MK-2866 Ostarine SRM [Discontinued] by Xcel Sports Nutrition

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Anxiety. Although there has been interest in using oral cowhage for anxiety, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Erythema. Although there has been interest in using topical cowhage for erythema, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Hyperprolactinemia. Although there has been interest in using oral cowhage for hyperprolactinemia, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Myalgia. Although there has been interest in using topical cowhage for myalgia, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Parkinson disease. It is unclear if oral cowhage is beneficial in patients with Parkinson disease. Details: Very small clinical studies in patients with Parkinson disease suggest that taking a specific cowhage seed extract standardized to 3.3% levodopa (Zandopa, formerly HP-200; Zandu Pharmaceuticals), or other cowhage products that contain levodopa 75-400 mg orally once daily for up to 12 weeks modestly improves Parkinson disease scores when compared with baseline (7020,7203). Two very small clinical trials enrolling a total of 26 patients with Parkinson disease suggests that taking a single dose of cowhage powder, providing levodopa 1000-2000 mg or 12.5-17.5 mg/kg, is similarly effective after 90 minutes when compared with prescription levodopa 200 mg or 3.5 mg/kg as a single dose, with or without carbidopa and benserazide (12232,97266). It is unclear how these products would compare if they provided similar amounts of levodopa, or if they were taken for an extended duration.
• Rheumatoid arthritis (RA). Although there has been interest in using topical cowhage for RA, there is insufficient reliable information about the clinical effects of cowhage for this purpose.
• Sexual desire. Although there has been interest in using oral cowhage to increase sexual desire, there is insufficient reliable information about the clinical effects of cowhage for this purpose. More evidence is needed to rate cowhage for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Athletic performance. Although there is interest in using oral ostarine to improve athletic performance, there is insufficient reliable information about the clinical effects of ostarine for this use.
• Breast cancer. Although there is interest in using oral ostarine for breast cancer, there is insufficient reliable information about the clinical effects of ostarine for this condition.
• Cachexia. It is unclear if oral ostarine is beneficial for cachexia in patients with cancer. Details: Some preliminary clinical research in non-obese cancer patients who have experienced a 2% or greater decrease in body weight in the past 6 months shows that taking ostarine 1 mg or 3 mg daily for up to 16 weeks increases lean body mass by around 1-1.5 kg when compared with placebo (98832). The clinical significance of this finding is unclear. Furthermore, the use of a per-protocol analysis in this study may overestimate the effects of ostarine.
• Muscular dystrophy. Although there is interest in using oral ostarine for muscular dystrophy, there is insufficient reliable information about the clinical effects of ostarine for this condition.
• Sarcopenia. It is unclear if oral ostarine is beneficial for sarcopenia in older adults. Details: Clinical research in healthy, non-obese elderly adults shows that taking ostarine 3 mg daily for 12 weeks increases lean body mass by around 1.3 kg when compared with placebo. Patients taking ostarine 3 mg had reduced fat mass and increased stair climb power when compared with placebo; however, no improvements in total body weight or stair climb speed were observed. Additionally, patients taking ostarine 1 mg daily experienced no improvements in any outcomes (98833). The clinical significance of these findings is unclear. Additionally, the use of a per-protocol analysis in this study may overestimate the effects of ostarine.
• Urinary incontinence. Although there is interest in using oral ostarine for urinary incontinence, there is insufficient reliable information about the clinical effects of ostarine for this condition. More evidence is needed to rate ostarine for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. Powdered formulations of cowhage seed that are standardized to provide levodopa 75-400 mg daily have been used with apparent safety for up to 20 weeks (7020,7203,97266).

POSSIBLY UNSAFE ...when the hair of the cowhage bean pod is used orally or topically. The bean pod hairs are strong irritants and can cause severe itching, burning, and inflammation (18).

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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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.

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ANESTHESIA Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of cowhage and anesthesia might increase the risk of arrhythmias.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with cyclopropane or halogenated hydrocarbon anesthesia has led to arrhythmias. Other anesthetics have not been implicated (15). Use other anesthetics in patients taking cowhage or tell patients to stop taking cowhage at least 2 weeks before surgery.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of cowhage and antidiabetes drugs might increase the risk of hypoglycemia.  Details Animal research shows that cowhage might have hypoglycemic effects (7221).

ANTIPSYCHOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of cowhage might decrease the clinical effects of antipsychotic drugs.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa might counteract the antidopaminergic effects of antipsychotic medications (15).

GUANETHIDINE (Ismelin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and guanethidine might increase the risk of hypotension.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with guanethidine might cause additive hypotension (15); avoid using.

LEVODOPA Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = D Concomitant use can increase the risk of levodopa-related adverse effects.  Details Cowhage contains levodopa. Some cowhage products have been standardized to contain 75-400 mg of levodopa per dose (7020,7205,46334,46336,94723,94724).

METHYLDOPA (Aldomet) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and methyldopa might increase the risk of hypotension.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with methyldopa might cause additive hypotension. In addition, methyldopa may inhibit peripheral decarboxylation of levodopa and increase levodopa levels in the central nervous system (15); avoid using.

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, concomitant use of cowhage and non-selective MAOIs might increase the risk of hypertensive crisis.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of levodopa with non-selective MAOIs might cause hypertensive crisis. However, this interaction has not been reported with MAO-B selective inhibitors such as selegiline (15).

TRICYCLIC ANTIDEPRESSANTS (TCAs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.  Details Cowhage contains levodopa (7020,7205,46334,46336,94723,94724). Use of TCAs might reduce the absorption of levodopa. Some case reports describe patients that developed hypertension and dyskinesia when taking both levodopa and TCAs (15).

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CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, ostarine might increase levels of drugs metabolized by CYP2C9, although clinical research suggests this is not clinically relevant.  Details Although in vitro research suggests that ostarine inhibits CYP2C9, more robust clinical research shows that ostarine does not significantly affect CYP2C9 (98834).

CYTOCHROME P450 3A4 (CYP3A4) INDUCERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of ostarine with CYP3A4 inducers could decrease the clinical effects of ostarine.  Details 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).

CYTOCHROME P450 3A4 (CYP3A4) INHIBITORS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B 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.  Details 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).

HEPATOTOXIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use with hepatotoxic drugs might increase the risk of adverse hepatotoxic effects.  Details 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).

PROBENECID (Benemid) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of ostarine with probenecid could increase the effects and adverse effects of ostarine.  Details 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).

RIFAMPIN (Rifadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concomitant use of ostarine with rifampin could decrease the clinical effects of ostarine.  Details 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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General ...Orally, adverse effects to cowhage seem to be rare; however, a thorough safety evaluation has not been conducted. Topically, cowhage bean pod or seed may be unsafe.
Most Common Adverse Effects:
Orally: Diarrhea, flatulence, mucosal irritation.
Topically: Erythema, pruritus, rash.

Cardiovascular ...Orally, cowhage has been reported to cause palpitations (7021,7203)

Dermatologic ...Orally, ingestion of hairs from the bean pod or seed can result in significant mucosal irritation and should be avoided.
Topically, hairs on cowhage bean pod or seed can cause severe pruritus (6898). Symptoms include severe itching, burning, inflammation, and erythematous macular rashes (18,6898). Symptoms resolve spontaneously within several hours, but may also be relieved with antihistamines (6898). The hairs can be removed from the skin by washing, but the hairs can also be retained, and transferred to other people, in fabrics and carpets. Clothing and other materials that come in contact with cowhage hairs should also be thoroughly washed (6898).

Gastrointestinal ...Orally, cowhage has been reported to cause flatulence, diarrhea, and dry mouth (7021,7203). Orally, a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) has been reported to cause nausea, abdominal distention, and vomiting in clinical research when taken in amounts of 22.5-67.5 grams divided into 2-5 doses per day (7020).

Musculoskeletal ...Orally, dyskinesia has been reported in clinical research in about 3% of patients taking a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) 22. 5-67.5 grams divided into 2-5 doses daily (7020).

Neurologic/CNS ...Orally, cowhage has been reported to cause headaches (7021,7203). Orally, insomnia has been reported in clinical research in about 3% of patients taking a specific powdered cowhage seed extract (Zandopa, formerly HP-200; Zandu Pharmaceuticals) 22.5 grams to 67.5 grams divided into 2-5 doses daily (7020).

Psychiatric ...In a case report, cowhage caused an outbreak of acute toxic psychosis. Symptoms of psychosis included confusion, giddiness, agitation, hallucinations, and paranoid delusions. The cowhage-induced psychosis was successfully treated with intravenous chlorpromazine (7021).

Other ...Orally, cowhage has been reported to cause sweating and changes in urine color, (7021,7203). Theoretically, due to the levodopa constituent, cowhage is likely to cause the same adverse effects that have been attributed to purified, prescription levodopa. Some of these side effects include elevated liver enzymes, respiratory disturbances, urinary retention, muscle cramps, and priapism (15). However, these effects have not yet been reported for cowhage.

(Read more about COWHAGE)

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).

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