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Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Alzheimer's, cardiovascular, and other chronic diseases; biomarkers, lifestyle, supplements, drugs, and health care.
GenePoole0304
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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby GenePoole0304 » Sun Feb 15, 2015 11:10 am

Allermax contains quercetin...

J Nutr. 2010 Feb;140(2):278-84. doi: 10.3945/jn.109.117655. Epub 2009 Dec 23.
Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype.
Egert S1, Boesch-Saadatmandi C, Wolffram S, Rimbach G, Müller MJ.
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Abstract

Our objective was to examine the effect of a quercetin supplementation on blood pressure, lipid metabolism, markers of oxidative stress, inflammation, and body composition in an at-risk population of 93 overweight-obese volunteers aged 25-65 y with metabolic syndrome traits in relation to apolipoprotein (apo) E genotype. Participants were randomized to receive 150 mg/d quercetin in a double-blinded, placebo-controlled, crossover trial with 6-wk treatment periods separated by a 5-wk washout period. Retrospectively, 5 apoE genotype variants were found (epsilon2/epsilon3, n = 3; epsilon3/epsilon3, n = 60; epsilon3/epsilon4, n = 23; epsilon2/epsilon4, n = 4; and epsilon4/epsilon4, n = 3). Participants were classified into the following 3 apoE phenotypes: apoE2 (n = 3), apoE3 (n = 60), and apoE4 (n = 26). Data were analyzed for apoE3 and apoE4 subgroups. Quercetin decreased systolic blood pressure by 3.4 mm Hg (P < 0.01) in the apoE3 group, whereas no significant effect was observed in the apoE4 group. Quercetin decreased serum HDL cholesterol (P < 0.01) and apoA1 (P < 0.01) and increased the LDL:HDL cholesterol ratio (P < 0.05) in the apoE4 subgroup, whereas the apoE3 subgroup had no significant changes in these variables. Quercetin significantly decreased plasma oxidized LDL and tumor necrosis factor-alpha in the apoE3 and apoE4 groups, whereas no significant inter-group differences were found. Serum C-reactive protein and nutritional status (body weight, waist circumference, fat mass, fat-free mass) were unaffected compared with placebo. In conclusion, quercetin exhibited blood pressure-lowering effects in overweight-obese carriers of the apo epsilon3/epsilon3 genotype but not in carriers of the epsilon4 allele. Furthermore, quercetin supplementation resulted in a reduction in HDL cholesterol and apoA1 in apo epsilon4 carriers.

PMID:
20032478
[PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/20032478

circular
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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby circular » Wed Oct 14, 2015 3:58 pm

I've got to come back to this whole thread. Have still not focused in on resveratrol. For now adding this 2015 study:

"A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease"

http://www.neurology.org/content/early/ ... 5.abstract
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Phlogiston » Sat Oct 17, 2015 11:59 am

Thank you for sharing this study, Circular. The results seem to raise some red flags about supplementing with resveratrol.

What I find disturbing is the fact that brain volume loss was greater in the treated (resveratrol) group than in the placebo group. At first I wondered whether I was misreading this, or whether the author had expressed himself poorly. But it is reaffirmed in detail that resveratrol increased brain volume loss, although the greater atrophy "was not associated with cognitive or functional decline."

As someone without academic training in this area, I have always seen loss of brain volume offered as a prima facie indicator of neurodegeneration, with arrest or reversal of that loss always seen as a positive indicator. For example, the recent letter from Dr. Bredesen which stated that a patient's increased hippocampal volume after a year of adherence to the protocol showed that "we're on the right track." And that patient's increase in hippocampal volume correlated with dramatic cognitive improvement.

In addition, the AB40 levels declined more in the placebo group than the treatment group. Am I wrong in assuming that this is another ominous indication?

I have some high dose (500 mg) resveratrol ordered. This study makes me wonder whether I should send it back unopened.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby circular » Sat Oct 17, 2015 9:09 pm

Since Dr. Bredesen includes resveratrol on his list of supplements, I wonder if the patient whose brain volume increased was taking it or not. If so, maybe in the context of lots of inputs the support neurogenesis the effect is nullified? Not that we have a study of that, but if Dr. Bredesen can show that in the context of his *network* approach resveratrol doesn't lead to volume loss, then that's good.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Juliegee » Mon Oct 19, 2015 9:09 am

Whoa! Good catch, Phlogiston. This is something I plan to keep an eye on. It contradicts a much larger body of work...but gives me pause. It's worth noting that the dosage used was quite high- 500mg. I wonder of any other studies corroborate this finding?

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Phlogiston » Mon Oct 19, 2015 9:40 am

Julie, the study actually used 2,000 mg of resveratrol daily, so this is a megadose in comparison to what most supps contain. This kinds of seems parallel to the UCLA study where they're using 8 400 mg caps of Longvida circumin.

Just as antioxidants can become pro-oxidant at a high enough dosage level, perhaps this study has documented the dosage level where resveratrol somehow accelerates cellular aging and death rather than slowing it. It's not surprising that such a point might exist, but the authors seem oddly noncommittal about results which appear so negative.

The 500 mg dose is the potency of the resveratrol I ordered from Nutrigold. I was congratulating myself on finding such a high dose, and this thread is making me reconsider my enthusiasm.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Juliegee » Mon Oct 19, 2015 10:11 am

Ah, thanks for that important clarification, Phlogiston. It actually helps explain these disparate results. They actually started at 500 mg, but then gradually increased to 2,000 mg- a whopping dose :shock:
METHODS: Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52.

I've been taking 200mg of trans resveratrol daily and just learned that is also the dose recommended by Dr. Bredesen. Even 500 mg seems really high...

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby circular » Mon Oct 19, 2015 10:29 am

Shame on them for not testing at each point before upping the dose to see if there was this dose-response relationship: Did the brain areas start out increasing in size and then fall off?

"Just as antioxidants can become pro-oxidant at a high enough dosage level" …

I've been cautious about too high doses of antioxidants because one could through of their redox status in the opposite direction, but I'm curious what the mechanism is that too many become pro-oxidant, if you know?
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Phlogiston » Mon Oct 19, 2015 12:40 pm

Circular, I don't know much about that phenomenon (paradoxical effects of antioxidants at high doses). I have seen it referred to at www.Longecity.org where many posters seem to have academic training in biochemistry.

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Re: Resveratrol found to activate ancient stress response and at 1,000 times lower doses

Postby Phlogiston » Mon Oct 19, 2015 9:33 pm

If you copy and paste the shortcut below into your address bar, you will be able to access a study titled "Pterostilbene, But Not Resveratrol, Is A Potent Neuromodulator in Aging and Alzheimer's Disease".

http://www.longecity.org/forum/index.ph ... h_id=13366

The researchers compared equal doses of pterostilbene and resveratrol in mice bred to mimic late-onset Alzheimers. Short version: Resveratrol is good, but pterostilbene is substantially better. And yes, there are pterostilbene supps on the market.


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