Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU

Korean paper: Urolithin A prevents age-related hearing loss in C57BL/6J mice likely by inducing mitophagy 2024

Urolithin A (UA) prevents hearing decline with aging and preserves mitochondria in the auditory system.
UA effectively induces mitophagy and preserves molecules associated with mitochondrial metabolism in the auditory system.
UA can be used as a potential preventive agent by activating mitophagy against age-related hearing loss.

Are rodent models good for hearing loss?

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Urolithin A has been very helpful to me. At the end of last year, I experienced sudden hearing loss in my right ear, with low-frequency hearing impairment. Although I later recovered, the sounds I heard remained distorted. After taking Time line Urolithin A for two months, I have almost fully recovered

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Incredible! Did you take it for this purpose? Is it known to improve hearing (besides the recent article shared)? How much did you take? Daily?

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I take 500mg of Urolithin A on an empty stomach every morning. In the first month, I often felt fatigued around noon and in the afternoon, so I would lie down to rest for a while. However, after about two months, that fatigue disappeared, and now I feel great. Due to work, my sleep time is often shortened, but whenever I wake up, I feel energized throughout the entire day.

Ah I experienced this whenever I tried Urolithin A. That urge to have a nap around 2 pm was weird. So I stopped taking it. But it might be that it is doing its work as suggested earlier by @John_Hemming :thinking:

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I think it is a timing of autophagy. I think autophagy has two effects that can be felt
a) Less energy whilst it is happening (not surprising as the recycled mitochondria will not be replaced immediately)
b) A disruption of sleep. (in that it disrupts circadian proteins).

As an interesting test I have just taken two mitopure UA sachets with a total of 1g of UA. Making reasonable assumptions about the half life and effect of GFJ I am perhaps in a state equivalent to taking 20mg of Rapamycin (enteric coated, but without accelerator) today.

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By the way, why on an empty stomach? Mitopure recommends with the first meal: Timeline Longevity on Instagram: "Whenā€™s the best time to take MitopureĀ®? šŸ•• ā  ā  Digestion slows down at night to give your body a chance to repair itself from the dayā€™s stress. Taking MitopureĀ® with your first meal of the day ensures maximum absorption. (We like ours with a breakfast smoothie or cup of coffee. šŸ˜‰)ā  ā  When do you take MitopureĀ®?ā  #timelinelongevity #longevity #healthyaging #mitopure #cellularhealth #wellnesstips"

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Thank you for providing this information. I indeed take it on an empty stomach in the morning and have achieved the expected results. I will consider the suggestion provided by the official source to take it with food. Thank you!

If it is good for hearing loss, it can probably be good for tinnitus as well. Many people complain of tinnitus and unfortunately there is no known effective cure.

Itā€™s still questionable and very very expensive. I was lucky enough to be able to test for almost 12 months. What did I feel? ā€¦ Nothing. No difference also in my blood test.
I consider myself a healthy person, so maybe this is the point. Itā€™s probably very low gains.

But I do see and read several good papers about it.

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After researching UA and seeing how costly Mitopure was i purchased UA made by Neurogan in the USAā€¦ 700 mg per servingā€¦ 42,000mg per bottle. It gave me incredible energy but I had to stop taking it because of incredible insomnia. I felt like i never had to sleep again! Not good for me and i wanted to see if it could stave off dry macular degeneration. I am going to try rapa next since it has good results in mouse studies. There is only recently approved injections for dry AMD turning into geographic atrophy and doctors are reluctant to give them since the side effects are numerous and could cause total blindness.

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UA is thought to be an mTOR inhibitor. It has a half life of 17-22 hours. I wonder, therefore, if it causes similar effects to Rapamycin on blood glucose, lipids and the immune system. I am tempted to try this out using a highish dose of UA whilst wearing a CGM to see if anything shifts. If its mode of action is via mTOR it is clearly quite a bit weaker given dosing, but it is probably synergistic.

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Iā€™m always looking for more energy, so Iā€™m going to give the Neurogan version a shot. Thanks for the referral.

Chinese paper: Assessment of Urolithin A effects on muscle endurance, strength, inflammation, oxidative stress, and protein metabolism in male athletes with resistance training: an 8-week randomized, double-blind, placebo-controlled study 2024

We recruited twenty male individuals for this study (average age: 24.1 Ā± 1.59 years, average height: 177.4 Ā± 5.92 cm, average weight: 84.55 Ā± 2.72 kg, average training experience: 4.40 Ā± 1. 07 years), all of whom had engaged in long-term resistance training.
Participants were instructed to consume two capsules of UA(Mitopure, USA) daily(1 g/ day), each containing 250 mg of UA, after both breakfast and dinner on a daily basis.
After 8 weeks of UA supplementation, compared to baseline measurements, the UA group exhibited increases in 1RM bench press and squat, although these changes were not statistically significant (Ī” = 3.00 Ā± 0.17 kg, p = 0.051, Ī” = 1.35 Ā± 2.73 kg, p = 0.499). However, significant improvements were noted in Maximum Voluntary Isometric Contraction (MVIC) and repetitions to failure (RTF) performance (Ī” = 36.10 Ā± 0.62 NM, p = 0.000; Ī” = 2.00 Ā± 0.56, p = 0.001). When compared to the placebo group, the UA supplementation for 8 weeks led to an increase in 1RM bench press and squat, although statistical significance was not reached (Ī” = 3.50 Ā± 0.79 kg, p = 0.462; Ī” = 2.55 Ā± 1.36 kg, p = 0.710). Furthermore, the group receiving UA supplementation, compared to the placebo group, showed significant improvements in MVIC and RTF (Ī” = 43.50 Ā± 0.77 NM, p = 0.048; Ī” = 2.00 Ā± 1.22, p = 0.011), indicating that the UA group exhibited superior performance enhancements in these metrics compared to the placebo group. After 8 weeks of UA supplementation, the UA group showed a significant decrease in 3-methylhistidine (3-MH) compared to baseline measurement (Ī”=-2.38 Ā± 1.96 Ī¼mol/L, p = 0.049). Additionally, the UA group exhibited a significant increase in C-reactive protein (CRP) compared to baseline (Ī” = 0.71 Ā± 0.21 mg/L, p = 0.001). However, there was no significant changes observed in Interleukin-6 (IL-6) (Ī”=-1.00 Ā± 1.01 pg/mL, p = 0.076), or superoxide dismutase (SOD) (Ī”=-0.004 Ā± 0.72 U/mL, p = 0.996) compared to baseline in the UA group. When compared to the placebo group, there was no significant difference observed in 3-MH in the UA group (Ī”=-3.20 Ā± 0.31 Ī¼mol/L, p = 0.36). In terms of inflammation markers, the UA group exhibited a significant decrease in CRP (Ī”=-0.79 Ā± 0.38 mg/L, p = 0.032) compared to the placebo group, whereas there was a decrease in IL-6 without statistical significance (Ī”=-1.75 Ā± 0.45 pg/mL, p = 0.215). Furthermore, the UA group showed a significant decrease in SOD compared to the placebo group (Ī”=-4.32 Ā± 0.90 U/mL, p = 0.041).
After 8 weeks of UA supplementation at 1 g/day, resistance-trained male athletes showed improvements in muscle strength and endurance. Additionally, UA supplementation was also associated with reduced oxidative stress levels and a decrease in inflammation response levels.

So CRP increased in both groups but more so in the placebo? :thinking:

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The problem with CRP as a measurement is that infection causes it to jump. Hence you need to identify what the uninfected value is by doing a number of measurements.