Cell Fit by Kroeger Herb Products Co.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral dimethylglycine for aging, there is insufficient reliable information about the clinical effects of dimethylglycine for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Although there has been interest in using oral dimethylglycine for ADHD, there is insufficient reliable information about the clinical effects of dimethylglycine for this purpose.
• Athletic performance. Although there has been interest in using oral dimethylglycine to improve athletic performance, there is insufficient reliable information about the clinical effects of dimethylglycine for this purpose.
• Autism spectrum disorder. It is unclear if oral dimethylglycine is beneficial in males with autism spectrum disorder. Details: A very small clinical crossover study in males aged 4-30 years shows that taking low doses of dimethylglycine daily for 1 month does not improve symptoms of autism when compared with placebo (5819).
• Cardiovascular disease (CVD). Although there has been interest in using oral dimethylglycine for CVD, including hyperlipidemia, there is insufficient reliable information about the clinical effects of dimethylglycine for these conditions.
• Cognitive function. Although there has been interest in using oral dimethylglycine for cognitive function, there is insufficient reliable information about the clinical effects of dimethylglycine for this purpose.
• Epilepsy. It is unclear if oral dimethylglycine is beneficial in patients with frequent generalized or myoclonic seizures. Details: A small clinical study in patients institutionalized with frequent generalized-onset, myoclonic, or atonic seizures shows that taking dimethylglycine 300 mg daily for 2 weeks followed by 600 mg daily for 2 weeks does not reduce seizure frequency when compared with placebo (5823).
• Multiple sclerosis (MS). It is unclear if oral dimethylglycine is beneficial in patients with progressive MS. Details: A small clinical study in patients with primary or secondary progressive MS shows that taking dimethylglycine 125 mg daily for 12 months does not improve cognition, fatigue, or motor performance when compared with placebo (108050).
• Stress. Although there has been interest in using oral dimethylglycine for stress, there is insufficient reliable information about the clinical effects of dimethylglycine for this purpose. More evidence is needed to rate dimethylglycine for these uses.

(Read more about DIMETHYLGLYCINE (DMG))

EFFECTIVE

• Sunburn. PABA is an FDA-approved sunscreen (266,8952). PABA seems to be effective during sweating, but not when skin is immersed in water (272).

POSSIBLY EFFECTIVE

• Peyronie disease. PABA is FDA-approved for use in this condition. Clinical research shows that taking the specific PABA product (POTABA, Glenwood LLC.) can reduce penile curvature and deterioration (1067,8951,67982,68031).

POSSIBLY INEFFECTIVE

• Scleroderma. Although PABA is FDA-approved for scleroderma, as well as morphea, a localized form of scleroderma, evidence supporting its use is limited. Some retrospective studies suggest it might help for some symptoms of scleroderma, but the most convincing evidence shows that it is not beneficial (1071,1073,1074,1075).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Herpes keratitis. Preliminary clinical research shows that, in most patients, using a specific PABA 0.007% ophthalmic solution (Actipol), given as eye drops with or without concomitant local injections, can be effective in treating herpes keratitis, a type of corneal eye infection caused by herpes simplex virus. Clinical research suggests this PABA solution is as effective or more effective than acyclovir and more effective than idoxuridine (67957,67963).
• Inflammatory myopathies. PABA is FDA-approved for use in dermatomyositis, a type of inflammatory myopathy, but there is limited evidence to support this use (10).
• Pemphigus. PABA is FDA-approved for use in pemphigus, but there is limited evidence to support this use (10). More evidence is needed to rate PABA for these uses.

(Read more about PARA-AMINOBENZOIC ACID (PABA))

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.

(Read more about SUPEROXIDE DISMUTASE (SOD))

POSSIBLY SAFE ...when used orally, short-term. Dimethylglycine has been used with apparent safety in small clinical trials lasting up to 28 days (5819,5823).

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

(Read more about DIMETHYLGLYCINE (DMG))

LIKELY SAFE ...when used topically and appropriately. PABA is FDA approved for topical use and there have not been reports of significant toxicity (266,272).

POSSIBLY SAFE ...when used orally and appropriately (10). PABA is an FDA-approved drug, but some potentially serious side effects have been reported (10). ....when applied topically and appropriately to the eye as a 0.007% ophthalmic solution (67957,67963).

POSSIBLY UNSAFE ...when used orally in high doses. Doses greater than 12 grams per day have been associated with leukopenia (1061).

CHILDREN: LIKELY SAFE
when used topically and appropriately (266,272).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately (10). PABA is an FDA-approved drug for use in children, but serious side effects have been reported (10).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses. Doses greater than 220 mg/kg/day have been associated with fatal toxic effects (1061).

PREGNANCY AND LACTATION: LIKELY SAFE
when used topically and appropriately (266,272). There is insufficient reliable information available about the safety of the oral use of PABA during pregnancy and breast-feeding; avoid using.

(Read more about PARA-AMINOBENZOIC ACID (PABA))

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.

(Read more about SUPEROXIDE DISMUTASE (SOD))

(Read more about DIMETHYLGLYCINE (DMG))

(Read more about PARA-AMINOBENZOIC ACID (PABA))

(Read more about SUPEROXIDE DISMUTASE (SOD))

General ...Orally, no adverse effects have been reported in clinical trials in adults and children using dimethylglycine. However, a thorough evaluation of safety outcomes has not been conducted.

Gastrointestinal ...Theoretically, dimethylglycine might react with nitrites in the gastrointestinal tract to form carcinogenic substances (5827). However, research suggests that dimethylglycine does not react with nitrites and is not carcinogenic (13172).

(Read more about DIMETHYLGLYCINE (DMG))

General ...Orally, PABA seems to be well tolerated. The most commonly reported side effects are diarrhea, nausea, vomiting, anorexia, dyspepsia, fever, and rash (1074). Allergic reactions including fever and skin rash have also occurred (1074). In rare cases, hepatotoxicity has been reported at high doses (12-48 grams daily) (1061,1094). High doses of PABA (up to 48 grams per day) might also cause a decrease in white blood count (1061). PABA should be discontinued if adverse effects prevent the patient from eating (10). In one report, up to 25% of patients discontinued PABA due to intolerance of side effects (1074). Topically, PABA can cause contact dermatitis and sometimes paradoxical photosensitivity (272).

Dermatologic ...Topically, PABA can cause contact dermatitis and sometimes paradoxical photosensitivity (272).

Gastrointestinal ...Orally, the most commonly reported side effects of PABA are diarrhea, nausea, vomiting, anorexia, dyspepsia, fever, and rash (1074). PABA should be discontinued if adverse effects prevent the patient from eating (10). In one report, up to 25% of patients discontinued PABA due to intolerance of side effects (1074).

Hematologic ...High dose PABA (up to 48 grams per day) can cause decreased white blood count below 4000 mm3 in approximately 30% of patients (1061).

Hepatic ...Liver toxicity, including fatal hepatitis has been reported in patients taking PABA in high doses (12-48 grams per day) (1061,1094). In one case, 12 grams per day for 2 months caused liver toxicity (1094). Increased liver function tests from PABA have also been noted (1084), and jaundice was reported in one case of treatment with PABA (68049). Despite these reports, a study reviewing the charts of 274 patients with scleroderma who were taking the potassium salt form of PABA as treatment found no evidence of hepatotoxicity (1065).

Immunologic ...Orally, PABA can cause allergic reactions including fever and skin rash (1074).

Neurologic/CNS ...Orally, PABA may cause headaches, which resolve upon discontinuation of treatment (1074).

Other ...Death has been reported in 3 children treated with 24 grams of PABA per day for rheumatic fever or arthritis. At autopsy, all had fatty changes in the liver, kidney, and myocardium (1061). Topical PABA and its derivatives have a tendency to discolor clothing due to a photo-oxidative reaction (68025).

(Read more about PARA-AMINOBENZOIC ACID (PABA))

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.

(Read more about SUPEROXIDE DISMUTASE (SOD))