Can C Eye Drops by Innovative Vision Products Inc

POSSIBLY INEFFECTIVE

• Autism spectrum disorder. Oral carnosine does not seem to improve symptoms of autism spectrum disorder. Details: A meta-analysis of three clinical trials in children aged 3-16 years with autism shows that taking carnosine does not improve symptoms of autism, including socialization, behavior, and communication, when compared with placebo (106082). Studies included in the analysis were small to moderate in size and used carnosine 500-800 mg, or 10-15 mg/kg, daily for 8 weeks (39926,100483,106081).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related cognitive decline. Oral carnosine has only been evaluated in combination with anserine; its effect when used alone is unclear. Details: Meta-analyses of a few small clinical studies suggest that taking a combination of carnosine and anserine 1 gram daily in a 1:2 or 1:3 ratio for 3 months improves some, but not all, measures of cognitive function and memory when compared with placebo (106086,111263). It is unclear if these findings are due to carnosine, anserine, or the combination.
• Alzheimer disease. Although there is interest in using oral carnosine for Alzheimer disease, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Athletic performance. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some research has evaluated carnosine in combination with beta-alanine. One small clinical study in muscle-fatigued healthy males shows that taking a combination of carnosine 2 grams plus beta-alanine 2 grams as a single dose 4 hours prior to testing increases maximal voluntary muscle contractions during knee extensions by 15% and jump height by 6% when compared with placebo. However, muscle pain was increased after 24 hours following use of carnosine and beta-alanine (94232). In another small clinical trial in healthy males, taking a single dose of carnosine 2.5 grams plus beta-alanine 2.5 grams (DDM Carnosina, Omeopiacenza Srl, Pontenure) does not affect most measures of athletic performance, including perceived exertion, work rate, maximum workload, and oxygen use, when compared with placebo. However, there was a small benefit on the ventilatory threshold during one test (106079). Other research has evaluated carnosine in combination with anserine. One small clinical study shows that taking a single dose of a specific chicken breast extract (CBEX) 40 grams containing 1.5 grams of carnosine and anserine orally does not affect power during maximal cycle ergometer sprints when compared with placebo in healthy active males (39938). However, a very small study shows that taking a single dose of pure carnosine and anserine 20 mg/kg each improves power by 6.1% in the first 5 seconds of a cycling performance test following 6-minutes of high intensity cycling. There was no effect on mean power, time to peak power, or time to power drop during the performance test. When power was measured over three consecutive cycling performance tests, peak power was increased by 2.5% when compared with placebo (106085).
• Cataracts. Although there is interest in using oral carnosine for cataracts, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Cognitive impairment. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of three clinical trials shows that taking a combination of carnosine and anserine 1 gram daily in a 1:2 or 1:3 ratio for 12 weeks modestly improves global cognitive function when compared with placebo (106086). However, there was no evidence of benefit in any of the individual small studies included in the analysis. Also, only one study was limited to patients with mild cognitive impairment.
• Corneal ulceration. Although there is interest in using topical carnosine for corneal ulceration, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Depression. It is unclear if oral carnosine is beneficial for depression. Details: Preliminary clinical research in patients with major depressive disorder shows that taking carnosine 400 mg twice daily while initiating treatment with citalopram, titrated up to a dose of 40 mg daily, for 6 weeks improves symptoms of depression, as measured on the Hamilton Depression Rating Scale (HAM-D), when compared with placebo plus citalopram (103289). It is unclear whether carnosine is beneficial as an adjunct treatment in patients who have already been treated with antidepressants.
• Diabetes. It is unclear if oral carnosine is beneficial for diabetes. Details: A meta-analysis of three small clinical studies in patients with type 2 diabetes shows that taking carnosine 1 gram two or three times daily for 12 weeks or 6 mg/kg three times daily for 8 weeks reduces glycated hemoglobin (HbA1c) by 1.5% and fasting blood glucose by 12.4 mg/dL when compared with placebo (111263). However, one of the studies included in this analysis evaluated carnosine in combination with alpha-lipoic acid 7 mg/kg and thiamine 1 mg/kg (98682).
• Diabetic nephropathy. It is unclear if oral carnosine is beneficial for diabetic nephropathy. Details: A small clinical trial in patients with type 2 diabetes and diabetic nephropathy shows that taking carnosine (Tokai Bussan Co., Ltd) 1 gram twice daily for 12 weeks does not improve levels of blood urea nitrogen or serum creatinine, or improve glomerular filtration rate, when compared with placebo. However, there is a small improvement in urinary levels of transforming growth factor (TGF)-beta, a marker of renal injury in these patients (106083).
• Diabetic neuropathy. Although there is interest in using oral carnosine for diabetic neuropathy, there is insufficient reliable information about the clinical effects of carnosine for this condition.
• Dry mouth. Topical carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with dry mouth shows that use of a specific mucoadhesive tablet (Aqualief, Helsinn Healthcare SA), containing a combination of carnosine and Hibiscus sabdariffa calyces, 400 mg three times daily after meals for 6 days increases saliva production and improves symptoms of dry mouth when compared to baseline. While saliva production was also increased in patients taking placebo, the increase was 3-fold greater with the combination product, and significant improvements in dry mouth symptoms were lacking in the placebo group (103288). In another small trial in patients with radiation-induced dry mouth, taking the same tablets (marketed as Salifluss, Metis Healthcare srl) for 8 days increases saliva production by about 30% when compared with placebo. However, symptoms of dry mouth were not improved (106087). It is unclear if these findings are due to carnosine, Hibiscus sabdariffa, or the combination.
• Dry skin. Topical carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with diabetes and severe dry skin of the foot shows that using a cream containing urea 5%, arginine 0.5%, and carnosine 0.01% (Ureadin Podos Db cream) twice daily for 8 months improves skin hydration and reduces xerosis when compared with a control emollient cream. The carnosine cream reduced xerosis by 91% over baseline, compared with a 23% reduction with the control cream (93999).
• Glaucoma. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with primary open angle glaucoma shows that taking a specific combination supplement (Gangliolife, SOOFT Italia) as two tablets twice daily for 1 year in addition to standard topical therapy results in a decrease in intraocular pressure when compared with standard therapy alone. One tablet of the supplement contains carnosine 50 mg, coleus extract 150 mg (standardized to 10% forskolin), homotaurine 100 mg, vitamin B1 1.1 mg, vitamin B2 1.4 mg, vitamin B6 1.4 mg, folic acid 0.2 mg, and magnesium 150 mg (91886). It is not clear if this effect is due to carnosine, the other ingredients, or the combination.
• Gulf war syndrome. It is unclear if oral carnosine is beneficial in patients with Gulf war syndrome. Details: In patients with Gulf war syndrome, preliminary clinical research shows that taking carnosine 500 mg, 1000 mg, or 1500 mg daily as add-on therapy for 4 weeks each, and then tapered over 2 weeks, has little benefit on symptoms associated with this illness. Taking carnosine modestly reduces the number of patients with diarrhea and also modestly improves some scores on specific cognitive tests. However, other symptoms of the illness, such as fatigue, pain, and reduced activity, were not improved (93996).
• Heart failure. It is unclear if oral carnosine is beneficial for heart failure. Details: Preliminary clinical research in patients using standard treatment shows that taking carnosine 500 mg daily for 6 months might improve the peak oxygen uptake by 4.5% during a cardiopulmonary stress test, compared to a decrease of 3.8% in patients not using carnosine. This change resulted in improvements in maximal workload and a 59.4-meter increase in 6-minute walking distance, compared to a decrease of 10.6 meters in the control group (94235).
• Hyperlipidemia. It is unclear if oral carnosine is beneficial in patients with hyperlipidemia. Details: Meta-analyses of mostly small clinical trials show that taking carnosine 1-3 grams daily for up to 12 weeks does not improve total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides when compared with placebo. (103287,111263). However, it is unclear if these findings can be generalized to patients with hyperlipidemia; the studies included in this analysis focused on patients who were obese or had diabetes or impaired glucose tolerance.
• Metabolic syndrome. It is unclear if oral carnosine is beneficial for patients with metabolic syndrome. Details: Observational research in adults at risk for metabolic syndrome has found that taking carcinine, a metabolite of carnosine, 60 mg daily for 8 weeks is associated with improvements in blood glucose, glycated hemoglobin, serum insulin, insulin resistance, and total cholesterol when compared with a control group (111265). The validity of these findings is limited the retrospective nature of the study, which includes a lack of randomization, blinding, and placebo control.
• Obesity. Oral carnosine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that taking a specific product containing cinnamon extract 456 mg, chromium guanylate 2.5 mg, and carnosine 400 mg (Glycabiane, PiLeJe) daily for 4 months reduces fasting blood glucose levels and fat-free mass when compared with placebo. However, there were no changes in glycated hemoglobin, insulin sensitivity, or body weight (94234). It is not clear if these effects are due to carnosine, the other ingredients, or the combination.
• Obsessive-Compulsive Disorder (OCD). It is unclear if oral carnosine is beneficial for OCD. Details: Preliminary clinical research shows that taking carnosine 500 mg twice daily in combination with fluvoxamine for 10 weeks reduces compulsive symptoms, but not obsessive symptoms, in adults with moderate to severe OCD when compared with fluvoxamine alone. However, the degree of symptom reduction might not be considered clinically meaningful (97338).
• Peptic ulcers. Although there is interest in using oral carnosine for peptic ulcers, there is insufficient reliable information about the clinical effects of carnosine for this use.
• Pressure ulcers. It is unclear if oral carnosine is beneficial for pressure ulcer healing. Details: Preliminary clinical research shows that taking carnosine might help with the healing of pressure ulcers in patients also treated with standard care. Taking carnosine 116 mg for 4 weeks increased the rate of healing by approximately 50% when compared with a control group receiving standard care alone (97601).
• Schizophrenia. Small clinical studies suggest that oral carnosine does not improve symptoms of schizophrenia. Details: One small clinical study of patients with schizophrenia or schizoaffective disorder who are on stable doses of antipsychotics shows that taking carnosine titrated from 500 mg daily up to 2000 mg over 4 weeks, continued for an additional 8 weeks and then tapered for 2 weeks, does not improve symptoms of depression or schizophrenia or improve quality of life when compared with placebo (93997). Another small clinical study in patients with schizophrenia with predominantly negative symptoms shows that taking carnosine 400 mg daily for 12 weeks and then titrating up to 800 mg daily until 24 weeks does not improve positive or negative symptoms when compared with placebo. Measures of cognitive function, with the exception of an executive functioning test, were not improved with carnosine over placebo (111264). More evidence is needed to rate carnosine for these uses.

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LIKELY EFFECTIVE

• Constipation. Rectal glycerol is beneficial in children and adults with constipation. Details: Glycerol rectal suppositories and enemas are approved by the US Food and Drug Administration (FDA) for over-the-counter use to treat occasional constipation in adults and children at least 2 years of age (15).

POSSIBLY EFFECTIVE

• Athletic performance. Oral glycerol may improve hydration during exercise, but clinical studies evaluating glycerol for improving measures of athletic performance are limited and conflicting. Details: Several clinical studies show that glycerol increases serum osmolality and improves hydration status during exercise (2475,2476,93757,93760,93761,93765). One meta-analysis, including 14 studies and 99 patients, shows that glycerol-induced hyperhydration increases body water by approximately 2.5-fold when compared with water-induced hyperhydration (93757). Also, taking glycerol along with table salt 7.5 grams per liter fluid seems to improve hydration status when compared withg glycerol alone (99162). Research regarding the effects of glycerol on thirst, comfort, temperature regulation, sweating, and heart rate is conflicting (2475,2476,93760,99162). While glycerol may improve hydration status during exercise, it is unclear whether it can improve measures of athletic performance. An early meta-analysis including a total of 36 athletes shows that taking glycerol increases endurance performance by 2.6%. Although this is a small difference, it might be considered meaningful to athletes (93757). Some small clinical studies in athletes suggest that glycerol increases endurance and time to exhaustion, with no effect on heat regulation (2475,2479,93764). However, other small studies suggest that glycerol does not reduce perceived exhaustion or improve exercise performance (2476,93760). Also, glycerol has not been shown to increase time to exhaustion in triathletes (2492). When used to improve athletic performance, glycerol is most often taken at doses of 1-1.5 gram/kg in conjunction with approximately 1.5 L of fluid, 60-120 minutes before competition, and in some cases continued during the competition (2475,93757,93760,93764).
• Ichthyosis. Topical application of a specific product containing glycerol and paraffin may improve symptoms of ichthyosis in children. The benefits of topical glycerol alone in these patients is unknown. Details: A large clinical trial in children aged 1 month to 18 years shows that applying a specific product (Dexeryl, Pierre Fabre Laboratoires) containing glycerol 15% and paraffin 10% for 4 weeks reduces symptoms of non-bullous ichthyosis by at least 50% in an additional 17% of children when compared with a placebo cream. Applying this specific product also improves pruritus by an additional 45% when compared with placebo (93756). It is unclear if these findings are due to glycerol, paraffin, or the combination.

POSSIBLY INEFFECTIVE

• Meningitis. Some clinical research suggests that oral glycerol does not reduce the risk of mortality or seizures in adults and children with bacterial meningitis, although it may reduce certain sequelae. Details: A meta-analysis of five low-quality clinical trials including 1,270 patients shows that adjunctive treatment with glycerol as an oral osmotic agent does not reduce the risk of mortality, seizures, or gastrointestinal symptoms in adults and children with acute bacterial meningitis, although it may modestly reduce the risk of deafness and residual neurological deficit in surviving children (99160). Clinical research included in the meta-analysis has used glycerol 1.5 grams/kg every 6 hours in children aged 2 months to 16 years (93762,93763).
• Prematurity. Rectal glycerol does not appear to reduce the time to enteral feeding in premature infants. Details: Glycerol is used as an enema or given by suppository to facilitate the evacuation of meconium in premature infants in order to reduce the time to enteral feeding. However, two meta-analyses of small studies in preterm infants, that include some of the same studies, show that administering glycerol suppositories does not reduce the number of days to full enteral feeds when compared with placebo or no treatment (99166,112003). However, the interpretation of these findings is limited by the heterogeneity of dosages used in the included studies.

LIKELY INEFFECTIVE

• Stroke. Intravenous glycerol may not improve mortality or symptoms in patients with acute ischemic stroke. Details: Several clinical studies show that intravenous administration of glycerol does not improve symptoms of acute stroke (2480,2481,2482,2484,2486). Additionally, one clinical study in elderly patients with acute ischemic stroke shows that while glycerol can improve initial survival, it does not reduce the risk of overall mortality when compared with placebo (2483).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dandruff. Topical glycerol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in adults with dandruff shows that applying a leave-in hair lotion containing glycerol 10%, stearic acid 2.5%, and sunflower seed oil 0.6%, 3 times weekly for 8 weeks, modestly reduces dandruff severity throughout use and for up to one week after the last application when compared with a placebo lotion. The glycerol lotion also reduced total water loss from the scalp by 8% and increased moisturization by 23% (93758). It is unclear if these findings are due to glycerol, other ingredients, or the combination.
• Dry skin. Topical glycerol has only been evaluated in combination with other ingredients for the management of dry skin associated with kidney failure; its effect when used alone is unclear. Details: One small, open-label clinical study in adults with kidney failure and moderate to severe uremic xerosis shows that applying an emulsion containing glycerol 15% and paraffin 10% twice daily for 7 days reduces the severity of xerosis when compared with a placebo emulsion. The glycerol-containing emulsion produces a treatment response in an additional 29% of patients, improves quality of life, and reduces scale density and thickness when compared with placebo (93754). It is unclear if these findings are due to glycerol, paraffin, or the combination.
• Glaucoma. Although there has been interest in using oral glycerol for glaucoma, there is insufficient reliable information about the clinical effects of glycerol for this purpose.
• Intracranial hypertension. Although there has been interest in using intravenous glycerol to reduce intracranial pressure in patients with brain tumors, central nervous system (CNS) trauma, encephalitis, idiopathic intracranial hypertension, meningitis, and Reye syndrome, there is insufficient reliable information about the clinical effects of glycerol for this purpose.
• Meniere disease. It is unclear if intravenous glycerol is beneficial in patients with Meniere disease. Details: A small, uncontrolled clinical study in adults with unilateral, intractable Meniere disease shows that intravenous administration of glycerol 10% at a dose of 0.5 grams/kg once daily for 2 consecutive days, twice monthly for 6 months, reduces the frequency of vertigo attacks and improves quality of life when compared to baseline. Patients reported an average of 3.2 vertigo attacks per month at baseline and 1.2 vertigo attacks per month after 6 months of treatment (106649). The lack of a control group limits the validity of these findings.
• Neonatal jaundice. It is unclear if rectal glycerol improves jaundice-related outcomes in premature infants. Details: A small clinical study in neonates receiving phototherapy for jaundice shows that administering glycerol suppositories has no effect on the duration of phototherapy needed for jaundice treatment, or on bilirubin levels or the rate of bilirubin decline when compared with no glycerol suppositories (99165).
• Obesity. It is unclear if oral glycerol is beneficial in patients who are overweight or obese. Details: One small clinical study in adults on a low-calorie diet shows that taking glycerol 7.5 grams before meals for 6 weeks does not increase weight loss when compared with placebo (2485).
• Otitis externa. Topical glycerol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in adults with otitis externa shows that inserting ribbon gauze soaked in glycerol and ichthammol into the ear canal reduces pain and swelling as effectively as the application of antibiotic and steroid drops three times daily (93759). It is unclear if these findings are due to glycerol, ichthammol, or the combination. More evidence is needed to rate glycerol for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. In clinical trials, carnosine has been used safely at doses of 200-1500 mg daily, alone or in combination with other ingredients (91886,93996,94000,103289). There is insufficient reliable information available about the safety of carnosine when used topically.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Carnosine has been used in with apparent safety in children 3-16 years of age at doses of 500-800 mg daily for up to 8 weeks (39926,100483).

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

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LIKELY SAFE ...when used rectally and appropriately. Glycerol rectal suppositories and enemas are approved by the US Food and Drug Administration (FDA) for over-the-counter use to treat occasional constipation (15,272). ...when used topically and appropriately as a lotion, emulsion, or humectant (15,272,93754,93758,93759,99164).

POSSIBLY SAFE ...when used orally, short-term. Glycerol has been used with apparent safety in clinical trials at doses of up to 1.5 grams/kg (2474,2475,99162).

POSSIBLY UNSAFE ...when used intravenously. While some research suggests that intravenous glycerol can be safely administered for two consecutive days twice monthly for up to 6 months (106649), in another study, hemolysis was reported in 98% of patients treated with intravenous glycerol for acute ischemic stroke (2482).

CHILDREN: LIKELY SAFE
when used rectally and appropriately. Glycerol rectal suppositories and enemas are approved by the US FDA for over-the-counter use to treat occasional constipation in children 2 years of age and older (15,272). ...when used topically and appropriately as an emulsion or humectant in children 1 month of age and older (15,272,93756).

CHILDREN: POSSIBLY SAFE
when used orally, short-term. Glycerol has been used with apparent safety in clinical trials in children 2 months to 16 years of age at doses of 1.5 gram/kg, up to a maximum dose of 25 grams, taken every 6 hours (93762,93763).

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

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking carnosine with antidiabetes drugs might increase the risk of hypoglycemia.  Details Some, but not all, preliminary clinical research shows that carnosine might reduce fasting blood glucose levels (98682,103287,106083,111263).

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General ...Orally and topically, carnosine is generally well tolerated.

Dermatologic ...Orally, rash and itchiness have been reported with carnosine (93997).

Gastrointestinal ...Orally, decreased appetite, dry mouth, and small weight changes have been reported with carnosine (93997).

Musculoskeletal ...Orally, foot and joint pain have been reported with carnosine (93997).

Neurologic/CNS ...Orally, sporadic hyperactivity has been reported with carnosine. This may be alleviated by decreasing the dose (39926). Other adverse effects reported with oral use include sleepiness, slurred speech, lethargy, and feelings of pins and needles (93997).

Psychiatric ...Orally, vivid dreams have been reported with carnosine (93997).

Pulmonary/Respiratory ...Orally, pneumonia has been reported with carnosine (93997).

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General ...Orally, rectally, and topically, glycerol seems to be well tolerated. Intravenously, glycerol may be unsafe.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, nausea, vomiting, dizziness, and headache.
Topically: Burning, irritation, and pruritus.
Intravenously: Hemolysis in patients with acute ischemic stroke.

Dermatologic ...Topically, glycerol has been reported to cause burning, irritation, and pruritus (93754,93756). Rectally, the regular administration of glycerol 50% enemas has been reported to cause generalized urticaria in at least two patients; in both patients, symptoms resolved after discontinuation (110019,110025).

Gastrointestinal ...Orally, glycerol can cause bloating, nausea, vomiting, thirst, and diarrhea (15,2475).

Hematologic ...Intravenously, glycerol has been reported to caused hemolysis in people treated for acute ischemic stroke (2480,2482).

Neurologic/CNS ...Orally, glycerol can cause mild headache and dizziness (15,2475).

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