10 replies to this topic

[Colin]

Hey everybody,

 

First post on here.

 

So I just got my resveratrol in the mail and I'm going to take it (500mg) with a little bit of yoghurt at around noon as I only eat from 12-8. I hear David Sinclair (on the Joe Rogan Podcast) takes it in the morning which is confusing to me because he also says that he does intermittent fasting but eats snacks at night haha.

 

Anyway, I was wondering how you guys take it. Can I take it in the morning with just water to avoid breaking fasting? Is it generally recommended to take it with food?

 

Cheers,

Colin

[Kimer Med]

I take mine with dinner.

 

For most people, Resveratrol will lower your blood sugar somewhat, so taking it while fasting has the potential of making you feel poorly as a result. Taking it with a meal, though, helps reduce the blood sugar spike that normally accompanies meals, which in turn helps keep glycation and insulin down -- both of which are very good for long-term health.

 

[recon]

I take mine with meals.

My idea is that resveratrol activates the sirtuin genes, which are heavily activated when you are fasting / sleeping (and thereby fasting) anyways.

Therefore, I'll take those sirtuin activators when I break my fast since they are activated when I am fasting anyways. That way I'll have them activated most of the time, or at least shortens the time of inhibition during my eating window.

[Oakman]

Quite a bit of research shows that R is pro-oxidative in daytime, anti-oxidative at night. Here's one...

 

http://www.resveratr...dant-by-day/45/

[MankindRising]

Quite a bit of research shows that R is pro-oxidative in daytime, anti-oxidative at night. Here's one...

 

http://www.resveratr...dant-by-day/45/

Its pretty obvious by now though that multiple studies also have shown that women dont eat for atleast 3hours before bed have quite a lot of decreased risk for breast cancer, also melatonin is considered anti-breastcancer. The link? melatonin is an aromatase inhibitor... and what is resveratrol? yes a mixed agonist/antagonist? possible outcome in situations like this? well humans can only guess its like tossing a coin.

 

Also from what I have noticed so far is that resveratrol is powerfully energizing both mentally and physically. Lots of people have also noticed waking up more often and harder time getting to bed when taking resveratrol too late in the day.

 

Also resveratrol being a sirt1 activator would be used best in early morning for healthy circadian gene expression.

 

Regarding the pro-oxidative effect at low doses, well you need some ROS to function properly, even exercise and light itself create ROS, its the adaptation response and how your body handles it what matters.

 

I for one cant imagine myself going to bed on resveratrol.

 

On top of that studies that purely measure resveratrols effect itself on dna, oxidative stress and god knows what makes me laugh, kind of gets old n boring.

 

Heres a study for example showing that administrating resveratrols METABOLITE might even be better for humans than administrating resveratrol itself (since res-3-o-sulp. can act as a pool and transform back into regular resveratrol):

 

Sulfate Metabolites Provide an Intracellular Pool for Resveratrol Generation and Induce Autophagy with Senescence

http://stm.sciencema...49-560a232864a9

 

"Sulfate metabolites induced autophagy and senescence in human cancer cells; these effects were abrogated by inclusion of a sulfatase inhibitor, which reduced intracellular resveratrol. Together, our findings suggest that resveratrol is delivered to target tissues in a stable sulfate-conjugated form and that the parent compound is gradually regenerated in selected cells and may give rise to the beneficial effects in vivo. At doses considered to be safe in humans, resveratrol generated via this route may be of greater importance than the unmetabolized form."

[maxwatt]

The Boocock (spelling?) study of the pharmokinetics a few years ago showed resveratro was better absorbed taken on an empty stomach than with food. IT reached a higher peak level, and  faster, and blood levels stayed higher longer.

 

Also, there is a secondary peak in blood levels about eight hours after dosing, due to hepatic recirculation.

 

And it has wonderful effects added to a skin cream.  But only on the skin.  And if you are able you might try taking it vaginally.  (Not completely a joke.  Mucus membrandes absorb and bypass first pass liver metabolism, resulting in higher blood levels..  The oral mucosa are not large enough to work well.)

 

Oakman is right, different effects AM vs PM.  Depends on what you are trying to accomplish,  But remember that rodents are nocturnal, so primates might have a reversed response to the mice.

[MankindRising]

Taking a compound that is known to activate SIRT1 in the evening makes no sense though IMHO. Sleep is critical to health, by administrating resveratrol in the evening and activate SIRT1 you start activating genes that are supposed to be active during morning/daytime.

 

Anyway thats just my 2cents, what other people do with my health is their concern.

[recon]

The Boocock (spelling?) study of the pharmokinetics a few years ago showed resveratro was better absorbed taken on an empty stomach than with food. IT reached a higher peak level, and faster, and blood levels stayed higher longer.

Also, there is a secondary peak in blood levels about eight hours after dosing, due to hepatic recirculation.

And it has wonderful effects added to a skin cream. But only on the skin. And if you are able you might try taking it vaginally. (Not completely a joke. Mucus membrandes absorb and bypass first pass liver metabolism, resulting in higher blood levels.. The oral mucosa are not large enough to work well.)

Oakman is right, different effects AM vs PM. Depends on what you are trying to accomplish, But remember that rodents are nocturnal, so primates might have a reversed response to the mice.

Interesting with regards to the empty stomach portion. Another reason I have it with meals was because I remembered something about the absorption for both was the same but AUC for with meals is larger.

[recon]

Taking a compound that is known to activate SIRT1 in the evening makes no sense though IMHO. Sleep is critical to health, by administrating resveratrol in the evening and activate SIRT1 you start activating genes that are supposed to be active during morning/daytime.

Anyway thats just my 2cents, what other people do with my health is their concern.

Same as my thoughts.

When I first learn about Sirtuins, from videos of Dr Sinclair, he said that Sirtuins are mainly activated by lack of food and therefore are activated upon sleep anyways. Therefore, isn't it intuitive that we want to activate it during daytime when we eat.

[ceridwen]

Does that mean one should drink red wine in the morning?

[MankindRising]

Resveratrol Stimulates Cortisol Biosynthesis by Activating SIRT-Dependent Deacetylation of P450scc

https://www.ncbi.nlm...les/PMC3380297/

 

"In the human adrenal cortex, cortisol is synthesized from cholesterol by members of the cytochrome P450 superfamily and hydroxysteroid dehydrogenases. Both the first and last steps of cortisol biosynthesis occur in mitochondria. Based on our previous findings that activation of ACTH signaling changes the ratio of nicotinamide adenine dinucleotide (NAD) phosphate to reduced NAD phosphate in adrenocortical cells, we hypothesized that pyridine nucleotide metabolism may regulate the activity of the mitochondrial NAD+-dependent sirtuin (SIRT) deacetylases. We show that resveratrol increases the protein expression and half-life of P450 side chain cleavage enzyme (P450scc). The effects of resveratrol on P450scc protein levels and acetylation status are dependent on SIRT3 and SIRT5 expression. Stable overexpression of SIRT3abrogates the cellular content of acetylated P450scc, concomitant with an increase in P450scc protein expression and cortisol secretion. Mutation of K148 and K149 to alanine stabilizes the expression of P450scc and results in a 1.5-fold increase in pregnenolone biosynthesis. Finally, resveratrol also increases the protein expression of P450 11β, another mitochondrial enzyme required for cortisol biosynthesis. Collectively, this study identifies a role for NAD+-dependent SIRT deacetylase activity in regulating the expression of mitochondrial steroidogenic P450."

 

It would be interesting to see how long after oral resveratrol intake the increase 11beta hsd expression takes place.

 

The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats*(they used resveratrol for sirt1 activation)

https://www.ncbi.nlm...les/PMC4786719/

 

"Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH."

 

ACTH, CRH and CORTISOL peak upon awakening due to the CARS (cortisol awakening response), a poor CARS response has been associated with adhd, asd, borderline (only in males from what I remember, female borderline patients even had increased cortisol during awakening compared to healthy controls). This jolt of cortisol is extremely important, people underestimate this in health. You need that jolt of cortisol in the morning, not only to get out of bed, but also for the body to start up all other processes. Its like comparing a pc that has trouble starting up getting into window or a pc that instantly boots from the moment you press the powder button.

 

So correct me if im wrong, afaik the general rule of thumb is to have cortisol spike in the morning (30mins long), then get a drop over the day and being lowest in the evening. Interesting is also that in mental disorders with poor CARS is that they often have high evening cortisol. Its almost as if its extremely crucial for the body that cortisol is high upon awakening... if not it seems there is misalignment and spillover in the evening.