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Comment from Martin Tornberg:

“One thing that gives me pause with respect to consuming too much glycine is the study on that “identified glycine consumption and expression of the mitochondrial glycine biosynthetic pathway as strongly correlated with rates of proliferation across cancer cells” and noted that “Antagonizing glycine uptake and its mitochondrial biosynthesis preferentially impaired rapidly proliferating cells.”

While this may be of primary concern to cancer patients (who might therefore be well advised to limit both glycine and methionine, which basically means sticking to a low protein diet), it may also be relevant for any of us who feel we might be at risk of cancer and might have small amounts of cancer cells in our bodies that are not yet large enough to form a tumor but that we don’t want to feed. The study is described in an article here:

Dr. Brind, I would naturally welcome your thoughts on this, as it implies that just eating a lot of glycine (or glycine-rich foods) to offset high methionine consumption from dairy and animal proteins may not be a wise strategy; consuming only moderate amounts of both glycine and methionine (ie, avoiding high protein diets and consuming only modest amounts of animal protein) would seem to be a safer approach (and one that is more consistent with what we know about the typical diets of very long lived people across different cultures).

On the other hand, perhaps that study on glycine was flawed or misleading, I am not sure; I am only posting it for informational and discussion purposes and would love to find out what others think about this.”

Response from Dr. Joel Brind

Thanks for this thoughtful comment, Martin. My answer will not be a short one, as this issue actually gets to the heart of my whole philosophical approach to science. The 2012 article in Science, the abstract of which you link to, by Mohit Jain et al., I am well familiar with (BTW, the second link you gave, to a popular journal article about the Jain article, no longer works). The Jain article actually follows on a 2009 article in Nature (Nature and Science are probably THE most prominent scientific journals begin published, btw), which showed a high prevalence of glycine production in human prostatic tumors, and claimed a tumor growth-promoting effect of sarcosine, the product of GNMT. There were warnings then also in some quarters about the hypothetical dangers of glycine supplementation.

Re: the Jain article, in that issue of Science, there was an editorial touting the study, and waxing philosophically about the emerging predominance of “data-driven science”, at the expense of “hypothesis-driven science”, the two studies we are discussing being examples of “data-driven science”. My view: Hypothesis-driven science is what we used to call “science”. Data-driven science starts with the mountains of data now possible to generate by new biochemical assay techniques that can simultaneously measure hundreds of metabolites, proteins, genes, etc., thus generating whole new fields of enquiry called, respectively, metabolomics, proteomics, genomics, etc. In actuality, these are not really new scientific disciplines, but advanced data mining techniques. It has become fashionable, however, to generate scientific research projects with such “-omics-generated” datasets. So, in the example you provided, Jain et al. ran such a metabolomic profile of 219 metabolic intermediates in 60 human-derived cancer cell lines developed at the US National Cancer Institute operation, to see if any particular metabolites stood out as correlating with these cancers, compared to normal cells. They found that glycine synthesis and utilization was highly correlated with these cancers, from which finding they generated the most simplistic hypothesis, namely, that too much glycine might give you cancer or make an existing cancer worse.

So you see, in this typical “data-driven” approach, the researchers start by figuratively throwing mud up against a wall to see what sticks, and then try to figure out why the mud stuck to the cancer side of the wall and not the normal side of the wall. To me, that’s not good science. (Back in the day, reviewers used to call that a “fishing expedition”, not generally worthy of grant funding. If you like fishing analogies, “data-driven science” is to “hypothesis-driven science” as trawling is to fly-fishing.)

Please don’t get me wrong: These “-omics” techniques are enormously valuable, enabling the testing of many more hypotheses much more thoroughly and quickly than ever before. But they are no substitute for good scientific reasoning.

Now let me give you my interpretation of the results obtained by Jain et al. in 2012, and those of Sreekumar et al. in 2009. It starts with an understanding of how cancer develops in the body. The prevailing wisdom (which I believe is essentially correct) is that abnormal, potentially cancerous cells develop all the time, even in healthy bodies, but a healthy immune system normally eliminates them efficiently. But when conditions—usually some form of chronic inflammation—makes cells multiply abnormally quickly, mutations develop at a much higher rate. The abnormal cells which result ultimately develop such mutations as to breed independently of normal cell growth control mechanisms, and they may overrun the immune defenses and become a dangerous, invasive tumor. During this process, a Darwinian natural selection process selects those cells which are most able to grow, escape immune surveillance, and invade other tissues; thus exploiting the weaknesses of the immune system and the body’s internal environment as a whole. (I know we are used to thinking of natural selection as occurring over eons, rather than months and years, but when we are talking about individual cells, whose generations are measured in hours instead of years, evolution is very quick.)

Now let’s take a look at some well established findings re: human cancer. Many human cancers—perhaps a majority—are actually much more methionine-dependent than normal cells. They have lost the ability to recycle and regenerate and salvage methionine. In fact the use of the bacteria-derived enzyme methioninase, to help deny methionine to cancer cells in afflicted patients, is an active and somewhat fruitful area of cancer research and therapy. Now let’s refer back to the metabolic pathways, and the intimate relationship of methionine and glycine metabolism. The easiest way for a cell to waste methionine is to override the “off switch” to THE methionine-wasting enzyme, GNMT (glycine-N-methyltransferase). Why would a cell do this? It will do this if there is a selective advantage to avoid the energy expenditure of conserving and recycling methionine. Under what circumstances would this be advantageous? It would be advantageous in an environment that is chronically methionine loaded. Of course, when GNMT is always active, the synthesis of glycine is always maximal also, so there will be lots of glycine produced (as well as sarcosine, the product of GNMT.) So then, what did the metabolomics people—Sreekumar in 2009 and Jain in 2012—actually find? They really just found the flip side of the increased methionine-dependence of many human cancers, i.e., the increased glycine-independence of many human cancers.

So my interpretation of these results is that they offer hard evidence that many human cancers are selected for, and therefore arise in, bodies which are chronically methionine-loaded and glycine-deficient. Thus, they underscore the need for the proper balance between glycine and methionine. As far as diet is concerned, all that means is that the high intake of methionine in muscle meats needs to be balance with a proportionally high intake of glycine, which we usually throw away with the collagen of the bones and connective tissues. If you don’t care for bone broth or gelatin, just a glycine supplement will do the trick.

About the Author

Joel BrindJoel Brind, Ph.D. has been a Professor of Biology and Endocrinology at Baruch College of the City University of New York for 28 years and a medical research biochemist since 1981. Long specializing in steroid biosynthesis and metabolism and endocrine-related cancers, he has specialized in amino acid metabolism in recent years, particularly in relation to glycine and one-carbon metabolism. In 2010 he founded Natural Food Science, LLC to make and market glycine supplement products via , which includes his own blog HERE.