150 replies to this topic

[Nate-2004]

It was posted in the NR thread that Rosmarinic acid is a better age *breaker* than Alagebrium (ALT-711).

 

Granted this all appears to be in vitro from what I can tell and I'm not aware of any in vivo studies involving rosmarinic acid.

 

I see Swanson makes rosemary extract but it's only 6% rosmarinic acid, not nearly the levels required supposedly.  The study appears to use this: http://www.sigmaaldr...ng=en&region=US

 

According to this page an effective dose is 200+mg of the stuff, I assume 96% or greater. Where they got this information I'm not sure.

 

The story with ALT-711 was that it didn't break glucosepane and I don't believe anyone has tested it on glucosepane. I'm not sure why they didn't in the study linked above, since that would be highly relevant.

 

Would be good to have more info on this.

[LearningFromThePast]

I love RA. It's a fantastic agent for a multitude of reasons.

 

What do you mean exactly by "age *breaker*" 

 

SWIM uses the 20% at TLR.

375-500 mg a capsule, 3x a day.

 

https://teamtlr.com/...20-extract.html

[Tom Andre F. (ex shinobi)]

Yes this is the study I have too. It was conduced by a french company and published first in the japanese paper.

 

They then performed vivo test in human to see if it changed the wrinkles profile in 93 women, average 57yo for 1 month

 

they even used the elasticity test Cutomètre® wich is a reliable method and got a +17% increase for elasticity of the skin. Rest of  the parameter performed even better

 

However, in the vitro study you can see they used a ribose instead of a glucose, means, we dont know if it break glucosepane with this study. They guy admited that it is unlikely it will break glucosepane "even if we dont know". Glucosepane problem is the bond is too strong you can break it without damaging around. Thats why we still today look for a good candidate

Edited by Tom Andre F. (ex shinobi), 30 June 2016 - 11:31 AM.

[Nate-2004]

I love RA. It's a fantastic agent for a multitude of reasons.

 

What do you mean exactly by "age *breaker*" 

 

SWIM uses the 20% at TLR.

375-500 mg a capsule, 3x a day.

 

https://teamtlr.com/...20-extract.html

 

AGE (advanced glycation end products) breaker. I didn't capitalize it in that post sorry.

 

They sell 30g for $35 and at that dosage it comes out to about 20 days on the conservative side. Relatively expensive.

 

I also noticed that carnosine on that graph was -2.73%. Negative? Meaning it's helping create AGEs?

Edited by Nate-2004, 30 June 2016 - 12:04 PM.

[ironfistx]

The topic of AGE is new to me.  Do these make us old as they go through our body?

[Nate-2004]

The topic of AGE is new to me.  Do these make us old as they go through our body?

 

Yes, glycation is a major contributing factor to aging. Glucosepane in humans is specifically the type of AGE that needs breaking. The breaking refers to cross-links. You can learn more about this in Aubrey De Grey's book on "Ending Aging", though it's a bit outdated (2008). Things move faster than he projects I think.

 

You can also read about it online.

 

I'm still baffled by the negative carnosine results in that chart. I realize it isn't an AGE "breaker" but rather it's considered or theorized to be a blocker. I'm not sure to what degree.

[tunt01]

Rosmarinic Acid came up a few times in some of my notes on ALZ.  I will just quickly add what I have written down and hopefully this doesn't derail the thread away from the AGE discussion.

 

 

 

A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta(25-35).

Alkam T1, Nitta A, Mizoguchi H, Itoh A, Nabeshima T.

Author information

 

Abstract

Peroxynitrite (ONOO(-))-mediated damage is regarded to be responsible for the cognitive dysfunction induced by amyloid beta protein (Abeta) in Alzheimer's disease (AD). In the present study, we examined the protective effects of rosmarinic acid (RA), a natural scavenger of ONOO(-), on the memory impairment in a mouse model induced by acute i.c.v. injection of Abeta(25-35). Mice daily received i.p. several doses of RA after the injection of Abeta(25-35). RA prevented the memory impairments induced by Abeta(25-35) in the Y maze test and novel object recognition task. RA, at the effective lowest dose (0.25mg/kg), prevented Abeta(25-35)-induced nitration of proteins, an indirect indicator of ONOO(-) damage, in the hippocampus. At this dose, RA also prevented nitration of proteins and impairment of recognition memory induced by ONOO(-)-i.c.v.-injection. Co-injection of the non-memory-impairing dose of ONOO(-) with Abeta(25-35) blocked the protective effects of RA (0.25mg/kg). These results demonstrated that the memory protective effects of RA in the neurotoxicity of Abeta(25-35) is due to its scavenging of ONOO(-), and that daily consumption of RA may protect against memory impairments observed in AD.

 

 

 

 

Peroxynitrite (radical) formation causes high GSK3beta activity which ultimately leads to hyperphospho tau.  Rosmarinic Acid scavenges peroxynitrite and limits tyrosine nitration.

 

There was a point where I was dabbling with rosemary tea, rosemary essential oil (it can be inhaled).  Rosemary is really great.

 

 

[Nate-2004]

However, in the vitro study you can see they used a ribose instead of a glucose, means, we dont know if it break glucosepane with this study. 

 

What do you mean by used a ribose instead of a glucose? You mean the AGE types they tested on or the formula of RA?

[Skyguy2005]

Does Rosmarinic Acid have anything to do with Rosmaric Acid and Salicylic Acid? Plant Hormones? 

[normalizing]

nate, did you figure out why carnosine is -2.73% age breaker? it doesnt make sense to me at all either. im confused now and also a bit worried, i was taking it for quite a while.

[Tom Andre F. (ex shinobi)]

 

However, in the vitro study you can see they used a ribose instead of a glucose, means, we dont know if it break glucosepane with this study. 

 

What do you mean by used a ribose instead of a glucose? You mean the AGE types they tested on or the formula of RA?

 

 

To make the reaction they used a ribose to get albumin polymer that they then tried to break the bond using different compounds.
 

[gamesguru]

it has to do with mitochondrial metabolism and acetylation, but that is such an insignificant percentage. if you eat certain fruits or veggies (natural AGE breakers or blockers) with ALCAR you will fair far better than the average American who eats neither the veggies nor the ALCAR.

also doesn't rosmarinic acid inhibit GABA-T, that might cause anxiogenic effects to crop up in the long-term user.

[LearningFromThePast]

it has to do with mitochondrial metabolism and acetylation, but that is such an insignificant percentage. if you eat certain fruits or veggies (natural AGE breakers or blockers) with ALCAR you will fair far better than the average American who eats neither the veggies nor the ALCAR.

also doesn't rosmarinic acid inhibit GABA-T, that might cause anxiogenic effects to crop up in the long-term user.

Forgive me if I'm mistaken, but why would inhibiting GABA-T induce anxiety? If anything, I'd think it'd do the opposite.

[Nate-2004]

ALCAR is easier to get than Rosamiric Acid so far as I can tell. I don't know of a good, inexpensive source of pure RA. You also have to take a lot of ALCAR to do any good. With each meal. I took some over the past 3 weeks and it runs out quickly. It gets expensive and I'm not sure to what degree it helps in humans. It'd be the same with RA I'm sure.

 

Off topic here but I did find this source of ALCAR just now by the way. It's quite a bit cheaper than you'd get on Amazon and it's got high ratings, though I can't find a source for lab tests on label accuracy and purity.

Edited by Nate-2004, 06 July 2016 - 01:32 PM.

[gamesguru]

Forgive me if I'm mistaken, but why would inhibiting GABA-T induce anxiety? If anything, I'd think it'd do the opposite.

 

i mean for the first few weeks, then tolerance and dependence. you try to quit it, what happens? anxiety. because your GABA receptors are downregulated in response to the increased GABA.... but sorry chum, you just pulled the plug on GABA, and now you have low receptors and low neurotransmitter. thus, an anxiogenic state emerges.

[Nate-2004]

I can attest to that, as Topiramate does the same thing. Terrible anxiety and insomnia after stopping usage.

[LearningFromThePast]

Forgive me if I'm mistaken, but why would inhibiting GABA-T induce anxiety? If anything, I'd think it'd do the opposite.

i mean for the first few weeks, then tolerance and dependence. you try to quit it, what happens? anxiety. because your GABA receptors are downregulated in response to the increased GABA.... but sorry chum, you just pulled the plug on GABA, and now you have low receptors and low neurotransmitter. thus, an anxiogenic state emerges.

RA isn't going to cause you any problems like that, regarding down-regulation of the GABA receptors. It's a very weak GABA-T inhibitor. I've ran it for weeks at a time, 3x a day, and experienced no issues during cessation.

Forgive me if I'm mistaken, but why would inhibiting GABA-T induce anxiety? If anything, I'd think it'd do the opposite.

i mean for the first few weeks, then tolerance and dependence. you try to quit it, what happens? anxiety. because your GABA receptors are downregulated in response to the increased GABA.... but sorry chum, you just pulled the plug on GABA, and now you have low receptors and low neurotransmitter. thus, an anxiogenic state emerges.

RA isn't going to cause you any problems like that, regarding down-regulation of the GABA receptors. It's a very weak GABA-T inhibitor. I've ran it for weeks at a time, 3x a day, and experienced no issues during cessation.

[gamesguru]

It's a very weak GABA-T inhibitor. I've ran it for weeks at a time, 3x a day, and experienced no issues during cessation.

 

Then how does it exert its anxiolytic effect? How many weeks, what dose?

[LearningFromThePast]

It's a very weak GABA-T inhibitor. I've ran it for weeks at a time, 3x a day, and experienced no issues during cessation.

Then how does it exert its anxiolytic effect? How many weeks, what dose?

The anxiolytic effect is weak. It's barely noticeable, and I am extremely, abnormally sensitive. You must also take into account its Serotonergic action through IDO inhibition. I ran 375 mg, 3x a day on a 20% extract. Normal dose is 500 mg. I'm sensitive, like I said.

[stefan_001]

It's a very weak GABA-T inhibitor. I've ran it for weeks at a time, 3x a day, and experienced no issues during cessation.

Then how does it exert its anxiolytic effect? How many weeks, what dose?

The anxiolytic effect is weak. It's barely noticeable, and I am extremely, abnormally sensitive. You must also take into account its Serotonergic action through IDO inhibition. I ran 375 mg, 3x a day on a 20% extract. Normal dose is 500 mg. I'm sensitive, like I said.

May I ask what positive effects you have noticed from RA? As it sounds that you are a long term user have you noticed that your skin is in a better shape?

[gamesguru]

I doubt it has much effect on the skin. Probably more on the internal organs, especially the cardiovascular and digestive. Might get better results from topical application, assuming atopic permeability.

[LearningFromThePast]

I haven't noticed my skin changing at all, but I also haven't been paying attention. RA's ability to drastically diminish brain fog is remarkable. It aids in the reduction of hot flashes, which I suffer from. It seems to be a pretty effective vasoconstrictor, but I've noticed that I'm sensitive and others don't experience that effect as much. This is actually why I'm forced to take 375 mg instead of 500 mg. I could say it slightly enhances mood, but I pair it with GLYX-OX, so I more attribute the mood boosting effects to GLYX-OX. Although, when I pair them, I experience increased verbal fluency and increased overall cognitive functionality more than when I take GLYX-OX alone. I've taken RA alone plenty of times and don't experience much a mood increase. Maybe a slight decrease in irritable, but the combo is truly next-level. I don't think it should be used as an anxiolytic if someone is suffering from somewhat severe anxiety. I look at the GABA-T inhibiton as an minor 'add-on' and not really as a primary mechanism, ya know? It has helped with my allergies a bit too. My allergies seem to cause the hot flashes, so...
I wasn't aware of its effect on improving organs, etc etc. Does anyone have studies to link me regarding this?

[Nate-2004]

The only reason one would think it might have a good effect on aging skin is that if it is indeed effective at breaking AGEs, then one would expect skin condition to improve because of their key role in aging skin. There are probably more and better references out there with a search on advanced glycation end-products and skin on Google.

 

This is one of my main interests, given how vain I can be lol.

 

One question for those of you taking RA, what is your source of RA? How much are you taking?

[stefan_001]

I haven't noticed my skin changing at all, but I also haven't been paying attention. RA's ability to drastically diminish brain fog is remarkable. It aids in the reduction of hot flashes, which I suffer from. It seems to be a pretty effective vasoconstrictor, but I've noticed that I'm sensitive and others don't experience that effect as much. This is actually why I'm forced to take 375 mg instead of 500 mg. I could say it slightly enhances mood, but I pair it with GLYX-OX, so I more attribute the mood boosting effects to GLYX-OX. Although, when I pair them, I experience increased verbal fluency and increased overall cognitive functionality more than when I take GLYX-OX alone. I've taken RA alone plenty of times and don't experience much a mood increase. Maybe a slight decrease in irritable, but the combo is truly next-level. I don't think it should be used as an anxiolytic if someone is suffering from somewhat severe anxiety. I look at the GABA-T inhibiton as an minor 'add-on' and not really as a primary mechanism, ya know? It has helped with my allergies a bit too. My allergies seem to cause the hot flashes, so...
I wasn't aware of its effect on improving organs, etc etc. Does anyone have studies to link me regarding this?

 

Thanks for your reply, appreciated! The glycation bond breaking that is discussed here should lead to healthier tissues. I would not know how to measure that but if your skin would have  improved that could be a sign. 

[LearningFromThePast]

I haven't noticed my skin changing at all, but I also haven't been paying attention. RA's ability to drastically diminish brain fog is remarkable. It aids in the reduction of hot flashes, which I suffer from. It seems to be a pretty effective vasoconstrictor, but I've noticed that I'm sensitive and others don't experience that effect as much. This is actually why I'm forced to take 375 mg instead of 500 mg. I could say it slightly enhances mood, but I pair it with GLYX-OX, so I more attribute the mood boosting effects to GLYX-OX. Although, when I pair them, I experience increased verbal fluency and increased overall cognitive functionality more than when I take GLYX-OX alone. I've taken RA alone plenty of times and don't experience much a mood increase. Maybe a slight decrease in irritable, but the combo is truly next-level. I don't think it should be used as an anxiolytic if someone is suffering from somewhat severe anxiety. I look at the GABA-T inhibiton as an minor 'add-on' and not really as a primary mechanism, ya know? It has helped with my allergies a bit too. My allergies seem to cause the hot flashes, so...
I wasn't aware of its effect on improving organs, etc etc. Does anyone have studies to link me regarding this?

Thanks for your reply, appreciated! The glycation bond breaking that is discussed here should lead to healthier tissues. I would not know how to measure that but if your skin would have improved that could be a sign.

In which way would be skin 'improve'?
In which way would my skin be 'improved'?

[gamesguru]

Its ability to reduce brain fog is cos of AChE inhibitors (probably). I was also reading how non-RA components of lemon balm contribute.

I really just don't think much reaches the skin. It probably synergizes well with other anti-AGE compounds, like proanthocyanidins and sulfurophane. Not that blueberries or garlic did too too much for my skin complexion or elasticity. Maybe it is a little softer, clearer (of acne), and harder to sunburn (although it tans more easily).

[Nate-2004]

Its ability to reduce brain fog is cos of AChE inhibitors (probably). I was also reading how non-RA components of lemon balm contribute.

I really just don't think much reaches the skin. It probably synergizes well with other anti-AGE compounds, like proanthocyanidins and sulfurophane. Not that blueberries or garlic did too too much for my skin complexion or elasticity. Maybe it is a little softer, clearer (of acne), and harder to sunburn (although it tans more easily)

 

I was assuming that it'd have an indirect effect on skin by reducing AGEs in general. 

 

Where are you guys getting your RA?

[gamesguru]

Yes, but AGEs also form inside the cell and affect intracellular processes. As well, they get pretty tied up in the extracellular matrix and are not readily distributed around the body in blood (they tend to deposit at the site they were formed).

 

That's why I said RA is likely to be most helpful on the digestive and cardiovascular system, where it will be distributed (it comes in contact with your stomach/intestines, and then your veins and arteries... other organs receive a lower dose, especially the skin). This is why lotions and some medicines are applied to the skin.

[Nate-2004]

I also wonder if RA is small enough a molecule to be absorbed into the skin, and if then whether it would help at all there, or as you say atopic permeability. How can that be tested? 

Edited by Nate-2004, 07 July 2016 - 02:20 PM.

[gamesguru]

it seems to absorb through the skin quite readily and to accumulate in the lungs, spleen, heart, and liver. perhaps rosemary in your homemade oat and coconut oil body-butter (i also add cocoa+shea butter, olive oil, and a touch of beeswax). process the oats and rosemary in a vitamix/blendtec, simmer in the oils, strain into jars (tempered!)

Percutaneous absorption of rosmarinic acid in the rat.
Ritschel WA1, Starzacher A, Sabouni A (1989)

Rosmarinic acid (RA) is a nonsteroidal anti-inflammatory agent. The purpose of the study was to investigate the transdermal absorption of RA, its tissue distribution and absolute bioavailability. In ex vivo experiments, permeation of RA across excised rat skin was about 8 times higher from alcoholic solution than from water, indicating that ethanol may act as sorption promoter. The flux from water or alcoholic solution was 4.4 or 10 micrograms/cm2/h, and the tleg was 7.8 or 3.7 h, respectively. After I.V. administration, RA is best described by a 2-compartment open model; t1/2 = 1.8 h, t1/2 alpha = 0.07 h, V tau = 2.3 L/kg, V beta = 15.3 L/kg. Upon topical administration of RA in form of a W/O ointment (25 mg/kg, 50 cm2), the absolute bioavailability was 60%. 0.5 hours after I.V. administration, RA was detected and measured in brain, heart, liver, lung, muscle, spleen and bone tissue, showing the highest concentration in lung tissue (13 times the blood concentration), followed by spleen, heart and liver tissue. 4.5 hours (peak time) after topical administration of about 3 mg on the hind leg over 20 cm2, RA was measured in blood, skin, muscle and bone tissue. The percutaneous route of administration seems to be a promising one for the therapeutic use of RA as nonsteroidal anti-inflammatory agent.

Edited by gamesguru, 07 July 2016 - 02:43 PM.