150 replies to this topic

[Nate-2004]

Has anyone tested rosmarinic acid on glucosepane?

 

Not yet, the only test so far has been on some other unknown type in vitro so it's really just speculation here. Expensive speculation. It'd be nice if someone would do more testing but no one is willing for whatever reason.

[Nate-2004]

 

I am 42 and through most of my 30's I did not look my age. Only just in the last 2 years have people begun believing that I'm 42 because I'm starting to look 42. I guess aging kicks in at any time after some kind of tipping point. I hit a tipping point around 40. That's one of the many reasons I'm fighting it. I've seen no diminishment of deep wrinkles around my eyes that appear when I smile and the sagging that has begun or the deeper dark circles under my eyes that have started or the bulging of the eyes that begins for people around this time (loss of subcutaneous fat around that area).

 

Ok thanks its informative and I hope to delay this using the supplements strategy I use right now at least... you was not on supplements before your 40s right ?

 

I really hope rosmarinic acid will help with that

 

 

The only supplements I took in my 30's and late 20's was fish oil and whey protein (before and after workouts). I stopped taking whey after 36 or so because I wasn't sure it was even really doing anything for me. I stopped taking fish oil for a period of time after I turned 37 because they came out with all these reports showing it was all a hoax (as far as heart health and cognition are concerned) based on some single study that nobody tried to question or reproduce. Further studies showed it was still good for depression, skin, microbiome and inflammation among other things so I started taking it again last year. I am unsure if that's why I aged faster between 37 and 42 or not.  

 

Now the supplements I take are numerous, mostly targeting inflammation at this point, NR and pterostilbene being the only exception. I take curcumin, ginger, magnesium, creatine and fish oil in addition to anything that's said to feed akkermansia (glutamine, NAG, etc), carnosine and RA, D, K, hydrogen water and MK-677.

 

Of all these things the only things having any noticeable effect on anything whatsoever is hydrogen water, and that's only on my essential tremor, and MK-677 on strength gains and lower back pain. Everything else could be total bunk. Though my rotary cuff injury has healed considerably faster (by months) than the last time I injured it just as badly. That could just be because I know what to do to help it recover this time. Hydrolyzed collagen was bunk. Vitamin C is bunk. D and K do nothing really for increasing or recovering facial bone density. 

 

Best I can hope for right now, best place I probably could be investing my money, is in crowdfunding synolitics and efforts to find age breakers and other projects that I wish people would try crowdfunding.

[aconita]

My take is that most supplements are not going to lead to any noticeable outcome unless there is an insufficiency of a specific compound for whatever reason, insufficiency which is usually unlikely unless malnourishment or a pathology.

 

Another factor is health, for example if someone testosterone is very low there are quite a lot of supplements able to return it to normal levels, something as simple and inexpensive as onions do work wonders in this context.

 

But if testosterone is in normal range in order to rise it even a little bit further I can only wish you good luck with supplements...

 

If someone intake level of vitamin C is already adequate by means of correct diet supplementing ascorbic acid is very unlikely to produce any noticeable positive effect.

 

Maybe about some supplements the fact that they don't show any NOTICEABLE effect doesn't necessarily mean they don't induce positive influences on some health factors which in the long run do make a difference indeed.

 

Another thing about skin rejuvenation I noticed, there are a lot, really A LOT, of compounds that do show in studies very noticeable improvements in elasticity, thickness, inflammation and so on...but is very unlikely the effects are cumulative.

 

It means that if compound y improves skin parameters by 15% and compound x improves skin parameters 18% it doesn't mean that using both together or one after the other one in cycles leads to a 33% improvement, likely not even to a 20% since very likely they effects the same causes even if sometimes by way of different routes.

 

In this perspective I think it is relatively easy to find a compound which in studies shows beneficial outcomes on subjects whom are in a relatively "bad shape" and never did much about it, a whole another story is to achieve improvements on someone whom is in "good shape" for its age and/or is already taking care by mean of supplementing or by the use of beneficial topical compounds.

 

It is a bit like in training, it is easy to double in a relatively short time the strength of someone totally untrained and unfit, a different story is to improve the strength even only of 10% in an experienced powerlifter.

 

My take home message is that a study showing promising outcomes doesn't necessarily guarantee a particular compound to elicit any improvements to everybody, in many instances is just adding more water to an already full bucket: it is not going to make the bucket any fuller.

 

Rosmarinic acid likely works...like many other compounds do...for someone "new" to supplementing likely will show interesting outcomes but it is nothing really "special" or "unique"...same or similar results are likely achievable by other means and adding it will not make any dramatic change. 

[Nate-2004]

I agree with most of what you're saying. Thing is, if RA does in fact break AGE crosslinks in vivo (at this point that's doubtful, at least so far as glucosepane), then one should expect more than just an 18% change if they're older and less taken care of themselves. They should expect some pretty dramatic changes, theoretically, that would look a lot like becoming considerably younger in some ways, at least in terms of appearance. That is, if the theory is that AGEs are one of the major contributors to age in terms of appearance and other factors.  I don't know if glucosepane type AGEs are what causes a loss in collagen, subcutaneous fat and bone density resulting in the sagging and loss of elasticity in skin. Pentosidine is another AGE that's been talked about.

Edited by Nate-2004, 17 January 2017 - 02:01 AM.

[Tom Andre F. (ex shinobi)]

I understand you guys but do not agree, RA clearly showed AGE breaking property, not on glucosepane, but this one is harder to test, but still a good thing and 18% if the study is true is a lot.

 

Dont forget, with aging AGE is NOT the only cause ! you still have inflammation due to mutation / polution, UV, loss of cells etc (see hallmark of aging)

 

This in turns increase for instance elastase, hyaluronidase, collagenase... that makes the skin looks more and more aged.

 

I didnt seen any others supplements able to break AGE, only the drug ALT-711, and we see RA performed better. Then we have to consider pharmacokinetic, dosage..

 

 

[aconita]

My post actually is not specific to rosmarinic acid but more in general to supplements and topical skin rejuvenators 

 

If rosmarinic acid is able to break AGEs and doing so leads to skin rejuvenation it would be definitely something quite unique...but some doubts in regard are legitimate since by now that effectiveness should be well known, which doesn't seem to be the case.

 

Not a good reason enough to rule out the possibility, of course,

 

Keeping an eye on it could be wise. 

[mrkosh1]

Nate,

 

I am unsure if Rosmarinic Acid would have a strong effect on aging skin due to the fact some studies say (I'm not claiming they are correct) that glucosepane is the dominant (composing over 99% of the crosslinks in the skin) AGE in humans. If RA cannot break glucosepane, then I doubt it would have a huge effect by a crosslink breaking mechanism. Conversely, if it is having a significant impact on human skin, I would think it is either breaking glucosepane OR having an impact by some other mechanism.

 

I think that somehow having Rosmarinic Acid tested on glucosepane should be a top priority. How would we need to go about making this happen? If a lab already has the equipment to measure glucosepane in the skin, then I'd think we'd just need an older person willing to donate a small skin biopsy. The scientists could measure the levels of glucosepane before and after treating it with Rosmarinic Acid.

 

Since glucosepane is such a big deal with anti-aging, I think that a crowd funding effort could potentially bring in the money to cover such testing.

 

Thoughts?

[Nate-2004]

Nate,

 

I am unsure if Rosmarinic Acid would have a strong effect on aging skin due to the fact some studies say (I'm not claiming they are correct) that glucosepane is the dominant (composing over 99% of the crosslinks in the skin) AGE in humans. If RA cannot break glucosepane, then I doubt it would have a huge effect by a crosslink breaking mechanism. Conversely, if it is having a significant impact on human skin, I would think it is either breaking glucosepane OR having an impact by some other mechanism.

 

I think that somehow having Rosmarinic Acid tested on glucosepane should be a top priority. How would we need to go about making this happen? If a lab already has the equipment to measure glucosepane in the skin, then I'd think we'd just need an older person willing to donate a small skin biopsy. The scientists could measure the levels of glucosepane before and after treating it with Rosmarinic Acid.

 

Since glucosepane is such a big deal with anti-aging, I think that a crowd funding effort could potentially bring in the money to cover such testing.

 

Thoughts?

 

Crowdfunding a study would be the best bet. Lifespan.io is having a tough time with the senescent cells campaign though, probably because they marketed it wrong. It's not appealing to emotion.

[Tom Andre F. (ex shinobi)]

mrkosh,

 

glucosepane is 10 to 1000 times more present in human tissue than any others but still is not the worst one some discussed on longecity.

 

about testing on glucosepane, we are willing to move forward and do it, but it will take time as we will test others candidate and make it all official and proper science

 

I will keep you in touch

[Adaptogen]

Effect of piperine on the bioavailability and pharmacokinetics of rosmarinic acid in rat plasma using UPLC-MS/MS

"The relative bioavailability of RA in presence of 20, 40, 60, 80 mg/kg PP was 1.24-, 1.32-, 2.02-, and 2.26-fold higher respectively, compared to the control group given RA alone. Compared with RA, the pharmacokinetic modulations of RA glucuronide were even more apparent, and the glucuronidation of RA was remarkedly inhibited."
 

[Logic]

Skin rejuvenation:
People taking the senolytic combo Dasatinib+Quercetin are reporting skin rejuvenation. and the disappearance of age spots and other skin anomalies.
I wonder what effect the removal of senescent cells and SASP might have on AGEs?
The effect is probably due to less inflammation meaning less elastase, collagenase, etc, but perhaps these are upregulated in a natural effort to clear AGEs and senescent cells and/or SASP gets in the way somehow..?
 

[Adaptogen]

is anyone worried about the antiandrogenic/antispermatogenic effects of rosemary (along with many other common Lamiaceae)?

[Nate-2004]

Skin rejuvenation:
People taking the senolytic combo Dasatinib+Quercetin are reporting skin rejuvenation. and the disappearance of age spots and other skin anomalies.
I wonder what effect the removal of senescent cells and SASP might have on AGEs?
The effect is probably due to less inflammation meaning less elastase, collagenase, etc, but perhaps these are upregulated in a natural effort to clear AGEs and senescent cells and/or SASP gets in the way somehow..?
 

 

I did have some rejuvenation as well, on the last round of D+Q (sublingual DMSO+Q). It's not a shocking amount of rejuvenation but the deep wrinkles when I smile have shallowed, especially around the crows feet. So perhaps this could be true but it's hard to measure.

 

I also get a lot of comments on how good my skin looks from people who have no idea what I'm up to here. None of this self-reporting is all that useful to me though, skin tests still put my age pretty young but I will not see myself as the age these tests put me at till I see no deep wrinkles at all when I smile and no dark circles under my eyes. When I look in the mirror and see the face of a 25 year old me, not a 43 year old me.

 

I'm still experimenting with the DMSO+RA+Urea+Trehalose solution. Certainly no detrimental effects. I'm also trying lipowheat, so I can't discount that as a root cause for the results I've gotten.

[normalizing]

in the thread trehalose i believe we came to the conclusion that trehalose benefits are not capable to be induced in humans due to the enzymes we have to break it down too quickly for any result. perhaps check that thread for more info on this?

 

my question about rosmarinic acid is not about skin though, its about GABA effect. from what i gather it seems to affect GABA in one way or another, im curious of experiences of people who can say or have read good documentation of this effect??

[dazed1]

nate, dont be foolish. its just another herbal stuff that wont work. why dont you concentrate on advancement in technology, like stem cells?

 

 

What? are you serious? plants are mighty powerful, much more then one can imagine, especially if used as CO2  (total) extracts.

 

To address the question in the tread, refined avocado oil is the best transporter of agents for deep penetration to the layers of the skin. I use it personally and its amazing.

 

Peppermint has 1300mg/100 grams of rosmarinic acid. @Nate - check out this thread for flawless skin.

Edited by dazed1, 12 November 2017 - 02:11 AM.

[Logic]

 

Rosmarinic acid is a tau-aggregation inhibitor, like cinnamon, curcumin, panax ginseng, green tea, aged garlic and others.

 

IIRC all those are chelators...  Especially of copper.
It's worth looking into IMHO.

[Nate-2004]

Dazed I don't see where you got the info that peppermint has that much RA.

 

I was getting my Rosmarinic Acid standardized to 38% from Dynveo which I think Tom Andre on the board runs. I checked and the site is back online but haven't bought any more lately. Trying GHK-CU for a bit if I can ever get my order from Hairevo.

[Oakman]

 

nate, dont be foolish. its just another herbal stuff that wont work. whydont you concentrate on advancement in technology, like stem cells?

 

 

What? are you serious? plants are mighty powerful, much more then one can imagine, especially if used as CO2  (total) extracts.

 

To address the question in the tread, refined avocado oil is the best transporter of agents for deep penetration to the layers of the skin. I use it personally and its amazing.

 

Peppermint has 1300mg/100 grams of rosmarinic acid. @Nate - check out this thread for flawless skin.

 

 

You underestimate the amount of rosmarinic acid in peppermint. This study shows 28 mg/g for Peppermint (Mentha piperita), but the best is Spearmint (Mentha spicata) at 58.5mg/g Rosemarinic acid!

 

Comparative study of rosmarinic acid content in some plants of Labiatae family

[pamojja]

You underestimate the amount of rosmarinic acid in peppermint. This study shows 28 mg/g for Peppermint (Mentha piperita), but the best is Spearmint (Mentha spicata) at 58.5mg/g Rosemarinic acid!

 

Comparative study of rosmarinic acid content in some plants of Labiatae family

 

Hmm. An other study, an other favorite. Phenol explorer give as a mean value 9 mg/g for Spearmint and 17 mg/g for Peppermint (the highest content in this database). Rosmary in this comparison isn't as bad with 9.9 mg/g either.

 

[Nate-2004]

 

You underestimate the amount of rosmarinic acid in peppermint. This study shows 28 mg/g for Peppermint (Mentha piperita), but the best is Spearmint (Mentha spicata) at 58.5mg/g Rosemarinic acid!

 

Comparative study of rosmarinic acid content in some plants of Labiatae family

 

Hmm. An other study, an other favorite. Phenol explorer give as a mean value 9 mg/g for Spearmint and 17 mg/g for Peppermint (the highest content in this database). Rosmary in this comparison isn't as bad with 9.9 mg/g either.

 

 

In response to both you and Oakman, this is highly informative. I saw this study earlier but I am not as good at math. This quote here:

 

 

 

The results showed that RA content in different species of Labiatae was 0.0-58.5 mg g-1 of dried plants. The highest amount of RA was found in Mentha species especially M. spicata.

 

I'm not sure what g-1 is or means and that's a pretty broad range. Can one of you point to which chart or figure you're looking at in the study Oakman linked?

 

I wonder how much RA is in my peppermint oil (which is ridiculously strong) or my peppermint tea. I should get the spearmint oil assuming it's edible. This may explain why lifeextension had an article on spearmint in hot chocolate as an anti-aging formula.

Edited by Nate-2004, 29 November 2017 - 10:03 PM.

[Oakman]

g-1 means mg/g; in the study, click on Table 2 "Collection areas and concentration of rosmarinic acid in plants of Labiatae family"

 

[stefan_001]

@nate-2004 its not RA but didn't know where to post it and I think it might interest you:
https://link.springe...0068-017-0252-6

Quickly looking the highest mouse dose was 200mg/kg/day so that would make 1-1.5g/day for a 70kg person

[Nate-2004]

As with so many herbal extract supplements, there is a very low bioavailability. 

 

I wonder why.

 

http://pubs.rsc.org/...7g#!divAbstract

 

Piperine, apigenin and luteolin may help improve bioavailability.

Edited by Nate-2004, 01 February 2018 - 06:52 PM.

[sthira]

I wonder why.

Sometimes it's due to "poor lipid solubility or improper molecular size..."

https://www.ncbi.nlm...les/PMC3634921/

Bodies may also be trying to protect you by kicking out poisons. Good body. Be careful of metabolism; maybe quantum powered AI will enlighten us about our bodies in about oh ten years -- let's be polite to them when that happens.

[normalizing]

funny how the body tries to protect us from what it considers poisons when it comes to "natural ingredients" and it kicks them out with little bioavailability and yet it accepts all the drugs with high availability and somehow it doesnt see them as poisons? very stupid body actually

[Nate-2004]

Especially methamphetamines. LOL

 

Just to add a point here though, everything is natural. It's not whether it's natural or not but rather whether it's good for you or not and yes the body should accept more things that are actually good for you.

 

Though a lot of these things it rejects are plant hormetic compounds and by definition poison, however, the good is dose dependent.

Edited by Nate-2004, 02 February 2018 - 02:30 PM.

[StanG]

Skin rejuvenation:
People taking the senolytic combo Dasatinib+Quercetin are reporting skin rejuvenation. and the disappearance of age spots and other skin anomalies.
I wonder what effect the removal of senescent cells and SASP might have on AGEs?
The effect is probably due to less inflammation meaning less elastase, collagenase, etc, but perhaps these are upregulated in a natural effort to clear AGEs and senescent cells and/or SASP gets in the way somehow..?
 

 

 

Thanks for letting me know about this Logic. I found some age spot lightening taking this combo. 

[Nate-2004]

So I went back and read the original study I posted about RA performing better than ALT-711 at breaking AGEs in vitro. Having re-read the study from a fresher perspective with my morning coffee, this should be pointed out here:

 

In 1996, a thiazolium derivative, Alagebrium or ALT-711 (Alteon Inc., Montvale, NJ, USA) was reported as a potent AGE-derived crosslinks breaker 9), without describing the type of crosslink being broken by the molecule. Later in 2013, it was shown that it was able to break alpha-dicarbonyl groups present in Amadori products before formation of crosslinks.

 

 

I think it should be emphasized that ALT-711 was only able to break alpha-dicarbonyl groups before the formation of crosslinks. It doesn't sound like they were able to actually break crosslinks.

 

As a layman amateur here I'm still trying to grasp what an Amadori product is exactly, whether it's another way of saying AGE or if it's a broader or more specific term for a specific kind of AGE or what. I found this study interesting as they used x-ray diffraction to determine just how deep a potential enzyme to break crosslinks would have to go in vivo.

 

My experimentation with RA is probably at an end though. I've tried various means of ingestion, dosing and usage and without lab work or a better means of determining progress it's really pointless. My last method involved mixing it in a strong proof ethyl alcohol and heavy cream to improve sublingual absorption and bioavailability. I also took bioperine along with an oral dose. I would periodically redose with this mix all day. I've done this on about five separate days with a 30% extract. The original study I posted doesn't mention anything about how much time it took to break the specific type of crosslinks they were trying to break using glycated milk protein. I was trying to give my body a longer, more steady exposure to it. This was pretty much the same way I have been doing resveratrol on occasion. My skin looks great as always but I'd attribute that more to keto and fasting than this experiment. I am a horrible scientist, considering that I'm doing way too much simultaneously and not taking any before and after measurements. I might as well be spitting into the wind with a blind fold and expecting to hit a target. This is where impatience gets you.

 

Side note, the study I linked just above mentions fructosamine as another type of AGE involved in skin and collagen. This is also referred to as an "Amadori product".

 

 

Edited by Nate-2004, 11 March 2018 - 03:14 PM.

[sthira]

But at least you're trying, even if it's not perfect. Other than the boring ole basics, there is nothing for us yet. Experimenting with hope is fun, though, just try not to get too discouraged, like I've become. Frustrated. Discouraged. Because wouldn't we just love it if we could discover that perfect concoction easily purchased on, oh, Amazon, and we could just take it and -- Bam! -- I'm 12-years old again. Honestly I don't know how to sustain hope in this world of hyped up aging interventions that appear so promising in rodents, then fail within us before they're even given a proper study. George Church seems really hopeful, though.

Future ancestors, if they look back us, will probably shake their golden and immortal heads and sigh out oh those poor ignorant fucks. Kinda like we do to those people in hats in b/w photos from 1863, before anesthesia existed, and if you got hit by a bullet in a field, they'd just cut off your leg, tell you to be a man, clamp down with your jaws on this rag and keep swigging whiskey.

Sorry for the Sunday morning dreary off topic pointless time wasting rant. I wish I could eat rosemary sprigs and be 12 again.

[normalizing]

you can eat rosemary sprigs and imagine you are 12 again... while on shrooms