Fructose and Glucose (and a Bit of Salt)

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Key Takeaways:

  • Fructose and glucose are very similar simple carbohydrates.
    • Fructose is found in fruits and vegetables.
    • Glucose is made by plants, mostly consumed in bonded form (lactose, starch, etc.).
  • Fructose and glucose play a role in the storage and production of energy.
  • Fructose mostly triggers energy storage.
    • Ancient adaptation.
    • During starvation, fructose metabolism triggers preservation mode, store fat.
  • Today: fructose has mostly adverse consequences.
    • Food abundance.
    • Fructose metabolism plays a role in inflammation, increased food consumption, gout, high blood pressure, fatty liver, lower metabolism.
    • Factor in insulin resistance, obesity, elevated cholesterol and triglycerides.
  • Sugar = fructose + glucose.
    • Fructose content of sugar is cause of issues with sugar intake.
  • Avoid or reduce overly sweet and salty foods.
    • Reduce intake of sugar (contains fructose), especially sugary drinks.
    • Reduce intake of high glycemic carbs (glucose may be converted into fructose).
    • Reduce intake of high salt foods (may stimulate fructose creation).

Fructose and glucose are carbohydrates

  • One of the three macro molecules (carbs – fats – proteins).
    • Consist of carbon, hydrogen and oxygen.
    • Stored with the aid of insulin.
  • All organisms generate energy from the breakdown of carbohydrates.
    • Converted into ATP for body fuel.
    • 4 calories per gram.
  • Simple carbohydrates:
    • Monosaccharides.
      • Fructose: one ring of five carbons.
      • Glucose: one ring of six carbons.
    • Disaccharides.
      • Lactose (milk).
      • Sucrose (table sugar): combination of fructose and glucose.
      • Maltose (starch digestion).
  • Complex carbs:
    • Polysaccharides:
      • Starch (storage form of glucose in plants)
      • Glycogen (storage form of glucose in animals)
      • Fiber (not an energy source, not broken down; includes cellulose).
    • Examples: cereals, bread and pasta.

Fructose

  • Found in fruits, vegetables, honey.
    • As fructose (free).
    • As sucrose (bonded to glucose), for instance table sugar.
  • Humans absorb it.
    • Through food intake.
  • Produce it.
    • Salt and other factors drive fructose production.
    • From glucose to fructose.
  • Store it.
    • As fat or glycogen.
    • Mostly in the liver.
  • Metabolize it through fructolysis.
    • Phosphorylation by fructokinase.
    • By-product is uric acid.
  • Excessive consumption of fructose may contribute to:
    • Insulin resistance.
    • Obesity.
    • Elevated LDL cholesterol and triglycerides.
    • Metabolic syndrome.
  • Issue with sugar is related to its fructose content.
    • The (hepatic) metabolism of fructose: see below.
    • The impact of fructose on food consumption: it doesn’t satiate you.
  • Sweetest of all naturally occurring carbohydrates.
    • Commonly added to food to improve taste.

Glucose

  • Plants.
    • Make it.
      • During photosynthesis.
      • From water and carbon dioxide, using energy from sunlight.
    • Use it.
      • To make cellulose in cell walls, the most abundant carbohydrate.
    • Store it.
      • As starch.
  • Nature:
    • Glucose does not occur much in its free form.
    • But in the form lactose, sucrose, starch (energy storage) and cellulose (components of cell walls in plants).
  • Humans:
    • Produce it as needed.
      • Gluconeogenesis.
      • Mostly in the liver, but also in the kidney.
      • About 180 to 220 grams of glucose produced in the liver in 24 hours.
    • Get it from from food.
      • Degraded from complex carbohydrates -> glucose using enzymes.
    • Store it as glycogen.
      • In the liver (150 grams) and muscle tissue (250 grams).
      • Liver cell glycogen can be converted to glucose and returned to the blood when insulin is low or absent.
    • Circulate it in the blood as blood sugar.
      • Insulin (and other hormones) regulates the concentration of glucose in the blood.
      • About 4 grams of glucose present in the blood.
      • Too high: diabetes.
      • Too low: hypoglycemia.
    • Metabolize it through glycolysis.
      • Glycolysis, and later the citric acid cycle and oxidative phosphorylation.
      • Eventually forms carbon dioxide and water.
      • Yielding energy mostly in the form of ATP.

Issues associated with fructose

  • Fructose triggers processes associated with energy and fat storage.
  • Issue 1: inflammation.
    • Both fructose and glucose bind to other proteins in the browning reaction.
      • In fruit: produces over-ripe browning color.
      • In humans: (glucose) binds to haemoglobin.
        • Which is why we use HA1c as a measure for blood sugar.
    • Negative effects of browning reaction:
      • Proteins become less flexible.
      • Produces reactive oxygen species, potentially causing inflammation.
    • Fructose browning rate is 7x faster than glucose.
  • Issue 2: increased food consumption.
    • Glucose lowers ghrelin (hunger hormone).
    • Fructose doesn’t.
    • Brain doesn’t know it’s been fed.
  • Issue 3: addiction.
    • Glucose in the brain is mostly associated with sensory motor cortex.
    • Fructose in the brain is associated with dopamine, reward centers.
    • Each excitatory stimulus causes down-regulation of the receptor.
    • Tolerance, addiction.
  • Issue 4: gout.
    • Fructose metabolism produces uric acid as by-product.
    • Uric acid causes gout.
  • Issue 5: high blood pressure.
    • Fructose metabolism:
      • Phosphorylation by fructokinase (fructolysis).
      • Fructose takes one phosphor from ATP, which becomes ADP.
      • ADP loses another phosphor to become AMP.
      • Fork in the road at AMP (see “AMPK“):
        • AMP Kinase pathway (AMPK): burn fat, energy.
        • AMP Deaminase pathway (AMPD): storage of fat, energy.
      • Due to fructose related ATP depletion – (see below), AMPD is activated.
      • AMP becomes IMP becomes uric acid.
      • Uric acid blocks nitric oxide synthase (NOS).
      • NOS regulates blood pressure (relaxes arteries).
    • Fructose consumption may cause high blood pressure.
  • Issue 6: fatty liver.
    • Fructose makes more fat (see ATP depletion below).
    • Fructose also inhibits fat burning.
    • Excess fatty acids:
      • Mostly stay in the liver: fatty liver.
      • To some extent, exported out: higher VLDL, triglycerides in the blood stream.
      • Are broken down through oxidation (lesser extent).
  • Issue 7: ATP depletion, lower metabolism.
    • Breaking down and metabolizing glucose or fructose requires spending ATP.
      • Glucose: process is regulated (stops).
      • Fructose: process is not regulated (does not stop).
    • Fructose ATP depletion signals body to go into energy reservation / hibernation mode.
      • Reduces metabolism.
      • Triggers fat and glycogen storage.
      • Triggers hunger and thirst.

Fructose, uric acid and gout

  • Uric acid is a purine.
    • One of the building blocks of nucleic acids (such as DNA and RNA).
  • Gout is driven by excess uric acid consumption or creation.
    • Consumption:
      • Proteins: uric acid is contained in the (DNA and RNA inside the) proteins we eat.
      • Certain meats, beer (yeast), etc.
    • Creation:
      • When we eat sugary food and the fructose is metabolized.
      • Generates uric acid as by-product.

Fructose, salt, uric acid and blood pressure

  • High blood pressure (BP):
    • Ideal BP = 120 over 80.
    • High BP >160.
    • High BP -> heart failure, stroke.
  • Previous hypothesis:
    • Defect in kidney -> difficulty excreting salt -> salt retention -> high BP.
    • Therefore: too much salt -> high BP.
    • Not about amount of salt, but concentration of salt you take in.
    • Salt + water = better.
  • Updated hypothesis:
    • Kidney autoimmune reaction -> inflammation -> immune response -> injury -> lower blood flow –> salt retention -> fructose creation -> uric acid -> high blood pressure.
      • Autoimmune reaction: heat shock proteins doing their usual “cleaning”
      • In some cases, causes an immune response
      • Immune response can injure the kidney, lowering blood flow
      • Injured kidney holds on to salt.
      • High levels of salt activate enzymes that convert glucose to fructose.
      • Fructose metabolism produces uric acid.
      • High uric acid drives high BP.

Fructose and cancer

  • Cancers prefer fructose as fuel because it helps support them surviving in a low oxygen state.
  • Block fructose metabolism (fructokinase), many cancers don’t do as well.

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