Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

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circular
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Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

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I'm unclear on how supplements like ashwagandha and curcumin work in the context of amyloid, and whether on balance it's good or bad to use such supplements to interfere in a process we can't measure in our brains. I read the other day that in some of the studies of pharmaceuticals to block amyloid dementia worsened. If amyloid is protective in the context of infection, and we're susceptible to infection, and some of us even have CIRS, maybe we should just be focused on sleep and circulation to have the healthiest clearance possible but without blocking the formation? Or do these supplements help us avoid toxic plaques without blocking the generation of the protein when it's needed? How in the dark are we on this, or is it just me?
ApoE 3/4 > Thanks in advance for any responses made to my posts.
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by Sandy57 »

Thought I was clear as a bell. Dark very dark, it is not clear science for sure. IMHO.

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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by Harrison »

Hi Circular,

I think Frank has succinctly stated the bottom line, which is we don't know. I'll address your question on pharmaceutical research and offer a bit of speculation.

Nearly all of the amyloid trials to date have failed, with the exception of aducanumab. I am only aware of one trial that actually worsened patients in a severe enough manner to stop the trial, and that was the gamma secretase inhibitor semagacestat. This class of drugs was always a risky proposition because of potential off target effects on the notch receptor.

As to why the amyloid targeting trials have failed, there is quite a bit of after the fact reasoning: the patients were too far along, the patients didn't actually have amyloid (i.e., not Alzheimer's dementia), the drug target was wrong, etc. Amyloid may range from being a causative agent in combination with tau tangles to being purely a result of whatever is the real culprit causing Alzheimer's.

We do know that things like lack of sleep increase amyloid levels, and in general I would not take the approach of wanting to increase amyloid. While amyloid levels do not strictly correlate with cognitive ability, E4s with lower amyloid have better memory than E3s or E4s with higher levels of amyloid. Decreasing amyloid with aducanumab improved cognition, and while solanuzamab did not work, this trended in a positive direction. Based on this, I would go with trying to prevent amyloid accumulation as part of an overall strategy to reduce inflammation and insulin-resistance.

Ashwaganda and curcumin have some data in cell culture and/or in mice showing beneficial effects in reducing amyloid, but I don't expect we'll ever see a randomized, double-blinded, placebo-controlled human trial with amyloid imaging to conclusively demonstrate this. In the end, if one decides to take these, the best they can do is try to use reputable companies that actually sell what they say they are selling, and hope for the best.
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by Sandy57 »

Great advice Harrison. I agree completely. Testing is hard, expensive and complicated. Best we can do is find great supplements and take in moderation.

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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

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Ashwaganda and curcumin have some data in cell culture and/or in mice showing beneficial effects in reducing amyloid, but I don't expect we'll ever see a randomized, double-blinded, placebo-controlled human trial with amyloid imaging to conclusively demonstrate this. In the end, if one decides to take these, the best they can do is try to use reputable companies that actually sell what they say they are selling, and hope for the best.
The case for curcumin has just been bolstered with this new human double blind/placebo controlled RCT that demonstrated improved cognition, mood, and a reduction in abeta and tau signaling via PET scan. You can read the press release here. It was a small study, just 40 people running 18 months. The results were significant enough to warrant a larger trial.

I'm particularly gratified by these results as curcumin was the first supplement I trialled and it had an amazing impact for me. I experienced a reduction in widespread body pain, a lifting of fatigue, a significant boost in mood and a noticeable improvement in my cognition. Curcumin remains a staple in my supplement arsenal.
The people who took curcumin experienced significant improvements in their memory and attention abilities, while the subjects who received placebo did not, Small said. In memory tests, the people taking curcumin improved by 28 percent over the 18 months. Those taking curcumin also had mild improvements in mood, and their brain PET scans showed significantly less amyloid and tau signals in the amygdala and hypothalamus than those who took placebos
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

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I wonder what brand of curcumin was used...anyone with access to the full article?
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

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Memory and Brain Amyloid and Tau Effects of a Bioavailable Form of Curcumin in Non-Demented Adults: A Double-Blind, Placebo-Controlled 18-Month Trial

https://www.sciencedirect.com/science/a ... 8117305110
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by RJones »

I haven't caught up with this full thread yet, but the paper that Julie G just posted seems impressive.

It's it's double blind / placebo controlled -- the gold standard!

It achieves statistical significance despite having only about 20 people each in the control group and the intervention group. That means it's a big effect.

And the effect is found both via cognitive tests AND brain imaging (PET scans). (The brain imaging is "FDDNP-PET", which is somehow a measurement of "brain amyloid and tau accumulation" (quoting the paper).

Test is done on a commercial brand of curcumin--Theracurmin. It's not clear whether the makers of Theracumin provided some funding, but there do appear to be other sources of funding, and the authors are from a prestigious place--UCLA Longevity Center and other UCLA departments.
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by Harrison »

Thanks for posting this Julie. I said I doubted we would see this kind of trial, and even though it is a small trial I am happy to be proven wrong. Gary Small is a bit of a controversial figure, as he has received a warning letter from the FDA about his attempts to market the PET scan used in the study. So consider this as much as a commercial for FDDNP as it is for theracurmin. Nonetheless, there is more science behind this the the majority of supplements on the market. Looking into if I should switch from Longvida to Theracurmin.
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Re: Ashwagandha, Curcumin and Other Amyloid Interfering Supplements

Post by Julie G »

Looking into if I should switch from Longvida to Theracurmin.
Me too. Here's the best and most recent review I could find. I'm taking a BCM-95 version and getting a distinctive benefit. Per this, I could really up my game (bioavailability) with Theracurmin. IMO, the "science" here is so sketchy and full of propaganda that this is a hard one to sort out, but I think I'm going to bite and give this one a whirl. Anyone else confused?
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