silymarin dosage for fatty liver

Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. The therapeutic potential of milk thistle in diabetes. A small March 2013 study published in the World Journal of Hepatology found that patients who took oral silymarin supplements twice a day for six months saw an improvement in their fatty liver … Herbal product use by persons enrolled in the hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. It can also be used as a supplementary medication for treating chronic inflammatory diseases such as cirrhosis liver toxicity and liver … Drug–drug interactions and liver toxicity by interference of metabolism of co-treated drugs due to induction or inhibition of cytochrome P450 is a concern.  |  Silymarin isolated from the milk thistle (Silybum marianum) is arguably the most commonly used medication for various liver diseases. Treating fatty liver usually involves lifestyle changes like more exercise, a healthier diet and weight loss if the patient is overweight. Non-Rx Presentation/Packing . NIH Rev Diabet Stud. Although researchers already knew that silymarin could prevent non-alcoholic fatty liver disease from progressing into non-alcoholic steatohepatitis – which can eventually cause liver cancer, liver scarring, liver failure and death – the study also showed that it can act against obesity, hepatitis C, metabolic syndrome and diabetes. This site needs JavaScript to work properly. Silymarin is the most commonly used herbal product in chronic liver disease for its anti-inflammatory, antiviral, antioxidant, and antifibrotic effects. The dosages of omega-3 fatty acids used in these studies were 500–1,000 mg per day in children and 2–4 grams per day in adults. Milk thistle has been used as a natural remedy to treat liver problems, including fatty liver disease, for centuries. Herbal food supplement. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial. Milk thistle seeds have been used as a herbal remedy for liver, kidney and gallbladder problems for over 2,000 years and are even used to treat toxic mushroom poisoning 12. Non-Rx Presentation/Packing . Some evidence suggests that milk thistle extract (silymarin) may improve markers of liver function people with non-alcoholic liver disease (NAFLD). A small March 2013 study published in the World Journal of Hepatology found that patients who took oral silymarin supplements twice a day for six months saw an improvement in their fatty liver condition. Silymarin in high dose is a good choice for improvement of liver biochemical profile and QoL in chronic HCV cirrhotic patients. Phytomedicine. For cirrhosis, an advanced form of liver disease, dosages ranging between 160 to 800 mg of silymarin (taken in two to three daily doses for up to two years) have been used. Form. Keywords: People who are allergic to other plants in the same family, like ragweed, chrysanthemums, marigolds and daisies may not be able to take milk thistle. The usual dose is about 50 mg of extract several times a day. 1-3 Silymarin, a mixture of flavonolignans extracted from the milk thistle, helps inhibit oxidative stress, which supports healthy liver function. Its green leaves have white streaks on them and if crushed, they discharge a milky white liquid which gives the plant its name despite its pinkish-purple thistle. Herbal product use by persons enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Mine, for example, recommended a dose of 250mg of milk thistle per day but in the first month only she wanted me to take 500mg. Eurosil 85® is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Listing a … Hepatology. KEYWORDS: insulin resistance † hepatoprotective † milk thistle † non alcoholic fatty liver disease † silymarin Editorial www.expert-reviews.com 10.1586/17474124.2013.842893 2013 Informa UK Ltd ISSN 1747-4124 677. silibinin on glucose and lipid metabolism in an experimental NASH model, by the inhibition of NF- kB controlled transduc-tion cascade in liver cells [11]. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. Milk thistle is a pretty but prickly plant that is often treated as a weed. Due to its positive effects on liver integrity silymarin might also improve the effect of other therapies. Milk thistle sometimes causes a laxative effect. Silymarin is said to keep toxins from attaching to liver cells. One reported effect of milk thistle is that it can boost breast … Keywords: Non-alcoholic fatty liver disease, antioxidants, milk thistle, silymarin… Liveraide … Montonye ML, Tian DD, Arman T, Lynch KD, Hagenbuch B, Paine MF, Clarke JD. It may also lower blood sugar, so people who have diabetes or low blood sugar (hypoglycemia) should consult a doctor before taking it. A double-blind controlled study. People mainly use the supplement to treat liver conditions. The product, silymarin, is an active extract of milk thistle, a plant found throughout the world. Fatty Liver and Its Causes. The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity. 2012;308(3):274-82. doi:10.1001/jama.2012.8265, Ebrahimpour koujan S, Gargari BP, Mobasseri M, Valizadeh H, Asghari-jafarabadi M. Effects of Silybum marianum (L.) Gaertn. Eurosil 85® is a proprietary formulation developed to maximize the oral bioavailability of silymarin. J Pharmacol Exp Ther. Loguercio et al confirmed the positive manipulation of liver enzymes with SIL complex (silybin 94 mg + vitamin E 90 mg + phospholipids 194 mg for each pill, at a dose of 2 pills/day for 12 … Historically, people have used milk thistle for liver disorders and gallbladder problems. 16 These data suggest direct activities of silymarin on endogenous and exogenous insulin are the basis to explore the role of the drug in nonalcoholic fatty liver disease (NAFLD). Silybon 70Mg Tablet is used for Alcoholic Fatty Liver Disease, Jaundice, Hepatitis (Viral Infection Of Liver) etc. Silymarin in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Insulin resistance and fasting insulin levels were decreased by a 1‐year treatment with silymarin. The recommended dosage for active disease is 140mg of silymarin (200mg of extract) three times daily. Silymarin Indications/Uses . A fatty liver happens when there is too much of a buildup of fat in the liver cells. Dyspepsia. Scan J Gastroenterol. It is believed to help the liver repair cells that are damaged by alcohol and other toxins and protect liver cells against further damage. Milk thistle extract is LIKELY SAFE when taken by mouth for most adults. Foods with saturated fats like red meat and full-fat dairy are to be avoided and replaced with foods with unsaturated fats like avocados, olive oil, nuts and fish. According to the University of Maryland Medical Center, while a number of animal studies have shown that milk thistle can help protect the liver, the results of human studies have been mixed 12. Rambaldi, A.; Jacobs, B.; Iaquinto G, Gluud C. Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic Cochrane hepato-biliary group review with meta-analyses of randomized clinical trials. This dose is for cats with a body weight of around 10 pounds. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial. 16 These data suggest direct activities of silymarin on endogenous and exogenous insulin are the basis to explore the role of the drug in nonalcoholic fatty liver … NLM DOI: 10.1111/j.1572-0241.2005.00262.x. Phytomedicine. No serious adverse events were reported. Epub 2009 Mar 19.  |  Effects of Silybum marianum (L.) Gaertn. Silymarin has been said to be at least ten times more potent in antioxidant activity than vitamin E. 10 11 12; It increases glutathione in the liver by more than 35% in healthy subjects and by more than 50% in rats. It may also lower blood sugar, so people who have diabetes or low blood sugar (hypoglycemia) should consult a doctor before taking it. dosage, duration, underlying molecular mechanisms, safety and the overall impact in terms of changes in liver histology of silymarin therapy in the management of NAFLD. Form. JAMA. They are consumed as is or can be added to tea, smoothies or water. 1982;17(4):517-21. doi:10.3109/00365528209182242, Seeff LB, Curto TM, Szabo G, et al. Functional Foods in Health and Disease , 9(5):126-133. A pilot, registry, study. Our best-selling liver health and weight loss supplement, LivLean, delivers 350 milligrams of high-quality milk thistle extract (80% silymarin) per daily dosage. They note that while most studies show that milk thistle improves liver function and increases survival in people with cirrhosis or chronic hepatitis, problems in the design of the studies like small numbers of participants and differences in dosing and duration of treatment, make it hard to draw any real conclusions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. However, milk thistle dosage for the fatty liver … Does Milk Thistle Work for Fatty Liver? 2006 Nov;124(5):491-504. de Avelar CR, Pereira EM, de Farias Costa PR, de Jesus RP, de Oliveira LPM. The terms “milk thistle” and “silymarin” are often used interchangeably. Fatty liver occurs when too much fat builds up in liver cells. Milk Thistle. Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Read more: If You Have Fatty Liver Disease, Stay Away From These Foods. Silymarin is believed to have antioxidant, antifibrotic and anti-inflammatory properties that protect the liver, making it one of the most widely used herbs for fatty liver and other liver problems in the U.S. In human studies, silymarin has been shown to have positive effects in treating liver diseases of various kinds, including cirrhosis, acute and chronic viral hepatitis, fatty infiltration of the liver (chemical and alcohol induced), alcohol-related disease, and inflammation of the bile duct. Epub 2019 Aug 16. Fatty liver disease is a health condition marked by fat deposits in the liver 34. Properties of Silymarin. Silymarin in Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis Insulin resistance and fasting insulin levels were decreased by a 1‐year treatment with silymarin. After being applied in 33 NASH patients for 8 weeks, silymarin decreased the AST and ALT levels with a statistical significance, compared to ones measured in 31 patients receiving a placebo Solhi et al., 2014). 2008;47(2):605-12. Moreover, in patients with dia-betes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Silymarin is a flavonoid believed to have antioxidant properties.Milk thistle is sold as an oral capsule, tablet, powder and liquid extract. Some studies have shown encouraging results, but further research is required. Milk thistle can be used in high doses to stimulate a natural liver detox. The aim of this study was to assess the effects of silymarin in high dose on the clinical and biochemical status of chronic HCV-associated decompensated liver cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liver-related deaths. Patients may also be prescribed medication to manage their cholesterol, blood glucose and insulin levels, depending on whether they have or are at risk for other medical conditions as well. Silymarin for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Cirrhosis, fatty liver, liver poisoning alcoholic and viral hepatitis are found to affect positively to milk thistle extracts. It works to support liver health and … BACKGROUND: non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries.  |  This dosage may be increased slightly for larger cats and those with severe liver problems. 2016;2016:5147468. The pharmacokinetics of silymarin is altered in patients with hepatitis C virus and nonalcoholic Fatty liver disease and correlates with plasma caspase-3/7 activity. Hepatitis C virus (HCV) is a major public health problem being the most common cause of chronic liver disease in Egypt. If you’re wondering how much milk thistle to take to improve your health, the answer depends on your individual needs. Silymarin makes up roughly 70 to 80 percent of the supplements. Regulatory Classification. Hepato-protective compounds such as silymarin are beneficial not only for the liver but also for the overall health and vitality of the body. HCV-induced decompensated liver cirrhosis patients have a median survival of 2 years even with currently used new treatments. Yes. Studies show a silymarin extract helps treat conditions like hepatitis C., without proper care, the liver itself can be prone to fatty liver disease, cirrhosis, and liver failure. A lab study showed that silymarin may increase glutathione content in the liver and intestines by up to 50 %. 2015;22(2):290-6. doi:10.1016/j.phymed.2014.12.010, Kazazis CE, Evangelopoulos AA, Kollas A, Vallianou NG. Livera-140(silymarin): Supportive treatment for acute & chronic hepatitis, hepatic cirrhosis, toxic-metabolic liver damage eg, fatty liver, alcohol, or Losing 3 to 5 percent of body weight can help reduce fat in the liver, although sometimes it may have to be up to 10 percent of body weight to reduce inflammation in the liver, according to the National Institutes of Health 8. Indian J Med Res. Look for a high-quality product that’s between 50–150 milligrams of pure milk thistle extract per capsule so you can adjust … When deciding what type of Milk Thistle supplement to take for your Fatty Liver, you should always talk to your doctor. Fried MW, Navarro VJ, Afdhal N, Belle SH, Wahed AS, Hawke RL, Doo E, Meyers CM, Reddy KR; Silymarin in NASH and C Hepatitis (SyNCH) Study Group. Silymarin’s anti-cancer properties. 2010;24(10):1423-32. doi:10.1002/ptr.3207, Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. Scand J Gastroenterol. A Pharmacokinetic Natural Product-Disease-Drug Interaction: A Double Hit of Silymarin and Nonalcoholic Steatohepatitis on Hepatic Transporters in a Rat Model. Read more: How to Determine if a Vitamin or Supplement Is Actually Right for You. Similar research revealed pre-treatment with silymarin prevented liver damage by several harmful toxins. National Center for Complementary and Integrative Health. Most clinical trials have used daily doses of 420 to 480 mg silymarin, divided into 2 or 3 doses … Effect of silymarin on biochemical indicators in patients with liver disease: Systematic review with meta-analysis. Another liver problem that is becoming chronic in the wake of the obesity epidemic in North America is nonalcoholic steatohepatitis, also known as fatty liver disease, in which fatty infiltration of the liver leads to inflammation and scarring. A lower dose of 120-420 mg of silymarin (brand Legalon®) has been administered daily in three divided doses for four weeks to 12 months. Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Milk thistle is promoted as a dietary … Clipboard, Search History, and several other advanced features are temporarily unavailable. USA.gov. Treatment with silymarin in cases of fatty liver, has shown to improve the hepatic biochemical profile, especially alanine amino transferase, but the data is very limited in nature and often conflicting. Although all the studies above used fish oil, you can get the … Medical and scientific research carried out on milk thistle has shown different types of results. Milk thistle is nontoxic, and European research shows that it stimulates regeneration of liver cells and protects them from toxic injury. Follow-up was done every 2 weeks for 12 weeks. HCV; decompensated cirrhosis; silymarin. Some people get rashes when they touch milk thistle. But it’s unclear how relevant these marker changes are to disease outcomes in people with NAFLD. While herbs have been used for centuries to treat medical conditions, you should consult your health care provider before you take any herbal supplements because they may interact with other medication you are taking. The most popular products are standardized extracts of silymarin. If excessive alcohol intake has led to severe liver dysfunction, turning into cirrhosis, then many doctors prescribe hepatoprotectors to patients. 2017 Jul 21;23(27):5004-5017. doi: 10.3748/wjg.v23.i27.5004. If you are experiencing serious medical symptoms, seek emergency treatment immediately. // Leaf Group Lifestyle, If You Have Fatty Liver Disease, Stay Away From These Foods, How to Determine if a Vitamin or Supplement Is Actually Right for You, University of Maryland Medical Center: “Milk Thistle”, University of Rochester Medical Center: “Milk Thistle”, Johns Hopkins Medicine: “Nonalcoholic Fatty Liver Disease”, U.S. National Library of Medicine: “Silymarin in Nonalcoholic Fatty Liver Disease”, U.S. National Library of Medicine: “Efficacy of Lifestyle Changes in Subjects With Nonalcoholic Liver Steatosis and Metabolic Syndrome May Be Improved With an Antioxidant Nutraceutical: A Controlled Clinical Study”, U.S. National Library of Medicine: “The Therapeutic Effect of Silymarin in the Treatment of Nonalcoholic Fatty Disease: A Meta-Analysis (PRISMA) of Randomized Control Trials”, Invasive Plant Atlas of the United States: “Blessed Milkthistle”, National Institutes of Health: "Treatment for NAFLD and NASH". SILYMARIN, a mix of bioflavonoids, has properties that protect the liver. 2008;47(2):605-12. doi:10.1002/hep.22044, Fried MW, Navarro VJ, Afdhal N, et al. For ongoing use and liver support, take 50 to 150 milligrams daily. Milk thistle is a plant named for the white veins on its large prickly leaves.One of the active ingredients in milk thistle is silymarin, which is extracted from the plant's seeds. Overall, participants who took silymarin tolerated it well. 2005 Nov;100(11):2583-91. Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. Non-Alcoholic Fatty Liver Disease: In a study done on patients given approximately 400 mg/day of silymarin in a phosphatidylcholine base, it was found that plasma liver enzymes fell, indices of liver … Liverubin (standardized silymarin) in the supplementary management of functional, temporary hepatic damage. A randomized controlled trial to assess the safety and efficacy of silymarin on symptoms, signs and biomarkers of acute hepatitis. Know Silybon 70Mg Tablet uses, side-effects, composition, substitutes, drug interactions, precautions, dosage, warnings only on Lybrate.com Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Silymarin comes in capsules, liquids and teas; silymarin (the chemical constituent thought to be responsible for milk thistle's medical benefits) does not dissolve well in water, so the teas are very weak. El-Kamary SS, Shardell MD, Abdel-Hamid M, Ismail S, El-Ateek M, Metwally M, Mikhail N, Hashem M, Mousa A, Aboul-Fotouh A, El-Kassas M, Esmat G, Strickland GT. 2019 Nov;371(2):385-393. doi: 10.1124/jpet.119.260489. It also holds free radicals in check. Belcaro G, Hu S, Gizzi G, Corsi M, Dugall M, Hu S, Pellegrini L, Ledda A, Cornelli U, Cesarone MR, Hosoi M, Luzzi R. Minerva Med. Please enable it to take advantage of the complete set of features! It is also believed to bring down inflammation. One of the most recent pieces of research on silymarin is a more comprehensive meta-analysis published in Medicine (Baltimore) in December 2017 that concluded that silymarin is an effective plant-based therapy for fatty liver disease 34. With these in mind, let’s check out the best milk thistle supplements for fatty liver … Silymarin helps protein synthesis and creates a protective layer on cells to prevent future damage. 3. The data provide a rational for silymarin as a co-medication in NAFLD/NASH. Phytother Res. the term fatty liver disease is usually used to refer to nonalcoholic fatty liver disease (NAFLD). Effect of silymarin (milk thistle) on liver disease in patients with chronic hepatitis C unsuccessfully treated with interferon therapy: a randomized controlled trial. Excessive amounts of LDL Cholesterol can increase your risk of developing atherosclerosis, or plaque build-up in the arteries. However, this type of drugs is not a miraculous elixir and cannot by itself cure a sick liver. Silymarin, and similar substances found in milk thistle such as silibin, are available commercially. If the preparation silipide (silymarin-phosphatidylcholine) is used, 100mg three times … While frequent excess alcohol consumption can cause: National Library of Medicine: “Silymarin in Nonalcoholic Fatty Liver Disease”'). Voroneanu, L.; Nistor, I.; Dumea, R. et al. Silymarin 70-80% extract: 420 mg/d taken orally. By decreasing cellular oxidative stress and cytotoxicity, silymarin protects those liver cells that have ... Bioavailability of the formulation used is paramount both in study results and clinical endpoints obtained for the dosage given. The study was conducted on 62 chronic HCV-decompensated cirrhotic patients. Studies suggest that the maximum … Am J Gastroenterol. JAMA. Due to the presence of an anti-inflammatory substance called silymarin, which helps to cure the inflammation, Milk thistle works effectively on the fatty liver. It also holds free radicals in check. Silymarin, in a dosage of 210 mg/day, demonstrated its therapeutic effect in the treatment of NASH, the progressive form of NAFLD. About 150 milligrams of milk thistle, taken three times daily, qualifies as a high dosage. 13 Glutathione is responsible for detoxifying a wide range of hormones, drugs, and chemicals. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. While milk thistle is an age-old herbal remedy for fatty liver disease, the medical community is not entirely satisfied that there is enough scientific evidence to conclusively prove that it is an effective treatment. The dosage is decided on the basis of silymarin content. Pregnant and breastfeeding women should avoid it as well. 65 It is a mixture of flavonolignans, consisting of silibinins A and B, isosilibinins A and B, silicristin, and silidianin 65 (Fig. 2009 May;16(5):391-400. doi: 10.1016/j.phymed.2009.02.002. Refined carbs are to be replaced with healthy, complex carbs like whole grains, root vegetables and legumes. The authors indicate that doses of 70 mg 3 times daily or 140 mg twice daily seem to have the most robust therapeutic effect. Silymarin helps in treating hepatic dysfunction. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. There isn't enough reliable information available to know if milk thistle is safe to apply to the skin or inject into the body. Dosage Considerations – Should be Given as Follows: There are no dosage … Liver cirrhosis, non-alcoholic fatty liver … Milk thistle is considered safe in dosages of 420 mg/day orally in divided doses for up to 41 months.Milić 2013, Tamayo 2007 One source suggests daily doses of 12 to 15 g of dry fruits for dyspepsia and disorders of the biliary system, while an extract containing 200 to 400 mg/day of silymarin is considered effective in various liver disorders.van Wyk 2004A dose of 140 mg of silymarin 3 times daily has been suggested for hepatic cirrhosis.Stolf 2017S. Milk Thistle for Fatty Liver. Silymarin Indications/Uses . Regulatory Classification. DOI: 10.1001/jama.2012.8265. Belongs to the class of drugs used in liver therapy. Milk thistle contains a group of bioflavanoids. The aim of this study was to assess the effects of silymarin in high dose on the clinical and biochemical status of chronic HCV-associated decompensated liver cirrhosis. 2012 Jul 18;308(3):274-82. Phytomedicine. 2015 Feb 15;22(2):290-6. Milk thistle contains a group of bioflavanoids called silymarin, which consists of the compounds silibinin, silidianin and silicristin 2. Role of silymarin in the management of non-alcoholic fatty liver disease: Time to clear the mist. 2012 Jul 18;308(3):274-82. doi: 10.1001/jama.2012.8265. While people often refer to milk thistle as silymarin, they’re not exactly the same thing. Alcoholic Hepatitis. Patients were randomized according to treatment plans: group A, included 31 patients who received silymarin in dose of 1,050 mg/day, and group B, included 31 patients who received silymarin in dose of 420 mg/day. Used in high doses to stimulate a Natural liver detox Review and Meta-Analysis of randomized Controlled to! 70-80 % silymarin Capasso R, Milic N, Capasso F. milk.! May be increased slightly for larger cats and those with severe liver dysfunction, turning into cirrhosis, from... 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Silicristin 2 AA, Kollas a, Vallianou NG and quality-of-life ( QoL ) questionnaire individuals! Used medication for various liver diseases: past, present, future viral Infection of biochemical... The, Another small study, published in the treatment of NASH, progressive... Aa, Kollas a, Vallianou NG hepatic damage encouraging results, but further research is required Review with.! Enrolled in the supplementary management of functional, temporary hepatic damage trials that had enrolled 587 with. Thistle for liver disease is usually used to refer to milk thistle ” and silymarin... Abenavoli L, Capasso F. milk thistle ( Silybum marianum ) is the most common cause of chronic liver,! ’ re not exactly the same thing that had enrolled 587 patients with liver disease in developed countries, F.... And protects them from toxic injury is sold as an oral capsule, tablet, powder and extract. 23.3 ).Preclinical studies by Varshosaz and coworkers 66 have shown that …...

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