#223

Thanks. Good to have in mind. So a mice model from an obscure Chinese paper… :grimacing:

1 Like
#224

We started our Max-5 experiment about 8 months ago and hope to see what the results are in our next DunedinPACE score.

It includes Urolithin A.

What is in the Max-5 experiment?

I based the dosing on the most current studies I could find. Very few are offering these interesting compounds in the doses used in the top studies due to cost. At retail, at these doses, it would cost $500 to $600 per month.

MAX-5_list_dose

2 Likes
#225

Any subjective / qualitative feeling so far?

#226

It’s really hard for me to tell. I’ve felt pretty great for the past 15 months :slight_smile:

I’d love to be able to say A is doing this, B is doing that but I can’t for sure, so I won’t. That’s why I’m anxiously waiting on our DunedinPACE and Symphony Age results from Tru…

I find that for most things I do, not a lot changes in how I “feel” except for the weight loss and the return to working out. Those 2 on top of everything else we do is a big factor. I think the “how” in the weight loss is quite important in the whole process.

Over all I do feel pretty amazing though :slight_smile: my wife and I talk about that almost every day the past 15 months. We both amazed and “feel” better than we did when we were 50 and that was 18 years ago for me. I was in great shape then, walking miles a day, working out 4 days a week and ready for pretty much anything (had my last bar fight then LoL). I “feel” the same way today but with less effort :slight_smile: and more calmness.

One of the things that has amazed me in the past 7 months is how rapid our recovery is from any extended, hard physical effort. I attribute that primarily to the other peptides we take.

My new motto is “better living through biochemistry” LoL!

1 Like
#227

Amazing to read this, contrats!

When will you receive them?

#228

I ordered the kits Sept 5th and they have not arrived yet. Once I have the kit and send our samples back it usually take 3 to 4 weeks.

I think they are getting a bit swamped after the Kardashian bump :slight_smile:

1 Like
#229

I was lucky to have 12 months to try. I cannot say that I felt anything different. My Lactate threshold stayed quite similar on the bike (3,1 Watts/Kg) and my VO2 was also 62 on average.

I know this sounds very unbelievable, and I am a physician, but only in 2 weeks on rapamycin, my shoulder pain diminished by about 90%…

I don’t think we have enough data in humans to be paying 120 euros a month, investing your money on better quality food, a gym subscription it will give you much more

2 Likes
#230

if you read the studies, the lower dose in some endpoints was better than the 1g. I asked this to them, but they did not have an answer. also the gains were quite small

3 Likes
#231

May I asked what the % next to each compound stands for

1 Like
#232

Matt Kaeberlein had a similar shoulder pain healing anecdote. Perhaps it’s time we do a clinical trial on shoulder pain and rapamycin.

4 Likes
#233

The % indicates how much of the active ingredient is present.

Very few compounds are 100% of the active “ingredient”. Especially if it’s an extract. Extracts run anywhere from 5% to 50%. So it depends on how a compound is produced as to the % of the active ingredient. The other % 100 - 99 = 1% is of little concern in dietary supplements if you are getting it from a reputable mfg.

Also once a compound is made into a pill or put in a capsule various other things are added to allow the machinery to function properly. So no drug or dietary supp is 100% pure

1 Like
#234

What kind of blood markers you will be measuring for effects?

#235

Getting blood work done here is not inexpensive if it’s outside the health care system and not prescribed by a Doc. So the only testing I do is the Trudiagnostic Complete test. Which I have done 4 in 3 years and will be doing our 5th soon.

We do get annual blood panels done but they are not “longevity” oriented, just the standard stuff. My last one was the best it’s been in 15 years. I’ll be getting that done again in January.

I’ve posted some of my results in my intro thread.

#236

These Iranian meta-reviews found −5 to –8 mmHg reduction in systolic BP:

So, I would expect similar results with urolithin A. However I can’t find any evidence for hypotensive properties of UA in humans.

1 Like
#237

Pomegranate juice and UA isn’t interchangeable, the latter is just one substance that can be converted from iirc one of the substances in it.

The best way would be to test however :person_shrugging:

Could try comparing absorbed in the small intestine vs. stomach (with enteric capsules and a protocol for that).

Also as far as I know there are a lot of supplements that can lower blood pressure.

1 Like
#238

I dug more on UA. Here are some interesting 2024 papers, not of the highest quality though:

  • Chinese preprint on mice: Urolithin A improves motor dysfunction induced by copper exposure in SOD1 G93A transgenic mice via activation of mitophagy 2024: “Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1G93A mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1G93A mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.”
  • Japanese paper, on mice: Urolithin A-mediated augmentation of intestinal barrier function through elevated secretory mucin synthesis 2024: “We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.” (@约瑟夫_拉维尔 @DrFraser for gut health?)
  • Chinese paper, on mice: Urolithin A Ameliorates Athletic Ability and Intestinal Microbiota in Sleep Deprivation from the Perspective of the Gut-Muscle Axis 2024: “UA is gavaged to C57BL/6 mice (50 mg kg−1 bw) before 48-h SD. The results indicate that pretreatment of UA significantly enhances motor ability and energy metabolism. The inflammation is suppressed, and intestinal permeability is improved after prophylactic treatment with UA. The decreased level of serum lipopolysaccharide (LPS) is concomitant with augmentation of the intestinal tight junction proteins. 16s rRNA analysis of colonic contents reveals that UA significantly reduces the abundance of Clostridia_UCG-014 and Candidatus_Saccharimonas, and upregulates Lactobacillus and Muribaculaceae. UA probably influences on gut microbial functions via several energy metabolism pathways, such as carbon metabolism, phosphotransferase system (PTS), and ATP binding cassette (ABC) transporters.”
  • German-Swiss RCT by the Mitopure team, 1,000 mg UA/day: Impact of urolithin A supplementation, a mitophagy activator on mitochondrial health of immune cells (MitoIMMUNE): A randomized, double-blind, placebo-controlled trial in healthy adults. 2024: “Intake of UA was safe and well-tolerated in the intervention cohort of 25 participants. After the study period, total peripheral lymphocytes and circulating NK cells were expanded in the UA group. Performing a complete immunophenotyping via spectral flow cytometry, we found that UA elicits immune remodeling characterized by broad changes of immune surface markers and mitochondrial measurements. CD8+ cells of participants in the intervention arm displayed greater mitochondrial mass, while preferably taking on a naive phenotype and expressing more Ki67. In addition, circulating monocytes exhibited a less inflammatory signature. UA intake reduced plasma levels of several proinflammatory cytokines. […] Collectively, our study constitutes an unprecedented intervention-based assessment of immune aging that globally characterizes the effect of UA on the immune system, proposing validation in future confirmatory studies and potential combination with cancer immunotherapy.” (@Neo wdyt?)
  • Small (n=10) short (10 weeks) Iranian RCT, 1,000 mg/day: Evaluation of Urolithin A Efficacy in Heart Failure Patients with Reduced Ejection Fraction: A Randomized, Double-blind, Crossover, Placebo-controlled Clinical Trial 2024: “All patients completed the study. The results failed to reveal any significant effect of UA supplementation on echocardiographic measures (LVEF, LVEDD, LVESV, and TAPSE). Plasma concentrations of pro-BNP, glucose, and CRP (p >0.05) were also not altered. Serum HDL-C levels were increased with UA compared with placebo (+6.46 ± 2.33 mg/dL, p =0.026), whereas other lipid indices (LDL-C, triglycerides, total cholesterol, and VLDL-C) remained unchanged (p >0.05).” => At least it’s safe? :man_shrugging:
  • Chinese paper, on mice: Methylated urolithin A, mitigates cognitive impairment by inhibiting NLRP3 inflammasome and ameliorating mitochondrial dysfunction in aging mice 2024: “Our study used an in vivo aging model induced by d-galactose (D-gal) to show that mUro A notably improved learning and memory, prevented synaptic impairments by enhancing synaptic protein expression and increasing EPSCs, and reduced oxidative damage in aging mice. mUro A alleviated the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, leading to reduced glial cell activity and neuroinflammation in both accelerated aging and naturally senescent mouse models. Moreover, mUroA enhanced the activity of TCA cycle enzymes (PDH, CS, and OGDH), decreased 8-OHdG levels, and raised ATP and NAD+ levels within the mitochondria. At the molecular level, mUro A decreased phosphorylated p53 levels and increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), thus enhancing mitochondrial function. In conclusion, mUro A alleviates cognitive impairment in aging mice by suppressing neuroinflammation through NLRP3 inflammasome inhibition and restoring mitochondrial function via the p53-PGC-1α pathway. This suggests its potential therapeutic agent for brain aging and aging-related diseases.”

The Mitopure RCT looks quite good to me. It seems to confirm the Chinese studies on rodents (see also those: Urolithin A (UA) One of 4 Promising Agents 2024 by Brian Kennedy of NSU - #220 by sml491010 ).

6 Likes
#239

Sorry I don’t, more than thst overall healthier immune system may help in cancer treatment and they seems to see some improvements along those lines :frowning:

1 Like
#240

A summary of some Longecity user experiences with fatigue when taking Mitopure:

Longecity user Decimus and his mother took MitoPure (urolithin-A). After a big increase in energy after taking it for the first time, he experienced extreme fatigue. His mother subsequently had the same experience. Longecity user genereader, who posted later in the same thread, wrote that Decimus’s sudden onset fatigue sounded like low potassium.
Subsequently, in a post on 26 December 2021, Decimus found that he indeed had a potassium deficiency and that when he resolved it, he had no more extreme fatigue issues after taking MitoPure. Some posts are reproduced and further discussed here:

1 Like
#241

If you are in an autophagic state you should expect to feel fatigue.

2 Likes
#242

Yes. Good point. I should have added that to my post.