Balancing Methionine And Glycine

[Mito]

An article from Chris Masterjohn on balancing methionine and glycine with a “Glycine-to-Methionine Ratio” searchable food database.

https://chrismasterjohnphd.com/balancing-methionine-and-glycine-in-foods-the-database/

“......Methionine helps prevent fatty liver disease, which affects an estimated 70 million Americans. It makes us mentally more flexible, and can help cool our anxiety or lift us from depression when our minds are rigidly ruminating on negative thoughts. Glycine helps stabilize our blood sugar. It helps stabilize our mind, to prevent us from drifting into endless distractions. It promotes healthy sleep, and it revitalizes our skin and bones.”

How Much Glycine Do We Need?
“Estimates of how much dietary glycine we need range from 10 grams per day to 60 grams per day. Our needs are probably closer to 10 when we are in good health and closer to 60 when we are in poor health. In terms of what has been studied in humans, we can say the following:

• 3-5 grams of glycine before a meal helps stabilize blood sugar.
• 3 grams of glycine before bed helps improve sleep.
• 15 grams of gelatin before a workout helps improve collagen synthesis in our joints.
• 20 grams of glycine per day is used to treat some rare metabolic disorders.
• 60 grams of glycine per day has been used to treat schizophrenia.

If you were to add up the glycine from all of the specific uses you might use it for, it would all fall into the estimated 10-60 grams per day we need.”

How Much Glycine Do We Need to Balance Methionine?
“We do not have any rigorous human studies showing how much glycine we need to eat to make up for a given amount of methionine. We know, however, from biochemistry that methionine depletes glycine, and we know that our ancestors consumed much more glycine than we do.

The biochemistry predicts that every gram of methionine would increase our needs for glycine by 0.5-1 gram.”

 

[Zpol]

How did I miss this!? IDK but glad you posted it @Mito

 

[Terma]

I would go by the proposed 10g daily endogenous synthesis shortfall OR that improved collagen synthesis with gelatin as a maximum daily amount.

That 60g glycine is probably not as effective for schizos as 1-3g [edited, 4g is just what I do sometimes] sarcosine, which has far fewer side effects (believe me). Above 15g probably means start looking elsewhere.

 

[Terma]

Keep in mind mitochondria contain a glycine cleavage enzyme that wastes excess glycine to ammonia (well, it refurbs folate in process, but you won't care). And most likely in some disease states it goes straight to that. At 60g you might as well chug some bathroom cleaner.

 

[ExCarniv]

After searching on Chronometer different cuts of muscle meat, even Oxtail or Shank, most have a ratio of 1:2 of Methionine:Glycine

So, seems like just a bit of gelatin per day (like 5-6 grams) will gives you a total ratio of 1:3 and that should be enough right?

I'm bumping this up because I was eating like 20-30g of gelatin and maybe I'm wasting money on this one.

 

[Mito]

Show Notes for “Why You Need Glycine: A Panel Discussion”
00:44 Introducing Alex Leaf and Vladimir Heiskanen

02:43 Cliff Notes

16:43 Vladimir, Alex, and Chris each share their favorite underappreciated fact about glycine.

19:27 Roles of glycine include detoxification, glutathione synthesis, heme synthesis, creatine synthesis, collagen synthesis, removal of intermediates when metabolic pathways are backed up, and it acts as a calming neurotransmitter.

25:21 Glycine synthesis is almost entirely dependent on folate utilization and generates about 3 grams per day.

31:52 Glycine is consumed in the diet, but methionine, found abundantly in animal protein, increases the need for glycine.

34:49 MTHFR mutations worsen glycine status.

37:25 Over the course of evolution, our collagen requirements increased substantially, but our ability to synthesize glycine stayed the same.

41:41 We run a deficit of our ability to synthesize glycine relative to our needs of about 10 grams per day, according to the most conservative estimate.

46:25 Running a glycine deficit is an intrinsic part of the biology of large vertebrates, but our ancestors mitigated this deficit by eating collagen-rich diets.

50:10 Glycine competes with other amino acids for intestinal absorption, and free glycine is absorbed less efficiently than glycine in the form of di- or tripeptides, as found in collagen.

55:11 In animal studies, glycine protects against the metabolic consequences of obesogenic diets, diabetes complications, cancer, liver injury, and kidney injury; and it has anti-inflammatory effects that might protect against endotoxins.

59:34 In human studies, glycine supplementation promotes healthy sleep and blood glucose regulation.

01:02:40 Glycine is overwhelmingly safe.

01:05:16 Collagen supplementation may increase urinary oxalate excretion.

01:07:21 Strategies to minimize risk of kidney stones: ensure optimal B6 status; measure urinary oxalate excretion; monitor urine pH; get 800-1200 mg calcium; other protective factors are vitamin A, magnesium, and citrate.

01:19:12 Practicalities of glycine supplementation; how Vladimir, Alex, and Chris get their glycine; and how collagen and glycine fit into the overall protein requirement.

01:38:01 Lab tests to assess glycine status

https://chrismasterjohnphd.com/podcast/2018/01/08/why-you-need-glycine-a-panel-discussion/

 

[bdawg]

Show Notes for “Why You Need Glycine: A Panel Discussion”
00:44 Introducing Alex Leaf and Vladimir Heiskanen

02:43 Cliff Notes

16:43 Vladimir, Alex, and Chris each share their favorite underappreciated fact about glycine.

19:27 Roles of glycine include detoxification, glutathione synthesis, heme synthesis, creatine synthesis, collagen synthesis, removal of intermediates when metabolic pathways are backed up, and it acts as a calming neurotransmitter.

25:21 Glycine synthesis is almost entirely dependent on folate utilization and generates about 3 grams per day.

31:52 Glycine is consumed in the diet, but methionine, found abundantly in animal protein, increases the need for glycine.

34:49 MTHFR mutations worsen glycine status.

37:25 Over the course of evolution, our collagen requirements increased substantially, but our ability to synthesize glycine stayed the same.

41:41 We run a deficit of our ability to synthesize glycine relative to our needs of about 10 grams per day, according to the most conservative estimate.

46:25 Running a glycine deficit is an intrinsic part of the biology of large vertebrates, but our ancestors mitigated this deficit by eating collagen-rich diets.

50:10 Glycine competes with other amino acids for intestinal absorption, and free glycine is absorbed less efficiently than glycine in the form of di- or tripeptides, as found in collagen.

55:11 In animal studies, glycine protects against the metabolic consequences of obesogenic diets, diabetes complications, cancer, liver injury, and kidney injury; and it has anti-inflammatory effects that might protect against endotoxins.

59:34 In human studies, glycine supplementation promotes healthy sleep and blood glucose regulation.

01:02:40 Glycine is overwhelmingly safe.

01:05:16 Collagen supplementation may increase urinary oxalate excretion.

01:07:21 Strategies to minimize risk of kidney stones: ensure optimal B6 status; measure urinary oxalate excretion; monitor urine pH; get 800-1200 mg calcium; other protective factors are vitamin A, magnesium, and citrate.

01:19:12 Practicalities of glycine supplementation; how Vladimir, Alex, and Chris get their glycine; and how collagen and glycine fit into the overall protein requirement.

01:38:01 Lab tests to assess glycine status

https://chrismasterjohnphd.com/podcast/2018/01/08/why-you-need-glycine-a-panel-discussion/

thx!

 

[Amazoniac]

The biochemistry predicts that every gram of methionine would increase our needs for glycine by 0.5-1 gram.

Is..
..Met 1.0:0.5 Gly based on molecular weights (~150 g/mol and ~75 g/mol)?
..Met 1.0:1.0 Gly based on the following experiment (from their linked discussion)?
- Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet

- Problems With Sulphur (Met: 3 g/70 kg)
- The Metabolic Capacity For Glycine Biosynthesis Does Not Satisfy The Need For Collagen Synthesis (Gly: 11.5 g/70 kg)

Values aren't disconsidering the minimum requirement and are inflated, but give Met 1:4 Gly.

 

[Amazoniac]

- Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet

"In the present study, we used a low casein diet as a basal diet since Met toxicity is more severe in low-protein diets than in adequate or high-protein diets (1, 2). It should be noted that the low casein diet is the most deficient in Met. Hence, it is likely that the alleviating effect of Gly on growth depression caused by an excess Met diet is due to the increase in food intake and sufficient Met content in the diet in addition to direct detoxification."

"The activity of glycine N-methyltransferase in the rat liver was significantly increased by a high Met diet while it was not further increased by the addition of Gly to the high Met diet (26). This also supports the hypothesis that the effect of Gly on Met metabolism may not be mediated by a further increase in enzyme activity in the transsulfuration pathway."

"Feeding a high Met diet necessarily increases cysteine formation via cystathionine. It was reported that cystathionine b-synthase activity was depressed by dietary supplementation with cystine (30, 31), indicating feedback inhibition of the enzyme by cysteine. The hepatic cystathionine level was, however, increased in rats fed the 10C2M [control + methionine] diet and further increased by the dietary addition of Gly (Fig. 3) while no such a marked increase in the cysteine level was observed (data not shown). This might be explained by the finding of Yamaguchi et al. (28, 32, 33) that cysteine metabolism was enhanced in rats fed a high Met or high cysteine diet; they demonstrated an increase in the activity of cysteine dioxygenase, which catalyzes the conversion of cysteine to cysteine sulfinate by dietary Met and cysteine. The fact that the hepatic cystathionine level was markedly enhanced in rats fed the 10C2M2G diet also suggests the possibility that cystathionine y-lyase may be rate limiting in rats fed a Gly-added high Met diet."

"It has been observed that feeding a high Met diet results in a decrease in the levels of certain amino acids such as Gly, Ser, and Thr in the plasma and tissues, especially in the liver (22, 37-39). This decrease in amino acid levels is regarded as being mainly due to the ingestion of a large amount of Met, but the contribution of food intake reduction must also be considered to some extent when animals are fed ad libitum, The results of the present study are essentially in accord with those of previous reports. Our results also showed that the addition of Gly to a high Met diet effectively prevented the decrease in the hepatic Gly level, but it only partially prevented the decrease in the hepatic Ser level and it further lowered the hepatic Thr level (Figs. 2 and 3). It can be considered that the profound decrease in hepatic levels of Gly and Ser leads to a restriction of Met metabolism since the Km values of Gly and Ser for hepatic glycine N-methyltansferase and cystathionine b-synthase were shown to be 2.2mM (40) and 1.6mM (41), respectively, although a much lower Km value of Gly has also been reported (42). Hence, it is likely that the restoration of decreased Gly and Ser levels in the liver is one of the major causes of the effect of dietary Gly on Met metabolism. In the early period of experimental feeding, however, the hepatic Met level was not decreased by dietary addition of Gly despite the fact that a decrease in Gly and Ser levels was prevented to a considerable degree. The reason for this ineffectiveness of Gly is not known, but it may be related in some way to the fact that it takes a few days before an obvious effect of Gly on growth and food intake is elicited (18)."

Spoiler

"In addition to Gly, Ser is known to alleviate Met toxicity, but its effect is always less than that of Gly (18, 43). Girard-Globa et al. (39) have postulated that the limited effect of Ser might be ascribed to a Thr deficiency due to the induction of the hepatic serine-threonine dehydratase by the dietary addition of Ser. However, our results showed that the dietary addition of Gly also decreased the hepatic Thr level, suggesting that Thr deficiency may not be a major cause of the differential effects of Gly and Ser."

"In conclusion, it is suggested that the hepatic Gly level is the primary factor in determining the rate of Met metabolism in rats fed a high Met diet and that the effect of Gly added to a high Met diet is elicited through the restoration of the decreased Gly level."​

 

[Enhanced]

I would go by the proposed 10g daily endogenous synthesis shortfall OR that improved collagen synthesis with gelatin as a maximum daily amount.

That 60g glycine is probably not as effective for schizos as 1-3g [edited, 4g is just what I do sometimes] sarcosine, which has far fewer side effects (believe me). Above 15g probably means start looking elsewhere.

Keep in mind mitochondria contain a glycine cleavage enzyme that wastes excess glycine to ammonia (well, it refurbs folate in process, but you won't care). And most likely in some disease states it goes straight to that. At 60g you might as well chug some bathroom cleaner.

Hi. Do you have schizophrenia? Currently I'm doing 50g glycine a day but I'm worried about ammonia as well. Do you reckon supplementing with one of the amino acids from the urea cycle could help? 50g of protein without any extra arginine seems a lot (lands me at about 170g of protein a day I believe). Do you think the studies on it didn’t show any significant side effects because they were done for short amounts of time (4-6 weeks)?