by Dr. Joseph Mercola, Mercola:
STORY AT-A-GLANCE
- All dietary carbohydrates are digested into sugars called glucose. Glucose, in turn, can be metabolized (burned) for fuel using two different pathways. First, the glucose is metabolized into pyruvate. The pyruvate can then either enter the glycolysis pathway in the cytoplasm of the cell and produce lactate (this is an inefficient backup pathway), or it can be converted into acetyl-CoA and shuttled to the mitochondrial electron transport chain, which results in optimal energy production
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- The Warburg Effect refers to the observation that if your body has access to enough oxygen, it will preferentially burn (oxidize) glucose in your mitochondria by converting the pyruvate into acetyl-CoA
- The state of mitochondrial physiology that Warburg accurately identified occurs when your body has enough oxygen and the mitochondria are not maxed out, yet still uses the backup glycolysis pathway. This is also called cancer metabolism. It gives the false impression that cancer is using glucose to supply its metabolic needs for energy, but it is merely an illusion
- The primary reason glucose cannot be burned in your mitochondria is because the mitochondria are dysfunctional. This dysfunction is the result of the electron transport chain (ETC) being backed up with an excess of electrons that are unable to flow easily through the five complexes. This condition is known as reductive stress. In this situation, your body has no choice but to use the backup system, glycolysis
- Contrary to natural fructose (found in ripe fruits and honey, for example), refined sugars and many starches are more likely to cause gut dysbiosis that leads to the production of endotoxin. This endotoxin is one of the factors that destroys mitochondrial function, resulting in cancer metabolism (the Warburg Effect) where glucose is burned through glycolysis
There’s a common misconception that all sugar, i.e., carbohydrates in general, will act as fuel for cancer, but nothing could be further from reality. When it comes to the “sugar fuels cancer” issue, it’s important to make a distinction between the sources of the carbs.
While it is technically accurate to call all carbs sugar, there is a radical difference in the source of the carbs — ripe whole fruits versus starches, for example, and whole fruits versus refined processed sugar (ex: table sugar and high fructose corn syrup).
Many studies have indeed found a strong and accurate link between refined sugar intake and cancer risk. For example, research1 published in 2014 found that Stage 3 colon cancer patients who drank two or more servings of sugar-sweetened beverages per day had a 67% higher risk of cancer recurrence and death compared to those who consumed less than two servings per month.
The key term here is “sugar-sweetened beverages.” There are significant differences between liquid refined/processed sugar and unrefined sugars from fruits.
Refined sugars, as well as many starches, are a common cause of endotoxin production in your gut, which destroys mitochondrial function and results in cancer metabolism, whereas the fructose present in whole foods does not typically result in the production of endotoxin. This is one of the primary differences between refined sugar and fructose from ripe fruit and helps explain why refined sugars fuel cancer.
The Many Downstream Hazards of Glycolysis
The glycolysis pathway is great when you need quick fuel when you are activating your Type 2 muscle fibers. But if this is the primary way you burn glucose, then you are in a catastrophic metabolic state because you’re promoting insulin resistance and diabetes and creating loads of lactate as a waste product instead of healthy CO2 and metabolic water.
Lactate increases reductive stress, which causes reverse electron flow in the mitochondria and increases the ROS to 3% to 4%, which is 30 to 40 times more than when glucose is burned in the mitochondria. What’s more, glycolysis generates only two ATP for every molecule of glucose, which is 95% less energy than would be generated if the glucose were metabolized in your mitochondria.
You’re also promoting cancer, because cancer cells preferentially use glycolysis. But again, it’s not sugar that is driving the cancer process per se. It’s really rooted in mitochondrial dysfunction, and fatty acid oxidation (metabolism of fats instead of glucose) is part of what causes that dysfunction.
For a long time, I believed fats burned “cleaner” than carbs — that’s one of the “selling points” for keto — but I’ve since realized we had it backward. Glucose, when burned in the mitochondria, actually burns far cleaner than fat.
So, it’s important to get your macronutrient ratios right, because if the glucose you eat is constantly shuttled into glycolysis, you’re fueling cancer. At the same time, the fat you consume ends up in fat storage rather than being used up for fuel.
Ultimately, you want to burn glucose in your mitochondria. One exception is when you’re doing high-intensity exercise. When you’re engaging your Type 2 fibers, it’s safe to use the glycolysis pathway, but that’s the exception. When you’re resting, you want to burn glucose in your mitochondria.
The only way to ensure that is to keep your dietary fat content below 35% of your total calories. If you’re insulin resistant, which means you’re metabolically inflexible, that threshold may be closer to 20% or even 10%. So, if you’re insulin resistant, you’ll want to significantly lower your fat intake until your insulin resistance is resolved. Then you can increase it to 30%. All of this is easily calculated by using a free online program called Cronometer.
The Warburg Effect
You’ve probably heard that the Warburg Effect is involved in cancer. The Warburg Effect refers to the observation that cancer cells produce lactate even in the presence of adequate oxygen (aerobic respiration). Lactate is a byproduct of glycolysis (nonaerobic respiration).
I realize the above explanation of the Warburg Effect is technical, but the key point here, and what Warburg identified, is that if your body has access to enough oxygen, it will preferentially burn (oxidize) glucose in your mitochondria by converting the pyruvate into acetyl-CoA.
If you find this concept confusing, please be kind to yourself. Even some highly knowledgeable physicians in natural medicine misconstrue this point and incorrectly assert that Warburg demonstrated cancer is fueled by sugar. I, too, held this belief before delving into biologist and bioenergetic medicine pioneer Ray Peat’s work. However, it’s evident that such a claim is a profoundly serious misinterpretation of Warburg’s research.
