I’ve spent some time lately analysing these 1100 ketone vs glucose data points looking for the secret to achieving optimal ketone values for weight loss and health.
As you can see from this chart, there is a relationship between ketones and glucose. As your blood glucose levels decrease your blood ketones rise to compensate.
Different glucose : ketone relationships for different people
It seems that each person has a unique relationship between their blood glucose and ketone values that gives us an insight to understand their insulin resistance status and metabolic health.
Characterisation of different metabolic states
Similar to Dr Kraft’s insulin curves, we can characterise different levels of insulin resistance metabolic health using the relationship between glucose and ketones.
If you want to know why hyperinsulinemia is the “unifying theory of chronic disease” it’s worth taking the time to read up on it to provide some more context for the discussion later in this article.     
Type 2 Diabetes
If you have type 2 diabetes and your blood glucose levels are consistently high, you are not metabolising carbohydrates well, and will likely benefit from a lower insulin load dietary approach.
When you go a long time between meals, your ketones don’t kick in because of high insulin levels and / or your mitochondria are not functioning optimally. You feel tired and hangry.
Particularly in the early stages when someone is still insulin resistant, a lower insulin load dietary approach will help with satiety and carb cravings while keeping blood glucose levels under control.
Hyperinsulinemia and metabolic disorders
If your blood glucose levels are very low and ketone levels are also very low, you may have an infection or a metabolic disorder that is stopping you from producing enough energy.
The yellow line in the chart above is based on an actual person who is suffering from a range of metabolic related issues including obesity, PCOS, depression, etc. For these people, EXOGENOUS ketones may help to relieve the debilitating symptoms of acute Hyperinsulinemia.
Exciting research is currently underway looking at the use of EXOGENOUS ketones as an adjunct treatment for cancer or to provide energy directly to the mitochondria for people with epilepsy, dementia, Alzheimer’s and the like. 
Patrick Arnold, who worked with Dr Dominic D’Agostino to develop the first ketone esters and BHB salts, has noted that exogenous ketones may help alleviate the symptoms of the ‘keto flu’ during the transition from a high carb to a low carb dietary approach.
However, as noted by Robb Wolf, once you have successfully transitioned to a lower carb eating style you would need to reduce or eliminate the exogenous ketones to enable your body to fully up-regulate lipolysis (fat burning), maximise ENDOGENOUS ketone production and access your ENDOGENOUS FAT stores.
Someone with diabetes who persists with a nutrient dense low insulin load dietary approach may be able to successfully normalise their blood glucose and insulin levels. When this happens your body will be able to more easily release ENDOGENOUS ketones which will help improve satiety between meals, and decrease appetite which will in turn lead to weight loss. Exercising to train your body to do more with less is also helpful.
If you are insulin resistant you are probably not able to metabolise carbohydrates, protein or fats very well. The light blue “mild insulin resistance” line is based on my ketone and glucose values when I started trying to wrap my head around this ketosis thing.
I enthusiastically started adding unrestricted amounts of fat from all the yummy stuff (cheese, butter, cream, peanut butter, BPC etc) in the hope of achieving higher ketone levels and therefore weight loss, but I just got fatter and more inflamed as you can see in the photo on the left. My blood tests suggested I was developing fatty liver in my mid 30s! And I thought I was doing it right with the bacon and BPC?!?!?
The photo on the right is after I worked out how to decrease the insulin load of my diet and learning about intermittent fasting from Jason Fung. I realised that ENDOGENOUS ketosis and weight loss is caused by a lower dietary insulin load, not more EXOGENOUS fat on your plate or in your coffee cup.
I recently had my HbA1c tested at 4.9%. It’s getting there. But knowing what I know now about the importance of glucose control, I would love to lose a bit more weight and see my HbA1c even lower.
This metabolic jet fuel is definitely fascinating stuff! My experience is that it gives me the buzz like a BPC, but also has an acute diuretic effect (meaning I need to stay close to a toilet and long drives to work in slow traffic were sometimes humiliating).
I had hoped it would have a weight loss effect like some people seemed to be saying it would.
I did find it had an amazing impact on my appetite. While it was in my system I didn’t care as much about food. However once the ketones were used up my appetite came flooding back. It was like I had ‘bonked’ all of a sudden and needed LOTS OF FOOD NOW!
Unfortunately my hunger and subsequent binge eating seemed to offset the short term appetite suppression. And it was not going to be financially viable for me to maintain a constant level of artificially elevated ketone levels.
I asked around to see if anyone had come across studies demonstrating long term weight loss effects of exogenous ketones. It was a VERY enlightening discussion if you want to check it out here. Wow!
The Pruvit FAQ says that one of the benefits of Keto//OS is weight loss, however no reference to the research studies was provided to Pruve this claim.
Also, the studies that were referenced in the Pruvit FAQ all appear to relate to the benefits of ENDOGENOUS or nutritional ketosis rather than EXOGENOUS ketone supplementation.
According to a Pruvit tele-seminar the EXOGENOUS ketone salts were not designed to be a weight loss product and hence have not been studied for weight loss.
The only studies that we could find that mentioned EXOGENOUS ketone supplementation and weight loss were on rats an they found that there was no long term effect on weight loss.
So in spite of my hopeful $250 outlay it seems that exogenous ketones ARE just a fuel source after all.
Even the experts don’t seem to think exogenous ketones help with fat loss.
Confused yet? I don’t blame you.
The “metabolically healthy” line in the chart above is based on RD Dike man’s ketone and glucose data when he recently did a 21 day fast.
Due to his hard earned metabolic health and improved insulin resistance he has developed the ability to fairly easily release ketones when goes longer periods between meals.
RD has achieved a spectacular HbA1c of 4.4%. Perhaps a two or three day water only fast testing blood glucose and ketones with no exercise would be a useful test of your insulin status? You could use RD’s line as the gold standard.
In spite of his improvement in insulin resistance and blood glucose control, he still says the “siren” of hunger is incredibility difficult to resist and mastering appetite is more challenging than particle physics. As a Chief Scientist at Lockheed Martin, he would know.
RD also told me that when he is not fasting and is eating his regular nutrient dense higher protein meals his ketone levels are not particularly high. While RD fairly easily produces ketones, it seems they are also quickly metabolised so they do not build up in his bloodstream.
I know Luis Villasenor of Ketogains finds the same thing.
Total energy = ketones + glucose
Where this gets even more interesting is when we look at the glucose and ketone data in terms of TOTAL ENERGY. That is, from both glucose and ketones.
The average TOTAL ENERGY of the 1100 data points from these 26 fairly healthy people working hard to achieve nutritional ketosis is 6.1mmol/L. It seems the body works to maintain homeostasis around this level.
When the TOTAL ENERGY in our bloodstream increases outside of the normal range it appears the body raises insulin to store the excess energy. That is, unless you have untreated Type 1 Diabetes, in which case you end up in diabetic ketoacidosis with high blood glucose and high ketones.
Regardless of whether your energy takes the form of glucose, ketones or free fatty acids they all contribute to acetyl-coA which is oxidized to produce energy. Forcing excess unused energy to build up in the bloodstream is typically not desirable and can lead to long term issues (gyration, oxidized LDL etc).
I’m not sure if ketones can be converted to glucose or body fat, but it makes sense that excess glucose would be converted to body fat via de novo lip genesis to decrease the TOTAL ENERGY in the blood stream to normal levels.
A number of studies seem to support this view including Roger Unger’s 1964 paper the Hypoglycemic Action of Ketones. Evidence for a Stimulatory Feedback of Ketones on the Pancreatic Beta Cells.
Ketone bodies have effects on insulin and glucagon secretions that potentially contribute to the control of the rate of their own formation because of antilipolytic and lipolytic hormones, respectively. Ketones also have a direct inhibitory effect on lipolysis in adipose tissue.
Looking at the glucose and ketones together in terms of TOTAL ENERGY was a bit of an ‘ah ha’ moment for me. It helped me to understand why people like Seyfried and D’Agostino always talk about the therapeutic benefits and the insulin lowering effects of a calorie restricted ketogenic diet.    
Dealing with high ketones and high glucose typically a concern fro the body because it just doesn’t happen in nature with real whole foods. But now we have refined grains, HFCS, processed fats and exogenous ketones to ‘bio-hack’ our metabolism and send it into overdrive.
While fat doesn’t normally trigger an insulin response, it seems that excess unused energy in the blood stream, regardless of the source, will trigger an increase in insulin to reduce the TOTAL ENERGY in the blood stream.
I am concerned that if people continue to enthusiastically zealously focus on pursuing higher blood ketones “through whatever means you can” in an effort to amplify fat loss they will promote excess energy in the bloodstream which will lead to insulin resistance and hyperinsulinemia.
Using multi-level marketing tactics to distribute therapeutic supplements to the uneducated masses who are desperate to lose weight with a ‘more is better’ approach also troubles me deeply.
My heart sank when I saw this video.
MORE investigation required?
There are anecdotal reports that use of exogenous ketones provide mental clarity, enhanced focus and athletic performance benefits. At the same time there are also people who have been taking these products for a while that don’t appear to be doing so well.
A July 2016 study Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? didn’t find that EXOGENOUS ketones were very exciting.
Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes’ performance under conditions where evidence-based nutritional strategies are applied appropriately.
Another study by Veech et al (who is trying to bring his own ketone ester to market) from August 2016 Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes found in favour of ketones.
Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.
I can understand how exogenous ketones could be beneficial for someone who is metabolically healthy and consuming a disciplined hypo-caloric nutrient dense diet. They would likely be able to auto regulate their appetite to easily offset the energy from the EXOGENOUS ketones with less food intake.
While it seems that EXOGENOUS ketones assist in relieving the symptoms of metabolic disorders I’m yet to be convinced that a someone who is obese and / or has Type 2 Diabetes would do as well in the long term, especially if they were hammering MOAR fat and MORE exogenous ketones (along with maybe some sneaky processed carbs on the side) in an effort to get their blood ketones as higher in the hope of losing body fat.
Some questions that I couldn’t find addressed in the Pruvit FAQ that I think would be interesting to study in a long term controlled environment in the in the future are:
- What is the a safe dose limit of EXOGENOUS ketones for a young child? How would you adjust their maximum intake based on age and weight?
- IF EXOGENOUS ketones do have a long term weight loss effect what is the upper limit of intake of EXOGENOUS ketones to avoid stunting a child’s growth?
- Is there a difference in the way EXOGENOUS ketones are processed in someone is metabolically healthy versus someone who is very insulin resistant?
- Does the affect on appetite continue beyond the point that the ketones are out of your system?
- Do you need to take EXOGENOUS ketones continuously to maintain appetite suppression? Does the effect of ENDOGENOUS wear off as your own ENDOGENOUS ketone production down regulates? Do you need to keep taking more and more EXOGENOUS ketones to maintain healthy appetite control?
- How should someone with Type 2 Diabetes adjust their medication and insulin dose based on their dose of EXOGENOUS ketones? Should they be under medical supervision during this period?
- Is there a difference in health outcome if you are taking EXOGENOUS ketones in the context of a hypo-caloric ketogenic diet versus a hyper-caloric ketogenic diet? What about a diet high in processed carbs?
- Is there a minimum effective dose to achieve optimal long term benefits to your metabolic health or is MORE better?
- Are the long term health benefits of EXOGENOUS ketones equivalent to a calorie restricted ketogenic diet?
Unfortunately, I think we will find the answers to these questions sooner rather than later with the large scale experiment that now seems to be well underway.
Perhaps the burden of proof is actually on Pruvit to prove it rather getting their Pruvers to demonstrate that within 59 minutes they are successfully peeing out the product they’ve just paid some serious money for!
The lower the better?
Alessandro Ferretti recently made the observation that metabolically healthy people tend to have lower TOTAL ENERGY levels at rest (and hence have a lower HbA1c), but are able to quickly mobilise glycogen and fat easily when required (e.g. when fasting or a sprint). They are metabolically flexible and metabolically efficient.
These people would have been able to both conserve energy during a famine and run away from a tiger and live to become our ancestors, while the ones who couldn’t didn’t.
Similar to RD Dikeman, John Halloran is an interesting case. Recently he has been putting a lot of effort into eating nutrient dense foods, intermittent fasting and high intensity exercise.
He is also committed to improving his metabolic fitness to be more competitive in ice hockey. His resting heart rate is now a spectacular 45 bpm!
And he’s been able to lose 10kg (22lb) during July 2016!
At 5.2mmol/L (i.e. glucose of 4.0mmol/L plus ketones of 1.2mmol/L) John’s TOTAL ENERGY is lower than the average of the 26 people shown in the glucose + ketone chart above. Looking good John!
It seems excellent metabolic health is actually characterised by lower TOTAL ENERGY.
MORE is not necessarily BETTER when it comes to health.
Fast well, feed well
To clean up the data a little I removed the ketones vs glucose data points for a couple of people who I thought might be suffering from pancreatic beta cell burnout and one person that was taking exogenous ketones during their fast that had a higher TOTAL ENERGY. I also removed the top 30% of points that I thought were likely high due to measuring after high fat meals.
So now the chart below represents the glucose and ketone values for a group of reasonably metabolically healthy people following a strict ketogenic dietary approach, excluding for the effect of high fat meals, BPC, fat bombs and the like.
The average ketone value for this group of healthy people trying to live a ketogenic lifestyle is 0.7mmol/L. Their average glucose is 4.8mmol/L (or 87mg/dL). The average TOTAL ENERGY is 5.5mmol/L or 99mg/dL.
blood glucose (mmol/L)
total energy (mmol/L)
The table below shows this in US units (mg/dL).
It seems we may not necessarily see really high ketone levels in our blood even if we follow a strict ketogenic diet, particularly if we are metabolically healthy and our body is using to ketones efficiently.
The real ketone magic
When we deplete glucose we train our body to produce ketones.
This is where autophagy, increased NAD+ and SIRT1 kicks in to trigger mitochondrial biogenesis and ENDOGENOUS ketone production (i.e. the free ones). The REAL magic of ketosis happens when all these things happen and ketones are release as a byproduct. I do not believe that simply adding EXOGENOUS ketones will have nearly as much benefit to your mitochondria, metabolism and insulin resistance as training your body to produce ENDOGENOUS ketones in a low energy state.
Everything improves when we train our bodies to do more with less (e.g. fasting, high intensity exercise, or even better fasted HIIT). Resistance to insulin will improve as your insulin receptors are no longer drowning in insulin caused by high TOTAL ENERGY building up in your bloodstream.
Driving up ketones artificially through EXOGENOUS inputs (treating the symptom) does NOT lead to increased metabolic health and mitochondrial biogenesis (cure) particularly if you are driving them higher than normal levels and not using them up with activity.
You may be able to artificially mimic the buzz that you would get when the body produces ketones ENDOGENOUSLY, however it seems you may just be driving insulin resistance and hyperinsulinemia if you follow a “MORE is better” approach.
Simply managing symptoms with patented products for profit without addressing the underlying cause often doesn’t end well.
Just like having low blood glucose is not necessarily good if it is primarily caused by high levels of EXOGENOUS insulin couple with a poor diet, or having lower cholesterol due to statins, having high blood ketone values is not necessarily a good thing if it is achieved it by driving up the TOTAL ENERGY in your blood stream with high levels of purified fat and EXOGENOUS ketones.
When we feed our body with quality nutrients we maximise ATP production which will make us feel energised and satisfied. Nutrient dense foods will nourish our mitochondria and reduce our drive to keep on seeking out nutrients from more food. Greater metabolic efficiency will lead to higher satiety, which leads to less food intake, which leads to a lower TOTAL ENERGY, greater mitochondrial biogenesis, improved insulin sensitivity and lower blood glucose levels.
Prioritising nutrient dense real food is even more important in a ketogenic context. While we can always take supplements, separating nutrients from our energy source is never a great idea, whether it be soda, processed grains, sugar, glucose gels, HFCS, protein powders, processed oils or exogenous ketones.
Based on my analysis of nutrient density I don’t think you should be trying to avoid protein and carbohydrates in the pursuit of higher ketone levels unless you have a legitimate medical reason for perusing therapeutic ketosis (e.g. cancer, Alzheimer’s, epilepsy, dementia etc).
I believe the best approach is to maximise nutrient density as much as possible while working within the limits of your metabolic health and your pancreas’ ability to maintain normal blood glucose levels.
If your goal is metabolic health, weight loss and improving your ability to produce ENDOGENOUS ketones, then developing a practice of FEASTING and FASTING is important.
To start out, experiment by extending your fasting periods until your TOTAL ENERGY is decreasing over time. This will cause your circulating insulin levels to decrease which will force your body to produce ENDOGENOUS ketones from your ENDOGENOUS fat stores.
Check out the how to use your glucose meter as a fuel gauge article or Jason Fung’s Intensive Dietary Management blog for some more ideas on how to get started with fasting. Rebecca Skvorc Latham has also developed a fasting protocol using weight to guide your eating schedule if your primary goal is weight loss rather than blood glucose control.
If you really want to measure something, see how low you can get your glucose levels before your next meal. Then when you do eat, make sure you choose the most nutrient dense foods you possibly can to build your metabolic machinery and give your mitochondria the best chance of supporting a vibrant, active and happy life.
As my wise friend Raymund Edwards keeps reminding me, FAST WELL, FEED WELL.
Like most people dabbling in this low carb thing, I’m still on a journey.
I’d love to be able to share shirtless photos like Ted and Dom but I’m still working to overcome my own genetic propensity for diabetes, obesity, Alzheimer’s and Parkinson’s. I’m still learning and working out how to apply these things in my own life.
Although I do sometimes check blood glucose levels before meals to see how I’m tracking I haven’t been testing ketones much for a year or so after I realised chasing high ketones with more dietary fat wasn’t helping me lose weight.
However after writing this article using other peoples’ data, I was intrigued to see how my ketones were travelling.
This was mid-morning after a kettlebell session.
I was able to get my heart rate up to 190 bpm which is my highest ever! My daughter joined me today so there was some downtime between sets. Usually I do an exercise until my heart rate gets up to at least 170 bpm. I then stop and wait until it drops back down to 140 bpm and then go again.
My aim is to train my mitochondria to pump out more power with less energy (i.e. fasted) to improve insulin sensitivity as well as mitochondrial efficiency and drive mitochondrial bio-genesis.
You can get a lot of work done in an intense 25 to 30-minute session with these weapons of torture that I keep downstairs in my garage (although I don’t think it really matters what you do as long as you push your body to do more with less).
My appetite today was great so I didn’t feel the need to eat until I had dinner with my family.
Previously I would have not been happy with these ketone readings and would have wanted to drive my ketones higher to get into the ‘optimal ketone zone’. I would have wondered “Maybe I should have eaten some MORE butter or had a BPC to drive ketones higher to facilitate fat loss?”
But given I’d still like to lose some more body fat I’m pretty happy with these numbers.
- My total energy is low (4.5mmol/L and 5.1mmol/L). Check.
- Ketones are present but not too high which means I’m able to mobilise fat but not building it up in my bloodstream. Check.
- Blood glucose is low. Check.
All good! Feeling crisp, happy and vibrant thanks to ENDOGENOUS ketones!
(Sorry. I can’t sell you mine. You’ll have to make your own.)