Latest / Fork U with Dr. Terry Simpson / GLP-1 Drugs, the Mediterranean Diet, and the Science of Living Longer

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GLP-1 Drugs, the Mediterranean Diet, and the Science of Living Longer · Fork U with Dr. Terry Simpson

• 0:04
  >> Dr. Terry Simpson: We talk a lot about aging, aging with good health,
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  aging with a good health span and longevity. And
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  we talk a lot about supplements that don't work or
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  to diets that are rather silly. But today, the
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  biggest anti aging story isn't in a pill or a cold
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  plunge or a fasting app. Uh, it's in your
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  metabolism. And it starts with a class of drugs we
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  once thought were just for diabetes, the GLP1
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  receptor agonists, you know, Ozempic, Zepbound,
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  etc. These medications are now being primarily
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  used for obesity. And they're doing remarkable
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  things, not only reducing weight, but reversing
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  many of the diseases that travel with and maybe
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  because of obesity. And since obesity clearly
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  shortens your health span, it's not surprising
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  that these drugs are now being looked at as tools
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  to improve health. Spanish the years you live
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  well, not just lengthening a, uh, miserable life.
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  But it turns out there is much more to these drugs
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  than weight loss. These drugs have anti
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  inflammatory effects, cardiovascular protection,
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  reductions in stress physiology, and emerging
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  evidence they may delay cognitive decline. And
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  many of those benefits appear to be independent of
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  weight loss. So the idea that GLP1 drugs, and now
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  triple agonists like pitoutatride might represent
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  a new class of anti aging medicine isn't hype.
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  It's a serious scientific question. Even Peter
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  Attia, whose clinic focuses almost exclusively on
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  longevity and health span, has discussed using
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  GLP1 drugs at lower doses in select patients to
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  support metabolic health and long term health.
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  Spanish this week, Eli Lilly released striking
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  phase three data on their newest compound,
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  retatrutide, a triple hormone drug that isn't just
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  helping people lose weight. It may be resetting
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  the biology of aging. Today on 4Q, we're going to
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  make sense of the madness of Healthspan and GLP1.
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  I am, um, your chief medical explanationist, Dr.
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  Terri Simpson, and this is 4Q Fork University,
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  where we bust myths, make sense of the madness,
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  and teach you a little bit about food and
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  medicine. When we talk about longevity, we're
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  really talking about metabolic stability, blood
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  sugar control, lower inflammation, lower oxidative
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  stress, the ability of cells to repair. And GLP1
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  agonists touch all of these systems. They were
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  designed to mimic a gut hormone, the glucagon,
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  like peptide 1, which signals satiety and improves
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  glucose regulation. But over the last decade,
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  we've learned they do far more than lower
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  hemoglobin A1C and make diabetes better control.
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  They reduce systemic inflammation, they improve
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  mitochondrial efficiency, they lower oxidative
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  stress, and they improve vascular function. The
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  same biology that reduces appetite may also make
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  cells behave younger. Enter UH retatrutide. In
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  Lilly's Phase 3 Triumph 4 trial, participants lost
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  nearly 29% of their body weight over 70 pounds on
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  average, and saw UH major improvements in
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  inflammation, blood pressure, lipids and joint
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  pain. But weight loss is just the surface.
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  Retatutride targets three key pathways. There's
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  the GLP1 pathway, which reduces appetite and
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  inflammation. There's the GIP, which improves
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  insulin sensitivity and nutrient handling. And
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  this one adds a glucagon, which increases energy
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  expenditure and fat oxidation. If GLP1 calms the
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  system and GIP balances it, glucagon fights a
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  controlled metabolic fire, keeping metabolism from
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  slowing down as weight is lost. That's not just
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  slimming, that's metabolic rejuvenation. Let's
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  talk about inflammaging. Aging isn't just wear and
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  tear. It's driven by chronic low grade
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  inflammation, where gerontologists call
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  inflammaging. Inflammaging fuels heart disease,
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  strokes, type 2 diabetes, fatty liver, arthritis
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  and likely cognitive decline. In the Triumph 4
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  trials, retatutride decreased CRP, triglycerides
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  and blood pressure. Classic anti aging biomarkers.
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  Less inflammation means fewer senescent cells,
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  healthier blood vessels and better organ function.
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  Let's talk about heart disease and GLP1s. And if
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  you want to talk about aging, you have to talk
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  heart disease because nothing ages you faster than
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  a heart attack. Across multiple cardiovascular
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  outcome trials, GLP1 receptor agonist, which is
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  all these new drugs, have shown a 13% reduction in
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  cardiovascular death, a uh, 9% reduction in non
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  fatal heart attacks or myocardial infarctions. In
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  the so called leader trials, liraglutide reduced
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  cardiovascular mortality by 22%. Now semaglutide
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  and lugotide show similar reductions, enough that
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  the FDA now recognizes certain GLP1 drugs as
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  cardiovascular red risk reducing therapies in
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  patients with type 2 diabetes and established
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  heart disease. These benefits are not just about
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  sugar control. Turns out the GLP1s lower blood
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  pressure, reduce inflammation, improve endothelial
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  function. That's the cells that surround the
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  vessels, reduce oxidative stress and decrease what
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  we call RAS activation, which means at the
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  cellular level they protect heart cell muscles
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  from multiple forms of cell death and enhance
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  autophagy and mitophagy. That means the heart is
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  cleaning up old cells and old mitochondria. They
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  don't dramatically treat heart failure the way
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  SGLT2 inhibitors do, but they are safe and reduce
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  atherosclerotic risk. Avoiding a heart attack is
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  one of the most powerful anti aging interventions
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  and powerful ways to increase your health span.
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  People who live a long time aren't free from heart
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  disease, but what they are free from is heart
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  disease for a little while. Meaning healthspan
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  puts it off.
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  Now, let's talk about the brain. Let's be careful
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  here. GLP1 drugs do not reverse dementia. They do
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  not improve cognition once dementia is
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  established. Recent trials in people with
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  diagnosed Alzheimer's disease have shown no
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  meaningful cognitive improvement. And that's
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  critical for me to tell you that clearly the
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  promise of GLP1 drugs is prevention and delay, not
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  cure. And in large observational drugs, GLP1 users
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  had roughly 33 to 45% lower risk of developing
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  dementia compared with other diabetic drugs. The
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  2025 Journal of the American Medical association
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  of Neurology had a study that showed uh, a 33%
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  lower risk of Alzheimer's and related dementias,
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  especially in people who have cardiovascular
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  disease. Randomized trial meta analysis show a
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  real but m more modest protective signal stronger
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  than what we actually see with other types of
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  drugs. Mechanistically, GLP1s reduce
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  neuroinflammation. That's inflammation of the
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  brain. They improve insulin signaling in the
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  brain, they enhance vascular health in the brain.
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  They perform neurogenesis and they may reduce
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  amyloid and tau pathology. Age matters. The
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  benefit appear stronger when started earlier,
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  before neurodegeneration is established. But our
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  goal here is not immortality. The goal is to push
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  dementia far enough into the future that many
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  people never reach it. That's healthspan.
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  Let's talk about ultra processed food and brain
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  aging. This may be the real Ultra processed food
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  isn't a terribly difficult concept, but you
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  probably get the general idea. These foods hijack
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  the brain's dopamine reward system, increasing
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  wanting while reducing pleasure. They're soft,
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  fast, hyperpalatable and engineered to be consumed
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  before the gut can signal fullness. Ultra
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  processed food intake is linked to higher
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  inflammation, lower gray matter density, worse
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  metabolic health and faster brain aging. They
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  disrupt that gut brain access, damage the
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  microbiome and worsen insulin signaling in the
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  brain. GLP1 drugs are in many ways repairing
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  damage caused by a food environment designed to
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  exploit our biology. What about the Mediterranean
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  diet and alcohol? Well now, here's the empowering
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  part. If there is one dietary pattern with the
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  strongest evidence for protecting the heart and
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  the brain, it's the Mediterranean diet.
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  Vegetables, legumes, fruit, whole grains, olive
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  oil, fish. Minimally ultra processed food. This
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  pattern reduces inflammation Supports the
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  microbiome, um, improves vascular health and slows
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  cognitive decline. GLP1 drugs calm the biology.
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  The Mediterranean diet keeps it calm. And one more
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  hard truth, we've talked about this before.
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  Alcohol. The idea that alcohol protects the brain
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  has never been held up. Even moderate drinking is
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  associated with higher dementia risk, worse sleep,
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  hippocampal injury and increased neuro
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  inflammation. If your goal is to protect your
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  brain, thus alcohol is better. No, alcohol is
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  best. So what does this really mean now? Aging
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  isn't about the years, it's about systems. GLP1
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  drugs support metabolism. The Mediterranean diet
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  supports biology. Avoiding alcohol protects the
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  brain and the heart and the kidneys and the eyes,
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  movement and sleep. Lock it in. If we delay heart
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  disease, dementia and disability long enough, many
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  people will never live long enough to experience
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  them. That's not cheating death, that's winning.
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  At Healthspan. If you're thinking about GLP1
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  drugs, work with a qualified obesity or metabolic
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  health specialist. Not one of those peptide mills.
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  Avoid research grade compounds sold online. That's
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  lab reagent. That's not medicine. And if you want
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  to go deeper into longevity medicine and
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  Mediterranean eating, metabolic health and
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  evidence based anti aging, join us on the
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  Mediterranean Longevity Cruise. In August of 2026,
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  you'll have 10 days of real food, real science,
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  movement and conversations that actually matter.
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  Details will be forthcoming. This was written and
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  researched by me, Dr. Terry Simpson. And while I
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  am a board certified physician, I am not your
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  physician. Always consult your own board certified
• 10:41
  physician and a registered dietitian before making
• 10:44
  or starting any changes in medications and diets.
• 10:47
  All things audio are from my friends at Simpler
• 10:49
  Media and the pod God himself, Mr. Evo Tara. All
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  right everybody, have a good week. Hey evo. At
• 11:08
  GLP1's the Mediterranean Diet and not drinking
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  help people live longer and think clearer. Are we
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  obligated to keep doing this podcast into our 90s?
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  I mean, maybe. And like also, what the hell else
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  we going to do, man?