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Hydrogen Insight ft. Professor Ostojic

Contributor Bio

Alex Tarnava is the CEO of Drink HRW, and the primary inventor of the open-cup hydrogen tablets. Alex runs the clinical outreach program for our company, working with over a dozen universities coordinating research. Alex has also published research of his own. You can find it on his ResearchGate. Additionally, he has been interviewed for many prominent publications, such as Entrepreneur and Forbes, and on many popular Podcasts. You can find all of his interviews and articles on his media page.

Hydrogen Insight ft. Professor Ostojic


In this recorded conversation I discuss everything hydrogen water, and go a bit into general H2 research, with one of the pioneers in the field Prof. Ostojic. Prof. Ostojic is an MD and has a PhD in medical sciences which he is a Professor of at the University of Novi Sad and the University of Belgrade in Serbia. Prof Ostojic was one of the very first researchers to explore the benefits of molecular hydrogen in humans and the first researcher outside of Asia to publish clinical work with hydrogen therapy and hydrogen water. We discuss trends in the research, exciting developments in being accepted more and more, and go into how his work on hydrogen water and H2 in general as a exercise performance and recovery aid, as well as exploration into the benefits on issues of lifestyle such as his recent study using our hydrogen tablets for NAFLD. This likely won’t be the last time I record a talk with Prof Ostojic as he has some extremely exciting work using our tablets underway which I am excited to share, once through review. 

For anyone wanting to support Prof. Ostojic’s research, donations can be made at his site here

Alex Tarnava: Hello, my name is Alex Tarnava. You probably know me, I'm the CEO of Drink HRW and Natural Wellness Now. I'm here with my friend, Professor Ostojic. Now, Professor Ostojic is the very first human hydrogen researcher outside of Asia and Europe since 2010?

Prof. Ostojic: Yes, 2010.

Alex Tarnava: You've been studying hydrogen in human subjects. He is a medical doctor and a PhD in Medical Sciences, and you are a professor at the University of Novi Sad?

Prof. Ostojic: Exactly, and University of Belgrade as well.

Alex Tarnava: University of Belgrade teaching Medical Sciences.

Prof. Ostojic: Exactly.

Alex Tarnava: We're going to discuss a little bit of what his research, his insight into hydrogen. He is one of the true pioneers on the subject. Importantly, for us, he's been conducting research on our tablets. That's interesting. First off, congratulations. You were just telling me you were published in Nature Medicine?

Prof. Ostojic: Yes.

Alex Tarnava: Yeah. Last week.

Prof. Ostojic: Yes. Thank you.

Alex Tarnava: Not for hydrogen, but ...

Prof. Ostojic: Not yet.

Alex Tarnava: Not yet.

Prof. Ostojic: It was actually a paper on general obesity. I was a member of the group, which is located in Imperial College London and our paper got accepted a couple of weeks ago. It was published last Friday about differences in obesity between rural and urban population. It is a big deal.

Alex Tarnava: Yeah. No, absolutely. For anyone listening, who doesn't know, Nature Beta is probably the most prestigious scientific journal there is. It covers a wide range of subjects. Not just medical, everything but Nature by impact doctor anyways, is quite prestigious. Very, very hard to get a journal into Nature.

Prof. Ostojic: It is.

Alex Tarnava: Which brings me to the question, because you've been published in a lot of great journals. Like The Lancet, The BMJ, I believe, right?

Prof. Ostojic: No BMJ. But Lancet a couple times. [crosstalk 00:01:56] Endocronology and that always may of legal proceedings.

Alex Tarnava: What early indicators on hydrogen got you to dedicate so much research to it? Because, especially in 2010, it was incredibly esoteric.

Prof. Ostojic: Yeah. That's true, you know. Everything ... It is actually a funny story. Everything started because a colleague of mine, who was a faculty back then, and a chemist, he brought me a hydrogen supplement. He told me, because I already has so much experience doing all of the research regarding dietary supplements, he brought a new stuff. He told me, “This is something really special.” Back then, back in 2010, he told me, “This is a very effective buffering agent.” He provided a couple of tablets that produces ferrous and tablets.

I started using it anecdotally with myself and a couple of my colleagues. I give a couple of tablets to my colleague medical doctor, who is also very interested into exercise. He didn't exercise for a couple of years, and I told him to use it during his training program. He told me a couple of days after he took the first dose. He told me, it is amazing, because he didn't have any fatigue or any muscle soreness after a very heavy exercise. He started testing it regularly and do a couple of studies back in 2010 and 2011. There is one nice paper published in 2012 in Mayo Clinic Proceedings about the effects of hydrogen as a buffering agent after metabolic synthesis usually by exercise.

Alex Tarnava: Yeah.

Prof. Ostojic: This is the first one and after that, many different studies followed using different formulations of hydrogen and in real different populations. From top level of leads to collegiate leads, but also in different populations of cardio metabolic diseases even with cognitive impairments.

Alex Tarnava: Yes. I'm going to skip ahead and our talk a little bit because it leads into perfectly. Your research has actually been next between sports performance, you know, everywhere from pro athletes to middle-aged out of shape people, to at risk populations with pre-disease states like metabolic syndrome, nonalcoholic fatty liver disease, which is our recent subject. Recently some of the researchers had been proposing that hydrogen actually works as an exercise metabolic as a form of [inaudible 00:04:29]. That parallels your research have on exercise. These metabolic syndromes, right? How do you feel about that for the future of your research because was so MRI along with what you've been studying all these years?

Prof. Ostojic: That's a great question. You know I found hydrogen somehow a proxy for my lab, my lab back in, in Serbia. The name of my life is Applied Bioenergetics and it's focused on understanding the physiology and part physiology behind the impaired bioenergetics in health and disease, with mitochondria as the center of the process. How to utilize and use energy. Also we try to develop new different interventions, particularly tight integration to prevent that impaired bioenergetics. Impaired bioenergetics is linked with poor athletic performance, cardiometabolic health also with different neurodegenerative diseases. Somehow hydrogen could be used as a very specific targeted mitochondria nutraceutical, I called it like that. That is very small molecule goes into the mitochondria, probably regulates mitochondria, two very different mechanisms including the neutral neutralizing reactive oxygen species.

Also probably acting especially hydrogen is water, acting as a buffering agent. But also through longterm effect, it might fact the gene expression particularly genes that are related to mitochondrial bioenergetics. Hydrogen is probably the more my favorite a dietary supplement, and agent that I'd like to see applied in many, many different disorders in the future.

Alex Tarnava: Another point that actually goes along with that. I just sent you the article I wrote where I think it's not just an exercise mimetic but a calorie restriction mimetic also.

Prof. Ostojic: Yeah.

Alex Tarnava: Really, for some of these states like nonalcoholic fatty liver disease, it's called the disease, but it's a disease of lifestyle and there are no medications for it. The first line of defense is diet and exercise.

Prof. Ostojic: Yeah.

Alex Tarnava: That study we just had out is very promising because there is no treatment, right?

Prof. Ostojic: Yeah. Exactly. I would like to take you again for supporting my research in this direction. The study in my opinion is very promising. We did it with not look too many subjects. It was only 12 people, but still we did it as a double blind randomized controlled trial, which is extremely important to really talk about effects of hydrogen from scientific perspective. We did find that none of the qualified liver disease or the fat accumulation in liver decrease after the 28 days of hydrogen intervention, which is extremely important because we don't have any treatment approved so far for this very prevalent disease because non alcoholic fatty liver disease is the most prevalent liver disease in the world. Many, many people around the world, particularly in United States and Canada are suffering for this very complex disease.

Alex Tarnava: One, three, or four, for our listeners. Between one and four, to one and three people are afflicted by it.

Prof. Ostojic: Exactly.

Alex Tarnava: I mean even like my dad has it.

Prof. Ostojic: Yeah, yeah. Many people had it and still we don't know what is the real mechanism for that. It is probably lifestyle disease with many different aspects and hydrogen appears to be very effective for that. We measured with very advanced technology, magnetic resonance spectroscopy. We measured the level of fat accumulation in the liver and it appears that a hydrogen decrease the liver significantly, decrease the liver in specific focal points around the liver and also, what we also found that it tended to affect body composition. We didn't find statistical significance, but body fat decreases as well and also ...

Alex Tarnava: Just in 28 days.

Prof. Ostojic: 28 days, yes it's a pilot study, but still the robust methodology and design we use is pretty good so far. I would like to see other lives confirming these data in the future.

Alex Tarnava: That's actually one point. As you know, we, we have a study that finished, and being written right now on metabolic syndrome that was six months, 60 participant. A lot of what has been observed in the shorter trials is ... I don't want to talk too much about it because it still has to go through peer review, but from the raw data and observations, it looks even more prominent over a longer effect. That's important, and it's not quite replicative, but it's very supportive because, correct me if I'm wrong, but NAFLD metabolic syndrome or at least about 90% bi-directionally causative, and a lot of researchers think that they're actually one in the same disease, with a different expression of the same condition.

Prof. Ostojic: Yeah. That's right. I'm very grateful, you sent me the preliminary data, and I took a look at that, and it was a really nice to see that this is another study confirming the pro-metabolic effects of hydrogen. I like to say that we did another study last year, the paper has been publishing that with general medical sciences, and we found a similar effects using different formulation of hydrogen. It appears that at least you probably know that also, a dozen of human studies confirmed that pro-metabolic effects acting as agent that improves the zero lipids, improved the insulin secretion. It appears that it might be recognized as some kind of mimetic of exercise but in my opinion, the best option is to use both. If you want to improve that lifestyle diseases we are suffering of. [00:10:04]

Alex Tarnava: To not just replace exercise but potentiate the benefits exactly the size and likely there're other proponents on, you know, more commercial in the United States that push it for potentiating fasting. They'll do water fast, which are getting research. I mean, just wrote an article on ... I think it actually just came out a few weeks ago once you get to see this, and you will have seen the whole study. I wrote a seven part on hormesis. Part three was on fasting, water fast and time restricted eating. Some of the research is showing that a couple, three to five day water fasting a year mimics the benefits of a lifetime of calorie restriction for a lot of these markers.

A lot of people are suggesting that hydrogen, which is also potentially working as a mimetic in this fasting calorie restriction sense can be used in conjunction with the short three to five day water fast to potentiate the benefits even further which is just great, more strategies we have. Now, with the NAFLD study, another big marker which showed benefit was the AST.

Prof. Ostojic: Yeah.

Alex Tarnava: You were saying that there's an abstract that you have to analyze more data even?

Prof. Ostojic: Yes, it's really a preliminary, this is actually a news. I just told Alex that it has been secondary analysis of data and the extracts has been accepted to the BMC journal. He's just going to publish probably in June 10th. We analyze the same data from the same population, but now from HOMA2 analysis, this is integrative index that analyzes border insulin secretion in the blood, also glucose and other markers and give some kind of general information about the whole glucose homeostasis in the blood after hydrogen intervention. It appears that the hydrogen mimics the effects of insulin. We could talk about that and we could ... For sure, Maurice investigates in the future that pro insulin effect of hydrogen that might be very important for population with diabetes, particularly diabetes type two.

Alex Tarnava: Yeah, and I mean all this information is fantastic because we're just gathering more and more knowledge on how hydrogen works. When it can work? Why it works, right? What we can do to get it to work better? Where it might not work? One of the biggest skepticisms on hydrogen is that we don't have well defined and pharmacodynamics and there's odd bias that comes with hydrogen because it's new. I think it's a little bit of a familiarity here at stake that people have never heard of it so they think it's quackery, whereas we still don't have well defined pharmacodynamics for things like lithium, which we're using as a drug for things like acetaminophen, which is Tylenol for things penicillin even, right?

Prof. Ostojic: Yeah.

Alex Tarnava: We don't know how these drugs work, but we know they do work.

Prof. Ostojic: Yes.

Alex Tarnava: Hydrogen, we're showing that it does work and we're actually getting closer and closer every year to knowing how it works, right?

Prof. Ostojic: Yeah.

Alex Tarnava: I think it's a bit of a unfair criticism and skepticism on hydrogen. Possibly I think, people associate hydrogen water with magic water.

Prof. Ostojic: Exactly.

Alex Tarnava: Because there's so many magic water frauds out there. My next question, we get just lambasted in the industry. Everyone thinks it's a scam, thinks that there's no science on it, you know?

Prof. Ostojic: Yeah.

Alex Tarnava: Then when we showed them the data, right? These skeptics have no choice but to say, "Well, it needs more research. We don't know this or this." Then we say, "Well, we don't know this or this about drugs. This drug that's approved. Or, hydrogen has more research than CBD by a long shot for instance, but yet everyone's excited about CBD. Why is there a double standard here?" We're, we're just attacked constantly in industry. Have you found similar attacks in the scientific community at all? Have your peers been skeptical?

Prof. Ostojic: That's a very good question, but I never experienced any kind of problem. Seem no problems from the scientific community because I regularly write papers on hydrogen and they are well accepted by this community. I present my research on conference, such as this one. We're here for the ACSM in Orlando. I also presented one small work on hydrogen. A lot of people are interested into it, and I have funded another Japanese people who started the whole story about hydrogen, but also people from United States from all around the world are more interested into hydrogen. Everybody would like to see what's going on with that new intervention because we recognize hydrogen as actually endogenous agent for many, many years. Nobody knows what it's in for. Right now, I think the biggest problem is the company and industry related, not the scientific community because we have the already ... I don't know, even close to 700 papers describing the effects of hydrogen.

Alex Tarnava: I think yes, 700 papers that are either in animals, humans or invitro.

Prof. Ostojic: Yeah, totally.

Alex Tarnava: There are 500 review and hypothesis, publications and everything.

Prof. Ostojic: Yes, that's another. Yes.

Alex Tarnava: There's a large.

Prof. Ostojic: They have good background. Yes.

Alex Tarnava: Only 12 years.

Prof. Ostojic: Yes. That's really interesting. Somehow I found that it's not good for the products such as hydrogen to be over marketed by many companies. They're seen as a miracle water, which is not, of course there is no such thing. I think that [crosstalk 00:15:44] ...

Alex Tarnava: Absolutely. It's interesting that the company's pushing hydrogen as the biggest miracle are the ones that don't actually have hydrogen in their product when they get tested.

Prof. Ostojic: Yeah. That' true. That's very interesting. I told you already about that.

Alex Tarnava: It's one of those interesting dynamics, and I think it's because they don't understand science.

Prof. Ostojic: Yeah.

Alex Tarnava: The companies can't figure out how to keep the hydrogen in the beverage, and then they see this one study, and they think that scientific proof, right? Whereas say for my product, we have more studies underway in clinical validation. We have gone through a battery of testing on our hydrogen concentration more than basically anyone else in the industry.

Prof. Ostojic: Yeah.

Alex Tarnava: I'm one of the most cautious people in claims in hydrogen because the more you know about their subject ...

Prof. Ostojic: Everybody should follow that pathway you started. I think your company is doing it right in the right direction with balancing the hydrogen rule in general health or medicine, and be skeptical is always a smart thing to do. Only a few companies have a similar path. Other companies I search through the internet and I communicate with, some of them over hyped the whole story. Which is not good for a hydrogen. In my opinion, there is enough good solid information. They should be promoted in a well balanced way. This is the way that hydrogen should be accepted by others who already didn't recognize the importance of this very important medical gas.

Alex Tarnava: No, absolutely. I mean, it has a lot of potential benefits, but is it going to cure everything and everyone? Is it a panacea? Absolutely not.

Prof. Ostojic: Absolutely.

Alex Tarnava: Right? Absolutely not.

Prof. Ostojic: There's no such thing, you know.

Alex Tarnava: No, there's no such thing. When companies make these claims, I think it just increased the skepticism, right? Even though we don't make these claims in marketing. We had everything we write, companies will Google, and they see that this company made this miracle claim and then I walked in to the same category as everything else.

Prof. Ostojic: Exactly.

Alex Tarnava: It's quite damaging in industry, how that happens. It's one of the reasons where we could be paying a lot of money for private studies under publication contracts where only what we want can get published. I just don't think that's right. That's not true. You know?

Prof. Ostojic: Yeah, absolutely.

Alex Tarnava: When you have an idea, and you say, "Hey, I'm, I'm wanting to study this," right? We go over it and I'm like, "Okay, I'll donate for some markers, donate some product," right? It doesn't make sense.

Prof. Ostojic: Yeah.

Alex Tarnava: I'm on the edge of my seat waiting for the results, right?

Prof. Ostojic: Yes.

Alex Tarnava: Because you can publish of course, no matter what.

Prof. Ostojic: Of course, yes.

Alex Tarnava: I'm not restricting you from publishing, it shows no benefit.

Prof. Ostojic: Absolutely.

Alex Tarnava: I don't know for sure.

Prof. Ostojic: Yeah.

Alex Tarnava: We have a good hunch that it can help but ...

Prof. Ostojic: We'll see what will the study brought.

Alex Tarnava: Exactly, but that's how science works.

Prof. Ostojic: Exactly.

Alex Tarnava: We have three finished clinical trials right now. One being written, the case studies that you've done. We have a handful of other that are underway and more in planning and a handful underway I have no idea if they're going to work or not. It's ...

Prof. Ostojic: Yup.

Alex Tarnava: ... Ed [Mercy 00:19:01].

Prof. Ostojic: That is the right way. I think, you know, we always discuss about that during those previous study that, that objective part of the story I'm offering to any company is the most important aspect because I'm going to verify or not verify that some kind of hunch we got at start. This should be done about doing a proper studies with right sample, enough people included in the study, right markers but also good interpretation and not over interpreting the data, which is sometimes used by the industry. This is the right way. I would like to see more people recruited as a scientist to advance the hydrogen into the right way

I just did a small paper small opinion paper about the hype behind the hydrogen comparing to real analysis of the number of good trials, clinical trials through the clinical trials that gone off. To see that actually, we have to be more careful when we are talking about hydrogen. Perhaps to educate people, not just the general public, but also the professionals. I think we are very close to the first international well organized event here in North America about hydrogen medicine. That might be a right way, how to educate the media, which is not sometimes well educated about the real science and good science behind the hydrogen. Also public, also professionals. Let us think about that perhaps in the next two or three years to organize such an event and to present the good data and to invite everybody who is interested to understand really the story behind hydrogen. That is where how we should influence the chemist you talk about.

So many people are not informed only by reading the scientific papers, which we're well aware of, in favor of hydrogen, but reading the internet, you could easily see many, many papers about miracle water or hydrogen, which is not exactly the truth. There are many benefits of hydrogen, but we have to communicate that in a more balanced way, for sure.

Alex Tarnava: I think a lot of the information yet translated properly. I know one of the big skepticisms that people say is that even in Japan and Korea where it's more popular, they'll bring up how the government warns against hydrogen water, but they aren't telling the full story. Like the government of Japan, you know, has approved hydrogen as a medical gas in hospitals.

Prof. Ostojic: Yeah. First country in the world.

Alex Tarnava: [crosstalk 00:23:50] a public warning that in 19 products that they evaluated, 17 didn't have therapeutic hydrogen.

Prof. Ostojic: Yeah, yeah. That's right.

Alex Tarnava: For media, let's say North America is seeing that as an example of that Japanese government is warning [crosstalk 00:24:02], but no, they're warning against companies that are misrepresenting their product.

Prof. Ostojic: Exactly.

Alex Tarnava: They're not warning about the benefits of hydrogen, they've already approved that for use in hospitals.

Prof. Ostojic: Yeah.

Alex Tarnava: They're saying this commercial product doesn't have hydrogen.

Prof. Ostojic: Yes.

Alex Tarnava: Right?

Prof. Ostojic: Yes. That is a great example of how the same information could be misinterpreted. I have a pretty nice context, a couple of Japanese companies. Actually, most prominent scientist in the hydrogen research are coming from Japan. This is the first country that actually recognize the hydrogen as medical agent and the information of medical hydrogen is really confirmed in couple of 39 studies in really different population. I think that, that trend will go into the different countries in European and United States as well in the future. There is a really promising a space for that type of thinking of hydrogen, but they should really educate people. The education in my opinion is the key how to spread good qualities of hydrogen are all over the world.

Alex Tarnava: It's starting to get a little bit more interesting in North America. As you know we have four ongoing clinical trials in the US, and we're talking to some other teams in the US and Canada that are interested, but it's really been a decade slower ...

Prof. Ostojic: Yes, that's true.

Alex Tarnava: ... than everywhere else. As you know, the organization starting up the IHSA, International Hydrogen Standards Association, they've already started office in Japan to verify the products actually contain, hydrogen that they're selling. At least minimum therapeutic dosages, they're starting an office in that the USA, and Korea, and China. I believe they're working on trying to find an option in Europe as well.

Prof. Ostojic: Yeah. That is very important about the story. We did small in-house trial, I told you already about that, and your product was one of the best products in the world. We analyzed a lot of different products and it appears that most or more than 50% of the products we analyze, didn't contain any hydrogen or contained below the biologically active levels. It's a big deal, we have to standardize the whole story behind the level of hydrogen marketed. It is of huge importance. I would like to highlight also another aspect that might be interesting. Couple of weeks ago, I did a recent analysis from the number of clinical trials using hydrogen and it appears that only 13 trials so far are registered at and the 12 trials are registered in the past five years. We are seeing a trend of the increased number of clinical trials in humans in

Alex Tarnava: That's interesting because there's about, there's 65 published trials and it is on hydrogen.

Prof. Ostojic: I'm talking about ongoing trials.

Alex Tarnava: Oh, ongoing.

Prof. Ostojic: Yeah, ongoing. I'm talking about ongoing trials and what I would like to highlight as well is that most trials still are supported by public funding bodies. There is no big pharma, no industry involved of 12 ongoing trials from 2015 to today. Only three trials are supported by industry. It appears that industry are using hydrogen, but there are ... Many companies are actually not doing the right way like your company is doing. To register the trials, to find the best ways how to address a specific research question. Not so many companies are involved. I talk a lot about hydrogen to many companies as some of the people told me, they answer like this, "Other companies will do the job for me, so I will use their marketing and their studies to promote my product," which is a really, really big problem.

Alex Tarnava: I see. Even our study on NAFLD, I've seen ionizing companies marketing our study, which is preposterous because, we might get a hundred ton for a hydrogen, than their ionizer plus ...

Prof. Ostojic: Absolutely, yeah. The product is different, the dosage is different. Everything is different. They are stealing your idea of CNM and then the research marketing.

Alex Tarnava: It blows me away, like the team in the United States that has a four ongoing registered clinical trials on my product, they had first gotten a hold of the other manufacturer of the water soluble tablet before they found me. They were happy they found me, because I have legal status in the US as a new dietary ingredient from the FTA. I have all the documents, I'm compliant with every governmental agency, which by the way, it drives me mad to be compliant, doubles my costs. When competitors are breaking the law and not compliant with the government and then trying to sell for cheaper, right? Then, they're not supporting clinical research and everything. Well when they contacted this guy, he sent them different products like some flavored, some unflavored, different lot, some are expired, and they're what about placebo? He said buy some Alka-Seltzer. All right? Then they found out about me because they're like, "This is wild, you know," They learn scale clinical trials you're doing. I said, "Oh, no. No. I'll make lots for you.

Prof. Ostojic: Yeah, yeah.

Alex Tarnava: I send them right to the pharmacy to do the randomization properly and like did all this, because like, they're getting public funds to do research. Yeah. I want to support them as much as possible. The same thing with you and I'm like, "Hey, if I make this placebo better, is it going to be easier?" You know? Like ...

Prof. Ostojic: Yeah, yeah. You did a great job with the last study we did because we discuss about that before the study started. It's preparation of placebo for example, when we are using hydrogen studies. He's extremely important, and I'm not really aware of many companies. They do it. They're doing a great job regarding the policy where they should be look like the real staff in every aspect. These small details are extremely important if you want to put the right context your product and you're doing a great job.

Alex Tarnava: For the viewers just to know, because obviously if you drop a tablet in a glass of water, people know, "Okay, this is this." If someone isn't dropping a tablet in the other bottle of water, it's not really, double volume placebo control, right?

Prof. Ostojic: Exactly.

Alex Tarnava: What we've done is we've made tablets that are the same size as a hydrogen tablet. They have the exact same amount of magnesium, right? Per weight. They actually dissolve plus minus five seconds to the hydrogen tablet creatine CO2 in the exact same cloud formation.

Prof. Ostojic: Yeah, yeah, same bubbles.

Alex Tarnava: Same bubbles as a hydrogen does. They're virtually indistinguishable from each other, which is how you're supposed to do it because it takes out the placebo [crosstalk 00:31:27] ...

Prof. Ostojic: Yes. That is a very interesting. Funny story, when the paper was accepted, I didn't notice that in the [metas 00:31:35], and one of the reviewers asked me, "Is it really the same, the bubbles and everything?" I included that in the final manuscript. It because this is a very important aspect to do a really good placebo control study.

Alex Tarnava: Yeah, no, absolutely. Can you speak at all, like I mentioned earlier, we have a couple of case studies that are completed. I know you've submitted them.

Prof. Ostojic: Yes.

Alex Tarnava: Right. I know you can't talk too much about them until they're accepted, but can you tell us anything?

Prof. Ostojic: Yeah, yup. The idea behind the case studies is actually to see a on a couple of patients. Is it really worth to do a proper study just to get us some kind of hunch about the effects of hydrogen? The first started he completed a couple of months ago was related with the user hydrogen for the sports injury. Actually, it was an ankle sprain and we recruited a couple of patients and finally decided to publish a one case study, one specific patient. It was pretty impressive because we regularly use RICE protocol. When you train to the ...

Alex Tarnava: That's rash, ice, compress, elevate.

Prof. Ostojic: Yes.

Alex Tarnava: When you tear a muscle like in your ankle or knee ...

Prof. Ostojic: This is a standard procedure, but you know, probably in the past couple of years we see that ice component, which is included in the traditional treatment appears to be very good for us because it decreases the pain and swelling, but it appears that it decreases or slowed down the recovery process.

Alex Tarnava: Decreasingly like blood plasma level? Or ...

Prof. Ostojic: Yes, it decreases the circulation in general, it is good regarding the swelling, but the recovery is slower. We would like to compare is it possible perhaps to think about it, to use hydrogen as a topical ... Actually, hydrogen water to put in an injured leg ... With water to see what is going on in the first 24 hours. The results are pretty positive. We found very impressive results regarding the better flexibility. Also the decrease in pain and the swelling is lower after intensive treatment. We actually did a several emergence of the leg during the first 24 hours, and the results are very positive. This is just a case study, and it is right now in review, and I'm really positive about that. I would like to see perhaps if ... Especially if the paper is accepted, I would like to see the complete RCT study done in the future of it.

Alex Tarnava: That's one of the things I'm talking about.

Prof. Ostojic: Yeah.

Alex Tarnava: It's something that anecdotally truly believe in. It was some of the photos I was sending and before and after is that you're like, "Okay, let's do this properly." First off, that burn I had that was basically healed overnight. Then, I potentially broke my arm skiing. A 400 meter tumble down a double black, and it was all swollen. Then after hydrogen bath, it was for a few days it was just an acute pain. My spouse, she was training for the Boston marathon there, which happened on her birthday last year.She got shin splints, right? I had to carry her from the train station during a run. After 10 days of hydrogen bath, she went and ran like 32 kilometers, and did the Boston marathon three weeks later.

It's stories like that, we have others, like a pro MMA fighter that broke her hand, and she had to get the pins taken out early because of poke through the skin because the swelling went down. Even last week, I had shoulder arthroscopic surgery two weeks ago. I didn't take a hydrogen bath for my first 10 days because of risk of infection. Even that, I had a piece of tape on the wall and doing the wall climb for mobility after I took a 45 minute hydrogen bath, you know, I use a crazy amount. I use above 500 tablets. I use a crazy, but in a two-hour period after the 45-minute bath and then waiting for an hour, I got three inches higher on the wall. You see? It was ...

Prof. Ostojic: [crosstalk 00:35:51].

Alex Tarnava: Cut the swelling down for sure.

Prof. Ostojic: This is aligned with a study. Actually, that was the first clinical trial registered on hydrogen for injury. We didn't use hydrogen as an individual treatment, but we use it as adjutant treatment to RICE. It appears that topical hydrogen is particularly effective for flexibility. The paper has been published by a postgraduate medicine. It is a very nice example how hydrogen might be effective for different soft tissue injuries. In my opinion, besides the many different possible mechanisms of action, the benefit of hydrogens related, it is really small molecule that causes very fast into the site of the injury and neutralize many different toxic biochemicals at the site of the injury. It's probably very smart and very perspective to conduct similar studies regarding the soft tissue injury. In general, the muscular and skeletal medicine, all those should see it as an experimental agent rather than a ...

Alex Tarnava: Of course. When we get these skeptics saying, "Well, it's still not medicine." Well, we're not saying it's a drug that should replace therapies. Nobody in their right mind is saying that at this point. I mean, when we're talking about the benefits of hydrogen, they're promising, right?

Prof. Ostojic: Exactly.

Alex Tarnava: There's again, this double standard and skepticism where say even on like Wikipedia, a CBD that has less research is talked about in this huge, like promising this big page on all the ongoing research. Hydrogen that has more research over a shorter time because CBD has been studying since 1970. Hydrogen has more clinical trials with more success, more publications in a decade that CBD has in 50 years. Yet CBD, maybe because it's a sexy molecule. Media has this like huge Wikipedia page talking about the benefits. Whereas hydrogen, everyone's skeptical about, and things doesn't work. They're like, "You're claiming it's a panacea." Well, no, researcher is claiming it's a panacea. Nobody who knows the science is claiming it's a panacea. People who know the science. No, it's promising.

Prof. Ostojic: Exactly.

Alex Tarnava: I mean even in your wording potential adjutant therapy.

Prof. Ostojic: Absolutely. I did a couple of review papers in pretty nice journalists about the hydrogen in the law. I always try to find a balanced way how to describe the positive effects, and the promising in the regarding general medicine in specific disorders, but also to outline what are the drawbacks regarding the limits in research so far. That balanced way I think is the, is the right way. We should use it. We should do a more research. We should, of course, try to find it right now as an experimental agent that is available. It's a dietary supplement. We could use it, but we should use it in a smart way.

Alex Tarnava: Absolutely. Another great example, and we were chatting about this a little bit. I mean, comparing say hydrogen therapy to something that gets huge media attention in nicotinamide riboside. Well, I mean, part of that is because ... A lot of the early rodent studies came out of Harvard, so everyone thinks it's amazing research even though nicotinamide riboside is literally zero for five in human clinical trials in showing a benefit.

Prof. Ostojic: Yeah, that's right.

Alex Tarnava: They've shown it safe in it raises NAD plus levels, but it hasn't lowered cholesterol or blood pressure, or you know, the general [crosstalk 00:39:28] ...

Prof. Ostojic: General biomarkers.

Alex Tarnava: ... muscle walking like any of the markers that we associate with aging, it hasn't worked in humans.

Prof. Ostojic: Yeah. That's right.

Alex Tarnava: That's the same thing with a lot of molecules. We've talked about that one paper, like they got a published in cell where they said [sosanate 00:39:42] cured obesity, right? By you know [crosstalk 00:39:50] ...

Prof. Ostojic: ... Something similar to ...

Alex Tarnava: ... activation and we know that there's dozens of molecules that cure obesity in rodents and they don't work in humans.

Prof. Ostojic: Most of the time, yeah.

Alex Tarnava: The ones that do work that DNP in humans will kill you.

Prof. Ostojic: Exactly.

Alex Tarnava: It's this weird skew because when it comes to the hydrogen research, I believe the average publications impact factor is around three, which is pretty good.

Prof. Ostojic: Pretty nice.

Alex Tarnava: That's a pretty good journal.

Prof. Ostojic: Yeah, it's nice.

Alex Tarnava: Even our NAFLD, trump, that was about the three impact fact.

Prof. Ostojic: Yeah. Yeah, yeah.

Alex Tarnava: Right?

Prof. Ostojic: Around three. Yes.

Alex Tarnava: The research on hydrogen is far more than some of these other sexy molecules.

Prof. Ostojic: Absolutely.

Alex Tarnava: Yet I think because it's attached to the word water.

Prof. Ostojic: Yeah. You may have been in part of skepticism. It's related to the fact that so far we don't have a proper safety tutorial. Just a safety tutorial, we always use some kind of performance studies with hydrogen in different populations. Proper safety styles, those response times, you already mentioned, the pharmacodynamics, a longterm safety. Although we know that hydrogen so far is really recognized as a safe agent without any major side effects. Still, it would be probably smart to conduct a classical FDA, according to FDA rules, the safety trial, 90 days trial. Maybe that might help everybody to recognize hydrogen as a properly analyzed agent. Of course one of the biggest issues, but you already mentioned this. This is the case with many drugs, is that we don't really fully understand right now the mechanism of its action.

Alex Tarnava: Yeah.

Prof. Ostojic: Better those response trials and safety trials might help us to be recognized by the people who still think hydrogen is not adequately researched or ...

Alex Tarnava: I'm glad you bring up dose response because even a few years ago, professor [Onos 00:41:47] review the 321 publications, he said that no dose response has been observed. Yes. Well, back then the technology didn't exist to get higher dosages of hydrogen. You know? The dose response was, "Are you getting 0.6 milligrams or 1.2 milligrams?" It's such a tight window.

Prof. Ostojic: Exactly. Yes.

Alex Tarnava: Now the technology exist for higher levels of inhalation for water getting ... You know, we deliver six milligrams up to 10 milligrams. Actually in the metabolic syndrome, it's 15 milligrams that they were getting a day that we've seen crazy markers. We're actually seeing the last few years that there is a dose response.

Prof. Ostojic: Exactly.

Alex Tarnava: That higher dose seems to be working better, quicker, more often, right? We are developing dose responses for the safety. It's one of those check boxes that people who think like a bureaucrat deal with.

Prof. Ostojic: Yes. Most medical doctors thinks like that.

Alex Tarnava: Say getting IRB approval and talking to the teams. I say, "Why do we need a safety study?" "We endogenously produced eight to 10 liters of hydrogen a day. It's been used at a thousand times the level in mixed deep sea diving. It needs a higher dose of hydrogen to create narcosis in mixed deep sea diving than nitrogen, which is the air we breathe."

Prof. Ostojic: Exactly.

Alex Tarnava: I mean the safety is so well established in other areas, but in terms of bureaucracy and skepticism, they want to see it exactly like this.

Prof. Ostojic: Check. Yeah. That's check.

Alex Tarnava: Base on this amount, but for context in the United States anyways, the FDA has declared hydrogen water as GRAS. Generally Recognized As Safe and they've declared our tablets as new dietary ingredient status, which means they did the same GRAS evaluation on our tablets that they would, if it was a food. That's the difference between NDI and GRAS is more of bureaucracy. Supplements have to be a new dietary ingredient. Foods have to be GRAS, right? It's a very similar process. It's the same level of safety and mission report required, but skeptics who look and say, "Where's the long term safety data?"

Prof. Ostojic: Yeah, yeah.

Alex Tarnava: Now you have to go into all the facts why the FDA would think it's safe in talking about the mixed sea diving and then dodging us production. You need a big explanation where the skeptics are looking for one papers submitted on this subject.

Prof. Ostojic: That's true. We probably have in the title. The safety on regular hydrogen. That would be great to have something like that. Yeah, I would like also to bare attention to the history of hydrogen use. You mentioned that it has exploded during the past 10 or 15 years, but still the first paper has been published in 1975 in science. It was a big deal.

Alex Tarnava: It was a project between, you know, Baylor and Texas handout, right?

Prof. Ostojic: Yes.

Alex Tarnava: That was a very different study and nothing happened since then because even though it showed such amazing benefits in rats for skin tumors and skin cancer. What were they .. Were they in a 96% hydrogen hyperbaric chamber ...

Prof. Ostojic: Extremely specific conditions.

Alex Tarnava: ... under eight atmospheres. The pressure was eight atmospheres. That would, I think kill a human being?

Prof. Ostojic: Probably.

Alex Tarnava: They have a 96% hydrogen, would kill a human being when we're only having 4% oxygen. The conditions that the rats were in, it could never be a human trial. I think people just forgot about it.

Prof. Ostojic: Yeah, that's true. Probably that is the reason, but still, when you're a published in science, back in 1975, it should draw attention of other researchers. I agree with you that it is a very specific product goal, but still that is really ...

Alex Tarnava: I've got an interesting anecdote on that about [crosstalk 00:45:40] one of my investors, his brother as a researcher at Duke University, right? When I was first looking into it, you know, and his brother's a biochemist and he said, "Hydrogen." He said, "That came out in the '70s." He said a chiropractor set up a clinic in the Cayman Islands or something and was claiming to cure people of cancer. He said it was such a black eye that nobody wanted to touch the research in the '70s, because of this chiropractor doing damage.

Prof. Ostojic: Yeah, yeah, yeah.

Alex Tarnava: I was trying to get information. He was like, "Oh, that's before the internet." You know? He was like, "I remember it. My memory could be a little bit wrong."

Prof. Ostojic: But still something happen like that.

Alex Tarnava: When I brought up molecular hydrogen he said, "There was a big publication in the '70s on cancer." Like he remembered it and then he told me the story of a chiropractor that did some really dangerous things and he was like, "Yeah, nobody in the research community wanted to touch it, you'd be associated."

Prof. Ostojic: Yeah, yeah, with agent. Yeah. That is a case with many other agents. Sometimes the people who use it inappropriately, particularly when they implement the studies from animals direct to humans. It was in similar idea, it's not a good idea how to promote the real of medicinal properties and qualities of a hydrogen.

Alex Tarnava: I think I was telling you one of the bigger reasons. Originally, I was going to not private label the product. I was just going to create a brand, right? How I want to market it.

Prof. Ostojic: Yeah.

Alex Tarnava: I was actually talking with Tyler Lebaron where he said, "You know, if they don't buy your product, they're going to buy another product that has no qualms about them making magic claims, and we're going to have the same problems that researchers had in Japan and Korea getting grants because these companies were claiming it was H3O or not understanding anything, claiming it was magic, not putting hydrogen." What Tyler saying, he's like, "Yeah, these other companies that want to market it, they don't understand the science." He said, "Why don't you put it in your contracts that you have that to their marketing and work with them because then they can give reasonably accurate messaging rather than it just being me in a sea of people making magic claims." That was a, I wrote an article, a month or two ago that went on the site called a hundred voices and why, the tablets are available in so many companies because I want to see this marketed properly in a hundred different channels. Talking about a hundred different ways.

Prof. Ostojic: Sometimes it's a good idea to recruit some kind of advisory board. There's some kind of team of people who has a good reputation and who are objectively absorbing the ideas and the products of your company. Some kind of team that guarantee that you're doing a good job. Many medical companies and big pharma companies actually has some kind of an independent advisory boards that guarantee the idea [crosstalk 00:48:48] ...

Alex Tarnava: A lot of supplement companies do. You know, even I do, I have a lot of different consultants to balance things off of, one thing in the series I'm writing. I don't trust the help that experts on absolute statements and just talking about how messaging in health has become so binary. Everything is black and white, everything going on. Even when we were talking about, say my article that I wrote on hydrogen as hormesis ...

Prof. Ostojic: By the way, you are writing extremely good articles.

Alex Tarnava: Thank you. I was talking with a few different people, yourself included and I'm like a few of them were like, "You should try and publish that."

Prof. Ostojic: Yes.

Alex Tarnava: I'm like, "Who am I to publish an article?" They were like, "Well, you certainly have enough references."

Prof. Ostojic: That's true.

Alex Tarnava: You could change it, you can write it and like ...

Prof. Ostojic: You did a good job. You should, you should try to publish it, you know? You are very objective. If you overview all the important papers and you'll give a very good perspective, you should do it. Probably publish it through a specific line such as opinion paper or letter to the editor or something like that. You should try it.

Alex Tarnava: Yeah. I'm thinking about it, but it's just that interesting thing that even though I know, I understand the topic much better than most people in the papers, that even I'm referencing and writing.

Prof. Ostojic: That's true.

Alex Tarnava: I'm looking at some of these papers, I'm like, "What does that conclusion they have? That makes no sense." Or, "This is wrong." Or, "That is wrong." They have eight references in a 3000-word article, and I have 172 to backup what I'm saying but ...

Prof. Ostojic: You need that self doubt.

Alex Tarnava: Right, and this is how science works and this is why you need an advisory board and all these people. Because anything I'm doing, I have someone else that is more of an expert about it than me.

Prof. Ostojic: Yeah. Yeah.

Alex Tarnava: Now, I put the pieces together.

Prof. Ostojic: It's smart way to talk ...

Alex Tarnava: [crosstalk 00:50:48] talk about the whole story better than anyone else, but there is no single thing that I'm doing in my business, in the clinical outreach program, in the development of the product, where I do not have an expert that knows one component of it a hundred times better than I do.

Prof. Ostojic: Yeah.

Alex Tarnava: Right?

Prof. Ostojic: Yeah. I think the community needs more people like you because this is the right way how to do it. I found your company, and I really appreciate the collaboration we have during the past couple of years as a proper scientifically grounded company because you always try to implement the principles of good science into the whole story we're having here. We need more people like you.

Alex Tarnava: That's why I got into it. I didn't get into it for the money. I mean, I rushed my mortgage, I spent every dime I had getting this going and I left at the time, way more profitable business that actually, back then more profitable than it even is today, years later. I think hydrogen will be more profitable in the future but certainly it was a massive risk, but I did it because of my interest in it from a scientific perspective, right? It was already a big jump for me philosophically because back then when I started, one of my hobbies was I was kind of skeptical troll, that I'd go into natural pages and troll them when they were making claims that didn't make sense. Had a lot of shooting in the band and a lot of like the biggest websites and everything. To go from that to lying and marketing is just something that I couldn't have done with who I am as a person. As you know, my founding partner is, PhD chemists, a medicinal chemists from the pharmaceutical industry. Everything he does, he wants to do ...

Prof. Ostojic: In a proper way. Yeah.

Alex Tarnava: We need all of the information, right? Because he's been trained throughout his schooling, throughout his professional career that we need to get this evidence, right?

Prof. Ostojic: Yeah. Yeah.

Alex Tarnava: If we don't have this evidence, we can't change, because we don't have the evidence.

Prof. Ostojic: Exactly.

Alex Tarnava: We kind of gone at this like a shoestring budget pharmaceutical model, right? To try and say, we need to gather this evidence. We need to see if we can say this. We need to see does it do this? How does our product compare to this? You know, even in my article comparing hydrogen technologies, I mean there're challenges. I mean, even with our product, we might get in gas probes they measured at the University of Beijing, we get about three PPM. Well, the rest that we test is this quality dissolved nano bubbles, right? But then the magnesium. Also, which, I wrote about it. It's hilarious. People bring up concerns to the magnesium where we're actually putting together studies to test because we believe that the bioavailability of the magnesium is superior to salt because of works done in the water and the reaction, right?

Prof. Ostojic: Yeah.

Alex Tarnava: A lot of the researchers are like thinking that like, "Man, how do we know that your magnesium based on the chemical reaction isn't better than the placebo magnesium?"

Prof. Ostojic: Yeah, yeah.

Alex Tarnava: Some of the Japanese companies are saying, "Oh, magnesium is dangerous."

Prof. Ostojic: Metallic magnesium is.

Alex Tarnava: Yeah, whereas like it's just magnesium ions and in fact, they're free in the water and probably better than most of the salts on the word ...

Prof. Ostojic: Probably is.

Alex Tarnava: ... purer, less heavy metal contaminants and everything like that.

Prof. Ostojic: Yeah, yeah.

Alex Tarnava: It's one of those interesting things, but it gets into dosing that, "Okay, maybe we can't claim the benefit of say that one company that gets seven to 10 PTM saturated, but at the same time they have aluminum, and what they're using ... It's under pressure for eight hours, whereas we're delivering a similar amount of total hydrogen. But what's the difference between our three PPM dissolved and the seven, eight PPM quasi dissolved then the magnesium, right? We can at least claim the benefits of hydrogen products that are lower in H2 than ours. There's only a couple of studies that have higher dissolved, but then they can't claim the benefits of our quasi dissolved and magnesium. It's one of the big issues in knowing what you can say about what, right? Because there's different technologies, dosing at different levels in different combinations.

Prof. Ostojic: Right, very different. Yeah, you're right.

Alex Tarnava: Does there, I mean the, the company in Japan that uses aluminum, it gets to what, nine or 10 pH or something. They're saying no aluminum gets into the water, but that doesn't make sense. Because if you start distilled water and it gets to 9-10 pH, that means hydroxide is getting in. That's aluminum hydroxide.

Prof. Ostojic: Yes.

Alex Tarnava: It's getting through their filter. We know that aluminum can be dangerous, right?

Prof. Ostojic: Yeah, very dangerous. Yup.

Alex Tarnava: What's going on with that and their claim? They're trying to say our magnesium is dangerous, which is not true.

Prof. Ostojic: Is not true probably.

Alex Tarnava: Not true, while they're using aluminum. It's just wild stuff. I think that goes into everything else while we're talking about like, these are the impediments we have in getting hydrogen mainstream.

Prof. Ostojic: Yup.

Alex Tarnava: Because it's confusing, a lot of people get confused, right? But at the end of the day, we're seeing in these reviews that say, we know that hydrogen water has a similar benefit to gas at a rate of 1% dosage, right?

Prof. Ostojic: Yup.

Alex Tarnava: We know that.

Prof. Ostojic: Yeah.

Alex Tarnava: We can say, okay, in most of these models, either inhalation or waterworks, right? "We know that it should be intermittent to not continuous throughout the days. We know that, one milligram of water would require a hundred milligrams of inhalation. In the skeptic saying that we can't directly compare. I don't think that's true because if we have a study on a subject where both water and inhalation works and we have these formulas worked out on the availability of the two methods, we can cross use those studies.

Prof. Ostojic: I think this is a very important point because besides the differences you mentioned, there is a fundamental difference between the inhalation and oral administration since inhalation is always seen as a medical way how to address that. That said, all inhalation agents are medical drugs.

Alex Tarnava: Yeah.

Prof. Ostojic: While the hydrogen rich water are different oral formulations are dietary supplements. It's basically different considering the FDA and every other aspects or laboratory wise.

Alex Tarnava: Completely different. Inhalation devices are medical devices.

Prof. Ostojic: Exactly.

Alex Tarnava: Whereas our tablets are dietary supplements or a bottle of hydrogen water is a [crosstalk 00:57:55].

Prof. Ostojic: Yes.

Alex Tarnava: That's more down to government, right? We can identify in science what dose to dose in different products is going to work. We could say from a scientific standpoint that taking this 10 milligrams of hydrogen a day in the water, you need a gram ...

Prof. Ostojic: Or more.

Alex Tarnava: ... or more from inhalation, so you're going to have to do this to probably see a similar benefit.

Prof. Ostojic: Yeah.

Alex Tarnava: Then the skeptics will say, "Well, inhalation is a medical." Water isn't medical, inhalation is, and that's a matter of bureaucracy.

Prof. Ostojic: It's a matter of bureaucracy and perhaps ...

Alex Tarnava: Not efficacy. You know?

Prof. Ostojic: Yeah. Not efficacy but also part of the answer might be related to those response studies, it's similar like vitamin C, you know? You'll give it in lower dosages. It's a part of the food, but in special type or routes of administration. In special dosages, it becomes a drug. We should do perhaps more education about the differences and similarities between two routes of unresearched, for sure.

Alex Tarnava: Exactly. It's something I've mentioned too. Researchers making up higher HSA because they've developed the minimum threshold of observed benefits that we have seen a benefit in humans at this important level and that it appears, the study that the Chinese team that Tyler Lebaron was on in rodents for NAFLD where they showed that I think it was 0.2 PPM of ionized water with hydrogen had no benefit, whereas I think it was 0.7 even like a low dose came with benefits, right?

Prof. Ostojic: Yes.

Alex Tarnava: We've now established 0.2 didn't work, while 0.7 did in that model ...

Prof. Ostojic: Works, yeah.

Alex Tarnava: ... I think a professor [Noda 00:59:49] had a study, showing similarities.

Prof. Ostojic: It's already published in the paper, yeah. Very nice work. Yeah.

Alex Tarnava: We are establishing these dose responses and we can do a better job in doing it and I think, and even talking with the IHSA they say, "Yes, we're going to need more publications and more work," But they're going to know what a high dose benefit? What the highest observed results are? What might work for this condition? Because it's probably going to come down to how many milligrams H2 or micrograms for H2 per kilogram of body weight, that we have, right?

Prof. Ostojic: That would be great. Yeah.

Alex Tarnava: Because it's going to be different for every person.

Prof. Ostojic: Absolutely.

Alex Tarnava: How much does a person weight? What damage do they have? What model is being used?

Prof. Ostojic: Also another interesting aspect, how exogenous hydrogen administered by inhalation or oral different formulations. What is the link between the endogenous and exogenous hydrogen?

Alex Tarnava: Because it's mixed right now using things like lactulose and other products to raise endogenous hydrogen because the results are mixed.

Prof. Ostojic: Exactly. That's true.

Alex Tarnava: We know, we have data on things like say for instance, turmeric raises hydrogen breath inhalation. We know the diabetic drug acarbose create hydrogen.

Prof. Ostojic: Yes. Exactly, increase the production of ...

Alex Tarnava: There's a couple of publication on acarbose for ulcerative colitis.

Prof. Ostojic: Exactly.

Alex Tarnava: Saying that the hydrogen creation would benefit ulcerative colitis.

Prof. Ostojic: Inline with that, I probably should have an opinion paper last year in trends in endocrinology and metabolism top generally in the field of endocrinology, about the possibility that the lack of endogenous hydrogen might be related with Parkinson's disease. It appears that there is a difference in gut microbiota and probably at the people in Parkinson disease has less hydrogen producing bacteria in the gut. Those population might need an exogenous hydrogen ...

Alex Tarnava: There's some studies on hydrogen positively influencing the gut microbiota.

Prof. Ostojic: Yeah. That is a very, very important ...

Alex Tarnava: Not only in hydrogen in this line of thinking, people with an impaired gut microbiota are producing less hydrogen, right?

Prof. Ostojic: Yup.

Alex Tarnava: Then when you put in exogenous hydrogen like through hydrogen water, not only are they getting the exogenous hydrogen, but it's improving their gut microbiota, which is ...

Prof. Ostojic: Exactly [crosstalk 01:02:17] go fast.

Alex Tarnava: ... hydrogen, right?

Prof. Ostojic: Yeah, that's true.

Alex Tarnava: It's quite interesting in Parkinson's disease. We know Parkinson's has a very mixed data so far.

Prof. Ostojic: Yeah.

Alex Tarnava: There was a first a 48-week human study that had very good benefits on Parkinson's, right?

Prof. Ostojic: Right.

Alex Tarnava: The route studies were mixed and found that water work in inhalation didn't really work so much. They did a short study on inhalation of hydrogen and it didn't work for Parkinson's disease, but it did affect the other markers. Then there was that big multicenter trial that failed in Parkinson's, but when you buy the study and read it, there was a mix up.

Prof. Ostojic: Yeah. That's true.

Alex Tarnava: Both groups were getting hydrogen water intermittently. The placebo group didn't get hydrogen every day, but they might've been getting accidentally hydrogen once every two or three days, which is a very intermittent like effect to it.

Prof. Ostojic: Yeah, yeah, it's a factor that might ...

Alex Tarnava: There was nothing different between the two groups, but they lost in the Parkinson's disease score, something like eight to 10 points less than what was expected and similar trials. Both groups were very beneficial over other trials of a similar duration. They were just not beneficial against each other, which just might show that having hydrogen water wants every two days is as beneficial in that model of Parkinson's as every day. It was a huge error, which I think doesn't show that hydrogen water doesn't work, but it doesn't show it does. We need to study it again. Unfortunately we are in the United States here, using our tablets, there's a study going on. 70 patients per 52 weeks.

Prof. Ostojic: Yeah, that is nice, I think, to know and also perhaps I know a couple of those studies you mentioned, I know those papers and it appears that the methodology is not the perfect, sometimes the primary outcomes are not good. Those authors usually use surrogate makers of Parkinson disease subjectively reported Americans because it's very expensive to evaluate the biomarkers, including the MRI scans of the brain or the muscle of very specific indicators of [inaudible 01:04:25]. It might be good perhaps to see what are the biomarkers and then discuss about the effectiveness of hydrogen in these population.

Alex Tarnava: I've heard a rumors from researchers that there's a team in China doing research on the inhalation of Parkinson's and they're finding that it's only working at a very high intermittent dosing, which again shows us ... I mean, we know that like a high concentration of water, a high dose drinking maybe once or twice a day is going to work better than someone's sipping a low concentration all day long, even if the total milligrams of hydrogen are the same, right?

Prof. Ostojic: Right.

Alex Tarnava: Because we want that higher dose intermittent.

Prof. Ostojic: Yeah. Some kind of hydrogen boost.

Alex Tarnava: The inhalation trials might be ... Exactly, a hydrogen boots to enact gene expression. The inhalation trials could be flawed too, because were they getting too low of a dose intermittently? A lot of them will talk about the concentration. The percent of hydrogen gas in the inhalation, but they're using a catalog that's only delivering a liter a minute but we breathe in seven or eight liters a day. That's a flawed perspective. You can't say you're inhaling 4.6% hydrogen, when it's only a litter a minute. The other studies are 4.6% hydrogen on eight liters.

Prof. Ostojic: Yeah, yeah.

Alex Tarnava: Yeah, it is a flawed methodology, with those inhalation studies as well. To finish up on this subject, you know, things we need to gain mainstream acceptance and awareness. I want to talk to us a little bit about responders versus non responders. I know we've talked about ... You have seen maybe trends and data that you're maybe think that maybe some people are responding better than others. I've talked to the other research teams. They see the same things, anecdotally it looks like a large group are getting much bigger benefits. Even on the study we have being written right now, one of the big reasons it's been reevaluated and dug through is because a couple of the markers that are super both statistically and clinically relevant seem to have a bit respond versus nonresponder. Then of course we have that recent a study on mild cognitive impairment, which found that only people with the APOE4 gene, responding.

Prof. Ostojic: Yeah. That is a very nice question because we are facing that responder non-responder story in the dietary supplement scientific community during the past couple of years. It appears the creatine has also a responder and non-responder story, caffeine as well. Depending on many different aspects including the genes, different genes that responds to those genes. About hydrogen responder and non-responder story. I think, we don't have a really exact data what is the reason why some people respond and other do not respond. Perhaps it might be the endogenous production of hydrogen or some specific genetic profile ...

Alex Tarnava: Don't we have a hypothesis paper?

Prof. Ostojic: About [crosstalk 01:07:25] respondents?

Alex Tarnava: About the endogenous ...

Prof. Ostojic: Yes, couple of papers.

Alex Tarnava: Yeah.

Prof. Ostojic: Couple of papers.

Alex Tarnava: About responders per se but talking about difference and benefit.

Prof. Ostojic: Yes, that's true. I have a hypothesis paper about that but at the moment I would like to talk about perhaps another aspect that will influence the story of responders and non-responders. This is the sample size. The most of the studies are still small sites studies. If we want to really address this issue, we have to recruit more people. The biggest study I conducted a recruited 48 subjects. It's a big study comparing to other hydrogen studies, but comparing to classical medical studies or big studies with creatine that recruit couple of hundreds of people, this is the reason why we should not tell about the percentages. How many people respond to hydrogen.

Alex Tarnava: Yeah.

Prof. Ostojic: Anecdotally, I think that more than 80% of people respond well to hydrogen. Just anecdotally, this is just my opinion. Particularly for those studies when we use it as an athletic performance, as performance enhancing agent. It depends ...

Alex Tarnava: That lines up, I literally texted one of my shareholders. He said, "If you had to guess how many people don't respond to hydrogen? and I said, "Maybe one in five."

Prof. Ostojic: That is similar to this. Yes.

Alex Tarnava: I said on a guess, my feeling is one in five people.

Prof. Ostojic: Yup.

Alex Tarnava: That is more to do with people talking about like pain, like aches and pains in their joints. Construction workers and stuff, even we have a lot of customers and our own brands in Vancouver that spread throughout trades workers and we're just finding anecdotally from a few hundred people about one in five say they don't get a benefit, and four and five go, "Wow, I slept for the first time through the night." You know, and one or five were like, "No matter how much I take, it doesn't do anything."

Prof. Ostojic: It depends on the biomarker or patient reported outcome you have with it. It's highly dependent on that. It's always good to have some objectively or clinically reported markers. For hydrogen and the responsiveness, I'm well aware that many people who use it as an endogenic agents are pretty satisfied with the effects, particularly for that buffering effect of hydrogen rich water we saw in the previous period of study, but we definitely need more research about that responders, nonresponder issue about hydrogen. Also ...

Alex Tarnava: That actually come ... Sorry, go ahead.

Prof. Ostojic: No, no problem. Also, I see the hydrogen agent with both effects, which are easily to understand continuing responder and non-responder effects, but also some longterm effects that are related to gene expression. If we, for example, administer hydrogen for a couple of months, not just a few weeks or one month or like that, we will for sure address that issue about responsive and non-responsiveness to hydrogen for different medical diagnosis and disorders.

Alex Tarnava: We need more longterm studies on this stuff for dosing frequency.

Prof. Ostojic: Exactly.

Alex Tarnava: Do we need to wash out? Do we need to change frequency, change dose every six months?

Prof. Ostojic: Yeah.

Alex Tarnava: I know just for myself anecdotally and a half dozen people close to me, we found that if every six months you take two or three days off taking hydrogen and change your dose and time of day. You get this ping where you get the benefits. Like maybe my shoulder pain would slowly start coming back after six months, but if I take two days off and then instead of in the morning take it at night. In a different dose within two days, my shoulder pain's gone again. Now that is completely anecdotal, right?

Prof. Ostojic: Yeah, but probably, there is some kind of tolerability effect or some kind of adaptation ...

Alex Tarnava: Well, even like exercise.

Prof. Ostojic: Of course with everything.

Alex Tarnava: If you have been doing exercise every day forever, it's no longer exercise to you, right?

Prof. Ostojic: Exactly.

Alex Tarnava: If hydrogen is working as a harmonic agent, as an exercise mimetic.

Prof. Ostojic: Yup.

Alex Tarnava: You do the same dose at the same time of hydrogen every day, you might build the tolerance to it.

Prof. Ostojic: Exactly. Probably the washout period is pretty smart thing to do. We do it routinely for scientific reasons, but during this adaptation and permeases theory, it's probably wise to spend some time without hydrogen and then take it again.

Alex Tarnava: Yeah. I want to get in, because it's responder versus non-responder studies are very expensive. You need a lot of people.

Prof. Ostojic: That's right.

Alex Tarnava: You need to go through a lot of data, you need to look at what genes they carry and all. There are hundreds of thousands if not millions, and millions of dollars to conduct even first responder versus non-responder studies. Now, is it an encouraging ... Just this last weekend from when we're talking, we're at American College of Sports Medicine right now in Orlando. That's why researchers are here for the conference, but back in Europe, just this past weekend, they did the heart transplants on pigs, which I think they got $400,000 and a grant or something to use hydrogen for these pig heart transplants. Now, I see the smile on your face that ...

Prof. Ostojic: That is huge.

Alex Tarnava: A big grant for a first pig transplant study. Do you think that will help you getting more funding for more hydrogen study in you own things close to home?

Prof. Ostojic: I do hope so. I sent congress the letter to one of the people who is involved with that study. It's a big deal, you know? As far as I'm concerned, this is the biggest grant that any hydrogen research received anytime now. I hope that positive marketing and information spread around about that study, will push other public bodies, big funding bodies include the NIH or Utopian Research Fundings, fund bodies to support research on hydrogen. I'm really looking forward to see the results of that study, but we need for sure the results published as soon as possible, of course, and hopefully positive to draw intention about it.

A couple of years ago, I applied for a big grant to the NATO. They have a very nice science for peace and security funding and I applied with a big a grant about hydrogen in traumatic injuries back then and I was into the final, it was very close to get the biggest, even grant like this in Slovakia, but I didn't want it. I hope this will push things forward and I'm looking forward very much to visit Slovakia because we are negotiating to make some kind of collaboration about that study in whole hydrogen medicine idea. That's great, really.

Alex Tarnava: It's very close to home, you're coming from Serbia to Slovakia.

Prof. Ostojic: That's very close. Yes. One and a half hour by plane.

Alex Tarnava: Yeah, no, exactly. You mentioned traumatic injury and I believe you're recruiting right now for ...

Prof. Ostojic: Yup. Waiting.

Alex Tarnava: Can I talk about this?

Prof. Ostojic: Yeah, you could. You could talk about this. We are waiting for the first lead that will suffer a brain concussion and we prepared a very specific protocol of 24-hour acute treatment with hydrogen. I want to talk more about it in details but ...

Alex Tarnava: We don't have any data yet, so I mean, it's interesting. I think there's good hypothesis on why it would work. There's the study that was done at the University of Washington, on traumatic brain injury in rats. There's all the post-stroke studies in human data on hydrogen ...

Prof. Ostojic: Yes, very positive so far.

Alex Tarnava: ... [crosstalk 01:15:31] rescuing effect. I believe it's a sound hypothesis that hydrogen, water will work, post-concussion to mitigate some of the damages, but we need the data.

Prof. Ostojic: I'm allowed to talk, to tell you that we were going to use a very good, very robust methodology to evaluate the recovery during the first 24 hours using the top tool to evaluate the many different symptoms, including the cognitive symptoms and many other interesting issues. I'm looking forward, it's not easy to provoke it. Yeah, of course but we are waiting for the first lead that will suffer a traumatic brain injury and we will relate to them. Actually, this is the part of the bigger projects, one of my PhD students that evaluate the use of hydrogen in athletic environment. First part of the study is related to athletic performance, but the second one is related to the different athletic injuries, including the soft tissue injuries, also the brain concussion.

Alex Tarnava: Very much sitting at the edge of my seat waiting for the data on that.

Prof. Ostojic: We're going to use, use your product.

Alex Tarnava: Yeah.

Prof. Ostojic: That's a great thing.

Alex Tarnava: Exciting. I do want to ask what direction you think the research is going to go? I mean, I have my own thoughts and hypothesis. I think if the theory is that hydrogen is a harmonic agent working as exercise mimetic, calorie restriction mimetic pan out and keep on being validated, then perhaps hydrogen will be explored more for athletics, more for lifestyle diseases like metabolic syndrome, NAFLD, even diabetes as adjuvant therapy. There's a lot of diseases, even many cancers, Alzheimer's that exercise does have the benefit to you, right?

Prof. Ostojic: Yeah.

Alex Tarnava: In cancer therapy they recommend you exercise because exactly it has a benefit.

Prof. Ostojic: Exactly. Yeah.

Alex Tarnava: I think the more that hypothesis is validated, if it's validated, it'll give us better direction in research to know these are the targets for hydrogen as a first line. These are the targets for hydrogen as adjuvant recommendation that it will do a benefit. It's not going to lift the whole weight of it, but it's going to have the benefit. Now, I'm sure you have more insights into this.

Prof. Ostojic: Yes, I have. In my opinion, first of all, I would like to see the comparison between a hydrogen and exercise to see is it really mimetic? Try to make some kind of controlled conditions and compare the effects on some biomarkers, but I'm more interested into the second line of research and I'm looking forward to address this in the years to come, which is related to do neurodegenerative diseases. You already know that most of the neurodegenerative diseases, do not any cure so far. We still don't understand really the mechanisms.

Alex Tarnava: Interesting, exercise has shown ... Leg exercise particularly is shown to be one of the best defenses and staving off neurodegenerative.

Prof. Ostojic: Yes, exactly. That's true. I see the one of the most important aspects of the hydrogen is that it is really small molecule that easily go into the brain. It's always the case. We have a many, many good drugs in the phase one of evaluation addressing the Parkinson's or Alzheimer's disease, but when we apply that in the humans, no results in many, many different agents are very positive. The problem is that it's not easy to deliver the effective drug from the gut or from the circulation to the brain.

Alex Tarnava: Or the blood brain barrier.

Prof. Ostojic: Because of blood brain barrier. Yeah, exactly. Hydrogen might be the first one that is easily driven to the brain and do the job inside the cell, inside the mitochondria, inside the hard to reach tissues such as the brain.

Alex Tarnava: One of the big problems in a lot of neurodegenerative disease bottles is runaway excess chronic inflammation, right? Because anti-inflammatories there aren't doing the work. We know that hydrogen isn't a anti-inflammatory per se, it more regulates the inflammatory response, which is actually how exercise works.

Prof. Ostojic: Exactly.

Alex Tarnava: By acutely raising, pro-inflammatory cytokines or mitochondria roles, eliciting a greater anti-inflammatory response, interleukin 6 might go up acutely, but then a greater response from interleukin 10 knocking it down. Hydrogen seems to be regulating production of our pro-inflammatory cytokines, not blunting inflammation, which could be very useful because if it's shooting it in the brain too and there is a good preliminary study on neuro-inflammation on hydrogen.

Prof. Ostojic: Yeah.

Alex Tarnava: I mean that's huge because that wouldn't necessarily treat or cure the disease, but it would ameliorate one of the issues preventing drugs from working in later stage of the disease.

Prof. Ostojic: Yeah, that's true. I am also interested into the possible effects of hydrogen on the gene expression of mitochondria and of the genes related to mitochondrial bioenergetics. One of my hypotheses is that hydrogen used even early on as an inhalation agent could improve the level of creatine and different biomarkers and bioenergetics in the brain. Because all these neurodegenerative diseases share the same symptoms or the same trait. It is a low level of cellular energy. It might be that hydrogen might increase the cellular energy in the brain or those populations that might be related to the better quality of life and different, different aspects of people suffering of Parkinson's or Alzheimer's.

Alex Tarnava: It's a point I brought up to the one researcher on the metabolic syndrome study going in. One of the markers that was not consistent. Some people lost a lot of weight, you know, and other people didn't lose any weight, right?

Prof. Ostojic: Yeah.

Alex Tarnava: That shows that it's a different factor. Well, if hydrogens working as say exercise mimetic, right? If it's making them have more energy, feel better, perhaps these people who are now 60 with metabolic syndrome, obese, prediabetes started feeling better so they all of a sudden sort of going for walks again, you're going to work up because they have more energy.

Prof. Ostojic: Yeah.

Alex Tarnava: They're walking around, whereas other people who had been sedentary for life, even though they have more energy, they never ever had the habit to use their energy anyways so they continue being sedentary. Whereas the others are feeling better, so they're getting more active again.

Prof. Ostojic: Yeah. That should be a strictly controlled in the future studying, if we want to prove that hydrogen is an exercise mimetic to be somehow balanced to regarding the capital physical activity during the research, but it might be really helpful to see is it a really a mimetic or not. Finally, perhaps to combine those two positive factors, lifestyle factors such as regular hydrogen use and a regular physical activity that might help us to tackle those competencies.

Alex Tarnava: It could, you know, one of the biggest anecdotes we hear, which sounds really quack, like people who say, "I just feel better." Right?

Prof. Ostojic: Yeah.

Alex Tarnava: Yeah. Well if you have more energy, you feel better.

Prof. Ostojic: Yeah, that's true. Right.

Alex Tarnava: If it's driving, mitochondrial energy production, you feel better, right? You're more active, you feel better, right?

Prof. Ostojic: Exactly.

Alex Tarnava: It sounds like a real placebo thing, I just feel better, but it has a sound basis on why someone could feel better drinking hydrogen water. Now you mentioned hydrogen maybe increasing cellular creatine, and I know you've talked with me in the past about ... You think there's a synergistic relationship between hydrogen and creatine a little bit. I have taken creatine on and off since I was 16 years old, in the past as a performance enhancer for sports and physical training. Now, I'm sort of thinking of it more as a daily health supplement. It's the same thing with caffeine.

You know, caffeine will show in a single dose maybe that you have the better sprint time or better endurance, like caffeine is an incredible ergogenic agent for sports performance. In fact, so many sports' products rely only on high doses of caffeine. That's the only thing that works in the product.

Prof. Ostojic: Yeah, that's true.

Alex Tarnava: Our next two essential is that we're launching on our site is actually just pure caffeine, just a hundred milligrams a tablet and creatine, because I am viewing both of them more as protective neuro degeneration daily supplements now.

Prof. Ostojic: More and more data are collected during the past couple of years regarding the use of creatine as a regular dietary supplement for general public. Because we already know that in many different diseases, not just ... We are talking about [inaudible 01:24:53] performance, the level of cellular energy is down. My interest in hydrogen and creatine is actually because of my lab is partly dedicated to addressing the problems of impaired bioenergetic, slow bioenergetics in many different issues. The creatine in hydrogen appears to share the ability to increase the level of the cellular bioenergetics. We just talk about that, one of the biggest company in the world, actually the owner of the whole creatine idea from Germany, they started to sell and promote the hydrogen for other creatine for general population.

They are advising, particularly the children with alarming disabilities or elderly, the regular daily usage of creatine every single day until the end of the life. Because the creatine appears to be very, very beneficial for many different, health biomarkers. You've got it right regarding the use of creatine in general population. Probably it might be interesting to think about making product that contains both hydrogen and creatine in the same mixture to get best of the both side.

Alex Tarnava: It would be hard.

Prof. Ostojic: It's not easy, I know that. It's extremely complicated.

Alex Tarnava: I've thought about it. I mean, for the listeners our tablet and a 12 millimeter tablet, the current one is a result of a 3000 iterative adjustments. Now to get that up to like a one inch tablet that we need to put a creatine dosage in, it would completely change everything to do with both the reaction and dissolution kinetics. Yeah, it would probably take me 3000 more turn of adjustments to get something working with. We talked about this at ACS on last year, just you know, privately and, I've been thinking about it for the last year and I'm like, "Man, could I do that? Could I make a tablet that big that's full of like another active ingredient that could make it?" I've done a few experiments and let's just say it'll be at least another year of my RE before I could get it right.

Prof. Ostojic: At least you should consume two tablets at the same time, because in my opinion, this is just my opinion. Hydrogen might increase the bio availability of creatine in the gut. It might increase the level of creatine, in the circulation if consumed together.

Alex Tarnava: We've gotten some wild anecdotes from other, private label customers of mine that sells supplements and monitor blood levels of bioavailability. They say, when we take this vitamin or this alongside hydrogen, we need way less of it to get the same levels. That's all just anecdotal, you know, I mean, there are internal studies. We did an internal-experiential study, even in conjunction with caffeine and in conjunction even with things like NR and PQQ where taking the full dose recommended by the manufacturers. Say if we 12 the pill with the hydrogen and had no effect but pressing them into the pill, right? Our heart rates elevating, crazy energy going on like things that we were monitoring and it could need, because we know that hydrogen is out of your system between five to 30 minutes. These capsules you're taking, they take 15-20 minutes to break down. The hydrogen is already out of your system.

Prof. Ostojic: Yeah.

Alex Tarnava: But when I pressed it all together and it was all like in the nano bubble emulsion, it was crazy. Just like, it was wild. Anyways, that's all I can say. I'm taking full dose of PQQ and NR with the H2, which NR is having a bio availability issue. There're studies coming out saying perhaps oral nicotinamide riboside isn't particularly bioavailable in humans. Yeah, that could be a cool subject because when I put it into a tablet, my heart rate went from 50 to 90.

Prof. Ostojic: To 75 or 90.

Alex Tarnava: My body was tingling, you know? I said, "Okay, is this placebo?" I had 10 other people internally with my company try it, and a similar response happened to like eight of them.

Prof. Ostojic: All the responders?

Alex Tarnava: Yeah. It's interesting, but again, we need data on that.

Prof. Ostojic: Yeah, yeah, yeah.

Alex Tarnava: We need to know, is this going to work? That's going to be important for drugs because so far, there's been a lot of studies with hydrogen using with a drug and there's been no adverse events. But if we put the drug into a hydrogen solution, is that going to change? Because the drug might take an hour to hit your system, and hydrogen is already gone.

Prof. Ostojic: Yeah. Yeah. Right.

Alex Tarnava: If you do it at the same time entering your gut, is that going to have a change?

Prof. Ostojic: Yeah, maybe.

Alex Tarnava: We just need studies.

Prof. Ostojic: More studies I need.

Alex Tarnava: I guess I need more money to donate more.

Prof. Ostojic: Thank you for that.

Alex Tarnava: All right. Well as always a pleasure.

Prof. Ostojic: Yeah, it is a pleasure. Thank you, Alex.

Alex Tarnava: All right. Thank you.

Prof. Ostojic: Thank you.