Category Archives: exogenous ketones

Is the acetone:glucose ratio the Holy Grail of tracking optimal ketosis?

Key points

  • The real magic of ketosis seems to occur in a lower energy state.
  • High levels of beta-hydroxybutyrate ketones (BHB) can be a good sign, particularly with lower blood glucose levels.
  • Unfortunately, forcing in extra energy in the pursuit of higher BHB levels (e.g. exogenous ketones or refined fat) has the potential to drive higher insulin and insulin resistance.
  • As we lose weight, improve our metabolic health and stop over fueling, many people start to see lower levels of BHB.
  • While it can be used as an alternative to glucose in the brain, BHB needs to be converted to acetoacetate to be used by the body.
  • If you are making and using ketones without consuming excessive energy you will likely see lower blood glucose, higher breath acetone and lower BHB levels.
  • The ratio between breath acetone and glucose can be a useful indicator of genuine nutritional ketosis and a healthy metabolism.


In previous articles we’ve looked at why chasing higher blood ketones with more dietary fat or exogenous ketones might not be smart.[1] [2]

We also looked briefly at the glucose:ketone ratio as a useful parameter to track therapeutic ketosis.[3] [4]

This article looks at the ratio between acetone (a form of ketones that can be measured on your breath) and your blood glucose.

It appears that this ratio may be helpful if you require therapeutic ketosis (e.g. to manage cancer, epilepsy, Parkinson, Alzheimers, dementia etc) or to optimise your metabolic health for weight loss, general health or longevity.

We crunch the numbers to see how you can use breath acetone to help you optimise your metabolic health.

[TL;DR…  Higher breath acetone with lower blood glucose seems to be a good place to be.  Breath acetone is potentially more useful than monitoring BHB in the blood.]

What is ketosis?

Ketosis is trending hard at the moment.


But what is it?

And do you really need more of it?

Some people think that we need to be “in ketosis” to burn fat.  Hence, many people think that more ketosis is better, especially if you have body fat you want to burn.

While this message helps sell keto-related products, it’s technically not correct.

Ketosis is an alternative metabolic pathway that our body uses when there is not enough oxaloacetate in our diet (from carbs or protein) to burn fat via the Krebs cycle.  When this occurs, fat that can’t be oxidised in the Krebs cycle is oxidised via ketosis.


This is a “sliding scale” sort of thing.  People following a typical western diet will have lower levels of blood ketones (e.g. 0.1 or 0.2 mmol/L),[5] while people eating more fat and less carbs may have higher levels.

The fact that we can use this backup metabolic pathway has helped us survive many a famine to procreate another day.

Ketosis is a critical component of our metabolism and our survival as a species.

Are ketones magical?

Our understanding ketones and ketosis is evolving fast.

Some people believe that ketones have unique and special signalling properties.[6] [7]  While others feel that these beneficial properties of ketosis are limited to endogenous ketosis (i.e. when we predominantly burn stored body fat).[8]

When our energy levels are low, we also see an upregulation of mitochondrial biogenesis, sirtuins, autophagy and NAD+ which are also highly beneficial.

But perhaps it’s actually all of these things working together that causes the benefits that many people associate with “being in ketosis”, not just the ketones themselves.

When energy levels are low, our body goes into repair mode to ensure survival and we switch over to burn body fat.  Our blood ketones rise significantly after a few days without food.

The chart below shows about three thousand data points from people following a low carbohydrate or ketogenic diet measuring blood ketones and blood glucose at the same time.  Blood ketones (shown in blue) are not necessarily high for most people while they are eating normally, even if blood sugar levels are low (shown as orange).


We can drive high blood ketones by taking exogenous ketones and/or lots of refined fat (the right-hand end of this chart).  But, unless you’re about to do some explosive exercise to burn off all this energy, this over fueling may not be optimal.

Oxidative priority

Our appetite does an excellent job of making sure we get the fuel if it’s available.  Our metabolism is pretty good at balancing the different fuel sources based on inputs and demand.

While our bodies are adapted to deal with a range of fuel sources, it struggles to deal with too much energy for a long time.

The chart below (from a paper by Ray Cronise, David Sinclair and Andrew Bremer, with the addition of exogenous ketones courtesy of Craig Emmerich) shows the order that we generally prioritise the use of different fuel sources.


  1. Alcohol will be burned off first because it’s effectively a poison that the body can’t store.  (Alcoholics can have really low HbA1c levels because insulin rises to shut off the release of glucose into the bloodstream while the alcohol is burned off.[9])
  2. Similar to alcohol, ketones are used up as a priority because we can’t channel them back into storage in the body.  Ketones are acidic and high levels of ketones in the blood lead to diabetic ketoacidosis.  (note: As discussed below, Beta-hydroxybutyrate (BHB) can be thought of as the storage form of ketones.  While BHB can be used directly by the brain, it needs to be converted back to acetoacetate to be used by the rest of the body.)
  3. Protein is not a great fuel, so we can’t store much of it in the blood.  It’s hard for the body to convert protein to energy so it’s hard to overeat.[10]
  4. Carbohydrates can be a useful source of fuel for explosive efforts.   But glucose can be toxic in large quantities (it leads to glycation) so the body tries to limit the amount in the bloodstream.
  5. If glucose levels are high, the body won’t burn off the fat from our diet.  Fat is last in line to be burned because it’s such an effective way of storing energy.
  6. Similarly, if the level of fat in our diet is high we won’t burn off the fat on our body effectively.  (High levels of fat in the bloodstream can lead to oxidised LDL, so the body wants to keep it moving rather than building up high levels.)

Your body increases insulin to hold back the release of stored energy until the energy in the blood decreases.  As you burn through all these fuel sources the body decreases your insulin levels to eventually allow the release of your stored fuel for use to make up the difference.

You can think of a lower energy state as one where you don’t have a lot of fuel lined up in front of our body fat, while a high energy state occurs where your body has to ramp up insulin levels to hold your stored energy back from being used while the energy from your mouth is being used.  

When you look at it from this perspective you see that nutrition is essentially a process of optimising our food choices to ensure we get the nutrients and fuel we need without stacking up too much energy in front of our body fat stores.[11] [12]

Low carb and weight loss

More stable blood glucose levels help people normalise appetite.  People often eat less when they are no longer on the blood glucose roller coaster.  For people with diabetes, weight loss is often a spontaneous response to reducing carbohydrates as demonstrated by the recently released Virta one year trial results.[13]


However, while high blood ketones (BHB) is often targeted as evidence of being “in ketosis”, BHB levels often typically taper off over time, especially if you are lean, active, metabolically healthy and weight stable.

It seems that as our fat stores become ‘less full’ we don’t store as much energy in the bloodstream.   And, as we will see later, once our NAD+: NADH ratio increases, less acetoacetate is pushed off to into storage as BHB.

One of the most fascinating outcomes of the one-year Virta study was that over the period of a year, participants’ BHB levels went from 0.17 mmol/L to an average of 0.54 mmol/L after 10 weeks and then settled back to 0.3 mmol/L after a year.[14]


I found it ironic that in this study of treating diabetes with a ‘ketogenic diet’ that, on average, these people only temporarily dipped into “nutritional ketosis” (defined as having BHB > 0.5 mmol/L).  Then in the long term, they settled back to much lower levels of BHB.


Even under the supervision of the doctors and dietitians who are the world experts in ketosis and literally wrote the book on the topic, at no time did they go near “optimal ketosis” (as defined as having BHB between 1.0 mmol/L and 3.0 mmol/L[15]).


Blood sugar and HbA1c

While the science around ketosis is still controversial, we do know that a lower HbA1c and lower blood sugar levels can be beneficial in terms of long-term health and avoiding many common killers (e.g. diabetes, heart disease, cancer, stroke etc).

The chart below shows that a HbA1c of 4.5% (i.e. a proxy for your average blood sugar level) gives the lowest hazard ratio (i.e. lowest risk of mortality from all causes).[16] [17]


As shown below, a lower HbA1c is beneficial in terms of reducing your risk of stroke, heart disease, cardiovascular disease and many of the modern diseases.



The risk  of focusing on beta-hydroxybutyrate as your measure of ketosis

However, if at first, you don’t succeed in achieving “optimal ketone levels” many people resort to the following to raise their blood ketone levels:

  • load up on high levels of refined fat such as Bulletproof Coffee with butter and MCT oil,

[warning: These foods are typically more energy dense and less satiating, so many people find them easy to overeat.  While most people don’t need to avoid dietary fat, simply eating ‘fat to satiety’ doesn’t lead to long-term weight loss for many people.]

  • eat less protein to reduce oxaloacetate and force more fat to be burned via ketosis rather than the Krebs Cycle,

[warning: Replacing energy from protein and carbohydrates with fat can lead to a less nutrient dense selection of foods as evidenced by many of the lower ranking people in the Nutrient Optimiser Leaderboard.  In this recent article Volek and Phinney suggested that protein intake is between 1.5 and 2.0 g/kg reference weight and that while reducing protein will help to increase ketosis you should not drop below 1.2 g/kg BW.[18]],


  • eat a more acidic diet with less electrolytes to ensure that the keto acids are not able to be balanced with alkaline minerals such as magnesium, potassium and calcium), or

[warning: This approach may lead to the keto flu in the short term and insulin resistance[19] and metabolic acidosis in the longer term.[20]]

  • eat a diet that contains less B vitamins to decrease your NAD+:NADH ratio to force more acetoacetate to be stored and converted to BHB.

[warning: B vitamins are important for efficient and effective energy production].

The glucose:BHB index

So we do know that lower glucose levels are a good thing and high blood ketones are not necessarily bad.  They can actually nourish the brain if we are insulin resistant and aren’t using glucose well and this is helpful where therapeutic ketosis is required (i.e. Alzheimer’s, epilepsy, Parkinson’s, cancer etc).

But high ketones are not great if they are also accompanied by high blood glucose levels and/or free fatty acids.

So, the way to make sure we are not overloading our system in our pursuit of ketosis is to ensure that our higher ketone levels are also accompanied by lower glucose levels.

Enter the glucose: ketone index which was developed by Professor Thomas Seyfried of Boston College[21] [22] to help optimise the metabolism of cancer patients.

Seyfried subscribes to the Warburg hypothesis of cancer which says that cancer cells ferment glucose and, hence, reducing the glucose supply to cancer cells can help them slow proliferation.


To help understand what this looks like in practice I have plotted more than 1200 blood glucose versus ketone values in the chart below and divided them up into five groups based on their GKI value.  The average GKI values of these groups of data points are shown on the charts (i.e. GKI = 1.5, 2.8, 4.5, 7.5 and 20).


The worst metabolic health is the GKI = 20 population (green dots at the bottom of the chart) with high blood glucose levels and low ketones.  This means that glucose values are twenty times that of the ketone values.

Meanwhile, the people with the lower glucose and the higher ketone are likely to be in a better place metabolically.  They will be more likely to experience the positive therapeutic benefits associated with “being in ketosis”.

Before you go chasing a super low GKI value, be aware that most people are not going to get GKI values under than 2.0 until they fast for a few days, even if they are following a ketogenic diet.  The chart below shows what you could expect if you fasted for seven days.


The glucose : acetone index

Both Michel Lundell from Ketonix and Dave Korsunsky from Heads of Health recently told me that, building on the GKI concept, a number of people are tracking the ratio between their breath acetone readings and their glucose levels.

In order to better understand the relationship between breath acetone and ketones, I have plotted about two and a half thousand glucose and breath ketone readings taken at the same time in the chart below.


You can see from this chart that there is a similar relationship between glucose and breath ketones as with blood ketones.  However, there is less scatter compared to the previous chart.  It seems that blood glucose and breath acetone are more closely correlated than blood ketones.

It’s hard to have high breath acetone with high blood glucose levels.   You can’t ‘game the system’ in the same way you can with BHB by forcing in exogenous fat or ketones.

As your energy and insulin levels start to rise, more of your acetoacetate will be shunted off to storage as BHB.  So, while some refer to BHB as ‘the gold standard”, it’s hard to know whether high blood ketone values are due to a low energy state or if your bloodstream is full of energy so you need to store more as BHB.

I think the optimal situation to be in is to have lower blood glucose levels with a solid amount of breath acetone in your system which suggests you are producing ketones without driving excess energy.

If you have good metabolic health, you’ll probably be in the purple or green area on this chart.  If you are achieving a therapeutic level of ketosis or fasting for longer periods, you will ideally be in the upper left corner of this chart (green or light blue) with low glucose and high breath ketones.

The chart above shows breath acetone (BrAce on the Ketonix scale of 0 to 100) and the blood glucose in mmol/L.  To calculate your BrAce:BG ratio you can divide your Ketonix reading by your blood glucose level.  If you’re going to measure it’s probably better to measure your glucose and ketones in the morning when you first wake up.  They key is to measure these values all at the same time.  While it’s interesting to see how you compare with others it’s most important to make sure your values moving in the right direction over time.

The chart below shows glucose vs breath acetone with glucose in mg/dL (American units).  If you have Ketonix and blood glucose meter you can test and see how you compare.


Are breath ketones a better measure of health than BHB?

If you’re really interested in this topic, I recommend you watch this video from Chris Masterjohn that explains in detail how ketones are made and used.


In summary:

  • Acetoacetate is the first ketone body made in the liver (unfortunately, it’s hard to measure).
  • If your NAD+:NADH ratio is low, more acetoacetate will be converted to BHB, which can be measured in the blood.
  • While the brain can use BHB directly, BHB needs to be converted back to acetoacetate to be used in the rest of the body.
  • When the level of energy in your bloodstream decreases, your NAD+:NADH ratio increases and insulin levels decrease. You will then be able to shuttle the ketones stored as BHB back to acetoacetate to be used for energy in the rest of the body.

Acetone is like a vapour that is released from acetoacetate, similar to nail polish fumes.  If you are releasing a high level of breath acetone, then people might say you have a ‘fruity’ smell on your breath or you will experience a different, metallic taste in your mouth.

It’s not easy to measure acetate in the blood, but devices like the Ketonix are becoming more popular to measure acetone in your breath.  Acetone on your breath is not a direct measure of the quantity of acetoacetate in your system but it’s a useful proxy.  Imagine the difference in smell if you have a small thimble versus a massive drum of nail polish.  You’re going to get more fumes coming off a large amount of acetone.

The take-home point here is that if our NAD+:NADH ratio is high, and our overall energy levels are low then not as much acetoacetate will be converted to BHB, and hence more acetoacetate will be available in the blood and more acetone will be measured on the breath.

Meanwhile, if you have excess energy in your system, you will have high levels of ketones in their “storage form” available for use only by the brain.  Conversely, if you have a lower energy state that is more conducive to burning body fat, you may have less BHB and more acetoacetate.

So, breath acetone is more of a measure of ketones ready to be used by your body while BHB is more of a measure of ketones being stored for later use.

Why does the balance of acetone vs BHB vs BrAce matter?

NAD+ is a metabolite that declines with age.[23]  A lot of the anti-aging research at the moment is focusing on how we can boost NAD+ levels.[24] [25] [26] [27] [28]   IV NAD+ treatments are being used for drug addiction, anti-ageing and quick recovery from a really big night.[29] [30] [31]


The secret here is that, while you can take supplements and injections to boost NAD+, most people can get plenty from B vitamins (particularly vitamin B3 (niacin) which is dirt cheap).[32]


NAD is also made from tryptophan in the diet.


NADH builds up when we become over-fueled and is typically higher in conditions such as diabetes.[33]  When we eat and get energy from food, a hydrogen ion (H+) and two electrons (2e-) attaches to NAD+ and we get NADH.  When we use the energy and go without foods the reverse reaction occurs.  NADH decreases and NAD+ builds up.


Too much energy in our system drives high NADH levels.  Just like in a car engine, we can drown our mitochondria in fuel and they choke.

When we have lots of fuel in our system NADH rises but then if we don’t have enough NAD+ we can’t use it.  So we’re drowning in fuel but we can’t use it!

Bringing this back to measuring ketones… if we have a higher NAD+:NADH ratio we will see higher breath acetone, lower blood glucose and lower levels of BHB (which is a good thing).

Tell me what to do!!!

So ideally we want to see:

  • higher breath acetone,
  • lower blood glucose levels, and
  • blood ketone values of maybe greater than 0.2 mmol/L (they’re not really a big deal unless you specifically require high levels of blood ketones to feed your brain in conditions such as epilepsy, Alzheimer’s or Parkinson’s).

How to get higher NAD+ levels and higher acetoacetate

Boosting your NAD+ levels can be achieved by:

  1. Eating nutrient dense foods with plenty of B vitamins (which are a precursor to NAD+),
  2. Not avoiding protein (particularly tryptophan), and
  3. Supplementing with niacin.


If you find your breath acetone is on the lower end you can try supplementing with Niacin.  When I supplement with Niacel or Niacin my BHB levels drop and my breath acetone rises substantially.

Be warned, you can get a flushing reaction so make sure you start slowly.  There is no need to take super high levels, particularly if you’re already keto-adapted.

You can supplement to the point that you start to see higher Ketonix readings.  Or, if you don’t have a Ketonix, to the point that you get a funky metallic taste in your mouth.

You might want to start with 25 mg or 50 mg of Nicotinic Acid and build up to 100 mg or even 200 mg if you don’t see any flushing or a rise in your breath acetone.

  • If you’re wanting to start gently, the Carson Lab niacin is the only one I’ve been able to find in 50 mg in Australia via iHerb.
  • The 100 mg Nicotinic Acid is actually a lot cheaper (only 5 c per tab).
  • Nicotinamide Riboside can be useful for people who can’t as easily convert niacin to NAD+, but it’s more expensive.

However, rather than supplementing, nutrient dense minimally processed whole foods are ideal, at least as a starting point before you start adding supplements.  The Nutrient Optimiser has been designed to help you find the most nutritious whole foods to balance your macro and micronutrients.

If you require therapeutic ketosis the Nutrient Optimiser free report will give you a suggested macro range that will also help you avoid excessive energy.  It will also give you a short list of nutrient dense meals and foods that will help boost your mitochondrial function.


If you’re interested, the Nutrient Optimiser full report will give you a longer list of foods and meals.  You also have the option to upload your Cronometer data to progressively fine-tune your diet to achieve your goals.

How to get lower blood glucose levels

The key to achieving lower blood glucose levels is:

  1. Avoid processed, and nutrient-poor high carbohydrate foods (e.g. processed grains, cereals and sugars),
  2. Eat less often / fast / avoid snacking,
  3. Eat less overall.

If you do these things, you will see your blood glucose levels decrease, your NAD+ levels increase, and your breath acetone levels increase.

You can stabilise your blood glucose levels by eating a diet with more fat and less carbohydrates, but to really shift your NAD+:NADH ratio in a favourable direction, you may need to reduce your body fat to more optimal levels.

The article How to use your blood glucose meter as a fuel gauge can guide you through how to use a glucose meter to re-calibrate your eating routine based on when you really need to eat.

The Nutrient Optimiser will suggest macronutrient ranges and nutritious foods that will help you stabilise your blood sugars.




Special thanks to:

  • Robert Miller for sharing his unique insights into biochemistry.
  • Michel Lundell from Ketonix for supplying all the data!
  • Weikko Jaross and Alessandro Ferretti for help with the initial database analysis.
  • Craig Emmerich. Mike Julian, Ben McDonald, Robin Reyes, Alex Leaf and Helen Kendall for their review and editing.



















[17] This chart is interesting because it shows that very low blood glucose levels can be association with issues such as autoimmune issues or alcoholism which can cause blood sugars to go very low while the body burns through the alcohol.

















are exogenous ketones right for you?

I’ve spent a lot of time lately analysing three thousand ketone vs. glucose data points trying to determine the optimal ketone and blood sugar levels for weight loss, diabetes management, athletic performance and longevity.

In this article, I share my insights and learnings on the benefits, side effects and risks of endogenous and endogenous ketosis.

Exogenous vs. endogenous ketosis

But first, I think it’s important to understand the difference between exogenous and endogenous ketosis:

  • Endogenous ketosis occurs when we go without food for a significant period. Our insulin levels drop, and we transition to burning body fat and ketones in our blood rise.
  • Exogenous ketosis occurs when we drink exogenous ketones or consume a ketogenic diet.

Ketones vs glucose

Ketones are important.  As blood glucose decreases, the ketones in your blood increase to keep our energy levels stable.

The chart below shows three thousand blood glucose vs ketone values measured at the same time from a range of people following a low carbohydrate or ketogenic diet.

BHB ketones vs blood glucose

While there is generally a linear relationship between glucose and ketones, each person has a unique relationship between their blood glucose and ketone values that provide a unique insight into a particular person’s metabolic health.


Some people produce more ketones than others.  Some people have higher blood glucose levels.

What our ketone and glucose values tell us about our metabolic health

Hyperinsulinemia has been called as the “unifying theory of chronic disease” [1] [2] [3] [4] [5].  It’s beneficial to understand where you stand on the spectrum of metabolic health and insulin sensitivity.

The chart below shows the typical relationship between blood glucose and blood ketone for a range of different degrees of insulin resistance/sensitivity.

2017-04-17 (11)

If your blood glucose levels are consistently high it’s likely you are not metabolising carbohydrate well.   When you go without food, endogenous ketones are slow to kick in because your insulin levels are also high.  You feel tired and hungry, and you are likely to eat again sooner and not stop until you feel good.

By contrast, if you are insulin sensitive you may be able to go longer between meals naturally and you will not feel as compelled to eat as much or as often.  If someone is insulin resistant, a lower insulin load dietary approach will help with satiety and carb cravings while keeping blood glucose levels and insulin under control.

hyperinsulinemia and metabolic disorders

Exciting research is coming out 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.[6]  [7]  

EXOGENOUS ketones may help to relieve the debilitating symptoms and side effects of acute hyperinsulinemia, Alzheimer’s, dementia, epilepsy or other conditions where glucose is not used well.

exogenous ketones and the low carb flu

Patrick Arnold, who worked with Dr Dominic D’Agostino to develop the first ketone esters and ketone 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, once you have successfully transitioned to a lower carb eating style it may be wise 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 body fat stores.

As discussed in the article Are ketones insulinogenic and does it matter? it exogenous ketones require about half as much insulin as carbohydrate to metabolise (or about the same amount as protein).  Hence the continual use of exogenous ketones will limit how much our insulin levels are able to decrease.

Someone with diabetes who follows 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 liver will be able to more easily produce 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.


my experience with exogenous ketones

The light blue “mild insulin resistance” line is based on my ketone and glucose tests when I started trying to wrap my head around low carb/keto.


I enthusiastically started adding generous 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 lots of 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.  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.

I initially purchased a couple of bottles of KetoCaNa after hearing a number of podcast interviews with Dominic D’Agostino and Patrick Arnold.[8] [9]

Part of the reasons shelling out the money for the exogenous ketones was to see if it would provide a fuel source that didn’t need insulin for my wife Monica who has Type 1 Diabetes.

This metabolic jet fuel is definitely fascinating stuff!  My experience is that it gave me a buzz like a BPC but also has an acute diuretic effect.

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.


Unfortunately, my hunger and subsequent binge eating seemed to more than offset the short term appetite suppression that had occurred while the exogenous ketones were in my system.  And it was not going to be financially viable for me to maintain a constant level of artificially elevated ketone levels which return to normal levels after a couple of hours.

do exogenous ketones help with weight loss?

I asked around to see if anyone had come across studies demonstrating long term weight loss effects of exogenous ketones.[11]   It was a VERY enlightening discussion if you want to check it out here.


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 prove his claim.

AVPageView 11082016 13036 PM.bmp.jpg

Also, the studies that were referenced in the Pruvit FAQ all appeared to relate to the benefits of ENDOGENOUS or nutritional ketosis rather than EXOGENOUS ketone supplementation.


According to Dominic D’Agostino in a Pruvit teleseminar, the EXOGENOUS ketone salts were not designed to be a weight loss product and hence have not been studied for weight loss after all!

The only studies that we could find that mentioned EXOGENOUS ketone supplementation and weight loss were on rats and they found that there was no long term effect on weight loss.[12]   

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.



image16 [13]


I don’t blame you.

Metabolically healthy

The “metabolically healthy” line in the chart above is based on RD Dikeman’s ketone and glucose data when he fasted for 21 days.


Due to his hard-earned metabolic health and improved insulin resistance RD has developed the ability to fairly easily release ketones when he doesn’t eat for a while.  RD still doesn’t find going without food effortless, but it is easier than when his insulin levels were much higher which prevented his body from accessing his body fat stores.

2016-08-10 (2).png

Through a disciplined diet and exercise habits 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 glucose : ketone gradient as the gold standard.

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 when fasting, it seems they are also quickly metabolised so they do not build up in his bloodstream.

I know Luis Villasenor from 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, the energy coming from both glucose and ketones.

The average TOTAL ENERGY of the three thousand data points from these healthy people working hard to achieve nutritional ketosis is around 6.0mmol/L. It seems the body works to maintain homoeostasis around this level.

optimal fasting ketone and blood sugar levels in ketosis

When the TOTAL ENERGY in our bloodstream increases outside of the normal range it 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 due to the lack of insulin available to keep your energy in storage.

Regardless of whether your energy takes the form of glucose, ketones or free fatty acids, they all contribute to acetyl-coA which is oxidised to produce energy.  Forcing excess unused energy to build up in the bloodstream is typically desirable and can lead to long term issues (e.g. glycation, oxidised 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 lipogenesis 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.[14]

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.[15]

image26[16] [17] [18]

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 Thomas Seyfried and Dominic D’Agostino always talk about the therapeutic benefits and the insulin lowering effects of a calorie restricted ketogenic diet. [19] [20] [21] [22]

Dealing with high ketones and high glucose is typically not a concern because it doesn’t happen in nature or when eating 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, 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[24] 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 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 to be 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.

However, 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 both more fat and 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 answer through a controlled study in the future are:

  1. What is the safe dose limit of EXOGENOUS ketones for a young child?  How would you adjust their maximum intake based on age and weight?
  2. 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?
  3. Is there a difference in the way EXOGENOUS ketones are processed in someone is metabolically healthy versus someone who is very insulin resistant?
  4. Does the effect on appetite continue beyond the point that the ketones are out of your system?
  5. 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?
  6. 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?
  7. Is there a difference in health outcome if you are taking EXOGENOUS ketones in the context of a hypocaloric ketogenic diet versus a hypercaloric ketogenic diet?  What about a diet high in processed carbs?
  8. Is there a minimum effective dose to achieve optimal long term benefits to your metabolic health or is MORE better?
  9. 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 mobilize glycogen and fat easily when required (e.g. when fasting or a sprint).

Metabolically healthy people are both metabolically flexible[25] and metabolically efficient.[26]   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.  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) in one month!


At 5.2mmol/L (i.e. glucose of 4.0mmol/L plus ketones of 1.2mmol/L) John’s TOTAL ENERGY is well below the average of the 26 people shown in the glucose + ketone chart above.  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 or coffee.

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.

ketones (mmol/L)

blood glucose (mmol/L)

total energy (mmol/L)





30th percentile




70th percentile




The table below shows this in US units (mg/dL).


glucose (mg/dL)

energy (mg/dL)





30th percentile




70th percentile




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 magic of ketones

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).[27]   The REAL magic of ketosis happens when all these things happen and ketones are released 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 flooded with insulin caused by high TOTAL ENERGY building up in your bloodstream (i.e. from glucose, ketones and even free fatty acids).


Driving up ketones artificially through EXOGENOUS inputs (treating the symptom) does NOT lead to increased metabolic health or 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.

Perhaps as more exogenous products come to market without the marketing hype that that comes with multi level marketing (e.g. Julian Baker’s Insta Ketone which are a sixth of the price of the Pruvit products) people will get to see if they really do anything useful.

Just like having low blood glucose is not necessarily good if it is primarily caused by high levels of EXOGENOUS insulin coupled 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/or EXOGENOUS ketones.

nutrient density

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, increased mitochondrial biogenesis, improved insulin sensitivity and lower blood glucose levels.

Prioritising nutrient dense real food is even more important in a ketogenic context.[28]  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.

the best exogenous ketone supplement

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.

best exogenous ketone supplement

Check out the how to use your glucose meter as a fuel gauge article or how to use your bathroom scale as a fuel gauge for some more ideas on how to get started with fasting.

If you 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.

































post last updated: July 2017