TUDCA / UDCA
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Tauroursodeoxycholic acid (TUDCA) and Ursodeoxycholic acid (UDCA) are bile acids themselves that are non-toxic to the liver and in fact have been proven to exhibit the exact opposite - they assist in bile flow through various different pathways which will be covered shortly. TUDCA is simply the taurine conjugate of UDCA (UDCA with a taurine amino acid bound to it), which has been claimed to exhibit greater oral bioavailability, but both variants have been proven to work very effectively. TUDCA and UDCA used to be extracted from the liver of bears, but synthetic methods have since been developed in order to manufacture these compounds, as well as the ability to derive them from other sources.

By far the most effective liver support compound available, TUDCA and UDCA are compounds that serve to speed up the metabolic transition of toxic bile acids to less toxic bile acids, and they also serve to increase the manufacture of non-toxic bile acids from cholesterol.[5] The result is a decrease in the toxicity of the bile pool. Remember when I mentioned above that liver toxicity from oral anabolic steroids (in the really bad stages) results in bile building up in the hepatocytes (liver cells) until they rupture and bile spills out onto other cells killing them? Well, the bile being spilled out consists of mostly toxic bile salts. TUDCA and UDCA are beneficial non-toxic bile salts that will essentially balance out the toxicity of the bile pool and serve to neutralize the toxicity making it less toxic to the surrounding resident liver cells. TUDCA and UDCA have also shown to increase amounts of the bile salt export pump (a transporter protein) in the liver cells, thus increasing the flow of bile as a result.[6] What this means is that they will facilitate the flow of bile in the liver so that the bile pool will not remain stagnant damage the surrounding liver cells. A good analogy to explain this is using the 'hot potato' analogy where a group of people in a circle are throwing a hot potato around from person to person fairly quickly. As long as the hot potato is passed around at a constant pace, no single person's hand will get burned, but if the hot potato is to remain in one person's hand for too long, they will end up doing damage to their hands by being burned (which is much like a stagnant bile pool in the liver damaging the surrounding cells). These compounds have also demonstrated to serve as antiapoptotics in liver cells, which means they effectively block the transcription factor known as AP-1, which is activated during cholestasis due to various toxic bile salts that will activate death receptors on liver cells.[7]

TUDCA and UDCA are by far the best quintessential treatments for both the prevention of cholestasis, as well as the recovery from it. They are, quite literally, the compounds specific to the treatment and mitigation of oral C17-alpha alkylated anabolic steroid liver toxicity - this cannot be said of any other liver support supplement/compound. In addition to treating cholestasis very effectively, it has demonstrated in studies to also reduce the risk of hepatitis B, where they had significantly decreased the risk of having abnormal serum alanine aminotransferase activity at the end of treatment compared to the beginning.[8] Other studies have also shown that UDCA and TUDCA are beneficial in the treatment necroinflammatory liver disease, such as (and especially for) hepatitis C-related chronic hepatitis in which bile duct damage and some degree of cholestasis are frequently seen at histology, and the study had observed that TUDCA had significantly improved the biochemical expression of chronic hepatitis.[9] In general, TUDCA seems to prevent hepatic cell death.[10]

Dosing of TUDCA and UDCA: 500-1000mg daily for the maintenance of healthy liver function during the use of a C17aa oral during a cycle. 1,000mg or higher daily for the purpose of repairing the liver following heavy hepatotoxicity and hepatocyte damage from cholestasis (and/or for individuals with serious liver disorders).

IMPORTANT: Do not exceed 8 weeks of TUDCA/UDCA use, as it can increase negative cholesterol values and decrease HDL. It is recommended to use these bile salts only during a cycle of oral C17aa anabolic steroids, or for the purpose of liver repair following periods of significant hepatotoxicity from the use of these compounds. Other compounds should be sought after for general year-round liver support.

According to this study (taken from Examine), TUDCA has been shown to decrease HDL levels when taken for extended periods of time. In normal people, this really isn't a big deal. In people who are constantly using steroids, like blasting and cruising (B&C), it can become counter-intuitive to run TUDCA for no reason due to decreased HDL levels. For example, on a cruise one wants to let their body recover, and ideally see good bloodwork before blasting again. One key reading on the bloodwork is the HDL, as HDL is one marker that almost always drops significantly while taking exogenous steroids in large dosages.

Also, according to the FDA as listed in UDCA's medication safety profile (two sources below), UDCA should not be taken without direct indication to do so, i.e. gallstones or primary biliary cirrhosis. The pros of taking TUDCA and UDCA while not on oral steroids or having one of the aforementioned indications do not outweigh the cons. TUDCA should not be used for year round general liver support, as there are other options (discussed below) which do not have these negative drawbacks, thus making the choice clear.

NAC (N-acetylcysteine)

NAC (N-acetylcysteine) is an excellent liver protectant/support compound that has demonstrated effectiveness in mitigating hepatotoxicity[11] as well as successfully treating acetaminophen (Tylenol) induced hepatotoxicity,[12] which is an added benefit for NAC that TUDCA does not do. NAC has also demonstrated some pretty good effectiveness at mitigating and preventing cholestasis as evidenced by studies. One particular study administered 300mg/kg of NAC orally to rats for 28 days, and not only did NAC administration reduce elevations of liver enzyme values that would otherwise be high without NAC administration, it also seemed to improve renal (kidney) function as well![13] That same study indicated, though, that NAC's activity in ameliorating cholestasis is not through the same pathway as TUDCA. NAC's ability to prevent or cure cholestasis stems from its antioxidant and immunomodulatory properties. Acetylcysteine serves to increase the glutathione reserves in the body and, together with glutathione, they both directly bind to toxic metabolites. This serves to protect hepatocytes (liver cells) from succumbing to toxicity from Tylenol or cholestasis. TUDCA instead operates through the direct action of essentially 'balancing' the content of bile salts (TUDCA is itself a bile salt), and while it does assist in mitigating cholestasis, it does not do anything for Tylenol-related toxicity. Another study also investigated NAC's ability to help alleviate cholestasis, which focused a little more on the observation of the renal (kidney) related effects, and found that in addition to improved liver enzyme values, NAC had the ability to vastly improve markers of kidney function and was actually able to even double the rate of sodium excretion.[14] This would also strongly indicate that NAC might prove very useful for the elimination of sodium and its related water retention in the body, which is something that might be of particular interest for anabolic steroid using individuals who might be having problems with water retention during a cycle.

The problem, however, with NAC is that it has demonstrated very poor oral bioavailability,[15] and this is the reason as to why high oral doses of NAC were utilized in studies for the treatment of Tylenol poisoning compared to when the subjects were administered NAC through the IV (intravenous) route of administration. Aside from NAC's ability as a nephroprotective (kidney protecting) and hepatoprotective (liver protecting) agent, it is well documented to serve a myriad of other benefits to the body. Although these benefits of NAC do not pertain to the main topic at hand (liver support during anabolic steroid use), it is very informative and helpful to know and understand that NAC has potential applications that are extremely far reaching beyond simply liver and kidney function.

Dosing of NAC: As previously mentioned, there are issues in regards to poor oral bioavailability with NAC. IV and inhalation formats of NAC do exist, but are generally prescription-only, depending on which country. However, the oral format of NAC is generally widely available for purchase almost anywhere. Be sure to look for a NAC product that has chelated it to an element or compound to provide greater bioavailability. With that being said, a proper dose for the purpose of maintenance of liver health during a cycle of C17-alpha alkylated anabolic steroids would be in the range of 1,000mg - 2,000mg of NAC per day. NAC can be used year-round as a general liver support, and should be run at 1,000mg per day or less when not utilizing C17-alpha alkylated oral anabolic steroids.

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