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Good Proteins, Bad Proteins…

1. Preface: Not All Protein Is Created Equal

scallops glycineA few months ago, an interesting Danish study was published, showing that a “high-fat/high-sugar” diet would cause obesity to mice consuming chicken, cod, or crab as their main protein source. However, the group of mice eating scallop protein didn’t develop these problems at all. The researchers performed some statistical analyses, and suggested that the particularly high glycine and taurine content of scallop protein might explain some of these effects.

 

scallop-adipose-tissue

The mice in scallop protein group were remarkably lean compared to all the other groups. The figure shows the weights of various adipose tissues: for example, “AbWAT” refers to “abdominal white adipose tissue”.  (Tastesen et al. 2014)

 

The scientific literature also includes several reports of anti-inflammatory and hypocholesterolemic effects of fish protein in humans and rodents. Some of the researchers explain these effects by the high content of arginine, glycine, and taurine in seafood.[2]

Lately, I have spent a lot of time thinking about the metabolic effects of various amino acids. It seems that not all protein is necessarily created equal, and the effects are largely mediated by their amino acid content (yet there are other factors as well).

 

2. Metabolic Effects of Amino Acids: Glycine

When I started reading protein research, one of the first things I noticed was the fact that many of the healthy protein sources contain a fair amount of glycine.

Since there are numerous studies showing that this simple amino acid protects rodents from inflammation, metabolic syndrome, cancer, diabetes, animal protein, endotoxin, hypoxia, hemorrhagic shock, lead and cadmium toxicity, dental caries, intestinal damage and many other things, I started to consider that altering amino acid composition of diet might have very far-reaching health effects. In one study, a high-glycine diet was also associated with 28% increased median lifespan of rats.[3]

A Mexican research group has also shown that in rats, 1.5% glycine (added in drinking water) can reverse the metabolic syndrome caused by a high-sugar diet. The same research group has also shown that glycine can prevent most of the harm caused by high ethanol consumption in rats.[4]

In my previous article, I wrote about their study as follows:

This research group did something quite nasty to their rats. They added 30% sucrose to their water for 20 weeks. Consequently, the rats got a huge amount of calories from their drinking water and thus their food intake decreased by more than fifty percent. That equals a huge decrease in protein, mineral, and vitamin intake as well.

The rats developed full-blown metabolic syndrome in 20 weeks. But after that, the researchers also added 1% glycine to the drinking water. In 4 weeks, the sugar-fed rats became almost as healthy as the control group. With glycine, the rats’ blood pressure, fat cells, blood markers and many other things quickly became normalized despite the continued sugar feeding and low nutrient intake.

 

glycine-mexican

The blood pressure was decreased after the addition of 1% glycine to the drinking water. The adipocyte size was also normalized in the group receiving glycine in addition to their high-sucrose diet. (El Hafidi et al. 2004)

 

In humans, two studies examining the effects of glycine on metabolic syndrome have been published (15 grams a day for 3 months). The noted effects aren’t nearly as remarkable as in rodent studies, but the changes in some markers related to oxidative stress still appear quite beneficial.[5]

A1C levels of patients given glycine were significantly lower after 3 months of treatment than those of the placebo group.” (Cruz et al. 2008)
A significant reduction in TNF-receptor I levels was observed in patients given glycine compared with placebo.” (Cruz et al. 2008)
“Individuals treated with glycine showed a 25% decrease in TBARS compared with the placebo-treated group. Furthermore, there was a 20% reduction in SOD-specific activity in the glycine-treated group, which correlated with SOD2 expression. G6PD activity and SNO-Hb levels increased in the glycine-treated male group.” (Díaz-Flores et al. 2013)
Systolic blood pressure (SBP) also showed a significant decrease in the glycine-treated men (p = 0.043).” (Díaz-Flores et al. 2013)

A research group from Houston has also shown that high doses of glycine and N-acetyl-cysteine (NAC) had very quick beneficial effects in diabetic patients, HIV patients, and healthy elderly people.

In their studies, the subjects received approximately 100mg/kg/d of both amino acids for two weeks. If we look at the study of healthy elderly subjects, for example, we can see that the treatment improved the subjects’ energy-metabolism, insulin sensitivity, and oxidative stress to the levels of healthy young persons. Based on these results, it seems possible that the combination of glycine and cysteine has beneficial effects that cannot be achieved with glycine alone.[6]

 

gly-cys3

The combination of Glycine+NAC improved the fat oxidation (NEFA Ox), insulin sensitivity (HOMA-IR) and (HOMA-IR) oxidative stress levels (DROMs, F2-isoprostanes, lipid peroxides). (Sekhar et al. 2011, Nguyen et al. 2013)

 

3. Metabolic Effects of Amino Acids: Glycine:Methionine Ratio and The “Animal vs. Plant Protein” (Paleo vs. Vegan) Controversy

When thinking about glycine, it might be also wise to consider the effects of another amino acid, methionine. According to animal studies, excessive amounts of methionine might predispose to the metabolic syndrome. In some animal studies methionine restriction has been shown to protect against obesity, and to prolong lifespan.[7]

In many studies, the restriction has been quite large (80%), which isn’t very easy to achieve in real life. However, some researchers have reported beneficial effects even with a moderate methionine restriction (40%).[7]

However, it seems that the main “benefits” of methionine restriction also require simultaneous cysteine restriction, and many of the beneficial effects are likely to be a consequence of some kind of a deficiency.

It has also been suggested that some of the harmful effects of excess methionine might be caused by glycine depletion, because glycine is needed in the clearance of excess methionine. Animal studies have shown that glycine can also protect from the harmful effects of methionine, e.g. by dramatically decreasing homocysteine levels.[7]

Some scientists have been explaining some of the possible benefits of vegetarianism or plant protein by their low methionine content or high ratio of glycine to methionine. For example, potatoes, soy, rice, almonds, lentils, and beans have quite a high glycine:methionine ratio while meat, milk, and eggs usually contain much more metionine and less glycine.[7]

gly-met-proteins

Amino acid profiles of casein, soybean, potato and rice proteins. Milk protein (casein) contains more methionine and less glycine than most plant proteins. (Morita et al. 1997)

Rice protein has been studied in animals, and it has been reported to have a positive impact on metabolism (fat mass, cholesterol, inflammation). Rice protein has twice as much glycine and a little bit less methionine than casein, and it is possible that this is an important factor causing these beneficial effects. According to some studies, the ratio of lysine to arginine might also affect some health variables (especially cholesterol levels).[8]

Here in Finland, some researchers at my university have been studying the health effects of whey proteins. Whey seems to protect mice from obesity, and the main anti-obesity factor seems to be the alpha-lactalbumin (ALA) protein. It has also been shown that ALA has an aspirin-like effect on inflammation, thus protecting mice from colon cancer and probably other diseases as well.[8]

A study showed that the effects of ALA are mainly mediated by its amino acid composition, which has much higher glycine:methionine ratio than casein or the predominant whey protein, beta-lactoglobulin (Shi et al. 2011). High content of cysteine and/or tryptophan might also mediate these beneficial effects.[8]

Collagen is the most abundant protein in mammals, and accounts for 25-30% for the total body protein in humans. Biologist Ray Peat talks about proportion of 50%, but I don’t know to which animal he is referring to. However, collagen is an important source of glycine, containing 22% glycine by weight.

In the Western culture, few people eat the collagen-containing parts of the animal (skin, bones, cartilage), and thus, the low intake of collagen usually leads to a low glycine:methionine ratio of the Western diet. I think that the unbalanced way of eating animal protein (eg. eating only the muscles) might be one reason why in some studies, “animal protein” is associated with degenerative diseases.

This is an example of the graphs that the Vegan/ChinaStudy/ForksOverKnives folks often like to show us. (Source: http://joshmitteldorf.scienceblog.com/2013/02/12/china-study-a-voice-for-veganism/ )

 

4. Metabolic Effects of Amino Acids: Taurine and GABA

Taurine and GABA have also been shown to protect humans and rodents against some of the harmful effects of junk food.

In animal studies, taurine has been shown to be beneficial in the prevention of metabolic syndrome, liver injury, brain damage and several other conditions. Epidemiological studies also support the idea of its beneficial effects for health. One Japanese research group went as far as to suggest that taurine is “the nutritional factor for the longevity of the Japanese“.

In clinical human studies, taurine (1.5-6.0 grams a day) has been quite useful for metabolic syndrome, heart failure, liver diseases, and the alleviation of the side effects of chemotherapy. While the preliminary results are promising, the quality of the these studies isn’t very high.[9]

GABA seems to protect rodents from the metabolic syndrome, and some special protective effects have been noted in the islet cells of the pancreas. A moderate protective effect on mice can be observed even with a very small dose (0.06% GABA added to drinking water).[9]

In humans, the effects of GABA haven’t really been studied. Some papers seem to show that it might alleviate high blood pressure, but we have no information about other possible beneficial effects (or harms).[9]

Fish and shellfish are a decent source of taurine. (Yamori et al. 2010, Fig. 12)

 

5. Metabolic Effects of Amino Acids: Histidine (and Carnosine)

Histidine and the histidine-containing dipeptides (carnosine/anserine) protect humans and rodents from metabolic syndrome and some other problems associated with inflammation. In mice, even the addition of 0.1% histidine or carnosine to the drinking water has a strong protective effect against the many harms caused by a high-fat diet.[10]

These excellent results have also been reproduced in humans. In a recent 3-month study, the daily use of histidine was associated with a 30% decrease in inflammatory markers (TNF-alpha, IL-6, CRP) and a 2.7kg fat loss (5 pounds). The dose was 4 grams a day, which is 2-3 times the average amount of histidine obtained from food (1.5 grams).[10]

 

In the histidine group, the treatment effects were surprisingly good: fat mass decreased (FM), chronic inflammation decreased (TNF-α, IL-6), oxidative stress decreased (SOD, GSH-Px), insulin sensitivity improved (HOMA-IR), free fatty acid level decreased (NEFA). (Feng et al. 2013)

 

 6. The Mechanisms of Amino Acids: Chloride Channels, Endotoxemia, Inflammation, Bile Acids, Antioxidant Effects

In my earlier article (Thyroid, Inflammation, and Metabolic Syndrome: The Surprising Power of Context), I wrote that metabolic syndrome isn’t necessarily caused by sugar, alcohol, or fat itself, but generally, junk foods allow the entry of bacterial endotoxin (LPS) into the bloodstream. This activates the immune system, and the subsequent inflammation is the real reason behind metabolic syndrome and many other issues. I think it’s probably good to focus on endotoxin as the cause of the inflammation, even though we can’t completely ignore factors like energy overload (lipotoxicity, glucotoxicity) that also can activate inflammatory processes.

 

diet-inflammation-metsyn

 

If amino acids have a protective effect against metabolic syndrome, it is likely that they affect some part of this chain of events. And it seems that inflammation is the part in question.

The most important effects of glycine, taurine, and GABA are probably related to their inhibitory effects via chloride channels (glycine and GABA receptor). Glycine hyperpolarizes macrophage cells and endothelial cells, thus limiting the secretion of cytokines and growth factors stimulated by endotoxins and other harmful things. This anti-inflammatory action is the main reason why glycine has a strong protective effect against almost every kind of physical illness.[11]

Some of the effects of glycine and taurine are also related to their effects on the conjugation of bile acids. Bile acids protect intestines against bacterial overgrowth and endotoxemia, and they can also activate intracellular thyroid hormone metabolism.[12]

Different animal species conjugate bile acids in different ways. Mice conjugate bile acids mainly with taurine. Rats conjugate them with glycine and taurine, but mostly with taurine. Humans conjugate them with glycine and taurine, but mostly with glycine. These differences might explain some of the varying results between different animal models.[12]

Taurine also activates glycine receptors, and it has some similar effects as glycine.[11]

Histidine and carnosine appear to have anti-inflammatory, antioxidant, anti-nitrosative and metal-chelating effects. Some of their effects seem to be related to histamine metabolism, but there is also some evidence of anti-histamine effects. It’s unfortunate that these compounds have strong effects but the mechanisms seem to be partially unknown.[13]

 

7. What Else Besides The Amino Acid Composition Matters? (Intact Protein vs. Hydrolyzed Protein)

In addition to its amino acid profile, some other properties such as structure and fat-absorptive effects also mediate the health effects of proteins.

If milk protein (casein) is given to mice in the pre-digested (hydrolyzed) form, the fat mass of mice is dramatically reduced by 70%.[14]

intact-hydrolyzed-casein

The fat mass of mice eating hydrolyzed casein was only one-third of the fat mass of mice eating intact casein. [I-16 = intact casein (16E%) // H-16 = hydrolyzed casein (16%) // eWAT = epididymal white adipose tissue // iWAT = inguinal white adipose tissue] (Lillefosse et al. 2013)

These effects might be mediated by gut hormones such as cholecystokinin (CCK) or glucagon-like peptide (GLP-1), but so far, very little research on this topic has been conducted.

Casein also seems to decrease fat absorption in the intestines a little bit. This might lead to a slight or moderate anti-obesity effect.[14]

 

8. Conclusions

– In health blogs and nutrition discussions, the health effects of carbohydrates and fats are often emphasized. However, it also seems that carefully choosing your proteins might also have important effects.

– The health effects of different proteins are largely mediated by their amino acid profiles. Some amino acids such as glycine and histidine might decrease low-grade inflammation, while high intake of methionine might be harmful. These effects have been mostly studied in rodents with very beneficial results, but currently there is quite little human research on the subject. Therefore, it’s impossible to draw strong conclusions about the effects of these amino acids in humans.

– Examples of protein sources with a good glycine:methionine ratio would include: gelatin, scallop, fish, potatoes, lentils and beans. Many popular animal foods such as milk, eggs and meat tend to have quite a poor ratio of these amino acids. The amino acid profiles of plant proteins might explain some of the beneficial effects of vegetarian diets.

– Amino acids are not the only factor affecting the biological effects of dietary protein. In some cases, hydrolyzed protein (peptide) might be more suitable for weight control than intact protein, and the effect might be mediated by gastrointestinal hormones. Casein might decrease the harmful effects of a high-fat diet by decreasing fat absorption in the intestines.

– Some studies have been showing that individuals with insulin resistance might have lower plasma levels of glycine, histidine, and taurine than healthy people. Because this “deficiency” of anti-inflammatory amino acids might lead to more inflammation, it is possible that people with insulin resistance would benefit most from the amino acid supplementation.[15]

 

About the Author

Vladimir Heiskanen2Vladimir Heiskanen of Finland has been researching and writing about health for several years. Currently a dental student at the University of Helsinki and a blogger since 2010, he has a keen interest in human biology, and has studied scores of books, reports, and cutting-edge health websites, especially the work of Chris Masterjohn, Steven Hamley, Ray Peat, and Matt Stone. You can read all of his fascinating articles published at 180D HERE.

 

Appendix: Further Reading

180DegreeHealth – Thyroid, Inflammation, and Metabolic Syndrome: The Surprising Power of Context (by Vladimir Heiskanen)
180DegreeHealth – Fibromyalgia: A Disease of Low Metabolism (by Vladimir Heiskanen)

180DegreeHealth – Diet and Inflammation, part I (by Joel Brind)
180DegreeHealth – Diet and Inflammation, part II (by Joel Brind)
180DegreeHealth – Diet and Inflammation, part III (by Joel Brind)
180DegreeHealth – Diet and Inflammation, part IV (by Joel Brind

180DegreeHealth – Glycine and Cancer (by Joel Brind)
180DegreeHealth – Glutathione: Is More Better? (by Joel Brind)

Valtsu’s – Health Benefits of Glycine

References

[1] Health effects of scallop protein

[glycine-scallop] Amino Acids. 2014 Jul;46(7):1659-71. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B.

[glycine-scallop] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014)

 

[2] Health effects of fish protein

[fish-protein] Br J Nutr. 2013 Feb 28;109(4):648-57. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults. Vikøren LA, Nygård OK, Lied E, Rostrup E, Gudbrandsen OA. “The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P< 0·05), 2 h postprandial glucose (P< 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P< 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P< 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P< 0·05), and reduced LDL-cholesterol (P< 0·05). Body muscle % was increased (P< 0·05) and body fat % was reduced (P< 0·05) after 4 weeks’ supplementation”

[fish-protein] J Nutr. 2008 Dec;138(12):2386-91. doi: 10.3945/jn.108.092346. Dietary cod protein reduces plasma C-reactive protein in insulin-resistant men and women. Ouellet V, Weisnagel SJ, Marois J, Bergeron J, Julien P, Gougeon R, Tchernof A, Holub BJ, Jacques H.

[fish-protein] Biochim Biophys Acta. 2009 Apr;1791(4):254-62. Fish protein hydrolysate elevates plasma bile acids and reduces visceral adipose tissue mass in rats. Liaset B, Madsen L, Hao Q, Criales G, Mellgren G, Marschall HU, Hallenborg P, Espe M, Frøyland L, Kristiansen K.

[fish-protein] Diabetes Care. 2007 Nov;30(11):2816-21. Dietary cod protein improves insulin sensitivity in insulin-resistant men and women: a randomized controlled trial. Ouellet V, Marois J, Weisnagel SJ, Jacques H.

[fish-protein-bile] J Biol Chem. 2011 Aug 12;286(32):28382-95. Nutritional regulation of bile acid metabolism is associated with improved pathological characteristics of the metabolic syndrome. Liaset B, Hao Q, Jørgensen H, Hallenborg P, Du ZY, Ma T, Marschall HU, Kruhøffer M, Li R, Li Q, Yde CC, Criales G, Bertram HC, Mellgren G, Ofjord ES, Lock EJ, Espe M, Frøyland L, Madsen L, Kristiansen K. “Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. […] Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion.” “[W]e conclude that the increased plasma BA level in the SPH-fed rats was likely due to higher intestinal influx. “

“The benefits of activating Tgr5 or Fxr for the prevention of the metabolic syndrome have stimulated the development of synthetic ligands for these receptors (24, 25). Another strategy to increase Tgr5 and/or Fxr signaling would be to alter endogenous BA metabolism. As hepatic bile acid conjugation is important for secretion of BAs into bile (2) and rats conjugate BAs to both taurine and glycine with high efficiency (26), the dietary levels of these amino acids might be crucial for BA conjugation and secretion (27).”

[fish-protein] J Nutr. 2004 Jun;134(6):1320-7. Fish protein hydrolysate reduces plasma total cholesterol, increases the proportion of HDL cholesterol, and lowers acyl-CoA:cholesterol acyltransferase activity in liver of Zucker rats. Wergedahl H, Liaset B, Gudbrandsen OA, Lied E, Espe M, Muna Z, Mørk S, Berge RK.

[fish-protein] Int J Mol Med. 2012 Feb;29(2):311-8. doi: 10.3892/ijmm.2011.836. Epub 2011 Nov 11. Dietary sardine protein lowers insulin resistance, leptin and TNF-α and beneficially affects adipose tissue oxidative stress in rats with fructose-induced metabolic syndrome. Madani Z, Louchami K, Sener A, Malaisse WJ, Ait Yahia D.

[fish-protein] Physiol Genomics. 2010 Feb 4;40(3):189-94. Fish nutrients decrease expression levels of tumor necrosis factor-alpha in cultured human macrophages. Rudkowska I1, Marcotte B, Pilon G, Lavigne C, Marette A, Vohl MC.

[fish-protein] PLoS One. 2013 Oct 4;8(10):e77274. Beneficial effects of cod protein on inflammatory cell accumulation in rat skeletal muscle after injury are driven by its high levels of arginine, glycine, taurine and lysine. Dort J, Leblanc N, Maltais-Giguère J, Liaset B, Côté CH, Jacques H.

[fish-protein] Appl Physiol Nutr Metab. 2012 Jun;37(3):489-98. doi: 10.1139/h2012-021. Epub 2012 Apr 17. Beneficial effects of cod protein on skeletal muscle repair following injury. Dort J, Sirois A, Leblanc N, Côté CH, Jacques H.

[fish-protein] Nutr Metab Cardiovasc Dis. 2009 Dec;19(10):690-6. Consumption of cod and weight loss in young overweight and obese adults on an energy reduced diet for 8-weeks. Ramel A, Jonsdottir MT, Thorsdottir I. “According to linear models weight loss was 1.7 kg greater among subjects consuming 150 g 5x/week compared to the control group”

 

[3] Health effects of glycine

[glycine] Vladimir Heiskanen: Health Benefits of Glycine (2013)

[glycine] Amino Acids. 2013 Sep;45(3):463-77. doi: 10.1007/s00726-013-1493-1. Epub 2013 Apr 25. Glycine metabolism in animals and humans: implications for nutrition and health. Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G.

[glycine] The FASEB Journal. 2011;25:528.2. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Brind J , Malloy V, Augie I, Caliendo N, Vogelman JH, Zimmerman JA, Orentreich N. “Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF.”

 

[4] Glycine and metabolic syndrome (animal studies)

[glycine-metabolic-syndrome] Am J Physiol Regul Integr Comp Physiol. 2004 Dec;287(6):R1387-93. Glycine intake decreases plasma free fatty acids, adipose cell size, and blood pressure in sucrose-fed rats. El Hafidi M, Pérez I, Zamora J, Soto V, Carvajal-Sandoval G, Baños G.

[glycine-metabolic-syndrome] Clin Sci (Lond). 2014 Jan 1;126(1):19-29. Glycine restores glutathione and protects against oxidative stress in vascular tissue from sucrose-fed rats. Ruiz-Ramírez A, Ortiz-Balderas E, Cardozo-Saldaña G, Diaz-Diaz E, El-Hafidi M.

[glycine-metabolic-syndrome] Amino Acids. 2014 Mar 23. Scallop protein with endogenous high taurine and glycine content prevents high-fat, high-sucrose-induced obesity and improves plasma lipid profile in male C57BL/6J mice. Tastesen HS, Keenan AH, Madsen L, Kristiansen K, Liaset B.

[glycine-metabolic-syndrome] Can J Physiol Pharmacol. 2011 Dec;89(12):899-910. Effect of glycine on the cyclooxygenase pathway of the kidney arachidonic acid metabolism in a rat model of metabolic syndrome. Pérez-Torres I1, Ibarra B, Soria-Castro E, Torrico-Lavayen R, Pavón N, Diaz-Diaz E, Flores PL, Infante O, Baños G.

[glycine-metabolic-syndrome] Cell Biochem Funct. 2004 Mar-Apr;22(2):123-8. Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocyte of rats with alcohol-induced liver injury. Senthilkumar R, Sengottuvelan M, Nalini N

 

[5] Glycine, metabolic syndrome and stroke (human studies)

[glycine-humans] J Endocrinol Invest. 2008 Aug;31(8):694-9. Glycine treatment decreases proinflammatory cytokines and increases interferon-gamma in patients with type 2 diabetes. Cruz M, Maldonado-Bernal C, Mondragón-Gonzalez R, Sanchez-Barrera R, Wacher NH, Carvajal-Sandoval G, Kumate J.

[glycine-humans] Can J Physiol Pharmacol. 2013 Oct;91(10):855-60. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Díaz-Flores M, Cruz M, Duran-Reyes G, Munguia-Miranda C, Loza-Rodríguez H, Pulido-Casas E, Torres-Ramírez N, Gaja-Rodriguez O, Kumate J, Baiza-Gutman LA, Hernández-Saavedra D.

[glycine-humans-stroke] Cerebrovasc Dis. 2000 Jan-Feb;10(1):49-60. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Gusev EI, Skvortsova VI, Dambinova SA, Raevskiy KS, Alekseev AA, Bashkatova VG, Kovalenko AV, Kudrin VS, Yakovleva EV.

 

[6] Glycine and cysteine and the metabolic health of elderly people, diabetic patients and HIV-infected patients

[glycine-cysteine-humans] Diabetes Care. 2011 Jan;34(1):162-7. Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine. Sekhar RV, McKay SV, Patel SG, Guthikonda AP, Reddy VT, Balasubramanyam A, Jahoor F. [dose was 100mg/kg/d, according to the calculation of the author of this paper]

[glycine-cysteine-humans] Am J Clin Nutr. 2011 Sep;94(3):847-53. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. Sekhar RV, Patel SG, Guthikonda AP, Reid M, Balasubramanyam A, Taffet GE, Jahoor F.

[glycine-cysteine-humans] Aging Cell. 2013 Jun;12(3):415-25. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. Nguyen D, Samson SL, Reddy VT, Gonzalez EV, Sekhar RV.

[glycine-cysteine-humans] J Clin Endocrinol Metab. 2014 Jan;99(1):169-77. Effect of increasing glutathione with cysteine and glycine supplementation on mitochondrial fuel oxidation, insulin sensitivity, and body composition in older HIV-infected patients. Nguyen D1, Hsu JW, Jahoor F, Sekhar RV.

 

[7] Methionine, methionine restriction and glycine’s effects on methionine metabolism (animal studies)

[methionine] Aging Cell. 2006 Aug;5(4):305-14. Methionine restriction decreases visceral fat mass and preserves insulin action in aging male Fischer 344 rats independent of energy restriction. Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N. “Conversely, MR rats show significantly reduced visceral fat compared to CF and PF with concomitant decreases in basal insulin, glucose, and leptin, and increased adiponectin and triiodothyronine. Daily energy expenditure in MR animals significantly exceeds that of both PF and CF.”

[methionine] Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R728-39. Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states. Hasek BE, Stewart LK, Henagan TM, Boudreau A, Lenard NR, Black C, Shin J, Huypens P, Malloy VL, Plaisance EP, Krajcik RA, Orentreich N, Gettys TW.

[methionine] Exp Gerontol. 2013 Jul;48(7):654-60. Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Perrone CE, Malloy VL, Orentreich DS, Orentreich N. “These beneficial effects of MR involve a host of metabolic adaptations leading to increased mitochondrial biogenesis and function, elevated energy expenditure, changes of lipid and carbohydrate homeostasis, and decreased oxidative damage and inflammation.”

[methionine] PLoS One. 2012;7(12):e51357. Methionine-restricted C57BL/6J mice are resistant to diet-induced obesity and insulin resistance but have low bone density. Ables GP, Perrone CE, Orentreich D, Orentreich N.

[methionine] Biogerontology. 2008 Jun;9(3):183-96. Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Caro P, Gómez J, López-Torres M, Sánchez I, Naudí A, Jove M, Pamplona R, Barja G.

[methionine] Rejuvenation Res. 2009 Dec;12(6):421-34. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, López-Torres M, Pamplona R, Barja G.

[glycine-methionine] The FASEB Journal. 2011;25:528.2. Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats. Brind J , Malloy V, Augie I, Caliendo N, Vogelman JH, Zimmerman JA, Orentreich N. “We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde.”

[glycine-methionine] J Nutr Sci Vitaminol (Tokyo). 1987 Jun;33(3):195-205. Effect of dietary glycine on methionine metabolism in rats fed a high-methionine diet. Sugiyama K, Kushima Y, Muramatsu K.

[glycine-methionine] Proc Soc Exp Biol Med. 1949 Feb;70(2):327-30. The effect of feeding excess glycine, L-arginine, and DL-methionine to rats on a casein diet. ROTH JS, ALLISON JB.

[glycine-methionine] Biosci Biotechnol Biochem. 2006 Oct;70(10):2403-9. Epub 2006 Oct 7. Suppression of methionine-induced hyperhomocysteinemia by glycine and serine in rats. Fukada S, Shimada Y, Morita T, Sugiyama K.

[glycine-methionine] Arch Biochem Biophys. 1993 Feb 1;300(2):598-607. Methionine toxicity in the rat in relation to hepatic accumulation of S-adenosylmethionine: prevention by dietary stimulation of the hepatic transsulfuration pathway. Regina M, Korhonen VP, Smith TK, Alakuijala L, Eloranta TO.

[glycine-methionine] J Nutr Sci Vitaminol (Tokyo). 1990 Oct;36 Suppl 2:S105-10. Significance of the amino acid composition of dietary protein in the regulation of plasma cholesterol. Sugiyama K, Muramatsu K. “diets high in methionine and low in cystine and glycine content tend to increase the plasma cholesterol level and diets of opposite amino acid content tend to decrease the plasma cholesterol level.”

[glycine-methionine] Br J Nutr. 2005 Sep;94(3):321-30. Dietary proteins with high isoflavone content or low methionine-glycine and lysine-arginine ratios are hypocholesterolaemic and lower the plasma homocysteine level in male Zucker fa/fa rats. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Berge RK.

[glycine-methionine-cholesterol] J Nutr. 1997 Mar;127(3):470-7. Cholesterol-lowering effects of soybean, potato and rice proteins depend on their low methionine contents in rats fed a cholesterol-free purified diet. Morita T, Oh-hashi A, Takei K, Ikai M, Kasaoka S, Kiriyama S. “There was a significant negative correlation between serum cholesterol concentration and fecal total steroid excretion (r = -0.490, P = 0.01). However, a stronger positive correlation was observed between serum cholesterol concentration and dietary methionine concentration (r = 0.674, P = 0.0003) or methionine:glycine ratios (r = 0.656, P = 0.0005). In a separate experiment in rats fed diets containing amino acid mixtures simulating the RP, PP and SP diets, serum total cholesterol concentrations were lower than in rats fed simulated casein.”

[glycine-methionine-cholesterol-vegetarians] Bratisl Lek Listy. 2005;106(6-7):231-4. Health benefits and risks of plant proteins. Krajcovicova-Kudlackova M, Babinska K, Valachovicova M. “Vegetarians have a significantly higher intake of non-essential amino acids arginine and pyruvigenic amino acids glycine, alanine, serine.”

[glycine-methionine-cholesterol-vegetarians] Med Hypotheses. 2009 Feb;72(2):125-8. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. McCarty MF, Barroso-Aranda J, Contreras F. “Whole-food vegan diets that moderate bean and soy intake, while including ample amounts of fruit and wine or beer, can be quite low in methionine, while supplying abundant nutrition for health (assuming concurrent B12 supplementation).” 

 

[8] Health effects of rice protein, alpha-lactalbumin and some other exotic protein sources (animal studies). Also, some papers on lysine:arginine ratio.

[rice-protein-glycine-lysine-arginine] Br J Nutr. 2013 Oct;110(7):1211-9. Rice protein ameliorates the progression of diabetic nephropathy in Goto-Kakizaki rats with high-sucrose feeding. Kubota M, Watanabe R, Kabasawa H, Iino N, Saito A, Kumagai T, Fujimura S, Kadowaki M. “These results strongly indicate that dietary RP can ameliorate the progression of diabetic nephropathy at an early stage compared with C.” “RP had higher arginine and proline contents, but a lower lysine content compared with C (P,0·01).” [rice protein also did also contain 148% more glycine than casein]

[rice-protein] Prev Nutr Food Sci. 2013 Sep;18(3):210-3. Cholesterol-lowering Effect of Rice Protein by Enhancing Fecal Excretion of Lipids in Rats. Um MY, Ahn J, Jung CH, Ha TY. “Compared with rats fed a HCD with casein, the total cholesterol (TC) level in the plasma was significantly reduced in the rats fed rice protein. However, no significant differences were observed in the triglycerides, high-density lipoprotein (HDL), and glucose levels among the experimental groups. […] In addition, rice protein significantly increased the levels of TC and bile acids in the feces.”

[rice-protein] Life Sci. 2012 Oct 5;91(11-12):389-94. Rice protein improves oxidative stress by regulating glutathione metabolism and attenuating oxidative damage to lipids and proteins in rats. Yang L, Chen JH, Xu T, Zhou AS, Yang HK. “These results suggest that RP can prevent hyperlipidemia in part through modifying glutathione metabolism, and sulfur amino acids may be the main modulator of this antioxidative mechanism.”

[rice-protein] Lipids Health Dis. 2012 Feb 13;11:24. Rice protein improves adiposity, body weight and reduces lipids level in rats through modification of triglyceride metabolism. Yang L, Chen JH, Lv J, Wu Q, Xu T, Zhang H, Liu QH, Yang HK. “Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P < 0.05), as well as hepatic accumulation of lipids (P < 0.05). RP-A and RP-E significantly depressed the hepatic activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PD) and malate dehydrogenase (MDH) (P < 0.05), whereas the activities of lipoprotein lipase (PL) and hepatic lipase (HL) were significantly stimulated (P < 0.05), as compared to CAS.” “[H]igher contents of glycine were found in RP groups, as compared with CAS (P < 0.05).”

[rice-protein] J Agric Food Chem. 2011 Oct 26;59(20):10927-33. Lower weight gain and hepatic lipid content in hamsters fed high fat diets supplemented with white rice protein, brown rice protein, soy protein, and their hydrolysates. Zhang H, Bartley GE, Mitchell CR, Zhang H, Yokoyama W. “The brown rice protein hydrolysate (BRPH) diet group reduced weight gain 76% compared with the control. Animals fed the BRPH supplemented diet also had lower final body weight, liver weight, very low density lipoprotein cholesterol (VLDL-C), and liver cholesterol, and higher fecal fat and bile acid excretion than the control.”

[rice-protein] Atherosclerosis. 2010 Sep;212(1):107-15. Dietary rice protein isolate attenuates atherosclerosis in apoE-deficient mice by upregulating antioxidant enzymes. Burris RL, Xie CH, Thampi P, Wu X, Melnyk SB, Nagarajan S. “The mean lesion areas for apoE−/− mice fed the RPI diet were lower (55% reduction) compared to those in CAS-fed mice (P < 0.01; Fig. 1B).”

[rice-protein] Exp Biol Med (Maywood). 2010 Sep;235(9):1102-13. Rice protein isolate improves lipid and glucose homeostasis in rats fed high fat/high cholesterol diets. Ronis MJ, Badeaux J, Chen Y, Badger TM.

[arginine-lysine-ratio-rabbits] Kritchevsky, D., Tepper, S. A., & Klurfeld, D. M. (1987). Dietary protein and atherosclerosis. Journal of the American Oil Chemists’ Society, 64(8), 1167-1171. “Carroll and his colleagues demonstrated that, in general, proteins of animal origin were more cholesterolemic for rabbits than were plant proteins, although there was a wide range of individual effects within both classifications. Carroll also showed that partial hydrolyzates of casein or soy protein were less cholesterolemic than the intact proteins. We have hypothesized that the lysine/arginine ratio (L/A) of the protein influences its effects on lipid metabolism. The L/A of casein is about 2 and that of soy about 1. Addition of enough arginine to casein to lower its L/A to 1 reduces its atherogenicity; adding enough lysine to soy isolate to raise its L/A to 2 enhances atherogenicity. The atherogenicities of fish protein (L/A, 1.44), casein (L/A, 1.94) and whole milk protein (L/A, 2.44) are correlated directly with their L/A (p<0.05). Other amino acids (methionine, glycine, arginine) have been shown to affect cholesterolemia.”

[arginine-lysine-ratio-rats] Br J Nutr. 1982 Sep;48(2):211-21. Effects of arginine and lysine addition to casein and soya-bean protein on serum lipids, apolipoproteins, insulin and glucagon in rats. Sugano M, Ishiwaki N, Nagata Y, Imaizumi K. “Male rats received semi-purified diets containing soya-bean protein isolate or casein supplemented respectively with varying amounts of lysine or arginine for 40 d and blood samples were taken after a 5 h fast. 2. Neither the addition of arginine to casein nor lysine to soya-bean protein modified the intrinsic effect of these proteins on serum cholesterol.”

[arginine-lysine-ratio-rats] J Nutr. 1982 Oct;112(10):1892-8. Effects of dietary protein and amino acids on the metabolism of cholesterol-carrying lipoproteins in rats. Park MS, Liepa GU. “Animals fed arginine-supplemented casein diet showed a decrease in both serum and HDL-cholesterol when compared to the casein control group, whereas the addition of lysine to cottonseed protein diet caused an increase in the same two cholesterol fractions.”

[whey-alpha-lactalbumin] Br J Nutr. 2009 Aug;102(3):337-41. doi: 10.1017/S0007114508199445. Effects of high-calcium diets with different whey proteins on weight loss and weight regain in high-fat-fed C57BL/6J mice. Pilvi TK, Harala S, Korpela R, Mervaala EM. “only the ALA diet significantly reduced fat accumulation during weight regain” “The glycine content of LF and ALA is greater than in BLG or WPI and it may contribute to the effect on adipocyte size, since glycine intake has been shown to reduce adipocyte size(25). Interestingly, adipocyte size after weight loss was significantly smaller only in the ALA group even though body fat percentage decreased significantly also in the LF group.”

[whey-alpha-lactalbumin] Shi, J., Ahlroos-Lehmus, A., Pilvi, T. K., Korpela, R., Tossavainen, O., &amp; Mervaala, E. M. (2012). Metabolic effects of a novel microfiltered native whey protein in diet-induced obese mice. Journal of functional foods, 4(2), 440-449. “Our findings indicate that MFNW protects against diet-induced obesity, and suggest that the beneficial effects of MFNW are due, to a great extent, to its α-lactalbumin content.”

[whey-alpha-lactalbumin] Shi, J., Ahlroos-Lehmus, A., Pilvi, T. K., Kekkonen, R., Korpela, R., &amp; Mervaala, E. M. (2011). Comparison of the metabolic effects of milk-derived α-lactalbumin and amino acids mixture with equal composition in diet-induced obese mice. Journal of Functional Foods, 3(2), 70-78. “The anti-obesity effects of -lactalbumin are mediated mainly via its amino acids.”

[whey-alpha-lactalbumin] Biosci Biotechnol Biochem. 2014;78(4):672-9. Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice. Yamaguchi M, Takai S, Hosono A, Seki T. “Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. […] α-Lactalbumin decreased PGE2 in both plasma and colon.” [a diet high in α-lactalbumin (7% casein, 7% α-lactalbumin) inhibits inflammation as powerfully as 0.1% aspirin contained diet]

[whey-lactoferrin] Shi, J., Finckenberg, P., Martonen, E., Ahlroos-Lehmus, A., Pilvi, T. K., Korpela, R., &amp; Mervaala, E. M. (2012). Metabolic effects of lactoferrin during energy restriction and weight regain in diet-induced obese mice. Journal of Functional Foods, 4(1), 66-78. “In conclusion, LF supplementation enhances the outcome of weight loss and subsequent weight regain, ameliorates fatty liver formation, and exerts beneficial effects on glucose tolerance and adipocyte tissue inflammation without interfering energy intake.”

[porcine-placenta-protein] Can J Physiol Pharmacol. 2014 Sep 15:1-8. Anti-fatigue effects of porcine placenta and its amino acids in a behavioral test on mice. Moon PD, Kim KY, Rew KH, Kim HM, Jeong HJ. “Whole PE or individual amino acids decreased immobility times in the FST. PE, Pro, and Arg all lowered blood levels of lactic acid and alanine aminotransferase (ALT). PE and Gly improved glycogen content and catalase activity. As determined from the serum after the FST: PE regulated the effects of interferon (IFN)-γ and tumor necrosis factor (TNF)-α; GA regulated the effects of IFN-γ; Gly and Arg regulated the effects of interleukin (IL)-6; and all of the amino acids present in PE regulated the effects of TNF-α. As determined from the spleen after the FST: Gly and Arg regulated the effects of IL-1β; Gly, Pro, and Arg regulated the effects of IL-6; PE and all of the amino acids present in PE regulated the effects of TNF-α.”

[porcine-placenta-protein] Nutrition. 2013 Nov-Dec;29(11-12):1381-7. Porcine placenta mitigates protein-energy malnutrition-induced fatigue. Han NR, Kim KY, Kim MJ, Kim MH, Kim HM, Jeong HJ.

[pork-liver-protein] Biosci Biotechnol Biochem. 2006 Jan;70(1):112-8. Consumption of pork-liver protein hydrolysate reduces body fat in Otsuka Long-Evans Tokushima Fatty rats by suppressing hepatic lipogenesis. Shimizu M, Tanabe S, Morimatsu F, Nagao K, Yanagita T, Kato N, Nishimura T. 

[single-cell-protein] Br J Nutr. 2008 Oct;100(4):776-85. Dietary single cell protein reduces fatty liver in obese Zucker rats. Gudbrandsen OA, Wergedahl H, Liaset B, Espe M, Mørk S, Berge RK. “We therefore examined the effects of feeding obese Zucker rats a single cell protein (SCP) with low ratios of methionine:glycine and lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and lowered the plasma transaminase levels when compared with casein-fed rats (controls). The fatty acid oxidation was increased in liver mitochondria and peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG biosynthesis were unaffected.”

 

[9] Health effects of taurine and GABA (human and animal studies)

[taurine-humans] Eur J Nutr. 2014 Apr;53(3):823-30. Oxidative stress and inflammation in obesity after taurine supplementation: a double-blind, placebo-controlled study. Rosa FT, Freitas EC, Deminice R, Jordão AA, Marchini JS. “Plasma taurine levels were significantly decreased (41%) in the obese volunteers. Both the placebo and taurine groups showed significant reduction in weight (3%), with no differences between groups. Different from placebo, taurine-supplemented group showed significant increase in plasma taurine (97%) and adiponectin (12%) and significant reduction in the inflammatory marker hs-C-reactive protein (29%) and in the lipid peroxidation marker thiobarbituric acid reactive substances (TBARS) (20%).”

[taurine-humans] Diab Vasc Dis Res. 2010 Oct;7(4):300-10. Two weeks taurine supplementation reverses endothelial dysfunction in young male type 1 diabetics. Moloney MA, Casey RG, O’Donnell DH, Fitzgerald P, Thompson C, Bouchier-Hayes DJ.

[taurine-humans] Amino Acids. 2008 Aug;35(2):469-73. Dietary amino acid taurine ameliorates liver injury in chronic hepatitis patients. Hu YH, Lin CL, Huang YW, Liu PE, Hwang DF.

[taurine-humans] Am J Clin Nutr. 1995 May;61(5):1115-9. Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G. “The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol).”

[taurine-humans] Clin Cardiol. 1985 May;8(5):276-82. Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial. Azuma J, Sawamura A, Awata N, Ohta H, Hamaguchi T, Harada H, Takihara K, Hasegawa H, Yamagami T, Ishiyama T, et al.

[taurine-humans] Adv Exp Med Biol. 2009;643:13-25. Taurine as the nutritional factor for the longevity of the Japanese revealed by a world-wide epidemiological survey. Yamori Y, Liu L, Mori M, Sagara M, Murakami S, Nara Y, Mizushima S.

[taurine-humans] J Biomed Sci. 2010 Aug 24;17 Suppl 1:S6. Taurine in health and diseases: consistent evidence from experimental and epidemiological studies. Yamori Y, Taguchi T, Hamada A, Kunimasa K, Mori H, Mori M. “The preventive effects of T, good for health and longevity, first noted experimentally, were also proven epidemiologically in humans.”

[taurine-humans] Amino Acids. 2014 Oct 17. Taurine attenuates chemotherapy-induced nausea and vomiting in acute lymphoblastic leukemia. Islambulchilar M, Asvadi I, Sanaat Z, Esfahani A, Sattari M. “The present study successfully demonstrated that taurine can decrease the incidence of chemotherapy-induced nausea and vomiting and attenuate chemotherapy-induced taste and smell impairment and fatigue in ALL patients during their maintenance chemotherapy. Furthermore taurine supplementation could lead to a more tolerable chemotherapeutic treatment for the patients.”

[taurine-humans] Eur J Clin Nutr. 2004 Sep;58(9):1239-47. Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus. Brøns C, Spohr C, Storgaard H, Dyerberg J, Vaag A. “Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels.”

[taurine-humans] Diabetologia. 2008 Jan;51(1):139-46. Oral taurine but not N-acetylcysteine ameliorates NEFA-induced impairment in insulin sensitivity and beta cell function in obese and overweight, non-diabetic men. Xiao C, Giacca A, Lewis GF. “NAC failed to prevent the lipid-induced increase in levels of the plasma oxidative stress marker malondialdehyde and did not prevent the lipid-induced reduction in S(I) or DI, whereas TAU completely prevented the rise in malondialdehyde and decreased 4-hydroxynonenal, and significantly improved S(I) (91% of SAL) and DI (81% of SAL).”

[taurine] Am J Clin Nutr. 1994 Aug;60(2):203-6. Taurine supplementation at three different dosages and its effect on trauma patients. Paauw JD, Davis AT. Even 7 d of a high-dose taurine supplementation does not fully correct the hypotaurinemia of trauma.”

[taurine] Am J Physiol. 1995 Sep;269(3 Pt 2):F429-38. Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH, et al.

[taurine] Free Radic Biol Med. 2014 Apr;69:403-16. Chronic ethanol ingestion induces oxidative kidney injury through taurine-inhibitable inflammation. Latchoumycandane C, Nagy LE, McIntyre TM.

[taurine] Singapore Med J. 2005 Feb;46(2):82-7. Effect of taurine on biomarkers of oxidative stress in tissues of fructose-fed insulin-resistant rats. Nandhini AT, Thirunavukkarasu V, Ravichandran MK, Anuradha CV.

[taurine] Amino Acids. 2012 Jun;42(6):2223-32. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Jong CJ, Azuma J, Schaffer S.

[taurine] Life Sci. 1999;64(1):83-91. Improvement in cholesterol metabolism in mice given chronic treatment of taurine and fed a high-fat diet. Murakami S, Kondo-Ohta Y, Tomisawa K. “These observations, together with prior findings, suggest that the cholesterol-lowering action of taurine may relate to the increased conversion of cholesterol to bile acids via stimulation of cholesterol 7a-hydroxylase activity.”

[taurine] J Nutr. 1999 Sep;129(9):1705-12. Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. Yokogoshi H, Mochizuki H, Nanami K, Hida Y, Miyachi F, Oda H. “These results suggest that the hypocholesterolemic effects of taurine observed in the hypocholesterolemic rats fed the HC diet were mainly due to the enhancement of cholesterol degradation and the excretion of bile acid.”

[taurine] J Nutr Sci Vitaminol (Tokyo). 2011;57(2):144-9. Dietary taurine reduces hepatic secretion of cholesteryl ester and enhances fatty acid oxidation in rats fed a high-cholesterol diet. Fukuda N, Yoshitama A, Sugita S, Fujita M, Murakami S. “These results suggest that taurine-induced reduction in hepatic accumulation of cholesteryl ester was associated with reduced hepatic secretion of this lipid molecule, and was inversely related to enhanced ketone body production and fatty acid oxidation.”

[taurine] Amino Acids. 2011 Oct;41(4):901-8. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. “TAU supplementation did not change glucose homeostasis, insulin secretion and action, but reduced plasma and liver lipid levels in MSG rats.”

[taurine] Endocrinology. 2006 Jul;147(7):3276-84. Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. Tsuboyama-Kasaoka N, Shozawa C, Sano K, Kamei Y, Kasaoka S, Hosokawa Y, Ezaki O. “In high-fat diet-induced and/or genetically obese mice, a decrease in the blood taurine concentration was observed along with a decrease in CDO expression in adipose tissue but not in liver. Dietary taurine supplementation prevented high-fat diet-induced obesity with increased resting energy expenditure. Thus, taurine deficiency observed in association with obesity may create a vicious circle promoting obesity. Dietary taurine supplementation interrupts this vicious circle and may prevent obesity.”

[gaba] Clin Exp Hypertens. 2009 Jun;31(4):342-54. Anti-hypertensive effect of gamma-aminobutyric acid (GABA)-rich Chlorella on high-normal blood pressure and borderline hypertension in placebo-controlled double blind study. Shimada M, Hasegawa T, Nishimura C, Kan H, Kanno T, Nakamura T, Matsubayashi T.

[gaba] J Anim Physiol Anim Nutr (Berl). 2014 Sep 30. Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet. Xie ZX, Xia SF, Qiao Y, Shi YH, Le GW. “One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation.”

[gaba] PLoS One. 2011;6(9):e25338. Oral treatment with γ-aminobutyric acid improves glucose tolerance and insulin sensitivity by inhibiting inflammation in high fat diet-fed mice. Tian J, Dang HN, Yong J, Chui WS, Dizon MP, Yaw CK, Kaufman DL. “Collectively, our data indicated that activation of peripheral GABA receptors inhibited the HFD-induced glucose intolerance, insulin resistance, and obesity by inhibiting obesity-related inflammation and up-regulating Treg responses in vivo. Given that GABA is safe for human consumption, activators of GABA receptors may be valuable for the prevention of obesity and intervention of T2DM in the clinic.”

[gaba] Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud’homme GJ, Wang Q. “Remarkably, in severely diabetic mice, GABA restores β-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production.”

[gaba] Transplantation. 2013 Oct 15;96(7):616-23. GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone. Prud’homme GJ, Glinka Y, Hasilo C, Paraskevas S, Li X, Wang Q. “GABA improved human islet cell survival and had suppressive effects on human immune cells. It inhibited canonical NF-κB activation in both islet and immune cells.”

[gaba] Hepatology. 1984 Mar-Apr;4(2):180-5. Identification of an acceptor system for gamma-aminobutyric acid on isolated rat hepatocytes. Minuk GY, Vergalla J, Ferenci P, Jones EA. “gamma-Aminobutyric acid (GABA) is a potent inhibitory neurotransmitter which is synthesized by the enteric bacterial flora and delivered into portal venous blood. To determine whether the liver is likely to play an important role in regulating serum GABA levels, the uptake and metabolism of [3H]GABA by three populations of cells isolated from rat liver were studied. GABA was specifically taken up by hepatocytes but not by endothelial or Kupffer cells.”

 

[10] Health effects of histidine (human and animal studies)

[histidine-humans] Diabetologia. 2013 May;56(5):985-94. Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial. Feng RN, Niu YC, Sun XW, Li Q, Zhao C, Wang C, Guo FC, Sun CH, Li Y.

[histidine-humans] Arch Gerontol Geriatr. 2014 May 2. Anserine and carnosine supplementation in the elderly: Effects on cognitive functioning and physical capacity. Szcześniak D, Budzeń S, Kopeć W, Rymaszewska J. [13 weeks, 0.33g/d carnosine + 0.66g/d anserine -&gt; BMI decreased by 0.51]

[histidine-humans] Nutr Clin Pract. 2013 Oct;28(5):609-16. Effects of L-carnosine and its zinc complex (Polaprezinc) on pressure ulcer healing. Sakae K, Agata T, Kamide R, Yanagisawa H. “After 4 weeks, the rate of pressure ulcer healing, assessed by the mean weekly improvement in PUSH score, was significantly greater in the CAR (1.6 ± 0.2, P = .02) and PLZ groups (1.8 ± 0.2, P = .009) than in the control group (0.8 ± 0.2).”

[histidine] Br Med J. Jun 6, 1936; 1(3935): 1156–1158.  Histidine Treatment of Peptic Ulcer. Alec Wingfield

[histidine] Br J Nutr. 2014 Aug 28;112(4):477-85. Histidine supplementation alleviates inflammation in the adipose tissue of high-fat diet-induced obese rats via the NF-κB- and PPARγ-involved pathways. Sun X, Feng R, Li Y, Lin S, Zhang W, Li Y, Sun C, Li S.

[histidine] Nutrition. 2004 Nov-Dec;20(11-12):991-6. Histidine supplementation suppresses food intake and fat accumulation in rats. Kasaoka S, Tsuboyama-Kasaoka N, Kawahara Y, Inoue S, Tsuji M, Ezaki O, Kato H, Tsuchiya T, Okuda H, Nakajima S. “According to our nutrition survey [12] and [13], the Japanese consume about 1.5 g/d of histidine”

[histidine] Nutrition. 2005 Jul-Aug;21(7-8):855-8. Gender effects in dietary histidine-induced anorexia. Kasaoka S, Kawahara Y, Inoue S, Tsuji M, Kato H, Tsuchiya T, Okuda H, Nakajima S. “The suppressive effect of histidine on food intake was greater in female rats than in male rats, and the suppressive effect of histidine on food intake was less in ovariectomized rats than in female rats.”

[histidine] Neurosci Lett. 2007 Jun 13;420(2):106-9. Bitter taste and blood glucose are not involved in the suppressive effect of dietary histidine on food intake. Goto K, Kasaoka S, Takizawa M, Ogawa M, Tsuchiya T, Nakajima S.

[histidine] Eur J Pharmacol. 2011 Feb 25;653(1-3):82-8. Histidine and carnosine alleviated hepatic steatosis in mice consumed high saturated fat diet. Mong MC, Chao CY, Yin MC. [Histidine and carnosine concentrations of liver are significantly decreased by a high-fat diet (by 33% and 78%). Supplementing either histidine OR carnosine counteracted the decreases in both histidine and carnosine almost equally, and both supplements had almost equivalent effects on metabolic parameters. It seems that both histidine and carnosine can be used interchangeably with similar biological effects.]

[histidine] Eur J Pharmacol. 2005 Apr 18;513(1-2):145-50. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Lee YT, Hsu CC, Lin MH, Liu KS, Yin MC. “1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (P < 0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (P < 0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (P < 0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (P < 0.05).”

[histidine] Food Chem Toxicol. 2008 May;46(5):1503-9. Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Liu WH, Liu TC, Yin MC.

[histidine] J Food Sci. 2009 Oct;74(8):H259-65. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC.

[histidine] Tohoku J Exp Med. 2000 Jun;191(2):85-99. Effect of carnosine on rats under experimental brain ischemia. Gallant S, Kukley M, Stvolinsky S, Bulygina E, Boldyrev A.

[histidine] Nutr Res Pract. 2011 Oct;5(5):421-8. Effects of α-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats. Kim MY, Kim EJ, Kim YN, Choi C, Lee BH.

[histidine] PLoS One. 2011 Mar 15;6(3):e17971. Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice. Corona C, Frazzini V, Silvestri E, Lattanzio R, La Sorda R, Piantelli M, Canzoniero LM, Ciavardelli D, Rizzarelli E, Sensi SL.

[histidine] J Physiol Biochem. 2014 Jun;70(2):385-95. Effect of carnosine alone or combined with α-tocopherol on hepatic steatosis and oxidative stress in fructose-induced insulin-resistant rats. Giriş M, Doğru-Abbasoğlu S, Kumral A, Olgaç V, Koçak-Toker N, Uysal M.

[histidine] J Neurochem. 2007 May;101(3):729-36. Epub 2007 Jan 24. Neuroprotective actions of a histidine analogue in models of ischemic stroke. Tang SC, Arumugam TV, Cutler RG, Jo DG, Magnus T, Chan SL, Mughal MR, Telljohann RS, Nassar M, Ouyang X, Calderan A, Ruzza P, Guiotto A, Mattson MP. “We recently synthesized and characterized histidine analogues related to the natural dipeptide carnosine, which selectively scavenge the toxic lipid peroxidation product 4-hydroxynonenal (HNE)[…]”

[histidine] Gastroenterology. 2009 Feb;136(2):564-74.e2. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T, Hashimoto M, Okutsu T, Shimbo K, Takeda T, Matsumoto H, Sato A, Ohtsu H, Suzuki M, Hibi T.

[histidine] Am J Physiol Lung Cell Mol Physiol. 2007 May;292(5):L1095-104. Epub 2007 Jan 12. Protective effect of orally administered carnosine on bleomycin-induced lung injury. Cuzzocrea S, Genovese T, Failla M, Vecchio G, Fruciano M, Mazzon E, Di Paola R, Muià C, La Rosa C, Crimi N, Rizzarelli E, Vancheri C.

[histidine] Diabetes. 2013 Jul;62(7):2266-77. Histidine augments the suppression of hepatic glucose production by central insulin action. Kimura K, Nakamura Y, Inaba Y, Matsumoto M, Kido Y, Asahara S, Matsuda T, Watanabe H, Maeda A, Inagaki F, Mukai C, Takeda K, Akira S, Ota T, Nakabayashi H, Kaneko S, Kasuga M, Inoue H.

[histidine] Hum Exp Toxicol. 2010 Aug;29(8):659-65. The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats. Artun BC, Küskü-Kiraz Z, Güllüoğlu M, Cevikbaş U, Koçak-Toker N, Uysal M. “In conclusion, carnosine prevented the increases in serum transaminase activities and lipid peroxides in liver of ethanol-treated rats, without any change on steatosis in liver.”

[histidine] Neurosci Lett. 2012 Feb 21;510(1):1-5. Effects of L-carnosine on splenic sympathetic nerve activity and tumor proliferation. Horii Y, Shen J, Fujisaki Y, Yoshida K, Nagai K. “The tumor volumes of the control mice given water gradually and markedly increased and reached a value of 869.8 ± 132.9 mm3 on day 22 after implantation (Fig. 3b). The tumor volumes of the l-carnosine group also increased; however, the increase was less than that of the control group, reaching a value of 407.8 ± 121.7 mm3 (46.9% of the tumor volume of the control group) on day 22.”

[histidine] Stroke. 2014 Aug;45(8):2438-43. Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES, Yu SW, Majid A, Bae ON. “However, treatment with carnosine significantly attenuated autophagic signaling in the ischemic brain, with improvement of brain mitochondrial function and mitophagy signaling. The protective effect of carnosine against autophagy was also confirmed in primary cortical neurons.”

[histidine] Brain Res. 2005 Mar 28;1039(1-2):220-3. Prevention of brain infarction by postischemic administration of histidine in rats. Adachi N1, Liu K, Arai T. “The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. […] These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.”

[histidine] Bull Exp Biol Med. 2002 Jun;133(6):559-61. Effect of carnosine on Drosophila melanogaster lifespan. Yuneva AO, Kramarenko GG, Vetreshchak TV, Gallant S, Boldyrev AA. “A positive dose-dependent effect of carnosine (beta-alanyl-L-histidine) on the lifespan of male Drosophila melanogaster flies was shown. The mean lifespan of male flies receiving 200 mg/liter carnosine approached that of females. […] Addition of 200 mg/liter histidine and beta-alanine (separately or in combination) had no effect on the mean lifespan of flies.”

[histidine] Br Poult Sci. 2013;54(4):454-65. Influence of different histidine sources and zinc supplementation of broiler diets on dipeptide content and antioxidant status of blood and meat. Kopeć W, Jamroz D, Wiliczkiewicz A, Biazik E, Pudlo A, Hikawczuk T, Skiba T, Korzeniowska M. “Histidine supplementation of the diet increased glutathione peroxidase activity in plasma and superoxide dismutase activity in erythrocytes. Moreover, the addition of SDBC or pure histidine in the diet increased histidine dipeptide content and activated enzymatic and non-enzymatic antioxidant systems in chicken blood and muscles. However, it led to lower growth performance indices.”

[histidine] Neurol Res. 2010 Feb;32(1):101-5. Carnosine inhibits ATP production in cells from malignant glioma. Renner C1, Asperger A, Seyffarth A, Meixensberger J, Gebhardt R, Gaunitz F. “Carnosine might be considered as a potential drug for the treatment of malignant glioma or other tumors since it inhibits the glycolytic energy metabolism that is crucial for cancer cells and malignant gliomas as shown in the current study.”

 

[11] Studies on glycine receptor (“glycine-gated chloride channel”)

[glycine-receptor] Am J Physiol. 1997 Jun;272(6 Pt 1):G1581-6. Kupffer cells contain a glycine-gated chloride channel. Ikejima K, Qu W, Stachlewitz RF, Thurman RG.

[glycine-receptor] Nutr Cancer. 2001;40(2):197-204. Endothelial cells contain a glycine-gated chloride channel. Yamashina S, Konno A, Wheeler MD, Rusyn I, Rusyn EV, Cox AD, Thurman RG. “Importantly, glycine diminished serum-stimulated proliferation and migration of endothelial cells. Collectively, these data indicate that the inhibitory effect of glycine on growth and migration of endothelial cells is due to activation of a glycine-gated Cl- channel. This hyperpolarizes the cell membrane and blocks influx of Ca2+, thereby minimizing growth factor-mediated signaling.”

[glycine-receptor] Infect Immun. 2001 Sep;69(9):5883-91. Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.

[glycine-receptor] FASEB J. 2000 Mar;14(3):476-84. Glycine-gated chloride channels in neutrophils attenuate calcium influx and superoxide production. Wheeler M, Stachlewitz RF, Yamashina S, Ikejima K, Morrow AL, Thurman RG.

[taurine-GlyR] J Leukoc Biol. 1998 Nov;64(5):615-21. Taurine blunts LPS-induced increases in intracellular calcium and TNF-alpha production by Kupffer cells. Seabra V, Stachlewitz RF, Thurman RG. “Taurine significantly blunted the LPS-induced increase in [Ca2+]i in a dose-dependent manner (IC50, 0.1 mM). This effect was reversed by strychnine (1 microM) and was prevented when chloride was removed from the extracellular media. Moreover, taurine increased 36Cl- uptake by Kupffer cells in a dose-dependent manner (EC50, 0.2 mM). […] These results indicate that taurine activates a glycine-gated chloride channel in Kupffer cells causing chloride influx. In addition, LPS-induced TNF-alpha production was reduced by more than 40% by taurine, an effect that was also reversed by strychnine.”

[taurine-GlyR] Am J Clin Nutr. 1990 Oct;52(4):758-64. Taurine concentrations in plasma and whole blood in humans: estimation of error from intra- and interindividual variation and sampling technique. Trautwein EA, Hayes KC. “The normal plasma taurine concentration was 44 +/- 9 mumol/L (mean +/- SD; n = 40) in fasting subjects”

[taurine-GlyR] Ann Nutr Metab. 2007;51(4):379-86. Taurine induces anti-anxiety by activating strychnine-sensitive glycine receptor in vivo. Zhang CG, Kim SJ.




[12] Bile acids, glycine, taurine, gut, obesity, intracellular thyroid hormone activation…

[bile] Hepatology. 2003 Mar;37(3):551-7. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Lorenzo-Zúñiga V, Bartolí R, Planas R, Hofmann AF, Viñado B, Hagey LR, Hernández JM, Mañé J, Alvarez MA, Ausina V, Gassull MA.

[bile] Am Surg. 1992 May;58(5):305-10. Absence of intestinal bile promotes bacterial translocation. Slocum MM, Sittig KM, Specian RD, Deitch EA.

[bile] 2007 Oct;35(10):2367-74. Conjugated primary bile salts reduce permeability of endotoxin through intestinal epithelial cells and synergize with phosphatidylcholine in suppression of inflammatory cytokine production. Parlesak A, Schaeckeler S, Moser L, Bode C.

[bile] Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3920-5. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor. Inagaki T, Moschetta A, Lee YK, Peng L, Zhao G, Downes M, Yu RT, Shelton JM, Richardson JA, Repa JJ, Mangelsdorf DJ, Kliewer SA. “Obstruction of bile flow results in bacterial proliferation and mucosal injury in the small intestine that can lead to the translocation of bacteria across the epithelial barrier and systemic infection. These adverse effects of biliary obstruction can be inhibited by administration of bile acids. Here we show that the farnesoid X receptor (FXR), a nuclear receptor for bile acids, induces genes involved in enteroprotection and inhibits bacterial overgrowth and mucosal injury in ileum caused by bile duct ligation. Mice lacking FXR have increased ileal levels of bacteria and a compromised epithelial barrier.”

[bile] Best Pract Res Clin Gastroenterol. 2014 Aug;28(4):573-583. Bile acids, obesity, and the metabolic syndrome. Ma H, Patti ME. ”Bile acids are synthesized from cholesterol through two dominant pathways: the classic pathway and the alternative pathway (Fig. 1). In the classic (or neutral) pathway, CYP7A1 catalyses the initial and rate-limiting step converting cholesterol into 7α-hydroxycholesterol, with CYP8B1 subsequently regulating synthesis of 12α-hydroxysterols including cholic acid (CA). In the alternative (or acidic) pathway, CYP27A1 first hydroxylates the cholesterol side chain, converting cholesterol into 27-hydroxycholesterol, which is then 7α-hydroxylated by CYP7B1 prior to CYP8B1 action. In humans, the classical pathway produces the primary BA cholic acid (CA) and chenodeoxycholic acid (CDCA) in roughly equal amounts, whereas the alternative pathway produces mainly CDCA [8]. Most bile acids are conjugated with either glycine or taurine, with a 3:1 predominance of glycine over taurine [3], [5] and [9].”

[bile-farnesoid-x-receptor-intestines] Gut. 2011 Apr;60(4):463-72. Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, Penna G, Laverny G, Adorini L, Moschetta A, van Mil SW.

[bile-farnesoid-x-receptor-inflammation] Biochim Biophys Acta. 2011 Aug;1812(8):851-8. Activation of bile salt nuclear receptor FXR is repressed by pro-inflammatory cytokines activating NF-κB signaling in the intestine. Gadaleta RM, Oldenburg B, Willemsen EC, Spit M, Murzilli S, Salvatore L, Klomp LW, Siersema PD, van Erpecum KJ, van Mil SW. “Together, these results indicate that intestinal inflammation strongly reduces FXR activation, probably via NF-κB-dependent tethering of FXR. Therefore, FXR not only inhibits inflammation, but also is targeted by the inflammatory response itself. This could result in a vicious cycle where reduced FXR activity results in less repression of inflammation, contributing to development of chronic intestinal inflammation.”

[bile-protective-mechanism-thyroid] Nature. 2006 Jan 26;439(7075):484-9. Epub 2006 Jan 8. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. “Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2-/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption.”

[taurine-bile-thyroid-hormone-activation] FEBS Lett. 2011 Feb 4;585(3):539-44. The chemical chaperones tauroursodeoxycholic and 4-phenylbutyric acid accelerate thyroid hormone activation and energy expenditure. da-Silva WS, Ribich S, Arrojo e Drigo R, Castillo M, Patti ME, Bianco AC.

[bile] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) “The affinity of the bile salt export pump is greater for conjugated than for non‐conjugated BA [137]. Conjugation of BA therefore increases biliary secretion of BA [138] and may thus in turn enhance BA synthesis leading to the increase in BA pool seen with increased dietary taurine and glycine in rats [123, 124]. The conjugation of bile acids is highly species specific [139, 140]; rats conjugate primarily with taurine but also to some extend with glycine, rabbits conjugate exclusively with glycine, mice conjugate almost exclusively with taurine, while human subjects conjugate with both glycine and taurine, usually in the proportions 3:1 [141]. It has been demonstrated that taurine and glycine supplementation increases BA pool in hamsters [142] and as described above that seafood protein rich in glycine and taurine increases plasma BA in rats [123, 124].”

 

[13] Histidine and carnosine: mechanisms

[histidine-carnosine-mechanisms] Physiol Rev. 2013 Oct;93(4):1803-45. Physiology and pathophysiology of carnosine. Boldyrev AA, Aldini G, Derave W. “Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide.”

[histidine-carnosine-mechanisms] Peptides. 2009 Jul;30(7):1306-12. Inhibitory effect of carnosine and N-acetyl carnosine on LPS-induced microglial oxidative stress and inflammation. Fleisher-Berkovich S, Abramovitch-Dahan C, Ben-Shabat S, Apte R, Beit-Yannai E.

[histidine-carnosine-mechanisms] J Neurosci Res. 2007 Aug 1;85(10):2239-45. Carnosine interaction with nitric oxide and astroglial cell protection. Nicoletti VG, Santoro AM, Grasso G, Vagliasindi LI, Giuffrida ML, Cuppari C, Purrello VS, Stella  AM, Rizzarelli E. “A comparison of carnosine with its homologues or derivatives (homocarnosine and carcinine) as well as with its amino acid constituents (L-histidine and beta-alanine) highlighted that only histidine showed significant scavenging activity.”

[histidine-carnosine-mechanisms] Neurochem Res. 2005 Jun-Jul;30(6-7):797-807. Protective effect of carnosine during nitrosative stress in astroglial cell cultures. Calabrese V, Colombrita C, Guagliano E, Sapienza M, Ravagna A, Cardile V, Scapagnini G, Santoro AM, Mangiameli A, Butterfield DA, Giuffrida Stella AM, Rizzarelli E.

[histidine-histamine] Clin Exp Pharmacol Physiol. 2010 Jan;37(1):62-8. Oral L-histidine exerts antihypertensive effects via central histamine H3 receptors and decreases nitric oxide content in the rostral ventrolateral medulla in spontaneously hypertensive rats. Toba H, Nakamori A, Tanaka Y, Yukiya R, Tatsuoka K, Narutaki M, Tokitaka M, Hariu H, Kobara M, Nakata T. “These results suggest that L-histidine decreases blood pressure by attenuating sympathetic output via the central histamine H3 receptor in SHR. In addition, the antihypertensive effects of L-histidine appear to be associated with an increase in nitric oxide in the RVLM.”

[histidine-histamine] The American Journal of Digestive Diseases July 1944, Volume 11, Issue 7, pp 209-223 The therapeutic use of the amino acid histidine in allergy and shock— “Histidine as a factor in histamine epinephrine balance” Simon L. Ruskin “A role of therapeutic usefulness of the amino acid histidine is indicated in allergic and related conditions. Histidine is antagonistic to histamine and plays an important part in histamine-adrenalin balance in shock. Histidine produces a feeling of well being and energy that could be useful in the care of post-operative patients and the treatment of shock.”

[histidine-histamine] Brain Res. 2013 Aug 21;1527:246-54. Role of histidine/histamine in carnosine-induced neuroprotection during ischemic brain damage. Bae ON, Majid A. “In primary astrocytes, carnosine significantly reduced ischemic cell death after oxygen-glucose deprivation, and this effect was abolished by histamine receptor type I antagonist. However, histidine or histamine did not exhibit a protective effect on ischemic astrocytic cell death.

[histidine-histamine] J Neurochem. 1972 Mar;19(3):801-10. Histamine formation in rat brain in vivo: effects of histidine loads. Schwartz JC, Lampart C, Rose C. “Administration of l-histidine at the rate of 500 mg/kg induced an increase of nearly 50 per cent in the level of histamine in rat brain which lasted several hours.”

[histidine-mitochondria] Biochemistry. 1971 Jan 5;10(1):102-7. Participation of L-histidine in the maintenance of mitochondrial integrity. Connelly JL, Myron DR. 

[histidine-PDK4] Amino Acids. 2014 Apr;46(4):1009-19. The antineoplastic effect of carnosine is accompanied by induction of PDK4 and can be mimicked by L-histidine. Letzien U, Oppermann H, Meixensberger J, Gaunitz F. “The experiments identified a strong induction of expression of the gene encoding pyruvate dehydrogenase 4 (PDK4) under the influence of carnosine and L-histidine, but not by the other substances employed. In addition, inhibition of cell viability was only detected in cells treated with carnosine and L-histidine, with the latter showing a significantly stronger effect than carnosine. Since the tumor cells expressed the tissue form of carnosinase (CN2) but almost no serum carnosinase (CN1), we conclude that cleavage by CN2 is a prerequisite for the antineoplastic effect of carnosine. In addition, enhanced expression of PDK4 under the influence of carnosine/L-histidine opens a new perspective for the interpretation of the ergogenic potential of dietary β-alanine supplementation and adds a new contribution to a growing body of evidence that single amino acids can regulate key metabolic pathways important in health and disease.”

 

[14] How protein affects health independently of the amino acid composition

[hydrolyzed-protein] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) GLP‐1 is important for maintaining normal glucose homeostasis as it induces glucose stimulated insulin secretion, while CCK stimulates digestion by inducing release of pancreatic digestive enzymes and bile from the gallbladder and both hormones furthermore reduces appetite and energy intake. These stimulatory effects of peptides on hormone release, compared to intact protein and free AA, suggest a way in which hydrolyzed proteins may affect DIO, impaired glucose and insulin metabolism and other morbidities”

[hydrolyzed-protein] J Nutr. 2013 Sep;143(9):1367-75. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice. Lillefosse HH, Tastesen HS, Du ZY, Ditlev DB, Thorsen FA, Madsen L, Kristiansen K, Liaset B. “The physiological changes induced by hydrolyzed casein ingestion translated into decreased body and adipose tissue masses”

[casein-vs-salmon] Ibrahim, M. M., Fjære, E., Lock, E. J., Naville, D., Amlund, H., Meugnier, E., … &amp; Ruzzin, J. (2011). Chronic consumption of farmed salmon containing persistent organic pollutants causes insulin resistance and obesity in mice. PloS one, 6(9), e25170.

[casein-vs-chicken] PhD Thesis by Hanne Sørup Tastesen: Dietary protein in the prevention of diet‐induced obesity and co‐morbidities (University of Copenhagen, 2014) [Paper 2: “A Mixture of Cod and Scallop Protein Reduces Adiposity and Improves Glucose Tolerance in High‐Fat, High‐Sucrose Fed Male C57BL/6J Mice”] “The reduced adiposity in the casein-fed, compared to the chicken-fed mice, was likely related to the three percent lower apparent fat digestibility in casein-fed compared to chicken- and cod/scallop-fed mice.”

[dairy-fecal-fat] Int J Obes (Lond). 2008 Dec;32(12):1816-24. Effect of dairy calcium on fecal fat excretion: a randomized crossover trial. Bendsen NT, Hother AL, Jensen SK, Lorenzen JK, Astrup A. “The main protein source in the low-Ca diet was pork meat, whereas most of the protein in the high-Ca diet was of dairy origin.”

 

[15] Low glycine and histidine levels in individuals with insulin resistance

[ínsulin-resistance-amino-acids] Br J Nutr. 2012 Jul 14;108(1):57-61. Histidine and arginine are associated with inflammation and oxidative stress in obese women. Niu YC, Feng RN, Hou Y, Li K, Kang Z, Wang J, Sun CH, Li Y. “Among the amino acids determined, serum histidine, arginine, threonine, glycine, lysine and serine were found to be significantly lower in obese women as compared to non-obese controls (P < 0·001). The difference was the greatest for histidine (P < 0·001).”

[insulin-resistance-amino-acids] PLoS One. 2013 Dec 31;8(12):e84034. Serum glycine is associated with regional body fat and insulin resistance in functionally-limited older adults. Lustgarten MS, Price LL, Phillips EM, Fielding RA.

[insulin-resistance-amino-acids] PLoS One. 2010 Dec 10;5(12):e15234. Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, Adams SH. [Diabetic patients have 26% lower serum glycine levels than the “normal” population.]