GM-H3 [Discontinued] by Loomis Enzymes

EFFECTIVE

• Lactose intolerance. Lactase is effective for reducing gastrointestinal symptoms from consuming lactose in lactose intolerant individuals. Details: Multiple clinical trials show that taking lactase orally is effective for reducing GI symptoms in lactose-intolerant people when used before the consumption of lactose or when added to milk prior to consumption (2371,2372,2373,106669).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Colic. It is unclear if oral lactase is beneficial in infants with colic. Details: Preliminary clinical research in infants with colic shows that supplementing human milk or formula with lactase (Crosscare Ltd) for 10 days reduces breath hydrogen levels, but not time spent crying, when compared with placebo. However, approximately 30% of infants in this study were considered to be noncompliant. When only infants considered to be compliant were included in the analysis, time spent crying during the 10-day treatment period was reduced by about 6 hours in the lactase group when compared with placebo (96347). In two other small trials, giving 5 drops of a specific lactase formulation (Colibid, RG Pharmaceutica or Yamoo, Walter Bushnell) to infants aged 0-6 months with colic before each feed, or 4 times a day, for 2-4 weeks significantly reduces crying time and fussing time when compared with placebo (104107,112190). However, measures of crying time were based on subjective parent recall only.
• Prematurity. It is unclear if oral lactase is beneficial in premature patients. Details: Clinical research shows that giving fortified human milk or preterm formula treated with lactase drops (Lactaid, McNeil Consumer Products Company) to preterm infants does not improve weight gain, feeding tolerance, weekly length gain, or gain in head circumference by 36 weeks' gestational age or discharge from the hospital (whichever comes first) when compared with giving untreated milk or formula (96346). More evidence is needed to rate lactase for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Celiac disease. Although there has been interest in using oral lipase for celiac disease, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Dyspepsia. It is unclear if oral lipase is beneficial for improving symptoms of postprandial distress syndrome. Details: A small clinical trial shows that taking a specific acid-resistant lipase (Amano Enzyme USA) 280 mg immediately before a high-fat meal does not reduce postprandial bloating and nausea when compared with placebo in individuals with postprandial distress syndrome (101900).
• Inflammatory bowel disease (IBD). Although there has been interest in using oral lipase for IBD, there is insufficient reliable information about the clinical effects of lipase for this purpose.
• Prematurity. It is unclear if adding a specific form of lipase, recombinant human bile salt-stimulated lipase (rhBSSL), to infant formula improves outcomes in premature infants. Some research suggests a potential increased risk for adverse effects. Details: Human breast milk contains rhBSSL, but it is inactivated when breast milk is pasteurized for donation. Clinical research in infants born before 32 weeks' gestation shows that adding rhBSSL as 8700 units per 100 mL formula or pasteurized breast milk, for 4 weeks does not increase growth velocity, body length, or head circumference over the next 12 months when compared with formula or pasteurized breast milk devoid of lipase. However, the infants who were small for gestational age (SGA), which made up approximately 15% of the study population, grew by an additional 1.9 grams/kg daily on average when compared with placebo (101940). More evidence is needed to rate lipase for these uses.

(Read more about LIPASE)

Proteolytic enzymes represent a wide group of enzymes that are used alone or in combination. See specific monographs for effectiveness information.

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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.

(Read more about SUPEROXIDE DISMUTASE (SOD))

LIKELY SAFE ...when used orally and appropriately with lactose-containing foods. Lactase has Generally Recognized as Safe (GRAS) status in the US when prepared from Candida pseudotropicalis or Kluyveromyces lactis (104108,104109). Lactase has been used safely in doses up to 9900 international units (IU) and up to 13,500 food chemical codex (FCC) units (2371,2372,2373,106669).

CHILDREN: LIKELY SAFE
when used orally and appropriately with lactose-containing foods.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately with lactose-containing foods.

(Read more about LACTASE)

There is insufficient reliable information available about the safety of lipase.

CHILDREN: POSSIBLY UNSAFE
when recombinant human bile salt-stimulated lipase (rhBSSL) is used orally by premature infants. Adding rhBSSL to infant formula or pasteurized breast milk increases the risk for serious gastrointestinal adverse effects in premature infants (101940).

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

(Read more about LIPASE)

POSSIBLY SAFE ...when used orally and appropriately. Various proteolytic enzymes have been safely used orally in clinical research (716,964,965,968,969,6252,6253,10622,11457,18281,18284) (91104,91105,91106,91111,96449). Side effects are typically mild to moderate and most often include gastrointestinal effects. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes. ...when used topically and appropriately. Various proteolytic enzymes have been safely used topically in clinical research (67835,67843,67845,91113). Some proteolytic enzymes might cause allergic reactions when used topically. See specific monographs for more detailed information related to the safety of individual proteolytic enzymes.

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

(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

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 LACTASE)

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(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

(Read more about SUPEROXIDE DISMUTASE (SOD))

General ...Orally, lactase is generally well tolerated.

Immunologic ...A case of lactase-induced contact dermatitis and immunoglobulin E (IgE)-mediated allergic rhinoconjunctivitis has been reported in a worker exposed to powdered lactase. Allergy to lactase was confirmed by prick test, open application test, and chamber challenge test (96348).

(Read more about LACTASE)

General ...No adverse effects have been reported in adults. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal adverse effects, such as necrotizing enterocolitis, when recombinant human bile salt-stimulated lipase is used in premature infants.

Gastrointestinal ...Orally, when added to the formula or pasteurized breast milk consumed by premature infants, recombinant human bile salt-stimulated lipase (rhBSSL) can cause gastrointestinal adverse effects, including abdominal distension, flatulence, constipation, colic, abdominal pain, gastroenteritis, vomiting, regurgitation, and rectal bleeding (101940). Premature infants receiving rhBSSL also had a slightly higher rate of necrotizing enterocolitis (NEC) when compared with those receiving placebo. After review by a panel of experts, it was determined that the rate of confirmed or suspected NEC in infants consuming rhBSSL was 3.3%, compared with 0.5% in those receiving placebo. Although this rate of NEC is lower than the historical rate of occurrence in premature infants (11%), a possible increased risk for NEC cannot be ruled out (101940).

(Read more about LIPASE)

General ...Orally, proteolytic enzymes are generally well tolerated. See specific monographs for detailed safety information related to individual proteolytic enzymes.
Most Common Adverse Effects:
Orally: Gastrointestinal upset.
Serious Adverse Effects (Rare):
Topically: Allergic reactions.

Gastrointestinal ...Orally, some patients taking proteolytic enzymes may have gastrointestinal complaints (101517).

Immunologic ...Proteolytic enzymes are commonly found in laundry detergents and pre-spotter products. Rarely, protease specific IgE positive tests possibly related to these products have occurred. Exposure may be airborne or topical (102705). In addition, in case reports, occupational exposure to the airborne proteolytic enzyme pepsin has resulted in allergic rhinoconjunctivitis or asthma (102706,102707).

(Read more about PROTEOLYTIC ENZYMES (PROTEASES))

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))