Supplements harm your liver?

[Derek Wilson]

Can supplements harm your liver? Is there any real study on it?

 

[Anabaholic]

Certainly some supplements can be harmful (obviously methylated prohormones are bad for your liver and some studies suggest high doses of EGCG can strain the liver) but in general, as long as you're healthy, and don't have any underlying health condition, the majority of supplements are just fine.

 

[justhere4comm]

A general question really. Define supplement.

Everything you put in your mouth and swallow probably flushes through your liver. Oil soluble vitamins in particular might be of a concern if you super dose them. Don't. Even water soluble come out in your urine, but drink a lot of water anyway. Don't forget about your kidneys.

Your liver is pretty damned strong. People have come back from transplants very well with supplementation of TUDCA with other stacks of compounds in order to speed their recovery.

"TUDCA and Multiple Drugs/Supplements
One study used a drug “cocktail” comprised of six drugs and supplements:

• Streptokinase
• Epoprostenol
• Thiazolidinediones (TZDs)
• N-Acetylcysteine (NAC)
• Hemin
• TUDCA

The cocktail was able to effectively treat damage to the liver, gallbladder, and bile ducts in liver transplant patients [R]."

https://www.selfhacked.com/blog/tudca-benefits/

 

[jameschoi]

Take it easy on the fish oil. I eat fish instead.

http://suppversity.blogspot.com/2011/05/too-much-of-good-thing-when-fish-oil.html

 

[rugger48]

Can you be scared of your own shadow and live a normal life?

 

[Derek Wilson]

Certainly some supplements can be harmful (obviously methylated prohormones are bad for your liver and some studies suggest high doses of EGCG can strain the liver) but in general, as long as you're healthy, and don't have any underlying health condition, the majority of supplements are just fine.

Thanks

 

[Derek Wilson]

A general question really. Define supplement.

Everything you put in your mouth and swallow probably flushes through your liver. Oil soluble vitamins in particular might be of a concern if you super dose them. Don't. Even water soluble come out in your urine, but drink a lot of water anyway. Don't forget about your kidneys.

Your liver is pretty damned strong. People have come back from transplants very well with supplementation of TUDCA with other stacks of compounds in order to speed their recovery.

"TUDCA and Multiple Drugs/Supplements
One study used a drug “cocktail” comprised of six drugs and supplements:

• Streptokinase
• Epoprostenol
• Thiazolidinediones (TZDs)
• N-Acetylcysteine (NAC)
• Hemin
• TUDCA

The cocktail was able to effectively treat damage to the liver, gallbladder, and bile ducts in liver transplant patients [R]."

https://www.selfhacked.com/blog/tudca-benefits/

Great reply! Got everything through this one.

 

[Derek Wilson]

Take it easy on the fish oil. I eat fish instead.

Right! Fish is a good choice.

 

[mawalega]

Be sure not to preload Tucda if you're planning on drinking. It is counter productive and it has a very long half life.

 

[muscleupcrohn]

Be sure not to preload Tucda if you're planning on drinking. It is counter productive and it has a very long half life.

Ironically NAC is the exact opposite haha.

Edit: do you happen to have a source for this? Some research I've seen seems to suggest that this is not the case regarding TUDCA:

Mice were fed high fat diet (HFD) or control diet for 9-10 weeks. We analyzed intrahepatic lipid accumulation, DNA replication, and various signaling pathways including cell proliferation and ER stress during liver regeneration after partial hepatectomy. In addition, some of mice were pretreated with tauroursodeoxycholic acid (TUDCA), a chemical chaperone which alleviates ER stress, and then we estimated TUDCA effects on liver regeneration.

In HFD mice, pretreatment with TUDCA reduced ER stress and resulted in improvement of delayed liver regeneration.

https://www.ncbi.nlm.nih.gov/pubmed/23512345

Similar results here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3032561/

Pre-treatment with TUDCA has also been found to help in some other perhaps non-related areas as well:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030606/

 

[mawalega]

Here's the article that I found that was pretty informative. Sorry for posting the entire thing... concerning alcohol is under benefits, right above safety and sides. I haven't looked at your studies atm but will after work.

Tauroursodeoxycholic acid, more commonly known as TUDCA, is an ambiphilic bile salt, the taurine conjugated form of ursodeoxycholic acid (UDCA).

That's a bunch of long words, but don't worry, we'll explain everything for you here.

TUDCA*is implicated in many protective effects in the body, primarily aiding in treatment of cholestasis, a condition that blocks or slows the flow of bile from the liver. However, as you'll read in this article, there are a number of additional positive effects of TUDCA that go beyond the liver.

Terms

This section will explain some general conceptsof bile acid synthesis, and give a simple explanation of relevant terms.

Bile

Bile is a bitter fluid that circulates from the liver to the duodenum (the first part of the small intestine) and aids in metabolism and the digestion of fats.

Primary bile acids are synthesized in the liver via oxidation of cholesterol into cholic acid and chenodeoxycholic acid. This process is rate-limited by an enzyme that is upregulated by cholesterol and downregulated by cholic acid.

Secondary bile acids are synthesized in the small intestine via intestinal bacteria (by dehydroxylating them into deoxycholic acid and lithocholic acid). There are additional forms of the secondary bile acids where the hydroxyl substitutions happen at different places on the molecule. Ursodeoxycholic acid (UDCA) is one of them, the prefix 'urso' hailing to the fact that this acid was first isolated from bears. These acids are typically found in only trace amounts in humans -- if at all.

Conjugated bile acids are acids that have been conjugated to a group that grants additional water solubility. These conjugates come in a wide range of forms but often include amino acids that are of particular interest to us. The amino acid taurine is one of these, and can be conjugated to UDCA to form our compound of interest, tauroursodeoxycholic acid (TUDCA).

In summary

Tauro + Urso + Deoxy + Cholic Acid

(Taurine conjugated) + (Found in bears) + (Dehydroxylated) + (Primary bile acid)

The cholestasis problem


Cholestasis is a condition in which the regular bile acids cannot flow from the liver to the intestine. It can be caused by a physical blockage (which TUDCA will not help with) or as a metabolic side effect of many substances (such as anabolic*steroids). This dangerous condition reduces the digestion of fats, and can result in jaundice and destruction of tissue in the liver.

Cholestasis causes

Cholestasis in athletes can be caused by supplementation with prohormones, becausesteroids and prohormones are hepatotoxic.[1] This can be further compounded by the use of methylated oral*steroids*since they pass through the liver repeatedly via the very process of enterohepatic circulation that is inhibited by cholestasis. This causes repetitive and extended stress on the liver and can result in major metabolic cholestasis.

When cholestasis is in effect,it triggers receptors (aptly named 'death receptors') that causes apoptosis (cell death).[2] TUDCA and other hydrophilic bile acids exert a cytoprotective effect on cells (that is, they prevent cell death) bytriggering receptors that promote cell survival.

This a very simplified explanation of the issue, and if you want to learn more, the linked articles are in mostly understandable terms. By increasing the portion of TUDCA in bile compared to harmful bile salts, you're diluting the ratio of harmful to protective bile acids.

TUDCA benefits

TUDCA exhibits neuroprotective effects, it can protect the brain against stroke and neurological injury, as well as the symptoms of various neurological diseases.[4, 5, 6, 7]
TUDCA's protection from cell death extends to cell death in general beyond that of just the liver via attenuating endoplasmic reticulum stress.[8, 9]
It has been demonstrated to restore glucose homeostasis in the liver, muscle, and fatty tissue.[10] This is probably linked to its attenuation of ER stress. But the exact method behind this action is unknown. In a separate study on humans, TUDCA was shown to increase insulin sensitivity in liver and muscle but not fatty tissue.[11]

TUDCA has undergone numerous studies on its potential for increasing metabolic rate, however most of these have been in animals, and the results are inconclusive.

In rats, TUDCA supplementation increased circulating adiponectin levels. Levels of this*protein*are reduced by obesity and it is responsible for regulating glucose levels as well as fatty acid metabolism.[10]

TUDCA can reduce damage to the liver caused by alcohol when taken with or after consumption of alcohol, but actually increases liver damage when taken before drinking.[12, 13]

Safety and side effects

TUDCA underwent ay ear long safety study in humans and was not associated with any adverse effects at all when taken at 500mg daily.[14] In the human study on insulin sensitivity, no adverse effects were noted when consumed at 1,750mg daily for a four weeks.

This establishes a good record for safety in humans, something worth touting as many dietary supplements do not have this going for them.

Recommended dosage


On that note, 500mg per day seems to be the preferred dosage. Some products have 250mg dosages, which can be taken one to two times per day.

As always, talk with your doctor before beginning any diet or supplementation program, especially with an advanced product like this one. An endocrinologist may help as well, if you are taking this for treatment of hormonal problems.


References

Ishak KG, Zimmerman HJ.; Seminars in Liver Disease; "Hepatotoxic effects of the anabolic/androgenic*steroids;" August 1987
Joana D. Amaral, et. al.; The Journal of Lipid Research; "Bile acids: regulation of apoptosis by ursodeoxycholic acid;" September 2009
Schoemaker MH, et. al.; Hepatology; "Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways;" June 2004
Rodrigues CM., et. al.; Proceedings of the National Academy of Sciences of the United States of America; "Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats;" May 2003
Rodrigues CM., et al.; Journal of Cerebral Blood Flow and Metabolism; "Neuroprotection by a bile acid in an acute stroke model in the rat;" April 2002
Dwan WN., et. al.; Cell Transplantation; "Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson's disease;" 2002
Ramalho RM; Journal of Neurochemistry; "Tauroursodeoxycholic acid modulates p53-mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells;" September 2006
Amaral JD., et. al.; The Journal of Lipid Research; "Bile acids: regulation of apoptosis by ursodeoxycholic acid;" September 2009
Ben Mosbah I., et. al.; Cell Death and Disease; "Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion;" July 2010
Ozcan U.; Science; "Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes;" August 2006
Kars M., Diabetes; "Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women;" August 2010
Henzel K., et. al.; Biochimica et Biophysica Acta; "Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid;" February 2004
Neuman MG, et. al.; Gastroenterology; "Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line;" August 1995
Angelico M. et. al.; Italian Journal of Gastroenterology and Hepatology; "One-year pilot study on tauroursodeoxycholic acid as an adjuvant treatment after liver transplantation;" August-September 1999

 

[mawalega]

I believe the half life to be about a week iirc... actually the reason I took it out of my personal rotation and supplement milk thistle and nac as it seems to better fit my lifestyle.

 

[muscleupcrohn]

Here's the article that I found that was pretty informative. Sorry for posting the entire thing... concerning alcohol is under benefits, right above safety and sides. I haven't looked at your studies atm but will after work.

Tauroursodeoxycholic acid, more commonly known as TUDCA, is an ambiphilic bile salt, the taurine conjugated form of ursodeoxycholic acid (UDCA).

That's a bunch of long words, but don't worry, we'll explain everything for you here.

TUDCA*is implicated in many protective effects in the body, primarily aiding in treatment of cholestasis, a condition that blocks or slows the flow of bile from the liver. However, as you'll read in this article, there are a number of additional positive effects of TUDCA that go beyond the liver.

Terms

This section will explain some general conceptsof bile acid synthesis, and give a simple explanation of relevant terms.

Bile

Bile is a bitter fluid that circulates from the liver to the duodenum (the first part of the small intestine) and aids in metabolism and the digestion of fats.

Primary bile acids are synthesized in the liver via oxidation of cholesterol into cholic acid and chenodeoxycholic acid. This process is rate-limited by an enzyme that is upregulated by cholesterol and downregulated by cholic acid.

Secondary bile acids are synthesized in the small intestine via intestinal bacteria (by dehydroxylating them into deoxycholic acid and lithocholic acid). There are additional forms of the secondary bile acids where the hydroxyl substitutions happen at different places on the molecule. Ursodeoxycholic acid (UDCA) is one of them, the prefix 'urso' hailing to the fact that this acid was first isolated from bears. These acids are typically found in only trace amounts in humans -- if at all.

Conjugated bile acids are acids that have been conjugated to a group that grants additional water solubility. These conjugates come in a wide range of forms but often include amino acids that are of particular interest to us. The amino acid taurine is one of these, and can be conjugated to UDCA to form our compound of interest, tauroursodeoxycholic acid (TUDCA).

In summary

Tauro + Urso + Deoxy + Cholic Acid

(Taurine conjugated) + (Found in bears) + (Dehydroxylated) + (Primary bile acid)

The cholestasis problem


Cholestasis is a condition in which the regular bile acids cannot flow from the liver to the intestine. It can be caused by a physical blockage (which TUDCA will not help with) or as a metabolic side effect of many substances (such as anabolic*steroids). This dangerous condition reduces the digestion of fats, and can result in jaundice and destruction of tissue in the liver.

Cholestasis causes

Cholestasis in athletes can be caused by supplementation with prohormones, becausesteroids and prohormones are hepatotoxic.[1] This can be further compounded by the use of methylated oral*steroids*since they pass through the liver repeatedly via the very process of enterohepatic circulation that is inhibited by cholestasis. This causes repetitive and extended stress on the liver and can result in major metabolic cholestasis.

When cholestasis is in effect,it triggers receptors (aptly named 'death receptors') that causes apoptosis (cell death).[2] TUDCA and other hydrophilic bile acids exert a cytoprotective effect on cells (that is, they prevent cell death) bytriggering receptors that promote cell survival.

This a very simplified explanation of the issue, and if you want to learn more, the linked articles are in mostly understandable terms. By increasing the portion of TUDCA in bile compared to harmful bile salts, you're diluting the ratio of harmful to protective bile acids.

TUDCA benefits

TUDCA exhibits neuroprotective effects, it can protect the brain against stroke and neurological injury, as well as the symptoms of various neurological diseases.[4, 5, 6, 7]
TUDCA's protection from cell death extends to cell death in general beyond that of just the liver via attenuating endoplasmic reticulum stress.[8, 9]
It has been demonstrated to restore glucose homeostasis in the liver, muscle, and fatty tissue.[10] This is probably linked to its attenuation of ER stress. But the exact method behind this action is unknown. In a separate study on humans, TUDCA was shown to increase insulin sensitivity in liver and muscle but not fatty tissue.[11]

TUDCA has undergone numerous studies on its potential for increasing metabolic rate, however most of these have been in animals, and the results are inconclusive.

In rats, TUDCA supplementation increased circulating adiponectin levels. Levels of this*protein*are reduced by obesity and it is responsible for regulating glucose levels as well as fatty acid metabolism.[10]

TUDCA can reduce damage to the liver caused by alcohol when taken with or after consumption of alcohol, but actually increases liver damage when taken before drinking.[12, 13]

Safety and side effects

TUDCA underwent ay ear long safety study in humans and was not associated with any adverse effects at all when taken at 500mg daily.[14] In the human study on insulin sensitivity, no adverse effects were noted when consumed at 1,750mg daily for a four weeks.

This establishes a good record for safety in humans, something worth touting as many dietary supplements do not have this going for them.

Recommended dosage


On that note, 500mg per day seems to be the preferred dosage. Some products have 250mg dosages, which can be taken one to two times per day.

As always, talk with your doctor before beginning any diet or supplementation program, especially with an advanced product like this one. An endocrinologist may help as well, if you are taking this for treatment of hormonal problems.


References

Ishak KG, Zimmerman HJ.; Seminars in Liver Disease; "Hepatotoxic effects of the anabolic/androgenic*steroids;" August 1987
Joana D. Amaral, et. al.; The Journal of Lipid Research; "Bile acids: regulation of apoptosis by ursodeoxycholic acid;" September 2009
Schoemaker MH, et. al.; Hepatology; "Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways;" June 2004
Rodrigues CM., et. al.; Proceedings of the National Academy of Sciences of the United States of America; "Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats;" May 2003
Rodrigues CM., et al.; Journal of Cerebral Blood Flow and Metabolism; "Neuroprotection by a bile acid in an acute stroke model in the rat;" April 2002
Dwan WN., et. al.; Cell Transplantation; "Tauroursodeoxycholic acid improves the survival and function of nigral transplants in a rat model of Parkinson's disease;" 2002
Ramalho RM; Journal of Neurochemistry; "Tauroursodeoxycholic acid modulates p53-mediated apoptosis in Alzheimer's disease mutant neuroblastoma cells;" September 2006
Amaral JD., et. al.; The Journal of Lipid Research; "Bile acids: regulation of apoptosis by ursodeoxycholic acid;" September 2009
Ben Mosbah I., et. al.; Cell Death and Disease; "Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion;" July 2010
Ozcan U.; Science; "Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes;" August 2006
Kars M., Diabetes; "Tauroursodeoxycholic Acid may improve liver and muscle but not adipose tissue insulin sensitivity in obese men and women;" August 2010
Henzel K., et. al.; Biochimica et Biophysica Acta; "Toxicity of ethanol and acetaldehyde in hepatocytes treated with ursodeoxycholic or tauroursodeoxycholic acid;" February 2004
Neuman MG, et. al.; Gastroenterology; "Effect of tauroursodeoxycholic and ursodeoxycholic acid on ethanol-induced cell injuries in the human Hep G2 cell line;" August 1995
Angelico M. et. al.; Italian Journal of Gastroenterology and Hepatology; "One-year pilot study on tauroursodeoxycholic acid as an adjuvant treatment after liver transplantation;" August-September 1999

I'll read through the studies they reference. The studies I referenced did supplement TUDCA pre-liver injury, but it wasn't ethanol induced, so perhaps that could be the difference? We'll see what these studies say.

 

[mawalega]

Yes sir concerning ethanol is the main problem I have seen. I've been off for a bit now and with the one week half life I didn't want to take the chance as I indulge more atm.... Just food for thought for those whom are contemplating it. It is an awesome supp if "popped responsibly" though.

 

[muscleupcrohn]

The second referenced study did find that preincubation increased toxicity. Interesting. It seems then that TUDCA is best suited for trying to heal/help the liver after cessation of exposure to compounds that could damage the liver, while NAC should be used before exposure to said compounds. Thanks for the links.

 

[Young Gotti]

I had bloodwork done a few months ago and my gallbladder levels came back a little off....something with the bile so the dr recommended I stop a lot of the supplements I'm taking, however also recommended milk thistle and NAC.....I went with TUDCA but have not gone back to follow up bloodwork yet, I would think at the beginning of the summer

 

[RiseAbove]

Very interesting that TUDCA taken before drinking is harmful but helpful if taken with alcohol or after. :scratchchin:

 

[muscleupcrohn]

Very interesting that TUDCA taken before drinking is harmful but helpful if taken with alcohol or after. :scratchchin:

Even more interesting that NAC is the exact opposite lol. Probably best to take them separately if you plan on drinking.

 

[mawalega]

Even more interesting that NAC is the exact opposite lol. Probably best to take them separately if you plan on drinking.

This and the further this... tucda's long half life and no real studies on how long before for next drink is safe, makes me hesitant to recommend unless you are drinking at most once a week.

 

[Derek Wilson]

Certainly some supplements can be harmful (obviously methylated prohormones are bad for your liver and some studies suggest high doses of EGCG can strain the liver) but in general, as long as you're healthy, and don't have any underlying health condition, the majority of supplements are just fine.

Thanks, I have heard about it last week.

 

[Derek Wilson]

Be sure not to preload Tucda if you're planning on drinking. It is counter productive and it has a very long half life.

When regular bile salts reach the intestines, they can be metabolized by bacteria into UDCA and then later bound to a taurine molecule to become TUDCA

 

[Derek Wilson]

Very interesting that TUDCA taken before drinking is harmful but helpful if taken with alcohol or after. :scratchchin:

Maybe you are right! Searching about it on Google. Thanks anyway!

 

[Derek Wilson]

This and the further this... tucda's long half life and no real studies on how long before for next drink is safe, makes me hesitant to recommend unless you are drinking at most once a week.

Thanks anyway!

 

[Derek Wilson]

Thanks guys!