Speak to the lead researcher involved in new study on the consumption of soy lowering the risk of dementia by producing a helpful metabolite and the right gut bacteria

October 21st, 2020. 3:30PM EDT

Media, please register HERE 

A metabolite produced following consumption of dietary soy may decrease a key risk factor for dementia—with the help of the right bacteria, according to a new discovery led by researchers at the University of Pittsburgh Graduate School of Public Health

The embargoed study will be published in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions on October 22nd.

The study found that elderly Japanese men and women who produce equol—a metabolite of dietary soy created by certain types of gut bacteria—display lower levels of white matter lesions within the brain. 

“White matter lesions are significant risk factors for cognitive decline, dementia and all-cause mortality,” said lead author Akira Sekikawa, M.D., Ph.D., associate professor of epidemiology at Pitt Public Health. “We found 50% more white matter lesions in people who cannot produce equol compared to people who can produce it, which is a surprisingly huge effect.” 

Dr. Sekikawa will take questions from the media in a Newswise Live Event on October 21st at 3:30PM.  The event will last approximately 30 minutes.

Media, please register HERE to take part in this event. 

Read the embargoed release providing further details here.

 TRANSCRIPT

Thom: Welcome to this Newswise live event. We have with us Dr. Akira Sekikawa to talk to us a little bit today about some research that he's published. It's coming out tomorrow morning, so the release is embargoed until 7am tomorrow. Dr. Sekikawa is MD and a PhD and MPH. He's an associate professor in epidemiology at the University of Pittsburgh Graduate School of Public Health. Thank you so much for joining us, Dr. Sekikawa.

Dr. Akira Sekikawa: Thank you for this press conference. Great opportunity.

Thom: Great. So, we took a lot of interest in your study. So, I'm curious for you to tell us more about this correlation that you've uncovered between consumption of soy and the presence of white matter in the brain, and that white matter being linked to later development of dementia and Alzheimer's. So, what did you find here in this correlation between the soy and the white matter?

Dr. Akira Sekikawa: Okay. First in this study, we selected 95 cognitively normal elderly, aged 75 and older from a prospective cohort study in Japan. And this study started in the 1990, this prospective cohort study. And we did imaging study including brain structural MRI, and Amyloid PET in this 95 elderly. And we measured blood level soy isoflavones, six to nine years prior to the imaging study. What we found is that soy isoflavone were not associated with white matter lesion or Amyloid. However, we found that the metabolite of soy isoflavone by good microbiome called equol had significant inverse association with the white matter lesion, which is very exciting. And from the data, all the participant we know ate soy and soy isoflavone but, however, only 50% produced equol. And we divided this equol producer into high and low group using the medium. Then, to our surprise, high equol producer had 50% lower white matter lesion as compared to non-producers.

Thom: Wonderful. I got a couple of questions here from Veronica Marshall at Wink News. And I'd like to ask and invite Veronica to ask those questions herself if she'd like. Veronica, if you want to enable your audio, you'd be welcome to ask those questions to Dr. Sekikawa. Go right ahead.

Veronica: Thank you for the opportunity. So, this study measures – I don't want to pronounce this incorrectly – but equol levels in Japanese citizens, do Americans have similar levels?

Dr. Akira Sekikawa: The issue here is - I will like to comment later, but Japanese people – their dietary intake of isoflavone 25 to 50 milligrams a day whereas Americans, we don't eat soy or soy isoflavone, just medium level is less than 2 milligram per day. Unless one consumes soy isoflavone, equol cannot be produced. That is a major point.

Veronica: Okay.

Thom: Go ahead with your other question, Veronica.

Veronica: Sure, thank you. If Americans wanted to encourage more production of that in their bodies, is there something they can do?

Dr. Akira Sekikawa: Oh, that – probably later question and currently. Yes, we're going to discuss that later. Yes.

Thom: Feel free to go ahead and get into that, Dr. Sekikawa. When we were talking beforehand and preparing some questions, the question came up whether people should take some kind of supplement of equol or if we should do something with our microbiome to enable it to produce equol. What are your thoughts about that? Is one route better than the other?

Dr. Akira Sekikawa: Okay, first of all, our study is just observational so whether equol actually work or not, we need to confirm in a randomized clinical trial setting. But the issue here is “Oh, if we are not equol producer, you may not benefit if equol has benefit. But the interesting thing is that equol is currently available as a dietary supplement, so the first step scientifically speaking is we need to confirm if equol supplementation has actually beneficial effects on cognition, white matter lesion or whatever.

Thom: Can you explain a little bit the difference in the microbiome between Japanese versus US people? And the capacity to, even if presuming like you said, Americans don't eat as much soy as Japanese people do – what's the difference, what's the comparison between the ability to even metabolize this way?

Dr. Akira Sekikawa: Okay. When one consume isoflavone, but not all Japanese can convert isoflavone to equol. Epidemiological studies generally say that 40 to 70% of Japanese can convert after they eat soy isoflavone to equol – 40 to 70%. And then Americans, we don't eat soy isoflavone but there are lots of randomized clinical trials of soy isoflavone. Some randomized clinical trials measure equol on this trial, and probably it is estimated 20 to 30% of Americans can produce equol. So, one question would be is this the genetic difference between the American and Japanese? But it is likely not. Probably difference in the microbiome. And what specific bacteria can produce isoflavone to equol, and is this bacteria already identified? So, some difference in the set of bacteria or microbiome, that is the reason.

Thom: Can you tell us a little bit about what types of soy products contain these isoflavones? Would that be primarily something like tofu and soy beans or there are other food products that would contain it as well?

Dr. Akira Sekikawa: Yea. Unfortunately, in the US FDA does not require us to put the isoflavone but generally tofu or soybean or those types, but not soybean oil, not at all.

Thom: Okay, very interesting. We have another question from Sophia. Sophia, I'm going to go ahead and enable your audio if you'd like to ask this question yourself. And please give us your full name and the outlet that you work for.

Sophia: Okay, I'm Sophia Ktori, I'm from Gen Bio, I'm actually calling from the UK this evening. I'm just wondering if it's a microbiome issue, would there be any way – and you mentioned that we need to find out more about the bacteria that are actually responsible for this, would there be any way of, rather than using equol itself, actually using a probiotic or a prebiotic to actually boost the levels of the bacteria that are then going to generate enough of this equol even if you eat only small amounts of soy?

Dr. Akira Sekikawa: Yes, that's an interesting question and that appears to be very hot topic. So, what is currently known is there are many observational epidemiological studies – what is the dietary association of equol producer and these results totally inconclusive difference that results differ study by study, so that there are more recent study from Japan that if you eat like soy isoflavone, you are more likely to be equol producer later. But this again poses another question that all the Japanese eat soy isoflavone but not 100% of them are equol producer. So, it's unanswered, but a very interesting question. Yes.

Thom: Is there any theory or prediction that there may be other types of substances that could be metabolized into equol or some other kind of metabolite that might have similar potential? Is there anything known about that?

Dr. Akira Sekikawa: Isoflavone can be metabolized to many - based on the microbiome or liver enzyme, and there is one study from China. This is a nested case control study of the cardiovascular disease. And what they did is that the case control cases are heart attack, and the controls are healthy people, and they examined all the isoflavone and they metabolized whether it is associated with cardio or heart attack. And what they found is that only equol had significant inverse association with the incidence of heart attack, indicating that the equol appears to be the most bioactive for one thing epidemiological study wise. And also, basic research shows why equol is the most bioactive – one, among isoflavone and all metabolite this is most potent anti-oxidant for one thing; second, half-life is longest among all the metabolites of isoflavone itself. So, for this reason, probably this equol be the most bioactive amongst all isoflavone and their metabolites.

Thom: So equol is highly antioxidative, and it has a very long half-life, so it remains in the system longer?

Dr. Akira Sekikawa: Yeah. As compared to other isoflavone and their metabolites. Yes, right.

Thom: Tell us a little bit about how the presence of that white matter hyperintensity – how has that been established to be correlative to the development of dementia and the test subjects that you've studied? Where are they in terms of prediction of potentially early diagnosis of dementia or Alzheimer's?

Dr. Akira Sekikawa: Okay. White matter hyperintensity came into attention in 1990’s. And the many epidemiological study including meta-analysis confirmed – it is a significant predictor for dementia, cognitive decline, also stroke and mortality. So, this is a very significant predictor for various disease. And also, it is associated with high blood pressure or [inaudible 12:12] or lipids or diabetes. But these associations are generally very small or minimal. For that reason, we found 50% difference between non-equol producer and equol producer. This difference is so huge, that's why we are very excited about this finding.

Thom: I'd love to call on Veronica Marshall again, and she had in mind a question that I also wanted to ask - Veronica, if you'd like to go ahead and ask it.

Veronica: Sure. My final question was what do you hope to do with this data? How is it applicable in the now and then what's next?

Dr. Akira Sekikawa: Okay, so next step obviously we'd like to do randomized clinical trial of equol on whatever - like white matter lesion or cognition or say, potentially other mechanistic link.

Thom: Are there plans for a trial to begin yet? Or are you just saying that that's what would be next? Is that in process yet?

Dr. Akira Sekikawa: We are preparing.

Thom: Wonderful. Wonderful.

Dr. Akira Sekikawa: I can’t say any more.

Thom: That’s fair enough. Fair enough. And of course, this is embargoed until tomorrow morning, and tell us about the study and any of the co-authors that you'd want to credit or anybody that you collaborated with?

Dr. Akira Sekikawa: Oh yes, this is a study like we have numerous investigators. One is this study was done in Japan so that the National Cerebral Vascular called the Vascular Center, NCVC and the investigator, so they are for one thing. And also, Pittsburgh is very famous for its Pittsburgh Compound B- Amyloid research and the aging research, so that the PET center, MRI center, and also Alzheimer's Disease Research Center investigator affiliated with those facilities that participated in this study. Yes, if I named all of them – over, more than I think ten or more than ten.

Thom: How many subjects were analyzed for this?

Dr. Akira Sekikawa:  96. And we still keep doing the study so that we could add 10 or 20 more, but this finding is –because of the COVID studies stopped, so it decreased the data at that time and better analyze the data. And wow, this is interesting.

Thom: And is the plan to revisit the same set of test subjects over time?

Dr. Akira Sekikawa: That's currently cooking.

Thom: Wonderful. Wonderful.

Dr. Akira Sekikawa:  In the next grant, yes, renewal.

Thom: Wonderful. If any of the media on the call have any further questions, please feel free to chat them to us. I want to share the PIO contact there at the University of Pittsburgh. It's Allison Hydzik and her email address I am entering into the chat. So, if you have further questions that you think of later for Dr. Sekikawa or you want to do any further investigating, if there's data that they can share or getting a copy of the study, please contact Allison for that. Dr. Sekikawa, what else would you feel is important for the public to know about this? Obviously, mentioning any research with Alzheimer's, people immediately want to know if there's something that they can start doing in their own life as a prevention or early detection? What do you feel that this discovery means that people who are concerned about that kind of thing should know?

Dr. Akira Sekikawa: Dietary or lifestyle is very essential in terms of the prevention of dementia. And currently, we know a lot in terms of Mediterranean diet or a healthy diet, or a healthy lifestyle is associated. But on top of that, is there any nutrient like equol or whatever that can further prevent. So, I hope these findings would add some evidence to further prevent cognitive decline or dementia in the future.

Thom: In some ways, you look at this as more of a holistic healthy lifestyle question that this may just be one component of living healthfully and being able to prevent those kinds of diseases later in life.

Dr. Akira Sekikawa: Yes, what we have learned in the past 10 years is that not one single thing can prevent dementia – it is the holistic approach that we need to take in our physical activity diet, sleep or microbiome. Yes, many aspects need to work together.

Thom: Wonderful. Thank you so much for taking the time to meet with us today, Dr. Sekikawa and congratulations on your paper. We will be very interested to hear what comes next with this, and I imagine that a lot of people who read about this might want to start looking at taking an equol supplement as a precaution we will say. Thank you so much for your time, and good luck with the next phase of your research.

Dr. Akira Sekikawa: Okay. Thank you very much for your time.

Thom: Thank you so much.

Dr. Akira Sekikawa: I really appreciate that. Thank you.

Thom: Media, please do take note of Alison's email. Feel free to contact her if you have further questions and we will actually have a video and a transcript of this that we will email out to you as well so that you can easily pull quotes from our discussion today. With that, we'll go ahead and conclude. Thank you very much, everyone. Have a great rest of your day. Stay safe, stay healthy and good luck.

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