Dietary Supplements Containing Inosine

Inosine is part of a chemical family called purine nucleotides and acts as a precursor to adenosine, an important molecule for cellular energy. Inosine can be found in brewer's yeast and organ meats, such as liver and kidney, and is available as a supplement in its purified form.

Dietary supplements containing inosine are often marketed with claims for increased energy levels and endurance performance, enhanced adenosine triphosphate (ATP) production, improved heart function, and reduced lactic acid accumulation during intense exercise.

Many of the effects attributed to inosine stem from its potential role in increasing levels of a compound known as 2,3 diphosphoglycerate (DPG) in red blood cells. An enhanced 2,3 DPG level would ease the release of oxygen from the blood cells to the tissues and, in theory, enhance energy generation, promote lactic acid removal, and improve exercise performance overall.

Because there are no convincing studies demonstrating the beneficial effects of inosine as a dietary supplement, it is not recommended as a stand-alone dietary aid. Inosine is commonly contained as part of an overall mixture of ingredients in dietary supplements that may contSeveral studies have investigated the effects of inosine supplementation on aerobic performance in athletes, yet none have shown convincing benefits associated with the supplement. In at least two studies, a potential for inosine to interfere with energy metabolism was suggested, particularly in high-intensity sprint-type events.

Inosine has many possible metabolic roles in the body. Preliminary information suggests that inosine might stimulate axon growth from healthy nerve cells to injured nerve cells in the brain and spinal cord of the central nervous system (Bianchi et al., 1999). It penetrates the cell walls of both cardiac and skeletal muscles, where it promotes the generation of ATP, the energy substance that allows muscles to contract (Febbraio and Dancey, 1999; Norman, 1995). It also serves as a precursor ribute to energy metabolism.

Hypoxanthine, which may be phosphorylated into the nucleotide inosine monophosphate (IMP). IMP is claimed to be an important regulator between adenine and guanine nucleotide synthesis and may lead to the formation of ATP. Increased production of ATP leads to improved respiration and oxygen transport and serves to enhance all athletic performance, whether aerobic or anaerobic in nature. IMP also helps to maintain glycogen breakdown by activating phosphorylase b and increasing the formation of uric acid.

Inosine also contributes to erythrocyte metabolism by promoting the production of 2,3 DPG, which is necessary for die transport of oxygen molecules from the red blood cells to the cell for energy. Both inosine and hypoxanthine are believed to be vasodilating agents, which may enhance blood flow to the heart and skeletal muscles and lead to improvement of various heart conditions (Iwasa et al., 1997; Kipshidze et al, 1978).

A double-blind, placebo-controlled, crossover trial was conducted on 9 highly trained endurance runners to investigate the ergogenic effect of oral inosine supplementation on a 3-mile run time and oxygen uptake (VO2) peak. Each patient underwent four trials, which followed the same protocol and measured three separate tests within each trial: a 13-rninute subrnaximal treadmill warm-up, a 3-mile treadmill run test, and a maximal treadmill run to test VO2 peak. Patients were instructed to prepare for each trial as if preparing for a race. The patients were given 6,000 mg (3 doses of 2,000 mg) of inosine per day for 2 days or matching placebo prior to testing. The last dose was taken within 2 hours of testing. The results showed no significant effect of inosine in the 3-mile treadmill run test or in the maximal VO2 peak test (Williams et al., 1989).

Another randomized, double-blind, placebo-controlled, crossover trial was conducted in 7 healthy male volunteers to evaluate the use of inosine over a period of 5-10 days at a dosage of 10,000 mg/day on measures associated with aerobic and anaerobic performance. All patients completed three trial sessions, which included a series of three stationary cycling performance tests; a 5-6-second sprint, a 30-second sprint, and a 20-minute time trial. These trial sessions were completed prior to the study (at baseline), on days 6 and 11. Patients completed the performance tests after supplementation with inosine (two equal doses taken early morning and late afternoon, dissolved in orange juice) or a placebo. Each trial was separated by a 6-week washout period. The results showed no significant differences for any of the variables measured. It was concluded that inosine has no ergogenic effects, does not improve performance, and may cause possible health problems if taken over long periods (McNaughton et al., 1999).

A similar double-blind, placebo-controlled, crossover trial was performed on. 10 competitive male cyclists. These patients completed a bike test, a 30-minute self-paced cycling performance, and a supramaximal cycling sprint following 5 days of oral supplementation with 5,000 mg/ day of inosine and a matching placebo. The results showed no differences between the inosine and placebo groups within each test performed(Starling et al., 1996). These findings demonstrate that prolonged inosine supplementation does not appear to improve aerobic performance and short-term power production during cycling.

Another 8-week, double-blind, placebo-controlled, crossover trial was conducted to examine the effects of the Coenzyme Athletic Performance System (CAPS) on endurance performance to exhaustion. Eleven highly trained male triathletes were given 3 daily doses of CAPS or a matching placebo for two 4-week periods. CAPS consisted of 100 mg of coenzyme QlO, 500 mg of cytochrome C, 100 mg of inosine, and 200 III of vitamin E. A 4-week washout period separated the two treatment groups. After each treatment period, an exhaustive performance test consisting of a 90-minute treadmill run followed by cycling until exhaustion was performed. The results showed that the mean time to exhaustion and blood parameters for the patients using CAPS were not significantly different from the placebo group. In conclusion, CAPS had no apparent benefit on exercise to exhaustion (Snider et al., 1992).

The overall results obtained from these trials suggest that the anecdotal effects of inosine as stated by athletes and manufacturers hold little weight when tested in the laboratory'-. Therefore, inosine supplementation has no athletic performance benefit and may be detrimental to general health.

According to Japanese researchers, inosine may be used as a treatment for various heart conditions. A study was performed to evaluate the effect of the nucleoside inosine on the intracardiac hemodynamics and the contraction and relaxation of a diseased myocardium. The study included 102 patients with a macrofocal myocardial infarction. Twenty-two patients received inosine by intravenous drip in a single dose of 200 mg in the acute stage of infarction, SO patients were given inosine pills in a daily dose of 800 mg in the restoration period for 1 month, and 20 patients were given a placebo. Comparative appraisal of treatments showed prevailing improvement in die condition of patients treated with inosine. These patients had positive EGG dynamics, increased cardiac output, and decreased peripheral resistance. Inosine achieved maximum effect by 60-90 minutes after the beginning of the infusion (Yabe and Yoshimura, 1981).

Another study administered 200 mg of inosine through a central vein to 16 patients with various cardiac diseases, including effort angina pectoris, myocardial infarction, valvular disease, idiopathic cardiomyopathy, and congenital heart disease. Left ventricular performance was assessed by the time course of various hemodynamic parameters, including ejection fraction. The results demonstrated that inosine caused a significant decrease in pulmonary wedge pressure, left ventricular end-diastolic pressure, and systolic left ventricular pressure. Inosine caused increases in all of the other hemodynamic parameters, such as cardiac output and ejection fraction. Quantitative evaluation disclosed the beneficial effects of inosine on the left ventricular function through the remarkable load-reducing effect and the unequivocal positive inotropic effects (Iwasa et al., 1997). In general, supplemental inosine appears to be safe at doses of as much as 5-6 g for several weeks. In susceptible people, however, inosine supplementation may lead to buildup of uric acid levels. Uric acid is a byproduct of inosine metabolism and may lead to painful symptoms of gout, such as arthritic joints and toes caused by deposits of uric acid crystals.

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