By Joel Brind
For many of us, the downside of the holidays is the dread of adding a few pounds of abdominal fat that will take more than a New Year’s resolution to work off. Even worse, we all also know that it’s the extra abdominal fat that causes insulin resistance and eventually?or maybe already?type 2 diabetes.
But more recent research tells a more precise?and cheerful?story about what is really going on. It’s not the actual fat (adipose) tissue that causes the problem after all: It’s the immune cells?the macrophages, to be specific?that are embedded in the adipose tissue, that stir up the trouble.
So why do the macrophages get stirred up, and what do they do that’s so damaging as to ultimately cause diabetes and all the morbidity and mortality that follows? The last two decades of research has demonstrated that excess abdominal fat?because of the associated macrophages?causes a condition of “metabolic inflammation” in the whole body. This systemic inflammation is characterized by elevated inflammatory markers in the blood, most notably a hormone called Tumor Necrosis Factor-alpha (TNF-?). We now know that TNF-? does a double whammy by directly causing insulin resistance in skeletal muscle AND the inhibition and ultimate destruction of the beta cells of the pancreas (the cells that make insulin).
A little more background is in order here: Insulin is the hormone secreted by the beta cells of the pancreas in response to and/or the anticipation of the rise in blood glucose (blood sugar) that happens after a carb-rich meal. What insulin actually does is command mainly three types of tissue: liver, adipose (fat) and skeletal (voluntary) muscle to get that glucose out of the circulation as quickly as possible, by burning it or storing it. These tissues can store glucose as glycogen (aka “animal starch”) or fat. What insulin does is to turn on the enzymatic machinery to store (or burn, in the case of muscle), as well as to open up specialized channels (called “GLUTs”; short for “glucose transporters”?pun intended by the creative researchers that came up with the term) in the cell membranes of adipose and muscle cells, so that glucose can be taken up rapidly by these tissues.
Trouble is, TNF-?, secreted by the activated macrophages embedded in the adipose tissue, directly interferes with the muscles’ deployment of GLUTs in their cell membranes, so they cannot take up glucose readily. This is manifest as the pre-diabetic condition known as “insulin resistance”. As a result, the pancreatic beta cells respond by cranking out more and more insulin. But at the same time, TNF-? also directly interferes with the ability of the beta cells to make insulin, and ultimately induces their self-destruction, causing actual type-2 diabetes. The reason this takes some years to occur is the existence of other chemical control mechanisms?hormones and other factors secreted by muscle cells and other types of pancreatic islet cells that help to protect the existence and function of the beta cells. The complex interplay of such chemical signals is currently being elucidated by ongoing research. But the bottom line is that ultimately, the chronic inflammatory condition and unrelenting action of TNF-? (and likely other pro-inflammatory chemical signals) crashes the system, and diabetes ensues.
So, getting back to the earlier key question, why do the macrophages embedded in the abdominal fat get stirred up in the first place? The answer, in a word, is glycine, or rather, insufficient glycine. Feel free to check out my earlier post (Diet and Inflammation, Part 2) on this blog for the details. But in short, glycine is the body’s most important regulator of inflammation, by keeping membrane channels open for the intake of chloride ions. A constant, low-level influx of chloride is needed to maintain the proper membrane voltage (0.07 volts): If the voltage deteriorates, the cell gets activated. That’s when these macrophages go into action to fight invading microbes. Normally, these cells only get activated when they detect the chemical signature of bacteria or viruses or fungi, but if the concentration of glycine is not high enough, the macrophages get activated to fight microbes that aren’t even there!
Now here’s a key error that the mainstream research and medical world is still laboring under: It is still generally thought that inflammation is also a natural response to tissue injury. I have discovered that–unequivocally?that is not true. When, for example, there is blunt injury?no microbes to kill?macrophages do need to be involved in gobbling up the mess of dead cells and cell debris. But they do not need to get activated, which involves the secretion of destructive chemicals like hydrogen peroxide and TNF?. They only cause damage and delay healing (That’s why it helps to put ice on such a wound, to inhibit inflammation.) And if you are not glycine-deficient, blunt injury does not cause inflammation, but just naturally heals quite quickly.
What about abdominal obesity? After all, there’s not even any tissue injury to activate the macrophages. It is not known what the signal is precisely that sets them off. But I can tell you that they do NOT get activated if glycine is adequate. So where’s the proof of this? Two lines of evidence provide confirmation: First, we find that insulin resistant (pre-diabetic) and type-2 diabetic patients have significantly lower blood levels of glycine than normal. Over the last few years, the evidence for this has been accumulating, thanks in some measure to the new technological advance known as metabolomics, which allows the simultaneous measurement of hundreds of metabolites from each blood sample collected, rather than just a few. So for example, in 2010, a study identified glycine as the single most reduced metabolite?among 485 different metabolites identified?in 143 insulin-resistant 30-60-year-old men and women from 13 European countries, compared to 256 subjects with normal insulin sensitivity. Similar results have been showing up in several other recent studies among subjects with insulin resistance and abdominal obesity, as well as subjects with type 2 diabetes, as had shown up in earlier studies on laboratory rats with diabetes.
Second, clinical trials are starting to show that when insulin resistant and diabetic patients’ diets are supplemented with glycine, the clinical markers of the condition improve markedly as was previously demonstrated in laboratory rats. So, for example, in a study in Mexico City in 2008 found that, in 3 dozen patients taking 15 g/day of glycine (v. placebo controls) mean fasting glucose went down from 183 mg/dL to 140: from way diabetic to right on the border of diabetes. In the same study, hemoglobin A1C (a standard measure of long-term blood sugar control) decreased from 8.3 to 6.9 (i.e., down to non-diabetic levels), and a measure of TNF-? decreased 4-fold! A clinical study of my own is also in the works.
Finally, let’s not underestimate the value of self-experimentation: My experience with my own 8g/day sweetamine supplement was that, with no change in weight, it reduced my fasting glucose?which had gone up over the years to 129; just over the border into diabetic territory?down to 110: the top of the normal range. (Some sweetamine users diagnosed with type 2 diabetes have also reported not needing their medication anymore to control their blood sugar.)
So we end where we began: Enjoy the holidays, and eat, drink and be merry?even if you do pick up a few pounds. Just don’t forget the glycine.
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.
Magnesium is another thing commonly low in diabetics. I have to wonder if there some interplay here between magnesium deficiency and glycine deficiency.
I must confess that I do not know much about magnesium deficiency, although much has been attributed to it. (Magnesium is an element that is essential to the function of many different enzymes, but I really don’t know if a deficiency is widespread.) The best natural source is green vegetables (Magnesium makes green plants green just like iron makes blood red.) I take a magnesium supplement myself right now, although I don’t notice any effect.
There is, however, one point at which Mg and glycine may intersect, i.e., one of the supplement forms is magnesium glycinate, an organic chelate of magnesium. Since magnesium is such a light element, and the glycinate contains two molecules of glycine, magnesium glycinate is actually about 85% glycine by weight. Therefore, it is possible that some benefits of magnesium glycinate are really due to the glycine, rather than the magnesium.
I need your help. I’m hypoglycemic and no doctor can figure out what’s causing it. I have modified my diet which worked for a few months but now I’m dropping again almost everyday. The only thing that works is glycine and it stabilizes me wonderfully but it started to make me very drugged up feeling and cold. I stopped it and now I’m dropping again. I’m going to try to lower the dose significantly. Perhaps my SSI med is interacting? If glycine helps does that mean I’m deficient? I eat plenty of fatty meat. HELP!
Ssri*
What are you dropping? I don’t understand.
My blood sugar is dropping – I have hyperinsulinism.
First! :D
“So for example, in 2010, a study identified glycine as the single most reduced metabolite?among 485 different metabolites identified?in 143 insulin-resistant 30-60-year-old men and women from 13 European countries, compared to 256 subjects with normal insulin sensitivity.”
Hi Joel. It would be nice to get a PubMed link to this study.
Thanks for the article!
It would have been. http://www.ncbi.nlm.nih.gov/pubmed/18852529
Oops .. wrong study :)
Can’t locate that one either.
Ok … think this is it. Dr. Brind references it in the other post mentioned.
“There was also a very interesting 2010 study by Gall et al (PLoS one, vol 5, No. 5 e10883. PLoS one is available free on line), who looked at the profile of hundreds of metabolites in a population of insulin resistant individuals v. normal controls. It is fascinating that in this long and detailed paper, they authors make no note whatsoever of the fact that glycine was the metabolite most reduced in the insulin resistant patients!”
The paper by Gall you reference does not seem to be the same paper Dr. Brind refers to in this article. The Gall paper had 40 diabetics and 60 controls, not 143 diabetics and 256 controls. Additionally, the Gall paper found NO decrease in serum glycine whatsoever. Also, they measured 201 metabolites, not 485.
So where is the reference to the paper he refers to?
What happened to the forums?
There still there. Neglected perhaps, but there. http://sp2018doajr59.wpengine.com/forums
So should you not take glycine if your fasting blood glucose is already normal? Mine is around 90 mg/dl. Would taking glycine reduce it to below normal levels?
I’m sure it wouldn’t be harmful to consume glycine with normal blood sugar, as that’s certainly not its only effect. There are varying opinions on the matter, but I think fasting glucose levels of 65-75mg/dl are actually “optimal,” generally-speaking. Of course, many artificially get there by starving themselves of carbohydrates or by other methods, and that’s simply not the same as naturally having that fasting glucose level spontaneously without effort.
I plan to supp glycine, even though my sugars weren’t bad. I have high inflammation markers that keep getting worse. I am a recovering low carber.
Most people are glycine deficient, and that shows up as some sort of inappropriate inflammation. It usually only shows up as insulin resistance if there is also some–even as little as 10-20 pounds–of extra abdominal fat. But remember that inappropriate inflammation may usually be thought of as normal, even though it’s not. For example, about two weeks ago I slipped on an icy brick walk and went right down directly on my left hip. So I just got up and walked away (carefully this time!). Other than the transient immediate pain of the bone hitting the pavement, there was no residual pain, swelling or immobility. My hip is still a little bit tender if you press on the injured spot, but that’s all. In my pre-glycine supplement days, that sort of injury would leave me hobbling around with pain and a limp for 2-3 weeks, and the consumption of a bottle of Advil. If not for such an injury, I would likely not notice the difference (although during the winter in the northeast, shoveling lots of snow no longer leaves me with a sore back).
Hi Joel, I get your example with the injury vs inflammation. On the other hand I think it’s difficult to attribute the lack of pain you’ve had to supposedly very low or no inflammation. The science of pain is very complex and often there are people who have little pain with serious injuries and some minor injuries would hurt for weeks. Basically there are many many inputs that go into the resulting sensation of pain and inflammation is but only one of them – therefore it’s probably not that simple as a simple correlation between pain and inflammation.
Oh, and here’s something else uncool about a low-carb diet: It lowers glycine, thus exacerbating a glycine deficiency. Why? Because when your blood is low in glucose (blood sugar), your liver uses amino acids–including glycine–to make the sugar your body needs (even though total blood sugar is lower).
“Here’s something else uncool about a low-carb diet…”
I love how you phrased that Joel! Uncool indeed!
I dunno, I always felt pretty cool on a low-carb diet.
Joel you sound like a MAD scientist..And how you know if the glycine is low with the low carbs? Read his entire article again and understand..
Your body will burn fat in place of glucose — which makes it a good diet for weight loss. I think the problem with low carb comes when ppl make it too low, refusing any and all carbs rather than the more unhealthy ones. Personally I find the glycemic index to be a much better source of learning which carbs to avoid & which to eat. I guess you could say I’m on a slow carb diet. No simple carbs for me
Matt, when it comes to keeping a high metabolism, is meal frequency of any importance?
I always try to eat something around 6am before work on weekdays but come weekends i snooze for hours, get up and feed the horses and then continue slacking. Dont feel like eating anything. Brrakfast is eaten 2-6 hours after awakening.
Is this a contra productive behavior? Should i just force something in asap?
Temps are fine but hands usually chilly in the morning. Stomach either fine or extremely sensitive, swells up over nothing (and along with that make feel like a living dead fron every aspect)
I started taking glycine a couple months ago but this has been a problem for years and years.
I am ED “recovered” for a couple years now and although i won’t admit it i still restrict here and there.
I did gain a few lbs over christmas. It was the chocolate!
I always buy it when i crave it but i seldom do. Then came christmas…
Is it prefered to follow cravings, or meal timing?
Tough to say. Consistent meal timing is generally a good thing when you have the rhythmicity to your day and life in general to be able to do it. But it’s nice to relax and eat only when you desire food as well. I don’t think anyone can answer this question better than you with some experimentation.
Thank you :)
Thank you for another enlightening post Dr. Brind. I have been urging my brother in law, who is badly insulin resistant with an A1C of 6.4, to take glycine but he doesn’t understand why it is important.
You said something that caught my attention- forgive me for focusing in on something so random. In regards to excessive immune activity and TNF alpha etc… You said that when there is excessive macrophage activity there will be release of harmful substances and you named Hydrogen Peroxide as one of them. Can you elaborate further on the cells production of Hydrogen Perooxide? I know it is a normal end-result of some processes in the mitochondria but there are doctors advocating for the use of Hydrogen Peroxide in IV form or oral, high dose from as a way to “kill pathogens” and enhance immune response in people with Lyme and Epstein Barr.
I apologize for the off-topic nature of this question but you always post such fascinating things and enlighten me quite a bit regarding things that are tossed around in the “alternative medicine” world
Thanks for the kind words, Sarah. I wish I could offer you some enlightenment re: the hydrogen peroxide therapy, but I have no expertise in its medicinal use for actual infections. My point about peroxide is that it is naturally used internally by the body to fight infection, but it is only destructive when there is no infection to fight. Whether it works for chronic infections like lyme or Epstein-Barr I do not know, although such therapeutic use sounds plausible.
Re: your brother-in-law, I would tell him that insulin resistance and diabetes are really evidence of a deficiency disease. If he had signs of scurvy, would he take Vitamin C? Unfortunately, the world of mainstream medicine does not yet recognize glycine deficiency, and it may well be another decade before it does. Some people will not believe it until they hear it from their doctor or the NIH. Of course, trying it is cheap, easy and harmless, but you can only lead a horse to water!
Thank you for your response. I will give him a bottle of glycine and some packets of sweet amine and hope for the best! It’s rather amazing what he IS willing to do, even though it’s much harder and arguably counterproductive- the “HCG Diet”. (Consists of eating 500 calories per day and having HCG injections. It’s extremely hard on the metabolism but does cause weight loss. I’m not a fan)
how much glycine for someone with normal but high end normal blood sugar. and any brands/form you recommend, thanks!
I have found that 8 grams/day is a good average amount to take, which is why I put that much in each packet of sweetamine that I sell. Of course, you can get glycine from any health food supplier: My product is formulated for taste and convenience (You just use it as a sweetener for tea or coffee; one packet being about as sweet as 2 tsp sugar.) I have tried glycine from several sources, and they are all OK except the one from Nestles (believe it or not!). It’s a brand called “Musashi”, a division of Nestle Australia Ltd, which I got from a friend in Australia. I found it to be contaminated with the industrial solvent pyridine.
I have been experimenting with glycine for last two months. I began after reading of studies suggesting its benefits.
My experience is that a dose of 1 teaspoon or greater results in kidney stones and gravel. The event has been painful and visible. I have tested this consistently during many days over the last two months. I realize there is a degradation pathway from glycine to oxalate.
Research, http://www.ncbi.nlm.nih.gov/pubmed/8140673,
suggests glycine contribution to oxalate formation is minimal, though I can not reach in personal use the 22 grams amount of glycine used in the study. I had opened once a “google book” on the topic of metabolism disorders that I have since lost the link to that mentioned several pathways that may be flawed or problematic in some people and results in the production of excess oxalate.
I have experimented with various free form amino acids over the last few years in various ratios, and glycine has been the most recent and the only one so far to produce this result.
I was after an opinion whether this presence of kidney stones after glycine use could be indicative of already sufficient glycine within the body or whether this can be an indication of some sort of acquired or primary hyperoxaluria?
Could this be a glycinuria or glycine transaminase issue that I have been experiencing, as mentioned here :
https://books.google.com.au/books?id=Bd9XAwAAQBAJ&pg=PA344&lpg=PA344&dq=hyperoxaluria+glycine&source=bl&ots=_1p11UX4O1&sig=m34r1KXc4YMGoTnYJewUnMdgJrY&hl=en&sa=X&ei=1TSyVPqaNcHtmQW0v4GYDQ&ved=0CDwQ6AEwCTgK#v=onepage&q=hyperoxaluria%20glycine&f=false
On the topic of the solvent pyridine. I am in Australia and have sourced two glycine powders and the taste is not identical between them, neither of the powders are from Musashi. They are both sweet in taste, though texture and other tastes/smell differ slightly. I guess that they are both imports.
Wow! I’ve never heard anything about glycine having any effect on the kidneys except protecting them from damage! Hence I would indeed suspect that you might have a variant of glycine transaminase activity–as you suggested–that would shunt glycine to the formation of glyoxylate and oxalate, which does not normally occur to any significant degree in human liver (more likely that glyoxylate is normally converted to glycine). I’m also wondering if you have looked at folate/folate deficiency in this regard, as folate is required for the normal catabolism of glycine via the glycine cleavage system (GCS)? You might also have a variant in the form of a defective component of the GCS (rare, but not that rare: perhaps a fraction of a % of the population has one bad copy of one of the enzymes). That would result in a very high plasma glycine concentration (likely somewhere between about 500 and 1000 micromolar). Have you checked your plasma amino acids levels?
Meanwhile, here is a link to another study abstract showing minimal contribution of glycine to glyoxylate synthesis (in guinea pigs, at least)http://www.ncbi.nlm.nih.gov/pubmed/9038835. And btw, the second link you provided does not work.
Hi Joel. Thank you for the reply. I appreciate you sharing your opinion. It is great news in a certain way.
I did some research and I started typing a reply to your message in a desktop program and got to over a thousand words. I don’t know if Matt or the “Overseers” of the website will allow that length.
I will attempt to post it in the next reply.
Matt, can I post that much as a reply? If not maybe you can forward it on to Joel.
** Matt – If this is too long then you are welcome to remove it from the comments **
The following is not a complete assessment, I am only mentioning that which may apply to the topic discussed.
I self-diagnosed myself with hyper-oxaluria 8 years ago after spending a year bed bound unable to walk, talk or function mentally in 2004 and then spending another 2 years in dietary experiments attempting to isolate the problem through fasting and food experiments.
I requested several doctors in hospital urinary clinics to perform tests and a biopsy of liver tissue to confirm my theory of hyperoxaluria and they rejected my request and claims, that last time was in 2007. I ended up using a low-oxalate diet in order to live without constant liver and kidney pain and kidney stones. I can produce a kidney stone within hours of consuming the “correct” foods for formation.
I think that this glycine experiment is the first self-confirmed validation I have had of my self-diagnosis by specific testing results that can be compared to known metabolic pathways and to the results from other studies and research papers. I had no way of self-testing the hyperoxaluria theory prior to this. It would be an interesting idea if some forms hyperoxaluria could be tested for by a glycine loading test rather than biopsy. I see this as a new avenue for research.
Your opinion also highlights the potential that it may not be the food level of oxalate that is dramatically increasing the systemic circulation of oxalate, it could be that food oxalate sources are adding to the existing circulation of oxalate from glycine. I am not sure how much of this applies to me.
On the topic of folate, I utilize folate regularly. During the last month along with the experiment I have made use of pre-methylated folate along with TriMethylGlycine. If folate was the issue then using it during my testing with glycine should have increased normal catabolism via GCS, I am guessing. Though at the same time some of my doses of glycine I forced toward 40 gram per day mark and so any benefits of the methylated folate may have been reduced. I have not been tested for genetic mutations of MTHFR. There are always variants to genetic flaws and GCS may play a role in a different way.
What follows is speculation based on some research done today.
The link you provided is interesting. I refer to the mentioning of Alanine to inhibit oxalate production and also the role of Lactate Dehydrogenase. Given the role of the enzyme within the body this is of concern somewhat. Keep it in mind for what follows.
Because my health problem did not show up until I was in twenties, I decided to look for late-onsets of hyperoxaluria. In the past I also speculated that I may have hypothyroid issues due to body temperature.
Here is some information on late-onset hyperoxaluria triggered by hypothyroidism, I can not get access to the complete work.
http://www.ncbi.nlm.nih.gov/pubmed/15356974
Given the mentions in the work of Ray Peat, Broda Barnes and others with regards to hypothyroid issues contributing to illhealth.
I wonder if hypothyroidism can act as an epigenetic trigger for a variety of illnesses. Either way the result is a cyclic feedback loop, a positive feedback loop.
To put more clearly the role of hypothyroidism in this case, the fact that Lactate Dehydrogenase is a response to tissue injury and a tumour marker; and has a presence and a role in glycine to oxalate degradation; and that there is a potential hypothyroidism in inducing certain types of hyperoxaluria by genetic expression without tissue injury or tumour; could this all be a sign of an “endocrine-shock-cascade-and loop” that is first caused by hypothyroid influences. This shock is first created by problems with the thyroid and then mixes messengers within the body. The presence of Lactate Dehydrogenase would therefore appear due to an auto-immune fault or reaction. This could then go on to alter glycine metabolism due to late-onset hyperoxaluria. Or in other people it would cause other metabolic disorder, possibly by epigenetic factors.
I apologize if my logic is incorrectly worded in English above.
I also wonder whether cellular senescence plays a role where senescent cells refuse apoptosis as per http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645988/
It may add to explaining why a long term metabolic disorder in the making, may take a long term in fixing that current medicine does not fathom. That being that senescent cells that send incorrect messages to surrounding cells need first to be removed through apoptosis otherwise they are contributing to the positive feedback loop if they are carrying the epigenetic influence of the problematic thyroid. They are preventing new cells from occupying the space and are therefore ageing the particular organ, this organ could be the vascular system or it could be a main organ like kidney or liver. This would mean a dietary formulation would have to be maintained over a longer term in order to see results from the changes at a cellular level. I am severely ignorant in this area of senescent research and so take my idea as “half-baked”. I could take this idea further using anecdotal evidence though as a response comment in an article I think I am reaching a limit.
The second link was to page 344 of Biochemistry by Satyanarayana. It had a half page description of glycinuria and the glycine transaminase issue. It provided the hypothesis at the time that an unknown issue of kidney reabsorption may play a role in glycinuria promoting oxalate stone formation inspite of stable/normal levels of urinary oxalate. Such an idea suggests that parts of the Glycine Cleavage Sytem may be at fault within a particular organ and not necessarily the entire system. It would also confirm that because glcyine cleavage occurs predominately within the liver, kidneys, and brain, and in that order, that therefore onset of glycine overload would therefore contribute to mental problems after the first two are already overloaded.
I admit that I function mentally best after fasting for several days. Maybe that is the detoxification of the excesses.
It’s about three years since this post, but I am curious how you are faring?
“Because my health problem did not show up until I was in twenties…”. Me too. And a whole lot of folks, actually. There is a chronic vitamin A toxicity hypothesis that has grabbed my attention and I would like to seed it elsewhere to get feedback. https://ggenereux.blog/
I missed answering your question with regards to having levels of amino acids checked. I have not had them checked. Thank you for the suggestion. I will add that towards the list of things to check for.
Yes, if increased intake of one amino acid reliably produces such symptoms, it seems a good bet that there is a defect in amino acid metabolism. Defects in the GCS can manifest in a number of phenotypes, including the severe, neonatal type, which results in siezures and death within months after birth. Those would be homozygotes, of course, and if you are heterozygous, it would likely be a very late onset. If it is a GCS defect, a low carb diet would actually be beneficial. In fact, it is known that a ketogenic diet (basically normal protein, but low carb and high fat) normalizes glycine levels. However, it’s not (as generally believed) because of the increase in ketone bodies due to the high fat, but the fact that the low carbs induce gluconeogenesis, which means the liver is forced to convert the excess glycine into glucose for fuel. Have you tried a low carb diet? Also, having a high-methionine diet can help clear excess glycine (most folks have the opposite problem). For High methionine, lots of boneless chicken is good, as are Brazil nuts.
But I would certainly think checking your plasma or serum amino acid profile would be a good thing to do. Genetic testing is now easily available (www.23andme.com), so you can identify genetic defects in your own genome for only $99 (maybe cheaper than the amono acid profile).
Although I have yet to perform any tests and obtain results, much of what you mention and I have observed I am content with. I will attempt to locate a doctor that is considerate to my observations.
In 2007, when I first self-diagnosed myself, the first dietary attempt was almost a complete elimination of everything but meat because I confirmed it had no oxalates. I ate only meat for a year, along with some root vegetables once in a while. Despite some books, websites, and doctors at the time, claiming this will cause more kidney stones and kidney damage, I went ahead with the test and had the first pain-free year in 10 years. After 3 months into the diet, from a state of being almost incapacitated I was driving a car and going hiking. As noted, methionine is higher in the muscle meats, I did not make conscious association until now. Ofcourse, the previous statement is based on assumption that GCS is the issue in my case. I made many mistakes with that experiment because of my lack of knowledge of basic nutrition and biochemistry, particularly with regard to the lack of fat, and the choice of vegetables.
I will not go into detailing every dietary modification and experiment over the last 8 years because of how many there were, and many which may not apply directly to the topic here. As many variants of diets that I have tested, the one that offers the most clarity to my mind is high-fat (By energy value).
I would like to mention that most of the experimentation with glycine over the last two months was performed during ketogenic states or close to. The failure which occurred none-the-less is suggestive that conversion of glycine to glucose via gluconeogenesis is not optimized. I will need to check complete pathway metabolic requirements later because given the right cofactors some pathways can be increased toward a better optimization. I also am aware that certain pathway loops are balanced in dose dependent amounts, similar to what can be seen with Alanine in the study you mentioned earlier. Maybe if I reproduce enough, several generations later there will be better adaptation.
Merely to share some ideas for those reading. There are some supplements which work quite well for low-carb diets in my experience which are seldom mentioned on internet websites and blogs, for example creatine monohydrate promotes ATP recycling. And so the lowering of carbohydrates can be offset with increases in loading of creatine to an extent. Minerals deplete or are removed faster due to lack of insulin, and so macro-minerals, specifically electrolyte consumption, can be increased four-fold if not more. I am not sure on long term results of this. I have a hypothesis surrounding this topic which I won’t go into here because I have no reference to support my claim, suffice to say, I refer to it as the pass-through effect, it may aid in preventing excess build up metalloproteins in tissues where they should not occur, which is a known contributor to age-related degeneration of some organs. Dr Gary Gordon, a promoter of chelation and mineral balancing, somewhat discusses such issues of mineral accumulation. It would be interesting to observe a long term study of such a deposition of minerals toward tissues in ketogenic diets. Other theories suggest mineral displacement by diet as better method for reducing mineral accumulation. That is, correct ratios promote correct utilization, though in senescent tissues the inter-cellular and endocrine communication is reduced and may play a role in the lack of clearance or mobilization of the accumulated minerals.
In personal anecdotal experience, the increase in electrolyte intake compensates for reduced glucose in the shorter term of aerobic activity only, the ketosis needs to be maintained at higher quality, MCTs are better for this state. Though they may generate digestive discomforts as the burden on the liver is increased and l-carnitine levels drop.
Roles of carnitine – http://www.ncbi.nlm.nih.gov/pubmed/2239757
There was a better study I read which was referring to altered liver metabolism in adults during MCT consumption, though I no longer have the reference. I could digress slightly into the Traditional Chinese Medicinal perspective of this, I won’t, though I do recommend people making a study of such a subject in order to consider that the energetics within the body are altered with high-fat diets, foods alone do not always offer enough supplementation to offset the excessive ‘yin’ state that sometimes can be generated by high-fat diets without correct nutrition.
L-carnitine supplementation may provide some help in ketogenic states. L-carnitine has been promoted in the past for weight and fat metabolism in general. Though it may play a specific role in circumstances where ketosis is a physiological requirement due to illhealth.
The above is merely some ideas that maybe readers would like to consider should they wish to experiment down that path. Though it is possible that such things have already been discussed on this website.
I will continue pondering on the ‘half-baked’ idea I mentioned before, partly because something acts as the trigger in the late-onset of any illness that is influenced by genetic predisposition.
As much fun as speculation of ideas can be, and they can add curiosity to others reading the material, I will attempt to obtain test results before broadcasting other speculation on my case.
Our communication has given me new avenues of experimentation, thank you and likewise thank you for your efforts in promoting glycine research.
Correction, for those interested -> Dr. Gary Gordon should be Dr. Garry Gordon
Thanks Ty for posting your story. Actually it’s not that uncommon, but telling yours on a public site, rather than the private yahoo group (Trylng Low Oxalates) is commendable.
I’m shocked that Dr. Brind had no knowledge of glycine’s connection to oxalates. This has been known for at least 60 years, but here’s a study from 1988 that suggests that pyridoxine (B6) deficiency also plays a role.
http://www.jbc.org/content/234/9/2391.short
Thanks again Ty. Your story is inspiring. Hopefully Dr. Brind will do some more research before jumping to simplified conclusions.
I’ve heard that there is a relationship between excess animal protein and osteoporosis, is this related to a glycine imbalance? Is there a relationship between glycine and gestational diabetes?
Question 1: I would have to give you a somewhat speculative answer here. Assuming “excess animal protein” to mean the high consumption of muscle meats, the excess methionine would cause and or exacerbate a glycine deficiency. So the question becomes, does low glycine contribute to osteoporosis? I Assume you mean the usual form of osteoporosis common in postmenopausal women, that is attributable to the hyperactivity of osteoclasts, which are bone macrophages. I would hypothesize that osteoclasts, like other macrophages, are stabilized by glycine and that low glycine levels would therefore contribute to their hyperactivity, thus contributing to osteoporosis. However, I am aware of no published research on glycine and osteoclasts, nor any clinical trials with glycine supplementation in osteoporosis. So I would have to leave you with such a connection being a plausible theoretical possibility.
Question 2: Yes, the same decrease in plasma glycine is found in gestational diabetes as in non-gestational diabetes type 2. Here’s a link to the abstract of a relevant study: http://www.ncbi.nlm.nih.gov/pubmed/17240238
Thanks Joel. I remember reading about the idea that pregnant women often feel an aversion to meat due to some evolutionary advantage in avoiding bacteria. This sounded like a pseudo-scientific/ convenient association without an actual driver that becomes popularized in health magazines. After reading your articles on glycine, I started leaning towards thinking that a glycine-deficiency may be a more plausible driver.
Glycine the new goji berry. Cures anything !
Nope! Glycine just cures a glycine deficiency. But glycine deficiency is responsible for lots of morbidity. And I certainly don’t mind your skepticism, fred, but would recommend you go back and read all my posts on the subject, and comments. You’ll note that glycine’s roles as a regulator of cellular electrochemistry (especially in regard to the immune system’s macrophages) and as a metabolic intermediate (especially in regard to its role in methionine clearance) are known with precision. Proof of the clinical benefits of supplementing with glycine (mainly for conditions rooted in inflammation, a process effected by macrophages) is being gathered over a period of years, but the fact that glycine is a simple and safe bulk nutrient, whose content in a typical omnivorous diet is deficient because it is mostly thrown away (with the bones and connective tissues), make trying glycine supplementation (or you might call it glycine replacement) to regain or maintain optimal health pretty much a no-brainer.
What foods are high in glycine and/or is their a recommended brand to supplement with?
Among foods there is nothing higher than gelatin (i.e., collagen)–about 22% glycine by weight. That’s the reason bone broths are so popular now, and why good ol’ chicken soup has always been recognized for its restorative properties. Muscle meats are relatively glycine poor, with certain exceptions like scallops (That’s why scallops appear at the top of Vladimir Heiskanen’s last post on this blog). So about 8 grams of pure glycine a day replaces what is thrown away when we eat boneless chicken or beef or fish fillets, etc., without having to actually eat the collagen in the bones and connective tissues. I have formulated my supplement–sweetamine–with proline, taurine and a little stevia–into single, 8-gram serving packets used as a sweetener, for more convenience and better taste than pure glycine powder. But pure glycine is just as effective, and you can get it from lots of health food sources. I have found the product from Life Extension Foundation (lef.org) to be of consistently high quality, and they sell it in 300 gram jars of powder.
Their european site seem to carry only 1000mg capsules of glycine :/
Capsules can be easily opened and emptied, although its a bit of a pain. I think its better to mix the powder in a drink; otherwise it soaks up lots of water from your stomach and can cause upset. So I guess you can calculate the cost of 8 one gram capsules per day and see if its worth it. I ship sweetamine to Europe, and the cost comes out to about $1.70 per day (8 grams of glycine/day; less if you subscribe autoship or buy in bulk).
Gelatin (collagen) is the best food source, at about 22% glycine by weight. But since glycine is an important bulk nutrient, it’s hard to get enough–about 8 grams per day, on average, for the typical person on an omnivorous diet–without supplementing. I formulated my sweetamine supplement for convenience and taste (in individual packets which each contains 8 grams of glycine), but pure glycine is just as effective and available from lots of health food sources. I have found glycine from the Life Extension Foundatiion (www.lef.org) to be of consistently high quality. They sell glycine in powder form in 300-gram jars.
My first response to you, David, seemed to be lost in cyberspace, so I wrote another one, whereupon the first one reappeared. It’s all magic! (like gogi berries:-)
Glycine and insulin come out of my butt!
Was that a Haiku Half Nav? Love your snippets of wisdom! 6 years of comment gold! :)
Half Navajo, is that what Big Pharma calls ANAL LEAKAGE!?? Haha!!
Can you comment on how long it might take someone to see the benefit of glycine supplementation in blood sugar testing -specifically AM fasting blood sugar results?
Thank you.
Hard to say, for two reasons:
1) Published data has generally looked at 3-month trials, so that Hb-A1c (which reflects blood sugar averages over the last 2-3 months) reductions show up.
2) If you are taking any medications, their effect will mask the effects of glycine.
That being said, I would think a difference would show up within about a week, providing it is high to begin with. As I observed earlier, my own morning fasting glucose went down from close to 130 (barely diabetic) to about 110 (high end of normal). I only measured it after a couple of months though. But theoretically, the effect should be within a matter of days.
I tried taking sweetamine, but after a few days it started giving me diarreah. Any idea why?
No idea actually. I know of one other person who reported that–out of hundreds. Are there any meds you are taking that might cause that? It could just be an idiosyncratic reaction, or possibly due to something else. I assume you took the sweetamine dissolved in some beverage, not as a straight powder, right? GI upset has been reported as an idiosyncratic reaction to pure glycine. Also, if it happened only after a few days, maybe dividing the single serving into two servings a day might fix it. Finally, I guarantee sweetamine, so if you don’t like (or it doesn’t like you) you can have your purchase price refunded for the asking (You don’t have to send anything back:).
I also experienced diarrhea around day 2 or 3 of starting glycine.
Isn’t there potent liver detoxification or normalization of detox pathways when deficiency is corrected? Besides cleansing of liver and kidneys I have read there is a bile channel restoration or correction with glycine, with improvement in fat metabolism.
So, would it make sense that initial loose stools would be a combination of liver and bile duct cleansing/flushing? I have continued 8 gm divided morning and night with no more diarrhea. To note original dosing was 2 gm a time 3-4 day. With each additional dose causing some stomach rumbling, until eventually everything was flushed via diarrhea.
I’m surprised you haven’t seen more of this in practice?
Also, I was wondering why you brush over the potential sleep benefits of glycine and the value of dosing before bed? Don’t study show increased deep sleep and REM? Most Internet purchasers seem to be exclusively buying for sleep.
when I read your comment- my first thought was your specific gut bacteria. I don’t really know too much about this but it’s my best guess- maybe it has something to do with which types of bacteria you have (bad or good ones). You can easily research this as there is so much talk about gut health and individual gut microbiomes these days.
My family has been doing a ketogenic diet for about 4mos. While my hubby lost 47lbs, my daughter 30lbs, I lost 10 at the beginning then by 3months in I became so constipated I have needed to take laxatives. I found Matt Stone, read about 4 of his books and have been following his “plan” for about a week. I am confused by “a ketogenic diet regulating glycine”.
So is it a good diet or unsafe? Thank you!
I think you may be referring to my earlier comment re: a ketogenic diet’s ability “to normalize glycine levels”, but that was in reference to those with a metabolic defect in the glycine clearance pathway. A ketogenic diet actually tends to strip glycine, because 1) It contains high levels of methionine, which requires lots of glycine to clear out the excess, and 2) it results in increased gluconeogenesis, which means your liver has to make glucose from non-carbohydrate precursors, like glycine. So the bottom line is that those on a ketogenic diet would generally require more glycine intake to keep down inflammation.
Anyone know why glycine might make someone nauseous? Started a glycine supplement (no fillers or additives, just glycine powder) and it causes nausea. I got the same reaction when I tried taking collagen/gelatin. For the glycine, I started with the smallest dose on the container, 1,000mg.
Any thoughts?
Taking it without food is unnatural and can cause nausea in some people.
Hi Joel/Matt
Really interesting article… Do you know if glycine would help insulin sensitivity if you’re a type 1 diabetic? I am type 1, on insulin injections, and I do know that at certain times in my cycle I become more insulin resistant. I wonder if supplementing with glycin may help?
Thanks :)
Nadia
Just saw this article from NOVA Next, talking about a correlation between inflammation and depression. http://www.pbs.org/wgbh/nova/next/body/depression-may-caused-inflammation/
It does not mention glycine deficiency as a possible cause of inflammation, but then again practically no one but Joel Brind does.
Would you be able to observe the positive effects of serum glycine in people with genetic nonketotic hyperglycinemia?
http://www.ncbi.nlm.nih.gov/books/NBK1357/?report=classic
“Mild outcome. Rare individuals with a very mild form of glycine encephalopathy have been described. They often present after age one year, have an IQ of >60, and sometimes can attend normal class in school. They have attention deficit and hyperactivity disorder (ADHD), typically have no (or rare) seizures, and can have episodes of severe lethargy with infections [Brunel-Guitton et al 2011].
The best outcome ever reported is normal intelligence, observed in individuals with a genotype associated with residual enzyme activity (p.Ala802Val) who received early and aggressive treatment in the first two years of life [Korman et al 2004].”
Would these people be resistant to inflammatory disorders
Please help! I was diagnosed with gestational diabetes after my 1 hour gtt came back at 214 although I have been testing my blood sugars and am not even close to that high since then! Most people suggest confirming with a second test which they didn’t do. In all fairness, I have been insulin resistant for years but anyway, most of my fasting blood sugars have been 105-122 and I hour post meals spiked to 180 only twice after white rice (1 cup) and pizza (3 slices). I tried restricting carbs and have felt miserable and hungry. Most of my other post meal blood sugars have not been bad. I have just gotten over dieting, and restrictive eating and now I’m hit with this. The crazy part is I am 22 weeks pregnant and have only gained 4 pounds and that’s with eating whatever I want! In my other pregnancys I gained 40-60 pounds! My question is, I bought the Carlson brand glycine and the serving size is 2grams- can I just take 4 scoops at once to equal 8 grams or should I spread it out? How long does it take to see effect on blood sugar? The doctor is hassling me to see a nutritionist but I already know how to eat! Any advice would be appreciated.
Again, you should probably raise carbs and decrease fat. Within reason.
If everyone ate a fat-free diet, they would ace that OGTT, as the glucose immediately clears out of the bloodstream and gets into the muscles and liver without being blocked by free fatty acids, intramuscular fat, and other things that are more directly causal of insulin resistance.
And also, don’t panic. Gestational diabetes is not a preferred physiological state, but artificially controlling blood sugar by restricting carbs is a much more stressful and dangerous alternative. I’ve written about GD in the past here: http://sp2018doajr59.wpengine.com/the-gestational-diabetes-controversy/
Thanks Matt! I agree that stressing over what to eat and drink and checking your blood sugar 4 times a day and emailing your doc once a week with your blood sugars only makes it worse from all the stress. I feel that they profiled me because I’m overweight- they made me take the test at 16 weeks! Anyway, I will try to lower fat and increase carbs- what about protein? Their advice is to always eat protein with your carbs? Thanks!
http://www.iflscience.com/health-and-medicine/scientists-reverse-aging-human-cells-line
Check out what they’re doing with glycine.
Just a question on your thought on this idea- do you think glycine deficiency (maybe coupled with other deficiencies or with other stresses) could contribute to recent rise in type 1 diabetes? I’m type 1 and am always and forever speculating on these things. Of course no one has these answers yet but what’s your general thought?
Last year my body composition changed dramatically. I’m 10 years post-menopausal, but in good shape. Suddenly my breasts became larger, I had more fat on my upper arms and I developed small saddlebags on my thighs I had never had. When I had my amino acids tested, my glycine was 525 and supposed to be under 325. I’ve talked to at least 5 doctors and no one knows why or what that means. I don’t eat a high protein diet. I had never had my amino acids tested before so can’t compare this result with previous tests. Could my body composition change have anything to do with my elevated glycine? Thank you!
We r in the same boat; right down to our names, lol. I’ve had high glycine past 2 AA tests. Waiting to c how they respond 2 this.
Yet another site that presumptuously assumes lower blood sugar is always better. People with hypoglycemia are ignored, yet again. And no, hypoglycemia is not “just a rebound to a blood sugar spike from too many simple carbs”, and no I’m not talking about reactions to prescription insulin medications, which we have never used nor needed. Not everyone has the HIGH sugar problem, there also exists a LOW sugar problem. I will be AVOIDING glycine, thanks.
A very provocative article, thank you Dr. Brind.
You mention Life Extension Foundation and cite the high quality of its glycine powder. Just as an FYI, they don’t seem to be selling the powder anymore, but their glycine is still available in capsules, which I assume is basically the same stuff. I like Source Natural and Carlson glycine also.
I’m just wondering if you might have an opinion on Life Extension Mix Powder (Without Copper) as a general multi-vitamin/multi-mineral product, i.e., is it your general sense that Life Extension products are good?
Have you heard of supplementing with Inositol, specifically a 40/1 ratio of myo inositol/D-Chiro Inositol to help control blood sugars? I read that it is one of the molecules that lets insulin do it’s job and actually get the glucose into the cells. Sounds like a good thing to me! It was recommended to me to help with hormonal imbalances stemming from PCOS. I’ve never been overweight or restricted calories and had irregular cycles from the beginning, so I have no idea what to do to fix it. I’ve tried cleaner eating (everything homemade – including plenty of carbs) to no avail. Vitex has worked in the past, but isn’t having an effect now. After baby #5 my weight (20 extra lbs) didn’t drop off like it did with all the others and my morning temps are lower than ever. I’m eating as much as I want and not losing or gaining, so maybe this is ok. I’m drinking collagen with my tea every day and taking magnesium. Also, I’m having trouble falling asleep at night and stay up later than I should to avoid tossing and turning in bed. Would it be a bad thing to try some melatonin short term to get back on track?
I have been insulin resistance since 2003, A1C normally
6.2 to 6.3. After reading this website, I took 5 grams
of Glycine with every meal. I did not change my diet. My recent blood test, A1C was 5.9. It has not been this low in 15 years.
Anyone ever heard of glycine gives you large infected cysts on your body? Type 1 diabetic here.