Glycine Methionine Balance Revisited: A

Matter of Timing
Apr 23, 2015 | Articles, Diseases and Disorders, Guest
Posts, Inflammation, Nutrition, Supplementation | 135 comments

In one of my earlier posts on this blog, I discussed the largely reciprocal nature of the
amino acids glycine and methionine. Specifically, too much dietary methionine depletes
glycine, because your body uses up glycine in order to get rid of the excess methionine.
This is a common condition these days, because the typical diet is high in methionine-
rich muscle meats, but low in glycine-rich bone and connective tissue. Many are waking
up to the benefits of getting more glycine by eating more wholesome meats by
supplementing with bone broths, or gelatin (collagen) products. (I take the easy way out,
by simply supplementing with the glycine product “sweetamine” which I formulated and
sell myself.)
The key to understanding the complex relationship between glycine and methionine is to
be aware that, in addition to the role of both of them in serving as protein building blocks,
they also both have many critical metabolic and other roles as free amino acids. As free
amino acids—which are small, water soluble molecules—both glycine and methionine
cycle very quickly through the body in a matter of hours, compared to the weeks-to-
months turnover time of protein molecules.
The key difference between glycine and methionine which has been the traditional focus
of nutritional and metabolic research, is the fact that methionine is essential, i.e., you’ll
eventually die if you don’t get adequate dietary intake, because your body cannot make it
from simpler materials; but glycine is non-essential, i.e., your body can make it from
simpler compounds. Hence, the importance of glycine in the diet has been largely
ignored.
Methionine—when activated to form S-adenosylmethionine, or SAMe—is the universal
methyl donor. As such, it performs the critical function of adding one-carbon methyl
groups, an operation necessary to form and modify DNA bases, detoxify drugs, and
make certain key molecules like the hormone adrenalin, to name a few examples. Since
methionine is so important, the body—mainly the liver—has a number of pathways to
reuse, regenerate and recycle methionine. Best known is the methionine cycle, whereby
the methyl group—once donated by SAMe—gets added back to the “spent” SAMe (the
amino acid homocysteine) to reform methionine. The result of all these pathways is to
render the minimal methionine daily dietary requirement very small, i.e., a few hundred
milligrams; more like a vitamin than a protein amino acid.
But the dark side of methionine—long ignored—is that too much is toxic, so that after
eating that methionine-rich steak, your liver is not operating the methionine cycle to
conserve methionine, but rather, getting rid of it as fast as it can. To do that, the liver
needs to use up glycine. Therefore, the more methionine in the diet, the more glycine is
needed to help get rid of it.
Although glycine is non-essential, your liver can’t make an unlimited amount, and the
typical diet usually comes up short 8-10 grams of glycine per day. Meanwhile, glycine
has critical functions in the body only recently discovered. Most relevant to human diet
and health is the fact that glycine is the most important endogenous regulator of
inflammation. In fact, I’m convinced that glycine deficiency lies at the core of most
conditions that make people sick and die these days, from diabetes and arthritis to heart
disease and cancer. That’s because they’re all traceable to chronic excess inflammation.
If you are glycine-deficient, it will show up as chronic inflammation sooner or later, one
way or another.
So that’s why I have been quick to say that most people eat too much methionine, and
really should avoid supplements such as SAMe, TMG, etc, which boost methylating
power. But in one of the comments after one of my posts on this site a few months ago,
the suggestion that some people are “under-methylators” prompted me to have another
look at what is going on. After all, it is well known that mutations of the gene for the
enzyme MTHFR—which is critical for the regeneration of methionine from
homocysteine—are quite common in all human populations (between 10 and 20%).
People with defective forms of MTHFR do not regenerate methionine efficiently.
Consequently, during periods of fasting (or even shorter periods of say, 4-6 hours
between meals), they may actually be somewhat methionine-deficient, precisely because
excess methionine is so efficiently removed after absorbing a meal’s worth of high
protein.
Therefore, such people may endure chronic health problems by being both glycine AND
methionine-deficient! So as a simple, harmless experiment, I suggested that one could
eat a rich natural source of methionine for a snack between meals. Brazil nuts are the
perfect such snack, comprised of 1% methionine by weight. That means a snack of 3
Brazil nuts provides about 100mg of methionine.
Then I looked further into the topic of “under-methylation” and realized that one of my
own daughters fit the profile perfectly: prone to hypoglycemia between meals and always
needing a high-protein snack to tide her over, and more seriously, suffering from
recurrent bronchitis—a borderline asthmatic since childhood. Of course, being my kid,
she’s been taking her sweetamine glycine supplement for a couple of years now, and
although feeling somewhat better, the respiratory problems persisted.
So I suggested she try a few Brazil nuts as a snack between meals. The first sign that
this suggestion was on the right track was the fact that she has always loved Brazil nuts
(Talk about intuitive eating!), but had avoided them because they are relatively expensive
compared to other high protein snacks (peanuts, string cheese, etc.).
But the most encouraging sign of spring (literally), is that for the first time I can
remember, my daughter has gotten through a northeast winter (and this year was the
worst in a long time) without a single major respiratory infection!
So at this point, my working hypothesis seems to be gathering some evidence for the
advantage —at least for undermethylators—of supplementing with both glycine and
methionine, starting the day with the former and taking Brazil nut snacks for methionine
in between meals. (And btw, Brazil nuts are also a rich source of usable selenium, in the
form of the rare but also essential amino acid, selenocysteine. Selenocysteine is
essential for the formation of glutathione reductase, the enzyme which regenerates the
key anti-oxidant glutathione.)
Finally, since I first made this suggestion on this blog, I’m very curious to know if anyone
else has taken it up, and whether it has helped. Do tell.

About the Author

 Joel 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 http://sweetamine.com , which includes his own blog HERE.