Reader Ketotic has drawn me into the forums demanding to know why we should not be in ketosis all the time
Most readers will wonder why anyone would think such a thing, but in a nod to the zero-carbers who have peopled my readership I'll address some of his concerns. Those who are bored with this or who are irritated that the post is not liberally sprinkled with references can skip this.
I think the key issue regarding ketosis and evaluating its pro/cons is the degree of ketosis. We cannot compare ketosis induced by a 4:1:1 KD to ketosis by IF/LCKD. I think we can achieve an optimal degree of ketosis by combining an IF with a VLCD, without necessarily restricting too many food choices. While the glycogen/anaerobic performance/glucocorticoid issue is debatable (I workout at high intensities 2-3/week while on a IF/KD scheme), I have yet to see formal evidence that ketosis is metabolically stressful. When the body enters the least metabolically favorable scenario (starvation) ketosis is developed. It doesn’t make sense that ketosis would be developed to be more stressful. I don’t think that starvation is stressful because of ketosis, either, considering BOHB is the most efficient fuel. Micronutrient deficiency is strongly related with this point, reducing glucose needs also reduces the minimal amount necessary for several micronutrients like thiamin and Vit C.
Based on metabolomics, there is evidence that reducing glycolysis is beneficial. In this scenario, sporadic carbohydrate intake might be hormetic. Relying constantly on glucose (and so on glycolysis) as your main fuel is not optimal. Assuming that ketosis acts via hormesis means that you think that ketosis is stressful. Again, I haven’t seen evidence of this. On the contrary, most evidence shows that dietary glucose produces an inflammatory/immune response.
Finally, ketonuria does not always correlates to ketonemia.
Here are his comments parsed with my responses in roman:
I think the key issue regarding ketosis and evaluating its pro/cons is the degree of ketosis. We cannot compare ketosis induced by a 4:1:1 KD to ketosis by IF/LCKD
KGH: No one I know is measuring serum ketones to define ketosis. I mean ketosis due to VLC or zero carb with ketones in the urine. I do not mean the mild degree that is measurable in the serum on high fat diets with merely relatively low carbs. I am sure you don't mean that either.
I think we can achieve an optimal degree of ketosis by combining an IF with a VLCD, without necessarily restricting too many food choices.
KGH: Why would it be optimal? It might be therapeutic sometimes but there is zero evidence it would be optimal - I think you are theorizing, but making this kind of constraint on your diet should require high confidence and good evidence, not just a more-or-less plausible theory.
While the glycogen/anaerobic performance/glucocorticoid issue is debatable
KGH: It is not too debatable, really. It is reasonably well established.
I have yet to see formal evidence that ketosis is metabolically stressful. When the body enters the least metabolically favorable scenario (starvation) ketosis is developed. It doesnt make sense that ketosis would be developed to be more stressful.
KGH: It is developed to spare our structural proteins and conserve precious glucose for the brain, whether it is "stressful" or not. It certainly involves extra metabolic work. The fact that this happens only when we deprive our bodies of dietary glucose suggests it is stressful. It happens to spare our glycogen - the body is detecting that the glucose reserves are threatened. And it either spares our own muscle or reduces our demand for extra dietary protein to turn into glucose.
I dont think that starvation is stressful because of ketosis, either, considering B-OHB is the most efficient fuel.
KGH: It is only efficient if you think the steps it took to get it don't count.
Micronutrient deficiency is strongly related with this point, reducing glucose needs also reduces the minimal amount necessary for several micronutrients like thiamin and Vit C.
KGH: It is not at all necessary to have ketosis to minimize respiration based on glucose. A merely high fat diet with adequate glucose will do it. And of course as glucose is turned into fatty acids as needed, there is plenty of beta oxidation of fat going on even on a "high carb" diet. Especially when fasting.
Based on metabolomics, there is evidence that reducing glycolisis is beneficial. In this scenario, sporadical carbohydrate intake might be hormetic. Relying constantly on glucose (and so on glycolisis) as your main fuel is not optimal.
KGH: Relying on glucose? Is that what you mean by glycolysis? Glucose is used aerobically for most of the energy extracted (when mitochondria are around) whenever it can be. "Glycolysis" is anaerobic and only happens by itself when speed is necessary - like weight lifting. Do you have an IV drip with glucose going at night? Otherwise when you fast on a diet that has, say, 20% of calories as starch, you are not in ketosis (the way it is typically defined) yet your metabolism is still mostly based on fatty acids. You don't have to be in ketosis to have most of your metabolism based on fatty acids.
Assuming that ketosis acts via hormesis means that you think that ketosis is stressful.
KGH: I did not say it acts via hormesis. I allowed that the benefits may be hormetic in the way that exercise or fasting could be. Depriving your body of a required metabolite and forcing it to adapt to same is pretty much a stress by definition.
Again, I havent seen evidence of this. On the contrary, most evidence shows that dietary glucose produces an inflammatory/immune response.
KGH: No, hyperglycemia may, but dietary glucose does not cause "inflammation" if you are normal. Fructose can be inflammatory, but under normal metabolic circumstances I don't buy that starch is.
Finally, ketonuria does not always correlates to ketonemia.
KGH: Agreed but not my point. Once you are keto-adapted after a few weeks, if you have ketones in the urine it means you are in ketosis enough that you are making more than you burn.
Ketosis is an adaptive state that beats the alternative of glycogen depletion or muscle wasting that it is designed to counter. This makes it "good". In the same way, muscle wasting to keep your brain supplied with glucose is "good". Good in the sense of beating the alternatives. That does not mean we should seek to live continuously in either state, though does it?
For a good discussion of mostly short term adverse effects of ketosis, based on a conversation I had with Peter a while ago, you can go here.
I will allow that there could be theoretical benefits to spending some time in ketosis. And there are therapeutic uses of ketogenic diets for people who are sick. But those who propose that a metabolic state that evolved as a response to a dietary deficiency is per se a desirable state to be in all the time have the burden of proof. This is the same burden of proof faced by those advocating anything that is outside the known evolutionary history of our species.
Synthetic resveratrol, megadoses of fish oil, 10,000 units a day of vitamin D year-round, statins, deriving the majority of your fuel needs from coconut oil, any supplement to a real food diet - for all of these things the advocates have the burden of proof.
So, once more for emphasis. Ketosis* can be useful therapeutic maneuver, but there is no evidence using current knowledge of metabolism or evolutionary reasoning that we should strive to be in this atypical state all the time.
* I define Ketosis in the usual paleosphere way. Eating a low enough digestible carbohydrate intake to induce serum levels of ketones much higher than those eating a carbohydrate replete diet. This will usually be a carbohydrate intake below the amount that would be necessary to run your brain on nothing but glucose, but still higher than the basal glucose requirement of the brain once keto-adapted, where the brain is running as much as half on ketones. We usually use ketones in the urine (ketonuria) as evidence of ketosis, but this is not 100% reliable, as the rate they are burned influences how many are spilled into the urine. The carbohydrate amount necessary to keep out of significant ketosis varies, but Kwasniewski uses 10% of kcal, and Lutz uses 70 g/day which is roughly the same if you are 2800 kcal/day but more if you eat less. Bernstein uses 30g/day for his diabetes diet, but this is meant to ensure micronutrient intake from non-starchy veggies and will not keep you out of ketosis.