Each capsule contains: Ostarine Ostarine ((S)-3-(4-Cyanophenoxy)-N-(4-cyano-3-trifluoromethyl- phenyl)-2-hy 10 mg • Milk Thistle 150 mg. Other Ingredients: Microcrystalline Cellulose, Magnesium Stearate, Silicon Dioxide.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Lean Mass Extreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Lean Mass Extreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately. A specific milk thistle extract standardized to contain 70% to 80% silymarin (Legalon, Madaus GmbH) has been safely used in doses up to 420 mg daily for up to 4 years (2613,2614,2616,7355,63210,63212,63278,63280,63299,63340)(88154,97626,105792). Higher doses of up to 2100 mg daily have been safely used for up to 48 weeks (63251,96107,101150). Another specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) has been safely used at doses of 140 mg daily for up to 6 months and doses of 420 mg daily for up to 6 weeks (95021,95029,102851,102852,105793,105794,105795). Some isolated milk thistle constituents also appear to be safe. Silibinin (Siliphos, Thorne Research) has been used safely in doses up to 320 mg daily for 28 days (63218). Some combination products containing milk thistle and other ingredients also appear to be safe. A silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) has been safely used in doses of 480 mg daily for 7 days (7356) and 240 mg daily for 3 months (63320). Tree turmeric and milk thistle capsules (Berberol, PharmExtracta) standardized to contain 60% to 80% silybin have been safely used twice daily for up to 12 months (95019,96140,96141,96142,97624,101158).
POSSIBLY SAFE ...when used topically and appropriately, short-term. A milk thistle extract cream standardized to silymarin 0.25% (Leviaderm, Madaus GmbH) has been used safely throughout a course of radiotherapy (63239). Another milk thistle extract cream containing silymarin 1.4% has been used with apparent safety twice daily for 3 months (105791,110489). A cream containing milk thistle fruit extract 25% has been used with apparent safety twice daily for up to 12 weeks (111175). A milk thistle extract gel containing silymarin 1% has been used with apparent safety twice daily for 9 weeks (95022). There is insufficient reliable information available about the safety of intravenous formulations of milk thistle or its constituents.
PREGNANCY AND LACTATION:
While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development (102850), there is insufficient reliable information available about its safety during pregnancy or lactation in humans; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A milk thistle extract 140 mg three times daily has been used with apparent safety for up to 9 months (88154,98452). A specific product containing the milk thistle constituent silybin (Siliphos, Thorne Research Inc.) has been used with apparent safety in doses up to 320 mg daily for up to 4 weeks in children one year of age and older (63218).
POSSIBLY UNSAFE ...when used orally. Ostarine 1-3 mg daily has been used with apparent safety under medical supervision for up to 12-16 weeks by most patients in clinical studies (98832,98833). However, there are concerns about the potential of ostarine and other selective androgen receptor modulators (SARMs) to cause serious adverse reactions, including hepatotoxicity, myocardial infarction, and stroke (98840,106197). No long-term safety studies have been conducted (98840).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Lean Mass Extreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
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Theoretically, milk thistle might inhibit CYP2B6.
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An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels (112229).
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It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
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In vitro research suggests that milk thistle might inhibit CYP2C9 (7089,17973,17976). However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide (13712,95026). Differences in results could be due to differences in dosages or formulations utilized (95026).
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It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
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Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
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Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
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Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase (7354), although the significance of this effect is unclear.
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Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
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Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin (16408).
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Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
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One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25% (8234). However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir (8234). Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir (93578).
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Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
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Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination (109505).
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Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
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Animal research shows that milk thistle reduces serum levels of morphine by up to 66% (101161). In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.
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Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
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Although in vitro research shows that milk thistle can inhibit P-glycoprotein activity (95019), clinical research does not agree. A small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein probe substrate (35825).
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Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
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Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines (93024).
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Milk thistle might decrease the clearance of sirolimus.
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Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients (19876). It is unclear if this interaction occurs in patients without hepatic impairment.
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Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
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Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite (109505).
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Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
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Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion (17101). Whether this interaction occurs in humans is not known.
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Theoretically, milk thistle might increase the effects of warfarin.
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In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement (101159). Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin (7089,17973,17976).
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Theoretically, ostarine might increase levels of drugs metabolized by CYP2C9, although clinical research suggests this is not clinically relevant.
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Although in vitro research suggests that ostarine inhibits CYP2C9, more robust clinical research shows that ostarine does not significantly affect CYP2C9 (98834).
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Theoretically, concomitant use of ostarine with CYP3A4 inducers could decrease the clinical effects of ostarine.
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Ostarine is partially metabolized by CYP3A4. Clinical research shows that taking rifampin, a potent inducer of CYP3A4, reduces the maximum plasma concentration of ostarine by 23% and the area under the curve by 43% (98834).
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Theoretically, concomitant use of ostarine with CYP3A4 inhibitors could increase the effects and adverse effects of ostarine, although this is unlikely to be clinically significant.
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Ostarine is partially metabolized by CYP3A4. However, clinical research shows that taking itraconazole, a potent inhibitor of CYP3A4, had minimal effects on the levels of ostarine in the body (98834).
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Theoretically, concomitant use with hepatotoxic drugs might increase the risk of adverse hepatotoxic effects.
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Some clinical research shows that ostarine can increase alanine aminotransferase, a marker of liver damage, in some patients (98832,98833). Additionally, the U.S. Food and Drug Administration warns that supplements containing SARMs, such as ostarine, have been associated with reports of liver toxicity (94879,94880,94881) and there are at least two reports of drug-induced liver injury attributed to the use of ostarine (106197,111385).
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Theoretically, concomitant use of ostarine with probenecid could increase the effects and adverse effects of ostarine.
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Clinical research shows that probenecid increases ostarine levels and slows the clearance of ostarine, likely via inhibition of UDP-glucuronosyltransferase (UGT). Ostarine is partially metabolized by UGT (98834).
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Theoretically, concomitant use of ostarine with rifampin could decrease the clinical effects of ostarine.
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Clinical research shows that taking rifampin with ostarine reduces the maximum plasma concentration of ostarine by 23% and the area under the curve by 43% (98834). Ostarine is partially metabolized by cytochrome P450 3A4 (CYP3A4), and rifampin is a potent CYP3A4 inducer.
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Below is general information about the adverse effects of the known ingredients contained in the product Lean Mass Extreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, milk thistle is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal bloating, diarrhea, dyspepsia, flatulence, and nausea. However, these adverse effects do not typically occur at a greater frequency than with placebo.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis, have been reported.
Dermatologic ...Orally, milk thistle may cause allergic reactions including urticaria, eczema, skin rash, and anaphylaxis in some people (6879,7355,8956,63210,63212,63238,63251,63315,63325,95029). Allergic reactions may be more likely to occur in patients sensitive to the Asteraceae/Compositae family (6879,8956). A case report describes a 49-year-old female who developed clinical, serologic, and immunopathologic features of bullous pemphigoid after taking milk thistle orally for 6 weeks. Symptoms resolved after treatment with prednisone and methotrexate (107376). Topically, milk thistle can cause erythema (110489).
Gastrointestinal ...Mild gastrointestinal symptoms have been reported, including nausea, vomiting, bloating, diarrhea, epigastric pain, abdominal colic or discomfort, dyspepsia, dysgeusia, flatulence, constipation, and loss of appetite (2616,6879,8956,13170,63140,63146,63160,63210,63218,63219)(63221,63244,63247,63250,63251,63320,63321,63323,63324,63325)(63327,63328,95024,95029,107374). There is one report of a 57-year-old female with sweating, nausea, colicky abdominal pain, diarrhea, vomiting, weakness, and collapse after ingesting milk thistle; symptoms subsided after 24-48 hours without medical treatment and recurred with re-challenge (63329).
Musculoskeletal ...In one clinical study three patients taking milk thistle 200 mg orally three times daily experienced tremor; the incidence of this adverse effect was similar for patients treated with fluoxetine 10 mg three times daily (63219).
General
...Orally, ostarine is possibly unsafe.
Most Common Adverse Effects:
Orally: Abdominal pain, anorexia, constipation, diarrhea, nausea, and transient increases in alanine aminotransferase (ALT) levels.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.
Cardiovascular ...Orally, in a 12-week study of healthy elderly patients taking ostarine daily, high-density lipoprotein (HDL) cholesterol levels decreased by 9 mg/dL and 15 mg/dL with ostarine 1 mg and 3 mg, respectively, when compared with placebo (98833). Theoretically, reductions in HDL reported with ostarine could potentially increase the risk for adverse cardiovascular effects. In fact, the U.S. Food and Drug Administration also warns that supplements containing SARMs, such as ostarine, have been associated with increased risk of myocardial infarction and stroke (94879,94880,94881,98840).
Gastrointestinal ...Orally, ostarine has been commonly reported to cause gastrointestinal adverse effects (98832,98833). In a 16-week study of cancer patients taking ostarine 1-3 mg daily, nausea, diarrhea, constipation, abdominal pain, and anorexia occurred in 10% or more of patients, which was more common than with placebo. Vomiting was also commonly reported, although the incidence was slightly lower than placebo (98832). In a 12-week study of healthy elderly patients taking ostarine 1-3 mg by mouth daily, diarrhea occurred more frequently with ostarine than with placebo. Nausea was also reported, but at the same rate as placebo (98833).
Hematologic ...Orally, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, anemia and thrombocytopenia were reported more frequently with ostarine than with placebo, although the rate of occurrence in both groups was similar (98832).
Hepatic
...Orally, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, a transient increase in alanine aminotransferase (ALT) of 2- to 4-times the upper limit of normal occurred in 7.
4% of patients taking ostarine 3 mg (98832). In a 12-week study of healthy elderly patients taking ostarine by mouth daily, an increase in ALT was reported in 4.2% of patients taking ostarine 1 mg and 20.8% of patients taking ostarine 3 mg. ALT levels did not change in the placebo group. In most cases, ALT levels resolved over the course of the study without the need to discontinue treatment. However, one patient's ALT increased to over 4-times the upper limit of normal, which required discontinuation of ostarine. The patient's ALT returned to normal after treatment discontinuation (98833).
The U.S. Food and Drug Administration also warns that supplements containing SARMs, such as ostarine, have been associated with reports of liver toxicity (94879,94880,94881). There are at least two reports of drug-induced liver injury (DILI) attributed to ostarine. In one case, a 40-year-male developed DILI, characterized by anorexia, diarrhea, lethargy, weight loss, and jaundice, after taking ostarine to improve weight training and increase muscle mass for 2 months. The patient's symptoms and liver function tests improved gradually over several months after discontinuation of ostarine (106197). In another case, a 31-year-old male presented with a probable DILI characterized by pruritus, dark urine, and elevated transaminases for 1 week after using ostarine for 3 weeks. The DILI and associated signs and symptoms resolved within weeks after discontinuation of ostarine (111385).
In one case, a 43-year-old male taking ostarine and cardarine to increase muscle mass presented with several signs and symptoms associated with DILI, including epigastric pain, dark urine, and elevated liver function tests. The patient claims the supplements were used short-term for a few days before cycling a long distance. However, based on the pharmacokinetic properties of these products and the levels detected in the patient's blood, hair, and urine, researchers suggest that longer-term use was present. The patient's symptoms resolved within a few weeks after discontinuation of both supplements (111382). It is unclear if these adverse effects are due to ostarine, cardarine, or the combination.
Musculoskeletal
...Orally, in a 12-week study of healthy elderly patients taking ostarine 1-3 mg daily, back pain was reported in 25% of patients (98833).
However, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, back pain occurred at a similar rate with ostarine and placebo (98832).
In one case, a 43-year-old male taking ostarine and cardarine to increase muscle mass presented with several symptoms, including myalgia and rhabdomyolysis with elevated creatine phosphokinase (CPK). The patient claims the supplements were used short-term for a few days before cycling a long distance. However, based on the pharmacokinetic properties of these products and the levels detected in the patient's blood, hair, and urine, researchers suggest that longer-term use was present. The patient's symptoms resolved within a few weeks after discontinuation of both supplements (111382). It is unclear if these adverse effects are due to ostarine, cardarine, or the combination.
Neurologic/CNS ...Orally, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, headache occurred more frequently with ostarine than with placebo. Fatigue was also commonly reported, but at a rate similar to placebo (98832). In a 12-week study of healthy elderly patients taking ostarine 1-3 mg daily, headache occurred in 29% of patients, which was more common than with placebo. Fatigue was also reported, but at a lower rate than with placebo (98833). The U.S. Food and Drug Administration also warns that supplements containing SARMs, such as ostarine, have been associated with increased risk of stroke (94879,94880,94881).
Pulmonary/Respiratory ...Orally, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, pneumonia occurred more frequently with ostarine than with placebo. Cough and dyspnea were also reported, but at rates slightly lower than placebo (98832). In a 12-week study of healthy elderly patients taking ostarine 1-3 mg daily, cough occurred more frequently with ostarine than with placebo (98833).
Other ...Orally, in a 16-week study of cancer patients taking ostarine 1-3 mg daily, pyrexia occurred more frequently with ostarine than with placebo (98832).