22 replies to this topic

[lucid]

Part of this discussion has already occurred in the Resveratrol Effectiveness thread. But where as I have been sick for the past month with one thing or another (Strep, cold, cold, Strep), I have more or less stopped taking it. When taking my rather large dose of resveratrol (2g/day), I notice small acne resembling infections characterized by redness around white center (not acne though), and an affinity for colds. In one since it is comforting to know that the dose that I am taking is effective, but I just can't do it through the winter months. I will also add that though I do not normally drink heavily, the two times that I got strepp were right after wild nights, so you can toss those out. My results are just one data point though.

Here is a study on immune suppression effects of Resv:

Clin Exp Immunol. 2007 Jan;147(1):155-63.
Resveratrol and curcumin suppress immune response through CD28/CTLA-4 and CD80 co-stimulatory pathway.
Sharma S, Chopra K, Kulkarni SK, Agrewala JN.

Immunology Laboratory, Institute of Microbial Technology, Chandigarh, India.
The role of resveratrol and curcumin is well documented in cancer, inflammation, diabetes and various other diseases. However, their immunosuppressive action on T cells, B cells and macrophages is not well documented. In the present study, we have ascertained the effect of resveratrol and curcumin on T and B cells and macrophages. The most striking findings were that both resveratrol and curcumin suppressed the activity of T and B cells and macrophages, as evidenced by significant inhibition in proliferation, antibody production and lymphokine secretion. Interestingly, curcumin imparted immunosuppression by mainly down-regulating the expression of CD28 and CD80 and up-regulating CTLA-4. Resveratrol also functioned by decreasing the expression of CD28 and CD80, as well as by augmenting the production of interleukin (IL)-10.

http://www.ncbi.nlm....Pubmed_RVDocSum

As to discussing the study, Resveratrol decreases the expression of CD28 (thereby decreasing TCell activation) and CD80 (Further decreasing TCell activation and decreasing survival). Resveratrol also increase the production of IL-10 which inhibits Th1 cytokine production (some of which are instrumental in viral, and tumor response) and suppress the antigen presentation capacity of antigen presenting cells.

Here are some graphs from the full text:

After 72 h of incubation, [3H]-thymidine was added and the cells were harvested 16 h later and radioactivity incorporated was measured.


Yeh, resveratrol crushes those white blood cell signals.


Hmmm... Here is the rest of the article:
http://www.blackwell...7.x?cookieSet=1

So these studies were in vitro so to extract these results to being taken orally in humans is a bit of a jump.
Oddly Resveratrol and Curcummin are anti cancerous despite their immune suppressive qualities; this leads to the option of further increasing mean lifespan by remodulating the immune system to a normal or optimal level.

So as it stands for me, I'm not going to take resveratrol till I'm feeling well again.

Edited by lucid, 29 November 2007 - 04:30 AM.

[niner]

Lucid, sorry to hear you're illin'... It looks like resveratrol has a dose-dependent effect there; while it's in vitro, the concentrations that they used (at least at the lower end) are obtainable orally at the kinds of doses we are using.

Nevertheless, I can offer some alternative explanations for your situation. Whenever you get a cold/URI or sore throat, your mucous membranes get inflamed, and their normal barrier function is compromised. Even after you get over the initial insult, the mucous membranes are not back to normal. That probably takes 6-8 weeks. In the meantime, you are more susceptible to infection. That's one of the reasons that bacterial secondary infections are so common in the later stages of a viral URI.

Another thing to consider is that there are some gnarly colds going around at the moment, at least in my region. Everyone in my family has been more or less sick for about six weeks. Except me. And I'm the only one taking resveratrol. (I've also been taking EpiCor for the past 7 weeks, which I'm starting to think is really working.) With each cold that's passed through here, I've noticed a little touch of it which quickly passed without my ever getting sick. This suggests to me that I have been exposed to the viri, but have fought them off. (And I usually get a lot of colds.) I take 2 grams of resveratrol in your Everclear/Miralax cocktail, every other day.

And finally, strep is famous for recurring. I had a strep throat infection four times one fall/winter a long time ago. So your recurrent illness is really pretty normal; resveratrol may or may not be involved. It wouldn't kill you to not take it for a while though. At least you save a few bucks, if nothing else.

[kenj]

Interesting, Lucid. I'll say that I also seem more prone to catch whatever current vira is around at work when I take rsv (I work with kids - bigtime exposure).
In fact, the first time I took higher doses (original Longevinex, several caps) I got a sore throat the day after, and, - the last 12 months with 600-~1000 mg, I've got a sore throat 4 times, - no bacterial infection though. I stop resveratrolling, and it goes away 2 days after. I do take vitamin C several grams, and a freight train of supposedly immune-boosting sups everyday, so this is remarkable to me.

[Matt]

Nevertheless, I can offer some alternative explanations for your situation. Whenever you get a cold/URI or sore throat, your mucous membranes get inflamed, and their normal barrier function is compromised. Even after you get over the initial insult, the mucous membranes are not back to normal. That probably takes 6-8 weeks. In the meantime, you are more susceptible to infection. That's one of the reasons that bacterial secondary infections are so common in the later stages of a viral URI.

This is interesting... When I had chronic sinusitis my nose would be constantly inflamed and bleeding all the time... along with PND. I had it for about a year and didn't take any strong antibiotics for it. What eventually cured my bacterial infection was a cold infection! (lucky eh?)

Anyway I found that the bacterial infection made me FAR more susceptible to respiratory infections, so much than It seemed like I was getting one every 5 weeks or so. Since the sinuses have returned to normal I haven't had a cold since!

Edited by Matt, 29 November 2007 - 08:07 PM.

[lucid]

Nevertheless, I can offer some alternative explanations for your situation. Whenever you get a cold/URI or sore throat, your mucous membranes get inflamed, and their normal barrier function is compromised. Even after you get over the initial insult, the mucous membranes are not back to normal. That probably takes 6-8 weeks. In the meantime, you are more susceptible to infection. That's one of the reasons that bacterial secondary infections are so common in the later stages of a viral URI.

Thanks for the info there Niner, hopefully the new humidifier will help those membranes rebuild.

It looks like resveratrol has a dose-dependent effect there; while it's in vitro, the concentrations that they used (at least at the lower end) are obtainable orally at the kinds of doses we are using.

After reading through an old post of yours I came arcoss the study: Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol...
So the 2.4 mumol/L serum levels found from 5g doses of resveratrol (which is arguably more or less than our effective dose taking into account our improved bio-availability), would put T-Cell proliferation decrease at about 15%. Then one has to resolves some of the other differences between these studies: First off the in vitro study measures the effects over the course 16 hours, and in vivo, resveratrol would hardly be traceable after 16 hours. Further, we take resveratrol every day, so some of the effects might compound, and then again they might not. So, its pretty hard to say what bearing the in vitro study has on us.

I stop resveratrolling, and it goes away 2 days after.

Thats how I feel, I went on and off a few times, I felt like I was able to control my cold by the abstaining of taking resveratrol. Still, me trying something 3 times is a very low 'n'.

Once I have about a 3-4 week track record of being healthy, I'll try taking some more resv.

Editted link to make it clickable, wrong use of tags (href iso. url).

Edited by brainbox, 02 December 2007 - 11:03 PM.

[edward]

I would not be surprised if Resveratrol had some immune suppressing properties and would not be alarmed either. One of the prominent theories of aging, the inflammatory or inflammation theory says that although our immune system is wonderful and necessary, the fact that the initial immune response comes with an inflammatory cascade of reactions that this over time especially in the case of chronic inflammation can lead to an increasing amount of damage to ones own cells thus aging. If Resveratrol does indeed prove to suppress some parts of the immune system this may prove to be a good thing.

[edward]

I have actually been increasingly interested in the inflammation/immune theory of aging recently and have been trying to come up with some ideas. Curcumin/Tumeric, aspirin and others were some of the compounds that looked interesting. So again this is not a bad thing for longevity. People assume that anything that depresses any part of the immune system is bad... this is not the case.

Edited by edward, 02 December 2007 - 09:43 PM.

[balance]

Hey everyone,

I'd like to add this study to this topic:

http://66.102.9.104/...lient=firefox-a


It acknowledges that high dose resveratrol has immune suppressive abilities, yet shows that at low doses, it actually enhances immunity.

Maybe that won't get us to necessarily lower our resveratrol dosage, but it might be interesting nontheless. Hopefully this adds something
useful.

Let me know if anyone has a problem opening the link.

[missminni]

Hey everyone,

I'd like to add this study to this topic:

http://66.102.9.104/...lient=firefox-a


It acknowledges that high dose resveratrol has immune suppressive abilities, yet shows that at low doses, it actually enhances immunity.

Maybe that won't get us to necessarily lower our resveratrol dosage, but it might be interesting nontheless. Hopefully this adds something
useful.

Let me know if anyone has a problem opening the link.

the link doesn't work.
Could you please give the high and low amounts you are referring to.
This is what I wonder about. How much of a good thing is too much? This would be a
great indicator. thanks

Edited by missminni, 03 December 2007 - 12:00 AM.

[lucid]

How much of a good thing is too much?

Don't expect a simple answer for this for resveratrol: As the sirtuins become more activated, they silence more and more of parts of our genome. Hence, we could still be getting lifespan benefits and taking an immune hit. The evolutionarily logic there would be: 'Its better to send energy to the search for and metabolism of food than expensive immune defense.' All that to say there will likely not be a clear 'too much'.

[missminni]

How much of a good thing is too much?

Don't expect a simple answer for this for resveratrol: As the sirtuins become more activated, they silence more and more of parts of our genome. Hence, we could still be getting lifespan benefits and taking an immune hit. The evolutionarily logic there would be: 'Its better to send energy to the search for and metabolism of food than expensive immune defense.' All that to say there will likely not be a clear 'too much'.

since I wasn't able to access the link with the information, I was trying to find out how much
high and low is in regards to the study that
acknowledges that high dose resveratrol has immune suppressive abilities, yet shows that at low doses, it actually enhances immunity.

In other words, what was the low dose that enhanced immunity and what was the high dose that suppressed it.

ETA~I was able to access the study. Unfortunately I can't really figure out the answer to my question. Maybe
somebody can help me out from the abstract:

ABSTRACT AIM: To study the immune modulating effect of low dose of resveratrol. METHODS: Concanavalin A (ConA) and Staphylococcus aureus Cowan (Sac) were used to induce the activation of T lymphocyte and antigen presenting cell and cytokine production. [ 3H]-Thymidine incorporation was used to evaluate the proliferation of lymphocyte. Cytokine production was detected by ELISA method. Dinitrofluorobenzene (DNFB) was used to induce mice delayed type hypersensitivity (DTH, delayed hypersensitivity) response and ear swelling was used as an evaluating indicator. Changes of lymphocyte subtypes were detected by flow cytometry. RESULTS: Resveratrol (0.75-6 μmol/L) concentration-dependently promoted lymphocyte proliferation and IL-2 production induced by ConA. Sac induced IL-12 and IFN-γ (interferon type II ) production were also concentration-dependently enhanced by resveratrol, while IL-10 production was inhibited. Resveratrol (4 mg/kg, ig) promoted DTH response of mouse, which was suppressed by ethanol (16 %, w/v) consumption. Resveratrol treatment had no significant influence on lymphocyte subtypes in mice, however it could reverse the suppressive effect of ethanol both on macrophage percentage and on macrophage MHC-II molecule expression. CONCLUSION: Low dose resveratrol enhanced cell-mediate immune response. Promoting Th1 cytokine production and influencing on macrophage function might be its mechanisms.

Edited by missminni, 03 December 2007 - 05:18 AM.

[niner]

How much of a good thing is too much?

Don't expect a simple answer for this for resveratrol: As the sirtuins become more activated, they silence more and more of parts of our genome. Hence, we could still be getting lifespan benefits and taking an immune hit. The evolutionarily logic there would be: 'Its better to send energy to the search for and metabolism of food than expensive immune defense.' All that to say there will likely not be a clear 'too much'.

since I wasn't able to access the link with the information, I was trying to find out how much
high and low is in regards to the study that
acknowledges that high dose resveratrol has immune suppressive abilities, yet shows that at low doses, it actually enhances immunity.

In other words, what was the low dose that enhanced immunity and what was the high dose that suppressed it.

Missminni, try this link: http://www.chinaphar...4083/23/893.pdf

ABSTRACT
AIM: To study the immune modulating effect of low dose of resveratrol. METHODS: Concanavalin A (ConA) and
Staphylococcus aureus Cowan (Sac) were used to induce the activation of T lymphocyte and antigen presenting
cell and cytokine production. [3H]-Thymidine incorporation was used to evaluate the proliferation of lymphocyte.
Cytokine production was detected by ELISA method. Dinitrofluorobenzene (DNFB) was used to induce mice
delayed type hypersensitivity (DTH, delayed hypersensitivity) response and ear swelling was used as an evaluating
indicator. Changes of lymphocyte subtypes were detected by flow cytometry. RESULTS: Resveratrol (0.75-6
micromol/L) concentration-dependently promoted lymphocyte proliferation and IL-2 production induced by ConA. Sac
induced IL-12 and IFN-g (interferon type II ) production were also concentration-dependently enhanced by resveratrol,
while IL-10 production was inhibited. Resveratrol (4 mg/kg, ig) promoted DTH response of mouse, which was
suppressed by ethanol (16 %, w/v) consumption. Resveratrol treatment had no significant influence on lymphocyte
subtypes in mice, however it could reverse the suppressive effect of ethanol both on macrophage percentage and on
macrophage MHC-II molecule expression. CONCLUSION: Low dose resveratrol enhanced cell-mediate immune
response. Promoting Th1 cytokine production and influencing on macrophage function might be its mechanisms.

It's all the way at the end of the paper, but here's the money quote:

As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

So, according to these guys, at the doses we are using, none of us are going to see immunosuppression. Our immune response should arguably be better. Assuming we are rodents... perhaps humans have a different immune response to resveratrol than rodentia, based on imminst anecdotia.

[missminni]

It's all the way at the end of the paper, but here's the money quote:

As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

So, according to these guys, at the doses we are using, none of us are going to see immunosuppression. Our immune response should arguably be better. Assuming we are rodents... perhaps humans have a different immune response to resveratrol than rodentia, based on imminst anecdotia.

Thanks, I know I saw that.
lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L),
My problem is that I don't know how to convert micromol into mg.

[niner]

It's all the way at the end of the paper, but here's the money quote:

As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

So, according to these guys, at the doses we are using, none of us are going to see immunosuppression. Our immune response should arguably be better. Assuming we are rodents... perhaps humans have a different immune response to resveratrol than rodentia, based on imminst anecdotia.

Thanks, I know I saw that.
lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L),
My problem is that I don't know how to convert micromol into mg.

In a human volunteer with an oral dose of 5 grams resveratrol, a peak plasma level of 2.4 micromolar was measured. I don't know the precise dosage form, but since it wasn't mentioned in the abstract, it was probably just powder in gelcaps. (Sorry for lack of ref; it's late.)

[missminni]

It's all the way at the end of the paper, but here's the money quote:

As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

So, according to these guys, at the doses we are using, none of us are going to see immunosuppression. Our immune response should arguably be better. Assuming we are rodents... perhaps humans have a different immune response to resveratrol than rodentia, based on imminst anecdotia.

Thanks, I know I saw that.
lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L),
My problem is that I don't know how to convert micromol into mg.

In a human volunteer with an oral dose of 5 grams resveratrol, a peak plasma level of 2.4 micromolar was measured. I don't know the precise dosage form, but since it wasn't mentioned in the abstract, it was probably just powder in gelcaps. (Sorry for lack of ref; it's late.)

Thanks so much. That's what I wanted to know. So one would have to take 50 grams to achieve 24 micromolar/l.
Am I correct? If so, that should end any concern about it acting as an immune suppresant. Thanks again.

[SWATgirl]

So what about curcumin? I've read so much about it's protective effects on the liver, but I have Hep B and don't want to depress my immune system!

[kenj]

Would supplementing Glutamine help boost immune function while taking rsv? Seems it's helpful for immunosuppressive conditions.

[Shepard]

Would supplementing Glutamine help boost immune function while taking rsv? Seems it's helpful for immunosuppressive conditions.

Glutamine is only useful in conditions where it becomes an essential AA. If resveratrol was inducing such a state, I don't know how comfortable I'd be with it.

Edited by shepard, 03 January 2008 - 06:41 PM.

[missminni]

Would supplementing Glutamine help boost immune function while taking rsv? Seems it's helpful for immunosuppressive conditions.

Glutamine is only useful in conditions where it becomes an essential AA. If resveratrol was inducing such a state, I don't know how comfortable I'd be with it.

I don't think it is inducing such a state. I have been healthy as a horse since taking it while others are falling sick around me. From my understanding, one would have to take massive amounts way beyond what any of us are taking to induce such a state.
(see Niner's post #14 back a few from here)

http://www.chinaphar...4083/23/893.pdf
As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

Edited by missminni, 03 January 2008 - 06:51 PM.

[kenj]

Well, IME, the immune system certainly takes a beating with rsv (for me 400-1200mg) + a lower calorie intake (mildish CR).
Lucid's idea with cycling rsv might be the practical solution, - necessarily, at least, for those whom fall sick from rsv!

QUOTE
http://www.chinaphar...4083/23/893.pdf
As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

Yea, we don't get this concentration, but no knowing what else might influence the lymphocyte proliferation, or whatever responsible for this mess ;-).

[maxwatt]

Well, IME, the immune system certainly takes a beating with rsv (for me 400-1200mg) + a lower calorie intake (mildish CR).
Lucid's idea with cycling rsv might be the practical solution, - necessarily, at least, for those whom fall sick from rsv!

QUOTE
http://www.chinaphar...4083/23/893.pdf
As for the contradictory of our finding and others,
which almost all stated the immune suppression effect
of resveratrol, we ascribed the inconsistence to the doses
of resveratrol used. In our testing system, the immune
promoting effect of resveratrol was found to be limited
to a relatively lower concentration (less than 12 micromol/
L). At higher concentration (24 micromol/L), resveratrol
significantly inhibited the lymphocyte proliferation
(induced by both mitogens and mixed lymphocyte reaction
(data not provided) and pro-inflammatory
cytokine (TNF-a, IL-6, etc) production. The result
was consistent with recent findings[9].

Yea, we don't get this concentration, but no knowing what else might influence the lymphocyte proliferation, or whatever responsible for this mess ;-).

What form of resveratrol are you using? (Purity, etc.)

I take two to three times what you do. I am seldom sick, even less since taking resveratrol regularly.

[kenj]

I take the 99% extract (P Cuspidatum), - besides possibly Lucid I don't know of anyone with this reaction to rsv.

[lucid]

I am just one data point, I have been taking it off and on since the start of this topic and can't say that I have seen an effect (meaning it doesn't look like resveratrol has made me anymore prone to illness); I still think it was worth asking around to see if anyone else thought they might have felt prone to illness given the study. Its likely that we aren't getting high enough serum levels to achieve an immune suppressant effect. Perhaps mega-dosing Resv + curcumin might give some slight immune suppression.