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.

Introduction

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.

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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.

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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).

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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.

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  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]

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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]

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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.

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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]).

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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]

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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.

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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]],

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  • 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.

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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).

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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.

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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.

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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.

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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.

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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]

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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]

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NAD is also made from tryptophan in the diet.

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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.

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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.

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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.

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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.

 

 

Thanks

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.

 

References

[1] https://optimisingnutrition.com/2016/08/08/how-to-make-endogenous-ketones-at-home/

[2] https://optimisingnutrition.com/2017/04/30/are-ketones-insulinogenic-and-does-it-matter/

[3] https://optimisingnutrition.com/2015/07/20/the-glucose-ketone-relationship/

[4] https://optimisingnutrition.com/2018/02/03/is-too-much-protein-on-keto-a-thing/

[5] https://link.springer.com/article/10.1007%2Fs13300-018-0373-9

[6] https://www.ncbi.nlm.nih.gov/pubmed/25686106?dopt=Abstract

[7] https://www.ncbi.nlm.nih.gov/pubmed/23223453?dopt=Abstract

[8] https://optimisingnutrition.com/2016/08/08/how-to-make-endogenous-ketones-at-home/

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125693/

[10] https://www.dropbox.com/s/zej4razn4dn993y/protein%20leverage%20hypothesis%20-%20simpson2005.pdf?dl=0

[11] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326984/

[12] https://www.amazon.com/Keto-Complete-Ketogenic-including-Simplified/dp/1628602821

[13] http://doi.org/10.1007/s13300-018-0373-9

[14] http://doi.org/10.1007/s13300-018-0373-9

[15] https://www.amazon.com.au/Art-Science-Low-Carbohydrate-Living/dp/0983490708

[16] http://circoutcomes.ahajournals.org/content/3/6/661

[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.

[18] https://blog.virtahealth.com/how-much-protein-on-keto/

[19] https://optimisingnutrition.com/2017/10/21/redesigning-nutrition-from-first-principles/

[20] https://optimisingnutrition.com/2016/11/19/the-alkaline-diet-vs-acidic-ketones/

[21] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0009-2

[22] https://www.bc.edu/bc-web/schools/mcas/departments/biology/people/faculty-directory/thomas-seyfried.html

[23] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2852209/

[24] http://www.lifeextension.com/Magazine/2018/2/Anti-Aging-Effects-Of-NAD/Page-01

[25] https://www.sciencedaily.com/releases/2017/03/170323141340.htm

[26] http://www.iflscience.com/health-and-medicine/preliminary-results-early-human-trials-anti-aging-formulas-reveal-no-adverse/

[27] https://bengreenfieldfitness.com/podcast/anti-aging-podcasts/what-is-nad/

[28] http://longevityfacts.com/nmn-nad-nicotinamide-mononucleotide-david-sinclair-interview-anti-aging-drug-trials-nicotinamide-adenine-dinucleotide-sirtuins/

[29] https://www.nadtreatmentcenter.com/6-major-benefits-of-nad-iv-therapy

[30] https://www.vice.com/en_us/article/bn3vmq/nad-plus-brain-reboot-infusion-injection

[31] https://bengreenfieldfitness.com/podcast/anti-aging-podcasts/what-is-nad/

[32] https://openi.nlm.nih.gov/detailedresult.php?img=PMC4588049_cells-04-00520-g001&query=&req=4&npos=-1

[33] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869616/

how much protein do I need on keto?

  • There is a lot of confusion about ‘excess protein’ and whether you can have too much protein on keto.
  • Insulin and protein are used to build and repair your muscles, organs and the other important parts of your body.  This is an important and beneficial use of protein and insulin.
  • Foods that contain the harder to find nutrients (e.g. potassium, magnesium, choline, vitamin D) typically contain plenty of protein.
  • Actively avoiding protein and can lead to a less nutritious diet.
  • Unless you require therapeutic ketosis for the treatment of cancer, epilepsy, Alzheimers, Parkinson or dementia, you should be chasing vitality, health and nutrition along with stable blood sugar levels rather than some arbitrary ketone level.
  • There are a range of different ways to quantify protein intake.  Thinking in terms of percentages can be more confusing than helpful.
  • It’s hard to over-consume protein because it is highly satiating.  However, if you avoid protein your body may drive you to consume more calories until you get the protein it needs.
  • If you follow your appetite and focus on foods that contain the vitamins and minerals you need you will probably get enough protein.

Virta Facebook Live Q&A

I recently had the opportunity to pose some questions about protein intake to the Godfather of Keto, Dr Stephen Phinney in a recent Facebook live Q&A.

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Dr Phinney’s response to my question is shown below, including his recommended protein intake levels of 1.2 to 1.75 g per kg reference body weight of protein.

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While I largely agree with Dr Phinney’s response, I think it’s worth elaborating on some of the issues that are causing so much confusion at the moment.

Will too much protein kick me out of ketosis?

If you’ve read previous posts on Optimising Nutrition you’ve probably seen my analysis of the food insulin index data that shows that our carbohydrate intake alone doesn’t explain our insulin response to food.

The food insulin index data shows that our insulin response to food is more accurately predicted when we consider the fibre and protein content of our food, not just the carbohydrate.

However, I fear that many people have used the insulin load concept as a reason to avoid protein.  I now understand that this is far from optimal within the broader context of good nutrition for health, weight loss and vitality.

If you are interested in learning more the implications of the insulin index data I recommend you check out the following articles:

Effect on blood sugar and insulin

While trading your calories from butter for steak will increase your requirement for insulin, the food insulin index data suggests that as a general rule, getting more of your energy from protein will reduce your insulin requirements as it forces out processed carbohydrates as shown in the chart below.

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Getting more energy from protein tends to decrease our glucose response as it forces out nutrient-poor refined high carb foods.  Your body can convert protein to glucose (i.e. gluconeogenesis) if it really needs to but it’s a lot of work, so it would much rather get energy from carbs or fat.

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Protein is also very satiating.  Once we have enough protein, our body tends to crave more fatty and carby foods for energy.[10] 

While it is both financially and metabolically expensive, protein is the most important component of your diet.  Different people will need different amounts of protein depending on their life stage and activity levels.

While you probably don’t need to be going out of your way to binge on more protein than you can comfortably consume, actively avoiding protein containing foods is a recipe for nutritional disaster.  If you are exercising or lifting heavy then you will naturally crave more protein.

If you actually need higher levels of blood ketones for therapeutic ketosis, it may be a good strategy to consciously restrict protein.  However, I don’t’ think the vast majority of people chasing ketones are looking for therapeutic keto for the management of cancer, Alzheimer’s, epilepsy, dementia or Parkinson’s but rather fat loss or diabetes control.

Protein number crunching

The numbers around protein can be confusing due to the units used.

  • Dr Phinney uses ‘reference body weight’ (RW) (which he says is ‘the weight you were when you were in college’).
  • The mainstream nutrition world talks in terms of total body weight (BW).
  • Meanwhile, the sports nutrition community talk in terms of lean body mass (LBM).

In order to understand what this means in practice, let’s look at an example of a woman who is currently 40% body fat but was 25% in college (i.e. her reference weight).  For argument’s sake let’s say she was 70 kg in college but she is currently 87 kg or 193 lb.  The images below will give you an idea of what these level of body fat levels look like.

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In the table below I have calculated what Dr Phinney’s recommended protein intake looks like for this person in terms of:

  • reference body weight (RW),
  • lean body mass (LBM), and
  • body weight (BW).

Based on Dr Phinney’s guidance, this person should be eating between 84 and 123 g of protein per day.

  body fat weight (kg) weight (lbs) lower limit upper limit
reference weight 25% 70 154 1.2 g/kg RW 1.75 g/kg RW
lean body mass 0% 52.5 116 1.6 g/kg LBM 2.3 g/kg LBM
body weight 40% 87.5 193 1.0 g/kg BW 1.4 g/kg BW
protein (g/day)       84 123

On a practical note, there is nothing low about 2.3 g/kg LBM protein.  While I do track my intake I find it hard to get above 2.2 g/kg LBM even when trying to maximise protein.  At the same time, the lower limit is well above the official Recommended Daily Intake of 0.84 g/kg for men and 0.75 g/kg for women which are set to maintain nitrogen balance and prevent disease (i.e. not achieve optimal health and vitality).

What about percentages?

Talking about protein in terms of percentages of energy intake can be confusing as it depends on your activity levels or whether you are dieting.   Theoretical energy intake requirements are based on your lean body mass and activity levels.

The table below shows what Dr Phinney’s protein recommendation of 1.2 to 1.75 g/kg RW (or 1.6 to 2.3 g/kg LBM) look like for our hypothetical woman above in terms of percentage of energy intake for different energy intakes depending if she was trying to lose weight, maintain weight or was more active.

scenario calories lower upper
30% deficit 1158 29% 42%
sedentary 1654 20% 30%
lightly active 1852 18% 27%
moderately active 2084 16% 24%
vigorously active 2431 14% 20%
protein (g)   84 123

Protein intake in terms of percentage energy intake can vary widely to the point that it’s practically useless.  It’s generally much more useful to talk in terms of protein intake in grams per weight lean body mass rather than percentages.

Protein and nutrient density

Since stumbling across the insulin index, one thing I have found consistently is that nutrient-dense foods are not low in protein.

If you are focusing on the foods that contain the harder to find nutrients (e.g. magnesium, magnesium, choline, vitamin D etc) you will be getting plenty of protein.

Conversely, the only way to really get the ultra-low protein intakes being recommended by many people without an energy deficit is to avoid most solid foods and prioritise macadamia nuts, butter and oils.  It should not be a surprise that it will be hard to get a broad spectrum of essential nutrients with this sort of dietary approach.

As shown in the chart below, nutrient density tends to increase up to about 50% of energy intake.   If you’re eating more than 50% protein you’re likely relying on processed foods and supplements.[11]

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The chart below shows the nutrient profile of the most nutritious foods in the USDA database.  If you could stick to these foods you would easily be getting a lot of the essential nutrients without having to consume too much energy.

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The problem with these foods is that they can be very satiating which makes it hard to get enough energy in if you are active.  However, if you are trying to lose weight these foods may help to ensure that you are getting the nutrients you need with less energy without being hungry.

It’s interesting to see many people who have been experimenting with the Nutrient Optimiser have commented on how little food they can get away with while experiencing minimal levels of hunger.   Nutrient dense foods tend to be hard to overeat and also provide you with the nutrients to prevent cravings and hence reduce appetite.

For comparison, the chart below shows the nutrient profile of the ketogenic diet foods.  That is, the foods that have the lowest percentage insulinogenic calories.   These foods are 80% fat, 15% protein and 3% net carbs).  Ironically, an individual consuming these foods will be meeting the minimum levels of protein but they will be missing out on a large number of other vitamins and minerals.

I find that it’s often the people who are trying to actively avoid protein that find themselves at the bottom of the Nutrient Optimiser Leaderboard with a very poor nutrient profile.

The chart below shows the nutrient profile that we get when we actively avoid protein.  The only nturients that we get enough of in this scenarios is sodium and vitamin C!

Unless you are chasing therapeutic ketosis for the treatment of cancer, epilepsy, Alzheimers or dementia I think your focus should be on building health and maximising nutrition rather than higher ketone values.

If you are getting the micronutrients you need to thrive you will be getting plenty of protein and won’t need to worry too much about getting adequate protein intake.  Conversely, if you are actively avoiding protein you will be unnecessarily sacrificing your other micronutrients (especially if you are replacing your calories from protein and carbs with refined fat).

But will too much protein kick me out of ketosis?

As I write this I have been experimenting with adequate protein with less fat and carbs and maximal nutrients on the Ketogains Bootcamp.  A typical daily Cronometer summary is shown below.

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My protein is sitting at about 2.2g/kg LBM for me given that I’ve been spending a lot of time in the gym lifting heavy during this time.  I’ve also been able to hit many of the nutrients targets while maintaining a significant calorie deficit.

Leading up to this period my blood glucose levels were sitting in the mid 5s (approx 100 mg/dL).  However, once I introduced the energy deficit my glucose levels plummet to the mid 4s (approx 80 mg/dL).

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And although I don’t worry much about ketones, they seem to be sitting at around 0.7 mmol/L, which I’m pretty happy with.

I know if I keep my blood glucose around this level I will continue to lose weight and continue to improve my glucose control and HbA1c.

I also get plenty of breath acetone from endogenous ketones as shown on my Ketonix below.

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Don’t forget the basal insulin!

While there has been a lot of focus on what we can do to not have too much insulin, we need to remember that insulin has a number of important roles including:

  1. to help us get glucose into cells to be used by our mitochondria,
  2. to help build and repair our muscles, and
  3. to control the release of glucose from our liver while the energy in our bloodstream is used up.

People with type 1 diabetes demonstrate happens if we don’t have enough insulin.  Not only would we not be able to store the energy we eat as fat and muscle, the brake comes off the liver and all the stored energy in our body comes flowing out in the form of excess glucose and ketones (i.e. diabetic ketoacidosis).

The image below is the same child, “J.L.”, in the 1920s before and after receiving insulin therapy.  In a healthy person, insulin suppresses the fuel flow from the liver to healthy levels.

In someone on a standard western diet, basal insulin represents about 30% of the today daily dose.  Basal insulin drops to about 50% for someone on a low carb or keto diet.  But you can never drop your insulin requirements to zero.  You always need this basal to stop the uncontrolled flow of fuel from your liver into your bloodstream.

We focus so much on the effect of the food we eat but we forget that it’s also the excess fuel on your body and floating around in our bloodstream that also plays a massive role in the insulin demand on our pancreas.

Whenever there are high levels of energy sitting in our bloodstream (from glucose, ketones or fat) the pancreas has to ramp up basal insulin production until the fuel in our bloodstream is used up.  The more fat there is on our body the harder our pancreas has to work to hold back the pressure of excess fat on our body from being released into our bloodstream.

So, you may believe that your mug of Bulletproof coffee or the fat bomb may not be raising your insulin levels because it does not contain glucose or protein.  However, your pancreas is still working overtime to produce more insulin to hold the fat on your bum and until the energy coming in via your mouth is used up.

You may be able to ramp up your energy expenditure for a while by shivering and fidgeting, more but after a time of overdriving energy you’ll likely end up fat and insulin resistant.

If you really want to reduce your insulin levels you need to work on reducing the excess level of energy floating around in your bloodstream (from any source, including fat, carbs, protein or exogenous ketones) so your pancreas will decrease its production of insulin to allow body fat to be used.

Focusing on obtaining the nutrients you need without too much energy seems like common sense to me.

Therapeutic ketosis

Someone targeting therapeutic ketosis to assist with the management of chronic conditions such as cancer, epilepsy, dementia or Alzheimer’s may benefit from higher levels of ketosis and less reliance on glucose.  But I don’t think the vast majority of people who are Googling “keto” at the moment are looking for a therapeutic treatment.

therapeutic keto

Understanding how to quantify the insulin load of our food enables us to accurately tailor or food choices to suit our goals.  When it comes to insulin load we need to keep it low enough to get the results we need without compromising the nutritional value of the food we eat too much.

The chart below shows that nutrient density peaks at around 40% insulinogenic calories.

  • If you are insulin resistant it would be prudent to have less than 40% insulinogenic calories.
  • Someone on a low carb diet might have less than 25% insulinogenic calories.
  • Someone targeting therapeutic keto will likely need to have less than 15% insulinogenic calories to see therapeutic levels of ketones.

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Unless you really require therapeutic keto then I don’t think there is a need to worry too much about the impact of protein on your blood ketone levels.  Actively avoiding protein tends to lead to compromising nutrient density unnecessarily which may lead to nutrient cravings or deficiencies in the long term.

The glucose : ketone index

People who require therapeutic ketosis should also ensure that they are not driving the total energy in their system too high.  To do this they can track their glucose as well as ketones.  The glucose:ketone ratio (GKI) which was developed by Dr Thomas Seyfried to measure the degree of therapeutic ketosis.[12]

If you’re interested, your GKI can be calculated by dividing your glucose (in mmol/L) by your ketone values.  For example, if your blood glucose is 108 mg/dL and your blood ketones are 0.5mmol/L, GKI = blood glucose / ketone = (108 mg/dL / 18) / 0.5 mmol/L = 6 mmol/L / 0.5mmol/L = 12.

People who are chasing therapeutic ketosis typically do not need to worry about ingesting too much energy.   Driving a hypercaloric state with refined fats is not a major concern for someone trying to keep weight on (e.g. cancer cachexia).  However, ensuring that they are achieving lower glucose levels will ensure that they are not driving insulin resistance.

For reference, the table below shows the relationship between HbA1c, average glucose, ketones and GKI for different scenarios showing how your GKI and ketones correlate with HbA1c and blood glucose.

 metabolic health HbA1c average blood glucose blood ketones GKI
 (%)  (mmol/L)  (mg/dL)  (mmol/L)  
low  4.1 3.9 70 > 0.3 < 4
optimal 4.5 4.6 83 > 0.3 < 15
excellent < 5.0 < 5.4 < 97 > 0.3 < 20
good < 5.4 < 6 < 108 < 0.3 < 40
danger > 6.5 7.8 > 140 < 0.3 > 40

Really low GKI values (i.e. very high ketones and very low glucose) are typically seen in extended fasting when glucose levels to drop and ketones from body fat increase in a low insulin state.

The chart below shows my blood ketone and glucose levels during a seven day fast.  Amazingly, as my blood glucose levels dropped below 4.0 mmol/L my ketones drifted up to 8 mmol/L.  During more recent, however, I haven’t been able to achieve such high ketone levels.

While we can get these high ketone levels during fasting, we typically don’t see them in the fed state.  To give you an idea of what to expect, the chart below shows GKI values over time during fasting for RD Dikeman (from Type 1 Grit), Jimmy Moore, Simon Saunders (Keto Island) and myself.   As a rule of thumb, you might expect to see a GKI value less than 2 after two or three days of water fasting.

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Nutrient density analysis

Being a big fan of Dr Phinney and the Art and Science books, I couldn’t help running his recommended diet through the Nutrient Optimiser.  I entered all the meals in the Art and Science of Low Carb Living into Cronometer and ran it through the Nutrient Optimiser.

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If you’re interested, you can see the full report here and where these meals rank on the leaderboard here.

So what should you do with all this information?

So, to summarise:

  1. If you have great blood sugars and just want to lose weight then you should focus on maximising nutrient density while reducing the energy levels in your bloodstream.  There is no need to worry about “being in ketosis”.  You will produce ketones if you are successfully achieving an energy deficit and burning your own body fat stores.
  2. If you are insulin resistant then you will want to limit your insulin load to a maximum of 2.9 g/kg LBM.  This will restrict carbohydrates in your diet so your blood sugars stabilise.
  3. If you are trying to manage diabetes then you want to keep your insulin load under 1.8 g/kg LBM.  This will restrict carbohydrates and may reduce your protein intake a little.
  4. If you require therapeutic keto then you will want to keep your insulin load less than 1.1 g/kg LBM and may need to consider limiting protein.

The recommended values for protein and insulin load are shown in the table below.

approach

min protein

(g/kg LBM)

max insulin load

(g/kg LBM)

therapeutic ketosis 0.8 1.1
diabetes / nutritional ketosis 1.8 1.8
weight loss (insulin resistant) 1.8 2.9
weight loss (insulin sensitive) 1.8

Can run the numbers for me?

I realise all this data can be confusing if nutrition is not your hobby.

Over the last few months, I’ve been working with a very talented programmer, Alex Zotov, to develop some handy software to help people navigate all this information and put it into practice.

The first instalment of the Nutrient Optmiser is a free calculator that will help you identify the ideal macronutrient ranges to suit your goals as well as a shortlist of optimal foods and meals.  The table below shows how we can determine the optimal approach for you based on your metabolic health, waist to height ratio and goals.

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We’d love you to check it out the Nutrient Optimiser.  We’d love to hear what you think and how we can refine it to suit your goals.

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We hope it will be really helpful for a LOT of people on their journey towards health through optimal nutrition

 

references

[1]https://www.amazon.com.au/Keto-Clarity-Definitive-Benefits-Low-Carb/dp/1628600071

[2]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737348/

[3]http://assets.virtahealth.com/docs/Virta_Clinic_10-week_outcomes.pdf

[4]http://www.ncl.ac.uk/press/articles/archive/2017/09/type2diabetesisreversible/

[5]https://www.ncbi.nlm.nih.gov/pubmed/25515001

[6]https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-12-164

[7]http://circoutcomes.ahajournals.org/content/3/6/661

[8]https://www.perfectketo.com/how-too-much-protein-is-bad-for-ketosis/

[9]https://nutritionfacts.org/video/the-great-protein-fiasco/

[10]https://digitalcommons.wku.edu/ijes/vol10/iss8/16/

[11]https://optimisingnutrition.com/2017/10/30/nutrition-how-to-get-the-minimum-effective-dose/

[12]https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-015-0009-2