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Inosine

Also known as: Inosine, Hypoxanthine riboside, Inosine monophosphate (IMP) precursor

Overview

Inosine is a nucleoside composed of hypoxanthine and ribose, naturally found in tissues and obtainable from organ meats and some fish. Primarily, it's used to elevate serum urate levels, explored for neuroprotective effects, particularly in Parkinson's disease. It's also investigated for immunomodulatory and antidepressant properties. Inosine metabolizes to uric acid, potentially offering antioxidant benefits. Administered orally, it's titrated to achieve specific serum urate levels. Research is moderately mature, with RCTs and follow-up studies, especially in Parkinson's. Evidence quality is generally high, but larger, longer-term studies are needed to fully understand long-term effects and benefits. Inosine interacts with purine metabolism, influencing uric acid levels and potentially the gut microbiota.

Benefits

Inosine's primary researched benefit is its ability to elevate serum urate levels, explored for potential neuroprotective effects in Parkinson's disease. However, clinical trials haven't shown significant slowing of Parkinson's symptom progression. A JAMA study showed inosine significantly increased serum urate (2.03 mg/dL) but didn't significantly slow clinical progression. Secondary benefits include ameliorating depressive and anxiety-like behaviors in animal models. Inosine improved sucrose preference and reduced anxiety-like behaviors in mice in a chronic unpredictable mild stress model. While it didn't slow disease progression, inosine was generally safe and well-tolerated in Parkinson's patients, showing a trend towards slower mood changes.

How it works

Inosine is metabolized into hypoxanthine, which is then converted to uric acid. Uric acid can act as an antioxidant, potentially providing neuroprotection. Inosine interacts with the purine metabolism pathway, leading to increased uric acid levels. Animal studies suggest it may also influence the gut microbiota. While the exact molecular targets of inosine are not fully elucidated, its effects on uric acid levels suggest involvement in antioxidant pathways and potentially in neuroprotective mechanisms. Inosine is administered orally and is well-absorbed, with significant increases in serum urate levels achievable through titrated dosing.

Side effects

Inosine is generally safe and well-tolerated, but it can cause some adverse effects. A common side effect is an increased risk of kidney stones. Inosine treatment is associated with an increased risk of kidney stones (7.0 vs 1.4 stones per 100 patient-years). Serious adverse events, including cardiovascular events, occurred, but they were not more frequent in the inosine groups compared to placebo. Caution is advised in individuals with a history of gout due to the urate-elevating effects of inosine. There is limited data on the use of inosine in pregnant or lactating women, and thus it should be used with caution. There are no well-documented drug interactions, but caution should be exercised when using inosine with medications that affect uric acid levels or kidney function.

Dosage

The minimum effective dose for elevating serum urate levels is not well-defined, but doses of up to 500 mg three times daily have been used in clinical trials. Optimal dosing involves titrating to achieve serum urate levels between 7.1 and 8.0 mg/dL, which can be achieved with doses up to 2 capsules (1000 mg) three times daily. The maximum safe dose is not explicitly defined, but doses up to 3000 mg per day have been used without significant adverse effects in clinical trials. Dosing should be adjusted based on serum urate levels, typically measured before the first daily dose. Inosine is typically administered orally in capsule form.

FAQs

Is inosine safe for people with kidney problems?

Inosine treatment is associated with an increased risk of kidney stones, so monitoring and adequate hydration are recommended. Individuals with pre-existing kidney conditions should consult their healthcare provider before use.

Can inosine help slow down Parkinson's disease?

While inosine elevates serum urate levels, studies have not shown that it significantly slows the clinical progression of Parkinson's disease. It may offer some mood benefits, but further research is needed.

How often should I monitor my urate levels when taking inosine?

Regular monitoring of serum urate levels is necessary to maintain target levels. Dosing should be adjusted based on these levels, typically measured before the first daily dose, as directed by your healthcare provider.

Is inosine safe for people with gout?

Caution is advised in individuals with a history of gout due to the urate-elevating effects of inosine. Consult with a healthcare provider before use.

Research Sources

https://jamanetwork.com/journals/jama/fullarticle/2784144 – This randomized clinical trial with 273 participants with early Parkinson's disease found that inosine significantly elevated serum urate levels over 24 months. However, it did not slow the clinical progression of Parkinson's disease as measured by the MDS-UPDRS score, leading to the study being closed early due to a prespecified interim futility analysis.
https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.697640/full – This animal study investigated the impact of inosine on chronic unpredictable mild stress-induced depressive and anxiety-like behaviors in mice. The study found that inosine improved depressive and anxiety-like behaviors and altered gut microbiota. These findings suggest a potential link between inosine, gut health, and mental well-being, though further research is needed to confirm these effects in humans.
https://jamanetwork.com/journals/jamaneurology/fullarticle/1790169 – This randomized clinical trial evaluated the safety, tolerability, and efficacy of inosine in raising serum and cerebrospinal fluid urate levels in participants with early Parkinson's disease. The study found that inosine was safe, tolerable, and effective in raising urate levels. However, it did not demonstrate significant clinical benefits in terms of disease progression.