On The Case: Methionine & Cancer Part III

Before launching into more shocking truths about methionine, I want to share a story told by Chef Ryan Callahan in the August issue of Conquer magazine. Chef Ryan’s best friend, Tommy, was diagnosed with stage 4 liver cancer at 21 years old and died just 2 months later. Chef Ryan writes that Tommy had a 4th-degree black belt in Taekwondo and a healthy lifestyle overall. However, once Tommy began an aggressive course of chemo, he could only manage to eat salty junk foods and cookies.

Chef Ryan believes that if he’d understood and been able to teach Tommy’s family cooking techniques for countering chemo’s eating-related side effects, Tommy would not have died so soon.

Tommy’s story does make me curious about the role of Registered Dietitians during the course of his treatment – an RD should have assessed Tommy’s nutritional status and counseled him and his family about all the available options. But whatever the case may have been, this tragic story highlights the critical yet all-too-often ignored component of fighting cancer:

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Nowadays, patients and their families do have great resources. Chef Ryan was inspired to write a cookbook and offers tips and how-to videos. A reader also recently reminded me about Rebecca Katz,

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Rebecca Katz wearing a zucchini noodle necklace

whose cancer-fighting food workshop I attended years ago as a dietetic grad student in Seattle. Rebecca has authored several cookbooks and released the Cancer Fighting Kitchen online course last month.

I’ve resolved to delve deeper into the material these two have developed as I continue to work on my cooking skills. Speaking of which, this weekend my fiance and I collaborated on making hamburger patties. We got a pound of grass-fed ground beef and mixed it with 1 pasture-raised egg, 2 cloves of minced garlic and a ½ teaspoon of turmeric along with salt & pepper.

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My fiance’s turmeric burger – I had mine sans bun alongside veggies

This was enough for three patties, and I had the leftovers for my Sunday lunch. We both enjoyed the beef but couldn’t really taste the turmeric, which was fine by my fiance. Still, the next time we make burgers, I might use a whole teaspoon of turmeric. If my fiance objects, I can up the seasoning on my portion only.

I’m leading this post with tales of my kitchen experiments in order to emphasize that the scientific literature on methionine restriction has not swayed me to cut out meat or otherwise alter my diet. As I’ve concluded in my previous post, far too much is still uncertain and the changes required would be maddeningly complicated at best – dangerous at worst.

Even if I could follow an ultra-low-methionine diet without jeopardizing my physical and mental health, the anticancer effect would not be assured. After all, researchers documented numerous cancer cell lines that were only slightly or not at all dependent on methionine. As far back as 16 years ago, an article in Cancer Research called for the development of a genetic test to identify methionine-dependent tumors in order to incorporate that information into efficacy studies for methionine-lowering treatments.

So where was this genetic test? Where were those efficacy clinical trials? Why did this promising research seemingly stall after Dr. Epner et al. published findings from a Phase I trial in 2002?

Google told me that Daniel Epner, M.D., was a Professor at The University of Texas MD bitmoji1174324671Anderson Cancer Center in Houston, TX. I reached out to Dr. Epner via email  to ask him why he left the field of methionine restriction research. To my surprise, he actually responded:

Marina,

I am sorry to learn about your cancer diagnosis. I wish you the very best in your treatment.

I led a basic science program for about 10 years at the beginning of my career during which I focused on abnormal nutrient metabolism as a potential target for cancer treatment. One of my main interests was methionine metabolism, since animal studies showed that dietary and or enzymatic methionine deprivation had anti-tumor activity. Methionine plays a key role in methylation of nucleic acids and proteins and is a key precursor for polyamines, both highly relevant to tumor growth.

We had support from Abbott laboratories for the phase I trial you mentioned in your email. In addition, Abbot supported a second clinical trial on which I collaborated with an investigator at MD Anderson (when I was still on the faculty at Baylor College of Medicine, before I moved to MD Anderson 8 years ago). That trial involved combining the experimental diet with chemotherapy for patients with primary brain tumors. However, my collaborator was unable to enroll a sufficient number of patients on that trial for reasons that were never clear to me. Perhaps his colleagues did not have faith in the strategy or perhaps patients were not enthusiastic about adhering to a strict dietary regime. Over time, Abbott became less enthusiastic about supporting the methionine restriction work since they did not think dietary methionine restriction would be commercially viable. 

Coincidentally at around that time, my career interests naturally evolved. I became very interested in psychosocial aspects of oncology, and I came to appreciate the power of relationships between doctors and their patients and families. This career evolution led to my interest and involvement in teaching communication skills and writing about relational aspects of oncology. Over time, my colleagues and I at MD Anderson decided I should transition to the department of Palliative Medicine, where I now reside, after having practiced medical oncology for about 20 years.  My main academic focus is now communication skills training and narrative medicine.   I still think methionine restriction is potentially viable as cancer treatment, but I have not actually worked in the field for many years. I know that Robert Hoffman PhD at Anticancer Inc. in San Diego has developed methioninase, the methionine degrading enzyme, as cancer treatment, but I do not know where that work stands now. You may want to contact him for an update and read his recent publications.

I still believe methionine deprivation is a very promising strategy from the purely scientific standpoint if you put aside marketing and other considerations. Nonetheless, I would strongly advise against anyone with cancer pursuing a methionine restricted diet outside of a clinical trial approved by an institutional IRB, just as I would advise against anyone receiving any form of experimental therapy outside of a clinical trial.

My thoughts and prayers are with you as you battle cancer.  I hope this information is helpful.

Best Regards,
Daniel E. Epner, MD, FACP

I appreciated his thoughtful reply. He confirmed my suspicion that funding was one of the barriers to moving forward with clinical trials, but also gave me a fuller picture of some of the other factors at play.

I do wonder why the follow-up clinical trial that Dr. Epner and his collaborator attempted had to focus specifically on brain cancer rather than, say, breast cancer or all metastatic cancers for that matter. But it’s usually not productive to ruminate about the past.ryanlerch-warning-cows-roadsign-2400px Besides, Dr. Epner had given me another lead to follow: Dr. Robert Hoffman. Searching for his work led me to AntiCancer, Incorporated. This company has a patent for and sells L-Methionine-g-lyase (METase), an enzyme that degrades methionine. genious-emoji

So there’s no need to follow a complicated diet, methioninase can do the job of breaking down methionine before tumor cells have a chance to feed on it, right? If that’s the case,  where are the clinical trials? Why aren’t researchers jumping on the chance to test this potentially life-saving treatment?

I emailed the company’s COO, Charlene Cooper, to find out if any human studies with methioninase were planned. I’ll share her reply, and more about methionine degrading enzymes as a treatment option for cancer, in my next post.
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