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Edward Calabrese - An Introduction to Hormesis and How It Can Affect Our Lifespan - Timepie Lecture — Transcript

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0:00Before
0:04we start today's interview, could you
0:06give a self introduction on you and also
0:09the study you are focusing on to our
0:11audiences?
0:13Okay. So, a little bit about me and uh
0:15and what I do. Okay.
0:17Yeah.
0:18All right. Thank you very much and nice
0:20to be here again. Um the um well in
0:23terms of me
0:25I'm a University of Massachusetts at
0:28Amherst Massachusetts uh professor. I'm
0:31in a school of public health and health
0:34sciences and within that I'm within an
0:37environmental health sciences program.
0:39So I've been a longtime professor here.
0:42Um I've been actually I've been here 48
0:45years. So I've been at UMass an awful
0:49long time. Put it that way.
0:51But my interest in hormesis, I'd have to
0:53say, is even older than um than my stay
0:57at UMass. I I actually got um my first
1:01introduction to the concept of hormesis
1:05um as an undergraduate
1:08back in 1966.
1:11Um I was 20 years old then and I was
1:15taking a plant physiology course. I um
1:20uh professor came in one day and we were
1:23doing experiments, but one of the
1:24experiments was a dose response study
1:27with uh a synthetic chemical that was an
1:30inhibitor on the peppermint plant. and
1:34and he came in one day, it was November
1:36of 1966,
1:38and he said that the plants were
1:40stimulated and uh and all the other
1:43previous years they had been inhibited
1:46uh in a dose response fashion, and he
1:48didn't know why that happened. And he
1:50wanted to know what what happened and
1:53did we use the wrong chemical? Um
1:57did we mislabel something? What was
1:59going on here? So he invited the
2:01students to come back and try to figure
2:03it out after the semester was over. And
2:05we had 24 uh kids in the class or 24
2:08students. And and I was the only one who
2:11came back to see him to try to figure it
2:14out. And so this started my my my
2:18research. And as it turns out, I was
2:21able to show that at low doses, the
2:24plants were stimulated, but at higher
2:26doses uh they were inhibited. And that
2:28the reason why they were stimulated in
2:31the class was that we had made a mistake
2:33when we made up our stock solution with
2:36a delusional error by about tenfold. And
2:39so by a m because of a mistake I was
2:42able to discover that these plants were
2:44stimulated at low doses. And and he made
2:47me you know uh I I did I I replicated
2:50this study probably almost a dozen
2:53times. Uh it was done in plant it was
2:56done in soil. Then he then I did the
2:58work in hydroponics so I could avoid the
3:00soil and see if there was I would still
3:03get the stimulation and I got the
3:05stimulation. And so I I never knew the
3:08term hormesis but we we published the
3:11paper uh and I just called it a lowdose
3:14stimulation and a highdose inhibition.
3:17And so that was in the 19 late mid 1960s
3:21late
3:22late 1960s.
3:24And so then I went up and got my PhD
3:28and uh in toxicology. And then probably
3:32in 1985
3:34I noticed that there was a conference uh
3:37in California on radiation hormmesis.
3:41And I read about it and it talked about
3:44a bifphasic dose response relationship
3:47and at low doses that radiation may be
3:49protective. at high dose it was causing
3:52could cause cancers and other things. So
3:55I I said well gee I said you know this
3:58bifphasic response that I saw so many
4:00years ago with peppermint I bet that
4:03biology is biology and I bet that
4:05they're related to each other. So I
4:07called the person up who was in charge
4:09of the conference told him of uh what I
4:12found so many years ago and he invited
4:15me to put together a paper on chemical
4:18hormesis and invited me to speak at the
4:22conference and that's how I got back
4:24involved with uh hormesis back in the 19
4:27mid 1980s and then and then what
4:30happened after that was um in 1989
4:36there was a paper a debate in the
4:38journal of science on uh by two people
4:40who were leading the conference uh one
4:43was Leonard Sean the other was this guy
4:45Dr. wolf and they called it hormesis's
4:49point counterpoint and when I read their
4:51paper in science uh it it it stimulated
4:54me to get get reactivated and I started
4:58to organize people to focus I got a lot
5:01of research money and and now it's 30 35
5:05years later almost and u and this is
5:08where I am today so that's how I got
5:10started with it if that's helpful.
5:14Well, that's a quite long journey and
5:16you have been studying on homesis for
5:18such a long time. So over the like
5:20decades of studying, what do you think
5:22is the general concept of homesis? What
5:25is it truly is?
5:28Well, you know, the way I define it is
5:30that it's a dose response relationship
5:33and it's a bifphasic dose response, but
5:36it really um uh I I think embodies two
5:41different things. uh most people tend to
5:44focus on hormesis as an example of what
5:47I'd call adaptive homeostasis.
5:51you know, when you stress if you're
5:53stressing a system uh with a pollutant,
5:56with radiation or with with um aging or
6:00or any kind of biological stress that
6:03the the the system um the system
6:08responds to stress by by trying to
6:11repair any damage that the stress might
6:14cause. and and that what happens is that
6:17not only does it repair the stress
6:19that's in the the damage that's induced,
6:21but it tends to slightly overcompensate.
6:24And by overcompensation,
6:27it means that you add a certain sort of
6:29um um benefit to this B. You make the
6:33system stronger. That's what it's really
6:35doing. it when you stress a system uh
6:37you you can cause injury but the system
6:40responds to that stress and and can make
6:43it itself a bit stronger. And the
6:46hormetic response is really as I said an
6:50an example of of I think adaptive
6:53homeostasis
6:54that that essentially what that just
6:57makes you stronger at a when you have a
6:59a low stress. Now the other thing that I
7:01found is that is that just about every I
7:05think enzyme system in cells that they
7:08all show a bifphasic dose response
7:11relationship and and this uh and this
7:14occurs for what I call not adaptive
7:17responses but for um constitutive
7:21responses those responses that that that
7:24sustain the normal daily operations of
7:26life and their dose response response is
7:30is is very is the same uh quantitative
7:34features as the hormetic response and
7:37and so to me they're they're all
7:39examples of hormesis this bifphasic dose
7:42response relationship and so um so it it
7:47it it addresses both constitutive as
7:50well as adaptive responses and therefore
7:52becomes extremely uh extremely
7:55significant in trying to understand how
7:57biological systems respond all the way
8:00from bacteria up to humans and
8:02everything in between. It's very
8:04significant, but it's very difficult to
8:07study uh because the responses are are
8:10modest uh and they're at maximum only 30
8:14to 60%
8:16um more or less greater than background.
8:19And and this is why people tend to to
8:22not see it because it can get lost in
8:25background variability and you have and
8:27and that's why my my initial advisor
8:30when I did that work with peppermint, he
8:33made me replicate my study about 12
8:36times in the in the soil and then about
8:39six or seven times in the hydroponics
8:42because because the results were always
8:45positive but they were always, you know,
8:4830 60% and he wanted to know well was
8:51this just by chance or was this
8:53variability and and was it reproducible
8:57and uh and and and so and so you really
9:00have to have very strong study designs.
9:03you have to have lots of doses. Uh and
9:06sometimes you actually have to have a
9:08dose time response. So you can measure
9:11not just the dose response but how that
9:13dose response changes over time because
9:16if you cause damage initially you're
9:18then looking for a compensatory response
9:21and the the overcompensation response.
9:23So you'll see the stimulation. So it's
9:25it's a it's it's it's very interesting,
9:28but it's very challenging uh how you you
9:31know how you're supposed to do that
9:32work. But I' I'd say that that and so
9:35and so in in the 1990s what I did was I
9:38tried to find most people had at least
9:42for Hormesis Hormesis was not very uh
9:46not established at all in the big data
9:49set database called Web of Science that
9:52I'm sure you're all familiar with. um
9:55that that very large database in the
9:581980s
9:59only uh only referred to hormesis or
10:03hormetic about about 10 or 15 times per
10:07year per per year. So um
10:12which meant that it it was the the term
10:14really wasn't very well understood. the
10:17concept really wasn't very well
10:19understood and and so
10:22and at the same time there was at least
10:26u in the environmental area there was a
10:29lot of new developments uh the
10:32environmental what I call the
10:34environmental revolution was taking
10:36place certainly in the in the United
10:37States but many other places in the
10:40world and that was that people were
10:42recognizing you know how much pollution
10:45existed and they were now trying to
10:47actually have um correction and improve
10:51the the environment and and have
10:54stronger regulations. And so in in the
10:57United States, it it there there became
11:00a a a lot of uh a lot of uh
11:03confrontation and battles, fights
11:06between big industry, what I call
11:09polluting industries at the time and the
11:11the newly created environmental
11:13protection agency that was trying to
11:15regulate these. And they were they they
11:18they debated and they kind of fought
11:20over what was the nature of the dose
11:22response in the lowd dose zone and and
11:25and and how could you assess um the
11:29effects of pollutants on human health
11:32and and the environment and and it
11:34really they didn't know what the nature
11:36of the dose response in the lowd do zone
11:38was. Was it was it a threshold response?
11:42Was it a a linear response? And and and
11:45what happened is that is that the US EPA
11:49uh in 1975 or 1976
11:53made the decision to uh to to u uh to
11:58accept that the that they were going to
12:00use for risk assess for for carcinogen
12:03risk assessment purposes the assumption
12:05that the dose response for carcinogens
12:08was a linear dose response. And so this
12:11this was very significant because for
12:13for non-carcinogens they were going to
12:16assume that the dose response was a
12:18threshold. And so when you have a
12:20threshold dose response then well then
12:23you can say if you're below the
12:24threshold uh the agent doesn't cause any
12:28any adverse biological effects. But when
12:31you have a linear dose response then
12:34there's a for a cancer then there's an
12:36adverse effect all the ways down to u as
12:40you approach zero. So it was very a very
12:43controversial decision I thought by the
12:46US EPA
12:48to adopt the linear dose response and it
12:51made the cost of cleaning up uh
12:54carcinogen pollution carcinogen uh
12:58contamination in the environment very
13:00expensive extremely expensive um um just
13:05thousand time you know many many fold
13:07more expensive than trying to clean up
13:09the pollution from non-car carcinogens.
13:12So there are always disputes between
13:15industry and and the US EPA. They're
13:19always fighting with each other over um
13:22over what's the proper regulatory
13:25situation and that's why people got
13:28involved with the first Hormesis
13:30conference because it was really put
13:32together by by the electric power
13:35research operations from Japan as well
13:39as the United States and and they were
13:42concerned because um they were concerned
13:44with regulations tied into radiation but
13:48But um but the same kinds of issues were
13:51going on in the chemical world. It
13:53wasn't just radiation. It was was also
13:56chemical carcinogens. And and that's how
13:58I entered into this situation was was
14:01trying to say, well well, who's right?
14:04Is it a threshold? Is the threshold
14:06right or is it the the uh the linear
14:10model that's right? And so then I go and
14:13look at it and I say, well, you know,
14:15actually I think both of them are wrong.
14:17It's not a linear dose response. It's
14:19not a threshold response. The actual
14:21correct model is a hormetic dose
14:23response model. So I said everybody's
14:26wrong and I'm right. [laughter]
14:28And so and so but but then I didn't have
14:31a lot of evidence to prove it. But I re
14:33but I remembered when I was young when I
14:36was 20 years old I had I did a lot of
14:38work on hormesis with these peppermint
14:40plants and I and I knew that hormesis
14:42was real. So it started me on my my
14:46effort to try to see how how um uh how
14:51general the hormesis concept was and and
14:54how reproducible it was. And so over the
14:57years I have I have had to try to uh
15:01convince the world that that the world
15:04was wrong and that and that I was right.
15:07Um and and that's been um that's been a
15:10big challenge uh when you when you try
15:13to think that everybody thinks that
15:15you're crazy and you know you're not
15:18crazy so to speak that you think that
15:20you're correct. And so and so I would
15:23have to say now it's it's 2024.
15:27Many years have passed since this all
15:29started. and and and it's interesting I
15:32mentioned to to the class that back in
15:34the 1980s the web of science database uh
15:38u essentially reported uh you know
15:42hormes cited hormesis or hormetic about
15:4510 to 15 times last year it was over
15:4820,000 times so we've gone from 10 in a
15:51year to 20,000 in a year so the interest
15:54and growth in hormesis has been very
15:58significant And um and it's not just see
16:02I got involved with with with this
16:04initially because I was an environmental
16:07toxicologist.
16:08Um and so the the these these these
16:11discussions were were within the context
16:13of cancer risk assessment the US EPA and
16:17and other countries and and now the last
16:2015 years or so I've been very much
16:23focused on hormesis and its uh public
16:26health and and biomedical
16:29um benefits and and and a lot of my
16:31papers in the last 10 years or so have
16:33been looking at uh how you can um
16:37improve
16:38uh you and protect your your your brain,
16:41how you can protect your heart and other
16:43other systems, how you can slow down the
16:46process of aging, uh how you can take uh
16:50actually I've got very much into into um
16:53uh yeah, I'd say uh traditional Chinese
16:56medicine and and and and the the and and
16:59and and looking at the the plant
17:02extracts and and and and and
17:05so forth. And actually I I I today I I I
17:09take about 40 different uh uh dietary
17:12supplements and most of them are are
17:15based upon uh you know traditional
17:17Chinese medicine. So this is I start my
17:19day with
17:21Yeah. And I and I
17:22it's like a biohazard.
17:24Yeah. And and I do that because most of
17:27the the traditional Chinese medicines
17:29when you actually study them uh you know
17:32within the laboratory they all act in a
17:34very in a hermetic fashion and they act
17:36to to protect one's health on on many
17:39different systems. And so I've I've been
17:42uh and and most recently in the last
17:45month or so I published two large
17:47papers, one large paper, one concept
17:50paper on hormesis and aging in the
17:52journal aging research reviews and um um
17:56but a lot of these that go back really
17:58into um you know traditional Asian
18:01medicine and um and and and and it's
18:05interesting I I find that that in uh
18:08even though there are a lot of people
18:09who are studying hormesis today across
18:12all the countries that the strongest uh
18:15the strongest efforts are really coming
18:18out of China and that that to me is is
18:21really very uh it's exciting to see that
18:24and I and I've seen uh uh you know it's
18:27it's it's it's actually great. It's it's
18:29u and one of my friends uh um he is from
18:33CIT. He has a PhD he's from Cree. Then
18:36he took a posttock in in uh in Japan.
18:40Then he has a faculty position in China.
18:43Eugeneius uh uh you can see you know on
18:47my papers he's a professor in China and
18:49and so and it gives me insights into
18:52into you know his teaching of his
18:55lectures on hormesis within China and
18:57and and other connections there. So I
18:59have a indirectly I have some some some
19:02uh insights into all the you know
19:05research that's going on you know within
19:06your country and it's exciting to me
19:08because I I'm a you know really into the
19:11hormesis thing and it's nice nice to see
19:14u uh how how actively
19:18researched it is within China. It's
19:20great.
19:22Yeah, you have just mentioned the
19:24traditional medicine and it reminds me
19:26of some fictions like in the past there
19:27were some people some characters that
19:29taking toxins and poisons to want to
19:33treat themselves and to build a kind of
19:35like resistance. Is this kind of
19:37behavior like taking the toxins also be
19:40considered as homesis and does the long
19:42accumulation of these toxins affect our
19:46health? Well, they they they can it
19:48depends on the halflife of the toxin and
19:51the tissue distribution. But say for
19:53example, I I I know that um some toxic
19:57heavy metals, let's say for example,
19:59cadmium. Cadmium uh there's a lot of
20:02evidence of hormetic dose responses with
20:04cadmium. However, cadmium has a very
20:08very long halflife in the human body. Uh
20:12decades actually, a very long halflife.
20:14And so if you keep taking uh doses of
20:17cadmium over the course of your your you
20:20know your life then what'll happen is
20:23that within a certain period of time you
20:25will pass from the the um let's say
20:29hormetic zone uh into a toxic zone and
20:33so it you it becomes what what you think
20:36was good for you at one point becomes
20:39harmful for you uh in a little bit later
20:42point and so you you you actually have
20:44to to understand all of this and how it
20:48fits together and and to try to make it
20:50it uh you know work for you. And that
20:52would be true for other things. This is
20:55kind of crazy, but it's true. Um but I
20:59most countries are really very uh
21:01concerned with lead in the environment
21:03and and for all good reasons. But I I
21:06have lots of studies that show that lead
21:09is um is very hormetic in many different
21:11systems. However, like cadmium, if you
21:14take too much, if you take it for too
21:16long a time period, uh it stops being
21:18hormetic and it becomes uh becomes very
21:21toxic. Um and and and this is true, you
21:25know, in in in the United States, but
21:26other countries, uh pregnant women have
21:29to be careful um uh with uh exposure to
21:33fish that have methyl mercury um to
21:36protect the developing um developing
21:39fetus. And but as it turns out there
21:41there are probably a good 20 25 studies
21:45with methyl mercury which shows its it's
21:47its hormetic dose responses even in even
21:50in neuronal cells. And so most people
21:53would think that well that's crazy.
21:55That's not possible. But it actually
21:58isn't. It's not just possible. It
22:00actually is. It does exist. But the the
22:03issue is is uh you know it's it's all it
22:07doesn't mean that that just because
22:09there's hormesis down there doesn't mean
22:10you can't you shouldn't be concerned
22:12with potential toxicities. You have to
22:14be. Um but it's it's it's just
22:17interesting biology to understand how
22:19systems respond uh just about every
22:22system responds to stress by trying to
22:25protect itself. go back to the concept
22:28of adaptive homeostasis and that is that
22:31we wouldn't be here on earth today if we
22:34didn't know how to fight and protect
22:36ourselves. I mean, this is really what's
22:39going on and that is that when when
22:41you're stressed, uh, the body recognizes
22:44stress and it and it needs to protect
22:47itself from threats to itself and and
22:50that's where hormesis, I think, in
22:53general, fits into the to the overall
22:56spectrum. So, in um, you know, people
22:59might say, well, why do you believe in a
23:02in a harm dose response? Why do you
23:04think that the LNT the linear model is
23:06wrong? Uh and I'd say well the reason
23:09why I think the L&T model is basically
23:12wrong is um
23:15is that biological systems uh have
23:18evolved u many many ways to protect
23:22themselves against all kinds of
23:24stressors and and those those organisms
23:28that didn't develop those systems they
23:30died. they were selected against the
23:33ones that developed them um and uh out
23:37competed other species or however it
23:39worked for them. uh they survived and
23:42and they ultimately led to you know
23:45we're the product of all that and and
23:47and so we actually when we look at
23:50biological systems today we're very
23:52strong very robust and we and and these
23:56systems
23:58there's all kinds of adaptive systems in
24:00every cell type to protect ourselves.
24:03doesn't mean that they're fully
24:04protective, but it means that that that
24:06it can handle a wide range of chemical,
24:10physical, mechanical stresses that we
24:12have. And um and and that's why I think
24:16that that the hormetic dose response is
24:19is actually makes the most sense because
24:22it's it's founded in evolutionary
24:24biology, whereas the the linear dose
24:28response is is founded in in fear.
24:31actually fear uh of um of harm and and
24:36and and and uh and it doesn't and it's
24:41decoupled from a a really um better
24:44understanding or using the
24:46understandings of what we know about you
24:48know evolutionary biology.
24:52Yes. True. And you have also just
24:54mentioned the dose and also the halflife
24:57like the low doseis will produce
24:59beneficial effects but like is this
25:02effect persistent is it related to or
25:05like from a longer time scale because of
25:07the halflife of different like elements
25:10and things the the beneficial effects
25:13will decay as it goes.
25:16Well I think it depends on on the
25:18circumstances. I think that that when
25:20you take a look at um um
25:24at at at agents that are inherently
25:27highly toxic that have a long halflife
25:29then then you as I mentioned like things
25:32especially like cadmium um you you have
25:36to be very careful with your exposures
25:38to these you have to keep the those
25:40exposures uh extremely low because you
25:43don't want these exposures to be to
25:46build up in the body to become within a
25:49toxic within a toxic zone. So you I you
25:52really try to stay away from those when
25:54when you when you um u and that's why u
25:58you know one has to know everything
26:01about the the agents that you're
26:02studying their their tissue distribution
26:05um you know how how how long they stay
26:08in the body and and what their
26:10biological half- livives are. You have
26:12to know everything uh so that you can
26:14make really the the the correct sorts of
26:17judgment. I'd have to say that that the
26:20the when I mentioned a lot of these uh
26:22you know ancient u traditional Chinese
26:25medicines and traditional other Asian
26:27medicines a lot of these agents that
26:29that that are ingested they're
26:31inherently toxic um and they they are
26:35designed to protect plants from being
26:36eaten actually but when we eat them they
26:40they can stress our systems now they
26:42they actually do they they a lot of our
26:45you know I mean I I try to activate
26:49adaptive systems in in my my cells every
26:52day. Every day I I I purposefully I have
26:56to I purposefully stress my body uh
27:00through exercise through the foods that
27:02I eat and and I even my in my my the
27:07food my my my let's say my meals per day
27:10I about x number I don't know how many
27:13years ago but I started um eating only
27:15one meal a day. So I just eat a meal in
27:17the evening. So I go 23 hours without
27:20eating all day long. All all day I don't
27:22eat anything in between, right? And and
27:25I do that mostly to stress my systems.
27:28So I'm always I'm I'm stressing my
27:31[clears throat] there's some you know
27:32underlying mechanism reasons for this.
27:34But everything that I do in life,
27:36whether it's my the I exercise for an
27:38hour a day, I do this this one meal a
27:41day. I take these supplements and the
27:44supplements are designed to provide
27:46oxidative stress. They're actually
27:48provide oxidative stress to upregulate
27:52um the synthesis of antioxidant enzymes
27:56to protect myself against all kinds of
27:59oxidative stresses that that my systems
28:02will will have. And and I think that
28:04this is this this is uh um this is what
28:08what I think needs to be to be done
28:10within schools of public health when
28:12they're educating their their students
28:14and their students have to then go and
28:15educate the general public is is to try
28:18to tell is to try to uh educate people
28:22as to how they can make their own
28:24personal life um much more healthy than
28:29um you know it's it's not just that you
28:31shouldn't smoke or drink to excess. But
28:34it's there are so many other things that
28:36you you can do. But but all these really
28:40come down to from my point of view is is
28:43you have to make sure you stress your
28:45body modestly modestly stress your body
28:48to enhance your overall health. And and
28:52this needs to start at a very young age
28:54because the diseases of I mean I'm 77
28:58years old now so I'm old so to speak,
29:00right? Right. But and and it's dur when
29:03you're old at this stage of the game for
29:05me many many people are developing all
29:08kinds of diseases. It's uh you know
29:11various neurological diseases um the
29:14neurodeenerative diseases. They they
29:17have you know risks of heart attack and
29:19stroke and things all kinds of these but
29:22but you you start to protect yourself
29:24from these when you're younger. If you
29:27want to protect yourself from these and
29:29have a a healthier lifespan, you have to
29:32start introducing hormesis behaviors
29:36when you're in your 20s and 30 years of
29:39age. Like when at your you're you're
29:41very young. So you you need to be in,
29:44you know, introducing hormesis into your
29:46lifestyle now because when you're my age
29:50now, you know, so many years from now,
29:53um you'll be you'll have a much
29:55healthier lifespan. and and and and
29:58things of that that nature.
30:01Yes, that's true. I've just noticed that
30:02you have taken only one meal a day. So,
30:04it's like related to fasting and
30:06fasting, intermittent fasting, these
30:08kind of things has also been seen as
30:10homesis. And I've tried this as well
30:13myself for like a couple of weeks, but I
30:15didn't stick to it. But I think it's it
30:19will be better if I just uh pick it up,
30:22pick it up again, and just try to do the
30:24fasting thing.
30:26because it can stimulate our autophagy
30:28and it's good for our health, right? And
30:30there's another thing that I'm really
30:32interested in just now in your talk is
30:35just you have mentioned the agricultural
30:38purpose that that the ingredients and
30:39substances we build for the agricultural
30:41purpose to kill the insects and
30:43paracquant is one of them and it has it
30:46has been proved to extend the lifespan
30:49of sea elegance. Do you think it is
30:51possible that we use like things like
30:53parakquant to extend the lifespan of
30:55human beings?
30:57Well, I I actually I tell you the truth
31:00I I' I've seen all those data on
31:02parakquot and other agents. They they
31:05did they definitely can you know in
31:06experimental models they can protect
31:08against a lot of different uh stresses
31:11put it that way. But there are there are
31:13many things that are um less toxic you
31:16might less inherently toxic than
31:18something like parakquot
31:20I try to extend I I try to prevent the
31:23occurrence of let's say Parkinson's
31:25disease in myself and so forth but I
31:27don't take paraquot
31:29[laughter] I I would take uh you know
31:32various types of uh uh plantderived u um
31:38um supplement sort of activities that
31:40are that are studied very Well, and that
31:43that actually uh um and you have to
31:46watch out for for anything that acts
31:48hormetically, it has to be in the right
31:51dose because you have you take too much
31:52and it becomes toxic. And and one of the
31:55nice things about about um dietary
31:58supplements is that a lot of them have a
32:01relatively poor bioavailability.
32:05And so it's it's hard it's hard to
32:08become uh you know intoxicated by them.
32:12And so and so uh so when I when I take
32:15my supplements, my wife looks at all
32:18these little capsules that I take in the
32:20morning and she thinks that that I'm
32:22crazy. Uh and why would anybody do this?
32:26And I said well I that's what I study.
32:28But I said it's it's also um you know
32:31these might have a bioavailability of
32:34you know less than 2% less than 1%. And
32:37so and so you know it's it's a question
32:39of uh I I you my my biggest concern is
32:43making sure that I get enough of the
32:45stress uh to activate my systems because
32:50uh you need a certain level of stress
32:53but I but I wouldn't want to I wouldn't
32:55want to take a a lead supplement or a
32:58caffeine supplement or a paracqu I'd
33:02stay away from all those pollutants.
33:03Right. um uh the uh but I would find my
33:08stressors with with other things. For
33:11example, the intermittent fasting, the
33:13exercise, I do other other ways to to
33:17try to bring stress into my life. Um you
33:20know, rather than I mean rather than you
33:24know I'd have to say even you know it's
33:27interesting ionizing radiation
33:30um at u at a certain dose range. This is
33:34a very interesting, you know, before
33:36society had things like penicellin and
33:39other sorts of drugs to to help us avoid
33:43um problems like pneumonia and things
33:46like that that could kill you. Um, but
33:48back in in in the United States in the
33:511930s and 40s before there were things
33:55like antibiotics that you could use in
33:57the hospital to treat a sick patient,
34:00they they really didn't know, you know,
34:02they didn't know how to treat people.
34:04They were they were you when when my my
34:08father was born in 1911. Okay, so he was
34:11born in 1911. my my my father um and and
34:16so when he grew up as a child in in in
34:19the United States when if he got sick or
34:22something there there were no real drugs
34:24to treat him.
34:25You know, you got you got a headache, if
34:28you got a if you got an infection or
34:31something like that, you [clears throat]
34:32you really they didn't have drugs to
34:34treat people like like we have today.
34:37you know, you get sick, you you go to a
34:39physician, they give you a a nice drug
34:42to help you get over your your
34:44condition. Back a hundred years ago,
34:46they really didn't have that.
34:48And and so just think if you have u you
34:52know arthritis or if you have pneumonia
34:54or you have back if we if we were born a
34:57hundred years ago, our lives would not
34:59have been nearly as good as they would
35:02be today. I mean, seriously, you know,
35:04but but what happened in the 19 30s as
35:07people started to use uh because they
35:09didn't know what else to do. They
35:11started treating people who had both
35:13arthritis and and pneumonia, they
35:16started treating them with X-rays
35:18and a certain level. And uh and what
35:22they found, this is really strange, but
35:23if you were in the right the right dose
35:26zone
35:28that that in in many studies in the
35:31United States showed that people who
35:34were given a certain treatment of X-rays
35:37uh they actually um survived the
35:40pneumonia and re back in those days half
35:44the people died who had were admitted to
35:46the hospital in the United States for
35:47pneumonia. Half lived. But if you
35:48treated them with X-rays, um the
35:52mortality went from 50% down to only 8%.
35:55Was really amazing. And and then
35:58ultimately penicellin came and it outco
36:00competed the the the um sulfa drugs and
36:03and radiation. But it's it's interesting
36:08that I've gone back and looked at this
36:10and if you're right in the right zone,
36:12the the radiation induces um a whole
36:15series of of uh it creates an
36:18anti-inflammatory phenotype. It it it
36:22induces these antioxidant enzymes like
36:24like many of the the the the supplements
36:27do actually. And and in Germany today,
36:30this is Germany, I think, is the only
36:31country, but if if you don't if if if
36:35traditional drugs do not help your
36:37arthritis, the the uh the German
36:40government funds uh research or funds
36:44funds the payment of treating people who
36:47have arthritis
36:48uh with what I call lowdosese radiation
36:52treatment and it's very effective in
36:55reducing the the u uh the pain and and
36:59inflammation that's associated with with
37:02uh with arthritis. And and in studies
37:06with animal models, if you take six or
37:09seven different animal models that have
37:11been studied, give them a wide dose
37:13range of X-rays, you will find that that
37:16the X-rays actually decrease the
37:19inflammation just as well as a drug
37:22does. And it does it in a J-shaped dose
37:25response. beautiful hormetic dose
37:27response. Yeah. And and the and the
37:30underlying mechanisms are are are pretty
37:32well understood today. So, so hormesis
37:35is occurring in a lot of different ways
37:38and and there's a convergence on on how
37:41it works and and it typically works by
37:44the activation of uh of protective
37:47mechanisms, a whole host of those, but
37:50ultimately leading to these
37:52anti-inflammatory
37:54phenotypes that protect us from in
37:57inflammatory conditions. and and and and
38:00the the problem with aging is that you
38:03know as you get older and older there
38:06there there's a there's a movement
38:08towards uh much greater inflammatory
38:11[clears throat]
38:11uh processes in your body and and that
38:15creates the condition for the
38:18neurodeenerative diseases but cancer and
38:20other things and you and and one of my
38:22goals my personal goals is I want to I
38:26want to ratchet down high um
38:30inflammatory markers.
38:33I want to have far less inflammatory
38:36markers in my body than than um than
38:40than otherwise would be the case. And I
38:42think that that that's that's what that
38:45that's what I think uh is a public
38:48health message is that is that as you're
38:50going forward, you know, we have all
38:52kinds of these pro-inflammatory markers
38:55and and and and we should try to do what
38:58we can do to reduce those. And you know,
39:01you can do that with with very little
39:03cost. You can do that with your
39:05lifestyle and um and other and what you
39:08know, some of the things that you eat.
39:10But that that's why I do what what I try
39:12to do. It's all hormesis based.
39:17Yes, that's true. And arthritis, there
39:19is also something that is less fatal
39:22than paragon has been
39:25proven to treat arthritis, which is the
39:27B venom. Venom has also been proved to
39:30like treat arthritis. But there's a lot
39:33of like subranches of B venons out
39:35there. So one B venom is okay for
39:37arthritis. Is it does it mean that all
39:40of the bean venom family can treat like
39:42diseases and be helpful to us?
39:44Well, you know, I saw I saw I saw that
39:46in the uh in the uh series of questions
39:49that you sent me last week and I I have
39:51to tell you that I don't know much about
39:53you know be venom and so I'm not going
39:56to be uh and I didn't um I've been so
39:59busy in the last week that I didn't
40:00actually go back and try to figure try
40:03to learn more about it. So I'm going to
40:05have to pass on that question. But I but
40:07there are but I'd have to tell you that
40:09that there are um many different u
40:13things that you can do um without using
40:16B be B venom. Well, that be venom may be
40:19great and I' I'd have to look at that,
40:21but but that for example, um I'd have to
40:25say that that I I start my day taking
40:28like uh a thousand milligrams of let's
40:30say fish oil and and I and I drink and I
40:34and I actually today I today how I
40:36started my because I don't have
40:38breakfast. I started I started my day
40:41before I came to to this this talk to
40:44with you. So at 6:00 in the morning, I
40:46took 1,000 milligrams of fish oil. I
40:49took uh about 750 milligrams of of uh
40:54extract from u green tea. So it was
40:57decaffeinated extract from green tea.
40:59Then I took u
41:02um about a thousand milligrams of
41:05curcumin. I took some ginko biloba and I
41:09took uh um what did I take? Uh gensing.
41:14Yeah, I took uh my gensing sample and a
41:16couple of other things this morning. And
41:18so and so I I start my day with a uh
41:22with an effort to try to load myself up
41:25with something that's going to stimulate
41:28the production of uh anti- you know move
41:32me towards towards a less inflammatory
41:35state and towards a um but they'll it
41:38does this by by stressing your system.
41:41These are the these are these molecules
41:43themselves are inherently modestly
41:46stressful, but they activate u they
41:49activate your body um
41:52to upregulate various types of uh um oh
41:59um pathways that will lead to a whole
42:02series of you know antioxidant
42:05protection.
42:06And and so that's that's what that's how
42:09I start my day. start my day
42:11and and I believe that that most people
42:15uh you know need to do that and and
42:17throughout the day I will have I I will
42:19just continually drink uh green tea um
42:24because I'm going to be it's again it's
42:26the the same way of trying to be exposed
42:28to something that's potentially
42:30beneficial for you. Then at 1:00 I'll go
42:33to my recreation center and work out for
42:35one hour. And so I will um and so I'll
42:39go on a bicycle. I'll do something like
42:41that. And but it's all tied into to
42:44stressing yourself. And even even uh the
42:47work that we do is intellectually
42:49stressing. Um but it's but it's in a
42:52positive way. It's intellectually
42:54stressing. So it's it's good for our
42:56systems to uh to have what I'll say
43:00consistent modest stress um from a
43:04physical to emotional to all sorts of
43:07all sorts of ways. and and and and it
43:11and and what we've been brought up in
43:13the environmental
43:15range is to feel that everything is
43:17harmful even at the lowest possible
43:19doses and and and even if something
43:23causes damage at the lowest possible
43:25dose, it doesn't mean that the body
43:28doesn't respond to that and protect
43:30against it. The body will will uh the
43:33the body if there is damage the body has
43:36the capacity to d you know it has
43:39sensors it can m it has all kinds of
43:42sensors and it's measuring change in
43:45temperature changes in structure changes
43:47in oxygen tension all kinds of sensors
43:50you know nutrient sensors every kind of
43:53sensor you know you can imagine you you
43:56know when you have a a modern automobile
43:58and you back up it can sense if there's
44:01a person walking behind you. It it
44:03senses everything. That's what goes on
44:05within ourselves. Our cells are loaded
44:08with all kinds of sensors. And if
44:11something uh goes off with within our
44:15equilibrium,
44:16it it it brings it it creates a process
44:20of adaptation and it helps us to to get
44:24stronger to fight that off and to fight
44:27off the next challenge. and and and I
44:29think that that that's it's really an
44:31optimistic message uh for uh for humans
44:37if we are smart enough to figure out how
44:40to protect ourselves. But but humans um
44:44a lot of times aren't very disciplined
44:47and they don't do their research and
44:49they and they and they and they and they
44:52live um very unhealthy lives. Um and um
44:57it's everywhere but because living a
45:00healthy life um it doesn't necessarily
45:03cost a lot of money but you have to be
45:05disciplined and you have to have
45:07knowledge and then you have to bring
45:09those together to actually make that
45:11happen. Um and uh and so it's it's it's
45:15it's very very it's very interesting.
45:20Yeah, that's true. So apart from those
45:22food supplements, do you have other like
45:25recommendations or other things that
45:27related to home that you think is good
45:29for our health? Like apart from food
45:31supplements?
45:33Well, I have to say that um the the big
45:36things as I was just kind of mentioning
45:37was I I I think that the best medicine
45:40that you can take, the best thing you
45:43can do for yourself is exercise. That is
45:46and I and why I say that is I I believe
45:49that exercise the effects of exercise I
45:52think affects just about every uh it
45:54affects every organ and every system
45:56within your body. So it's a very general
45:59stress which is um which is good. uh
46:03many of the the supplements that I would
46:05that I would take that I would s say
46:08they're t see I get the reason why I
46:10take so many is that each of them has a
46:13different tissue distribution some pass
46:15the bloodb brain barrier some don't pass
46:18the bloodb brain barrier some some only
46:21go to the liver and the kidneys others
46:24go to other locations and so I try to
46:26understand uh what the tissue
46:29distribution is of every agent that I
46:32take so that I'm I'm trying to make sure
46:35that that um all my all the systems this
46:38the skin the you know the um um the
46:42bladder the the liver that that they're
46:45all somehow uh stressed and it's just
46:48not one particular system that that's
46:51stressed. So I I that the the the diet
46:53actually is is critical as I as I
46:57mentioned and the stress within the diet
47:00is I think important and that is that
47:03the um the the
47:06issue of the intermittent fasting I
47:08think can be very important at a
47:11particular age and to m maintain that.
47:14Um I I think that uh I actually think
47:18that that there are so many there are
47:20social factors that are that are
47:22important from what I've what I've read.
47:25You know just you know having a
47:28having a positive job is really
47:30important. Having a good family life is
47:32really important. you know, these things
47:35are are they they they they they come
47:37together and bring a lot of a lot of joy
47:41and and and and and also, you know, one
47:44I'm I'm it's very interesting. I have to
47:46tell you this, the project that I'm on
47:48right now and I'll be publish submitting
47:50a paper very soon on it um within within
47:53days. But but um through
47:58women as they get into their late 30s
48:00and 40s, a lot of women and certainly in
48:02this country, they they tend to delay
48:05their starting a family until 35 to to
48:0940 years old. And and as they get older,
48:12they they tend to re their fertility
48:15decreases.
48:17Um and it's sometimes it's harder to get
48:20pregnant, things of that nature. And so
48:22I've been looking at the um the OO site
48:26and um and factors that affect aging and
48:30I have found that that area is just it's
48:33been studi it's being studied by a lot
48:35of people in a lot of countries and I
48:38can tell you for sure that it is uh
48:42enormously
48:43u uh impacted by by um hormetic factors.
48:49It's really very interesting. you you
48:51can protect the oite uh you can you
48:54certainly can you know en enhance oite
48:58maturation you can um protect it from
49:01all sorts of oxidative stresses and
49:04other stresses um um within hormetic
49:08within a harm fashion it and I also have
49:11to tell you that I mean I have hundreds
49:13of examples of this hundreds um and and
49:16yet none of the research this is
49:18interesting none of the research church
49:20is in that area ever mentions the word
49:23hormesis. Now I've done the same thing
49:27in the world of stem cells which is a
49:30very big area wound healing very big
49:32area and what I and I have found these
49:35loaded with examples of hormesis and and
49:38in the stem cells I published 14 papers
49:41on stem cells a couple years ago right
49:43and and just about every one of those
49:46and I looked at you know adapose derived
49:48stem cells neuro stem cells embryionic
49:50stem cells all kinds of stem cells right
49:53almost Never do the investigators who
49:57are studying these and and how to
49:59stimulate them, how to uh direct them,
50:02how to protect them, things of that
50:03nature and they show many many examples
50:06of hormesis. Almost never do these
50:09people, these researchers ever mention
50:13the term hormesis. They don't have any
50:16understanding that this bifphasic dose
50:18response is a hormetic dose response and
50:21that it's a very general dose response.
50:24the scientific community is for the most
50:26part very um very ignorant of what
50:30hormesis is and and and I and I find
50:34that this is it's very frustrating to me
50:36because because this is my field and at
50:40the same time uh it gives me an
50:42opportunity to to educate these other
50:44people but but [clears throat]
50:46u one of the big challenges is uh in in
50:49in the world of science you know
50:52[clears throat] the the the area of
50:53aging and biogentology has adopted
50:56hormesis and the language of hormesis
50:59and so has in exercise science and a few
51:01other other areas but most of the areas
51:04most of the biomedical areas they have
51:07no understanding very little
51:09understanding of the hormesis concept
51:11it's very very interesting and and I
51:14think they do that because they don't
51:16they're so uh they're so what what I
51:18call silo they're there they're so
51:21specialized that they don't read what
51:24goes on in other disciplines. And so
51:26they have no understanding of anything
51:29other than their little little little
51:31tiny thing that they study and that's
51:33all they know. They have no no knowledge
51:36that this bifphasic dose response is all
51:39general and it's a hormetic thing and
51:41and why it's supposed to be there. The
51:44scientific community is is really needs
51:47to be educated on hormesis.
51:51Yes, that's true. It's just like when we
51:53went into the medical school, we get a
51:56comprehensive knowledge of all the
51:57things but as our study goes on, it has
52:00been narrowed down again and again again
52:02and later on we'll be studying just on a
52:04tiny part of it like uh you have just
52:07mentioned the paper on the oide aging
52:10and which is related to homesis. I'm
52:12really looking forward to the
52:13publishment of that paper as well. And
52:16what do you think professor that we can
52:18use to utilize in the drug development?
52:21How can homis be utilized to optimize
52:24the dosage or effectiveness of all the
52:27drugs and supplements?
52:29Well, I have to tell you this is
52:30interesting. I I haven't talked about
52:32this but um for example in the world of
52:35uh let's say um anti-anxiety drugs and
52:41that's a very very gigantic business
52:43throughout the world is you know
52:46anti-anxiet anxolytic drugs anti-seizure
52:49drugs just about every most families of
52:52drugs if you go into the clinical um I
52:55call it the preclinical literature the
52:57the pre where the animal studies where
53:00they're studying these I'll tell you
53:03when I go into the the pre-clinical
53:05literature on like anti-anxiety drugs or
53:08anti-seizure drugs and things of that
53:10nature all of those studies for the most
53:13part they show a bifphasic dose response
53:16it's really very interesting and then
53:19when when these studies then get tested
53:22in a clinical trial they just take the
53:24optimal dose maybe two you know within
53:27that that protective zone and then they
53:30test it and let's say that it's
53:31successful in humans and the clinical
53:33trial becomes a drug. But though most of
53:36the drugs are actually hormetically
53:39acting, but the pharmaceutical companies
53:42and the research community doesn't even
53:45understand that they're [laughter]
53:47dealing with a hormetic dose response.
53:49They are fundamentally ignorant. And um
53:53and these very smart people, great
53:55researchers, uh big-time companies, they
53:58they tend to be they don't understand
54:00what we're talking about today.
54:03It's very it's very very interesting.
54:05Very very interesting.
54:07Yes. There there's a like a lot ignorant
54:11on the homesis and the overall concept
54:13of it like from the very beginning like
54:15homesis we think it when we think of
54:18this word we are related to like toxins
54:20and poisons right? So from the very
54:22beginning how human beings get noticed
54:24and come up with the idea of treating
54:26diseases or like the life lifespan
54:29issues with these homies with homesis is
54:32it out of coincidence?
54:35Well, you know, it's hum human behavior
54:39is um it's really hard to understand.
54:43you know, it's uh uh exper
54:46experimentally
54:48um you know, I mean, I I've gone back on
54:50hormesis to try to understand its
54:53history and and and it's I'm not sure if
54:56you've had a chance to read some of the
54:59the historical papers that I've written
55:02because I could send those to you if you
55:04if you'd like because it really the the
55:07problem of you know, Hormesis had a it
55:10it it's u it was really first um
55:14conceived of, you might say,
55:15experimentally shown back in the 1880s
55:18by this fellow Hu uh Hugo Schultz and
55:22and with with yeast. Uh but Hugo Schultz
55:27um he did really good work, but but Hugo
55:31related his work to the medical practice
55:33of homeopathy. And homeopathy was very
55:37controversial and it was very
55:39competitive in the late 1800s with what
55:42I call traditional medicine. and and and
55:45the concept of hormesis was was um um
55:50rejected by traditional medicine because
55:53Hugo Schultz had associated it with
55:56homeopathy
55:58and and it and um and so for the for
56:02most of the 20th century the the medical
56:05community um the medical community was
56:08very biased towards uh the concept of a
56:12bifphasic dose response.
56:14And and plus the bifphasic dose response
56:17is very hard to study because you need
56:19lots of doses. You need you're only
56:22going to see a modest response 30 to
56:2460%. You need lots of lots of uh
56:28samples, lots of subjects that you're
56:30going to need to be studying and it's
56:32hard to it's it's it's harder to prove.
56:34And so for a lot of reasons, Harmesis um
56:38was uh had was difficult to to to
56:42successfully make it into the biomedical
56:45literature. It's doing it now u because
56:48of all of our work. But nonetheless, um
56:51you know, there's an awful lot more work
56:53that that the next generation has to do,
56:56your generation has to do to move this
56:59thing forward really. Um but there's uh
57:02but you've got um you know Well, you've
57:05got a lot of, you know, you're on the
57:06right track because there's a lot of
57:08evidence now to support hormmesis. You
57:10have mechanisms, you have reproducible
57:13findings, you have good applications.
57:16You're you're in a good position to do
57:17some great work actually.
57:21Yes, that's true. like um homie you have
57:24just uh just now like few questions late
57:27earlier you have mentioned the radiation
57:30use radiation to treat arthritis but
57:32there is also some problems right now
57:34these days like when we are doing the
57:38radiological examinations
57:41and
57:43so we might get into about those new
57:45nuclear power plants they might some
57:48there's some accident happening and some
57:50contaminated water being released So
57:52what are these unexpected like high dose
57:55of these toxins relate to us and how
57:59will it affect our life?
58:01Well in in in general I think you have
58:03to look at everything pretty carefully.
58:06Um I I tend to think that a lot of what
58:09happens in the environmental domain uh
58:13is um but as I said prefacing it by you
58:17really have to look very objectively at
58:19what's actually happening. But a lot of
58:21times these these situations become very
58:23politicized. And so you have you have
58:26different groups that are that that look
58:29at things not scientifically but they
58:32look at them I call it ideologically or
58:35politically and and that to me is the
58:37wrong way to do things. Um, and but
58:40that's what actually gets reported in
58:42the certainly in the United States media
58:45which is very politically oriented and
58:48but they they don't actually do a good
58:50job on getting down to what is the
58:53scientific uh basis for either concern
58:57or or lack of concern. So each one of
59:00these issues needs to be really looked
59:03at very carefully, very objectively in a
59:07very nonbiased way so that the public uh
59:12can actually be educated properly rather
59:15than be pulled to one side or the other
59:18mostly by politically motivated groups.
59:22And so I'm very I'm very opposed to
59:24politically motivated groups when it
59:27comes to science. Science needs to be,
59:30you know, follow the science and and
59:33then it'll lead to much better answers
59:36rather than you see a lot of people they
59:39believe they know the answer and then
59:41they try to fit the science into what
59:43their beliefs are. And it needs to be
59:45the other way around. Your beliefs
59:47should come from your scientific data.
59:50uh and then you can make good decisions.
59:52Uh when you think you know the right
59:54answer, that's a bad that's very bad
59:57start. Uh and and so I think that when
1:00:00you educate students like you're in an
1:00:03educational system, it's really
1:00:05important for them to to you know f
1:00:08create hypotheses, test hypothesis,
1:00:11follows those hypotheses and and and
1:00:13then don't be afraid to be wrong. uh
1:00:16when in my whole life as a professor I I
1:00:19I had maybe a hundred graduate students
1:00:22for getting their doctoral dissertations
1:00:24and and and other things, master's
1:00:26thesis and and I would have to say that
1:00:29about 60% of those dissertations proved
1:00:32my ideas were wrong. Okay, when they
1:00:35actually I thought I knew something, but
1:00:38when they tested these ideas in the
1:00:40laboratory, the students showed that my
1:00:42ideas were wrong at least 60% of the
1:00:45time. And so and and I thought that I
1:00:47was very knowledgeable and but but yet
1:00:50uh and so I think that that society
1:00:53needs to be be very careful u and with
1:00:57information always has to be very
1:00:59objective about information and and this
1:01:02way we we don't get um we make less
1:01:05mistakes. We're more objective about it
1:01:08and we're less emotional like when it
1:01:10comes to environmental and other sorts
1:01:12of fact. try to get the facts right and
1:01:15even even on you know the kinds of
1:01:17things that I'm talking about you know
1:01:18the fasting or the this supplement uh I
1:01:21don't take I do not take a supplement
1:01:24until I have reached re researched it uh
1:01:27enormously and so everything that I take
1:01:30I never look at the advertisements that
1:01:32a company sells I get all the scientific
1:01:34papers and I evaluate the scientific
1:01:38papers then I make a decision most
1:01:41people can't do that because they don't
1:01:43have our training. See, we're trained to
1:01:46to evaluate things, right? But other
1:01:48people, um, most people can't do that. I
1:01:52mean, my wife couldn't do it. She's
1:01:54she's like a uh like a, you know, like a
1:01:58a fifth grade teacher. She teaches
1:02:00English. She she couldn't do the science
1:02:02that I do. You know, she has to rely
1:02:04upon somebody else's judgment to tell
1:02:07her or or other people do. So, we're
1:02:09very lucky that we are trained
1:02:13in the sciences because we can actually
1:02:15evaluate things. Most people can't do
1:02:18that. Most people they're totally
1:02:22um they might be smart and they may know
1:02:24something about other things but they
1:02:26can't evaluate what you and I can
1:02:28evaluate. Makes it really you know it's
1:02:31an interesting situation to be in.
1:02:36Yes, that's true. Science is about like
1:02:38facts but our inter
1:02:41our interpretations might be subject
1:02:43subjective and when we impose those
1:02:46subjective interpretation to sign is
1:02:48actually not a very ideal action. So we
1:02:51we need to choose it and take it
1:02:53objectively and just to look at the
1:02:55facts and then to decide what we will go
1:02:57on and doing things. It's a very good
1:02:59way to to educate us and to tell us what
1:03:03is currently right and what is currently
1:03:05wrong. That's what I think
1:03:08and it's a and it's a good thing not to
1:03:10be afraid to be wrong. You know,
1:03:12everybody makes mistakes and and and but
1:03:14but it's good to it's good to be
1:03:16objective and that's and that's the goal
1:03:18and to make it less emotional. Stick to
1:03:21the facts.
1:03:22I think that's that would be my biggest
1:03:24message really and that's true for
1:03:26hormesis. be be as critical on hormesis
1:03:28as I'd be on every and anything else.
1:03:31Just always stick to the facts and see
1:03:34if it convinces you or how to test how
1:03:37[clears throat] to test something to see
1:03:38if it's correct. That's very very
1:03:40important.
1:03:43Yes. And you have been always like um
1:03:46not challenging but like trying to find
1:03:49different things in the scientific world
1:03:51like one of your research background has
1:03:54been focusing on cancer and you have
1:03:56also highlighted the flaws or the
1:03:59insufficient of the L&T model that has
1:04:02existing in the cancer assessment
1:04:05method. So what in your opinion,
1:04:07professor, there can be a very
1:04:09comprehensive and accurate cancer risk
1:04:11assessment that we can carry out right
1:04:13now. Well, I I' I'd be happy someday to
1:04:16give a talk on the LNT thing to your to
1:04:19your group if if you're ever interested,
1:04:21but I would have to tell you that that
1:04:24uh my evaluations of LNT came out of my
1:04:28work on hormesis because I I was
1:04:30studying dose responses. And so I ended
1:04:32up, you know, needing to look at the LNT
1:04:35history as well. And what I found just
1:04:37very briefly was that the L&T model that
1:04:40really was was uh came out of work in
1:04:43the United States during the 1940s and
1:04:4550s and 60s was is actually
1:04:49fundamentally um um flawed. It's it's uh
1:04:54loaded with uh mistakes. It's load it's
1:04:57loaded with terrible bias. Uh and it's
1:05:00also loaded with deliberate
1:05:02misrepresentations of the scientific
1:05:05record. it this was carried out by the
1:05:07US National Academy of Sciences. The
1:05:10journal science participated in in in
1:05:13these sorts of things and and and what's
1:05:15happened and then and then to make it
1:05:17all worse the US regulatory community
1:05:20like the EPA adopts these uh these in
1:05:24the mistakes and perspectives and they
1:05:26never go back to actually uh researching
1:05:30the historical foundations of it. they
1:05:32they they adopted the the biased
1:05:35recommendations of of previous US
1:05:37National Academy panels and and I think
1:05:41that they got the dose response wrong
1:05:43because of their biases. And so and so
1:05:46what's happened is that here I am now
1:05:48it's 2024 and I'm saying that that the
1:05:52the entire US regulatory program is
1:05:56totally flawed and corrupt and u and so
1:05:59they don't like me very much. Um
1:06:03although many people do and uh but but
1:06:06the thing of it is is I I publish a lot
1:06:08of papers on this. I published probably
1:06:10a hundred papers on this history of LNT
1:06:13and and and I believe that that my story
1:06:15is a correct story and I um you know I'd
1:06:19be happy to um to uh if if your class is
1:06:23interested you know give a talk on this
1:06:25sometime uh sometime in the future. It
1:06:28would it would take about two hours to
1:06:29tell you the whole story, but I'd be
1:06:32happy to do that [laughter] if people
1:06:34are interested in in in hearing my view
1:06:37on the historical foundations of cancer
1:06:39risk assessment. It has lots of
1:06:41implications for every country in the
1:06:43world including China and u and I
1:06:46believe that um I believe every country
1:06:48is wrong. Every country is adopting LNT
1:06:51and I believe every country is wrong. I
1:06:53think they should listen to to Calibri
1:06:56on this matter and then see um and then
1:06:58see see where we go from there.
1:07:02That would be great. Maybe maybe in the
1:07:04future there will be this kind of
1:07:06chances that you can elaborate on the
1:07:08air model as well and today we have been
1:07:11you have been you and I have been
1:07:13discussing for like more than an hour.
1:07:16So there is also many audiences that
1:07:18wouldn't to uh ask you some questions
1:07:21and their opinions onis as well. Can I
1:07:23hand these questions to you as well?
1:07:25Uh sure why not we're here. Let's do it.
1:07:28Um I've received one message from our
1:07:30online audiences. You you can just seen
1:07:33that they have been typing in the chat
1:07:35boxes. I will translate it for you. So
1:07:37the first question is free radicals are
1:07:40always put on the hat of evil but a lot
1:07:44of research show that free radicals also
1:07:47has a beneficial side. What do you think
1:07:51for of free radicals as poisons? Do we
1:07:55need to take these take antioxidants or
1:07:58what antioxidant do you recommend if
1:08:01necessary?
1:08:02That's a that's actually a great
1:08:04question and and it's fundamental to to
1:08:07the whole discussion today and that is
1:08:10that I'll give you an example um that
1:08:13that'll answer the question. Uh there
1:08:16was a um there was a study that was done
1:08:19with respect to exercise in in humans.
1:08:22It was a human study and they were
1:08:24people were studying um u uh humans that
1:08:28had type 2 diabetes and so they wanted
1:08:32to give them uh have them exercise
1:08:35because they felt that exercise could
1:08:36improve the type two diabetes condition
1:08:39and so they also gave them a high dose
1:08:41of vitamin E. Okay. So they had a group
1:08:44that got that the you know a control
1:08:47group and a group that got the the
1:08:48different sorts of conditions and what
1:08:51they found was that the exercise was
1:08:54very protective.
1:08:56Um but what what they found was that
1:08:59when you gave the people who exercised
1:09:01the uh the the vitamin D vitamin E
1:09:05vitamin E which is a strong antioxidant
1:09:08when you gave them this along with the
1:09:10exercise it totally blocked the
1:09:13protection and eliminated the protection
1:09:15that the exercise gave. So you think
1:09:18that you were doing something good for
1:09:20you when you exercised and you took the
1:09:22vitamin E, but the vitamin E totally
1:09:25blocked the protection of the exercise
1:09:28and it's and it relates to the to the
1:09:31person's question of free radicals
1:09:33because because the exercise is actually
1:09:35inducing um uh is actually creating
1:09:38reactive oxygen species or free radicals
1:09:41that are activating some of these
1:09:43pathways that induce the the protective
1:09:46effects and the vitamin E comes in and
1:09:48the vitamin E can actually block that.
1:09:51And and I'd have to tell you I I I
1:09:53stopped I I was a reviewer of that
1:09:56paper. I was a re that paper was
1:09:58originally submitted to the to the New
1:10:00England Journal of Medicine and after
1:10:02about six months was rejected and then
1:10:05it was submitted to the US uh the
1:10:07proceedings of the National Academy of
1:10:09Sciences where it was accepted. It's now
1:10:10been cited about a thousand times. It's
1:10:12a very big paper. Uh but as a result of
1:10:15that, what I did was I I I I no longer
1:10:18take uh vitamin E supplements because I
1:10:21exercise all the time and I want to get
1:10:23the benefits from exercise or and these
1:10:26other factors that I have and I don't
1:10:27want something coming in to uh to block
1:10:30that. And so I want to have a low level
1:10:34of uh free radicals operating. I want to
1:10:37have this low level of uh you know
1:10:40generated ROS or reactive oxygen species
1:10:43within my cells. Uh I don't want too
1:10:46much but I want enough to that activates
1:10:49um processes that uh that are necessary
1:10:52to then give me a very strong you know
1:10:55protective antioxidant response. We want
1:10:57I think we want that response to be to
1:11:00be enzyatic as compared to uh you know
1:11:03through through chemical
1:11:07Yes and thank you for your answer. I
1:11:10think that the audience will be very
1:11:11glad for all these messages that you
1:11:13have conveyed and I right now I see that
1:11:16one of our audience have raised his
1:11:18hand. So let's welcome uh you can unmute
1:11:22yourself and this will be the last
1:11:24question today. You can unmute yourself
1:11:26and just talk to our professor.
1:11:29Thank you very much for making me the
1:11:30last person to talk here. Um, professor
1:11:33calibers uh thank you very much for the
1:11:37fascinating uh talk. I was very
1:11:39intrigued that you mentioned you only
1:11:41eat once a day and you are taking 40
1:11:45substances. Uh so my two related
1:11:48question is
1:11:50so with those 40 the combination of the
1:11:5240 substances what is the methodology?
1:11:55How do you choose those 40 substances?
1:11:58And I I if if it's okay for you to share
1:12:02your recipe with us and would you
1:12:04recommend the same uh for us to take if
1:12:06we're able to do the uh the fasting?
1:12:09That's that's my question. Thank you.
1:12:11Well, that's a big question, but I'll
1:12:12try to answer it. Okay. What I what I've
1:12:15tried to do is I'd have to say each each
1:12:17one of these I have actually uh done a a
1:12:20major uh literature review on each of
1:12:23them. many probably at least half of
1:12:26them I've actually now published papers
1:12:28on. So I most substances that I take
1:12:31I've published a paper on. I've done a
1:12:33lot of work on it and have evaluated it
1:12:36from a hormetic perspective and and then
1:12:40go forward and publish on it. So I I
1:12:42actually do that and but but but what
1:12:44actually drives me here is that I'm I'm
1:12:46very interested in their
1:12:47bioavailability. I'm very interested in
1:12:50their u their tissue distribution um and
1:12:53and and many other factors and so it's
1:12:56kind of putting together putting
1:12:58together uh supplements that are very
1:13:00complimentary to to each other um some
1:13:04are able to uh to reach the brain some
1:13:07can't some some some distribute are only
1:13:10located within the GI tract and the
1:13:12liver some go to other the lung and so
1:13:14forth so I'm I'm really I have this I
1:13:17have this big
1:13:18matrix thing on my wall at home and it's
1:13:22telling me, you know, the relative
1:13:24capacity for for agents to be
1:13:26distributed throughout, you know, let's
1:13:28say a mammal's body and and that
1:13:31actually helps me um decide the the
1:13:36matrix of of u of supplements that I
1:13:40take. I try to take them so that they
1:13:41they they complement each other and
1:13:44present uh a a unified hole, you know.
1:13:48So that that's what I and and also I try
1:13:50to do it so that I uh and I'd have to
1:13:54tell you every uh every three months or
1:13:57so I have my my blood tested to see if
1:14:00I've caused any toxicity to myself, you
1:14:03know, like so I'll have liver enzymes
1:14:04and other kinds of things tested because
1:14:06I'm I'm trying to make sure that that I
1:14:09haven't taken too much and I don't want
1:14:12to go too high on that dose response
1:14:14spectrum so that I be leave the the the
1:14:17optimal zone and go into a toxicity
1:14:19zone. And so I I'm so every three or
1:14:23four months I'm I'm having a blood
1:14:24sample to make sure that I'm I'm not
1:14:26toxic to this is, you know, like how a
1:14:29scientist might think. The general
1:14:31public wouldn't do that, you know, that
1:14:33sort of thing, right? They just want to
1:14:34know will this work or won't it work and
1:14:36and and things like that, but I and so
1:14:40the this is how I go about what I do.
1:14:42I'll be very happy to to send my my
1:14:45recipe of supplements, you know, um and
1:14:48you can check those out and and you can
1:14:50write back and and we can have a
1:14:52dialogue and so you can say, "Well, I I
1:14:55like what you're doing, but I don't like
1:14:56this. Why don't you try that?"
1:14:58[laughter] And so we could have a
1:15:00discussion about that at the personal
1:15:02level.
1:15:03Great.
1:15:04And and for anyone who's listening, if
1:15:06you have questions to to me or if you
1:15:08want anything that I have, I'd be feel
1:15:11free to email me. I'd be happy to to
1:15:13hear from you and happy to send you
1:15:15different things. So, um and happy to to
1:15:19meet you sometime and if I am lucky
1:15:21enough to uh to make it over to your
1:15:23great country.

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