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).
- Monosaccharides.
- 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.
- Polysaccharides:
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.
- Make it.
- 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.
- Produce it as needed.
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.
- Both fructose and glucose bind to other proteins in the browning reaction.
- 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.
- Fructose metabolism:
- 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.
- Breaking down and metabolizing glucose or fructose requires spending ATP.
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.
- Consumption:
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.
- Kidney autoimmune reaction -> inflammation -> immune response -> injury -> lower blood flow –> salt retention -> fructose creation -> uric acid -> high blood pressure.
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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