This is a direct link to the paper (4 mM Proline, molecular weight about 115)
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)00066-4
To have this effect would probably need a lot of proline.
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Thinking about dosing. If diet is normally 5g proline per day then to make a difference would probably take at least 5g. To get to a concentration of 4mM in 5 litres of blood with a molecular weight of 115 would take 2.3 grams. However,
a) It would not create a steady state of 2.3 grams as some would be absorbed into cells.
b) Not everything that is eaten gets into serum anyway.
Rat experiments have identified an upper limit of perhaps 2% of diet per day. If people eat something like 2kg of food per day then that limit would be 40grams, but we cannot be certain that this limit is the same for humans.
It strikes me, therefore, that we are probably looking at dosing somewhere around the 10-20 grams per day level to make progress on supplementing to get any noticeable result.
Speaking personally I am inclined to cycle high dose proline building up to the higher dosage and see what happens. That way if it disrupts anything at a lower dose I can stop.
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Will try too. Already have glycine in one protein drink and taurine in the second. Thinking Iāll add Proline to either or both.
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@John_Hemming Interesting. A quick look-see shows proline is made by the body from glutamate. Why would the body not make enough? Also, is the target supplementation proline or l-proline?
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Continual mitophagy would not IMO be a good idea. Hence i would not expect the body to create the levels needed for this.
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So itās not a deficiency thingā¦itās a āpoisonā to induce autophagy once in a while to offset a reduced mitophagy function caused by something else? Accordingly, we shouldnāt take the high proline dose all the time? High proline foods were shown to cause depression in an old study, FWIW.
At this point we dont know, but it is unlikely that chronic high proline would be a good idea.
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JosƩ
#28
Deliver Proline by IV, you will achieve a constant level.
One of many brands available.
Yes you would require a prescription to purchase in the US.
I have no financial interest in this or any other brand of injectable Proline.
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JosƩ
#29
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Do you have any feedback from this experiment?
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I am thinking of adding collagen (glycine / proline) to my anabolic / catabolic cycle ā¦to support mitophagy in pulses.
I currently emphasize fish and dairy proteins on my post lifting 24 hours. (Higher: leucine, methionine, arginineā¦and calories)
I will add a large dose of collagen to my post recovery / pre-lifting extra day off lifting on weekends where I already reduce calories and fish/animal proteins. This goes against my effort to reduce protein but Iām expecting a non-āproteinā (non-anabolic) response.
Any thoughts? Dose? (Iām guessing a @John_Hemming approach would be to take 40 grams of proline once a month)
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I have lost the proline that I ordered earlier this year. I need to look for it.
Ray1
#33
It seems like periodic dosing of proline would be best. The beneficial effect of proline is thought to be due to blocking glutamine.
" The pathway from glutamine to proline synthesis involves the intermediate P5C (pyrroline-5-carboxylate), generated from glutamate by P5C synthase, and its conversion to proline by P5C reductases (PYCRs), the pivotal step in proline biosynthesis.36,37 Given the interconnectedness of glutamine and proline metabolism, we hypothesized that proline might also affect cellular senescence"
DON is an interesting drug which blocks glutamine.
6-diazo-5-oxo-L-norleucine (DON) is a glutamine antagonist that inhibits glutamine-utilizing enzymes and has shown promise in treating solid tumors:
Upping proline every other week, using DON, or perhaps both might rejuvenate the mitochondria.
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Ulf
#34
Is there any contradiction between high-dose proline every second week and what is described in the article āProline treatment for 14 days restored impaired mitochondrial function in senescent MSCsā? (Treatment for 7 consecutive days was not enough).
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Ray1
#35
That is a huge contradiction isnāt it. I assumed the elevated proline was in the mouse chow. Is that optimum? Perhaps consuming proline first thing in the morning after a 15 hour overnight fast would be more effective than consuming proline all day long? The intention is to block glutamine. Are there side effects to high daily proline consumption? I certainly would not wish to take DON daily unless I had cancer. So many questions. Fixing our mitochondria would be a very big deal.
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I put some proline powder in my coffee this morning. It dissolved well and I couldnāt taste it. This will be part of the new routine.
Wondering how many supplement powders I can add to a cup of coffee before I notice it and gag. 
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I have found the proline, but I donāt think I can test it until 2025.
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Ulf
#38
Itās a gamble but restoring full mitochondrial function is a tempting targetā¦
Based on that study and on what John Hemming wrote, I would go for 14 days x say 15 g of proline, followed by a long break.
Except for the rare cases of the genetic disorder hyperprolinanemia, it appears that fairly high-dose prolin does not have adverse effects:
āThe only relevant information for humans is a study that detected no overt side effects when 3ā10 g/d proline was given to four patients with [gyrate atrophy] for 2 - 4 yearsā(https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/retina-gyrate-atrophy ([98](I could not access the referenced article).
Ulf
#39
The linked article shows great and consistent results from proline supplementation on mitochondrial health, but itās all lab studies. Canāt find much on humans.
But still itās temptingā¦ what could be a practical baseline? DNA testing for mitochondrial DNA (mtDNA) mutations, VO2max and lactic acid levels on a test bike, kits assessing mito health if these are attainableā¦ My lactate/pyruvate ratio is fine as it is.
One 10 mg dose followed by 20 mg proline daily in one dose for 14 daysā¦? A shot in the dark, but it appears safe.
From proline risks summarized in 2.5 of the article below, I conclude that 20 mg of proline daily for 14 days is unlikely to pose any risk. There is a 10:1 safety factor, (200 mg daily for 90 days vs a 20 mg dose) rather than the desired 100:1 when translating from rats to humans, but the highest no-harm dose for rats was the highest dose used there was no dose with harm.
Risk Assessment of āOther Substancesā ā L-proline
Full Article - PDF Review History
Published: 2018-12-15
DOI: 10.9734/EJNFS/2019/45635
Page: 25-27
Dr.Bart
#40
Wouldnāt be just easier to take collagen which is mainly proline and glycine along with taurine ?
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