Life Extension Magazine®

Issue: Sep 2003

Creatine, Cholesterol, Serrapeptase, Sun Damage

Scientifically reviewed by: Dr. Gary Gonzalez, MD, on January 2021.


Health implications of creatine: can oral creatine supplementation protect against neurological and atherosclerotic disease?
Major achievements made over the last several years have highlighted the important roles of creatine and the creatine kinase reaction in health and disease. Inborn errors of metabolism have been identified in the three main steps involved in creatine metabolism: arginine:glycine amidinotransferase (AGAT), S-adenosyllmethionine:N-guanidinoacetate methyltransferase (GAMT) and the creatine transporter. All these diseases are characterized by a lack of creatine and phosphorylcreatine in the brain, and by (severe) mental retardation. Similarly, knockout mice lacking the brain cytosolic and mitochondrial isoenzymes of creatine kinase displayed a slightly increased creatine concentration, but no phosphorylcreatine in the brain. These mice revealed decreased weight gain and reduced life expectancy, disturbed fat metabolism, behavioral abnormalities and impaired learning capacity. Oral creatine supplementation improved the clinical symptoms in both AGAT and GAMT deficiency, but not in creatine transporter deficiency. In addition, creatine supplementation displayed neuroprotective effects in several animal models of neurological disease, such as Huntington’s disease, Parkinson’s disease or amyotrophic lateral sclerosis. All these findings pinpoint to a close correlation between the functional capacity of the creatine kinase/phosphorylcreatine/creatine system and proper brain function. They also offer a starting-point for novel means of delaying neurodegenerative disease, and/or for strengthening memory function and intellectual capabilities. Finally, creatine biosynthesis has been postulated as a major effector of homocysteine concentration in the plasma, which has been identified as an independent graded risk factor for atherosclerotic disease. By decreasing homocysteine production, oral creatine supplementation may, thus, also lower the risk for developing, e.g., coronary heart disease or cerebrovascular disease. Although compelling, these results require further confirmation in clinical studies in humans, together with a thorough evaluation of the safety of oral creatine supplementation.

Neuroscience 2002;112(2):243-60.

Methylation demand and homocysteine metabolism: effects of dietary provision of creatine and guanidinoacetate.
S-adenosylmethionine, formed by the adenylation of methionine via S-adenosylmethionine synthase, is the methyl donor in virtually all known biological methylations. These methylation reactions produce a methylated substrate and S-adenosylhomocysteine, which is subsequently metabolized to homocysteine. The methylation of guanidinoacetate to form creatine consumes more methyl groups than all other methylation reactions combined. Therefore, we examined the effects of increased or decreased methyl demand by these physiological substrates on plasma homocysteine by feeding rats guanidinoacetate- or creatine-supplemented diets for two week. Plasma homocysteine was significantly increased (~50%) in rats maintained on guanidinoacetate-supplemented diets, whereas rats maintained on creatine-supplemented diets exhibited a significantly lower (~25%) plasma homocysteine level. Plasma creatine and muscle total creatine were significantly increased in rats fed the creatine-supplemented or guanidinoacetate-supplemented diets. The activity of kidney L-arginine:glycine amidinotransferase, the enzyme catalyzing the synthesis of guanidinoacetate, was significantly decreased in both supplementation groups. To examine the role of the liver in mediating these changes in plasma homocysteine, isolated rat hepatocytes were incubated with methionine in the presence and absence of guanidinoacetate and creatine, and homocysteine export was measured. Homocysteine export was significantly increased in the presence of guanidinoacetate. Creatine, however, was without effect. These results suggest that homocysteine metabolism is sensitive to methylation demand imposed by physiological substrates.

Am J Physiol Endocrinol Metab 2001 Nov;281(5):E1095-100

Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia.
OBJECTIVE: To investigate the metabolic and functional status of muscles of fibromyalgia (FM) patients, using P-31 magnetic resonance spectroscopy (MRS). METHODS: Twelve patients with FM and 11 healthy subjects were studied. Clinical status was assessed by questionnaire. Biochemical status of muscle was evaluated with P-31 MRS by determining concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), ATP and phosphodiesters during rest and exercise. Functional status was evaluated from the PCr/Pi ratio, phosphorylation potential (PP) and total oxidative capacity (Vmax). RESULTS: Patients with FM reported greater difficulty in performing activities of daily living as well as increased pain, fatigue and weakness compared with controls. MRS measurements showed that patients had significantly lower than normal PCr and ATP levels (P < 0.004) and PCr/Pi ratios (P < 0.04) in the quadriceps muscles during rest. Values for PP and Vmax also were significantly reduced during rest and exercise. CONCLUSION: P-31 MRS provides objective evidence for metabolic abnormalities consistent with weakness and fatigue in patients with FM. Noninvasive P-31 MRS may be useful in assessing clinical status and evaluating the effectiveness of treatment regimens in FM.

Arthritis Rheum 1998 Mar;41(3):406-13.

Creatine supplementation and health variables: a retrospective study.
PURPOSE: Long-term safety of creatine supplementation has been questioned. This retrospective study was performed to examine markers related to health, the incidence of reported side effects and the perceived training benefits in athletes supplementing with creatine monohydrate. METHODS: Twenty-six athletes (18 M and 8 F, 24.7 +/- 9.2 y; 82.4 +/- 20.0 kg; 176.5 +/- 8.8 cm) from various sports were used as subjects. Blood was collected between 7:00 and 8:30 a.m. after a 12-hour fast. Standard clinical examination was performed for CBC and 27 blood chemistries. Testosterone, cortisol and growth hormone were analyzed using an ELISA. Subjects answered a questionnaire on dietary habits, creatine supplementation, medical history, training history and perceived effects of supplementation. Body mass was measured using a medical scale, body composition was estimated using skinfolds and resting heart rate and blood pressure were recorded. Subjects were grouped by supplementation length or no use: Gp1 (control) = no use (N = 7; 3 F, 4 M); Gp2 = 0.8-1.0 yr (N = 9; 2 F, 7 M); and Gp3 = 1(+) (N = 10; 3 F, 7 M). RESULTS: Creatine supplementation ranged from 0.8--four year. Mean loading dose for Gp2 and Gp3 was 13.7 +/- 10.0 and the maintenance dose was 9.7 +/- 5.7 g.d(-)1. Group differences were analyzed using one-way ANOVA. CONCLUSIONS: Expected gender differences were observed. Of the comparisons made among supplementation groups, only two differences for creatinine and total protein (P < 0.05) were noted. All group means fell within normal clinical ranges. There were no differences in the reported incidence of muscle injury, cramps or other side effects. These data suggest that long-term creatine supplementation does not result in adverse health effects.

Med Sci Sports Exerc 2001 Feb;33(2):183-8

Adverse effects of creatine supplementation: fact or fiction?
The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by one to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well-controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (four weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (five days), medium term (nine weeks) and long term (up to five years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.

Sports Med 2000 Sep;30(3):155-70.

American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation.
Creatine (Cr) supplementation has become a common practice among professional, elite, collegiate, amateur and recreational athletes with the expectation of enhancing exercise performance. Research indicates that Cr supplementation can increase muscle phosphocreatine (PCr) content, but not in all individuals. A high dose of 20 g x d(-1) that is common to many research studies is not necessary, as 3 g x d(-1) will achieve the same increase in PCr given time. Coincident ingestion of carbohydrate with Cr may increase muscle uptake; however, the procedure requires a large amount of carbohydrate. Exercise performance involving short periods of extremely powerful activity can be enhanced, especially during repeated bouts of activity. This is in keeping with the theoretical importance of an elevated PCr content in skeletal muscle. Cr supplementation does not increase maximal isometric strength, the rate of maximal force production, nor aerobic exercise performance. Most of the evidence has been obtained from healthy young adult male subjects with mixed athletic ability and training status. Less research information is available related to the alterations due to age and gender. Cr supplementation leads to weight gain within the first few days, likely due to water retention related to Cr uptake in the muscle. Cr supplementation is associated with an enhanced accrual of strength in strength-training programs, a response not independent from the initial weight gain, but may be related to a greater volume and intensity of training that can be achieved. There is no definitive evidence that Cr supplementation causes gastrointestinal, renal and/or muscle cramping complications. The potential acute effects of high-dose Cr supplementation on body fluid balance has not been fully investigated, and ingestion of Cr before or during exercise is not recommended. There is evidence that medical use of Cr supplementation is warranted in certain patients (e.g.. neuromuscular disease); future research may establish its potential usefulness in other medical applications. Although Cr supplementation exhibits small but significant physiological and performance changes, the increases in performance are realized during very specific exercise conditions. This suggests that the apparent high expectations for performance enhancement, evident by the extensive use of Cr supplementation, are inordinate.

Med Sci Sports Exerc. 2000 Mar;32(3):706-17

Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine or CK activity in men and women.
Creatine monohydrate (CrM) administration may enhance high intensity exercise performance and increase body mass, yet few studies have examined for potential adverse effects, and no studies have directly considered potential gender differences. PURPOSE: The purpose of this study was to examine the effect of acute creatine supplementation upon total and lean mass and to determine potential side effects in both men and women. METHODS: The effect of acute CrM (20 g x d(-1) x 5 d) administration upon systolic, diastolic and mean BP, plasma creatinine, plasma CK activity, and body composition was examined in 15 men and 15 women in a randomized, double-blind experiment. Additionally, ischemic isometric handgrip strength was measured before and after CrM or placebo (PL). RESULTS: CrM did not affect blood pressure, plasma creatinine, estimated creatinine clearance, plasma CK activity or handgrip strength (P < 0.05). In contrast, CrM significantly increased fat-free mass (FFM) and total body mass (P < 0.05) as compared with PL, with no changes in body fat. The observed mass changes were greater for men versus women. CONCLUSIONS: These findings suggest that acute CrM administration does not affect blood pressure, renal function or plasma CK activity, but increases FFM. The effect of CrM upon FFM may be greater in men as compared with that in women.

Med Sci Sports Exerc 2000 Feb;32(2):291-6

Creatine supplementation does not affect kidney function in an animal model with pre-existing renal failure.
BACKGROUND: Creatine is widely used as an ergogenic substance among athletes. Safety of prolonged creatine intake has been questioned, based upon case reports and animal data. We investigated the effect of prolonged creatine ingestion on renal function in animals with normal kidney function or pre-existing kidney failure, respectively. METHODS: Male Wistar rats were randomly allocated to four experimental groups: (i) sham-operated, control diet; (ii) sham-operated, creatine-supplemented diet (2% w/w (0.9+/-0.2 g creatine/kg body weight/day)); (iii) two-thirds nephrectomized, control diet; and (iv) two-thirds nephrectomized, creatine supplemented diet. Glomerular filtration rate was determined using inulin and creatinine clearance, together with albumin excretion, urea clearance, muscle and serum creatine and serum cystatin C concentrations. RESULTS: In contrast to previous reports, no detrimental effects of creatine supplementation on the renal function indices were observed in two-thirds nephrectomized or sham-operated animals. No differences were observed in inulin (0.28+/-0.08 vs 0.25+/-0.08 ml/min/100 g; P=NS) or creatinine clearance rates. Serum cystatin C concentration, urinary protein excretion and albumin and urea clearance were comparable between creatine-supplemented and control-diet fed animals in both sham-operated and two-thirds nephrectomized animals. Serum creatine and intramuscular total creatine concentrations were higher in creatine-supplemented groups (P<0.05). CONCLUSIONS: Creatine supplementation at a dosage of 2% w/w for four weeks does not impair kidney function in animals with pre-existing renal failure or in control animals.

Nephrol Dial Transplant 2003 Feb;18(2):258-64


Statins and risk of polyneuropathy: a case-control study.
BACKGROUND: Several case reports and a single epidemiologic study indicate that use of statins occasionally may have a deleterious effect on the peripheral nervous system. The authors therefore performed a population-based study to estimate the relative risk of idiopathic polyneuropathy in users of statins. METHOD: The authors used a population-based patient registry to identify first-time-ever cases of idiopathic polyneuropathy registered in the five-year period 1994 to 1998. For each case, validated according to predefined criteria, 25 control subjects were randomly selected among subjects from the background population matched for age, sex and calendar time. The authors used a prescription register to assess exposure to drugs and estimated the odds ratio of use of statins (ever and current use) in cases of idiopathic polyneuropathy compared with control subjects. RESULTS: The authors verified a diagnosis of idiopathic polyneuropathy in 166 cases. The cases were classified as definite (35), probable (54) or possible (77). The odds ratio linking idiopathic polyneuropathy with statin use was 3.7 (95% CI 1.8 to 7.6) for all cases and 14.2 (5.3 to 38.0) for definite cases. The corresponding odds ratios in current users were 4.6 (2.1 to 10.0) for all cases and 16.1 (5.7 to 45.4) for definite cases. For patients treated with statins for two or more years the odds ratio of definite idiopathic polyneuropathy was 26.4 (7.8 to 45.4). CONCLUSIONS: Long-term exposure to statins may substantially increase the risk of polyneuropathy.

Neurology 2002 May 14;58(9):1333-7

A new approach to cholesterol.
Although much is known about hypercholesterolemia and the associated risk for the development of atherosclerosis, very little research has focused on altered cholesterol biosynthesis. Recent discovery that the biochemical basis for the human malformation syndrome, Smith-Lemli-Opitz syndrome appears to lie in altered cholesterol biosynthesis has changed this situation. Cholesterol has an extraordinary important functions in organism. Recommendations to lower serum cholesterol are widespread, yet low serum cholesterol is associated with poorly understood morbidity. Cholesterol is still an enigmatic, essential metabolite and much remains to learn about it.

Cas Lek Cesk 2001 Nov 8;140(22):685-7

Fatal rhabdomyolysis caused by cerivastatin.
Cerivastatin was recently withdrawn from the market after the report of more than 30 deaths in the United States among patients receiving a combination of cerivastatin and gemfibrozil, a fibrate which is no longer on the Belgian market. The cause of death was attributed to severe rhabdomyolysis. Cases were also reported among patients treated by cerivastatin only. Recommendations for better use of lipid-lowering drugs are given in order to optimize the benefit/risk ratio of such treatment.

Rev Med Liege 2001 Aug;56(8):592-4.

New criteria of normal serum lipid levels in Japanese children: the nationwide study.
AIM: To make new criteria of serum lipid levels in current Japanese children using the large nationwide data provided from Japan Association of Health Service for the analysis. METHODS: The subjects were schoolchildren who received screening and care programs for lifestyle related diseases since 1993 to 1999. Serum total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and triglyceride (TG) levels were measured, and low-density lipoprotein cholesterol (LDLC) levels were calculated. Serum lipid levels were analyzed by age and sex. For each serum lipid, we extracted age- and sex-specific group which the mean value was not statistically different from that in 1999 by Student’s t-test analysis. RESULTS: The level below the 75th percentile was defined to be acceptable, from the 75th to 95th to be borderline and over the 95th to be high in TC/LDLC. The level below the fifth percentile in HDLC was defined to be low and the level over the 95th percentile in TG to be high. Therefore, TC level was categorized as follows: acceptable < 190 mg/dL; borderline 190 to 219 mg/dL; and high > 220 mg/dL. The LDLC level was also categorized into: acceptable < 110 mg/dL; borderline 110 to 139 mg/dL; and high > 140 mg/dL. The cut-off value in TG was determined to be 140 mg/dL and in HDLC was 40 mg/dL. CONCLUSIONS: This new criteria should prove valuable in health strategies for rational prevention and intervention in children. It should be emphasized to provide some intervention for Japanese children immediately.

Pediatr Int 2002 Dec;44(6):596-601.

Hormone replacement therapy in postmenopausal women and its effects on plasma lipid levels.
Postmenopausal women run the same risks of coronary heart disease as men. The lipid alterations observed at this time reflect increased blood levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a), and reduced high-density lipoprotein cholesterol (HDL-C) levels. These changes lead to a higher risk of coronary artery disease, and hormonal therapy has a favorable effect on lipid metabolism. In this paper we review the literature on hormone replacement therapy (HRT) in postmenopausal women with the emphasis on the role of lipids in the pathogenesis of coronary heart disease, and on the action of estrogens and their correlation with progestogens, as well as routes of HRT administration. We conclude that the HRT changes the lipid profile in a potentially anti-atherogenic direction, usually reducing LDL-C and increasing HDL-C and triglycerides. Otherwise, for postmenopausal women with established coronary disease HRT is not recommended.

Clin Chem Lab Med 2002 May;40(5):446-51.

Hypocholesterolemia during mixed manic episodes.
BACKGROUND: An association of relatively low serum cholesterol with both depression and suicide has been reported. Depressive symptoms, including suicidality, are defining features of mixed mania. Few studies have considered differences in cholesterol levels in subjects during mixed bipolar episodes. METHODS: Fasting serum cholesterol levels obtained from 174 subjects evaluated during mixed and pure manic episodes were compared using ANOVA statistics. Sex was included in the analysis and age was used as a covariate. Cholesterol levels in the total manic cohort and in the mixed and pure manic subgroups were compared with national norms. RESULTS: Fasting serum cholesterol levels were lower in the mixed manic subtype compared to the pure manic subtype. As expected, cholesterol levels increased with age. No differences were noted between males and females. Cholesterol levels were lower in both the mixed and pure manic subtypes when compared with national norms. CONCLUSION: Fasting serum cholesterol levels are low in manic patients, especially during mixed bipolar episodes. Cholesterol, which has been reported to be a negative acute phase reactant, may be lower during mixed states as a result of an immune activation.

Eur Arch Psychiatry Clin Neurosci 2002 Jun;252(3):110-4

The cholesterol controversy.
OBJECTIVE: To provide information about the controversy associated with lowering of cholesterol concentrations to prevent coronary heart disease (CHD). DATA SOURCES: Studies, review articles and editorials identified from MEDLINE searches (from 1966 to 1995) and bibliographies of identified articles. STUDY SELECTION: Studies, review articles and editorials addressing controversial issues related to cholesterol lowering. DATA EXTRACTION: Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS: Hypercholesterolemia is a well-known CHD risk factor. Reduction of serum cholesterol concentrations has been shown to reduce the incidence of CHD. Unfortunately, cholesterol lowering also appears to increase the risk for cancer, accidental and violent death, stroke and oddly enough, CHD when certain medications are used. CONCLUSIONS: Significant reductions in serum cholesterol concentrations can be achieved with cholesterol-lowering interventions. However, the benefits associated with cholesterol reduction may not outweigh the risks in all patients with hypercholesterolemia. Cholesterol-lowering interventions should be recommended with caution in patients at increased risk of cancer, stroke and depression. Caution should also be used when recommending fibric acid derivatives for patients with existing CHD.

Ann Pharmacother 1996 May;30(5):495-500

Cardiovascular disease: a historic perspective.
Cardiovascular disease (CVD) is the leading cause of death and disability in the United States and in most industrialized nations. Major breakthroughs to modern day cardiovascular/lipid research have been attributed to the findings of the Framingham Heart Study and Gofman and colleagues who made associations between lipoprotein levels (LDL, VLDL and HDL) and CVD. Unfortunately, half of all CVD patients have none of the established coronary risk factors (hypertension, hypercholesterolemia, cigarette smoking, diabetes mellitus, obesity) and new strategies for identifying patients need be considered. Although there remains little disagreement regarding the necessity to lower elevated plasma cholesterol levels, there remains much controversy regarding appropriate dietary means of accomplishing this goal. The National Cholesterol Education Program (1993) proposed a dietary reduction (Step I and Step II diets) to the percent saturated fat and cholesterol consumed by at-risk patients. Many currently question the effectiveness of these diets. An alternative diet, replacing saturated fats by monounsaturated fats (olive oil), has attracted recent attention. While diet modification is considered the foundation of primary treatment, other interventions are frequently required. Although early drug trials demonstrated that agents such as nicotinic acid, clofibrate, gemfibrozil, bile acid-binding resins generally slowed progression of atherosclerotic lesions, lowered plasma cholesterol levels and decreased mortality from CVD, the greatest advance to current drug therapy involved the discovery of the “statins” (HMG-CoA reductase inhibitors). In the current work, mechanisms for vascular dysfunction resulting in myocardial ischemia were explored and potential nutritional (dietary) and pharmacologic interventions were reviewed.

Jpn J Vet Res 2000 Nov;48(2-3):147-66.


Serrapeptase-induced lung injury manifesting as acute eosiniphilic pneumonia.
An 84-year-old man was referred to our hospital because of fever, cough and hemoptysis. The patient had acute respiratory failure (PaO2 < 40 mmHg) on admission, with diffuse interstitial infiltration and bilateral pleural effusion. The bronchoalveolar lavage fluid was bloody, and contained a high percentage of eosinophils (32%). A diagnosis of acute eosinophilic pneumonia was established, and the patient made a rapid recovery after corticosteroids were administered. When the DLST (drug lymphocyte stimulation test) was performed after the corticosteroid therapy was stopped, it was positive for serrapeptase, which had been prescribed for chronic cystitis for three months before the onset of the pneumonia. This was a case of drug (serrapeptase)-induced pneumonitis manifesting as acute eosinophilic pneumonia.

Nihon Kokyuki Gakkai Zasshi. 2000 Jul;38(7):540-4.

The treatment of breast engorgement with Serrapeptase (Danzen): a randomised double-blind controlled trial.
We evaluated an anti-inflammatory enzyme drug Danzen (Serrapeptase: Takeda Chemical Industries, Ltd.) on 70 patients complaining of breast engorgement. These patients were randomly divided into two groups, a treatment group and a placebo group. A single observer, unaware of the group the patients were in, assessed the severity of each of the symptoms and signs of breast engorgement before treatment was commenced, and daily for three days, during which therapy was administered. Danzen was noted to be superior to placebo for improvement of breast pain, breast swelling and induration, and while 85.7% of the patients receiving Danzen had “Moderate to Marked” improvement, only 60.0% of the patients receiving placebo had a similar degree of improvement. “Marked” improvement was found in 22.9% of the treatment group and 2.9% of the placebo group. These differences were statistically significant (P less than 0.05). No adverse reactions were reported with the use of Danzen. Danzen is a safe and effective method for the treatment of breast engorgement.

Singapore Med J 1989 Feb;30(1):48-54.

A preliminary trial of serratiopeptidase in patients with carpal tunnel syndrome.
OBJECTIVES: This study was planned to assess the response of serratiopeptidase in patients with carpal tunnel syndrome (CTS). METHODS: Twenty patients with CTS were evaluated clinically. After baseline electrophysiological studies, these patients were given serratiopeptidase 10 mg twice daily with initial short course of nimesulide. Clinical and electrophysiological reassessment was done after six weeks. RESULTS: Mean age was 43.9 years with male to female ratio of 1:2.33. Sixty five percent cases showed significant clinical improvement which was supported by significant improvement in electrophysiological parameters. Recurrence was reported in four cases. No significant side effect was observed. CONCLUSIONS: Serratiopeptidase therapy may proved to be a useful alternative mode of conservative treatment. Larger study may be further helpful to establish the role of serratiopeptidase in CTS.

J Assoc Physicians India 1999 Dec;47(12):1170-2.

A multi-center, double-blind study of serrapeptase versus placebo in post-antrotomy buccal swelling.
A multi-center, double-blind, placebo-controlled trial was carried out to investigate the clinical efficacy of the anti-inflammatory enzyme serrapeptase in a total of 174 patients who underwent Caldwell-Luc antrotomy for chronic empyema. Eighty-eight patients received 10 mg serrapeptase three times on the day before operation, once on the night of the operation and three times daily for five days after operation; the other 86 received placebo. Changes in buccal swelling after operation were observed as a parameter of the response to treatment. The degree of swelling in the serrapeptase-treated patients was significantly less than that in the placebo-treated patients at every point of observation after operation up to the fifth day (p less than 0.01 to p less than 0.05). Maximal swelling throughout all the post-operative points of observation was also significantly smaller in size in the serrapeptase-treated group than in the placebo-treated group. No side effects were reported.

Pharmatherapeutica 1984;3(8):526-30

Evaluation of Serratia peptidase in acute or chronic inflammation of otorhinolaryngology pathology: a multicentre, double-blind, randomized trial versus placebo.
The efficacy and tolerability of Serratia peptidase were evaluated in a multicentre, double-blind, placebo-controlled study of 193 subjects suffering from acute or chronic ear, nose or throat disorders. Treatment lasted seven to eight days, with the drug or placebo being administered at a rate of two tablets three times a day. After three to four days’ treatment, significant symptom regression was observed in peptidase-treated patients. There was also a significant reduction in symptoms after seven to eight days for patients in both treatment groups but the response was more marked in those patients receiving the active drug. Statistical comparison between the two groups confirmed the greater efficacy and rapid action of the peptidase against all the symptoms examined at both stages. Tolerance was found to be very good and similar for both groups. It is concluded that Serratia peptidase has anti-inflammatory, anti-oedemic and fibrinolytic activity and acts rapidly on localized inflammation.

J Int Med Res 1990 Sep-Oct;18(5):379-88.

Sun damage