Bile Acid Stimulates Mitochondrial Function, Could Treat Parkinson And Alzheimer's

haidut

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I posted a few studied some time ago showing that bile acids increase metabolism but stimulating the synthesis of T3. This increase in metabolism is perhaps the main mechanism behind the ability of "obesity surgery" to provide long-term benefits for the people who undergo the procedure. Aside form surgery, several steroids like allopregnanolone and progesterone also act upon the bile acid receptor and likely have similar effects. So does taurine, as a result of increasing bile acid synthesis.
How Taurine May Treat Diabetes
How Pregnenolone And Progesterone Raise Metabolism

This new study below found that one of these bile acids - ursodeoxycholic acid (UDCA) increases mitochondrial function, and as a result was beneficial for Parkinson disease (PD).
Ursodeoxycholic acid - Wikipedia
The authors think that the same mechanism may benefit patients with Alzheimer's disease (AD), which once again strongly suggests that both disease are metabolic in origin.

Ursodeoxycholic Acid Improves Mitochondrial Function and Redistributes Drp1 in Fibroblasts from Patients with either Sporadic or Familial Alzheimer's Disease - ScienceDirect
https://medicalxpress.com/news/2018-08-liver-disease-drug-cells-alzheimer.html

"...The pioneering study, funded by Alzheimer's Research UK, discovered the drug ursodeoxycholic acid (UDCA) improves mitochondrial dysfunction – which is known to be a causative factor for both sporadic and familial Alzheimer's disease. Mitochondria play a pivotal role in both neuronal cell survival and death as they regulate energy metabolism and cell death pathways acting as a cell's battery. Mitochondrial abnormalities have been identified in many cell types in Alzheimer's disease, with deficits occurring before the development of the classical pathological aggregations. The energy changes have been found in many different cells from people with Alzheimer's. It is thought they are one of the earliest changes to occur in the brain cells, perhaps even before symptoms are reported by people living with the disease. Dr Heather Mortiboys, Parkinson's UK Senior Research Fellow at the University of Sheffield's Institute of Translational Neuroscience (SITraN), said: "For the first time in actual Alzheimer's patient tissue this study has shown that the drug UDCA acid can boost the performance of the cells' batteries, the mitochondria. "We also found that the drug, which is already in clinical use for liver disease, acts by changing the shape of the batteries which could tell us more about how other drugs can be beneficial in Alzheimer's. "Most importantly we found the drug to be active in cells from people with the most common type of the devastating disease – sporadic Alzheimer's – which could mean it has potential for thousands of patients." Dr Mortiboys, who led the study, added: "As the drug is already in clinical use for liver disease; this speeds up the potential time it could take to get this drug to the clinic for patients." The ground-breaking research also found the drug changed the shape of mitochondria by redistributing Dynamin-related protein 1 (Drp1) to the mitochondria in people with Alzheimer's skin cells. Drp1 is a regulator of mitochondrial shape and locates at the mitochondria to initiate fission events. It is thought this could have neuroprotective effects in Alzheimer's disease. This study suggests this pathway could be manipulated by drugs which are then neuroprotective in patients themselves."

"...Previous laboratory studies conducted by SITraN in 2015 showed UDCA could be an effective treatment in halting the progression of Parkinson's disease. The collaborative study demonstrated the effects of the drug in patients that carry the LRRK2 mutation. The study showed improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels."
 

ddjd

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Taurine and glycine both essential for bile production I believe.

Choline also has something to do with healthy bile flow.
 

griesburner

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Would the supplement "TUDCA" do the same then as the drug UDCA? I know here in germany UDCA is prescription only but you can get TUDCA as a supplement very easy. Anyone know the difference between these substances and why one is prescription only and one not? taurine i tried several times, but always had pounding heart from it dont know why so that is not an option for me (sadly as it is the cheapest :))
 

stsfut

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Could you weigh in on ox bile supplements? For someone with a gallbladder still.
 

Tarmander

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I had some good results with TUDCA but it increased gyno for me...Taurine does that...probably LH rising.
 

haidut

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Would the supplement "TUDCA" do the same then as the drug UDCA? I know here in germany UDCA is prescription only but you can get TUDCA as a supplement very easy. Anyone know the difference between these substances and why one is prescription only and one not? taurine i tried several times, but always had pounding heart from it dont know why so that is not an option for me (sadly as it is the cheapest :))

Yes, it should, and in fact has been found to be superior to UDCA in several studies.
 

haidut

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Could you weigh in on ox bile supplements? For someone with a gallbladder still.

Should be fine. Taurine/glycine also stimulate bile production as @Joeyd mentioned. I think thyroid does too.
 

haidut

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I had some good results with TUDCA but it increased gyno for me...Taurine does that...probably LH rising.

Interesting. How much were you using of each? I have never had problems with taurine in doses under 3g daily.
 

nwo2012

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Should be fine. Taurine/glycine also stimulate bile production as @Joeyd mentioned. I think thyroid does too.

Coffee certainly does. It could also be the fact they all stimulate the liver, cleaning out toxins that bile acids and stimulation of bile release is so beneficial.
 

Tarmander

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I had some good results with TUDCA but it increased gyno for me...Taurine does that...probably LH rising.
Iirc...and it was a long time ago, taurine did not give as much gyno as tudca...I took taurine for awhile and had good energy before gyno slowly crept in. Tudca seemed to make nips swollen after one day. Maybe like @ecstatichamster says and it raises prolactin
 

Hans

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It's important to excrete that bile with something like carrot salad, as secondary bile (which is reabsorbed bile), is associated with obesity and diabetes.
 

Mufasa

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I believe that Chris Masterjohn recommends eating fibrous food for increasing bile acid production.
 

Mufasa

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I send this study to Ray Peat asking if eating food like carots, bamboo shoots and mushrooms may stimulate bile acid production. His answer was that they probably stimulate bile acid production in the liver but he didnt know how that would affect the amount that gets absorbed in the general circulation.
 

Motif

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I can't tolerate taurine at all unfortunately.
My bile flow is really bad. Probably this is what made me sick.

I surmise progesterone helps a bit with it. I started a few days ago and my stools are darker.

But not sure if it's safe to stay on progesterone.
 

Amazoniac

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At times I have the impression that these are discussed and used without having an idea of their significance. Not Jorge, he knows everything.


- cholic acid - Wiktionary
- chenodeoxycholic acid - Wiktionary

- Cheno and Urso: What the Goose and the Bear Have in Common


- Bile acid - Wikipedia

"Bile acid synthesis occurs in liver cells which synthesize primary bile acids (cholic acid and chenodeoxycholic acid in humans) via cytochrome P450-mediated oxidation of cholesterol in a multi-step process. Approximately 600 mg of bile salts are synthesized daily to replace bile acids lost in the feces, although, as described below, much larger amounts are secreted, reabsorbed in the gut and recycled. The rate-limiting step in synthesis is the addition of a hydroxyl group of the 7th position of the steroid nucleus by the enzyme cholesterol 7 alpha-hydroxylase. This enzyme is down-regulated by cholic acid, up-regulated by cholesterol and is inhibited by the actions of the ileal hormone FGF15/19."

"Prior to secreting any of the bile acids (primary or secondary, see below), liver cells conjugate them with one of two amino acids, glycine or taurine, to form a total of 8 possible conjugated bile acids. These conjugated bile acids are often referred to as bile salts because of their physiologically-important acid-base properties. [Check out the first video link'd.] The pKa of the unconjugated bile acids are between 5 and 6.5, and the pH of the duodenum ranges between 3 and 5, so when unconjugated bile acids are in the duodenum, they are almost always protonated (HA form), which makes them relatively insoluble in water. Conjugating bile acids with amino acids lowers the pKa of the bile-acid/amino-acid conjugate to between 1 and 4. Thus conjugated bile acids are almost always in their deprotonated (A-) form in the duodenum, which makes them much more water-soluble and much more able to fulfil their physiologic function of emulsifying fats."

"When these bile salts are secreted into the lumen of the intestine, bacterial partial dehydroxylation and removal of the glycine and taurine groups forms the secondary bile acids, deoxycholic acid and lithocholic acid. Cholic acid is converted into deoxycholic acid and chenodeoxycholic acid into lithocholic acid. All four of these bile acids can be taken back up into the blood stream, return to the liver, and be re-secreted in a process known as enterohepatic circulation."

"Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis producing 400–600 mg daily. Human adults secrete between 12-18 g of bile acids into the intestine each day, mostly after meals. The bile acid pool size is between 4–6 g, which means that bile acids are recycled several times each day. About 95% of bile acids are reabsorbed by active transport in the ileum and recycled back to the liver for further secretion into the biliary system and gallbladder. This enterohepatic circulation of bile acids allows a low rate of synthesis but with large amounts being secreted into the intestine."​


- Advanced Nutrition and Human Metabolism (978-1-133-10405-6)

"Chenodeoxycholic acid and cholic acid are primary bile acids and make up 80% of the body’s total bile acids. The remaining 20% of the bile acids is made up of secondary products produced in the large intestine from bacterial action on chenodeoxycholic acid to form lithocholic acid and on cholic acid to form deoxycholic acid." "Chenodeoxycholic acid and cholic acid, once formed, conjugate primarily (∼75%) with the amino acid glycine to form the conjugated bile acids glycochenodeoxycholic acid (glycochenodeoxycholate) and glycocholic acid (glycocholate), respectively." "Alternately and to a lesser (25%) extent, chenodeoxycholic acid and cholic acid conjugate with the amino acid taurine to form two additional primary conjugated bile acids."

"In addition to being conjugated to amino acids, most conjugated bile acids are present in bile as bile salts owing to bile’s pH (∼7.6–8.6). Sodium is the predominant biliary cation, although potassium and calcium bile salts may also be found in the alkaline bile solution."


"The pool of bile is thought to recycle at least twice per meal."

"Although bile acids and salts make up a large portion of bile, other substances are also found in bile. These other substances include both cholesterol and phospholipids, especially lecithin, and make up what is referred to as the bile acid–dependent fraction of bile. In addition, water, electrolytes, bicarbonate, and glucuronic acid conjugated bile pigments (mainly bilirubin, biliverdin, or both—waste end products of hemoglobin degradation that are excreted in bile and give bile its color) are secreted into bile by hepatocytes."


"This alkaline-rich fraction of the bile is referred to as bile acid independent. The bile components must remain in the proper ratio to prevent gallstone formation (cholelithiasis), although other factors influence gallstone production."


upload_2019-11-12_10-43-35.png


Despite being at the end, these are valuable:

- Bile Acids | JJ Medicine
- Bile acids and bile salts | AK Lectures

- Bile salts: definition, function, synthesis from cholesterol
 
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