The Peter Attia Drive – Robert Lustig, M.D., M.S.L. on Fructose, Processed Food, NAFLD, and Changing the Food System

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Key Takeaways
  • When you eat glucose, ghrelin levels (the hunger hormone) drop
  • When you eat fructose, ghrelin levels don’t change
  • Uric acid can be used as an indirect measure of fructose levels over time
    • The more sugar you consume, the higher your serum uric acid level goes
  • As fructose consumption ^, uric acid levels ^, blood pressure ^, risk of stroke ^
  • Eating a diet high in sugar while you’re pregnant, will have an effect on offspring genes, in a negative way
  • It’s been proven that human taste buds densensitize over time – this is why we keep wanting more and more sweets (our taste buds get down-regulated)
  • “If there’s a label on the food, it’s a warning label. That means it has been processed. Real food doesn’t need a label.”
  • Fructose is driving the development of NAFLD in humans
  • Prolonged high insulin levels allow for a constant activation of the MAPK/ERK pathway (the proliferation pathway)
    • This pathway is responsible for making coronary arteries tighter, and less likely to vasodilate when they need to – this increases the risk for a heart attack
  • “If you don’t consume fiber, your gut bacteria are not getting the food they need”
Intro
  • Dr. Lustig (@RobertLustigMD) has quite the presence on Youtube
  • Rob is a researcher, an expert in fructose metabolism, and a former pediatric endocrinologist
  • Rob – “My issue is with processed food. Processed food has several things wrong with it – sugar being one, but also a lack of fiber, which is equally as bad.”
Glucose vs. Fructose
  • They are both carbohydrates (specifically monosaccarrhides)
    • Every cell on the planet burns glucose for energy
    • Even if you consume zero glucose, you will still have a blood glucose level (so you’ll have some level of glucose in your blood) – your body makes it 
      • The body can make it from amino acids (i.e. from protein)
        • Note from Podcast Notes – This is why you can’t eat high levels of protein and stay in ketosis (the state in which your body runs on fat). If you eat protein, it will be converted to glucose, which the body would then use for fuel.
      • Or from fatty acids (it’s a side effect of ketone production)
        • Note from Podcast Notes – This is talked about more in this blog post from Peter. Check out the graph. Even after someone has been fasting for 40 days, they still have a blood glucose level. 
    • Biochemistry: 6-membered ring
    • When you eat glucose, ghrelin levels (the hunger hormone) drop
    • Plants can utilize fructose for energy
      • It’s more of a plant food than animal food
    • Biochemistry: 5-membered ring
    • When you eat fructose, ghrelin levels (the hunger hormone) don’t change
      • “When you eat a lot of fructose, your brain doesn’t know you’ve eaten, so you end up consuming more”
    • Fructose lights up the reward center of the brain
      • It’s been shown to induce the same physiology in the brain that cocaine, heroin, nicotine, alcohol, or any hedonic substance also generates
  • Summing Up
    • “Glucose and fructose are not the same”
  • The Browning Reaction
    • In the linear form for glucose and fructose, a normal biochemical process occurs (called the browning reaction) (aka Mailliard reaction aka Amadori rearrangement)
      • This is what causes bananas to brown
      • This is the same reaction that causes humans to brown (very slowly) – “You can roast your meat in an oven at 375 degrees for an hour, or you can roast your meat at 98.6 degrees for 75 years”
        • Right now, the mitochondroa in your cells are engaged in this process – this is what makes people age
    • For fructose, the reaction occurs at 7x the rate it does for glucose
Fructose Biomarkers
  • You can gauge average blood glucose levels over time by measuring hemoglobin A1C
  • Uric acid can be used as an indirect measure of fructose levels
    • The more sugar you consume, the higher your serum uric acid level goes
    • Peter wants to see uric acid levels in his patients below 5
    • Rob’s research group has shown that serum uric acid in children and adolescents correlates with sugary beverage consumption
    • Uric acid is an inhibitor of something called endothelial nitric oxide sythase (eNOS)
      • This enzyme works to keep blood pressure down by dilating blood vessels (makes them larger – called vasodilation)
      • Rob’s group has found that with every 10% increase in fructose consumption, your blood pressure will rise by 2 millimeters of mercury consistently – this also increases your risk of stroke by 10 percent
      • Summary – as fructose consumption ^, uric acid levels ^, blood pressure ^, risk of stroke ^
  • ALT (Alanine Amiotransferase) is a surrogate marker for fructose consumption
    • ALT goes up when your liver stores fat – it’s a biomarker for the degree of liver fat
    • Rob likes to see results for his patients below 25, Peter wants ALT in his patients below 20
Is there something that fructose does better than glucose?
  • It replenishes liver glycogen (glycogen is stored sugar) (note – not muscle glycogen) stores quicker
    • This is useful if you’re a high level endurance athlete in a race – that’s why they drink something like Gatorade (it’s filled with sugar/fructose)
  • But Peter has a good argument – “The limit to performance is not liver glycogen, it’s muscle glycogen”
    • Drinking a sports drink does not replenish muscle glycogen faster
Epigenetics, Nutrition, and Neurotransmitters
  • It’s known that animals that are stressed, or animals that consume large amounts of sugar during pregnancy, end up with offspring that will manifest various aspects of metabolic syndrome later on in life
    • “Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes.” from here
    • So ….maternal hyperglycemia (high blood sugar – caused by eating a diet high in sugar) will have an effect on offspring genes (in a negative way)
    • This isn’t confirmed in humans, but “It’s likely”
  • It’s been proven that human taste buds densensitize over time – this is why we keep wanting more and more sweets (our taste buds get down-regulated)
    • There’s also evidence that our dopamine receptors are desensitized over time 
      • This is why cocaine is such a dangerous drug. User experiences a downregulation of dopamine receptors as a tolerance develops, making it harder and harder to experience joy in real life.
      • This same thing could be applied to sugar consumption
  • A quick detour into neurons and neurotransmitters…
    • Neurotransmitters are either excitatory or inhibitory
    • Chronic overstimulation of any neuron leads to neuronal cell death
      • Note from Podcast Notes – to follow along, just know that neurotransmitters activate neurons by binding to its receptors
    • Any excitatory neuron (downstream of an excitatory stimulus) – has a protection method.
      • It downregulates its receptors if it’s over stimulated – this results in a lower liklihood that a neurotransmitter will find areceptor to bind to – this reduces the risk of cell death
    • So… with something like cocaine, each time you need a bigger and bigger dose because receptors on neurons are downregulated
    • Over time – neurons will actually die due to chronic stimulation
How are alcohol and fructose similar in the way they affect the brain?
  • They both stimulate the reward center of the brain, but through different mechanisms
    • They are dopamine stimulators
  • Other addictive dopamine stimulators? – Social media, porn, gambling
    • However, these are behaviors, so you won’t experience withdrawal symptoms
  • “In a way, we’re all addicts”
How can you better control how much sugar your kids eat?
  • “It’s not the added sugar you know, it’s the added sugar you don’t know”
    • 50% of the added sugar consumed by children comes from candy/cake/ice cream and soda
      • The median is about 90 grams of sugar per day for a kid
    • The other half comes from foods you didn’t know have sugar (pasta, bread)
      • Sugar is often added to bread to help it last longer without going stale (mostly bread from grocery stores, not a bakery)
  • “Processed food is the problem, because processed food is high in sugar, low in fiber’
    • You want a child to eat a low sugar, high fiber diet
    • “Every diet that works, is real food. Every diet that doesn’t work, doesn’t work because it involves processed food”
    • GROCERY STORE BREAD IS PROCESSED FOOD
    • “If there’s a label on the food, it’s a warning label. That means it has been processed. Real food doesn’t need a label.”
NAFLD (Non-Alcoholic Fatty Liver Disease)
  • Latino’s have a genetic predisposition for NAFLD
    • They have a specific polymorphism (known as the G;G mutation) of a specific gene called PNPLA3
    • With this mutation, consuming sugar is more likely to result in the production of liver fat – this is explained below
  • Fructose is driving the development of NAFLD in humans
    • Liver fat levels = liver fat production – liver fat clearance
    • There are 2 methods of production
      • Consuming dietary fat
      • de novo lipogenesis (DNL) – the process of turning the sugar you eat into stored body fat 
        • This has risen steadily on average for many people over the last few years, as sugar makes up a larger and larger % of the human diet 
        • This is the driver for the development of NAFLD
    • There are 2 ways to clear the liver fat
      • Fatty acid oxidation
      • Export – a VLDL particle carries it out of the liver
    • The one aspect of metabolic syndrome that everyone agrees upon is insulin resistance 
      • Where does the insulin resistance come from?
        • One way – You get fat, your fat cells make cytokines (inflammatory molecules), which then go to the liver and cause it to be dysfunctional, hepatic glucose output (HGO) is increased – this causes beta cells to overproduce insulin, which results in insulin resistance
          • So the cause is cytokines from subcutaneous fat (fat under the skin)
          • HGO is when the liver shuttles stored glucose out into the blood stream. This is useful during exercise, for example, so you have energy. But the stored glucose isn’t needed, it’s problematic.
        • Another way – Chronic stress increases cortisol (the stress hormone), which increases visceral fat (fat around your organs)
          • So the cause is cytokines from visceral fat
          • Cortisol drives visceral fat accumulation
        • The last way – sugar consumption
          • Our body produces cytokines when we consume sugar
    • Some side notes…
      • Muscle’s don’t need insulin to import glucose
        • Insulin works to import amino acids into muscles though – to aid in muscle growth
What are the actual mechanisms that links metabolic syndrome, insulin resistance, fatty liver, and type 2 diabetes?
  • Once you have metabolic syndrome from one of the 3 causes above…
    • You’ll be insulin resistant from either the cytokines (from the subcutaneous or visceral fat, or sugar)
    • You’ll have increased hepatic glucose output (HGO) – so your serum glucose is increased
    • Your beta cells has to make extra insulin (to shuttle that glucose into cells) causing you to be further insulin resistant
    • So there’s really no off switch for the insulin production…and insulin levels are always high
  • Some other effects of prolonged high insulin levels
    • It stimulates the MAPK/ERK pathway (the proliferation pathway)
      • This pathway is responsible for making coronary arteries tighter, and less likely to vasodilate when they need to – this increases the risk for a heart attack
    • Insulin is also a mitogen – it causes cells to divide
      • This might result in rapid cell division (cancer)
  • Soo……with type 2 diabetes
    • The object is to increase your insulin sensitivity – this can only be done by diet
      • “You can’t out run a bad diet. Exercise won’t fix the insulin problem by itself.”
    • Getting your insulin levels down, as well as your blood glucose levels are part of the battle as well
A Calorie is Not a Calorie
  • The food industry tends to argue against this
  • Rob gives an example
    • If you eat some almonds, you’ll absorb about 130 calories of the total 160 calories
      • The fiber in the almonds forms a gel on the inside of the intestines in an area known as the duodenum
      • This lining prevents the liver from getting the whole dose of calories – anything that’s absorbed in the duodenum will go right to the liver
      • So… some of the almond calories can’t be absorbed in the duodenum and are forced to travel onwards to the microbiome (aka the jejunum area of the intestine)
    • Take an apple – which has lots of fiber
      • The fiber does the same thing as described above, preventing fructose from getting to the liver
        • Note from Podcast Notes – this is why drinking juice is not so healthy, there’s no fiber preventing the absorption of fructose
      • So…some (about half) of the fructose in an apple would not get absorbed, and would in turn make its way to the microbiome – the gut bacteria would then digest it
    • “If you don’t consume fiber, your gut bacteria are not getting the food they need”
      • If they don’t get the food they need – the bacteria will autodigest the mucin layer that sits on the surface of your intestinal epithelial cells 
        • This may cause leaky gut, and other GI diseases like colitis, or even Cronh’s
      • “Feed your bacteria, or your bacteria will digest you”
Soluble vs. Insoluble Fiber
  • You need both – real food has both (like vegetables)
  • The food industry keeps adding soluble fiber, like psyillium husk, to food to make it appear healthier – like fiber bars
    • But without the insoluble fiber…. it doesn’t make a difference
Changing the Food Industry
    • 10 companies control 90% of the food industry (or 90% of the calories people consume)
    • “The food system needs to change, and it won’t change from the inside because right now sugar is their business model. It’s the thing that increases their sales.”
      • “They add more sugar, they sell more food”
    • The business model needs to change…how? Some ways…
      • Educate the public – so people don’t want sugary food, and in turn the food companies won’t sell it
      • Judicial Impact – lawsuits against the food industry
    • Rob wants to get rid of food subsidies
      • The food subsidies are what enable the junk food to be basically half the price of real food
      • “Any subsidy distorts the market. There’s no reason for food subsides. There’s no economist worth their soul today that believes in food subsidies, because they distort the market.”
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