Inosine is a purine ribonucleoside widely found in plants, animals and other forms of living matter. It is comprised of the purine base hypoxanthine and the sugar D-ribose. Inosine has been shown to exert potent effects on the immune, neural, and cardiovascular systems.
Inosine and athletic performance, physical activity,
Promoters claim an inosine supplement has a beneficial effect on overall physical strength and energy during exercise. However, I am not able to find any good studies confirming these claims. In fact, two studies that I found did not show benefit at all supplementation. I list these studies below:
Inosine supplementation has no effect on aerobic or anaerobic cycling performance.
Int J Sport Nutr. 1999. Sports Science Dept., Kingston University, Kingston upon Thames, Surrey, England.
The two basic aims of this study were to add to the limited literature concerning Inosine as an ergogenic aid, and to determine the effects of Inosine supplementation over a period of 5 and 10 days, at a dosage of 10,000 mg.d-1 on measures associated with aerobic and anaerobic performance. Seven trained, volunteer male subjects participated in this study. The subjects completed three test sessions, each comprising three tests. Supplementation was carried out in a random, double-blind manner, and the test sessions were undertaken prior to (Baseline, B), on Day 6, and on Day 11. An analysis of the data indicated no performance benefit of supplementation. Uric acid concentration increased significantly after both Days 6 and 11. It is concluded that Inosine has no ergogenic effects but may cause possible health problems if taken over long periods of time.
Effect of inosine supplementation on aerobic and anaerobic
Med Sci Sports Exercise. 1996. Human Performance Laboratory, Ball State University, Muncie, IN, USA.
Ten competitive male cyclists completed a Wingate Bike Test (WIN), a 30-min self-paced cycling performance bout, and a constant load, supramaximal cycling spring (SPN) to fatigue following 5 d of oral supplementation (5,000 mg.day-1) with inosine and placebo. Findings demonstrate that prolonged inosine supplementation does not appear to improve aerobic performance and short-term power production during cycling and may actually have an ergolytic effect under some test conditions.
Creatine supplementation reduces muscle inosine
monophosphate during endurance exercise in humans.
Med Sci Sports Exercise. 2005.
We hypothesized that creatine supplementation would improve muscle energy balance (as assessed by muscle inosine monophosphate accumulation) during intense endurance exercise. Seven well-trained men completed two experimental trials involving approximately 1 h of intense endurance exercise. Subjects ingested approximately 42 gram per day dextrose for 5 d before the first experimental trial (CON), then approximately 21 g Creatine monohydrate plus approximately 21 g.d dextrose for 5 d before the second experimental trial (CREAT). Creatine supplementation significantly increased muscle total Creatine. No difference was seen between treatments in any measured muscle or blood metabolite after the first 45 min of exercise. Despite the performance ride completion time being similar in the two treatments, inosine monophosphate at the end of the performance ride was significantly lower in CREAT than in CON. Raising muscle total Cr content before exercise appears to improve the ability of the muscle to maintain energy balance during intense aerobic exercise, but not during more moderate exercise intensities.
Brain injury, traumatic
Brain Res. 2014. Inosine improves functional recovery after experimental traumatic brain injury. Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100mg/kg i.p. at 1, 24 and 48h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score, an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze).
J Altern Complement Med. 2009.The treatment of multiple sclerosis with inosine. Markowitz CE, Spitsin S, Zimmerman V, Jacobs D, Udupa JK, Hooper DC, Koprowski H. Neurology Department, University of Pennsylvania, Philadelphia, PA, USA. These data suggest that the use of inosine to raise serum UA levels may have benefits for at least some MS patients. The effect of this treatment is likely to be a consequence of inactivation of peroxynitrite-dependent free radicals.
Q. I'm wondering if you have any information on inosine and its ability to repair peripheral nerve damage or neuropathic conditions. If this is true, what would be the dosage? I read, also, that it can assist in recovery of stroke. Dosage of this, as well.
A. I am not aware of such human studies to determine whether it works for neuropathy and what the dosage would be.
JAMA Neurol. 2014. Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial. To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups. Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD.
Inosine research review and
Inosine Reduces Ischemic Brain Injury in Rats.
Purinergic nucleoside inosine elicits protection and regeneration during various injuries. The purpose of this study was to examine the protective effects of inosine against cerebral ischemia. Adult Sprague-Dawley rats were anesthetized. Inosine, hypoxathine, or vehicle was administered intracerebroventricularly before transient right middle cerebral artery occlusion (MCAo). Animals were placed in behavioral chambers 2 days to 2 weeks after MCAo and then euthanized for tri-phenyl-tetrazolium chloride staining. Stroke animals receiving inosine pretreatment demonstrated a higher level of locomotor activity and less cerebral infarction. Intracerebroventricular administration of the same dose of hypoxanthine did not confer protection. Coadministration of selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) significantly reduced inosine-mediated protection. Inosine did not alter basal glutamate release, nor did it reduce ischemia-evoked glutamate overflow from cerebral cortex. However, inosine antagonized glutamate-induced electrophysiological excitation in cerebral cortical neurons. Inosine inhibits glutamate postsynaptic responses and reduces cerebral infarction. Its protective effect against ischemia/reperfusion-related insults may involve activation of adenosine A3 receptors.
Inosine infusion prevents mortality in endotoxic shock.
J Trauma. 2005.
Substances that inhibit Na/K ATPase activity appear in plasma during severe septic shock causing Na and fluid to move into cells and K to move out, resulting in cell swelling and an elevation of plasma K. These changes contribute to the morbidity of sepsis. Recently, we reported that inosine and other purine nucleosides stimulate Na/K ATPase activity, prolong survival in hemorrhagic shock, and lower the plasma potassium in that condition. Here, we determine whether inosine prolongs survival in lipopolysaccharide-induced sepsis shock. Pentobarbital-anesthetized rats underwent cannulation of a femoral artery and vein, and lipopolysaccharide was injected by intravenous bolus. Rats were than resuscitated with inosine in saline, saline alone, inosine with S-4-nitrobenzyl-6-thioinosine, an equilibrative nucleoside transporter blocker), NBTI alone, or no resuscitation. Inosine significantly and dramatically prolongs survival of rats in endotoxic shock as compared with saline resuscitation or to no resuscitation. Inosine prevents mortality in lipopolysaccharide-induced septic shock in rats. The mechanism of action must be intracellular, as blockers of the equilibrative nucleoside transporter prevented prolonged survival with inosine.
Inosine released after hypoxia activates hepatic
glucose liberation through A3 adenosine receptor.
Am J Physiol Endocrinol Metab. 2005
This work addresses the modulation of intermediary metabolism by inosine through adenosine receptors in isolated rat hepatocytes. We conducted an in silico search in the GenBank and complete genomic sequence databases for additional adenosine / inosine receptors, and for a feasible physiologic role of inosine in homeostasis. Inosine stimulated glycogenolysis, gluconeogenesis, and ureagenesis compared with basal values; these effects were blunted by the selective A3 adenosine receptor (AR) antagonist MRS-1220, but not by selective A1, A2A, and A2B AR antagonists. In addition, MRS-1220 antagonized inosine -induced transient increase (40%) in cytosolic Ca(2+) and enhanced (90%) glycogen phosphorylase activity. Inosine -induced Ca(2+) mobilization was desensitized by adenosine, in a reciprocal manner inosine desensitized adenosine action. Inosine decreased the cAMP pool in hepatocytes when A1, A2A, and A2B AR were blocked by a mixture of selective antagonists. Inosine -promoted metabolic changes were unrelated with cAMP decrease, but were Ca(2+)-dependent because they were absent in hepatocytes incubated in EGTA- or BAPTA-AM-supplemented Ca(2+)-free medium. Based on results obtained, the known higher extracellular inosine levels under ischemic conditions, and inosine's higher sensitivity for stimulating hepatic gluconeogenesis, it is suggested that after tissular ischemia, inosine contributes to maintain homeostasis by releasing glucose from the liver through stimulation of A3 adenosine receptors.
Do you have any information concerning inosine and NEP1-40
ability to activate brain cell growth? Any info would be greatly appreciated.
I have not seen human studies with inosine supplements and NEP1-40.