The Shocking Truth About Methionine: Part II

recap

In my last post, I discovered that many types of cancers have an absolute requirement for the essential amino acid methionine. When methionine is absent from petri dishes, malignant cells don’t grow and sometimes even die out completely. Normal cells in petri dishes can do ok without methionine provided they’re given homocysteine, methionine’s metabolic precursor.

That’s what happens in the lab. But how would it work in the real world? Methionine is in a lot of foods, especially animal foods. Yet becoming a Vegan wouldn’t be enough to eliminate dietary methionine –  it’s also abundant in seeds, nuts, soy, and beans. Besides, most every food has some amount of methionine, so a completely methionine-free diet isn’t feasible. And browsing through all those nutrition tables trying to approximate methionine content per typical portion was starting to drive me a bit crazy. aint nobody got time for that emoji

Still, if I could stick to an ultra-low methionine diet, would that help shrink my tumors? Is such a diet practical, or even safe? And would it be effective outside of petri dishes?

I turned to 720px-US-NLM-PubMed-Logo.svg .gov for answers. Studies testing the anticancer effects of methionine deprivation in mice looked promising. In one study, researchers injected 21 nude mice with Yoshida Sarcoma, a commonly used cancer cell line. One group of mice was fed 8.2g of methionine per kg, while the other group of mice got 0g of methionine per kg.

By day 12, all the mice with methionine in their diet were dead. In contrast, mice fed a methionine-free diet had slower tumor growth and even some regression of their tumors. At day 30, all the animals on the methionine-free diet were still alive, though the whole group died by day 38. Poor mice!

This literature is not the most fun to read. Still, survival time for one methionine-free mouse more than tripled, so they’ve gotta be onto something, right?

Researchers from the M.D. Anderson Cancer Center in Houston cast doubt upon these findings in a 1988 article; they reported that while three of the seven rodent tumor cell lines tested failed to grow in a petri dish without methionine, all 17 of the human tumor cell lines tested were able to grow in the methionine-free petri dishes. I'm over it emojiThe researchers concluded that methionine dependence is less likely to occur in human tumors than rodent tumors.

Just as I was about to dismiss the whole idea of methionine restriction, I found a study that was novel in its use of human (as opposed to rodent) breast, colon and lung tumors. Growth of these human tumors (transplanted as usual into nude mice) was significantly inhibited in the mice fed a methionine-free diet. This demonstrated that at least some types of human cancers require methionine in living (albeit all-too-briefly-living) animals. Maybe this did warrant further exploration.

Fast forward to 2016: scientists still seem stuck on using nude mice to investigate the role of methionine in cancer progression. One such study published this year focused specifically on breast cancer. Mice were injected with immortalized human breast cells and fed either a control diet consisting of 0.086% methionine or a methionine restricted diet with only 0.012% methionine. After 12 weeks, all the mice were euthanized (when will these poor little creatures catch a break?) and examined. Tumors weights in the methionine restricted mice averaged 11.4±4.0 mg compared to a 20.2±6.1 mg tumor weight average in the control mice. That’s a 55% tumor weight reduction for the methionine restricted diet vs. a standard control diet.

I’d be super excited by these results…sticker.crazyhamsterif I were a rodent injected with malignant cells (but not marked for euthanization).

More than 40 years have passed since the initial discovery at the University of California. Where were the human clinical trials? Ridic emojiI did finally dig up a small Phase I clinical trial from among all the mouse and petri dish experiments. This trial had modest objectives and only eight patients with various types of metastatic cancer.  Participants followed a methionine restricted diet for an average of approximately three months, and their plasma methionine levels fell by an average of 58%. The authors concluded that a methionine restricted diet can be safe and tolerable in adults with advanced cancer.

Not much more than that can be learned from a trial with so few participants, but I still felt underwhelmed by the results (or lack thereof). Certainly no miraculous recoveries for any of those eight patients. One patient with prostate cancer had a 25% reduction in serum prostate-specific antigen (PSA) after three months on the diet, and another patient with renal cell cancer experienced “an objective radiographic response.”

Otherwise, the trial didn’t find any notable anticancer effects from methionine restriction, not even in the patient who followed the diet for 38 weeks. Maybe a 58% drop in plasma methionine isn’t enough to cause the tumors to regress? In any case, I doubt I’d manage to be much more strict with my methionine intake than these eight trial participants.

The researchers called for more clinical trials to determine whether methionine restriction could enhance the anticancer activity of chemo and other treatments. Why couldn’t I find any of those follow-up trials?

what Happened emoji

I decided to contact one of the authors, Dr. Epner, to ask him directly why he abandoned this line of research after publishing the Phase I trial results in 2002. I’ll save Dr. Epner’s response and further adventures in methionine research for my next installment.

As for my progress in cooking turmeric dishes, I’ve been sticking with the tried and truly delicious turmeric potato salad.  I made and devoured it three more times since my last post. Maybe I’ll feel more venturesome and try a new recipe this week. Stay tuned!

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