ACE trial: Arterial Stiffness, Cognition and Equol

[NF52]

The ACE trial: Arterial Stiffness, Cognition and Equol may be of interest to those concerned about vascular contributions to brain aging and cognitive impairment, if you live near Pittsburgh PA, Winston-Salem, NC or Atlanta, GA and are between 65 and 85. That's about it for inclusion criteria, although a phone screening goes over a number of exclusionary criteria, which can be seen in the second link below. Study requirements are in bold below.

The main purpose of the ACE Trial (short for Arterial Stiffness, Cognition and Equol) is to determine if taking Equol, a plant-based supplement, could slow the progression of stiffening of the arteries, small blood vessel disease in the brain and memory decline.
The ACE Trial will recruit a total of 400 African American and Caucasian participants between the ages of 65 and 85 from three locations in the US (200 at the University of Pittsburgh, Pittsburgh, PA; 100 from Emory University in Atlanta, GA; and 100 at Wake Forest University in Winston-Salem, NC)...This study involves an initial phone call and screening visit to find out if you are eligible. We will ask you to complete 7 clinic visits over a two year period so that we can evaluate any changes.

As part of the study, we will complete several non-invasive tests like measuring your blood pressure and heart rate, height and weight, and doing tests of walking and thinking. We will collect a sample of your blood, urine and stool. If eligible after screening, participants will have more visits over 2 years and several phone calls.

Participants will be asked to have a magnetic resonance imaging (MRI) scan. MRI scans are not invasive and do not use radiation. We will also do an assessment of arterial stiffness and an ultrasound scan of your carotid arteries, both of which are non-invasive exams. We will ask ACE participants to be randomly assigned by a computer (by chance, like the flip of a coin) to a group that takes 10 mg Equol daily or to a group that takes a daily placebo.

This part shows the effect of a recent NIH-requirement that trials provide results and support needs of patients. This is an NIH-funded. trial.

You will receive results of some assessments, will be compensated for your time and, if needed, transportation can be provided at no cost.

I have no stake in this trial, and know much less than many about the benefit of soy for Apoe4 carriers. But what impresses me about this trial is that it's looking at the prevention of vascular disease and white matter lesions, a key issue for ApoE 4 carriers, using a soy-based derivative designed to be more bio-available to White and Black populations, who in prior studies often lacked the genetic ability to get the benefit of soy.

Primary and secondary outcomes are listed in the Clinical Trials.gov site, linked below, and are excerpted here:

Primary:

• Change in arterial stiffness at 12 and 24 months

Secondary:

• Change in white matter lesion (WML) volume percent at 24 months

• Change in cognitive score measured by the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) score at 12 and 24 months. The PACC-5 is a composite neuropsychological measure optimized to detect subtle changes over time in cognitively unimpaired older adults.

• Change in NIH Toolbox (NIH-TB) cognition battery, comprised of computerized tests of fluid [i.e. flexible] and crystallized [i.e. well-learned]cognitive abilities, via proctored iPad administration. score at 12 & 24 months

• Change in ultrasound measurements of carotid artery at 24 months.

• Plasma biomarkers of inflammation and endothelial function (C-reactive protein, intracellular adhesion molecule, vascular cell adhesion molecule, glial fibrillary acidic protein, neurofilament light) as well as amyloid-β40, amyloid-β42 and phosphorylated tau 181 will be measured at 24 months.

Effect of Equol Supplementation on Arterial Stiffness and Cognition in Healthy Volunteers (ACE)

[Julie G]

Thanks for announcing, Nancy. Just as an aside for those interested in arterial stiffness. I just did a pre and post 20-minute HIIT session using Exercise With Oxygen Therapy (EWOT) and dramatically reduced my arterial stiffness. I have the original iHeart gadget that tests pulse wave velocity and I shaved NINE years off of my biological age with one session- whoah. I was pretty shocked. I plan to repeat in an hour to see how long this improvement is sustained.

[Tincup]

Those who want to enroll may want to ask if the MRI uses a gadolinium contrast agent. Here is an FDA FDA Drug Safety Communication on these agents. Also one from a researcher at the University of New Mexico.

I happen to be in a couple of groups where some group members are doing multiple repeat 30 day intensive protocols to rid themselves of gadolinium. Anecdotally, they report great improvement by doing so. Hence, if I were going to participate in the study and found they use gadolinium contrast agents, I would look into those agents in some detail prior to deciding to join the study.

[Tincup]

Thanks for announcing, Nancy. Just as an aside for those interested in arterial stiffness. I just did a pre and post 20-minute HIIT session using Exercise With Oxygen Therapy (EWOT) and dramatically reduced my arterial stiffness. I have the original iHeart gadget that tests pulse wave velocity and I shaved NINE years off of my biological age with one session- whoah. I was pretty shocked. I plan to repeat in an hour to see how long this improvement is sustained.

Very interesting! Do you have a personal EWOT setup now?

[Julie G]

Very interesting! Do you have a personal EWOT setup now?

Yes, we recently splurged and we're both enjoying it. One of the biggest benefits is being able to get a pretty intense exercise session in 20 mins.

Ok, it's almost two hours later and my bio age is now 21 years younger! I've been subjectively feeling better with EWOT but today is the first time I did some actual pre and post testing. I'm pretty shocked at how effective it seems to be.

[NF52]

Those who want to enroll may want to ask if the MRI uses a gadolinium contrast agent. Here is an FDA FDA Drug Safety Communication on these agents. Also one from a researcher at the University of New Mexico.

I happen to be in a couple of groups where some group members are doing multiple repeat 30 day intensive protocols to rid themselves of gadolinium. Anecdotally, they report great improvement by doing so. Hence, if I were going to participate in the study and found they use gadolinium contrast agents, I would look into those agents in some detail prior to deciding to join the study.

Hi Tincup,
Thanks for the FDA link; I went to it since I hadn't heard of this. BUT, it appears that gadolinium is ONLY used in IVs for certain MRI procedures. I have never had an IV for my brain MRIs, so have not been exposed to it. I believe the MRIs for this study would be equivalent to the ones I receive.

GBCAs are used with medical imaging devices called MRI scanners to examine the body for problems such as cancer, infections, or bleeding. GBCAs contain gadolinium, a heavy metal. These contrast agents are injected into a vein to improve visualization of internal organs, blood vessels, and tissues during an MRI, which helps health care professionals diagnose medical conditions.

[Tincup]

BUT, it appears that gadolinium is ONLY used in IVs for certain MRI procedures. I have never had an IV for my brain MRIs, so have not been exposed to it. I believe the MRIs for this study would be equivalent to the ones I receive.

If they aren't using gadolinium, that would be wonderful! I have a family member who has had gadolinium contrasts for MRI's numerous times, but it was for glioblastoma brain cancer. Because of their diagnosis, it is impossible to determine what deficits they have are due to the cancer, the treatments (including surgery as well as multiple different chemo treatments and very high dose radiation treatments) or from the gadolinium. If I had brain cancer, I would likely do the the MRI's with gadolinium, but would be very selective in other situations.

[Tincup]

Ok, it's almost two hours later and my bio age is now 21 years younger! I've been subjectively feeling better with EWOT but today is the first time I did some actual pre and post testing. I'm pretty shocked at how effective it seems to be.

Curious, I recall a mention that Dr. Bredesen was not a fan of the Adaptive Contrast system, which has both mild hypoxia (about the same as a pressurized airliner - 8,000') and hyperoxia. I understand this protocol is to begin exercising in hypoxia and then switch to hyperoxia.

[Julie G]

Curious, I recall a mention that Dr. Bredesen was not a fan of the Adaptive Contrast system, which has both mild hypoxia (about the same as a pressurized airliner - 8,000') and hyperoxia. I understand this protocol is to begin exercising in hypoxia and then switch to hyperoxia.

True. He is not a fan as most working to prevent or reverse AD already have some degree of hypoxia. That said, he acknowledges that it would be very helpful for those working to acclimate to high altitude. I bought a standard system without adaptive contrast, so I'm just experiencing 20 minutes of hyperoxia while doing HIIT.

[Tincup]

True. He is not a fan as most working to prevent or reverse AD already have some degree of hypoxia. That said, he acknowledges that it would be very helpful for those working to acclimate to high altitude. I bought a standard system without adaptive contrast, so I'm just experiencing 20 minutes of hyperoxia while doing HIIT.

I looked into this a bit more. The developer of the adaptive contrast system had already developed a standard EWOT system (LiveO2). I believe he lives in Colorado and was backcountry skiing at 10,000' (3048m) elevation. He noticed he could feel his pulse in his tympanic membrane (in his ear). I had this experience yesterday, as I happen to be skiing at elevations up to 11,500' (3505m) this week. He said that using standard EWOT, his pulse didn't get that high. He got the idea that if he could exercise as if he were at elevation and get circulation intensity from that and then start breathing the high O2 EWOT, perhaps there would be benefit. He went home and modified his system to do just that. He noticed benefit in himself and others. Hence the genesis of the adaptive contrast system.

With more effort, it might be possible to mimic this on a standard system. French researcher, Xavier Woorons PhD, has published research and a book on reduced breathing techniques during exercise that create hypoxia. His book is "Hypoventilation training, push your limits!" I have the book at home. It is demanding but can be done. Their website. From a wiki on the topic, "Cardiac output, heart rate, stroke volume and sympathetic modulation to the heart are greater when exercise with hypoventilation is performed in running or cycling." I think this is the state the LiveO2 guy is trying to create, before starting the high oxygen breathing during exercise. Again from the wiki, "Generally, there are two ways to carry out hypoventilation: at high lung volume or at low lung volume. At high lung volume, breath holdings are performed with the lungs full of air (inhalation then breath hold). Conversely, during hypoventilation at low lung volume, breath holdings are performed with the lung half full of air. To do so, one has to first exhale normally, without forcing, then hold one's breath. This is called the exhale-hold technique. " Other sources of exercises that do this are breathing coach, Patrick McKeown's "Oxygen Advantage" high altitude techniques. I would refer you to his site, books, "The Oxygen Advantage," "The Breathing Cure" and his free app. I learned of Woorons' work from McKeown referencing it. If my memory is correct, I recall Woorons' approach would drop SpO2 into the 80s and keep it there during the training. I believe McKeown's approaches would as well.

When I have my book in hand, I will create and post a summary of the technique.

For more on the adaptive contrast system, see the LiveO2 site. The case study results are very impressive on many fronts.

I think your husband would love playing with this!