Stop Measuring Glucose Without Measuring Lactate
And for goodness sake someone make a home test for pyruvate. 🤦
Over on Twitter/X/whatever, Fire in a Bottle has been documenting how restricting branched-chain amino acids (BCAAs) has gotten his morning glucose down from the pre-diabetic range to about 90 milligrams per deciliter (mg/dL).
Then he hosted a friend’s birthday party and ate beef, cheese, and beans, with a much higher intake of BCAAs than he had been getting recently, and woke up to a glucose of 111 mg/dL.
The usefulness of this observation is extremely limited by the irrational testing of glucose without testing other fuel molecules.
There is no rational reason to ever measure glucose alone. As an index of diabetes, even, it is horrible. Diabetes is a “disease” of elevated glucose, ketones, free fatty acids, lactate, and triglycerides. I put “disease” in quotations because all it is, in its type 2 manifestation, is a broad collection of issues causing global dysregulation of energy metabolism. The fact that there are common risk factors like obesity and sedentariness that have risen to great heights in the whole population, making the prevalence of diabetes rise with time, hides the fact that the remainder of the risk factors are highly idiosyncratic.
Case in point, high protein decreases my blood glucose, and BCAAs do not stand out as majorly different than protein. But I can give myself a blood sugar of 111 mg/dL with biotin or some other nutrient that puts stress on complex I of the respiratory chain.
Why BCAAs are an idiosyncratic risk factor for his latent potential to become diabetic, and why biotin is an idiosyncratic risk factor for my latent potential to become diabetic, is infinitely more useful knowledge than the fact that all of us could reduce our probability of activating this latent potential by being lean and active.
Duh. Go forth and be lean and active.
Meanwhile, let’s figure out the highly actionable idiosyncratic portion.
Here are four reasons BCAAs would raise glucose:
BCAAs all require coenzyme A (CoA) to be metabolized. So does the pyruvate dehydrogenase enzyme. If the BCAA pathways complete themselves, CoA comes and goes. It is used and freed. There is no problem. If they get stuck in the middle, CoA becomes trapped and pyruvate dehydrogenase cannot move forward. Pyruvate rises and spills over into lactate. Glycolysis slows and glucose rises. Glucose, pyruvate, and lactate all rise together.
BCAAs disproportionately funnel into complex II of the mitochondrial respiratory chain, making them somewhat closer to fat and further away from carbs in how they enter the respiratory chain. If the problem was complex II impairment, this would cause reverse electron transport into complex I, elevate the NADH/NAD+ ratio, and elevate lactate without elevating pyruvate. Glycolysis would slow. Glucose and lactate would rise together, but pyruvate would not.
If BCAAs were simply competing with glucose as a source of energy, the ATP yield would slow glycolysis, but there would be no impact on pyruvate or lactate. Glucose would rise alone.
If BCAAs were competing with glucose at the level of acetyl CoA entering the citric acid cycle due to limited supply of oxaloacetate, acetyl CoA would slow pyruvate dehydrogenase and convert itself into ketone bodies. Ketones and glucose would rise, with a lesser rise in pyruvate and lactate.
If oxaloacetate were the limiting factor, leucine would cause more of a problem than isoleucine and valine, since they will generate succinyl CoA, which can become oxaloacetate.
If vitamin B12 were limiting, leucine would cause less of a problem than isoleucine and valine, since only those two amino acids require vitamin B12 in their metabolism.
If potassium or chloride were limiting, isoleucine would cause more of a problem than the other two, because only isoleucine requires potassium and chloride in its metabolism.
All other nutritional cofactors — B1, B2, B3, B5, B6, B7, lipoate, calcium, and magnesium — are shared among the BCAAs.
It would be useful to experiment with isolated amino acid powders from Bulk Supplements to test the above differences.
Glucose taken out of context tells you nothing about why it is high or low, whereas putting it into context by measuring ketones and lactate does help you understand why it is changing.
If home meters could measure pyruvate and acetoacetate in finger-prick blood, we could get even more context.
At least start with what is available.
Measuring glucose out of context continuously just gives you a continuous stream of out-of-context information. So, down with the continuous glucose monitor fad and up with measuring glucose, ketones, and lactate together.
For more information on how to interpret these markers, see Four Markers Every Expert Should, But Doesn’t, Analyze.