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SIR6 Activator - is it worth it?

sirtuins sir6 supplement

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6 replies to this topic

#1 starshade

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Posted 13 June 2021 - 10:19 AM


Professor Vera Gorbunova has recently promoted a supplement based on her research on SIR6 activation.

Activating SIR6 is without doubt very promising pathway. However, when commercial interests starts mixing in big time, I become very suspicious.

She spoke a lot about fucoidan, seaweed extracts etc and a particular unspecified compound from seaweed that is really good at activation.

The supplement that came out is on back order at DoNotAge company starting at whopping 590usd/year, but most people would need about 1100 usd per year...
no name of the compound, no papers describing it well, no clinical trials, etc. Pure business and leap of faith. Btw, there's no link from the front page of DoNotAge, they hide the supplement from non-subscribers.

Lamin A for example, is a compound that has research backing. However, I haven't seen it being sold.

Anyone would be willing to take this leap of faith? Me no, I'd wait for disclosed compounds and at least mice trials.



 



#2 maxwatt

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Posted 20 June 2021 - 05:30 PM

worthless beyond placebo effect



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#3 thompson92

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Posted 21 June 2021 - 12:34 AM

SIRT6 activators are in a paper by Akter et al  (2021)

 

Quercetin, Icariin, Kaempferol, Fucoidan, Delphinidin, Luteolin, Cyanidin, Fisetin, Oleic/Linoleic acids

 

I think some (maybe most) work as CD38 inhibitors and increase NAD+ availability, thereby providing substrate for SIRT6.  Exercise is probably the best bet.

 



#4 OlderThanThou2

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Posted 02 July 2021 - 10:12 AM

In the okinawan diet they were eating a lot of seaweed. Fucoidan grows in Japan.

 

Nicotinamide inhibits sirt6, so what is the effect of taking NAD+ precursors on sirt6? Instead of precursors, It might be better to try and increase NAD+ with apigenin, quercetin, luteolin and such, which increase NAD+ by inhibiting CD38, and which increase sirt6 directly. Me wonders if it might be better to get as many types of sirt6 activating polyphenols as possible because usually their absorption is very low. This being said, it's always a guess to say that the effect would be cumulative.

 

 



#5 Qowpel

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Posted 04 July 2021 - 11:07 PM

caloric restriction optimum nutrition  increases SIRT 6. So does excercise. I would say hey, just do those things.

 

Quercetin also activates SIRT 6, and so does luteolin and cyaninidins (the dark pigment in berries)



#6 Qowpel

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Posted 04 July 2021 - 11:11 PM

take a look here 



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#7 OlderThanThou2

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Posted 05 July 2021 - 06:59 AM

caloric restriction optimum nutrition  increases SIRT 6. So does excercise. I would say hey, just do those things.

 

Quercetin also activates SIRT 6, and so does luteolin and cyaninidins (the dark pigment in berries)

 

Pure quercetin and a couple other derivatives activate sirt6 at high concentration, and inhibits it at low concentration. I checked the type of quercetin in onion and cocoa, and they seem to contain mainly derivatives that don't have this effect at low concentration.

 

A Review of Sirtuin Inhibitors in Therapeutics, Pharmaceutics, and Plant Research -Journal of Life Science | Korea Science

 

 

 

Quercetin is a plant flavonol in the flavonoid group. Natural quercetin can be found in onions, leeks, and broccoli [46]. Two quercetin derivatives, diquercetin and 2-chloro-1,4-naphthoquinone-quercetin, were identified as SIRT6 inhibitors [23](Fig. 4). The IC 50 value of diquercetin and 2-chloro-1, 4-naphtoquinone-quercetin is 130 μM and 55 μM, respectively [24]. The mode of inhibition of these inhibitors is different because diquercetin competes with nicotinamide adenine dinucleotide (NAD+), whereas 2-chloro-1,4-naphthoquinone-quercetin competes with the acetylated substrate in the catalytic site of SIRT6 [24]. 

 

 

Onions don't have much pure quercetin:

Quercetin in onion (Allium cepa L.) after heat-treatment simulating home preparation - ScienceDirect

 

 

 

Quercetin content in onion (Allium cepa L.), represented mainly by 3,4′-O-quercetin diglucoside (3,4′-Qdg) and 4′-O-quercetin glucoside (4′-Qmg), was examined in five cultivars before and after three cooking treatments (sautéing, baking, and boiling). Baking and sautéing produced a 7–25% gain in quercetin concentration, while boiling produced an 18% decrease in quercetin concentration. Ratios of 3,4′-Qdg to 4′-Qmg in tissues ranged from 1:1.3 and 1:1.7, and combined the two conjugates represented 89–90% of total flavonol content in treatment and raw control means indicating heat stability of the flavonols. Changes in flavonol concentrations as a result of cooking method were consistent across all five cultivars.

 

 

Cocoa also:

More Antioxidants in Cocoa | The Journal of Nutrition | Oxford Academic (oup.com)

 

 

 

Our group has identified and quantified three flavonols, isoquercitrin, quercetin 3-glucuronide and quercetin, in cocoa powder using HPLC-DAD coupled with HPLC-MS. The major flavonols in cocoa are isoquercitrin (23 mg/100 g), quercetin 3-glucuronide (5 mg/100 g) and quercetin (2 mg/100 g). In general, cocoa powder contains 30 mg flavonols/100 g.

 

 

Pure quercetin supplements might cause a inhibition effect who knows.

 

Luteolin also seems to activate sirt6 only at high concentration and inhibit it at low concentration:

 

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus (nih.gov)

 

 

Phenolic compounds, such as quercetin and luteolin, also enhance SIRT6 deacetylation activity, albeit at very high concentrations

 

I don't know if celery seeds for instance would have derivatives of luteolins that are more likely to work at all concentration.

 

All this is not in vivo so it's hard to know for sure how it would turn out in vivo. Luteolin should increase NAD+ via CD38 inhibition, that might help.

 

Cyanidins don't seem to have that dual effect of concentration and also is more effective so perhaps it's the best way to try and do it. The richest source of cyanidins by far is black currant AFAIK, I've tried it but darn it it's hard to digest.

 

As for fucoidan, it seems to inhibit sirt6 at high concentration:

 

The Identification of a SIRT6 Activator from Brown Algae Fucus distichus (nih.gov)

 

 

Both methods demonstrate that fucoidan is an activator of SIRT6. Interestingly, it was demonstrated that higher concentrations of fucoidan (>16 µg/mL in the Western blot analysis method) resulted in the reduced activation of SIRT6 activity (data not shown). A similar observation was made in the HPLC-based assay at higher concentrations as well, indicating that fucoidan may have a dual role in SIRT6, similar to what was observed for quercetin and luteolin [13].

 

 

 


Edited by OlderThanThou2, 05 July 2021 - 07:06 AM.

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