Ketones and oxygen

If you have read my previous work regarding oxygen and carbon dioxide (CO2) you probably would expect, as I did, that on keto your oxygen saturation in the blood would be huncky dory. But it was not as expected to be 98% or 99%. Instead it is hovering around 96%. Yes there is a certain margin of error on these devices (pulse oximeter). So what is that all about? My wife measures 98%, not in ketosis so I decided to dig into it to understand what is going on.

Previous writings:

Actually after investigating and writing about all this stuff it made it easier to find out.

First we get back to basics and that is the oxygen dissociation curve.

The graph plots percent oxygen saturation of hemoglobin as a function of oxygen partial pressure. Oxygen saturation increases in an S-shaped curve, from 0 to 100 percent. The curve shifts to the left under conditions of low carbon dioxide, high pH, and low temperature, and to the right in conditions of high carbon dioxide, low pH, or high temperature.
source: https://openstax.org/books/biology-ap-courses/pages/30-4-transport-of-gases-in-human-bodily-fluids

For the same partial pressure of oxygen (x-axis) in the blood, a lower pH will cause a drop in haemoglobin oxygen saturation (y-axis). There are other factors such as 2,3 DPG content and temperature but our focus will be on pH for now.

Why zoom in on pH? Because the ketone bodies Acetoacetate (AcAc) and beta-hydroxybutyrate (BHB) are acidic bodies with AcAc having a 3.59 pKa and BHB with a pKa of 4.41. In comparison, lactic acid falls in between with a pKa of 3.86 and stomach acid (HCl) has a pKa of around – (sources vary) so the lower the pKa the more acidic. The ketone bodies are considered weak acids. We’re also interested in carbon dioxide or CO2 (? pKa) which react with water or H2O (15.7 pKa) to form carbonic acid or H2CO3 (6.1 pKa) which then further reacts to bicarbonate or HCO3 (10.3 pKa) by shedding hydrogen (-1.74 pKA) which further decreases the pH. They are all taking part in the system. (some more pKa’s for reference)

To give you a bit of an idea of the quantities of H2CO3 and HCO3, this graph shows you their balance across the pH range. Just keep in mind our ideal range is 7.35~7.45.

source: http://ion.chem.usu.edu/~sbialkow/Classes/3650/Carbonate/Carbonic%20Acid.html

OK, so they are acidic and that could cause a lowering of the pH and could explain the lowered oxygen saturation. Not so fast… we need evidence. Let’s look at some trials that recorded values for ketones and pH together.

The following first paper shows us that ketones do have an effect on the pH, although very mild.

Acetone is a neutral compound, and, unlike AcAc and 3-OHB, it does not affect blood bicarbonate concentration, arterial blood gases or pH (Sulway and Malins, 1970)

However, after a few days of starvation a new steady state develops, and the arterial pH stabilizes at about 7.35 (Reidenberg et al, 1966)

“Ketosis of starvation: a revisit and new perspectives.”, Owen OE, Caprio S, Reichard GA Jr, Mozzoli MA, Boden G, Owen RS, 1983, https://www.ncbi.nlm.nih.gov/pubmed/6347450 ; https://sci-hub.tw/10.1016/S0300-595X(83)80046-2

After a few days of fasting, we see in this publication that BHB has reached a level of about 1.5 mmol to only go up further after that. Interesting is that the pH is re-positioning itself at 7.35. There was no comment on what the original pH was. In any case 7.35 is at the bottom of the range which is considered OK. The body tries to keep it tightly within 7.35 to 7.45. Below 7.35 you are considered to be in acidosis but this is of course not a binary thing.

The next paper states a definition of metabolic acidosis. Useful to see if we can notice similar changes under ketosis (but in a more subtle form).

Clinically, metabolic acidosis is characterized by a decrease in serum HCO3– levels, accompanied by an increased arterial partial pressure of carbon dioxide (PaCO2) and pH of blood.

https://journals.lww.com/md-journal/Fulltext/2019/10110/Preoperative_prolonged_fasting_causes_severe.24.aspx

There isn’t that much data available but here’s a nice one that looked at exogenous ketones. The study compared ketone esters and ketone salts but we only want to focus on the esters because salts influence the pH as you can see in the graphs below.

When we administer ketone esters, we see a drop in pH and bicarbonate. Surely the time frame is short so we can’t say much about it long term but it is clear what effect there is with ketones. The pH even drops below the ideal value to stabilize at 7.35. The same value as observed under starvation. By the 2 hour mark we still have a value around 1.3 mmol


“On the Metabolism of Exogenous Ketones in Humans”, Brianna J. Stubbs, Pete J. Cox, Rhys D. Evans, Peter Santer, Jack J. Miller, Olivia K. Faull, Snapper Magor-Elliott, Satoshi Hiyama, Matthew Stirling, and Kieran Clarke, 2017, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5670148/

So we saw the natural production of ketones under starvation and here supplemental ketones. I also found an infusion of ketones. Unfortunately it was in a salt solution which increased the pH so effects cannot be derived to understand endogenous production. I’ll leave the reference because it is an interesting read anyway.

“Ketone Body Infusion With 3‐Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study”, Lars C. Gormsen, Mads Svart, Henrik Holm Thomsen, Esben Søndergaard, Mikkel H. Vendelbo, Nana Christensen, Lars Poulsen Tolbod, Hendrik Johannes Harms, Roni Nielsen, Henrik Wiggers, Niels Jessen, Jakob Hansen, Hans Erik Bøtker, and Niels Møller, 2017, https://www.ahajournals.org/doi/10.1161/JAHA.116.005066

The following paper makes reference to lower pH

Most research projects indicate a tendency towards lower blood pH and reduced blood base excess and bicarbonate levels after a ketogenic diet at rest; and especially after exercise with maximal intensity [34]

“The effects of a ketogenic diet on exercise metabolism and physical performance in off-road cyclists.”, Zajac A, Poprzecki S, Maszczyk A, Czuba M, Michalczyk M, Zydek G, 2014, https://www.ncbi.nlm.nih.gov/pubmed/24979615 ; https://mdpi.com/2072-6643/6/7/2493/pdf

I followed the reference but was unable to obtain full access. The abstract talks about post-exercise lower pH values and bicarbonate. They did report about 2 mmol post-exercise and stated 0.8mmol 1 hour after exercise so it looks like the post-exercise is a couple of hours after exercise.

OK now what does it all mean?

So the point is that being in ketosis presses down on the pH, give or take around 7.35. If you went through my previous write-ups (see links at the top) then you would understand that I derive a bad effect from the lowered pH due to CO2 production by glucose metabolism. My main interest is the tissue oxygen which, under insufficient oxygen, leads to diseases.

Under ketosis, I speculate, that due to the pressing effect on pH, there is a slight shift in the oxygen dissociation curve. The slightly lower pH also causes a bit less affinity for oxygen making it easier to release. There is however a difference with how CO2 affects this, namely that there is a lower production of tissue CO2 (!). So my theory is that we get better oxygenation in the tissue due to being in ketosis.

It’s a long shot given the little data but it would make sense as well because the oxygen is needed for fat metabolism. You certainly need that extra oxygen when exercising as a fat-adapted athlete but you also benefit from from that effect at rest. If I’m right, this is a very important factor in preventing chronic diseases. This could have direct implications for Alzheimer’s, cancer, CVD, COPD etc. These diseases are referenced in those write-ups at the top.

Next up I will write about how I further try to increase tissue oxygenation besides being in ketosis so stay tuned. You can also subscribe to get notified about new posts.

I would also want to invite you to leave a comment if you like it, if you don’t agree with some of the things I wrote etc.. There is so much information I’m sure I always miss out on something important.

Further reading:

“Carbon dioxide transport”, GJ Arthurs, M Sudhakar, https://watermark.silverchair.com/mki050.pdf

6 thoughts on “Ketones and oxygen

  1. You could be right about the better tissue oxygenation thing. I started eating a ketogenic diet because, due to severe emphysema, I had problems with too high CO2 levels after exercising moderately for more than a few minutes even while keeping O2 sat levels around 88%. Hypercapnia sucks monkey ass: headache, confusion, dizziness etc.
    I’ve noticed that now I’m fat-adapted I can exercise more intensely and keep my heart rate at what my Fitbit calls ‘cardio’ levels (120-140 ish) for MUCH longer while still keeping O2 sat levels relatively high (again 88-ish %).
    Of course this might also be caused by my lungs being able to absorb oxygen more easily, ketones are reported to be anti-inflammatory after all. Also, I’ve never eaten this amount of vegetables in my life before which could conceivably also play a role

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    1. Great to hear it improves for you. Then you’ll be interested in my next post where I will explain the breathing exercise I’m doing and what markers it changes, all for the good of tissue oxygenation 😉

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    2. Yes, ketogenic. Used to sti around 98-99%. Now it’s 89-94%. Exercise heavy and no shortness of breath. If others find information, pls post. I’ve searched google scholar with no luck.

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