Cellu-Erase [Discontinued] by Priority One Nutritional Supplements

POSSIBLY EFFECTIVE

• Aging skin. Oral collagen peptides seem to improve skin hydration and elasticity in older adults. However, it is unclear if any improvements related to wrinkles are cosmetically important. Details: Meta-analyses of the available research, as well as multiple individual clinical studies, show that collagen peptide products, taken in doses of 372 mg to 12 grams daily for 4-12 weeks, improve skin hydration and elasticity in older adults. Studied products include Peptan-F or Peptan-P (Rousselot), Wellnex (Nitta Gelatin), Gold Collagen Active (Minerva Research Labs), VERISOL (Gelita AG), and Nippi peptide FCP-EX (Nippi/Shizuoka) (97632,100703,101597,104647,107460,112457,115044). Pooled study results also suggest that hydrolyzed collagen sourced from fish improves skin hydration and elasticity, while collagen peptides originating from chickens seems to modestly improve skin elasticity but not hydration. Collagen peptides derived from bovine do not seem to improve skin hydration or elasticity (112457). Despite research showing improvement in skin hydration and elasticity, it is unclear if collagen peptides reduce skin wrinkles to a cosmetically significant degree, as most studies have not evaluated this outcome. In one clinical study, taking a freshwater fish-derived collagen peptide (Vinh Wellness Collagen, Vinh Hoan Corporation) 10 grams every morning reduced wrinkle count in the nasolabial region of the right side, but not the left side, of the face by 24% when compared with placebo. Collagen peptides did not improve participant-reported measures of wrinkles, elasticity, hydration, and others, when compared with placebo (104639). Another clinical study shows that taking a specific fish scale-derived collagen peptide (Wellnex, Nitta Gelatin) with either a high or low ratio of prolyl-hydroxyproline and hydroxylpropyl-glycine as 5 grams orally daily for 8 weeks modestly improves wrinkle depth and roughness, but not wrinkle volume, when compared with placebo. The product with a high ratio of dipeptides had a larger effect (97632). Also, one clinical study shows that taking a specific product containing porcine collagen type I peptides (VERISOL, Gelita AG) 2.5 grams daily for 8 weeks reduces eye wrinkle volume by 20% when compared with placebo (101648). Two similar moderate-size clinical studies in middle-aged adults with crow's feet wrinkles and dry skin show that taking specific low-molecular-weight fish-derived collagen peptide products (Geltech Co.; CPNS) at doses of 2000 mg or 1650 mg, respectively, daily for 12 weeks improves eye wrinkles, skin hydration, and elasticity when compared with placebo (110729,110730). While investigator satisfaction scores regarding wrinkle reduction were modestly improved, participant satisfaction was not improved (110729). A moderate-sized clinical study in middle-aged adults shows that taking a specific collagen peptide supplement (Peptan-P®, Rousselot) 5 grams daily for 12 weeks does not decrease the visibility of crow's feet wrinkles when compared with placebo (115044). Small clinical studies have shown contradictory findings when collagen peptides are taken in combination with other ingredients. In one clinical trial, a specific drink (Diva Luxe) providing fish collagen peptides 5.5 grams plus Chenopodium formosanum extract 1 gram daily for 8 weeks improved some measures of skin brightness and hydration, but not wrinkles and crow's feet, when compared with placebo (104646). Another small clinical study shows that taking collagen peptides 4 grams daily in combination with coenzyme Q10 50 mg, vitamin C, vitamin A, and biotin for 12 weeks reduces wrinkles and improves skin smoothness by a small amount when compared with placebo. However, there was no difference in skin elasticity or hydration (104638). A clinical study in older females shows that taking collagen peptides 9 grams in combination with zinc and vitamins A, C, and E daily for 90 days increases stratum corneum water content and skin viscoelasticity when compared with placebo. However, it is unclear if the improvement from baseline differed between groups. Small improvements in dermal echogenicity, wrinkles, or skin pores were noted in some facial regions, but the lack of statistical comparison to placebo limits the validity of these findings (107464). Some small clinical studies have shown mixed effects with low doses of collagen peptides from preliminary clinical research using BioCell Collagen (BioCell Technology, LLC) or Celergen (Laboratories-Dom) (28681,97930). It is unclear if any improvements from these studies are due to collagen peptides, other ingredients, or the combinations. Topical application of collagen peptides has been minimally evaluated. A very small observational study in older adults has found that application of a carbopol gel containing collagen peptides 1% to the periorbital area twice daily for 8 weeks is associated with increased skin hydration and elasticity and reduced transepidermal water loss, skin roughness, and wrinkles when compared with baseline (107459). The validity of these findings is limited by poor study methodology, lack of statistical comparison to baseline, and lack of a comparator group.
• Dry skin. Oral collagen peptides seem to improve skin hydration and elasticity in adults with dry skin. However, their effect on other measures of dry skin is unclear. Details: A meta-analysis of 19 clinical studies, along with several small and moderate-sized individual studies, some of which are included in the meta-analysis, show that taking collagen peptides 372 mg to 12 grams daily for 4-12 weeks improves skin hydration and elasticity when compared with placebo in healthy adults (107461,110729,110730,112457,112458,115044). Some studies show that collagen peptides improve skin roughness (107461), decrease peeling (110729,110730), and increase stratum corneum and epidermis water content (107462) but not skin gloss (107461) or elasticity (107462). Some research shows that collagen peptides reduce transepidermal water loss (107462), while another study shows no change (107461). Subgroup analysis of the meta-analysis suggests that hydrolyzed collagen sourced from fish improves skin hydration and elasticity the most, while collagen peptides originating from chicken seem to modestly improve skin elasticity but not hydration. Collagen peptides from bovine do not seem to improve skin hydration or elasticity (112457). Studied products include FCP-Z (Nippi Co., Ltd), Geltech Co., CPNS, and GPVGPS Collagen (Daehan Chemtech) (107462,110729,110730,112458). Collagen peptides have also been evaluated in combination with other ingredients. A small clinical study in healthy adults with low skin moisture shows that drinking 30 mL of a beverage containing fish scale-derived collagen peptides 10 grams and ornithine 400 mg (FUJIFILM) daily for 8 weeks does not improve skin moisture but seems to improve skin elasticity and reduce water loss when compared with placebo (101607). Another very small clinical study in a mixed population of patients with dry skin and mild atopic dermatitis shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). The validity of these findings is limited by the lack of a comparator group. Both of these studies are limited by their small size, and it is unclear if any improvements are due to collagen peptides, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Muscle strength. Most research suggests that oral collagen peptides do not improve leg strength. However, they may improve hand-grip strength and fat-free mass. Details: Small clinical studies in healthy male and female athletes or non-athletes undergoing resistance or other training show that taking collagen peptides 15-30 grams daily or after training sessions for up to 15 weeks, with or without vitamin C, does not improve leg strength (i.e. squat strength, knee extension, or flexor strength) when compared with placebo (101608,104641,107457,110668,110669). Similarly, 2 very small clinical studies in healthy adults show that taking a specific oral collagen peptide product (Bodybalance, Gelita AG) 5-15 grams daily while completing a resistance training program for 14-15 weeks increases patellar tendon cross-sectional area but does not improve most measures of tendinous tissue remodeling including patellar tendon size, vastus lateralis aponeurosis size, patellar tendon mechanical properties, tendon stiffness, maximal knee extension strength, or rectus femoris muscle cross-sectional area when compared with placebo (112452,112454). However, a small clinical study with the same product in untrained females aged 18-50 years shows that taking 15 grams daily in addition to resistance training three times weekly for 12 weeks improves hand-grip strength when compared with resistance training and placebo (101608). In untrained males aged 30-60 years, taking the same dose of this collagen peptide product along with resistance training for 12 weeks improves fat-free mass by 3 kg, compared with 2 kg with resistance training and placebo. A post-hoc exploratory analysis suggests that the effects seen in males are similar to those seen with whey protein (107457).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there has been interest in using oral collagen peptides for acne, there is insufficient reliable information about the clinical effects of collagen peptides for this condition.
• Androgenic alopecia. Oral collagen peptides have only been evaluated in combination with other ingredients, their effect when used alone is unclear. Details: A moderate-sized clinical study in adults with androgenic alopecia or telogen effluvium shows that taking a combination product containing hydrolyzed collagen 300 mg, taurine, cysteine, methionine, iron, and selenium (GFM Oral, Cantabria Labs) daily along with conventional therapy, consisting primarily of finasteride or minoxidil, for 12 weeks improves hair loss when compared with conventional therapy alone (111636). It is unclear if this effect is due to collagen peptides, other ingredients, or the combination.
• Athletic performance. It is unclear if oral collagen peptides improve performance in most athletes. Details: In recreationally active female runners undergoing resistance and endurance training 3 times weekly, clinical research shows that taking collagen peptides 7.5 grams twice daily for 12 weeks increases running distance by approximately 1,034 meters, compared with an increase of 703 meters in those taking placebo, although there was no effect on speed (104641). A clinical study in healthy young male athletes undergoing heavy strength and power training shows that taking collagen peptides 20 grams and vitamin C 50 mg daily for 3 weeks improves squat performance and countermovement jump performance when compared with placebo. However, removal of a single outlier negated the statistical significance of most of these findings (107456). Also, it is unclear if any improvements from this study are due to collagen peptides, vitamin C, or the combination.
• Atopic dermatitis (eczema). It is unclear if oral or topical collagen peptides are beneficial for improving the severity of eczema. Details: A small clinical study in patients with atopic dermatitis shows that taking a porcine skin-derived collagen peptide with a high ratio of tripeptides with glycine-X-Y sequences, 3.9 grams daily for 12 weeks, improves symptoms and severity of eczema when compared to baseline. There was no improvement in the group taking the same dose of porcine skin-derived collagen peptide without the high ratio of tripeptides (101605). Another very small clinical study in a mixed population of patients with atopic dermatitis and dry skin shows that twice daily application of an emollient containing collagen peptides, soluble proteoglycan, and hyaluronic acid for 4 weeks reduces itching severity from moderate at baseline to mild or almost none. Transepidermal water loss and skin hydration also improved when compared to baseline (107465). It is unclear if any improvements are due to collagen peptides, the other ingredients, or the combination. Both of these studies are limited by their small size and lack of comparator groups.
• Burns. Some preliminary clinical research suggests that oral collagen peptides might reduce the time needed for burn healing. Details: In male patients with 20% to 30% body surface area burns, a small clinical trial shows that taking a collagen-based supplement providing collagen peptides (Amutiya, Qom) 36 grams daily for 4 weeks improves wound healing when compared with taking an isocaloric supplement containing the same amount of soy protein. Complete wound healing occurred in 50% and 100% of patients taking collagen for 2 and 4 weeks, respectively, compared with 7% and 40% of those taking the isocaloric product. The duration of hospital stay was not significantly different between the two groups (104642). A small clinical study in hospitalized adults with 20-45% body surface area 2nd or 3rd degree burns shows that consuming a beverage containing collagen peptides 40 grams daily for 4 weeks shortens the time to wound healing, improves scar scores, and reduces the duration of hospital stays but does not limit wound infections when compared with placebo. Adding fish oil 3 grams daily did not further improve outcomes (110667).
• Brittle nails. One small clinical study suggests that oral collagen peptides may improve nail health in people with brittle nails. Details: A small clinical study shows that taking a specific porcine type I collagen peptide product (VERISOL, Gelita AG) 2.5 grams daily for 6 months improves overall symptoms of brittle nail syndrome, increases nail growth rate by 12%, and reduces broken nail frequency by 42% when compared with baseline (101606). This study was limited by its small size and lack of a comparator group.
• Cellulite. One small clinical study suggests that oral collagen peptides may reduce cellulite. Details: In people with cellulite, a small clinical study shows that taking specific collagen peptides (VERISOL by Gelita AG) 2.5 grams daily for 6 months seems to reduce cellulite, skin waviness, and dermal density by a small amount when compared with placebo (101619).
• Cognitive function. It is unclear if oral collagen peptides are beneficial for improving memory. Details: In healthy adults, preliminary clinical research shows that taking collagen peptides 5 grams daily for 4 weeks improves some measures of memory and verbal learning when compared to baseline (104643). This study was limited by its small size and lack of a comparator group.
• Dermatoporosis. One small clinical study suggests that using oral or topical collagen peptides does not improve this condition. Details: A small clinical study in post-menopausal patients aged 70 years on average with mild dermatoporosis shows that taking collagen peptides 5 grams daily, applying a collagen peptides 2.5% serum 3 pumps nightly to each forearm, or using these in combination for 6 months does not improve skin lesions, epidermal thickness, collagen or elastin density, or patient perception of skin improvement when compared with placebo (110731). However, it is unclear if these results apply to patients with more severe dermatoporosis.
• Diabetes. Some preliminary clinical research suggests that oral collagen peptides might have a small effect on glycemic indices. Details: Preliminary clinical research in patients with type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams orally twice daily for 3 months, in addition to treatment with antidiabetes drugs, may modestly reduce levels of fasting blood glucose, glycated hemoglobin, and fasting blood insulin and may increase levels of insulin sensitivity when compared with antidiabetes drugs and placebo (101626,101627).
• Erythema. It is unclear if oral collagen peptides are beneficial for erythema. Details: A moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces erythema index when compared with placebo (112458).
• Exercise-induced gastrointestinal (GI) symptoms. It is unclear if oral collagen peptides prevent GI symptoms due to exercise. Details: A small crossover study in moderately well-trained young adults shows that taking collagen peptides 10 grams daily for 7 days prior to rigorous treadmill exercise does not limit GI symptoms but may attenuate some markers of GI distress when compared with placebo (110665).
• Exercise-induced muscle soreness. It is unclear if oral collagen peptides prevent muscle soreness after exercise. Details: Preliminary clinical research in a small number of healthy, recreationally active adults shows that taking collagen peptides (Peptan, Rousselot BVBA, Collagen Peptides, Vital Proteins) 10-15 grams twice daily, starting 7 days prior to strenuous exercise and continuing for 2-5 days after, does not reduce muscle soreness when compared with placebo (100700,104648). However, there was a small benefit on the recovery of countermovement jump ability within 24 hours (104648). Furthermore, another small clinical study in adults unaccustomed to exercise shows that taking collagen peptides 10 grams daily for 33 days modestly reduces muscle soreness and fatigue immediately after the exercise load, but not 2 hours after exercise or the next morning, when compared with placebo (111639). Also, a small clinical study in active middle-aged adults shows that taking specific collagen peptides (SOLUGEL Collagen Peptides, PB Leiner) 10 grams daily for 6 months improves pain in those who exercise frequently (>188 minutes weekly) when compared with placebo. However, collagen peptides do not seem to improve pain in low frequency exercisers (<188 minutes weekly) (112455). Collagen peptides have also been evaluated in combination with other ingredients. One preliminary clinical study in healthy, recreationally active adults shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1.5 grams twice daily for 6 weeks prior to two bouts of intense resistance exercise attenuates increases in biomarkers of muscle damage and decreases delayed onset muscle soreness when compared with placebo (96301). It is unclear if these benefits are due to collagen peptides, other ingredients or the combination.
• Gingivitis. It is unclear if oral collagen peptides are beneficial for patients with gingivitis. Details: A small clinical study in patients with mild-to-moderate chronic gingivitis shows that taking a specific collagen peptide product (Verisol B, Gelita AG) 5 grams daily for 90 days following mechanical plaque removal reduces bleeding and inflammation but does not improve plaque scores when compared with placebo (110666).
• Hypertension. Limited research suggests that oral collagen peptides may lower systolic or diastolic blood pressure. However, results are inconsistent. Details: One preliminary clinical study in patients with hypertension and type 2 diabetes shows that taking fish-derived collagen peptides 6.5 grams twice daily for 3 months modestly reduces diastolic, but not systolic, blood pressure when compared with placebo (101626). Another small clinical study in patients with mildly elevated blood pressure shows that taking a test food containing chicken leg-derived collagen peptides 2.9 grams daily for 12 weeks lowers systolic, but not diastolic, blood pressure when compared with placebo (101610). An additional small clinical study in patients with mild hypertension shows that taking chicken leg-derived collagen peptides 5.2 grams daily 4 weeks reduces systolic blood pressure by 12 mmHg when compared with baseline (101618). This study was limited by its small size and lack of a comparator group. The reasons for conflicting data are unclear.
• Insomnia. It is unclear if oral collagen peptides are beneficial for insomnia. Details: A very small clinical study in physically active males with difficulty sleeping shows that taking collagen peptides 15 grams before bedtime for 7 nights reduces the frequency of nocturnal awakenings and improves cognitive accuracy but does not improve objective measures of total sleep time, latency, efficiency, stage changes, waking after sleep onset, other cognitive function measures, or subjective measures of sleepiness, fatigue, and sleep quality when compared with placebo (112459).
• Joint pain. Most research shows that oral collagen peptides might moderately reduce joint pain in young athletes. However, evidence in other adults is conflicting. Details: Preliminary clinical research in student athletes with joint pain shows that taking a specific collagen peptide product (FORTIGEL, Gelita AG) 10 grams in 25 mL of liquid daily for 24 weeks modestly improves pain during movement and at rest when compared with placebo (101601). Other clinical research in young adults exercising or participating in sports at least 3 hours weekly with activity-related knee pain shows that taking this same product 5 grams daily for 12 weeks reduces pain intensity during activity by 38% to 41%, compared with a 26% to 28% reduction in those taking placebo. However, there was no improvement in pain at rest or after the activity when compared with placebo (97623,107454). Furthermore, it is not clear if these effects are clinically significant. Research on the use of collagen peptides in older patients is conflicting. A large clinical study in generally healthy adults with functional knee and hip pain during daily activities shows that taking a specific collagen peptide product (FORTIGEL, Gelita AG) 5 grams daily for 12 weeks modestly reduces pain at rest and during walking, per a physician assessment, when compared with placebo (114907). The validity of this finding is limited by the use of per-protocol analysis. A small clinical study in otherwise healthy patients aged 40-65 years with joint discomfort shows that taking a specific collagen peptides product (AVC-H2, Avicenna) 1.25 grams twice daily for 8 weeks improves overall Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores by 37% at 4 weeks, compared with 14% in those receiving placebo. However, this difference in improvement was no longer significant at 8 weeks. Collagen peptides also improved the physical activity and stiffness subdomains, but not the pain subdomain, at 4 and 8 weeks when compared with placebo (107455). A larger clinical study in patients 50 years or older with general joint pain shows that taking a specific collagen peptides product (Genacol) 1200 mg daily for 6 months does not reduce pain or improve function when compared with placebo (97657). However, collagen peptides used in combination with other ingredients have shown benefit. Preliminary clinical research in patients 51-70 years of age shows that taking a specific combination product (Gold Collagen Active, Minerva Research Labs) containing fish collagen peptides 4 grams, glucosamine hydrochloride 1000 mg, chondroitin sulfate 500 mg, L-carnitine 200 mg, and other ingredients daily for 90 days reduces joint pain by 43% when compared with baseline, while patients taking placebo saw negligible improvement in pain. A greater percentage of patients taking this product also perceived improvements in joint discomfort, flexibility, mobility, and rigidity when compared with placebo (100703). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Obesity. It is unclear if oral collagen peptides are beneficial for weight loss. Details: A preliminary clinical study in adults with overweight shows that taking skate skin-derived collagen peptides 2 grams daily for 12 weeks modestly reduces body fat mass by 1.2 kg, compared with an increase of 0.3 kg in the placebo group (101621). It is unclear if collagen peptides improve weight loss or reduce body fat mass in the long-term.
• Osteoarthritis. Most research suggests that oral collagen peptides improve pain in patients with knee osteoarthritis; however, any improvement is modest and may not be considered clinically significant. Details: A meta-analysis of 3 clinical studies, all of which are included below, in adults with knee osteoarthritis shows that taking collagen peptides or hydrolyzed collagen reduces pain when compared with placebo (112456). Clinical research shows that taking specific collagen peptides (Colnatur, Protein SA) 10 grams daily for 5 months increases the number of patients who experience at least a 30% improvement in pain by approximately 42% when compared with placebo. However, there is no difference between groups when the Western Ontario and McMaster Universities (WOMAC) scale is used. Patients with the greatest joint deterioration at baseline, as well as those with the lowest dietary meat intake, seemed most likely to experience benefit from collagen peptides (97635). Another small clinical study shows that taking collagen peptides isolated from pork skin and bovine bone (Nitta Gelatin Inc.) 5 grams dissolved in 250 mL water or milk twice daily after food for 13 weeks modestly improves pain when compared with placebo (101611). Another small clinical study in patients over 40 years old shows that taking collagen peptides (Colatech) 10 grams daily for 90 days reduces pain by about 2 points on a 100-point scale, compared with a 0.9-point reduction with glucosamine sulfate 1.5 grams. Ibuprofen use was not affected (101622). One multicenter clinical study shows that taking collagen peptides 10 grams daily for 6 months does not relieve pain or improve joint function when compared with placebo, although a trend towards reduced pain and improved joint function was observed in patients with severe symptoms at baseline (7704). Collagen peptides have also been evaluated in combination with other ingredients. Clinical research in patients with osteoarthritis of the knee, hip, or hand shows that taking a specific product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 1 gram twice daily for up to 10 weeks reduces pain and the need for rescue analgesics and increases physical activity when compared with placebo (28678,28680). Similarly, a moderate-size clinical study in patients aged 45-75 years with mild to moderate knee osteoarthritis undergoing resistance exercise twice weekly shows that taking a specific product (Suntory Beverage and Food Asia) containing collagen peptides from chicken collagen type II, hyaluronic acid, and chondroitin sulfate 2 grams daily for 24 weeks does not improve WOMAC scores when compared with glucosamine 1.5 grams daily or placebo, but may modestly improve pain scores when compared with placebo. However, the use of rescue analgesics was not assessed. Adding essence of chicken 5.81 grams daily to collagen peptides did not improve WOMAC or pain scores (110670). Also, preliminary clinical research in patients with knee osteoarthrosis shows that taking a specific product (Ialoral 1500, PharmaSuisse Laboratories Srl) containing collagen peptides, chondroitin sulfate, hyaluronic acid, and keratin peptides for 4 weeks improves pain and function by a moderate amount when compared with baseline (104645). However, the validity of these findings is limited by the lack of statistical comparison to the control group. It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteopenia. It is unclear if oral collagen peptides prevent loss of bone mineral density (BMD) in postmenopausal adults. Details: A large clinical study in patients with reduced BMD after menopause shows that taking specific collagen peptides (Fortibone, Gelita AG) 5 grams daily for 12 months increases BMD of the spine and the femoral neck by 3% and 7%, respectively, compared with losses of 1% with placebo (101609). In a very small observational extension of this study, BMD continued to increase over an additional 4 years when compared with baseline. However, the validity of these findings is limited by the lack of a comparator group (107340). Collagen peptides have also been evaluated in combination with calcium and vitamin D. In patients with osteopenia after menopause, a small clinical study shows that taking collagen peptides calcium chelate 5 grams, containing elemental calcium 500 mg and vitamin D3 200 IU, daily for 12 months does not affect total hip, total body, or vertebral BMD when compared with calcium 500 mg and vitamin D 200 IU (101604). The validity of these results is limited by a high dropout rate and insufficient power to detect smaller effects. Conversely, another small study in this population shows that taking specific collagen peptides (Fortibone, Gelita AG) in combination with elemental calcium (as calcium lactate) 500 mg and vitamin D3 400 IU daily for 12 months improves trabecular bone mineral content, trabecular volumetric BMD, and cortical volumetric BMD, but not cortical bone mineral content, when compared with a combination tablet containing equivalent doses of elemental calcium (as calcium carbonate) and vitamin D (107453). It is unclear if these effects are due to collagen peptides, other ingredients, or the combination.
• Osteoporosis. It is unclear if oral collagen peptides improve bone mineral density (BMD) in adults with osteoporosis after menopause. Details: In patients with osteoporosis after menopause, clinical research shows that taking collagen peptides 10 grams daily in addition to twice weekly intramuscular calcitonin for 6 months does not improve BMD in the forearm when compared with calcitonin alone (104649). It is unclear if supplementation with collagen peptides improves BMD in the femoral neck or lumbar spine.
• Pressure ulcers. Oral collagen peptides might help to improve ulcer size and healing. Details: A small clinical study in patients with Stage II, III, or IV pressure ulcers shows that taking collagen peptides 5 grams orally three times daily for 8 weeks in addition to standard care improves ulcer size and exudate when compared with placebo and standard care (101612). This study was limited because it only used one scale to assess healing of the pressure ulcer. Another small clinical study in patients with stage II or III pressure ulcers shows that receiving standard care and collagen peptides with high levels of prolyl-hydroxyproline 5 grams twice daily for 16 weeks improves ulcer exudate, healing, and wound size when compared with standard care plus placebo (101620).
• Sarcopenia. Oral collagen peptides might help to increase fat-free mass. However, it is unclear if collagen peptides are more beneficial than other types of protein. Details: A small clinical study in elderly males with sarcopenia shows that taking collagen peptides from type I collagen 15 grams daily for 12 weeks along with three resistance training sessions weekly modestly increases fat-free mass and power when compared with resistance training and placebo (101624). It is unclear if supplementation with collagen peptides is more beneficial than supplementation with protein.
• Sprains. It is unclear if oral collagen peptides improve ankle instability after a previous sprain. Details: A small clinical study in athletes with chronic ankle instability from an ankle sprain shows that taking collagen peptides 5 grams daily for 6 months improves subjective ankle instability when compared with placebo. However, ankle stiffness, which is a more objective measure of ankle instability, is not improved when compared with placebo (101603).
• Tendinopathy. It is unclear if oral collagen peptides improve tendon pain. Details: A small clinical study in patients with Achilles tendinopathy shows that taking a specific collagen peptides supplement (TENDOFORTE, Gelita AG) 2.5 grams daily for 3 months in addition to a calf-strengthening program improves pain when compared with baseline (101615). The validity of this finding is limited by the lack of a comparator group.
• Wound healing. It is unclear if oral collagen peptides improve wound healing. Details: A small clinical study in healthy volunteers with wounds after photothermolysis shows that taking collagen peptides 3 grams daily for 4 weeks improves erythema, skin hydration, and skin elasticity when compared with placebo (101599). This study was limited by small size, short duration, and no direct measurement of wound healing or scar formation.
• Wrinkled skin. Some small clinical studies suggest that oral collagen peptides might help to reduce lines and wrinkles from sun damage. Details: Preliminary clinical research in females with photodamaged skin shows that taking a specific low molecular weight collagen peptide product (Evercollagen, Newtree Co.) 1000 mg daily for 12 weeks modestly improves most measures of skin wrinkling, hydration, and elasticity when compared with placebo. This specific collagen peptide product is standardized to contain more than 15% glycine-containing tripeptides, including 3% glycyl-prolyl-hydroxyproline (100702). Another moderate-sized clinical study in adults with dry and wrinkled eye skin shows that taking low-molecular weight collagen peptides (GPVGPS Collagen, Daehan Chemtech) 2000 mg daily for 12 weeks reduces skin wrinkling parameters including facial skin roughness, peak-to-valley values, maximum wrinkle height, and eye wrinkle volume and improves skin hydration and skin elasticity when compared with placebo. However, there was no improvement in maximum wrinkle depth (112458). Another preliminary clinical study shows that taking a specific combination product (BioCell Collagen, BioCell Technology, LLC) containing collagen peptides from chicken collagen type II 600 mg, low molecular weight hyaluronic acid 100 mg, and chondroitin sulfate 200 mg daily for 12 weeks reduces lines and wrinkles associated with both natural aging and photoaging by about 13% when compared to baseline (28681). This study was limited by the lack of a comparator group. Additionally, it is unclear if these effects are due to collagen peptides, other ingredients, or the combination. More evidence is needed to rate collagen peptides for these uses.

(Read more about COLLAGEN PEPTIDES)

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, short-term. Collagen peptides have been used with apparent safety at doses up to 10 grams daily for up to 6 months and in doses up to 40 grams daily for up to 4 weeks (97632,97635,101615,101621,104638,104643,104644,104647,101622,110667)(114907,115044). PREGNANCY &

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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General ...Orally, collagen peptides seem to be well tolerated.

Dermatologic ...Orally, a case of a mild skin rash has been reported for a patient who used a specific collagen peptide-containing product (BioCell Collagen) (28680).

Gastrointestinal ...Orally, collagen peptides may cause nausea, dyspepsia, diarrhea, and flatulence, but these adverse effects are rare (101622,104639).

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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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