Latest / In the Valley of Giants / Is GLP-1 the G-d Drug? | Dr. Brian Fertig | ITVOG #38

Transcript

Is GLP-1 the G-d Drug? | Dr. Brian Fertig | ITVOG #38 · In the Valley of Giants

• 0:00
  Had a patient who's an executive, he had a drinking
• 0:04
  problem. He had an argument with a cop
• 0:06
  and he agreed. He admitted it was his issue.
• 0:09
  He tried. I put him on the GOP and I'm
• 0:11
  waiting to see him back. But I can tell you that they
• 0:14
  have helped over the over the recent years.
• 0:17
  This sex addiction it it improves as well and yet it
• 0:23
  improves libido. So I had a a woman whose husband
• 0:27
  was cheating on her and I think I saved their marriage.
• 0:30
  She wanted me to see her husband who was overweight and diabetic.
• 0:33
  And so I put him on a GOP over six months, he evolved to their
• 0:39
  sex life improved and he no longer cheats and they're having
• 0:44
  nice. They're going to a counselor and
• 0:47
  the guy I think I saved their marriage GOP.
• 0:57
  Hello everyone. Today we're joined by Doctor
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  Brian Fertig. Dr. Fertig, aside from being a
• 1:02
  clinician with decades of experience, he is the Chair of
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  Diabetes and Endocrinology at HMHJFK University Medical Center
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  and the author of Metabolism and Science.
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  We discussed three critical things.
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  Number one is we took a little bit of a deep dive into
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  metabolism and how that works. 2 as you talked about GLP ones,
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  their effects on both weight loss and even addiction,
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  interestingly enough. And then lastly, we discussed
• 1:27
  the side effects of taking GLP once we also discussed GHPS.
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  So it's, it was a really interesting episode.
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  And with these drugs being so common and being pushed on the
• 1:36
  market, it's important for us as the consumers to understand a
• 1:39
  little bit more of what we're getting ourselves into.
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  So I thought that was a very eye opening episode and we hope that
• 1:44
  you do too enjoy Doctor Brian Fertig.
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  Thank you so much for joining us here on the show today.
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  You're welcome, Rabbi Dork. My pleasure.
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  So today we're going to be discussing GLP ones and
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  anabolics and to open up for GLP ones.
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  If I'm not mistaken, there was a, what was thought a
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  breakthrough and I think the 50s or the 60s where it became the
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  the medical understanding that adipose tissue or the
• 2:15
  enlargement of it releases this chemical called leptin.
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  Which the assumption was is that the increase amount of leptin in
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  the system would decrease the amount of hunger that a person
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  would feel. And that in the biological
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  system, the increase production of leptin is what is responsible
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  for the hunger response. And they found this out because
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  of genetic mutation that happened in mice.
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  And when they, when they began testing a leptin drug, what they
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  found is that it wasn't very effective.
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  And I believe the conclusion was the reason why it wasn't very
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  effective is because people that were incredibly overweight
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  having large amounts or enlarged adipose cells, adipose tissue
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  that the leptin response was somewhat dulled.
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  So that could either be for a variety of genetic factors or
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  just because they had they're for such a long period of time,
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  having so much lump in the, the bloodstream that the body was
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  used to such high levels. Interestingly enough, when they
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  gave leptin to people that did not have that much adipose
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  tissue, they actually lost the most weight.
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  So that was the the old, the old $20 billion question that
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  everyone thought was solved and everyone is going to lose weight
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  and it didn't work. So now we're introduced to a
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  totally new phenomenon with the GLP ones.
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  So I'd love to hear if what I said my left in was correct and
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  how GLP ones react differently and what the mechanisms are.
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  So please. Well, OK, regarding, I mean
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  regarding the, the relationship, it's all about the resistance to
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  to leptin and to insulin and they're very much connected when
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  you gain weight and they're not the other the only other
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  hormones. But let me, let me back up and
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  just give a, a little introduction to what, because I
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  think the discussion that you wanted to have was about
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  anabolics in the GLPS and in the role in, in clinical medicine.
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  And to understand this, I think it's, it's important to, to know
• 4:21
  what metabolism is because that lies at the core of, of, of
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  understanding all clinical medicine.
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  Metabolism comes from the Greek metabolismos, which is means
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  change. It's the totality of all
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  chemical reactions in the body. But that's at its core, it's
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  about energy, it's it's consumption from the food we
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  eat, it's storage and the fat cells are adipose tissue.
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  It's production in the biological currency of ATP.
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  It's utilization to do the work of of Physiology.
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  But at its core, it's about balance and and metabolic
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  efficiency. Any discussion in clinical
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  medicine about the standards of care would need to be centered
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  on the discussion of on on the idea of the metabolic building
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  blocks of Physiology. Otherwise it's
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  compartmentalized, it's fragmented, and it's it's
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  unnatural. Now the GOP's well, the the main
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  effect of GOP's on energy balance is to reduce the, the,
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  the, the dietary intake consumption of, of calories and,
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  and thus it's it's storage. And this is a pragmatic approach
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  in a modern world of abundance and the evolutionary mismatch of
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  obesity, binge and stress eating.
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  The anabolics are very complementary to the GOP system
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  because they promote weight or they promote muscle gain.
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  And, and, and this helps offset the muscle loss that's
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  associated with with weight loss.
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  Roughly 1/4 to 1/3 of weight loss is associated with muscle
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  loss. And why this is important is
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  when do you lose muscle, you reduce your basal metabolic rate
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  and and that makes it very difficult to prevent weight
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  regain, right? Though it's a put this in
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  context, when you lose for every kilogram body weight that you
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  lose, your basal metabolic rate decreases by 30 calories a day
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  and your craving for food increases 100 calories a day.
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  So if you lose 10 kilograms or 22 lbs, you have lost, you have
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  reduced your basal metabolic weight 300 calories a day and
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  your craving for food has increased 1000 calories a day.
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  So muscle is a major, it's a primary metabolic tissue that's
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  burns sugars and fats for energy and it it's essential for
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  maintaining blood glucose and blood lipid levels.
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  The presence and quality of muscle determines basal
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  metabolic rate and it's metabolic efficiency.
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  So metabolic rate is defined by the amount of energy produced
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  per unit time metabolic efficiency.
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  Now this is important is the amount of oxygen it consumes in
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  the process of making energy, because for the well that let me
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  explain this from the sense of of metabolic inefficiency.
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  The more oxygen you you consume to make it a given amount of
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  energy, the more of these oxygen derived highly reactive
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  molecules we call free radicals or liberated generated in in
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  that process inextricably. And the these oxidator free
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  radicals is what degrades the body's organizational beauty,
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  the molecular chemistry that is, you know, that defines the, the
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  aging process. Moreover, oxygen, these free
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  radicals, they promote inflammation and inflammation
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  feeds back and increases in a self amplifying fashion.
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  The the oxidative stress. The oxidative stress also
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  degrades the well the first thing it degrades is the
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  mitochondria that produced it, the power plants to the cell
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  where energy is produced. Those oxidative free radicals
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  are degrading that mitochondrial the tissue and the energy
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  producing machinery and it also reduces the OR degrades the
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  insulin signaling pathways in in the cell.
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  So each of these steps, the oxidative stress is where it
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  starts in the process of making energy.
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  Step one that then increases inflammation, that's a self
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  amplifying loop. The the degraded energy
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  producing machinery makes the oxidative stress worse, that
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  becomes a self amplifying loop. And the insulin resistance
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  becomes with the oxidative stress becomes a self amplifying
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  loop together forming a matrix is bi directional matrix of of
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  pathogenicity that lies at the core of the aging process and
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  and and chronic disease. OK, so I'm, I'm sorry, I'm going
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  to repeat what you said back in short form just to make sure
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  that I understand it properly. OK, so #1 there's a difference
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  between, or rather there's a tremendous amount of importance
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  placed upon muscle mass because of the fact that muscle mass
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  increases or helps determine your BMR, your basic metabolic
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  rate, your resting rate. And it does.
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  And you said that that it does so at a higher cost.
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  Meaning for every kilogram of, of muscle I might, I might
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  generate X amount of calories a day by just to uphold that.
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  But if I have a kilogram of adipose tissue, I'm going to I'm
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  going to spend less calories in order to upkeep, upkeep that is
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  that. Was that so far accurate?
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  Yeah, it well, we guess if you're, if you, if you're going
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  to lose a kilogram of body weight, 1/4 to 1/3 of that is
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  going to be muscle. And and that is going to lead to
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  for for that one kilogram of fat, the amount of muscle that's
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  lost is going to equate to 30 calories basal metabolic rate
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  less say less energy producing potential.
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  Right. So if we're so if one is going
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  to lose weight, they should be target if it was possible, which
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  I'm sure we'll discuss, but the more adipose weight that you
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  lose, the better because then you could retain a higher
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  caloric economy by keeping the most amount amount of muscle
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  tissue as possible, correct? Absolutely.
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  I mean, you're talking about we're, we're talking about fat
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  loss, which is good and the muscle mass which you know,
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  comes along with it. Now, the, the GLPS actually have
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  a favorable effect on promoting muscle and get me wrong.
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  It, it the stem cells, the precursor cells make the, the
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  myoplasts and that's encouraged by the GLP and the weight loss
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  is, is, I mean, fat lies at the core of of disease because it
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  makes the whole metabolic process inefficient.
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  And but tethered to this is muscle.
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  It's all about muscle fat ratio. That's so EP you see a lot of
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  the, you know, Filipino population that we have here in
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  Edison. It's a big patient population of
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  mine. And they, they're typically
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  they're sarcopenic obesity. They they're not, they don't
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  seem to have a lot of fat. They're very thin.
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  They have no muscle. That so they it's, it's, it's
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  all fat. You you want to lose, you want
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  to lose the fat and you want to try to keep that muscle.
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  You know, you want to maintain the muscle mass as best you can
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  in that in that process, if you were to lose the the weight.
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  I guess the point here is that it's all about weight regain.
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  And muscle is a big part of it's not the only part.
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  There's there's, yeah, there's if I mean, I can that this is a
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  little bit further down, I would think in the discussion.
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  But I'll just say that the one of the biggest concerns about,
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  you know, about, about the GLPS is do you have to take it for
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  life? And it the because it changes
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  the body weight set point and it's like a magnet.
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  And as soon as you stop taking this stuff, your weight's going
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  to come back. That's not really, that's not
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  the reality. There's actually a study just
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  came out of Harvard that showed 1/3 of the people that that
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  lose, you know, that lose weight on the GOP's and and stop the
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  GOP's. They continue to lose weight
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  even off of the GOP's. 1/3 of the people don't.
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  And they maintain that I understand they keep losing, but
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  they they maintain their their new weight like for a long
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  period of time. What's that?
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  They maintain their new weight for a long period of time.
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  They continue to lose it. A third of them, a third of them
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  will maintain the weight and a third will rebound, will go
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  right back to the prior weight. Now, why is that?
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  Because you just talked about muscle mass being so important.
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  It's not all about muscle mass. So what what GOP is a gut
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  hormone? And I think fundamental to the
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  benefit of of these drugs is, is it that changes the microbiota
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  and there's another reasons for that, but lumps, you know, just
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  not to get go down that rabbit hole.
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  It, it ultimately it changes not only the microbiota, but it
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  changes the bile acids and make them more susceptible with the
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  microbiota changes that it's that it, that it encourages to
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  promote these secondary bile acids that then stimulate the
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  endogenous production not only of GLP, but of GIP and V, you
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  know, PYY and fit the whole gut hormone axis.
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  So it's a triumvirate, a body weight set points of the the gut
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  hormones, the bile acid metabolism and the microbiota.
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  So it needs to be seen in that context and that's why these
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  drugs work and you cannot come off of them if that microbiota
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  hasn't been improved. So the the diet becomes.
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  Very. Why don't you?
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  Why don't you, why don't you define for us microbiota and why
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  it's important in this context of this conversation?
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  Oh boy, this is this is the other main part of of what makes
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  us who we are. I just want to say who is of 2.2
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  billion years ago when microbes inhabited the earth and humans,
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  I guess point 2 billion years in that time frame, it managed to
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  synchronize a super Organism within the human guts and they
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  are such an important part of what we are.
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  Without the microbes, we we wouldn't exist.
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  We we have 19,000 genes. The human genome, that's all a
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  worm has 90,000 genes. A worm protein coding genes,
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  right? We have 19,000 genes.
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  The coral rice is 250,000 genes. We have 19,000 genes.
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  The composite microbiome has 3.3 million chains.
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  But what makes it so complex and sophisticated?
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  You compare us to a worm, right? Or could to a fruit fly or so
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  it's it's that relationship of the human genome and and
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  expressing those chains, which is where all the complexity and
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  sophistication comes from. And the microbiota themselves,
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  they make these well, not only do they make the proteins that
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  express our genes, they make are very important in the production
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  of the neurotransmitters that control our cognition and our
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  mood and our motivation. They produce these well, the,
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  the, the B vitamins that are all eight of them right be 12357912.
• 18:57
  I think I missed 16. But in any event, they're all
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  cofactors that make energy and and they're critical, way more
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  critical and I think is recognized.
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  And that is another problem that comes when you lose weight
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  because you're not eating enough and you're not getting the
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  nutrient B vitamins, particularly vitamins one and
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  yeah, thiamine and niacin B3 are really critical in the whole
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  stage of things. And that is another topic, but
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  but they also make these short chain fatty acids that that
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  differentiate the the GI tract, particularly the colon prevent
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  cancer. There's a incredible energy
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  source. They are critical for
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  maintaining the gut integrity. They in terms of the the these
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  tight junctional complexes in the wall of the gut.
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  It's a it's a it's a life of its own and without which those
• 19:58
  microbes we. There there's just no way for
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  for our Physiology to be synchronized the way they've
• 20:07
  allowed it to be. So that that and and and and
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  here here's the the thing. So what what is what is it that
• 20:15
  that the GOP S do that have such a permissive effect on our our
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  microbiotic and healthy. We call it alpha diversity.
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  You want a, a, a rich diversity and evenness of these microbes
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  and the composition such that you want the good guys and not
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  the bad guys. And it's all about the
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  intersection with the yeah, with with the immune system.
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  So the immune system is tolerant and not stimulated.
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  And so these inflammatory disorders, autoimmune diseases
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  and malignancies are so inextricably coupled to and
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  neurodegenerative diseases and, and cardiovascular disease is,
• 21:17
  is cannot be separated from the, the.
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  This is why you need to understand metabolism as a
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  building block to to to think about these concepts and and and
• 21:34
  understand ultimately clinical medicine and how to how to
• 21:38
  manage disease states. Well, that's a that's that's
• 21:41
  that's going to be an episode in and of itself just to properly.
• 21:44
  Understand the tabular would be, yeah.
• 21:45
  Yeah, yeah. But but which which we plan on
• 21:48
  doing. But before that, let's go back
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  to the the mechanisms of of the GLP once what exactly are they
• 21:53
  doing and that affect our weight gain or excuse me, weight loss.
• 21:59
  OK, well, what they, they, they do GLPS have a well, I think
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  primarily they, they, they have, they reduce our food craving,
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  right? They by reducing satiety, they
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  have an effect on the reward motivation center, so addictions
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  and so the addictive quality of food.
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  And I think that in turn is helps us tame even more quality
• 22:36
  diet or the fibers, the diversity of the fibers and
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  Mediterranean diet, the processed food, less processed
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  food, less refined sugars, higher quality fats.
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  And and so it's going to foster a healthier microbiota and a
• 22:57
  less inflammatory system wide inflammatory state, which
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  reduces because you know, when you simulate the immune system,
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  you have a pro inflammatory state that circulates to the
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  brain, reduces the threshold for the perception of fear, right?
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  And you activate the stress response.
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  And now the stress response is a big part of Physiology to the
• 23:24
  whole bigger picture. But but Doctor Firth, I need on
• 23:27
  you. You just said that the mechanism
• 23:29
  is, is that it it, it increases satiating and and it decreases
• 23:34
  addictive behavior, at least within the context of food.
• 23:36
  We can talk about with that as other applications, but it
• 23:38
  decreases our hunger. So how?
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  How does it do this? So in, in terms of the, the, the
• 23:46
  mechanism of satiety, I said two things.
• 23:49
  One is satiety where you know, the ventromedial hypothalamus,
• 23:53
  the you've got the insulin is a satiety factor and grunt ghrelin
• 24:01
  is a hunger factor. That's a different ball game,
• 24:04
  but we're talking about satiety and the GLPS is another satiety
• 24:09
  factor now, so, so is leptin. So insulin, leptin, GLP, those
• 24:17
  are satiety factors. But then you've got the
• 24:19
  addictive quality of food, which is the emotional well, that's an
• 24:28
  emotional form of eating. And it has to do with the
• 24:33
  motivation reward center of the brain.
• 24:35
  So that's, that's two, but 3 is this is indirect, but it's still
• 24:43
  key because when you create a pro inflammatory state and you
• 24:52
  activate the immune, the the, the, the, the chronic activated
• 24:58
  branches of the stress response, what are the two emotions,
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  primary emotions that you feel? And what are the two hormones
• 25:07
  fear and hunger right now? Fear.
• 25:12
  That's where anger and resentment and guilt and anxiety
• 25:15
  and depression, all that comes from.
• 25:20
  But it the that's generated by cortisol, the fear response.
• 25:27
  Cortisol then promotes ghrelin. Ghrelin creates the hunger
• 25:32
  response because we well, this, this, there's, there's a class
• 25:37
  here because we need the energy for these high energy
• 25:40
  requirements of, of, of this trust response.
• 25:45
  So there that's evolutionarily or teleologically that that the
• 25:51
  role of growing. But in terms of, of, of, you
• 26:01
  know, in the, in the circumstance of stress, you sort
• 26:06
  of aren't going to look for food neat.
• 26:08
  You got to fight or flight. So there's a, a bit of a nuance
• 26:13
  there. And it's going to be an
• 26:15
  individual which one is going to override the other.
• 26:18
  But that so the, the cortisol, ghrelin are the 2 hormones and
• 26:24
  the two emotions, oddly enough, or hunger and fear.
• 26:28
  And so that's a mechanism indirectly by by the GLPS, by
• 26:35
  improving the diet you how how you eat effects how you feel and
• 26:41
  how you feel effects how you eat.
• 26:43
  And the, and the GLPS facilitate tame that process.
• 26:50
  And I think that's an more important part if the
• 26:53
  Mediterranean diet. There's a couple key things you
• 26:58
  have to say here, but the Mediterranean diet is it, it's
• 27:03
  really the only diet it's ever been studied and it really is
• 27:08
  amazing. You can't take any set of drugs
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  until the, the, by the way, until the, the, the GLPS came
• 27:15
  out. I'll tell you how staggering
• 27:18
  those statistics are. But if you take the ACE
• 27:21
  inhibitors and the, and the, and the statins and all the drugs
• 27:25
  and, and it aspirin and you put them all together and what's
• 27:28
  the, the, how, how much does it reduce the risk of dying and
• 27:34
  risk of disease? Nothing like a Mediterranean
• 27:39
  diet. 75% reduction in all 'cause mortality, all cause
• 27:43
  including accidents for it, it, it has to do with the focus and
• 27:48
  the stress response. So that I, I mean, it just just,
• 27:55
  that's incredible. But well, I'm going to let you
• 28:00
  see what you want to ask me at this point and you can share.
• 28:02
  Yeah, well, I'm just you have a lot of information, so I'm just
• 28:05
  deconstructing. So in terms of GLP ones and
• 28:07
  their effect to reduce what we eat and and change even what we
• 28:13
  eat. So you said three things.
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  One is that it makes us less hungry.
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  So I'm assuming the reason for this is when GLPS are naturally
• 28:23
  produced in in the body, so they decrease our our hunger
• 28:29
  response. So the production artificially
• 28:33
  of GLP ones and putting them into the bloodstream is going to
• 28:35
  decrease our hunger. So that's number one, I'm
• 28:37
  assuming we're going to overload our receptors.
• 28:39
  You'll tell me if that's wrong. Two, you said it was an
• 28:41
  emotional thing as well, which was separate from the third
• 28:46
  thing which you said, which was in an inflammation response and
• 28:51
  stress slash fear. So I don't know what you meant
• 28:54
  by the emotional thing. So maybe you'll break that down
• 28:56
  for me after you tell me if I was right about the receptor
• 28:58
  response. And then thirdly, if you could
• 29:00
  just explain a little bit more about the the stress response
• 29:05
  affected by the GLP, ones that ultimately lead to inappropriate
• 29:09
  eating, that'd be helpful. OK, I'm not.
• 29:14
  I'm going to ask you to to repeat that again because I'm
• 29:16
  not the second. One second, why don't, why don't
• 29:20
  we go step by step, We'll take one, one question at a time.
• 29:22
  So question number one is this is the, the way that GLP ones
• 29:25
  decrease hunger is because the presence of more GLP ones are
• 29:30
  going to be there are specific receptors in the brain.
• 29:34
  I think you mentioned even the DMH, although I'm not sure if
• 29:36
  that's related directly GLP wants.
• 29:37
  But by the way, there's there are particular receptors that
• 29:40
  are sensitive to GLP ones and our hunger goes down with the
• 29:42
  more presence of GLP ones. Is that correct?
• 29:45
  Yes, well there's two path, you know there's the GLP, there's
• 29:49
  both a hormone system and A and a neurotransmitter system.
• 29:53
  And we thought they were two separate systems didn't
• 29:56
  understand how they really act together, but they do, they do
• 30:01
  synchronize the hormonal and the neurotransmitter system act
• 30:05
  together. And so whether it's the
• 30:08
  neurotransmitter or the hormone that's working on the
• 30:11
  ventromedial, the hypothalamus that I guess, I guess it's the
• 30:16
  orkut nucleus that, that, that that causes the satiety reduces
• 30:24
  the threshold of food for you to feel sated and you feel sated
• 30:29
  longer. It also decreases the, the, the
• 30:38
  gastric emptying, right? So you slow gastric emptying due
• 30:41
  to Now when I I say it reduces the stress response initially
• 30:47
  the what these let's. Let's not go there.
• 30:52
  Let's not go there just yet. The number one.
• 30:53
  It's part of the hunger response, right?
• 30:56
  It's part of the whole, OK, part of what you try.
• 30:57
  You're getting at it. It's if, if you're going to slow
• 31:02
  the gastric emptying, that's, that's part of the, but I, I
• 31:06
  just want to make the, the distinction because I did say
• 31:09
  that it reduces the stress response, but it's us.
• 31:11
  But initially it's a calorie restriction and that's a stress.
• 31:15
  So it act and part of that stress is slowing the gastric
• 31:19
  emptying, which doesn't necessarily stay because that
• 31:23
  stress improves as you go from having a a sort of a a an
• 31:29
  activator with stress response to one that suppresses it.
• 31:32
  That effect on satiety is going to is going to be changed
• 31:37
  accordingly because of the the sympathetic tone that slows the
• 31:44
  gastric emptying that makes you feel full earlier and longer.
• 31:50
  That now that, that that wanes because of the activation of
• 31:55
  this stress response, but that, but there is an actual effect at
• 32:03
  the in the brain stem on the vagal fibers, sympathetic
• 32:09
  fibers, both, both autonomic systems that that does slow
• 32:16
  gastric emptying. That is persistent, but it's
• 32:19
  mild. And it's actually that's
• 32:22
  adaptive because it gives the microbes more time to digest the
• 32:27
  food and, and, and and promote the, the healthy physiological
• 32:35
  and metabolic effects as a result.
• 32:37
  But so that that's a distinction.
• 32:42
  But early on it may be too much because the the stress response
• 32:50
  and the effect of the GOP independently is, is separate.
• 32:55
  Now you also have the GI PS like with Manjaro and and and step
• 32:59
  bound their tirzepatide, they have a more modest effect.
• 33:06
  They attenuate the effect on that on that nausea.
• 33:10
  So those people might do better taking a GIP than a GLP, but I
• 33:16
  don't know if that clarifies if that was worth me.
• 33:19
  But go ahead, I'm sorry. Yeah, no, OK.
• 33:21
  OK. So that's, so that's, that's in
• 33:23
  terms of the, the IT might be hormonal, it might be
• 33:28
  neurotransmitter increase or receptors.
• 33:32
  We don't know exactly which one is involved if not both by the
• 33:36
  increased presence of GLP ones. And then you mentioned two other
• 33:39
  factors that were imperative that GLP ones do affect, that
• 33:43
  will affect how we eat and what we eat.
• 33:46
  You said emotion and then you said stress.
• 33:48
  So what is the difference between emotion and stress?
• 33:51
  What did you mean by those two categories?
• 33:53
  Emotion and stress, well, well stress changes the it's the type
• 34:04
  of initially, once you're it's an acute stress.
• 34:07
  It's different than a chronic stress.
• 34:08
  When you're acutely stressed, you it's like taking a a coil
• 34:14
  and stretching it. You remove the stress, that coil
• 34:16
  goes to its original form, right?
• 34:19
  If it's chronic, you remove the stress that that coil does not
• 34:23
  go back to its original form. And the so the stress, that's
• 34:30
  where the fear, which is no longer temporary and it
• 34:35
  germinates these negative emotions of anger and resentment
• 34:41
  and guilt and anxiety, mood disturbances and so forth.
• 34:46
  And that's a lot of what's wrong with society.
• 34:50
  That's, that is a discussion that would be fun to have.
• 34:54
  But the, the, the stress that, well, I mean, imagine if you
• 35:05
  didn't have stress that would solve the chronic stress that
• 35:08
  would solve the world's problems, because you can't have
• 35:12
  the neural circuits that are generating the feelings of
• 35:17
  negative emotions and positive emotions at the same time.
• 35:21
  So those positive emotions of humility and gratitude, empathy
• 35:28
  and compassion, social awareness and intuition, those are a it's
• 35:34
  a, an entirely on or off switch it.
• 35:38
  I mean in reality it's not. But if you, I mean it in reality
• 35:44
  it, it is. But there's, there's, there's a
• 35:49
  lot of ambivalence and mixed feelings and, and, and all of us
• 35:54
  and many different ways. But I it it's I think by turning
• 36:00
  off the stress response will make people better people and
• 36:04
  the. GLP ones do that they they
• 36:07
  encourage the turning off of the stress response.
• 36:09
  Is that what you're saying? Well, they, they the yes,
• 36:11
  because they primarily through the the system wide inflammatory
• 36:19
  effects it it, it affects the innate immune system, the first
• 36:23
  responders, those macrophages and so forth.
• 36:26
  I think it it the the adoptive immune system and the neuroglial
• 36:33
  cells in the brain. So it's got a very protective
• 36:36
  effect on on the brain. And so it the neurogenesis in
• 36:42
  the cognitive centers of the brain like the hippocampus, the
• 36:45
  synaptogenesis, the which is the communication between the cells.
• 36:53
  So it's, it's driven by two things.
• 36:58
  The the IT suppresses or remodels that the the neuroglial
• 37:07
  cells that's those are the inflammatory cells in the brain
• 37:11
  and it also promotes brain derived neurotrophic factor that
• 37:15
  helps the healthier that sort of resilience, if you will, in in
• 37:20
  the brain to stress that that is the the model that I you know
• 37:26
  that we've been talking about before and it will we'll discuss
• 37:29
  with with Jack that's it all has to do with his metabolic fitness
• 37:33
  landscape and and the terrain of metabolic decline over.
• 37:38
  Well, is, is there an association so well, if it, if
• 37:42
  there's a lessening of the stress response and part of that
• 37:45
  is lessening of the inflammatory response was part of that is
• 37:48
  lessening of the immune response, does that mean that
• 37:50
  that the immune system will be less efficient in any way since
• 37:54
  it's going to be somewhat suppressed by the presence of
• 37:57
  increased GLP once? Well, it's, I mean left, I mean,
• 38:01
  all of these drugs you can see have hormones.
• 38:03
  They're, they're, it's not just, they're very nuanced.
• 38:08
  It's not just one function. Yes, I mean leptin's associated
• 38:13
  with it's all about hormesis. What's at at what level is it
• 38:19
  associated with malignancies? Is it, is it playing its role in
• 38:24
  it in, in, in obesity with leptin resistance?
• 38:29
  Is, is it promoting along with the GOP?
• 38:34
  And you know, in insulin, it is the, you know, body weight set
• 38:42
  points, healthy body weight set points.
• 38:46
  It's they're, you know, they're, they're very much intertwined to
• 38:51
  separate them, You know, you really have to see there's and
• 38:55
  to understand medicine more than anything, because I mean, it's
• 39:00
  an example, but to understand anything medicine and and
• 39:04
  biology is so inherently on on so complex and so it
• 39:12
  unpredictable and it's constantly changing.
• 39:18
  It's it's it, it's a back up here for a second.
• 39:29
  You have to see the system of a part in a hole and you have to
• 39:33
  under you have to see patterns without patterns.
• 39:38
  Understanding something is as big as the world itself or
• 39:42
  understanding information as big as the world itself.
• 39:46
  To understand the system without seeing the parts in the holes is
• 39:50
  like trying to understand bird flocking behavior by studying a
• 39:53
  single bird. So you have to look back and
• 39:58
  say, well, what's the system? What's the integration of the
• 40:00
  system? None of these things live in
• 40:02
  their own parking lot. It's a very integrated soil.
• 40:06
  And I think that the. Gets to the core of the the
• 40:11
  problems when you talk about illness that illness is is
• 40:17
  isolation that disease is isolation and is if we're
• 40:21
  compartmentalizing diseases and putting Band-Aid solutions on
• 40:27
  disease states is and and and we're using population studies
• 40:34
  to to to orchestrate this model of care.
• 40:39
  These are just ways of of of or masquerading as science and it
• 40:49
  it's not the the real it's a sickness and, and, and itself.
• 40:54
  So I think medicine and the way we manage even even the, the
• 41:00
  very nature of a hypothesis in medicine is to be right at all
• 41:04
  costs, right? And it because you know, there's
• 41:09
  tenures and legacies and money and and, and, and, and by the
• 41:15
  way, when you compartmentalize things, you, you, you can
• 41:20
  control it, you can monetize it. So you always have to wonder
• 41:25
  who's first? Is it the money or is it the
• 41:27
  patient? So think about what's the very
• 41:31
  nature of my hypothesis in a much more mature.
• 41:35
  And this, this really drew my attention to physics because
• 41:39
  it's 100 years more mature and it's a it's a more mature
• 41:43
  science bit of A and it's and it's.
• 41:47
  But, but, but, but Doctor Fritzik, there's there's a very
• 41:49
  big. There's a nuance though, here
• 41:51
  that I want to focus on. You're right, obviously, which
• 41:54
  is the focus of the patient should come first.
• 41:57
  And indeed, in order to understand bird flocking
• 41:59
  behavior, to take one bird from a population of one species of
• 42:04
  birds would it be ridiculous. And it's even more ridiculous to
• 42:07
  say that this is the behavior of all birds that flock when you've
• 42:11
  only studied 1 bird from one species, right?
• 42:13
  But I have a luxury that you do not.
• 42:15
  I am not a doctor or, or or a professional in the sense.
• 42:20
  So, you know, if I have a particular question, I feel that
• 42:25
  instead of me watching 1 bird and coming to a conclusion and
• 42:28
  publishing it, which would be very foolish of myself, right,
• 42:31
  and very dishonest. What I can do is I can ask
• 42:34
  someone who has seen every species of bird known to man and
• 42:37
  ask them, well, is, is X occurring?
• 42:40
  So, and I would say the same thing for if someone came to me
• 42:44
  with a rabbinic question, meaning you could look online at
• 42:47
  certain rabbinic sources and maybe come up with, you know,
• 42:50
  one photograph of what's supposed to be this massive
• 42:53
  ecosystem. But if someone wants to ask me
• 42:55
  something with, you know, my rabbinic ecosystem, I could give
• 42:57
  them a particular understanding. So what I'm trying to ascertain
• 43:00
  is based off of what you're saying, and I'm not saying it's
• 43:03
  not more complex, it is, but based off of what you're saying
• 43:06
  in terms of GLP ones are not activating the immune response.
• 43:10
  Does it, does it suppress the immune response in any way?
• 43:15
  That that's my primary question. But do they, I'm sorry, do they
• 43:20
  express? Suppress, Suppress, suppress.
• 43:22
  Do they suppress the immune response?
• 43:24
  Well, they they do they they remodel the the the immune
• 43:31
  response in each form. For instance, even adopt, but
• 43:39
  you want to talk about integrated nature.
• 43:42
  Adipose tissue is an immune system is part of the immune
• 43:46
  system. There's you know, is it, are
• 43:49
  these visceral adipocytes? Do they come from the bone
• 43:53
  marrow? The the the precursors, the
• 43:58
  myeloid bone marrow precursor stem cells is what or inherently
• 44:05
  inflammatory cells. They form the immune system.
• 44:07
  One of the roles of them of, of that tissue is to, in the, in
• 44:13
  the gut, say to wall off a potential Abscess.
• 44:17
  And then it also is, and it's got the bio detoxification
• 44:23
  machinery. The liver does, the detoxified
• 44:26
  sitting between the gut and the liver and all these toxins that
• 44:29
  come from the gut to the liver, the adipose tissue sits right in
• 44:34
  front of it. And, and, and, and by the way,
• 44:37
  when you eat, it's not just the quantity of food that fills
• 44:42
  these fat cells, but the quality of the food.
• 44:46
  So if there's a lot of non foods in the diet, you're, you know,
• 44:50
  the solution to pollution is dilution, right?
• 44:54
  So you're going to, you're going to create more adiposity in that
• 44:59
  fat cell to, to sequester and bio detoxify those toxins.
• 45:06
  So that another thing. So it, it what, what the GOP is
• 45:13
  do there to the, to the visceral adipocytes is they, well, they
• 45:20
  actually, they, they utilize the fat cell and ultimately pop it
• 45:25
  like a balloon and it's, it's and replace it with with new
• 45:31
  wealth. It's a GIPGIP actually forms new
• 45:34
  fat cells, the GIP. You think that's
• 45:37
  counterintuitive? Why you making new fat cells?
• 45:40
  Because it's a different type of fat cell.
• 45:43
  That's a subcutaneous fat cell. Now they can also be pro
• 45:46
  inflammatory. Why?
• 45:49
  Why are the subcutaneous fats cells pro inflammatory?
• 45:53
  Well, because they've been overstuffed and you've got and
• 45:59
  they outgrow the blood supply and they become hypoxic that
• 46:03
  generates inflammation and they spill into the circulation and
• 46:07
  deposit and tissues where they don't belong ectopically such as
• 46:11
  muscle in the pancreas creating insulin resistance and impaired
• 46:15
  first insulin response of of the pancreas.
• 46:18
  That's both of those sites are where GLPS work it they in the
• 46:26
  muscle and microdroplets in the brain and in different areas
• 46:30
  affecting different parts of the brain.
• 46:34
  It that that can affect things like reward, motivation and, and
• 46:39
  satiety. And So what the GOP is do to the
• 46:44
  adipocytes that because you're producing more fat cells, well,
• 46:50
  but it's, it's allowing the overstuffed fat cells to, to
• 46:55
  burn themselves out while you're creating more fat cells to
• 46:58
  accommodate, you know, smaller fat cells, the better
• 47:02
  accommodate the existing fats. So they're neutral, benign,
• 47:09
  healthy stores of fat rather than the type of fat that's
• 47:14
  compromising your health by being over overstuffed.
• 47:19
  And, and so they remodel these fat cells are less inflammatory.
• 47:25
  You know, the M2 there's, there's these macrophages, M1 is
• 47:30
  inflammatory, M2 is anti-inflammatory.
• 47:32
  So that's what I mean by remodeling.
• 47:36
  And, and so that's, that is a, you know, a, a, those two points
• 47:45
  about 1, you know, the subcutaneous fat, that's not
• 47:48
  inherently inflammatory cell because it embryologically comes
• 47:52
  from mesenchymal cells as opposed to the visceral comes
• 47:56
  from the bone marrow. But, and, and so you're
• 48:00
  generating more of one while you're that you know, that the,
• 48:04
  the subcutaneous adipose cells and less of the visceral adipose
• 48:10
  cells. So, you know, testosterone does
• 48:13
  the the same thing. It increases that well that the
• 48:18
  the the the the ratio of the sub Q that that that but to the
• 48:24
  visceral adipocyte. I just don't want to confound
• 48:28
  what I'm trying to say here, but the inflammatory nature of of
• 48:35
  the anti-inflammatory nature of the GLPS has to do in large part
• 48:40
  to the effect on the adipocyte and both the actual by reducing
• 48:48
  the amount of fat and the actual effect it has on those fat
• 48:52
  cells. And the same thing in the the
• 48:55
  neuroglio cells, the glial cells in the brain that it change it
• 49:00
  remodels them and make that makes it more of an
• 49:03
  anti-inflammatory. So it's more protective and less
• 49:06
  neuroinflammatory and which the neuroinflammatory has to do
• 49:12
  with. You know, that's why the GOP's
• 49:16
  improve not only accelerated cognitive kind of aging, but
• 49:24
  vascular dementia and Alzheimer's and Parkinson's
• 49:27
  disease and other neurodegenerative disease.
• 49:29
  All of them. It's amazing.
• 49:31
  I, I, I, I can't let you finish this, by the way, without
• 49:37
  getting back at the at some point to to the the benefit of
• 49:42
  these drugs on cancer, because it's, it's absolutely stunning
• 49:48
  and. We'll talk about that because
• 49:52
  that I didn't even see that coming.
• 49:53
  I didn't even know that there was an effect that GLP ones had
• 49:56
  on cancer. Did I?
• 49:58
  Did do GLP ones have an effect on on?
• 50:03
  Because you said that it also effects reward behavior.
• 50:07
  So does it let's say smokers or drinkers?
• 50:10
  I believe I read a study on drinkers that GLP ones was able
• 50:14
  to help them in order to stop drinking.
• 50:16
  I think it's a study that came out two years ago.
• 50:18
  You can tell me if I'm right or wrong, but do they also have an
• 50:21
  effect on addictive behaviors? Yep, absolutely.
• 50:24
  Glad you brought, glad you brought that up.
• 50:28
  The effect on the addictive behaviors is one that's
• 50:34
  germinating when I wrote the metabolism medicine that well at
• 50:39
  the stage that that was at the early stage of volume 2.
• 50:44
  So it was, I don't know, maybe 2018, 2017 and, and I was
• 50:54
  fascinated by the effect of, of, of the GOP system of hormones
• 51:00
  that effect. And, and I even read that, you
• 51:04
  know, they talked about gambling behavior and, and here I
• 51:08
  actually have certainly smoking and drinking.
• 51:11
  Initially I think it was amphetamines and opiates.
• 51:14
  And these were animal models. And now they're doing human,
• 51:18
  human studying in humans. But it's alcohol and, and, and
• 51:24
  tobacco, which is really very, and you can see a noticeable
• 51:29
  difference in people. I use the, I give these drugs
• 51:33
  what lowers the threshold. I don't use it specifically for
• 51:37
  people with alcohol problems, but I had a patient who's an
• 51:42
  executive, he had a drinking problem.
• 51:43
  He had an argument with a cop and he agreed.
• 51:46
  He admitted it was his issue. He, I, I put him on the GOP and
• 51:50
  I'm waiting to see him back. But I can tell you that they
• 51:54
  have helped over the over the recent years and, and I haven't
• 51:58
  listened to this, this story, this sex addiction, it, it
• 52:03
  improves as well. And yet it improves libido.
• 52:08
  So I had a, a woman whose husband was cheating on her and
• 52:12
  I think I saved their marriage. She wanted me to see her husband
• 52:15
  who was overweight and diabetic. And and so I put him on a GLP
• 52:24
  and he she, she follows the social media, she she on the
• 52:32
  phone when he can track somebody And and the personal discussions
• 52:36
  they've had over six months. He evolved to their sex life
• 52:43
  improved and he no longer cheats.
• 52:46
  And they're having nice. They're going to a counselor and
• 52:50
  they got I think I saved their marriage GOP.
• 52:54
  So it is it, it does work. It's not just a, you know, an
• 53:01
  academic discussion. This is very real, these drugs.
• 53:05
  Now coming off the drug, coming off the drug, are you going to
• 53:07
  see the same ratio of 1/3 of people?
• 53:09
  Are you able to maintain staying off of those addictive
• 53:12
  behaviors? You know, that's an interesting
• 53:14
  question. You talk about the weight set
• 53:16
  point and how do these things relate to the I think the body's
• 53:20
  Physiology is, I think GOP's are are are critical, but it's it's
• 53:31
  it it a lot of it has to do with how, how that triumvirate a bio
• 53:37
  acid metabolism, the microbiota and the GL and the system of gut
• 53:43
  hormones have reset themselves as a result of the GLPS allowing
• 53:49
  you to come off of them. And for that to so there's
• 53:52
  secondary bile acids are key to simulating all those those gut
• 53:57
  hormones. You know what, the only question
• 54:01
  I have is that it's the the notion of hormesis is, you know,
• 54:08
  if, if we get to a discussion, there's so much to talk about,
• 54:12
  but about anabolics, nothing would be.
• 54:16
  Wait a minute. But Doctor Furtick, I need, I
• 54:20
  want to know the answer to the question though.
• 54:21
  I mean, what do you think? And as as a generality, do you
• 54:25
  think that people coming off the the the GLP wants that have seen
• 54:29
  a decrease in addictive behaviors, do you think a chunk
• 54:32
  of them will not see those addictive behaviors come back?
• 54:34
  Or do you think that? That yeah, well, it's OK.
• 54:38
  Yeah, I was, I, I always try to, to sort of bring it and into a,
• 54:45
  into a greater discussion because it, I feel we're in a
• 54:48
  microcosm. And if you look at the bigger
• 54:50
  picture, you can see the microcosm queer.
• 54:53
  But I, the, the bottom line is and, and, and the point I wanted
• 54:58
  to make because I, I, I, I hear you, I heard your question is
• 55:03
  that the, the, the everything is, is sort of, you have to see
• 55:08
  the bigger picture of the system of parts and holes and, and, and
• 55:12
  it has to do with this, the dose.
• 55:15
  And so when you're talking about clinical medicine using these
• 55:19
  GLPS to not only maintain body weight without having to take
• 55:25
  them for life, not only to maintain some of these other
• 55:27
  benefits, cancer benefits and, and, and addictive behaviors,
• 55:35
  It, it, it's I, I, yeah, I think it's these, that triumvirate has
• 55:40
  to be, has to be sort of set up. And, and that has a lot to do
• 55:46
  with the diet that the I, I think that Mediterranean diet is
• 55:53
  the only diet that we know that's been studied well.
• 55:55
  And it's 75% reduction in all 'cause mortality means that it's
• 55:59
  affecting the brain because it's not just about cancers and heart
• 56:04
  disease and strokes and, and Alzheimer's and cognition, but
• 56:10
  it's, it's about emotion and focus and preventing accidents
• 56:14
  and things like that as well. So I, I think that once you
• 56:21
  know, if it's all about lifestyle and once you, how you
• 56:26
  eat effects how you feel and you're enjoying life, you have,
• 56:31
  you know, less anger and fear in your heart and hatred and more
• 56:38
  love. Not to be corny, but it's, it's
• 56:42
  real as, as a rabbi, this is probably very close to your,
• 56:47
  your heart and, and, and soul. It is, it's, it's, but it's part
• 56:52
  of what the effects of these drugs are.
• 56:55
  And you want to change our behaviors so that that becomes
• 57:00
  sustainable. But the point I wanted to make
• 57:03
  is the hormesis too little or too much of anything is is
• 57:07
  toxic. Nothing is qualitative.
• 57:10
  Is is is categorically good. It's all about the dose.
• 57:15
  What concerns me about these drugs is the GLP's are released
• 57:20
  in in you know, in seconds and to a few minutes as opposed to
• 57:26
  giving a pharmacologic like a bullet China shop that's high
• 57:30
  levels all day long. Now they're coming out red a
• 57:33
  true tide. That's it.
• 57:34
  That's a monster. It's the Godzilla of of weight
• 57:38
  loss and obesity, but is too much not good.
• 57:43
  And then who is it good? And, and, and by the way, that's
• 57:47
  the whole reason for this physiological fitness landscape,
• 57:51
  which is not time to discuss, but the, the goal is it's a
• 57:55
  personalized precision and dynamic scale of medicine that
• 58:00
  changes with time and the, and the dynamic balance of metabolic
• 58:03
  interactions. And, and so you can't just do a,
• 58:08
  you know, a study that a population study that may apply
• 58:13
  to, to 40% and that's statistically significant.
• 58:17
  So everybody should take it. Well, the standards of care,
• 58:20
  half of them are wrong. Half.
• 58:23
  That's the Holy Grail standards of care.
• 58:27
  So, but that doesn't mean the drugs like a statin aren't great
• 58:32
  drugs. I believe they are, but to be
• 58:34
  used promiscuously in the way that we do it is not right and
• 58:38
  not there could be a whole talk on that, but it it's it's
• 58:43
  everything. So these, every one of these
• 58:47
  drugs that we talk about the GOP's and the which we're
• 58:51
  talking about now is a microcosm of any topic you want to pick.
• 58:57
  And it's but I'm sorry, I I don't ask me what you want.
• 59:02
  No, no, that, that, that was no, that was that, that was that,
• 59:05
  that was very, very informative and fairly targeted.
• 59:08
  But bottom, so bottom line you're, I still, I still don't
• 59:12
  know what the bottom line answer though about, do you?
• 59:15
  I think, I think, I think this is what you were saying.
• 59:18
  The bottom line answer is GOP ones will increase or can
• 59:21
  increase someone's life in a significant way so that when
• 59:24
  they come off of it, maybe they won't be engaging in those
• 59:27
  addictive behaviors because they'll already be happier and
• 59:29
  more well adjusted people. Is that what you're trying to to
• 59:32
  say? Yeah, I think and I think the
• 59:34
  it's, it's adjusted your, your there, there's, there's a
• 59:40
  revamping in how you live your life ultimately.
• 59:43
  And, and it starts with how you eat and changes your eating
• 59:47
  patterns and that changes the microbiota.
• 59:50
  And that microbiota has such an important part in our, you know,
• 59:56
  it, they make the neurotransmitters GABA and
• 59:58
  serotonin and acetylcholine and dopamine for motivation, right?
• 1:00:06
  And, and it's it changes the whole chemistry of of your brain
• 1:00:10
  and and that in turn changes behavior.
• 1:00:17
  And and and the benefits and even the motivation exercise and
• 1:00:21
  work large muscle group so you don't lose the muscle mass, for
• 1:00:25
  instance, it not muscle mass, not the whole thing, but it's a
• 1:00:29
  part of it and. Yeah, that's, that's why I tell
• 1:00:31
  people that go on diets. I tell them that one of the most
• 1:00:35
  important things is to do some resistance training to try to
• 1:00:39
  offset the loss of muscle mass. Because, you know, if you just
• 1:00:42
  starve yourself on a diet and then what's going to probably
• 1:00:45
  happen is you're going to have a yoyo effect.
• 1:00:46
  You're going to come back to the weight you were before, except
• 1:00:48
  you're not going to have the muscle mass to back that up.
• 1:00:51
  Yeah, You know, I, I have a nurse practitioner who's
• 1:00:55
  rotating with me now. She's not a, this is her last
• 1:00:58
  rotation and she happens to be a dietitian.
• 1:01:01
  She's a physician of physical therapy.
• 1:01:04
  And she's amazing, really. And and she reads the stuff that
• 1:01:10
  I write and she likes it, but she she comes back and says, I
• 1:01:15
  have something for you. And she takes this long article
• 1:01:19
  condensed it to one page to give to a patient.
• 1:01:23
  And it could it be the exercises, stand on a chair and
• 1:01:28
  she'll give the the picture and just sit on a chair and then sit
• 1:01:32
  up, stand up and go down. And don't, I mean don't, don't.
• 1:01:37
  You'll be amazed how hard that is to do.
• 1:01:39
  Just sit up, get down. That's an exercise in and of
• 1:01:42
  itself. And she gives a half dozen of
• 1:01:44
  them in with the short explanation on the back about
• 1:01:47
  why these things work. And you want to do large muscle
• 1:01:51
  groups like the legs, the ABS, the chest.
• 1:01:54
  Those are the three areas that are most important for most
• 1:01:58
  people. We're not doing it for Oh, and
• 1:02:02
  by the way, you'd be surprised that the the amount of exercise
• 1:02:08
  that should be for that that we should use is not well, what
• 1:02:16
  what's the optimal amount of exercise again?
• 1:02:18
  Dose there's a plateau and AU shaped curve.
• 1:02:22
  No, but there's type also it's not just dose, right, it's
• 1:02:25
  cardiovascular versus you know a focus on weight resistance that
• 1:02:29
  those are those are categorically different.
• 1:02:32
  Right, Yes, yeah, Well, yeah, I, I don't want to steal the time
• 1:02:38
  for whatever questions you want to ask and but, but I, I think
• 1:02:42
  you get the point. I I could, you know, I.
• 1:02:45
  No, I get the. Point It's fun talking about
• 1:02:47
  this stuff, but there there's some the more points we can
• 1:02:52
  without belaboring anyone idea I guess is or or there's specific
• 1:02:57
  things you want me to answer. I want to make sure I've
• 1:02:59
  answered them for you. Yes, yeah, no, So a lot of them,
• 1:03:02
  a lot of them, yeah, I'm going to ask a few more.
• 1:03:03
  So what are the the side effects that have been documented for
• 1:03:07
  taking GLP wants? Oh, of the of the GLPS.
• 1:03:12
  OK, now, well, let me let me say, well, what are the
• 1:03:22
  contraindications? OK, let's start with because
• 1:03:24
  there's only two of them really. And it, the multiple
• 1:03:27
  endocrineoplasia type 2 is, is is a contraindication because
• 1:03:37
  it's, it's been associated with, with these, Yeah, with, with,
• 1:03:43
  with these, you know, with these, with, with these drugs.
• 1:03:49
  But it's never been found in humans.
• 1:03:54
  Mice are not humans. And now what are there hundreds
• 1:03:57
  of millions of people that have been on?
• 1:03:58
  There's never been a single case.
• 1:04:00
  And everybody asks thyroid is, you know, I have thyroid cancer
• 1:04:07
  or had thyroid cancer or I'm worried about thyroid cancer.
• 1:04:11
  I don't want to get this because I'm taking this.
• 1:04:13
  It's that's a different type of thyroid cancer all together and
• 1:04:16
  it's never been found. I don't think people should be
• 1:04:18
  worried about this unless you have multiple endocrine
• 1:04:21
  replacing. It's very rare and it's just
• 1:04:23
  one. That's, that's one thing.
• 1:04:25
  The other is is significant gastroparesis, I don't know
• 1:04:30
  because you get tolerated now in in terms of the question.
• 1:04:35
  Doctor Fritzik, I don't know what you said, but could you,
• 1:04:37
  could you say that one more time?
• 1:04:38
  It's the second symptom. Could be what?
• 1:04:41
  With the oh significant gastroparesis.
• 1:04:46
  What is that so? You get in general, it's like a
• 1:04:50
  diabetic, they're constantly, it's just typically the type
• 1:04:53
  ones, right? A type 1 diabetic, they're
• 1:04:57
  nauseous and vomiting and they can't, they can't it's very
• 1:05:03
  difficult to control. Some people have that and
• 1:05:06
  particularly the diabetic type ones.
• 1:05:09
  And those people you can't use it, they're usually well half of
• 1:05:14
  diabetic, half of type ones are insulin resistant and so many of
• 1:05:18
  those are overweight and they could benefit from a GLP.
• 1:05:22
  And by the way, the GIP in that case would.
• 1:05:26
  Be more effective because it has less nausea.
• 1:05:29
  Yeah, but what's another reason it inhibits as opposed to the
• 1:05:33
  the GLP inhibits Glucagon, this inhibits Glucagon.
• 1:05:37
  So those type ones that tend to go hypoglycemic, they don't go
• 1:05:42
  hype that the Jeep, the tirzepatide, right, whether it's
• 1:05:48
  Zep bound or Manchero will be better drugs for them because
• 1:05:55
  the GLP, the GL, the GIP induced Glucagon from the pancreas,
• 1:06:01
  right? It inhibits the IT, it, it, it,
• 1:06:05
  it corrects the first phase release of insulin and it
• 1:06:09
  prevents hyperinsulinemia, which is one of the core 4 features of
• 1:06:14
  chronic disease, oxidative stress, insulin resistance,
• 1:06:18
  inflammation and power plant dysfunction, mitochondrial
• 1:06:23
  dysfunction, those four. So you want to correct you've
• 1:06:26
  you've fixed that, that pancreatic release of insulin,
• 1:06:29
  that first phase release. So you don't and you ultimately
• 1:06:32
  get improved insulin sensitivity with less hyperinsulinemia and
• 1:06:36
  insulin resistance. Those the high insulin levels,
• 1:06:39
  Dr. mitogenic pathways, cell proliferation, pro inflammatory
• 1:06:45
  and that's another loop with insulin resistance that's
• 1:06:48
  Parkinson type 3 diabetes. They they will call this it's a
• 1:06:53
  garbage diagnosis. It's a call that Alzheimer's,
• 1:06:57
  but nonetheless, it gets to the point that insulin resistance is
• 1:06:59
  important there. But in any event, so the GIP
• 1:07:05
  using it with for people that tend to go hypoglycemic for type
• 1:07:10
  1 because they have a very different effect on that
• 1:07:13
  Glucagon that prevents low sugar, right.
• 1:07:16
  So it it's it's helpful there. OK, So the other the, the
• 1:07:20
  negatives, you know, dehydration and GI motility.
• 1:07:24
  Why do people get well when you're dehydrated?
• 1:07:28
  Because it affects your thirst as well, not just your satiety
• 1:07:31
  for food. But you're you don't drink a
• 1:07:34
  bunch of water, so your kidney function can decline as a
• 1:07:38
  result. That's easy, just drink more
• 1:07:40
  water. Yes, that is easy.
• 1:07:43
  Yes, you're right. Why do people get pancreatitis?
• 1:07:47
  That's the question. That's not easy.
• 1:07:49
  Why is that? Why are they contraindicated for
• 1:07:53
  pancreatitis? They're not contraindicated for
• 1:07:55
  pancreatitis. But by the way, but you want to
• 1:07:59
  be careful with pancreatitis. But why?
• 1:08:02
  Because it actually improves the chronic inflammation of
• 1:08:06
  pancreatitis. And if it's an alcoholic
• 1:08:09
  pancreatitis or idiopathic or fat induced pancreatitis, it
• 1:08:14
  will actually improve it much improves the inflammation,
• 1:08:18
  right? So the key when you go from
• 1:08:20
  acute to chronic inflammation, like going from acute to chronic
• 1:08:24
  stress where you can't pull a stress away and it goes away.
• 1:08:29
  So but GLPS do that, they improve it.
• 1:08:32
  So they don't what's pancre? What does pancreatitis have to
• 1:08:35
  do with GLPS? The the dehydration and it
• 1:08:39
  changes the the bile acid composition causing bile stones
• 1:08:46
  and, and that can that that can interrupt the pancreatic duct.
• 1:08:53
  So it then obstructs the pancreatic duct causing
• 1:08:56
  pancreatitis because of the bile stones because of the
• 1:09:00
  dehydration and the impaired contractility.
• 1:09:03
  So that's. That's it.
• 1:09:05
  Those are all. Those are all the side effects.
• 1:09:08
  That. What's that?
• 1:09:09
  Those are all the side effects. That's it.
• 1:09:12
  Well, oh, no, no, no, there's, there's more.
• 1:09:14
  So what I mean the negative. So what are they the muscle loss
• 1:09:18
  that we talked about the, the under nutrition, because you're
• 1:09:24
  not going to, you know, that's a whole if, if there's a time, you
• 1:09:28
  have a minute to we'll talk about the, the nutrition and
• 1:09:31
  the, and the vitamins. But the, the, the GI complaints
• 1:09:36
  and it again, back to the, the volume.
• 1:09:39
  Orthostatic hypertension is is due to the the volume loss.
• 1:09:48
  But what about autonomic neuropathy?
• 1:09:51
  Just how the GLPS can promote. The contractility, right, It
• 1:10:02
  decreases the contractility through the gut, that's why.
• 1:10:06
  I'm gonna make an observation about the way you've been
• 1:10:08
  speaking for the past hour. It's interesting.
• 1:10:11
  I want you to address it. The way you speak about this
• 1:10:14
  drug is that it's like a wonder drug that fell from the heavens.
• 1:10:19
  A wonder drug that fell from the heavens.
• 1:10:21
  That's what it it sounds like the way like it sounds like if
• 1:10:24
  someone is 15 lbs overweight, let's just throw GOP at them
• 1:10:27
  because they'll probably get healthier anyway.
• 1:10:29
  I and that's not like that's not like my, you know, if you if you
• 1:10:35
  look how I I don't typically have.
• 1:10:39
  I'm a little bit surprised of the data so far that it is an
• 1:10:44
  amazing where the benefits are this high in the risk is very
• 1:10:49
  low. But like, look, let me finish
• 1:10:51
  with the with the side effects is it's not, it's, it's not that
• 1:10:56
  you know, these side effects should be significant to some
• 1:10:58
  people. But this is an important one
• 1:11:00
  about the, the the GLP, if it affects the autonomic nervous
• 1:11:05
  system of the gut, impairing the motility where you can get
• 1:11:08
  nauseous and have GI complaints of, of nausea and vomiting and
• 1:11:13
  Constipation and bloating and so forth.
• 1:11:17
  What about the cardiovascular system?
• 1:11:19
  Can it affect the autonomic nervous system that affects?
• 1:11:24
  So a lot of people go on this and they get lightheaded and
• 1:11:27
  dizzy. Well, is that due to the GLP?
• 1:11:31
  Because is there a risk of fatal arrhythmias?
• 1:11:33
  They've shown that it it reduces fatal non fatal heart attack,
• 1:11:38
  sudden death and stroke. So the but it does reduce heart
• 1:11:41
  rate variability, which is a key indicator of fatal arrhythmias.
• 1:11:46
  Right? So, but I'm just saying what the
• 1:11:49
  data is showing. They they, when you stop, it's
• 1:11:53
  not it, it's, it's not a pathological effect in this
• 1:11:58
  case. So the autonomic neuropathy that
• 1:12:00
  could explain. I've got cases of, of people
• 1:12:04
  that, you know, they get laid ahead and dizzy and I'm saying
• 1:12:07
  I, it might be the, the GLP that, and, and there's, there's
• 1:12:14
  involved some very complex circumstances.
• 1:12:17
  This is my biggest concern because there's GLP receptors
• 1:12:20
  all up and down that nervous system.
• 1:12:22
  And why is it sparing the heart? Why is it protecting us from,
• 1:12:28
  from cardiac arrhythmias and sudden death?
• 1:12:31
  Because, well, it, it that's, that's an open question, but,
• 1:12:37
  but particularly because it does reduce heart rate variability,
• 1:12:41
  which is a key indicator of sudden death.
• 1:12:45
  And, and, but we're not they're saying when it the drug has
• 1:12:50
  stopped that heart rate variability does not persist.
• 1:12:55
  It goes back to normal. And, and even when you're on the
• 1:13:01
  GOP and heart rate variability is impaired, that means, you
• 1:13:05
  know, when you breathe in and breathe out, sit, stand and lie,
• 1:13:08
  the boom, boom, boom, boom, boom, one beat to the next is
• 1:13:11
  going to vary. It's part of an orchestrated
• 1:13:14
  synchronization of the Physiology.
• 1:13:16
  When you lose that, things are not synchronized as well.
• 1:13:20
  And, and so that concerns me, but they're, they're not showing
• 1:13:26
  an increase in sudden death and millions of cases that have been
• 1:13:31
  looked at and which is kind of an odd, you know, that I, I
• 1:13:37
  think that needs to be looked at more squarely.
• 1:13:39
  But thus far, they're not finding any major adverse
• 1:13:43
  cardiovascular offense, including sudden death, on these
• 1:13:48
  drugs. Yeah, so Doctor Fertin.
• 1:13:50
  One more one more thing I want to mention though.
• 1:13:53
  Oh. No, no, no.
• 1:13:53
  So go ahead. No.
• 1:13:54
  So mention that thing. OK, and that's the eyes.
• 1:13:57
  What about this, this non orderitic optic neuropathy that
• 1:14:02
  people are afraid of sudden painless loss of vision.
• 1:14:05
  Oh my God, this life. I'm not going on that drug
• 1:14:09
  because because I I don't want to go blind.
• 1:14:13
  First of all, that can't happen. It it's the the, the incidence
• 1:14:20
  of, of absolute blindness. I'm not sure has gotten to that
• 1:14:26
  to, to, to that point where it's black but decreased vision.
• 1:14:30
  But it's about 1:00 and 5:00 or 10,000 people and it's rare.
• 1:14:35
  And it can. And that's why an eye doctor
• 1:14:38
  should be seen at the before as a baseline and every 12 to 18
• 1:14:44
  months. If you're diabetic, you're going
• 1:14:45
  to you go once a year anyway, at a minimum.
• 1:14:48
  Is it is it a permanent effect or is it temporary?
• 1:14:50
  Meaning when they get off the GOP once is their vision return.
• 1:14:53
  Well, it you go off the GOP, it goes away, but you don't want to
• 1:14:56
  continue taking it if that's the case.
• 1:14:58
  Sometimes you don't know because you know they're diabetic.
• 1:15:01
  You got blood sugars got out of control, your vision gets
• 1:15:03
  impaired. So you know, you get it checked,
• 1:15:07
  you know. But retinopathy macro
• 1:15:09
  degeneration in glaucoma, it can not glycoma, but macro
• 1:15:14
  degeneration, the wet form and retinopathy and retinal bleeds
• 1:15:18
  early on it. It's been shown to exacerbate
• 1:15:22
  these longer term in in a few cases, usually patients with
• 1:15:26
  sleep apnea, hypertension and diabetes.
• 1:15:30
  But if you content, you know, down the line the the three plus
• 1:15:36
  months out, it has a favorable effect on all those things,
• 1:15:40
  glaucoma, macro degeneration and retinopathy.
• 1:15:44
  So again, good stuff. There's not a lot of downside
• 1:15:48
  compared to the upside. I wish, I don't if how much time
• 1:15:55
  we have, but I could, I could tell you some of the benefits on
• 1:16:01
  the cancer if you're interested in it.
• 1:16:03
  So, so it's double edged sword here in the sense that I really
• 1:16:08
  want you to talk about it because that actually fascinates
• 1:16:10
  me. But we are out of time.
• 1:16:11
  I only have time for one more question, which I got to ask you
• 1:16:14
  as a generality. OK, As a general question, if
• 1:16:18
  you had a patient that was not very, that was not severely
• 1:16:22
  overweight, let's say 25 lbs overweight, would you feel
• 1:16:26
  confident enough from the data that you have from GLP ones as a
• 1:16:29
  generality to say, oh, you're 25 lbs overweight, take the GLP
• 1:16:34
  ones? Like, are you so convinced?
• 1:16:37
  I, I, I am and, and, and there's actually a new drug, Foundeo,
• 1:16:45
  that's out that has, you know, it's about it.
• 1:16:48
  And you look at how much weight loss percentage wise, whether
• 1:16:53
  it's 16% with, with a Zep Baker, 20% with the Zep bound or 30%
• 1:17:04
  with red and Glutide, which is sort of like bariatric
• 1:17:07
  procedures in that range that day was only 12%.
• 1:17:12
  And it's cheaper. But, but it's not a peptide.
• 1:17:15
  It's a synthetic. And, but the, you know, so that
• 1:17:21
  might be a drug that's, and it's also you can use low dose
• 1:17:24
  Wycovy. These the pills are coming out
• 1:17:26
  in different formulations. And it's very, I mean, I, I
• 1:17:30
  think it, it, Medicare is recommending that patients are
• 1:17:34
  going on this and they're paying for just $50.00 for I think it's
• 1:17:40
  a three month prescription. They must be pretty confident
• 1:17:45
  that this is going to save them money because they see the data.
• 1:17:49
  So I, I think this systemic health and that if of, of all
• 1:17:56
  the major chronic diseases, whether it's neurodegenerative
• 1:18:00
  cognitive decline, strokes, heart attacks and cancers.
• 1:18:05
  And the biological aging is reduced using the, the
• 1:18:08
  methylation approach, the methylation of DNA of autonomic
• 1:18:14
  nerve nerves that innervate the different tissues, which is a
• 1:18:18
  much better way than looking at the telomeres as a, an
• 1:18:21
  assessment of biological age, right?
• 1:18:24
  Chronological versus biological age.
• 1:18:26
  They're looking at. And this is just published,
• 1:18:29
  recently published University of California in San Diego.
• 1:18:34
  It, it, it a 9% reduction in, in cellular aging with these drugs.
• 1:18:41
  So something systemically and when I didn't get to say is and
• 1:18:46
  I'm not going to say because it's not time, but the
• 1:18:48
  fundamental reason how these things work on the set the the
• 1:18:54
  the I won't go into the details, so I'll just state it.
• 1:18:58
  The master metabolic regulators it which which are sensors of
• 1:19:06
  the the energy of the fuel gauge when they sense when the fuel
• 1:19:14
  gauges are on low and there's two of them really two Niacin
• 1:19:19
  makes something cool outside in any way Niacin makes NAD it's a
• 1:19:24
  it's. A we're really, we're, I'm
• 1:19:27
  sorry, we're really running out of time.
• 1:19:28
  Could you say the punch line for it?
• 1:19:29
  I apologize. No, that's OK.
• 1:19:31
  That's all right. That you want me to finish the
• 1:19:34
  point or just we can? If no, if you could finish it
• 1:19:37
  like under a minute, that'd be great.
• 1:19:39
  I just. Oh, yeah, yeah, yeah, yeah.
• 1:19:40
  No, no, I can't. It's OK.
• 1:19:42
  So the NAD is a metabolite of of of niacin and it extracts the
• 1:19:47
  the energy carrying electrons carried in sugars and fats and
• 1:19:52
  it passes it on through in those energy producing organelles and
• 1:19:57
  mitochondria to to making the ATP.
• 1:20:01
  So that's one fuel gauge when the NAD?
• 1:20:04
  Is high compared to the reduced form of it.
• 1:20:07
  The other is ATP, the biological currency of energy.
• 1:20:11
  When the ANP which is the building block of that and that
• 1:20:14
  ratio of eight AMP to ATP is high, that's the other fuel
• 1:20:20
  gauge. And when they're on empty, the
• 1:20:23
  master metabolic regulators, their sirtuins look at one the
• 1:20:28
  the AMP kinase, which is that the other one senses the the the
• 1:20:36
  ANPATP ratio. Those two things activated
• 1:20:41
  produce promote mitochondrial Biogenesis and their sirtoins is
• 1:20:48
  are important for turning for the cancer of of anti cancer
• 1:20:58
  program. The the stress resistance, the
• 1:21:00
  cancer resistance program of the body as well as the generalized
• 1:21:05
  stress resistance programs to the body cell and DNA repair.
• 1:21:11
  And and that that is really the foundation of why these drugs
• 1:21:16
  are so important. That last concept that I said
• 1:21:19
  the energy fuel gauge sensors Metformin is a a a calorie
• 1:21:27
  restriction memetic right, the GLPS or an actual calorie
• 1:21:33
  restriction. You put those two together and
• 1:21:36
  you have massive reduction, 67% reduction in all cause
• 1:21:41
  mortality. That was the point I wanted to
• 1:21:43
  make. Cancers, all of them, and that
• 1:21:46
  rivals the Mediterranean diet. You put the Mediterranean diet
• 1:21:49
  together with a combination of metformin and GLP.
• 1:21:53
  People are going to. Live maximum.
• 1:21:56
  Yeah, yeah, absolutely. Doctor Firthy, thank you so much
• 1:21:59
  for your tremendous wisdom. I know we only got the GLP
• 1:22:01
  wasn't even going to touch antibiotics, but we learned at
• 1:22:03
  least. I know I learned so much from
• 1:22:05
  what you had to say. And we look forward to the next
• 1:22:07
  time having you on the show. Thank you.
• 1:22:09
  Thank you very much, Rabbi. Take care, Take care.