Liver Efficiency Formula [Discontinued] by Life Extension

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there is interest in using oral schisandra for aging, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Asthma. Although there is interest in using oral schisandra for asthma, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Athletic performance. Although there is interest in using oral schisandra for athletic performance, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Coronavirus disease 2019 (COVID-19). Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with a history of COVID-19 infection and current symptoms of long COVID-19 shows that taking 30 mL of a specific combination product (Chisan / ADAPT-232, Swedish Herbal Institute) containing schisandra extract 300 mg, rhodiola extract 90 mg, and eleuthero extract 78 mg twice daily for 2 weeks increases exercise capacity, but does not reduce the number of days with fatigue, headache, cough, respiratory problems, or other symptoms of long COVID-19, when compared with placebo (109635).
• Cough. Although there is interest in using oral schisandra for cough, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diarrhea. Although there is interest in using oral schisandra for diarrhea, there is insufficient reliable information about the clinical effects of schisandra for this purpose.
• Diabetes. Although there is interest in using oral schisandra for diabetes, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Familial Mediterranean fever. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a combination product (ImmunoGuard, Inspired Nutritionals) containing schisandra extract 100 mg, andrographis, Siberian ginseng, and licorice reduces symptom duration, frequency, and severity when compared with placebo (12382). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Hepatitis. Although there is interest in using oral schisandra for hepatitis, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Hypercholesterolemia. Although there is interest in using oral schisandra for hypercholesterolemia, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Menopausal symptoms. It is unclear if oral schisandra is beneficial for improving menopausal symptoms. Details: A small clinical trial in healthy patients with moderate or severe menopausal symptoms shows that taking schisandra extract (BMO-30, Biomix Inc) 784 mg in two divided doses daily for 6 weeks improves hot flushes and other menopausal symptoms when compared with placebo (96632).
• Muscle strength. It is unclear if oral schisandra is beneficial for improving muscle strength. Details: A small clinical study in healthy middle-aged females shows that taking schisandra powdered extract (Bioport Korea Inc.) 500 mg twice daily for 12 weeks seems to modestly increase quadriceps muscle strength and grip strength, but does not affect overall muscle mass, when compared with placebo (105563).
• Myopia. Although there is interest in using topical schisandra for myopia in children, there is insufficient reliable information about the clinical effects of schisandra for this condition.
• Physical performance. It is unclear if oral schisandra is beneficial for improving physical function in older adults. Details: A small clinical study in healthy adults over 50 years of age shows that taking schisandra 500 mg twice daily, 30 minutes after breakfast and dinner, for 12 months improves knee extension peak torque, but does not improve hand grip strength or body composition, when compared with placebo (105562).
• Pneumonia. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with acute, nonspecific pneumonia shows that taking 20 mL of a specific combination product (ADAPT-232 CHI San, Swedish Herbal Institute) containing schisandra berry extract 51%, rhodiola root extract 27.6%, and eleuthero root extract 24.4% twice daily for 10-15 days reduces the duration of antibiotic treatment and may improve quality of life when compared with standard treatment alone (71152). It is unclear if these effects are due to schisandra, other ingredients, or the combination.
• Stress. Oral schisandra has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, fatigued females under experimental stress suggests that taking a single, 270 mg dose of a combination product (ADAPT-232, Swedish Herbal Institute) containing schisandra, rhodiola, and Siberian ginseng improves attention, as well as cognitive task speed and accuracy, when compared with placebo (19289). It is unclear if these effects are due to schisandra, other ingredients, or the combination. More evidence is needed to rate schisandra for these uses.

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POSSIBLY EFFECTIVE

• Osteoarthritis. Intra-articular injection of superoxide dismutase may reduce pain in patients with osteoarthritis of the knee. It is unclear if oral superoxide dismutase is beneficial in these patients. Details: Two clinical studies in patients with osteoarthritis of the knee show that intra-articular administration of superoxide dismutase 16 mg every 1-2 weeks for 3-6 weeks reduces pain for up to 3-6 months after initiation of treatment when compared with placebo or methylprednisolone (2228,2229).
• Rheumatoid arthritis (RA). Intra-articular injection of superoxide dismutase may reduce knee stiffness, flexion, and pain in patients with RA affecting the knees. It is unclear if oral superoxide dismutase is beneficial in these patients. Details: Three small clinical studies in patients with RA show that intra-articular administration of superoxide dismutase 4 mg weekly for up to 6 weeks improves knee stiffness, flexion, and pain for up to 12-24 weeks after initiation of treatment when compared with methylprednisolone or aspirin (2230,2231,2232).

LIKELY INEFFECTIVE

• Myocardial infarction (MI). Intravenous superoxide dismutase may not confer additional benefits in patients with acute MI undergoing thrombolysis or coronary angioplasty. Details: Clinical studies in patients undergoing thrombolysis or coronary angioplasty for acute MI show that intravenous administration of superoxide dismutase does not improve reperfusion or left ventricular function when compared with placebo (2241,2243).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acute respiratory distress syndrome (ARDS). It is unclear if subcutaneous superoxide dismutase can prevent bronchopulmonary dysplasia in neonates with ARDS. Details: A small clinical study in neonates with ARDS shows that subcutaneous administration of superoxide dismutase 0.25 mg/kg twice daily until ventilator support is no longer required reduces the risk of bronchopulmonary dysplasia by around 70% when compared with placebo. For every two neonates treated with subcutaneous superoxide dismutase, one additional case of bronchopulmonary dysplasia is prevented. Also, superoxide dismutase can reduce the incidence of wheezing and pneumonia in these infants (2242).
• Aging. Although there has been interest in using oral superoxide dismutase to prevent the signs and symptoms of aging, there is insufficient reliable information about the clinical effects of superoxide dismutase for this purpose.
• Aging skin. Although there has been interest in using oral superoxide dismutase to prevent and treat aging skin, there is insufficient reliable information about the clinical effects of superoxide dismutase for this purpose.
• Burns. Although there has been interest in using topical superoxide dismutase for burns, there is insufficient reliable information about the clinical effects of superoxide dismutase for this purpose.
• Corneal ulceration. It is unclear if ophthalmic superoxide dismutase is beneficial in patients with noninfectious corneal ulceration. Details: A case series of 19 patients with noninfectious corneal ulcers found that application of a specific lecithinated superoxide dismutase 0.1% ophthalmic solution for at least 2 weeks reduces ulcer size and improves healing in most patients (14815). However, the validity of these findings is limited by a lack of control group.
• Diabetic neuropathy. Oral superoxide dismutase has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in patients with diabetic neuropathy shows that taking a specific combination product (ALA600SOD, Alfa Wassermann) providing superoxide dismutase 140 IU and alpha-lipoic acid 600 mg daily for 4 months improves pain by 18% when compared to baseline. Small improvements in motor and sensory nerve conduction were also reported (20488). Another small clinical study in patients with diabetic neuropathy shows that taking a specific combination product (Combinerv, Libytec Pharmaceuticals) providing superoxide dismutase 10 mg, alpha-lipoic acid 570 mg, acetyl-L-carnitine 300 mg, and vitamin B12 250 mcg daily for 12 months improves pain scores by 16% when compared with placebo. Taking this combination product also improved diabetic quality of life scores and some measures of nerve conduction when compared with placebo (105502). It is unclear if these effects are due to superoxide dismutase, other ingredients, or the combination.
• Interstitial cystitis. It is unclear if injecting superoxide dismutase into the bladder wall is beneficial in patients with interstitial cystitis. Details: A small, uncontrolled clinical study in patients with radiation-induced or interstitial cystitis shows that administration of superoxide dismutase 4-12 mg as an injection into the bladder wall every 4-6 weeks for up to 6 treatments improves pain, urinary urgency, incontinence, bladder capacity, and micturition frequency when compared to baseline (2233). The validity of these findings is limited by a lack of control group.
• Male infertility. Oral superoxide dismutase has only been evaluated in combination with other ingredients; its effect when used alone is unclear for male infertility. Details: A moderate-size cross-sectional, propensity-score matched study in males with idiopathic infertility suggests that taking a combination product containing superoxide dismutase, hydroxytyrosol, and carnosol (FertiPlus SOD, Idipharma) for 3 months modestly improves progressive sperm motility, sperm morphology, and sperm DNA fragmentation index but does not affect semen volume or sperm concentration when compared with control (112091). However, it is unclear if this effect is due to superoxide dismutase, other ingredients, or the combination.
• Neck pain. Oral superoxide dismutase has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with chronic neck pain shows that taking a specific combination product (ALA600SOD, Alfa Wassermann) containing superoxide dismutase 140 IU and alpha-lipoic acid 600 mg daily for 2 months, along with physiotherapy, reduces neck pain when compared with physiotherapy alone. In addition to improvements in pain scores at rest and during movement, 81% of patients receiving the combination product reported their pain to be "much improved" or "slightly improved", compared with just 29% of patients receiving physiotherapy alone. For every two patients treated with this supplement plus physiotherapy, one additional patient will report pain improvement over physiotherapy alone (90440).
• Obesity. Oral superoxide dismutase has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in obese patients shows that taking superoxide dismutase 400 IU with Saccharomyces bouldardii 5 billion colony forming units twice daily for 60 days does not reduce body weight, body mass index, or measures of hunger and satiety when compared with placebo (106848).
• Pneumonia. It is unclear if intravenous superoxide dismutase is beneficial in patients with pneumonia. Details: A small clinical study in patients with idiopathic interstitial pneumonia shows that intravenous infusion of lecithinized superoxide dismutase 40 or 80 mg daily for 28 days does not improve lung function when compared with placebo (95212).
• Radiation fibrosis. It is unclear if topical superoxide dismutase is beneficial in patients with radiation fibrosis. Details: A small clinical trial in patients with post-radiation fibrosis following treatment for head and neck cancer shows that applying ¼ teaspoon of topical superoxide dismutase (Sodermix cream, Life Science Investments) twice daily for 3 months does not improve symptoms of fibrosis when compared with placebo (101080).
• Radiation-induced cystitis. It is unclear if injecting superoxide dismutase into the bladder wall is beneficial in patients with radiation-induced cystitis. Details: A small, uncontrolled clinical study in patients with radiation-induced or interstitial cystitis shows that administration of superoxide dismutase 4-12 mg as an injection into the bladder wall every 4-6 weeks for up to 6 treatments improves pain, urinary urgency, incontinence, bladder capacity, and micturition frequency when compared to baseline (2233). The validity of these findings is limited by a lack of control group.
• Stress. It is unclear if oral superoxide dismutase is beneficial in patients with stress. Details: A small clinical study in healthy individuals shows that taking a specific melon extract (Extramel, Bionov), providing superoxide dismutase 140 IU, daily for 12 weeks slightly reduces stress when compared with placebo. Stress scores were reduced by 6.6%, compared with a 2.6% reduction with placebo (95211). It is unclear if this difference would be considered clinically significant.
• Vitiligo. It is unclear if oral superoxide dismutase is beneficial in patients with vitiligo. Details: A small clinical study in patients with non-segmental vitiligo shows that taking a gliadin-protected formulation of superoxide dismutase (Glisodin, Isocell Laboratory) 500 mg twice daily for 12 weeks followed by 250 mg twice daily for 12 weeks along with twice-weekly phototherapy improves the degree of re-pigmentation when compared with placebo plus phototherapy (106849). More evidence is needed to rate superoxide dismutase for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Some evidence suggests schisandra fruit is a uterine stimulant (11).

LACTATION:
Insufficient reliable information available; avoid using.

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POSSIBLY SAFE ...when used orally and appropriately. A gliadin-protected formulation of superoxide dismutase (Glisodin, Isocell Laboratory) has been used with apparent safety at doses up to 1 gram daily for up to 12 weeks or 500 mg daily for up to 24 weeks (106849). In combination with other ingredients, superoxide dismutase 140 IU and 10 mg have been used with apparent safety for up to 4 months and 12 months, respectively (20488,105502). ...when used parenterally, short term. Intravenous, intramuscular, and local injections of superoxide dismutase have been used with apparent safety, short-term (2230,2231,2232,2233,2241,2243). However, since some preparations are derived from animals, there is concern about contamination with diseased animal parts (1825). So far, there are no reports of disease transmission to humans due to use of contaminated preparations. Lecithinized recombinant superoxide dismutase 20-160 mg as a single intravenous dose has been used with apparent safety (105503). There is insufficient reliable information available about the safety of superoxide dismutase when used topically or in the eye.

CHILDREN: POSSIBLY SAFE
when administered via subcutaneous injection. Superoxide dismutase 0.25 mg/kg twice daily until ventilator support is no longer required has been used with apparent safety in pre-term infants (2242).

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

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CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.  Details In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of cyclosporine.  Details A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.  Details In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.  Details In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.  Details Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of midazolam.  Details A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.  Details In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

SIROLIMUS (Rapamune) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of sirolimus.  Details A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).

TACROLIMUS (Prograf) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of tacrolimus.  Details Clinical research in healthy volunteers and transplant patients shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 48% to 73%. This effect is thought to be due to inhibition of CYP3A4 by schisandra, and possibly also inhibition of the P-glycoprotein drug transporter. It may also be related to the inhibition of CYP3A5 in people who are CYP3A5 expressors. Small clinical studies show that schisandra increases tacrolimus levels in both expressors and non-expressors of CYP3A5 (15570,17414,91387,96631,105623,109639,109641). However, some clinical and observational research shows that schisandra increases tacrolimus levels to a greater degree in CYP3A5 expressors when compared with CYP3A5 non-expressors (109638,109640). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564).

TALINOLOL Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Schisandra can increase the levels and clinical effects of talinolol.  Details A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386). tly.

VORICONAZOLE (Vfend) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might increase the levels and clinical effects of voriconazole.  Details Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, schisandra might decrease the levels and clinical effects of warfarin.  Details Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.

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General ...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.

Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).

Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).

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General ...Orally and parenterally, superoxide dismutase seems to be well tolerated.
Most Common Adverse Effects:
Parenterally: Pain and injection site reactions.
Serious Adverse Effects (Rare):
Parenterally: Anaphylaxis, possibly related to impurities in parenteral formulations.

Hematologic ...As an injection, superoxide dismutase may cause elevations in triglyceride and direct bilirubin levels. Cases of transient elevations in triglycerides and direct bilirubin have been reported after a single injection of lecithinized recombinant superoxide dismutase (105503).

Immunologic ...As an injection, superoxide dismutase can cause allergic reactions at the injection site in some patients (2235). It can also cause anaphylactic shock, which may be caused by product impurities (11008).

Musculoskeletal ...As an injection, superoxide dismutase can cause pain at the injection site in some patients (2235).

Neurologic/CNS ...Superoxide dismutase may be prepared from bovine liver. Products made from contaminated or diseased organs might present a human health hazard. There is also concern that spleen extracts produced from cows in countries where bovine spongiform encephalitis (BSE) has been reported might be contaminated with diseased tissue (1825). Thus far, there have been no reports of BSE transfer to humans from contaminated SOD products.

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