Nicotinamide (niacinamide) Induces Liver Regeneration & Improves Liver Function By Activating SIRT1

OP
olive

olive

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Did you test liver enzymes before and after or have you just noticed signs of better liver function?
I don’t have bloodwork on hand but there’s hundreds of positive reports/bloodwork online from bodybuilders who use T/UDCA after abusing liver toxic oral steroids with marked recovery. As well as a plethora of studies showing dramatic improvement to complete healing of the liver.
 
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I don’t have bloodwork on hand but there’s hundreds of positive reports/bloodwork online from bodybuilders who use T/UDCA after abusing liver toxic oral steroids with marked recovery. As well as a plethora of studies showing dramatic improvement to complete healing of the liver.
Awesome thanks man
 

Dobster

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Is there a specific type/compound/brand of T/UDCA that one takes ? Dosage ? Any other pertinent info please.
Thanks/Dobster
 
OP
olive

olive

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Joined
May 17, 2018
Messages
555
Is there a specific type/compound/brand of T/UDCA that one takes ? Dosage ? Any other pertinent info please.
Thanks/Dobster
250-500mg/day for 4 weeks. Do not drink alcohol or take any hepatoxic drugs while using the medication. Best to talk to your doctor though.
 
OP
olive

olive

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Choline can be obtained through diet; egg yolks and liver are the best sources I know.
 

Dobster

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Messages
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250-500mg/day for 4 weeks. Do not drink alcohol or take any hepatoxic drugs while using the medication. Best to talk to your doctor though.
I have Seen Supplements at a Gym shop marked T/udca..is that the same ? Thanks.
 
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250-500mg/day for 4 weeks. Do not drink alcohol or take any hepatoxic drugs while using the medication. Best to talk to your doctor though.

Why no alcohol? I drink sometimes with tudca and have been fine.
 
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Why no alcohol? I drink sometimes with tudca and have been fine.

Btw tudca has a very long half life of 3+ days, further as it builds in your bile pool it has an even longer lifetime, years potentially, so alcohol interactions are going to happen after the course either way - if you drink alcohol.
 

Inaut

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Regarding tudca.... I asked @Travis this question some time ago regarding the effectiveness of taurine vs tudca for gallstones specifically. Here’s what he sent me.. I miss the guy truly :(


TravisMember
The formation of biliary stones appears rather straightforward, and knowing the mechanism suggests methods for their reversal. Biliary stones are composed of mostly cholesterol, with the balance being predominately: bile salts, calcium, and mucin. Endogenous cholesterol or refined sugar intake appears a prerequisite for their formation, yet as you will see they alone are not sufficient.

'When it was demonstrated by Admirand and Small that gallbladder bile from cholesterol gallstone patients could be distinguished from controls by relating their relative lipid compositions to the cholesterol solubility limits in a model system, a rational physical-chemical basis for gallstone formation appeared straightforward.' Carey

Bile itself consists mostly of water, phospholipids, cholesterol, mucin, and bile salts—taurocholine being the most prevalent. The phospholipids and bile salts are polar lipids chemically-considered detergents, and as such form micelles in solution. Conditions in which the sum bile salts and phospholipids together to outnumber cholesterol approximately over 11∶1, all bile cholesterol will betrapped inside micelles composed of phospholipid–taurocholine mixed micelles and solubilized. Thus: the three-way ratio can be represented graphically on a 3-axis system, or triangular coordinates, where the small space contained within the solid line indicates bile compositions where cholesterol is completely-soluble. The larger space lying without represents supersaturated conditions of free cholesterol, and it's only in this compositional region where cholesterol can precipitate. The boundary line has been determined experimentally by solutions of cholesterol, taurocholate, and phospholipids—egg yolk lecithin in this case:⁽¹⁾

cholate-png.10499


In a manner harmonious with in vitro physical chemistry: the bile of subjects without stones is found to lie within the solubility region, and that of those with stones without. This has been confirmed by others in humans,⁽²⁾ nonhuman primates,⁽³⁾ and prairie dogs,⁽⁴⁾ and misgivings about mechanical means of their removal have been expressed as early as 1971; because it's quite obvious, really, that these can be dissolved using simple dietary modifications.

'The effort expended by clinicians to provide treatment for patients with biliary tract calculi has thus far outdistanced that directed toward research into the basic mechanisms of gallstone formation.'McSherry

Most bile samples cluster within a region where phospholipid and cholesterol concentrations appear the prime determinants, more important than the bile salt concentration. For this reason: dietary cholesterol could perhaps be reduced, to a degree, and low-dose olive oil could be appropriate. Dietary saturated fatty acids tend more towards neutral triglycerides for storage, whereas phospholipids tend more towards phospholipid incorporation. Of the dietary unsaturated fatty acids, oleic (18∶1ω−9) and α-linolenic (18∶3ω−3) acids are certainly the safest: The former is in fact produced de novo, via stearate (18∶0), and the latter is an essential DHA precursor. Although ω−6 fatty acids are phospholipid constituents: there are reasons, as you will see, that they would backfire to an extent.

'Prostaglandins are known to stimulate mucin release in stomach and appear also to be involved in gallbladder mucin release. We reported that arachidonate, when added to explants of prairie dog gallbladder in organ culture, caused a 2- to 5-fold release of mucin. This stimulatory effect was blocked by indomethacin, at doses which blocked prostaglandin release from the tissue.'LaMont

Although bile salt concentrations appear less causative by a superficial glance at the solubility plots, they are perhaps more important that initially thought. Bile salts derive from cholesterol, so the more that is converted to taurocholate the less could precipitate in the gallbladder. Moreover, high taurocholate could be better than phospholipids at dissolving stones in situ due to a more compatible solubility. Nothing would seem better for dissolving a cholesterol crystal, in my opinion, than a cholesterol analogue having a highly polar tail. The sterol end would likely better associate with cholesterol than would a phospholipid, intercalating itself using it's steroid core while solubilizing with its sulfonate tail. This has in fact been demonstrated with tauroursodeoxycholate,⁽⁵⁾ a bile acid which which happens to commercially available at reasonable price.

cholate2-png.10503


Yet it could be argued that the simple ingestion of taurine would be better on account of 'killing two birds with one stone,' increasing taurocholate synthesis while concomitantly decreasing cholesterol. This does in fact seem quite feasible, yet just as in vivo stone formation had conformed with theory so had this: The ability of supplemental taurine to completely abrogate biliary stone formation had been proven by Fujihira in 1977,⁽⁶⁾ by Yamanaka in 1984,⁽⁷⁾ and perhaps even by others unmentioned. Both studies demonstrate a complete lack of gallstone formation in cholesterolemic rats using 5% taurine, and both studies show a reduction in liver cholesterol. Taurine facilitates safe elimination of cholesterol by forming soluble taurocholates, even increasing the solubility of free cholesterol in by shifting the taurine∶glycine ratio of bile salts. The taurine-conjugated bile salts are more polar than those glycine-conjugated, and are generally more successful at dissolving biliary stones.

deoxycholate-png.10505


'Gallstone formation appeared after the 3rd week in cholesterol-fed mice, and the incidence was 100% at the 5th week. On the contrary, gallstone formation was not observed at all in the taurine-supplemented mice or the mice of the standard group.' Yamanaka

'The finding of this study that daily intake of large amounts of taurine during feeding of the lithogenic diet is remarkably effective in protecting gallstone formation in CsiBL/6 mice could be explained by a possible role of dietary taurine in enhancing the biliary excretion of absorbed cholic acid through the conjugation. Furthermore it is suggested that facilitating the conjugation and excretion of cholic acid may be associated with the increased degradation of excess cholesterol.'Fuhihira

cholate3-png.10504


Yet there is one important factor not considered under the classic micelle solubility paradigm, and that is mucin. In a series of studies in the early '80s, Thomas LaMont et. al. had demonstrated the fourth factor responsible for the differences in stone formation among boundary cases—a puzzling fact noted earlier by Carey. The LaMont studies had shown that mucin, a protein–oligosaccharide complex, precipitates cholesterol by nucleation.

'As the cholesterol content of a large number of fasting hepatic biles fall well outside the zone of metastability as defined in this work and yet did not precipitate their excess cholesterol as judged microscopically, one is forced to conclude that the metastable region of native bile is much larger than found with the model system. This suggests that the presence of certain other quantitatively minor components in human bile or the absence of nucleating agents maintain cholesterol in metastable supersaturated solution in most individuals. Nevertheless, the greater degree of cholesterol supersaturation in both the gallbladder and hepatic biles of cholesterol gallstone patients when compared to controls strongly suggests that this is the predominant driving force for cholesterol precipitation and gallstone growth.'Carey

Mucin is composed of a lipophilic protein chain—high in valine, alanine, and serine—surrounded by oligosaccharides arrayed like a pipe brush. The oligosaccharides lend the molecule high water-solubility, yet the valine–alanine core has considerable affinity for sterols. Studies have shown that stone formation is coincident with gallbladder mucin and that cholesterol induces its release.⁽⁸⁾ Although not entirely explicable in the '80s, I propose this is caused by: (1) an increased membrane cholesterol concentration inducing phospholipase A₂, as it is now known to do; (2) the subsequent release of arachidonate into the cytosol after which (3) it becomes cyclicized it into prostaglandin H₂ by cyclooxygenase. This prostaglandin then (4) spontaneously degrades into prostagaldin D₂, (5) dehydrates into prostaglandin J₂, and finally (6) induces mucin synthesis by activating PPARγ. LaMont does mention prostaglandins as being being involved in one of his another articles—the one reporting the prevention of gallstones by using aspirin. This had of course had coincided with a reduction in mucin synthesis, and not one of the three classic solubility parameters were effected.⁽⁹⁾ It should be no surprise that 2-series prostaglandins release mucin, as this could actually be an evolutionary indicator of the presence of yeast or helminths. It could be worth noting that yeast, fungi, and helminths all: (1) have Δ¹²-desaturase, (2) can produce ω−6 fatty acids, and (3) can even emit arachidonate and 2-series prostaglandins into the host.

cholate4-png.10507


This suggests another function of α-linolenic (18∶3ω−3), the only real essential fatty acid. The reason for this is because it elongates into DHA (22∶6ω−3), a cell membrane lipid that acts to exclude cholesterol more than any other. This fatty acid maintains membrane permeability to glucose, enhances myelination by excluding sterols towards the nerves, and prevents the ingression of the competing omega−6 osbond acid (22∶5ω−6). By excluding cholesterol from cell membranes in the gallbladder, this should attenuate phospholipase A₂ activity and arachidonic acid release. It's elongation product EPA (22∶5ω−3) can actually displace arachidonic acid, and any prostaglandins produced from this are of the less active 3-series. Prostaglandin J₂ can activate PPARγ, yet it hasn't been demonstrated whether Prostaglandin J₃ can even do this. Their high ω−3/ω−6 ratio could by why the Japanese have the lowest rates of biliary stones among industrialized countries,⁽¹¹⁾ perhaps along with their idiosyncratic use of supplemental choline.

'Gallstone disease in Europe is similar to the U.S., with a median prevalence in large population surveys, ranging from 5.9 to 21.9%. [...] The Indians of South America have a similar high prevalence of gallbladder disease. In Chile, the native Mapuche Indians demonstrate a high occurrence of gallbladder disease; 49.4% in women and 12.6% in men. [Potatoes are common in Chile, and these have a high percentage of phytosterols. Cholesterol has even been detected in potatoes.] The frequency is lower in Chilean Hispanics with a lesser American Indian admixture: 36.7% of women and 13.1% in men. The prevalence of gallstones in Mexican Americans is also a direct function of the degree of Amerindian admixture. White Americans have a somewhat lower prevalence: 16.6% of women and 7.9% of men. Superlative ultrasound-based surveys in Europe have revealed that higher overall prevalences occur in Norway (21.9%) and the former East Germany (19.7%), whereas lower rates are evident in Italy (Sirmione 6.2% and Chlanciano 5.9%). [The Italians consume higher concentrations of oleic acid, a phospholipid precursor that cannot become prostaglandins.] A fine example is the Multicentre Italian Study of Cholelithiasis (MICOL) that examined 29,739 subjects aged 30–69 years in 16 cohorts in 10 Italian regions. Overall, gallstone disease was present in 18.8% of women and 9.5% of men. Similar results came from the Sirmione study of 19,030 Italians between the ages of 18 and 65 years, yielding a total prevalence of 11%. Intermediate prevalence rates occur in Asian populations and Black Americans (13.9% of women and 13.9% of men). The lowest frequencies are in Black Africans (<5%), the best studied being the Masi tribe and the Bantu, in whom the entity is virtually non-existent. Ethnicity also determines the type of stone and where they reside in the biliary system. In developed countries, the majority (about 80–85%) consists predominantly of cholesterol crystals, while the remainder are of black pigment (calcium bilirubinate and mucin glycoproteins). Cholesterol and black pigment stones form in the gallbladder. [...] The frequency of hepatolithiasis, as a proportion of all biliary tract stones, varies from a high of 20% in China and Taiwan to 2–3% in Japan, Singapore and Hong Kong.' Shaffer

'Detrimental are diets with a high caloric intake and refined carbohydrates. Beneficial are diets high in fibre, vegetable protein, nuts, calcium, vitamin C, caffeinated coffee, and alcohol in moderation. Dietary fat is controversial, but a high intake of polyunsaturated and monounsaturated fats appears to reduce gallstone disease in the context of an energy-balanced diet.' Shaffer

Coffee is negative risk factor, perhaps explicable by cafestrol's known ability to increase bile flow.⁽¹²⁾Ethanol has also been shown protective, and although there could be many explanations for this a reabsorption of bile acids seems intuitive. Due the risk distribution by latitude, one could assume that melatonin and/or Vitamin D could play a role.

Supportive of high melatonin is that bile acid synthesis is under circadian control, with two peaks occurring during the daytime.⁽¹² Suggestive of low vitamin D being important is that: (1) it is eliminated through the bile;⁽¹³⁾ (2) it is more polar than most sterols, having a lipophilic core and a lipophilic 'tail' reminiscent of bile salts; (2) it could disrupt efficient cholesterol crystallization using its seco-steroidal core region.

On account of the aforementioned studies—and some others that I'd read previously—I would most suggest the following:
  1. Taurine (2 g/d): Decreases liver and gallbladder cholesterol while transforming some into taurocholates.
  2. Aspirin (1 g/d): Attenuates prostaglandin synthesis by inhibiting cyclooxygenase.
  3. Olive Oil (.5 oz/d): The safest way to increase phospholipids.
  4. α-Linolenic acid (1 g/d): Attenuates prostaglandin formation by elongating into DHA, thereby inhibiting membrane cholesterol incorporation. This should abrogate enhanced phospholipase A₂ activity, synthesis of 2-series prostaglandins, activation of PPARγ, and genetic expression of mucin. This should also increase the 3-series/2-series prostaglandin ratio by foming EPA, displacing arachidonate from the membrane by inhibiting its formation.
Tauroursodeoxycholate is also available and has been used clinically to dissolve cholesterol stones, yet taurine will do this and also reduce liver/gallbladder cholesterol in the process. Bright lights and moonlighting should lower melatonin output and prolong bile acid synthesis, yet vitamin D could be somewhat superfluous in the presence of enhanced taurocholate formation.

[1] Admirand, W. "The physicochemical basis of cholesterol gallstone formation in man." The Journal of clinical investigation(1968)
[2] Carey, M. "The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man." The Journal of clinical investigation (1978)
[3] McSherry, C. "Cholesterol gallstones and the chemical composition of bile in baboons." Annals of surgery (1971)
[4] Lee, S. "Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones: studies in the prairie dog." The Journal of clinical investigation (1981)
[5] Igimi, H. "Cholesterol gallstone dissolution in bile: dissolution kinetics of crystalline cholesterol with chenodeoxycholate, ursodeoxycholate, and their glycine and taurine conjugates." Journal of lipid research (1981)
[6] Fujihira, E. "Strain difference in mouse cholelithiasis and the effect of taurine on the gallstone formation in C57BLMC mice." Biochemical medicine (1978)
[7] Yamanaka, Y. "Effect of dietary taurine on cholesterol gallstone formation and tissue cholesterol contents in mice." Journal of nutritional science and vitaminology (1985)
[8] Lamont, T. "Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones: studies in the prairie dog." The Journal of clinical investigation (1981)
[9] Lamont, T. "Aspirin prevention of cholesterol gallstone formation in prairie dogs." Science (1981)
[10] Lamont, T. "Role of gallbladder mucin in pathophysiology of gallstones." Hepatology(1984)
[11] Shaffer, E. "Epidemiology of gallbladder stone disease." Best Practice & Research Clinical Gastroenterology (2006)
[12] Gälman, C. "Bile acid synthesis in humans has a rapid diurnal variation that is asynchronous with cholesterol synthesis." Gastroenterology (2005)
[13] Avioli, L. "Metabolism of [³H]-vitamin D₃ in human subjects: distribution in blood, bile, feces, and urine." The Journal of clinical investigation (1967)

Travis
 
Joined
Feb 26, 2018
Messages
988
Regarding tudca.... I asked @Travis this question some time ago regarding the effectiveness of taurine vs tudca for gallstones specifically. Here’s what he sent me.. I miss the guy truly :(


TravisMember
The formation of biliary stones appears rather straightforward, and knowing the mechanism suggests methods for their reversal. Biliary stones are composed of mostly cholesterol, with the balance being predominately: bile salts, calcium, and mucin. Endogenous cholesterol or refined sugar intake appears a prerequisite for their formation, yet as you will see they alone are not sufficient.

'When it was demonstrated by Admirand and Small that gallbladder bile from cholesterol gallstone patients could be distinguished from controls by relating their relative lipid compositions to the cholesterol solubility limits in a model system, a rational physical-chemical basis for gallstone formation appeared straightforward.' Carey

Bile itself consists mostly of water, phospholipids, cholesterol, mucin, and bile salts—taurocholine being the most prevalent. The phospholipids and bile salts are polar lipids chemically-considered detergents, and as such form micelles in solution. Conditions in which the sum bile salts and phospholipids together to outnumber cholesterol approximately over 11∶1, all bile cholesterol will betrapped inside micelles composed of phospholipid–taurocholine mixed micelles and solubilized. Thus: the three-way ratio can be represented graphically on a 3-axis system, or triangular coordinates, where the small space contained within the solid line indicates bile compositions where cholesterol is completely-soluble. The larger space lying without represents supersaturated conditions of free cholesterol, and it's only in this compositional region where cholesterol can precipitate. The boundary line has been determined experimentally by solutions of cholesterol, taurocholate, and phospholipids—egg yolk lecithin in this case:⁽¹⁾

cholate-png.10499


In a manner harmonious with in vitro physical chemistry: the bile of subjects without stones is found to lie within the solubility region, and that of those with stones without. This has been confirmed by others in humans,⁽²⁾ nonhuman primates,⁽³⁾ and prairie dogs,⁽⁴⁾ and misgivings about mechanical means of their removal have been expressed as early as 1971; because it's quite obvious, really, that these can be dissolved using simple dietary modifications.

'The effort expended by clinicians to provide treatment for patients with biliary tract calculi has thus far outdistanced that directed toward research into the basic mechanisms of gallstone formation.'McSherry

Most bile samples cluster within a region where phospholipid and cholesterol concentrations appear the prime determinants, more important than the bile salt concentration. For this reason: dietary cholesterol could perhaps be reduced, to a degree, and low-dose olive oil could be appropriate. Dietary saturated fatty acids tend more towards neutral triglycerides for storage, whereas phospholipids tend more towards phospholipid incorporation. Of the dietary unsaturated fatty acids, oleic (18∶1ω−9) and α-linolenic (18∶3ω−3) acids are certainly the safest: The former is in fact produced de novo, via stearate (18∶0), and the latter is an essential DHA precursor. Although ω−6 fatty acids are phospholipid constituents: there are reasons, as you will see, that they would backfire to an extent.

'Prostaglandins are known to stimulate mucin release in stomach and appear also to be involved in gallbladder mucin release. We reported that arachidonate, when added to explants of prairie dog gallbladder in organ culture, caused a 2- to 5-fold release of mucin. This stimulatory effect was blocked by indomethacin, at doses which blocked prostaglandin release from the tissue.'LaMont

Although bile salt concentrations appear less causative by a superficial glance at the solubility plots, they are perhaps more important that initially thought. Bile salts derive from cholesterol, so the more that is converted to taurocholate the less could precipitate in the gallbladder. Moreover, high taurocholate could be better than phospholipids at dissolving stones in situ due to a more compatible solubility. Nothing would seem better for dissolving a cholesterol crystal, in my opinion, than a cholesterol analogue having a highly polar tail. The sterol end would likely better associate with cholesterol than would a phospholipid, intercalating itself using it's steroid core while solubilizing with its sulfonate tail. This has in fact been demonstrated with tauroursodeoxycholate,⁽⁵⁾ a bile acid which which happens to commercially available at reasonable price.

cholate2-png.10503


Yet it could be argued that the simple ingestion of taurine would be better on account of 'killing two birds with one stone,' increasing taurocholate synthesis while concomitantly decreasing cholesterol. This does in fact seem quite feasible, yet just as in vivo stone formation had conformed with theory so had this: The ability of supplemental taurine to completely abrogate biliary stone formation had been proven by Fujihira in 1977,⁽⁶⁾ by Yamanaka in 1984,⁽⁷⁾ and perhaps even by others unmentioned. Both studies demonstrate a complete lack of gallstone formation in cholesterolemic rats using 5% taurine, and both studies show a reduction in liver cholesterol. Taurine facilitates safe elimination of cholesterol by forming soluble taurocholates, even increasing the solubility of free cholesterol in by shifting the taurine∶glycine ratio of bile salts. The taurine-conjugated bile salts are more polar than those glycine-conjugated, and are generally more successful at dissolving biliary stones.

deoxycholate-png.10505


'Gallstone formation appeared after the 3rd week in cholesterol-fed mice, and the incidence was 100% at the 5th week. On the contrary, gallstone formation was not observed at all in the taurine-supplemented mice or the mice of the standard group.' Yamanaka

'The finding of this study that daily intake of large amounts of taurine during feeding of the lithogenic diet is remarkably effective in protecting gallstone formation in CsiBL/6 mice could be explained by a possible role of dietary taurine in enhancing the biliary excretion of absorbed cholic acid through the conjugation. Furthermore it is suggested that facilitating the conjugation and excretion of cholic acid may be associated with the increased degradation of excess cholesterol.'Fuhihira

cholate3-png.10504


Yet there is one important factor not considered under the classic micelle solubility paradigm, and that is mucin. In a series of studies in the early '80s, Thomas LaMont et. al. had demonstrated the fourth factor responsible for the differences in stone formation among boundary cases—a puzzling fact noted earlier by Carey. The LaMont studies had shown that mucin, a protein–oligosaccharide complex, precipitates cholesterol by nucleation.

'As the cholesterol content of a large number of fasting hepatic biles fall well outside the zone of metastability as defined in this work and yet did not precipitate their excess cholesterol as judged microscopically, one is forced to conclude that the metastable region of native bile is much larger than found with the model system. This suggests that the presence of certain other quantitatively minor components in human bile or the absence of nucleating agents maintain cholesterol in metastable supersaturated solution in most individuals. Nevertheless, the greater degree of cholesterol supersaturation in both the gallbladder and hepatic biles of cholesterol gallstone patients when compared to controls strongly suggests that this is the predominant driving force for cholesterol precipitation and gallstone growth.'Carey

Mucin is composed of a lipophilic protein chain—high in valine, alanine, and serine—surrounded by oligosaccharides arrayed like a pipe brush. The oligosaccharides lend the molecule high water-solubility, yet the valine–alanine core has considerable affinity for sterols. Studies have shown that stone formation is coincident with gallbladder mucin and that cholesterol induces its release.⁽⁸⁾ Although not entirely explicable in the '80s, I propose this is caused by: (1) an increased membrane cholesterol concentration inducing phospholipase A₂, as it is now known to do; (2) the subsequent release of arachidonate into the cytosol after which (3) it becomes cyclicized it into prostaglandin H₂ by cyclooxygenase. This prostaglandin then (4) spontaneously degrades into prostagaldin D₂, (5) dehydrates into prostaglandin J₂, and finally (6) induces mucin synthesis by activating PPARγ. LaMont does mention prostaglandins as being being involved in one of his another articles—the one reporting the prevention of gallstones by using aspirin. This had of course had coincided with a reduction in mucin synthesis, and not one of the three classic solubility parameters were effected.⁽⁹⁾ It should be no surprise that 2-series prostaglandins release mucin, as this could actually be an evolutionary indicator of the presence of yeast or helminths. It could be worth noting that yeast, fungi, and helminths all: (1) have Δ¹²-desaturase, (2) can produce ω−6 fatty acids, and (3) can even emit arachidonate and 2-series prostaglandins into the host.

cholate4-png.10507


This suggests another function of α-linolenic (18∶3ω−3), the only real essential fatty acid. The reason for this is because it elongates into DHA (22∶6ω−3), a cell membrane lipid that acts to exclude cholesterol more than any other. This fatty acid maintains membrane permeability to glucose, enhances myelination by excluding sterols towards the nerves, and prevents the ingression of the competing omega−6 osbond acid (22∶5ω−6). By excluding cholesterol from cell membranes in the gallbladder, this should attenuate phospholipase A₂ activity and arachidonic acid release. It's elongation product EPA (22∶5ω−3) can actually displace arachidonic acid, and any prostaglandins produced from this are of the less active 3-series. Prostaglandin J₂ can activate PPARγ, yet it hasn't been demonstrated whether Prostaglandin J₃ can even do this. Their high ω−3/ω−6 ratio could by why the Japanese have the lowest rates of biliary stones among industrialized countries,⁽¹¹⁾ perhaps along with their idiosyncratic use of supplemental choline.

'Gallstone disease in Europe is similar to the U.S., with a median prevalence in large population surveys, ranging from 5.9 to 21.9%. [...] The Indians of South America have a similar high prevalence of gallbladder disease. In Chile, the native Mapuche Indians demonstrate a high occurrence of gallbladder disease; 49.4% in women and 12.6% in men. [Potatoes are common in Chile, and these have a high percentage of phytosterols. Cholesterol has even been detected in potatoes.] The frequency is lower in Chilean Hispanics with a lesser American Indian admixture: 36.7% of women and 13.1% in men. The prevalence of gallstones in Mexican Americans is also a direct function of the degree of Amerindian admixture. White Americans have a somewhat lower prevalence: 16.6% of women and 7.9% of men. Superlative ultrasound-based surveys in Europe have revealed that higher overall prevalences occur in Norway (21.9%) and the former East Germany (19.7%), whereas lower rates are evident in Italy (Sirmione 6.2% and Chlanciano 5.9%). [The Italians consume higher concentrations of oleic acid, a phospholipid precursor that cannot become prostaglandins.] A fine example is the Multicentre Italian Study of Cholelithiasis (MICOL) that examined 29,739 subjects aged 30–69 years in 16 cohorts in 10 Italian regions. Overall, gallstone disease was present in 18.8% of women and 9.5% of men. Similar results came from the Sirmione study of 19,030 Italians between the ages of 18 and 65 years, yielding a total prevalence of 11%. Intermediate prevalence rates occur in Asian populations and Black Americans (13.9% of women and 13.9% of men). The lowest frequencies are in Black Africans (<5%), the best studied being the Masi tribe and the Bantu, in whom the entity is virtually non-existent. Ethnicity also determines the type of stone and where they reside in the biliary system. In developed countries, the majority (about 80–85%) consists predominantly of cholesterol crystals, while the remainder are of black pigment (calcium bilirubinate and mucin glycoproteins). Cholesterol and black pigment stones form in the gallbladder. [...] The frequency of hepatolithiasis, as a proportion of all biliary tract stones, varies from a high of 20% in China and Taiwan to 2–3% in Japan, Singapore and Hong Kong.' Shaffer

'Detrimental are diets with a high caloric intake and refined carbohydrates. Beneficial are diets high in fibre, vegetable protein, nuts, calcium, vitamin C, caffeinated coffee, and alcohol in moderation. Dietary fat is controversial, but a high intake of polyunsaturated and monounsaturated fats appears to reduce gallstone disease in the context of an energy-balanced diet.' Shaffer

Coffee is negative risk factor, perhaps explicable by cafestrol's known ability to increase bile flow.⁽¹²⁾Ethanol has also been shown protective, and although there could be many explanations for this a reabsorption of bile acids seems intuitive. Due the risk distribution by latitude, one could assume that melatonin and/or Vitamin D could play a role.

Supportive of high melatonin is that bile acid synthesis is under circadian control, with two peaks occurring during the daytime.⁽¹² Suggestive of low vitamin D being important is that: (1) it is eliminated through the bile;⁽¹³⁾ (2) it is more polar than most sterols, having a lipophilic core and a lipophilic 'tail' reminiscent of bile salts; (2) it could disrupt efficient cholesterol crystallization using its seco-steroidal core region.

On account of the aforementioned studies—and some others that I'd read previously—I would most suggest the following:
  1. Taurine (2 g/d): Decreases liver and gallbladder cholesterol while transforming some into taurocholates.
  2. Aspirin (1 g/d): Attenuates prostaglandin synthesis by inhibiting cyclooxygenase.
  3. Olive Oil (.5 oz/d): The safest way to increase phospholipids.
  4. α-Linolenic acid (1 g/d): Attenuates prostaglandin formation by elongating into DHA, thereby inhibiting membrane cholesterol incorporation. This should abrogate enhanced phospholipase A₂ activity, synthesis of 2-series prostaglandins, activation of PPARγ, and genetic expression of mucin. This should also increase the 3-series/2-series prostaglandin ratio by foming EPA, displacing arachidonate from the membrane by inhibiting its formation.
Tauroursodeoxycholate is also available and has been used clinically to dissolve cholesterol stones, yet taurine will do this and also reduce liver/gallbladder cholesterol in the process. Bright lights and moonlighting should lower melatonin output and prolong bile acid synthesis, yet vitamin D could be somewhat superfluous in the presence of enhanced taurocholate formation.

[1] Admirand, W. "The physicochemical basis of cholesterol gallstone formation in man." The Journal of clinical investigation(1968)
[2] Carey, M. "The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man." The Journal of clinical investigation (1978)
[3] McSherry, C. "Cholesterol gallstones and the chemical composition of bile in baboons." Annals of surgery (1971)
[4] Lee, S. "Role of gallbladder mucus hypersecretion in the evolution of cholesterol gallstones: studies in the prairie dog." The Journal of clinical investigation (1981)
[5] Igimi, H. "Cholesterol gallstone dissolution in bile: dissolution kinetics of crystalline cholesterol with chenodeoxycholate, ursodeoxycholate, and their glycine and taurine conjugates." Journal of lipid research (1981)
[6] Fujihira, E. "Strain difference in mouse cholelithiasis and the effect of taurine on the gallstone formation in C57BLMC mice." Biochemical medicine (1978)
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Travis

Good stuff. Fwiw I experience better results from tudca 5oomg than from long periods on 2+ grams of taurine. I think tudca may just work faster.
 

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