10 replies to this topic

[Valijon]

I had a few questions regarding supplements for Sirt1 activation. Mostly I'm looking for the best and or cheapest ways to do this. I currently take resveretrol with pterostilbene. I just read that there's cheaper and more potent ways to do this. Is this correct and what substances are we talking about?

[mrkosh1]

The price of nicotinamide riboside is finally coming down. It boosts SIRT1 activity via an increase in NAD+.

 

R-ALA isn't insanely expensive (depending on your budget) and boosts SIRT1 and PGC1a via first activating NRF2 which activates NQO1 to recycle spent NAD.

 

Sulforaphane potently boosts NRF2 more potently than R-ALA or just about any other supplement. The recycling effect of NQO1 would probably be boosted very high via this supplement. The benefit here is that you could grow your own broccoli sprouts to obtain the sulforaphane. The seeds are a little pricey (maybe 25 dollars for a pound) but not outrageous. In bulk, the price of the seeds would come down.

 

Beta lapachone is another possibility, but it would be challenging to acquire.

[Valijon]

I've been following the beta lapachone conversations with great interest. Right now the price is very very high. Do you feel NR is truelly effective and not some snake oil? I thought it was a lot of hype and the same results could be had from nicotinamide?

I just placed my first order for ALA. What's the R stand for?

[RWhigham]

I just placed my first order for ALA. What's the R stand for?

Different Forms of Lipoic Acid: What You Need to Know

• "Alpha-Lipoic acid consists of a 50/50 mixture of the R-(natural) and S-(unnatural) enantiomers that are mirror images of each other and is called a ‘racemic’ mixture. It is the most widely available commercial form of alpha lipoic acid."

• "Much of the research over the past 30 years has been done with racemic Alpha-Lipoic acid because the R form was not commercially available."

• "R-Lipoic Acid (the R (+) enantiomer) is the form of lipoic acid that occurs naturally in plants, animals and the human body and is responsible for the specific beneficial effects of Alpha-Lipoic acid. R-lipoic acid (RLA) is the only form that functions as a co-factor for mitochondrial enzymes involved in energy production."

• "S-Lipoic Acid (The S (-) enantiomer) is not found in nature. S-Lipoic acid (SLA) is a by-product from chemical synthesis of racemic Alpha-Lipoic acid and may inhibit the most essential properties of the R form, including interactions with proteins, enzymes and genes."

The right hand version of a molecule is prefixed by "R-", but the left hand version can be prefixed by "L-", "S-". or "D-".  Life on Earth is mostly built from "L-" versions (eg L-thyroxine the thyroid hormone). R-ALA is unusual in this respect.

I had a few questions regarding supplements for Sirt1 activation. Mostly I'm looking for the best and or cheapest ways to do this. I currently take resveretrol with pterostilbene.

A special gynostemma pentaphyllum (aka jiaogulan) extract "AMPK activator", will activate AMPK even more strongly than the banned injections of AICAR which were responsible for several Tour de France wins. The cascade of events includes numerous downstream SIRT1 effects. I take Swanson's "ActivAMP" once/day (twice/day was too much). LEF's "AMPK Activator" is the same thing.

 

Resveratrol stimulation of SIRT1 has been controversial. Spindler's original discovery was shown to be based on questionable chemistry. An alternative test showed no stimulation from resveratrol, but by then the resveratrol craze had momentum.   

Edited by RWhigham, 19 January 2017 - 02:00 AM.

[Valijon]

Thank you for the information. This is the first I've heard of the R version.

[maxwatt]

 

Resveratrol stimulation of SIRT1 has been controversial. Spindler's original discovery was shown to be based on questionable chemistry. An alternative test showed no stimulation from resveratrol, but by then the resveratrol craze had momentum.   

 

That is not the whole story.  The positive for SIRT1 activation was shown to be due to the material used for the assay.  Subsequent tests with other methodologies did confirm SIRT1 activation by resveratrol.

Still not the whole story.  Other small molecules also activate SIRT1, but sirt1 activation was not the only thing resveratrol does. It activates some of the other sirtuins (as do other substances) and PPAR gamma improving exercise performance.  It probably does as much as pterostilbene, though higher doses are needed.  (Pterostilbene is methylated resveratrol, as codeine is methylated morphine.)   Resveratrol is not physiologically inert, and may improve healthspan, but is not likely life extending.  But so are other things.

 

Dihydromyricetin also binds to sirt1, and also binds to GABA receptors, alleviating some of the effects of alcohol.  Also stimulates mitochondria production via another sirtuin and thus improves exercise performance,

 

Baicalin activates SIRT1, and also binds to SIRT3, and unlike resveratrol stimulates regeneration of articular cartilage.  At lease in mice.  It may have to be injected into the joint for this to occur, or perhaps oral ingestion will result in sufficient concentrations to treat arthritis.

 

NAD ratios are associated with longevity, and many things have come along touted to improve this.  I believe resveratrol does.   Nicotinamide riboside does this more strongly.  Touted to work even better with pterostilbene, no confirmed results in humans and no reports from self-experimenters that cannot be ascribed to placebo effect.

 

R-lipoic acid tends to polymerize and be inactive.  Some forms are marketed as non-polymerizing.  Again, no spectacular results in human beings.

 

Probably the single most effective thing you can do for health and longevity is exercise.  The second thing is eliminate sugar from your diet, and simple carbs like bread and pasta and rice,  A program like Cron-o-meter which can estimate your intake of various nutrients and vitamins from the foods you eat will spot insufficiencies you can remedy.  

 

 

 

 

 

 

 

 

[Anthony_Loera]

Resveratrol activates the following 4 out of 7 Sirtuins (some better than others):

 

 20170103_113816_992.jpg   82.81KB   2 downloads

(Per Hector Valenzuela Ph.D. findings in CD4 and CD8 human immune cells)

 

Sirt1

Sirt2

Sirt4

Sirt5

 

Cheers

A

[Skyguy2005]

 

 

Dihydromyricetin also binds to sirt1, and also binds to GABA receptors, alleviating some of the effects of alcohol.  Also stimulates mitochondria production via another sirtuin and thus improves exercise performance,

 

 

I'm really interested in dihydromyricetin, it's like resveratrol if you read through many of the studies (inhibits MTOR and S6K, activates autophagy, SIRT-promoting, attenuates diabetes, neuroprotective, anti cancer, liver protective etc.), and I like resveratrol.

 

I also am a fan of south-east asian herbs in the sense that I like Resveratrol (Japanese Knotweed easily the best source), Ginkgo Biloba (native to China and widespread in China, Japan and Korea), Red Reishi (famous Chinese/Japanese mushroom, most Red Reishi is from that region). I've just noticed herbs from that region tend to be more powerful, at least for me. These three herbs are pretty much my "stack" (I also take glucosamine, and occasionally NAC for detox).

 

Anyway dihydromyricetin is found either exclusively or mostly in China-Japan neck-of-the-woods.

 

Unfortunately, I cannot find dihydromyricetin, or somethinge like Moyeam Tea, or Japanese Raisin tree etc. in the UK. So I can't give it a try.

 

Does anyone know where you could get it in the UK? I've seen it somewhere on amazon.com, but that's uber-expensive shipping...
 

[maxwatt]

 

 

Resveratrol stimulation of SIRT1 has been controversial. Spindler's original discovery was shown to be based on questionable chemistry. An alternative test showed no stimulation from resveratrol, but by then the resveratrol craze had momentum.   

 

That is not the whole story.  The positive for SIRT1 activation was shown to be due to the material used for the assay.  Subsequent tests with other methodologies did confirm SIRT1 activation by resveratrol.

Still not the whole story.  Other small molecules also activate SIRT1, but sirt1 activation was not the only thing resveratrol does. It activates some of the other sirtuins (as do other substances) and PPAR gamma improving exercise performance.  It probably does as much as pterostilbene, though higher doses are needed.  (Pterostilbene is methylated resveratrol, as codeine is methylated morphine.)   Resveratrol is not physiologically inert, and may improve healthspan, but is not likely life extending.  But so are other things.

 

Dihydromyricetin also binds to sirt1, and also binds to GABA receptors, alleviating some of the effects of alcohol.  Also stimulates mitochondria production via another sirtuin and thus improves exercise performance,

 

Baicalin activates SIRT1, and also binds to SIRT3, and unlike resveratrol stimulates regeneration of articular cartilage.  At lease in mice.  It may have to be injected into the joint for this to occur, or perhaps oral ingestion will result in sufficient concentrations to treat arthritis.

 

NAD ratios are associated with longevity, and many things have come along touted to improve this.  I believe resveratrol does.   Nicotinamide riboside does this more strongly.  Touted to work even better with pterostilbene, no confirmed results in humans and no reports from self-experimenters that cannot be ascribed to placebo effect.

 

R-lipoic acid tends to polymerize and be inactive.  Some forms are marketed as non-polymerizing.  Again, no spectacular results in human beings.

 

Probably the single most effective thing you can do for health and longevity is exercise.  The second thing is eliminate sugar from your diet, and simple carbs like bread and pasta and rice,  A program like Cron-o-meter which can estimate your intake of various nutrients and vitamins from the foods you eat will spot insufficiencies you can remedy.  

 

 

An addendum.  Baicalin binds to Sirt6, which regenerates joint cartilage.
 

[Andrews]

 

 

 

Resveratrol stimulation of SIRT1 has been controversial. Spindler's original discovery was shown to be based on questionable chemistry. An alternative test showed no stimulation from resveratrol, but by then the resveratrol craze had momentum.   

 

That is not the whole story.  The positive for SIRT1 activation was shown to be due to the material used for the assay.  Subsequent tests with other methodologies did confirm SIRT1 activation by resveratrol.

Still not the whole story.  Other small molecules also activate SIRT1, but sirt1 activation was not the only thing resveratrol does. It activates some of the other sirtuins (as do other substances) and PPAR gamma improving exercise performance.  It probably does as much as pterostilbene, though higher doses are needed.  (Pterostilbene is methylated resveratrol, as codeine is methylated morphine.)   Resveratrol is not physiologically inert, and may improve healthspan, but is not likely life extending.  But so are other things.

 

Dihydromyricetin also binds to sirt1, and also binds to GABA receptors, alleviating some of the effects of alcohol.  Also stimulates mitochondria production via another sirtuin and thus improves exercise performance,

 

Baicalin activates SIRT1, and also binds to SIRT3, and unlike resveratrol stimulates regeneration of articular cartilage.  At lease in mice.  It may have to be injected into the joint for this to occur, or perhaps oral ingestion will result in sufficient concentrations to treat arthritis.

 

NAD ratios are associated with longevity, and many things have come along touted to improve this.  I believe resveratrol does.   Nicotinamide riboside does this more strongly.  Touted to work even better with pterostilbene, no confirmed results in humans and no reports from self-experimenters that cannot be ascribed to placebo effect.

 

R-lipoic acid tends to polymerize and be inactive.  Some forms are marketed as non-polymerizing.  Again, no spectacular results in human beings.

 

Probably the single most effective thing you can do for health and longevity is exercise.  The second thing is eliminate sugar from your diet, and simple carbs like bread and pasta and rice,  A program like Cron-o-meter which can estimate your intake of various nutrients and vitamins from the foods you eat will spot insufficiencies you can remedy.  

 

 

An addendum.  Baicalin binds to Sirt6, which regenerates joint cartilage.
 

 

How do you know that baicalin binds to Sirt6?

Edited by Andrews, 25 January 2017 - 08:59 AM.

[BieraK]

Kelp:
https://examine.com/...hyllum-nodosum/

 

4.1. Mechanisms

Incubation of Ascophyllum Nodosum extract (18% Phlorotannins) is able to rapidly activate SIRT1 to 165% of baseline within 20 minutes, and over 24 hours of incubation peak at 233% baseline levels.^[1] At both timepoints, this extract outperformed resveratrol at 100uM (120% and 165%, respectively).^[1]

Appears to be more potent in activating SIRT1 than resveratrol itself according to one study (SIRT1 being the protein thought to underlie resveratrol's longevity actions, which are still admittedly questionable)

Edited by BieraK, 17 June 2017 - 09:29 PM.