Are you considering trying TUDCA, NAC or Milk Thistle supplements & confused what may be your best option? With each supplement having its own unique set of advantages, understanding the differences between them is essential. In this blog post we will provide a detailed overview comparing the similarities of TUDCA, NAC & Milk Thistle as well as what sets these three supplements apart.

What is TUDCA

Tauroursodeoxycholic acid or more simply referred to as TUDCA, is a natural bile acid that is produced in the human body. The liver releases bile salts into the intestines via the bile duct from there the bile salts are then metabolized into ursodeoxycholic acid (UDCA) by microbes in the large intestine. To create TUDCA, the UDCA is conjugated with a taurine molecule. Being a bile acid TUDCA supports digestion and in particular the utilisation of fats and oils. The body only produces relatively small quantities of TUDCA, which can be negatively impacted by factors such as poor diet, microbiome dysbiosis (parasites, pathogens etc), gallbladder dysfunction, certain medications and impaired liver function. TUDCA is also readily available in supplemental form & has come a long way from the days of sourcing it from bear bile - thankfully these days TUDCA supplements are not derived from animal sources.

TUDCA Health Benefits

TUDCA has been extensively studied for its benefits on liver and digestive health. TUDCA is known to help protect liver cells from damage caused by toxins and help reduce inflammation in the liver. Additionally, it has shown promise in treating and preventing certain liver diseases, such as non-alcoholic fatty liver disease (NAFLD) and liver cirrhosis. Studies have shown TUDCA to significantly lower raised liver enzymes (such as Serum ALT, AST and ALP) in patients with liver cirrhosis. Another study looking at TUDCA’s effects on liver function in patients with primary biliary cirrhosis found similar positive results.

TUDCA has also been shown to have protective effects on other organs, such as the brain (thanks to it’s ability to cross the blood brain barrier) in which case some interesting research has shown it's potential role in treatment approaches with neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington’s and Motor Neuron Disease.

For an in-depth article on TUDCA I recommend taking a look at the previous blog post “Unlocking the Health Benefits of Tauroursodeoxycholic Acid (TUDCA)”

Best TUDCA supplements

When it comes to liver support, TUDCA supplementation is certainly no new kid on the block, and bodybuilders have been well aware of TUDCAs liver supporting properties for a long time. There are several brands of TUDCA supplements on the market, but not all are created equal. When choosing a TUDCA supplement, it's important to look for one that is high-quality, pure, and free from unwanted additives. Seek out a supplement that has been third-party tested and has good reviews from other users. Our online store in Australia stocks two of the best TUDCA supplements, BodyBio & LVLUP Health, like with all our supplements we do a thorough review before we choose to add to our store.

What is N-acetylcysteine (NAC)

N-acetylcysteine, also known as NAC, is a synthetic derivative of L-cysteine, which is an amino acid found in the body. When taken orally, NAC is absorbed in the small intestine and transformed by the liver into cysteine. The liver then uses this cysteine to create glutathione. It's role in glutathione production is one of the main uses in medicine. NAC has been used clinically for over five decades.

NAC Health Benefits

N-acetylcysteine (NAC) is a supplement that has been gained significant attention for its health benefits over the last few decades. A large portion of the research undertaken on NAC has been centered around its role as a precursor to glutathione, a powerful antioxidant in the body that helps reduce oxidative stress and inflammation. At high doses NAC has traditionally been used as a treatment for acetaminophen intoxication & overdose. NAC has been shown to have antimicrobial effects largely due to it's biofilm disrupting and mucolytic properties. In the 1960s, the use of NAC as a mucolytic agent was first reported in patients with cystic fibrosis.

Studies have shown NAC to be quite a versatile compound with benefits seen in respiratory health, liver function, mental health, neurodegenerative diseases, obsessive-compulsive disorder (OCD) and addictive behaviors to highlight a few. It's quite possible that this versatility & broad mechanisms of action prompted researches to explore it's potential with COVID-19 prevention as well as an adjuvant therapy. Given NAC's positive track record regarding it's role in treating and management of disorders associated with glutathione depletion and oxidative stress further bolsters it's potential with the management of COVID-19.

COVID-19 can lead to multiple health complications such as pneumonia, acute respiratory distress syndrome, cardiovascular issues, and even multiple organ failure. These complications are believed to be caused by a cytokine storm, which is essentially an aggressive inflammatory and immune system response. Additionally, studies have shown that COVID-19 patients may experience an imbalance of oxidative stress in their bodies. In a review paper exploring the potential role NAC may play with the management of COVID-19 the authors concluded:

"Based on a broad range of antioxidant and anti‐inflammatory mechanisms, which are herein reviewed, the oral administration of NAC is likely to attenuate the risk of developing COVID‐19, as it was previously demonstrated for influenza and influenza‐like illnesses. Moreover, high‐dose intravenous NAC may be expected to play an adjuvant role in the treatment of severe COVID‐19 cases..."

On the topic of COVID-19, a somewhat common complication is the negative impact the virus can have on male fertility. One particular study showed that NAC may have in potentially help offset some of these complications from the virus...

"NAC consumption significantly improved sperm total motility, sperm morphology and sperm concentration."

What is Milk Thistle (Silybum marianum) ?

Milk thistle (Silybum marianum) is a medicinal herb with a rich history of therapeutic use spanning over 2,000 years. It contains silymarin, a mixture of flavonolignans found in its fruits, with silybin (also known as silibinin) being the primary component and major biologically active flavonolignan that makes up silymarin.

Benefits of Milk Thistle

Mothers have traditionally used the fruits of Silybum marianum to increase their milk production. The plant is also linked to an ancient legend that suggests the white veins on its leaves were created by a drop of the milk of the mother of Jesus - hence it often referred as St. Mary’s thistle.

Fast forward to the modern era and one of the primary benefits of milk thistle is its ability to protect and restore liver function. The herb contains a powerful compound called silymarin, which has been shown to have antioxidant and anti-inflammatory properties. In fact, in the 1970s, the World Health Organization recognized silymarin, as a medicine with hepatoprotective (liver protective) properties due to its health benefits.

Studies have also found that milk thistle through it's various mechanisms of action in the body has a favorable effect on parameters associated with metabolic syndrome. Such as modulating the cholesterol system via promoting an ideal ratio between HDL and LDL. Improvements with insulin resistance has also been shown in the studies as well as anti-diabetic and anti-obesity effect. and reduce the risk of certain types of cancer. Additionally, milk thistle may also aid in digestion and support the immune system.

Side Effects of TUDCA, NAC, and Milk Thistle

If you are considering taking TUDCA, NAC, or Milk Thistle, it is important to be aware of the potential side effects that may occur. TUDCA, whilst not overly common has been known to cause diarrhea, stomach discomfort, and headaches in some individuals, however this is generally when doses exceed those done in clinical studies. Clinically significant adverse events and side effect with NAC are rare. However, gastrointestinal discomfort whilst not overly common has been reported as the most frequently reported adverse event. At therapeutic doses, Milk Thistle/Silymarin is considered safe for humans and even at a high dose of 700 mg taken three times a day for 24 weeks. The only side effects observed were some gastrointestinal discomforts such as nausea and diarrhea. It is always best to consult with a healthcare professional before taking any supplement to determine the safest dosage and to ensure there are no potential interactions with any medications you are currently taking.

Concluding remarks

Ultimately, it is important to make informed decisions when it comes to dietary supplements. TUDCA, NAC, and Milk Thistle all offer effective liver support via differing mechanisms; however, based on the information outlined in this blog post, TUDCA stands out as one of the best options for individuals looking to protect and promote optimal liver health. NAC on the other hand has quite far reaching health benefits so I’d argue that’s the most versatile of the three. A simple PubMed search also highlights NAC’s extensive history of research studies which as the time of writing comes up with over 2000 studies, compared to TUDCA and Milk Thistle which both have just over 100 studies each.

If you're looking for where to buy TUDCA in Australia or where to buy NAC the Holistic Lifestyler online store stock only the highest quality supplements, such as BodyBio TUDCA and Thorne NAC . As for Milk Thistle, Quicksilver Scientific do a fantastic comprehensive Liquid Liver Cleanse Supplement “Liver Sauce” which contains not only Milk thistle but a few other key players such as DIM, Quercetin, Lipoic Acid, Dandelion plus other to support liver health and is also in the highly bioavailable liposomal form.

References

Abenavoli, L. et al. (2018) ‘Milk Thistle (silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases’, Phytotherapy Research, 32(11), pp. 2202–2213. doi:10.1002/ptr.6171.

De Flora, S., Balansky, R. and La Maestra, S. (2020) ‘Rationale for the use of n‐acetylcysteine in both prevention and adjuvant therapy of Covid‐19’, The FASEB Journal, 34(10), pp. 13185–13193. doi:10.1096/fj.202001807.

di Michele, F. et al. (2018) ‘N-acetyl cysteine and vitamin D supplementation in treatment resistant obsessive-compulsive disorder patients: A general review’, Current Pharmaceutical Design, 24(17), pp. 1832–1838. doi:10.2174/1381612824666180417124919.

Dodd, S. et al. (2008) ‘n-acetylcysteine for antioxidant therapy: Pharmacology and clinical utility’, Expert Opinion on Biological Therapy, 8(12), pp. 1955–1962. doi:10.1517/14728220802517901.

Hurst, G., A., Shaw, B. and LeMaistre, C.A. (1967) ‘Laboratory and clinical evaluation of the mucolytic properties of acetylcysteine’, Am Rev Respir Dis ., pp. 962–970. doi:10.1164/arrd.1967.96.5.962.

Invernizzi, P. et al. (1999) “Differences in the metabolism and disposition of Ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis,” Hepatology, 29(2), pp. 320–327. Available at: https://doi.org/10.1002/hep.510290220.

Mertens, K.L. et al. (2017) “Bile acid signaling pathways from the enterohepatic circulation to the Central Nervous System,” Frontiers in Neuroscience, 11. Available at: https://doi.org/10.3389/fnins.2017.00617.

Morley, K.C. et al. (2018) ‘N-acetyl cysteine in the treatment of alcohol use disorder in patients with liver disease: Rationale for further research’, Expert Opinion on Investigational Drugs, 27(8), pp. 667–675. doi:10.1080/13543784.2018.1501471.

Pan, X.-li et al. (2013) “Efficacy and safety of Tauroursodeoxycholic acid in the treatment of liver cirrhosis: A double-blind randomized controlled trial,” Journal of Huazhong University of Science and Technology [Medical Sciences], 33(2), pp. 189–194. Available at: https://doi.org/10.1007/s11596-013-1095-x.

Rafiee, B. and Bagher Tabei, S.M. (2021) ‘The effect of N-acetyl cysteine consumption on men with abnormal sperm parameters due to positive history of covid-19 in the last three months’, Archivio Italiano di Urologia e Andrologia, 93(4), pp. 465–467. doi:10.4081/aiua.2021.4.465.

Raghu, G. et al. (2021) ‘The multifaceted therapeutic role of N-Acetylcysteine (NAC) in disorders characterized by oxidative stress’, Current Neuropharmacology, 19(8), pp. 1202–1224. doi:10.2174/1570159x19666201230144109.

Soleimani, V. et al. (2019) ‘Safety and toxicity of Silymarin, the major constituent of milk Thistle Extract: An updated review’, Phytotherapy Research, 33(6), pp. 1627–1638. doi:10.1002/ptr.6361.

Tajmohammadi, A., Razavi, B.M. and Hosseinzadeh, H. (2018) ‘silybum marianum (milk thistle) and its main constituent, Silymarin, as a potential therapeutic plant in metabolic syndrome: A Review’, Phytotherapy Research, 32(10), pp. 1933–1949. doi:10.1002/ptr.6153.

Tardiolo, G., Bramanti, P. and Mazzon, E. (2018) ‘Overview on the effects of N-acetylcysteine in neurodegenerative diseases’, Molecules, 23(12), p. 3305. doi:10.3390/molecules23123305.

WESOŁOWSKA, O. et al. (2007a) ‘Influence of silybin on biophysical properties of phospholipid bilayers’, Acta Pharmacologica Sinica, 28(2), pp. 296–306. doi:10.1111/j.1745-7254.2007.00487.x.