Cordyceps CS-4 Strain [Discontinued] by MRM

EFFECTIVE

• Cardiovascular disease diagnosis. Adenosine intravenous infusion is FDA-approved for use in cardiac stress testing to diagnose coronary artery disease (CAD). Details: Adenosine is infused at a dose of 0.14 mg/kg/minute for 6 minutes as an adjunct to thallium stress testing in patients who are unable to exercise adequately (15). Caffeine is a competitive antagonist at adenosine receptors and should be avoided for 24 hours prior to the test (9157,11770).
• Paroxysmal supraventricular tachycardia. Adenosine intravenous injection is FDA-approved for acute management of paroxysmal supraventricular tachycardia (PSVT). Details: Adenosine is indicated for termination of PSVT. It is given intravenously as a bolus of 6 mg over 1-2 seconds, followed by 1 or 2 further boluses of 12 mg at 1-2 minute intervals if necessary (15).

POSSIBLY EFFECTIVE

• Cachexia. Intravenous adenosine triphosphate may be beneficial in cachexic patients with various cancers. Oral adenosine has not been evaluated for this purpose. Details: Administering adenosine triphosphate (ATP) intravenously, up to 75 mcg/kg/minute for 30 hours every 2-4 weeks for up to 28 weeks, seems to stabilize body composition, appetite, and dietary intake, and to improve quality of life in people with advanced non-small-cell lung cancer and other tumors (9149,9151,9152).

POSSIBLY INEFFECTIVE

• Myocardial Infarction (MI). Intravenous or intracoronary adenosine does not seem to be beneficial for acute coronary syndrome. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 17 clinical studies in patients with acute coronary syndrome undergoing revascularization shows that administration of intracoronary or intravenous adenosine does not reduce major adverse cardiac events when compared with placebo. Adenosine also does not reduce all-cause death, non-fatal MI, or heart failure when compared with placebo. However, adenosine is associated with an increased risk of atrioventricular block (111744). The interpretation of these findings is limited by the heterogeneity of the included studies. In addition, most studies were in patients treated with percutaneous coronary intervention; the generalizability of these results to patients treated with thrombolysis is unclear.
• Postoperative nausea and vomiting (PONV). Parenteral adenosine does not seem to be beneficial for PONV. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 4 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce PONV when compared with placebo (97981).
• Postoperative pain. Parenteral adenosine does not seem to be helpful for postoperative pain. Oral adenosine has not been evaluated for this purpose. Details: A meta-analysis of 9 clinical studies shows that adenosine, administered intravenously or intrathecally, does not reduce postoperative pain scores when compared with placebo (97981).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Androgenic alopecia. It is unclear if topical adenosine is beneficial in patients with androgenic alopecia. Details: Preliminary clinical research shows that topical application of adenosine 0.75% solution to the scalp twice daily for 6 months does not improve hair growth in males with androgenic alopecia. However, patients applying topical minoxidil 5% (Rogaine) also experienced no improvement at 6 months, with over 97% of patients in each group reporting less than 30% hair growth in the affected area (93689).
• Athletic performance. It is unclear if oral adenosine triphosphate is beneficial for improving athletic performance. Details: Preliminary clinical research in healthy males performing 10 repeated sprinting bouts shows that taking adenosine triphosphate (PEAK ATP, TSI USA, Inc) 400 mg orally daily for 2 weeks prior to the exercise increases muscle excitability during the first two bouts and attenuates reductions in power output and muscle excitability during the final three bouts when compared with placebo (97982).
• Erectile dysfunction (ED). Oral adenosine monophosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking adenosine monophosphate 200 mg plus arginine aspartate 8 grams orally 1-2 hours prior to sexual intercourse improves erectile function and sexual satisfaction scores when compared with placebo in patients with erectile dysfunction (93690). It is not clear if this effect is due to adenosine, arginine, or the combination.
• Hearing loss. Oral adenosine triphosphate has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with idiopathic sudden sensorineural hearing loss shows that taking adenosine triphosphate 300 mg orally daily with vitamin B12 1.5 mg orally daily for 8-16 weeks is associated with modestly reduced hearing loss after 4-6 months when compared with taking this combination for less than 8 weeks (104924). The validity of this finding is limited by the observational nature of the study and the lack of a control group.
• Herpes labialis (cold sores). It is unclear if intramuscular adenosine monophosphate is beneficial in patients with herpes labialis. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research shows that a gel formulation of adenosine monophosphate 1.5-2 mg/kg IM every other day for a total of 9-12 injections might accelerate the healing of cold sores and reduce the risk of recurrence (9590). The validity of these findings is limited by the lack of a control group.
• Herpes zoster (shingles). It is unclear if intramuscular adenosine monophosphate is beneficial in adults with herpes zoster. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in adults with shingles shows that giving adenosine monophosphate in a gel formulation, 100 mg IM three times weekly for 4 weeks, increases the number of patients classified as pain-free at 4 weeks by 45% and might also accelerate viral clearance when compared with placebo (9155,10067).
• Lung cancer. Intravenous adenosine triphosphate does not seem to be beneficial in patients with advanced non-small-cell lung cancer (NSCLC). Oral adenosine has not been evaluated for this purpose. Details: One very small clinical study in adults with advanced NSCLC shows that giving adenosine triphosphate in at least 3, 96-hour infusions at a dose of 50 mcg/kg/min or more does not induce complete or partial responses when compared to baseline (9154).
• Neuropathic pain. It is unclear if intrathecal adenosine is beneficial for experimentally-induced neuropathic pain. Oral adenosine has not been evaluated for this purpose. Details: Preliminary clinical research in healthy volunteers with areas of allodynia and hyperalgesia induced by topical capsaicin shows that giving single doses of intrathecal adenosine 0.5-2 mg modestly reduces these areas (9157). The clinical significance of this finding is unclear.
• Porphyria cutanea tarda. It is unclear if oral adenosine monophosphate is beneficial in patients with porphyria cutanea tarda. Details: A case series of 21 patients with porphyria cutanea tarda shows that taking adenosine monophosphate 160-200 mg orally daily for at least 4 weeks resolves or reduces symptoms, including photosensitivity, hyperpigmentation, and hypertrichosis, and decreases urinary and fecal excretion of porphyrins, when compared to baseline (106423). The validity of these findings is limited by the lack of a control group.
• Pulmonary hypertension. Adenosine given by central venous infusion might be beneficial in patients who develop pulmonary hypertension during cardiac surgery. Details: Preliminary clinical research in patients who develop pulmonary hypertension during cardiac surgery shows that giving a central venous infusion of adenosine, 50 mcg/kg/minute for 15 minutes after weaning from cardiopulmonary bypass, produces pulmonary vasodilation and reduces mean pulmonary arterial pressure (106424). The validity of these findings is limited by the lack of a control group. More evidence is needed to rate adenosine for these uses.

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POSSIBLY INEFFECTIVE

• Athletic performance. Taking cordyceps orally does not seem to improve athletic performance in adults. Details: One small clinical study in endurance-trained cyclists shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) 3.15 grams daily for 5 weeks does not improve endurance time trials or aerobic capacity when compared with placebo (12095). Another small study in healthy elderly adults shows that taking the same cordyceps preparation (CordyMax Cs-4) 3 grams daily for 12 weeks does not improve exercise performance when compared with placebo (46120). Research also shows that taking combination products containing cordyceps and other ingredients does not improve athletic performance when compared with control. These products have combined cordyceps (CordyMax Cs-4) 1000 mg with rhodiola 300 mg (46091) or cordyceps (CordyMax Cs-4) 2000 mg with roseroot 600 mg (Optygen, First Endurance) (15573); liquid and powdered cordyceps formulations with reishi mushroom, shiitake mushroom, bamboo, and honey (Fohow oral liquid and Fohow lingzhi capsules, FOHOW Technology Investment Group Co. Ltd.) (98686); and cordyceps (form unknown) 1.2 grams with a 930 mg mixture of extracts of ashwagandha root, green tea leaf, rhodiola root, and astragalus root (Shroom Tech Sport, Onnit Labs) (105079).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Arrhythmia. Although there is interest in using oral cordyceps for arrhythmia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Asthma. Oral cordyceps has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with asthma shows that a 619 mg capsule containing equal weights of the dried aqueous extracts of cordyceps, astragalus, skullcap, Radix stemonae, and Bulbus fritillariae daily for 6 months does not reduce the need for medication or improve symptoms when compared with placebo (32935).
• Chronic kidney disease (CKD). Small clinical studies suggest that oral cordyceps may modestly improve biomarkers in some patients with CKD. Details: A meta-analysis of clinical research in patients in China with CKD shows that taking cordyceps 0.6-2 grams orally three times daily, along with standard treatment, seems to decrease serum creatinine levels by 0.6 mg/dL and increase creatinine clearance by 9.2 mL/min when compared with standard treatment alone (92829). Another meta-analysis of clinical studies in patients in China with diabetic kidney disease shows that taking cordyceps 0.5-2 grams orally three times daily along with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) decreases blood urea nitrogen by 2 mg/dL and decreases serum creatinine levels by 0.1 mg/dL when compared with ACEI/ARB treatment alone (92830). Most individual studies in these analyses used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (92829,92830). Both of these analyses are limited by the low methodological quality and short duration (usually 1-6 months) of most of the included studies.
• Chronic obstructive pulmonary disease (COPD). Preliminary clinical studies suggest that oral cordyceps may modestly improve symptoms of COPD. Details: A meta-analysis of preliminary clinical research in patients with moderate or severe COPD shows that taking cordyceps alone or as part of a formulation containing other products for up to 12 months improves lung function and reduces the incidence of an acute exacerbation by a small amount. Also, the distance walked in 6 minutes is increased by about 45 meters, which was considered clinically meaningful. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products, in combination with conventional treatments with conventional treatments alone (109705). This analysis is limited by the low methodological quality of the included studies.
• Contrast induced nephropathy. Small clinical studies suggest that oral cordyceps may modestly reduce contrast induced nephropathy. Details: A preliminary clinical study in patients with diabetic nephropathy shows that taking a specific cordyceps mycelial product (Corbrin; CS-C-Q80) 2-3 grams orally three times daily for 3 days before and after angiography reduces the risk of contrast induced nephropathy by about 48% to 66% when compared to standard treatment (92827). However, other preliminary clinical research in patients with stable angina pectoris shows that taking the same cordyceps product 3 grams orally three times daily for 3 days before and after angioplasty does not decrease the prevalence of contrast induced nephropathy when compared to standard therapy (92826). Reasons for these discrepancies are not clear but may relate to the small size and heterogenous populations in these studies.
• Diabetic nephropathy. Early research suggests that oral cordyceps may modestly improve kidney function in patients with diabetic kidney disease. Details: A meta-analysis of low to moderate quality clinical research in patients with diabetic kidney disease shows that taking cordyceps as adjunctive therapy to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for 2-24 weeks modestly improves kidney function when compared to these medications alone. Kidney function was based on markers such as blood creatinine and urea nitrogen, as well as urinary albumin and total protein. There were also modest improvements in systolic and diastolic blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol. There was no effect on glycemic indices. The effect of cordyceps on disease progression or cardiovascular events is unclear (111903).
• Cough. Although there is interest in using oral cordyceps for cough, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Fatigue. Although there is interest in using oral cordyceps for fatigue, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Hepatitis B. Although there is interest in using oral cordyceps for hepatitis B, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Hypercholesterolemia. Although there is interest in using oral cordyceps for hypercholesterolemia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Kidney failure. Small clinical studies suggest that oral cordyceps may improve inflammatory markers in patients on hemodialysis. Details: A meta-analysis of small clinical trials in patients in China on hemodialysis suggests that adding cordyceps to standard treatment does not seem to improve serum creatinine levels but may improve certain markers of inflammation, such as C-reactive protein, when compared with placebo. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (105076).
• Kidney transplant. Small clinical studies suggest that oral cordyceps is no better than standard treatment in patients with kidney transplant. Details: A meta-analysis of 4 heterogeneous clinical trials evaluating patients in China immediately post-kidney transplant or patients with complications post-kidney transplant suggests that adding cordyceps to standard therapy with cyclosporine and steroids is no better than adding azathioprine 50-150 mg for improving overall survival or graft survival or reducing rejection risk. However, there was a non-significant trend to reduced risk of graft rejection in the cordyceps group (95905). A higher quality systematic review, which determined the available studies were too heterogeneous to pool together in a meta-analysis, suggests that adding cordyceps 3-6 grams to standard therapy daily is no better than azathioprine or cyclosporine for improving organ rejection, kidney function, or survival in patients after kidney transplant (92828). All individual studies in these analyses used Bailing (Cs-C-Q80) fermented cordyceps mycelial product (95905,92828).
• Sexual dysfunction. It is unclear if oral cordyceps is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) approximately 3 grams daily for 40 days can improve symptoms of hyposexuality in 66% of patients, compared with 32% of patients taking natural cordyceps and 24% of patients taking placebo (46145).
• Tinnitus. Although there is interest in using oral cordyceps for tinnitus, there is insufficient reliable information about the clinical effects of cordyceps for this condition. More evidence is needed to rate cordyceps for these uses.

(Read more about CORDYCEPS)

LIKELY SAFE ...when adenosine is used intravenously and appropriately. Adenosine injection (Adenocard, Adenoscan) is an FDA-approved prescription drug (15).

POSSIBLY SAFE ...when adenosine triphosphate (ATP) is used intravenously and appropriately. ATP appears to be safe in intravenous doses of 75 mcg/kg per minute for 30 hours given every 2 weeks for 28 weeks (9149,9154). There is insufficient reliable information available about the safety of adenosine when used orally or intramuscularly.

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

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POSSIBLY SAFE ...when used orally and appropriately. Cordyceps has been used with apparent safety in doses of 3-6 grams daily for up to 1 year (12,12095,92828,95905,105076,111903).

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

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CARBAMAZEPINE (Tegretol) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Carbamazepine might increase the risk of heart block when used concomitantly with adenosine.  Details Carbamazepine and adenosine can both cause heart block. Giving them concurrently might produce an additive effect (15).

DIPYRIDAMOLE (Persantine) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = D Dipyridamole can increase the therapeutic and toxic effects of adenosine.  Details Dipyridamole decreases the metabolism of adenosine. Intravenous infusion of adenosine in patients who are taking dipyridamole can cause dizziness, bradycardia, and syncope. Dipyridamole should be discontinued for several days prior to a cardiac stress test using adenosine (12209).

METHYLXANTHINES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Methylxanthines are competitive antagonists of adenosine and can block its pharmacologic effects.  Details The methylxanthines, aminophylline, caffeine, and theophylline, can block the effects of adenosine by acting as competitive antagonists at adenosine cell surface receptors (9157). It is recommended that methylxanthines be avoided for 24 hours prior to cardiac stress tests (11770).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cordyceps may increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details In vitro and animal research suggests that cordyceps extract inhibits platelet aggregation and function (3429,46112). However, this interaction has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concurrent use of cordyceps might interfere with immunosuppressive therapy.  Details Animal and in vitro research suggests that cordyceps stimulates the immune system (3403,3404,3414,3431,3432). However, limited clinical research suggests that taking cordyceps may lower the necessary therapeutic dose of the immunosuppressant cyclosporine (92828), which suggests that cordyceps may have an immunosuppressive effect.

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of cordyceps and testosterone might have additive effects.  Details Animal research suggests that cordyceps can increase testosterone levels (46087). The clinical significance of this finding is unclear.

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General ...Intravenously, the prescription form of adenosine can cause cardiovascular and respiratory adverse effects. When used orally or intramuscularly, no adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Intravenously: Chest pain, dizziness, dyspnea, facial flushing, headache, hypotension, nausea, nervousness, numbness, paresthesias, and tingling.
Serious Adverse Effects (Rare):
Intravenously: Arrhythmias, first- and second-degree heart block, hypersensitivity reactions, myocardial infarction, ST segment depression, and ventricular tachycardia.

Cardiovascular ...Intravenously, adenosine causes chest pain, palpitations, hypotension, and supraventricular tachycardia (15,9148). Intravenous adenosine has also been associated with arrhythmias, fatal or nonfatal cardiac arrest, ventricular tachycardia, and myocardial infarction (15). Intravenously, adenosine triphosphate (ATP) causes chest pain, particularly at doses greater than 50 mcg/kg per minute (9154).

Dermatologic ...Intravenously, adenosine causes flushing in up to 44% of patients in clinical research (15). Topically, folliculitis and pruritus can occur after application of adenosine to the scalp (93689).

Gastrointestinal ...Intravenously, adenosine can cause abdominal discomfort (15).

Neurologic/CNS ...Rapid intravenous injection of adenosine can cause headache, lightheadedness, insomnia, and anxiety (9148,9151,9152,9154,9158). New onset seizures, including tonic-clonic seizures, have also occurred (15). Intrathecally, adenosine has been reported to cause headache (9157).

Pulmonary/Respiratory ...Intravenously, adenosine can cause dyspnea, bronchospasm, bronchoconstriction, and respiratory arrest (15). Intravenously, adenosine triphosphate (ATP) causes dyspnea, which can be severe, particularly at doses greater than 50 mcg/kg/minute (9154).

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General ...Orally, cordyceps seems to be generally well tolerated when used for up to 1 year.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea.

Gastrointestinal ...Orally, cordyceps has been associated with diarrhea, constipation, abdominal discomfort, dry mouth, and throat discomfort in clinical research. However, these events were uncommon, and in some cases symptoms could be reduced by taking cordyceps after eating (92829,105076,109705).

Hematologic ...Two cases of lead poisoning, characterized by loss of appetite and other symptoms, have been reported for patients taking cordyceps powder. After discontinuing cordyceps supplementation, both patients were treated with chelating agents (46135).

Hepatic ...There is a case report of acute cholestatic hepatitis probably associated with the use of a product containing cordyceps. The 64-year-old male was asymptomatic except for jaundice and laboratory markers and recovered once the supplement was stopped. However, it is unclear whether the hepatitis is associated with the cordyceps or with an unknown contaminant (109704).

Renal ...One case of a mild increase in serum creatinine level (< 30%) has been reported (95905).

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