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*Consuming TMG in excessive amounts might lead to gastrointestinal distress and may disturb the body’s metabolism of methionine and choline. | *Consuming TMG in excessive amounts might lead to gastrointestinal distress and may disturb the body’s metabolism of methionine and choline. | ||
===Side Effects=== | ===Side Effects=== | ||
Trimethylglycine supplementation may cause [[wikipedia:Diarrhea|diarrhea]], bloating, cramps, dyspepsia, [[wikipedia:Nausea|nausea]] or vomiting.<ref name=":02">{{Citation|title=Betaine|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548774/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|access-date=2023-07-14|place=Bethesda (MD)|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31644082}}</ref> Although rare, it can also causes excessive increases in serum methionine concentrations in the brain, which may lead to [[wikipedia:Cerebral_edema|cerebral edema]], a life-threatening condition.<ref name=":02" /> | |||
Trimethylglycine supplementation lowers homocysteine but also raises [[wikipedia:LDL-cholesterol|LDL-cholesterol]] in obese individuals and renal patients.<ref>{{cite journal|vauthors=Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB|title=Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans|journal=PLOS Med.|volume=2|issue=5|pages=e135|year=2005|pmid=15916468|pmc=1140947|doi=10.1371/journal.pmed.0020135}}</ref> | |||
===Drug and Supplement Interactions === | |||
===Drug and Supplement Interactions=== | |||
*'''Anticholinergic Drugs''': TMG might interact with anticholinergic medications, which reduce the effects of acetylcholine, as TMG increases levels of choline, a precursor to acetylcholine. | *'''Anticholinergic Drugs''': TMG might interact with anticholinergic medications, which reduce the effects of acetylcholine, as TMG increases levels of choline, a precursor to acetylcholine. | ||
*'''Choline and Folate Supplements''': Concurrent use of TMG with other supplements that affect methionine metabolism, such as choline and folate, should be approached with caution, as they might synergistically increase levels of methionine, which could be detrimental. | *'''Choline and Folate Supplements''': Concurrent use of TMG with other supplements that affect methionine metabolism, such as choline and folate, should be approached with caution, as they might synergistically increase levels of methionine, which could be detrimental. | ||
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*'''Pregnant or Breastfeeding Women''': There is limited research on the safety of TMG supplementation during pregnancy and breastfeeding; thus, consultation with a healthcare professional is advised. | *'''Pregnant or Breastfeeding Women''': There is limited research on the safety of TMG supplementation during pregnancy and breastfeeding; thus, consultation with a healthcare professional is advised. | ||
*'''Pre-existing Health Conditions''': Individuals with pre-existing health conditions, particularly those affecting the liver, should consult a healthcare professional before beginning TMG supplementation. | *'''Pre-existing Health Conditions''': Individuals with pre-existing health conditions, particularly those affecting the liver, should consult a healthcare professional before beginning TMG supplementation. | ||
== Misc == | ==Misc== | ||
Although TMG supplementation decreases the amount of [[wikipedia:Adipose_tissue|adipose tissue]] in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet.<ref name="pmid12399266">{{cite journal|last1=Schwab|volume=76|doi-access=free|doi=10.1093/ajcn/76.5.961|pmid=12399266|date=November 2002|pages=961–967|issue=5|journal=Am. J. Clin. Nutr.|first1=U.|title=Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects|display-authors=etal|first3=L.|last3=Toppinen|first2=A.|last2=Törrönen|title-link=doi}}</ref> | Although TMG supplementation decreases the amount of [[wikipedia:Adipose_tissue|adipose tissue]] in pigs, research on human subjects has shown no effect on body weight, body composition, or resting energy expenditure when used in conjunction with a low calorie diet.<ref name="pmid12399266">{{cite journal|last1=Schwab|volume=76|doi-access=free|doi=10.1093/ajcn/76.5.961|pmid=12399266|date=November 2002|pages=961–967|issue=5|journal=Am. J. Clin. Nutr.|first1=U.|title=Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects|display-authors=etal|first3=L.|last3=Toppinen|first2=A.|last2=Törrönen|title-link=doi}}</ref> | ||
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|- | |- | ||
| colspan="1" rowspan="1" |Preserves/restores hepatic SAM: SAH ratios by regenerating SAM and lowering SAH and homocysteine levels in ALD | | colspan="1" rowspan="1" |Preserves/restores hepatic SAM: SAH ratios by regenerating SAM and lowering SAH and homocysteine levels in ALD | ||
| colspan="1" rowspan="1" |Male Wistar rats; hepatocytes; male C57BL/6 mice | | colspan="1" rowspan="1" | Male Wistar rats; hepatocytes; male C57BL/6 mice | ||
| colspan="1" rowspan="1" |[23,60,61,81,82,83,84,86,88,91,92,117,119,121,234,235] | | colspan="1" rowspan="1" |[23,60,61,81,82,83,84,86,88,91,92,117,119,121,234,235] | ||
|- | |- | ||
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|- | |- | ||
| colspan="1" rowspan="1" |Exerts hepatoprotection by preserving mitochondrial function in ALD | | colspan="1" rowspan="1" |Exerts hepatoprotection by preserving mitochondrial function in ALD | ||
| colspan="1" rowspan="1" |Male Wistar rats | | colspan="1" rowspan="1" | Male Wistar rats | ||
| colspan="1" rowspan="1" |[61] | | colspan="1" rowspan="1" |[61] | ||
|- | |- | ||
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| colspan="1" rowspan="1" |Prevents elevations of CD14, TNFα, COX2, GADD45β, LITAF, JAK3, TLR2, TLR4, IL1β, and PDCD4 and NOS2 mRNA levels in alcoholic liver injury | | colspan="1" rowspan="1" |Prevents elevations of CD14, TNFα, COX2, GADD45β, LITAF, JAK3, TLR2, TLR4, IL1β, and PDCD4 and NOS2 mRNA levels in alcoholic liver injury | ||
| colspan="1" rowspan="1" |Male Wistar rats | | colspan="1" rowspan="1" |Male Wistar rats | ||
| colspan="1" rowspan="1" |[115,133] | | colspan="1" rowspan="1" | [115,133] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Prevents serum ALT and AST activity elevations in models of ALD and MAFLD | | colspan="1" rowspan="1" |Prevents serum ALT and AST activity elevations in models of ALD and MAFLD | ||
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| colspan="1" rowspan="1" |[28] | | colspan="1" rowspan="1" |[28] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Remethylates homocysteine, protecting from oxidant stress and restoring phosphatidylcholine generation in MAFLD | | colspan="1" rowspan="1" | Remethylates homocysteine, protecting from oxidant stress and restoring phosphatidylcholine generation in MAFLD | ||
| colspan="1" rowspan="1" |C57BL/6 mice | | colspan="1" rowspan="1" |C57BL/6 mice | ||
| colspan="1" rowspan="1" |[161] | | colspan="1" rowspan="1" |[161] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Stimulates β-oxidation in livers of MCD diet-induced MAFLD | | colspan="1" rowspan="1" | Stimulates β-oxidation in livers of MCD diet-induced MAFLD | ||
| colspan="1" rowspan="1" |Male Sprague-Dawley rats | | colspan="1" rowspan="1" |Male Sprague-Dawley rats | ||
| colspan="1" rowspan="1" |[162] | | colspan="1" rowspan="1" |[162] | ||
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|- | |- | ||
| colspan="1" rowspan="1" |Alleviates ROS-induced mitochondrial respiratory chain dysfunction in MAFLD | | colspan="1" rowspan="1" |Alleviates ROS-induced mitochondrial respiratory chain dysfunction in MAFLD | ||
| colspan="1" rowspan="1" |Male Sprague-Dawley rats | | colspan="1" rowspan="1" | Male Sprague-Dawley rats | ||
| colspan="1" rowspan="1" |[163]. | | colspan="1" rowspan="1" |[163]. | ||
|- | |- | ||
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| colspan="1" rowspan="1" |[148] | | colspan="1" rowspan="1" |[148] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Suppresses alcoholic liver fibrosis | | colspan="1" rowspan="1" | Suppresses alcoholic liver fibrosis | ||
| colspan="1" rowspan="1" |Rats | | colspan="1" rowspan="1" | Rats | ||
| colspan="1" rowspan="1" |[116] | | colspan="1" rowspan="1" |[116] | ||
|- | |- | ||
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|- | |- | ||
| colspan="1" rowspan="1" |Inhibits lipogenic activity in liver by activation of AMPK | | colspan="1" rowspan="1" |Inhibits lipogenic activity in liver by activation of AMPK | ||
| colspan="1" rowspan="1" |ApoE−/− mice; Male C57BL/6 mice | | colspan="1" rowspan="1" | ApoE−/− mice; Male C57BL/6 mice | ||
| colspan="1" rowspan="1" |[159,160] | | colspan="1" rowspan="1" | [159,160] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Regulates colonic fluid balance | | colspan="1" rowspan="1" |Regulates colonic fluid balance | ||
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| colspan="1" rowspan="1" |[200] | | colspan="1" rowspan="1" |[200] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Attenuates alcoholic-induced pancreatic steatosis | | colspan="1" rowspan="1" | Attenuates alcoholic-induced pancreatic steatosis | ||
| colspan="1" rowspan="1" |Male Wistar rats | | colspan="1" rowspan="1" |Male Wistar rats | ||
| colspan="1" rowspan="1" |[125] | | colspan="1" rowspan="1" |[125] | ||
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| colspan="1" rowspan="1" |[218] | | colspan="1" rowspan="1" |[218] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Treats asthma-induced oxidative stress, thus improving airway function of lung tissue | | colspan="1" rowspan="1" | Treats asthma-induced oxidative stress, thus improving airway function of lung tissue | ||
| colspan="1" rowspan="1" |BALB/C mice | | colspan="1" rowspan="1" |BALB/C mice | ||
| colspan="1" rowspan="1" |[207] | | colspan="1" rowspan="1" |[207] | ||
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| colspan="1" rowspan="1" |Protects against isoprenaline-induced myocardial dysfunction | | colspan="1" rowspan="1" |Protects against isoprenaline-induced myocardial dysfunction | ||
| colspan="1" rowspan="1" |Male Wistar rats | | colspan="1" rowspan="1" |Male Wistar rats | ||
| colspan="1" rowspan="1" |[205] | | colspan="1" rowspan="1" | [205] | ||
|- | |- | ||
| colspan="1" rowspan="1" |Anti-nociceptive and sedative role via interactions with opioidergic and GABA receptors | | colspan="1" rowspan="1" |Anti-nociceptive and sedative role via interactions with opioidergic and GABA receptors | ||
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|} | |} | ||
== Taking TMG == | ==Taking TMG == | ||
Nutritionally, betaine is not needed when sufficient dietary choline is present for synthesis.<ref name="ze">{{Cite book|title=Handbook of vitamins|url=https://archive.org/details/handbookvitamins00jzem|url-access=limited|vauthors=Rucker RB, Zempleni J, Suttie JW, McCormick DB|publisher=Taylor & Francis|year=2007|isbn=9780849340222|edition=4th|pages=[https://archive.org/details/handbookvitamins00jzem/page/n471 459]–477}}</ref> When insufficient betaine is available, elevated homocysteine levels and decreased SAM levels in blood occur. Supplementation of betaine in this situation would resolve these blood marker issues, but not compensate for other functions of choline.<ref name="eu">{{Cite journal|date=2016|title=Dietary reference values for choline|journal=EFSA Journal|volume=14|issue=8|doi=10.2903/j.efsa.2016.4484|doi-access=free}}</ref> | Nutritionally, betaine is not needed when sufficient dietary choline is present for synthesis.<ref name="ze">{{Cite book|title=Handbook of vitamins|url=https://archive.org/details/handbookvitamins00jzem|url-access=limited|vauthors=Rucker RB, Zempleni J, Suttie JW, McCormick DB|publisher=Taylor & Francis|year=2007|isbn=9780849340222|edition=4th|pages=[https://archive.org/details/handbookvitamins00jzem/page/n471 459]–477}}</ref> When insufficient betaine is available, elevated homocysteine levels and decreased SAM levels in blood occur. Supplementation of betaine in this situation would resolve these blood marker issues, but not compensate for other functions of choline.<ref name="eu">{{Cite journal|date=2016|title=Dietary reference values for choline|journal=EFSA Journal|volume=14|issue=8|doi=10.2903/j.efsa.2016.4484|doi-access=free}}</ref> | ||
=== Side effects === | ===Side effects=== | ||
Trimethylglycine supplementation may cause [[wikipedia:Diarrhea|diarrhea]], bloating, cramps, dyspepsia, [[wikipedia:Nausea|nausea]] or vomiting.<ref name=":0">{{Citation|title=Betaine|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548774/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|access-date=2023-07-14|place=Bethesda (MD)|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31644082}}</ref> Although rare, it can also causes excessive increases in serum methionine concentrations in the brain, which may lead to [[wikipedia:Cerebral_edema|cerebral edema]], a life-threatening condition.<ref name=":0" /> | Trimethylglycine supplementation may cause [[wikipedia:Diarrhea|diarrhea]], bloating, cramps, dyspepsia, [[wikipedia:Nausea|nausea]] or vomiting.<ref name=":0">{{Citation|title=Betaine|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548774/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|access-date=2023-07-14|place=Bethesda (MD)|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31644082}}</ref> Although rare, it can also causes excessive increases in serum methionine concentrations in the brain, which may lead to [[wikipedia:Cerebral_edema|cerebral edema]], a life-threatening condition.<ref name=":0" /> | ||
Trimethylglycine supplementation lowers homocysteine but also raises [[wikipedia:LDL-cholesterol|LDL-cholesterol]] in obese individuals and renal patients.<ref>{{cite journal|vauthors=Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB|title=Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans|journal=PLOS Med.|volume=2|issue=5|pages=e135|year=2005|pmid=15916468|pmc=1140947|doi=10.1371/journal.pmed.0020135}}</ref> | Trimethylglycine supplementation lowers homocysteine but also raises [[wikipedia:LDL-cholesterol|LDL-cholesterol]] in obese individuals and renal patients.<ref>{{cite journal|vauthors=Olthof MR, van Vliet T, Verhoef P, Zock PL, Katan MB|title=Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans|journal=PLOS Med.|volume=2|issue=5|pages=e135|year=2005|pmid=15916468|pmc=1140947|doi=10.1371/journal.pmed.0020135}}</ref> | ||
== References == | ==References== | ||
<references /> | <references /> | ||
[[Category:Orally Consumable Longevity Molecules]] | [[Category:Orally Consumable Longevity Molecules]] |