years,” while attributing to him “DEEP knowledge about the biology of cancer tumors, more so than anybody I have encountered to date.”

If the claims made in the video above, and this video below about the NORI Protocol are any indication, I would be willing to contest the claim that Mark Simon has anything resembling “deep knowledge” about anything having to do with cancer or nutrition.

It doesn’t take too much knowledge to realize that the scientific claims in both videos and the NORI Protocol website are, at best, rather fishy and, at worst, downright quacky. As for Simon’s background, if he’s such an expert in neuroscience and biomedical engineering, why doesn’t he trumpet that background by including his degrees and what he did? He clearly doesn’t have an MD, PhD, or even an ND (the naturopath’s degree that I like to call “Not-a-Doctor”), and you know that if he had any of those degrees he’d include them, in his bio. Instead, he’s maddeningly vague. My guess is that he got an undergraduate or masters degree in some science-related field and/or worked as a technician in a neuroscience and/or biomedical engineering lab somewhere. Simon can, of course, prove me wrong by listing his degrees and his pre-2011 employment history somewhere prominent.

On to Simon’s protocol!

NORI Protocol: Methionine deprivation and selenium cure cancer!

In both videos above, we learn that Mark Simon was inspired by the work of someone named Dr. Daniel Epner, a faculty member at Baylor College of Medicine, who published an article on methionine deprivation in 2001. It was this article that inspired Mark Simon to look into methionine restriction as a treatment for cancer. A PubMed search reveals 36 articles from Daniel E. Epner, 41 if you leave out his middle initial. The last article Dr. Epner wrote about methionine and cancer dates back to 2003. It’s a study that found that methionine restriction targets synthesis of thymidylate synthase, an enzyme that plays a crucial role in the early stages of DNA biosynthesis. His article is interesting, because it summarizes the studies in cell culture and animals showing that methionine restriction can have antitumor effects in a number of cancer cell lines and animal models. Of course, we all know how hard it is to translate such findings to humans, and Dr. Epner notes that a phase I trial had been carried out to show that methionine restriction plus chemotherapy was achievable and safe.

Interestingly, Dr. Epner does not practice medical oncology any more. He’s moved from Baylor to M.D. Anderson Cancer Center, whose website states:

Dr. Epner is a palliative care physician at MD Anderson Cancer Center who practiced medical oncology for several years before moving to the Department of Palliative Care in 2012. He began his faculty career at Baylor College of Medicine as principal investigator of a basic science lab, but he now focuses on psychosocial aspects of oncology. His primary academic interest is communication skills training for medical oncology fellows, palliative care fellows, and a variety of other providers.

Interesting career trajectory.

So, basically, with Mark Simon, we appear to have an overenthusiastic evangelist glomming on to one interesting finding with respect to cancer cells and running straight off the cliff with it, as you can see by the claims made by Simon for his NORI Protocol. Basically, these claims involve massive oversimplifications of the science and as yet unproven (and therefore unjustified) extrapolation from cell culture and animal studies to humans, with none of the valid research being done by Simon himself, just cherrypicked from the literature and based on nonsense like this:

There are two types of DNA in human cells, nuclear and mitochondrial. Cancer appears to be the result of damage to mitochondrial DNA while nuclear DNA damage is “after the fact”. Mitochondrial damage prevents the normal process called apoptosis or natural programmed cell death which shuts down the cell so that it does not continue to divide without end. Cancer is the same condition regardless of the site or organ of origin. Cancer is not 200 different diseases. It is a process defined by common metabolic abnormalities within malignant cells that can be effectively exploited without toxic drugs. It is generally the side effects of conventional therapies that take a cancer patient’s life, not cancer itself.

Whenever you see someone say that it is the toxicities of conventional therapies that kill most cancer patients, it’s 99.99% likely (at least) that you’re dealing with a quack. Also, yes, there is a metabolic component to cancer. Cancer cells, in addition to having their genomes messed up badly, also have messed up metabolic pathways. (I do so love using scientific terms.) That does not mean that cancer is all one disease, nor does it mean that the mutations driving cancer are unimportant.

Then the NORI website claims:

The key difference between the NORI approach and other nutritionally based cancer treatments is that NORI attempts to limit the availability of essential nutrients necessary to cancer cell survival while supplying adequate nutrients to healthy cells. The NORI approach to cancer nutrition is not designed to build or enhance the immune system. Cancer cells, like normal cells, have built-in means of defense against immune system attack, what separates conventional from most alternative cancer therapies is selectivity, meaning that conventional treatments destroy healthy cells while alternative therapies attempt to spare them.

Well, that’s a new one, an alternative therapy that doesn’t claim to “boost the immune system”!

The idea behind the NORI Protocol is this. Because many cancer cells are sensitive to methionine restriction, first you restrict methionine using a fruit-heavy diet. (Fruit doesn’t contain much methionine.) The length of time for this diet is “individualized,” of course. Also of course, he declines to discuss what criteria are used to determine the length of time recommended for each patient, just this:

Methionine restriction is individualized for each patient according to weight, nutritional status, disease progression and past dietary preferences. A methionine restricted diet may be continuous or cycled on and off depending on individual circumstances. Methionine restriction involves the elimination of many foods and a focus on mostly fruits. The natural sugars in fruits will not feed cancer cells or cause tumors to grow. It is a common misconception that fruit equals sugar and that fruits raise blood sugar. Fruit can be a problem if there is a high fat intake (greater than 10% of total caloric intake) which will cause insulin resistance.

That’s nice. Give me the protocol and the evidence base behind its specifics.

I’m particularly amused at how Simon gets past the “sugar feeds cancer” woo by claiming that the “natural” sugars in fruits don’t feed cancer unless you also eat a lot of fat and develop insulin resistance; so, yes, his NORI Protocol involves low fat diets as well. It’s also rather interesting that Simon focuses on fruits so much, given that vegetables are also low in methionine. Also problematic is the observation that normal cells need methionine too, as it’s an essential amino acid that the body can’t synthesize, which means that methionine can’t be eliminated from the diet entirely.

The next step after the methionine restriction, the patient can then eat a high methionine diet. The idea is that the methionine restriction will cause the cancer cells to stop growing, to arrest their cell cycle, and then adding methionine back, which supposedly causes them, to grow again and undergo apoptosis (programmed cell death). Layered on to this core idea is the claim that methionine restriction sensitizes the cancer cells to selenium, as well as the claim that the digestive enzymes in fruits also combat cancer.

If you look at the full NORI Protocol list of “chemotherapeutic agents,” you’ll find sodium selenite, selenomethionine, vitamin K3, shikonin (derived from the bark of the Gromwell root), vitamin E succinate, pine bark and grape seed extract, green tea extract, and a number of others. Basically, if you listen to Simon in his video above and read all the scientific claims on the NORI protocol website, what you’ll hear and see is what I like to refer to as “woo babble,” which is basically like Star Trek technobabble, only with woo.

But is there any evidence that methionine restriction combats cancer in actual humans? The answer is: Not a lot. If you look at recent review articles (e.g., this one, this one, and this one) about methionine restriction and cancer, you’ll find that, 18 years later, scientists are still working on it, and there is a huge paucity of clinical data supporting methionine restriction as a treatment for cancer. You’ll also learn that there’s evidence that methionine restriction could extend lifespan. You’ll also see authors recommending clinical trials, which appear not to have been done yet. You’ll also learn that there is a compound, Methioninase, which breaks down methionine and can be used to restrict methionine. There’s evidence from patient-derived xenografts (tumors from humans clinical specimens grown in mice), but again little in the way of clinical evidence.

To Simon, however, the reason is obvious:

Why are alternative treatments like the NORI protocol not practiced by oncologists and researched through clinical trials? The answer is simple economics and excessive control by the pharmaceutical industry. Money and profits has become the primary driver in medical science in general. Medical science must serve all of us rather than the bottom line of multi-national corporations. NORI is a grassroots alternative cancer research institute that is carving out a path towards medical sanity within oncology.

It couldn’t possibly be because doing dietary studies of this sort of treatment is very difficult, could it? Oh, no! It has to be the big pharma conspiracy. So that’s why NORI sells a line of nutraceuticals, including—of course!—CBD oil. Not surprisingly, the protocol itself contains a disclaimer:

All statements regarding NORI nutraceuticals have not been evaluated by the United States Food and Drug Administration. NORI nutraceuticals are not intended to diagnose, treat, cure or prevent any disease. NORI nutraceuticals are provided as a component of a nutritional support program and are not intended as a substitute for conventional medical care.

Yep, it’s a quack Miranda warning! As is the case with so much cancer quackery, Simon has taken interesting scientific observations that aren’t ready for prime time yet treating patients and extrapolated mightily with them.

Testimonials galore!

So if all the science Mark Simon has is cherry picked science, does he have anything else? Like all good alternative cancer treatment advocates, he has testimonials! The most famous NORI protocol testimonial comes from Candice-Marie Fox, who claims to have cured her thyroid cancer using the NORI protocol:

We learn that Ms. Fox was diagnosed with thyroid cancer a few days before her 28th birthday in 2011. She claims it was stage III. Doing a bit of Googling reveals several things. First, she had papillary thyroid cancer, which is the most common and most treatable form of thyroid cancer. Indeed, there is controversy over whether papillary thyroid cancer always requires treatment given how much of it is overdiagnosed by ultrasound. (I doubt that applies here, because Ms. Fox states that she had a lump in her neck.) Also, there is no such thing as stage III papillary thyroid cancer in a 28 year old. If you look at the staging for this cancer, the highest stage a 28 year old can be is stage II, even with distant metastases. The survival rates are very high as well, with near 100% 5-year survival for localized and regional disease and 78% for even distant disease.

Also, Ms. Fox underwent standard-of-care surgery, a total thyroidectomy and what sounds like a central neck lymph node dissection, for the tumor. So at around the two minute mark, when she claimed that the cancer came back and had metastasized to her lungs, lymph nodes of the neck, and elsewhere. According to her, the doctors told her to come back in 6-9 months for more radiation and, if that doesn’t work, chemotherapy. That, too, caused my skeptical antennae to start twitching, because although radioactive iodine is used for metastatic papillary thyroid cancer, chemotherapy is not.

I’m not the only one who noticed holes in Ms. Fox’s story. Auma, a self-described “evil troll, Big Pharma employee and government spy,” noticed a lot of issues:

Based on these articles and her own writing on Facebook, there are several impossible or misleading claims about her diagnosis and “natural cure”:

Having cancer spread to liver . After those pesky cancer surviving trolls started asking her questions on Facebook, she admitted liver tumors referenced in Daily Mail were benign. Being stage IV . A few days back she claimed on FB that she had never called herself stage IV. How did the journalists get the idea of stage IV (in one article – grade IV) cancer then? Also, papillary thyroid cancer in people younger than 45 can only be stage I or II and 5 year survival is almost 100%. Mark Simon being an oncologist instead of a quack nutritionist without a medical degree . This she also later admitted on FB and Daily Mail actually made a correction. Rejecting chemo – in different sources Candice mentions having rejected radioactive therapy or chemotherapy. This sounds strange, because chemotherapy usually is not the first line of treatment for papillary thyroid cancer, but she makes it sound like she was certainly offered to do chemo and absolutely rejected it. The biggest claim of them all is her terminal diagnosis and being given 5 years to live . I am not sure if she actually believes that herself or exaggerated her claims to get attention and embellish her money-earning cancer story. This is what I want to explore the most. Please keep in mind that I am not a doctor, just a patient myself who remembers the process of treatment well. If a medical specialist reads this, please add your perspective. Also, because I am not from an English speaking country, I constantly call thyroglobulin TGB, because that is how we abbreviate it. In English documentation it is usually abbreviated as Tg.

Auma also took a bunch of screenshots of Ms. Fox’s Facebook page contemporaneous with her actual treatments that show she left out a lot of stuff. It’s worth reading both posts, as long as they are, because of the level of detail. The bottom line is that Ms. Fox was cured by conventional therapy, not the NORI Protocol, but attributes her “cure” to her dietary intervention.

But what about the other testimonials? Most of them are similar in that it’s clear that the conventional treatment was what cured the cancer. There are patients with colorectal cancer who underwent surgery but turned down chemotherapy (like Chris Wark). There’s someone with recurrent Hodgkin’s lymphoma who underwent chemotherapy and the NORI protocol but attributes the good outcome to NORI. There are a couple of prostate cancer testimonials that aren’t particularly convincing because of the highly variable and often indolent courses that prostate cancer can take. There was another one of metastatic pancreatic cance that regressed with the NORI protocol—and, of course, chemotherapy. Particularly distressing is that the the man and his wife totally attribute the man’s good outcome to the NORI protocol. I wonder if they’ll blame it when the pancreatic cancer recurs, which it almost certainly will if it truly is pancreatic adenocarcinoma.

NORI Protocol: An idea oversold

If there’s one common theme in cancer quackery, it’s the co-optation of preclinical science (i.e., science that hasn’t been tested in clinical trials yet) or inadequately tested clinical science, and running with it. In other words, this sort of quackery involves taking the gray areas of science and unjustifiably eliminating the gray in order to sell a treatment. Will the NORI protocol hurt cancer patients? Probably not, but it’s hard to tell. Nutritional manipulations are not without risk. Will it treat their cancer? Based on my reading of the literature, who knows? It’s unproven, and the track record of translating cell culture and rodent studies into treatments is littered with the wreckage of promising-sounding ideas.

In this case, the gray area is methionine restriction as a treatment for cancer. It’s a dietary intervention that shows promise based on preclinical studies in cell culture and in rodent models but as yet has not been convincingly demonstrated to work in humans. Might methionine restriction have a role in treating human cancer? Possibly. One thing I can say for sure, though, is that, if methionine restriction is ever validated in randomized controlled clinical trials as an approach to improving the efficacy of chemotherapy, the science-derived protocol will almost certainly look little like what Mark Simon’s quackery-derived NORI protocol. Simon has both oversimplified the science (e.g., his claim that cancer is a single metabolic disease) while adding unnecessary complexity to the protocol (e.g., selenium and all the additional supplements, the mystical “individualization” of methionine restriction) to produce a protocol that is being massively oversold to desperate patients with cancer.

No wonder naturopaths love it so much.