Ketogenesis and blood glucose

It is explained everywhere that the creation of ketones (ketogenesis) is done by the liver, converting fat in ketone bodies such as beta-hydroxybutyrate (BHB). Yet when measuring ketones, after being on the ketogenic diet for a longer period, people struggle with this concept when they measure low ketones.

People who have been on a ketogenic diet for a while tend to measure lower ketones. The high values they measured at the beginning ranged somewhere around or above 2 mmol easily and the longer they are on this diet, the measured values hardly reach 1 mmol with only exceptionally a higher value but never as high as before where values above 3 or 4 were less exceptional. There are exceptions to this which I’ll briefly mention at the end.

The lower measurement results are often explained as the body being more adept at utilizing ketones.

I have previously written about this before with a focus on fat mass in conjunction with metabolism and how that relates to ketogenesis but want to explore it a bit further with some more material related to glucose.

Previous post: https://www.reddit.com/r/ketoscience/comments/blbkzj/lean_keto_people_have_low_ketone_production/

Why glucose? Because BHB, the ketone we are measuring in our blood, has a suppressive effect on plasma glucose. So by looking at how much it is able to suppress glucose we can also obtain an idea of how much BHB we are producing and see if that is in line with an effect on glucose. Meaning that if we measure low BHB but have high BHB production, explained by better utilization, then we should still see the glucose lowering effect.

“Suppression of glucose production and stimulation of insulin secretion by physiological concentrations of ketone bodies in man”, Miles JM, Haymond MW, Gerich JE, 1981, https://www.ncbi.nlm.nih.gov/pubmed/7005257

The reason why BHB would be pressing down on glucose can be found in the pH of the blood. The ketone bodies Acetoacetate and BHB are acidic. If we would not press down on glucose, then glucose is utilized as a fuel resulting in increased CO2 production. The addition of CO2 would further lower the pH while, with BHB we are already on the borderline. See my previous posts on the topic of CO2 for more info.

Previous: https://designedbynature.design.blog/2019/12/12/ketones-and-oxygen/

BHB trend over time

First lets review again how BHB averages over time. The Virta health study, to help people controle their Type 2 Diabetes (T2D), included regular measurement of BHB. The result of it are shown in the picture below. One thing to keep in mind here is that people are T2D so they already started with elevated insulin and also gradually went off their insulin medication. Insulin prevents BHB production. This means we won’t see high BHB values at the beginning but towards the end we have less people on insulin meds and having better control over their own insulin production.

Fig. 4
source: https://rd.springer.com/article/10.1007%2Fs13300-018-0373-9

A lot can be said about the reasons why the trend goes down such as non adherence by carb creap etc but my argument is about total fat availability. This is the combination of both your own body fat and dietary fat that is able to reach your liver (while being low on glucose). The study also shows weight trend over time.

source: https://rd.springer.com/article/10.1007%2Fs13300-018-0373-9

Note that the weight change above is expressed in percentage, not in kg.

Another example is of an individual who has been tracking his BHB over a long time. This person is not a diabetic and considered a normal healthy person. He is of course an individual so not a scientific study but I’m just using his data to explain the general concept.

Don’t mind the trend line. As you can see here we have the same high values at the beginning with a downward trend. Let’s have a look at how that lines up with the blood glucose. Both solid lines are trend lines, 4 measure points average centered. For reference, the horizontal line at the level of the 70 (on the left) corresponds to 1.2 mmol BHB.

You can already see it instinctively but I’ve mapped that to a Pearson correlation, for factual data, where zero means there is no correlation and 1 means they are fully correlated. The first, big, circle on the left is what matches below with Part 1. Part 2 is everything else behind it.

Part 1 – Pearson correlation coefficient: -0.72

Part 2 – Pearson correlation coefficient: -0.509

As you can see, when we have higher levels of BHB, the suppressive effect on glucose is much stronger giving us a better correlation. The 2 other circles show this as well. Just by looking at the graph itself you can’t state that correlation but the point of those 2 markers is that we don’t see blood glucose going up. We should find a case where high BHB is matched with increasing blood glucose.

BHB is of course not the only thing that controls blood glucose but a high level does give it more weight in the final result of your blood glucose.

Exceptions

At the beginning I mentioned about exceptions when it comes to the correlation with fat mass. Some people may find that they easily get into the higher numbers despite being lean. As far as I can tell, this has to do with your personal rate at which you can free up fat from your adipose.

For me personally, one of those influencing components is the level of gene expression of IL-6. During exercise and in general during inflammation, this cytokine will signal to the adipose to release fatty acids. My genes will result in less IL-6 production.

IL-6 is not the only thing that frees up fatty acids but that goes beyond the point of this post.

Finally

The point I was trying to make, in addition to the data in my previous post, is that by looking at your glucose levels you can understand if you are producing high or low levels of ketones. When you are out of ketosis yet eat a low carb high fat style diet, you’ll notice a fairly stable blood glucose, always hovering around the same value. Whenever you notice a significantly lower blood glucose value you can assume a high enough ketone production in the range of >1 mmol.

You can of course have deviating numbers such as shortly after exercise where you still have an elevated glucose but already produce higher ketones thanks to the circulating fat so keep in mind when you measure and under what conditions.

Make sure it is a situation that resembles what you will experience most of the time. This is your fasted state so for example if you eat breakfast and skip lunch then measure right before dinner. If you skip breakfast then measure right before lunch etc.. Then you can see how your ketones relate to the time since your last meal. A normal meal will always create a drop in ketones.

If you want to be in ketosis or not is up to you but consider measuring <1 mmol (as a general reference!) that you are indeed not producing as much ketones.

The End

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