Tag Archives: protein insulin response

why do my blood sugars rise after a high protein meal?

There is a lot of controversy and confusion over gluconeogenesis and the impact of protein on blood sugar and ketosis.

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Some common questions that I see floating around the interwebs include:

  • If you are managing diabetes, should you avoid protein because it can convert to glucose and “kick you out of ketosis”?
  • If you’ve dropped the carbs and protein to manage your blood sugars, should you eat “fat to satiety” or continue to add more fats until you achieve “optimal ketosis” (i.e. blood ketone levels between 1.5 and 3.0mmol/L)?

  • Then, if adding fat doesn’t get you into the “optimal ketosis zone”, do you need exogenous ketones to get your ketones up so you can start to lose weight?

  • And what exactly is a “well formulated ketogenic diet” anyway?

This article explores:

  • the reason that some people may see an increase in their blood sugars and a decrease in their ketones after a high protein meal,
  • what it means for their health, and
  • what they can do to optimise the metabolic health.

Protein is insulinogenic and can convert to glucose

You’re probably aware that protein can be converted to glucose via a process in the body called gluconeogenesis.  Gluconeogenesis is the process of converting another substrate (e.g. protein or fat[1]) to glucose.

  1. Gluco = glucose
  2. Neo = new
  3. Genesis = creation
  4. Gluconeogenesis = new glucose creation

All but two amino acids (i.e. the building blocks of protein) can be converted to glucose.  Five others can be converted to either glucose or ketones depending on the body’s requirements at the time.  Thirteen amino acids can be converted to glucose.

Once your body has used the protein it needs to build and repair muscle and make neurotransmitters, etc. any “excess protein” can be used to refill the small protein stores in the bloodstream and replenish glycogen stores in the liver via gluconeogenesis.

The fact that protein can be converted to glucose is of particular interest to people with diabetes who go to great lengths to keep their blood sugar under control.[2]

Someone on a very low carbohydrate diet may end up relying more on protein for glucose via gluconeogenesis compared to someone who can get the glucose they need directly from carbohydrates.[3]

Obtaining glucose from protein via gluconeogenesis rather than carbs is that it is a slow process and easier to control with measured doses of insulin compared to simple carbs which will cause more abrupt blood sugar rollercoaster.

How much insulin does protein require?

The food insulin index data[4] [5] [6] is an untapped treasure trove of data that can help us understand the impact of foods on our metabolism.

Our glucose response to carbohydrate

The food insulin index testing measured the glucose and insulin response to various foods in healthy people (i.e. non-diabetic young university students).

To calculate the glucose score or the insulin index pure glucose gets a score of 100% while everything else gets a score between zero and 100% based on the comparative glucose or insulin area under the curve response.  So we are comparing the glucose and insulin response to various foods to eating pure glucose.

As shown in the chart below, the blood glucose response of healthy people is proportional to their carbohydrate intake.   Meat and fish and high-fat foods (butter, cream, oil) tend to have a negligible impact on glucose.

Our insulin response to carbohydrates

The story is not so simple when it comes to our insulin response to food.

As shown in the chart below, the carbohydrate content of our food only partially predicts our short-term insulin response to food.  Low fat, low carb, high protein foods elicit a significant insulin response.

As you can see in the chart below, once we account for protein we get a better prediction of our insulin response to food.  It seems we require about half as much insulin for protein as we do for carbohydrate on a gram for gram basis to metabolise protein and use it to repair our muscles and organs.

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But does this mean we should avoid or minimise protein for optimal diabetes management or weight loss?  Does protein actually turn to chocolate cake?

What happens to insulin and blood sugar when we increase protein?

While protein does generate an insulin response, increasing the protein content of our food typically decreases our insulin response to food.

Increasing protein generally forces out processed carbs from our diet and improves the amount of vitamins and minerals contained in our food.[7]  Similarly, increasing the protein content of your food will also decrease your glucose response to food.

What happens when you eat a big protein meal?

The food insulin index testing was done using 1000 kJ or 240 calories of each food (i.e. a substantial snack, not really a full meal).  But what about if we ate a LOT of protein?  Wouldn’t we get a blood sugar response then?

The figure below shows the glucose response to 80g of glucose vs. 180g of protein (i.e. a MASSIVE amount of protein).  While we get a roller coaster-like blood sugar rise in response to the ingestion of glucose, blood sugar remains relatively stable in response to the large protein meal.[8] [9] [10]

So, if protein can turn to glucose, why don’t we see massive glucose spike?  What is going on?

The role of insulin and glucagon in glucose control

To properly understand how we process protein, it’s critical to understand the role of the hormones insulin and glucagon in controlling the release of glycogen release from our liver.

These terms can be confusing.  So let me spell it out.

  • The liver stores glucose in the form of glycogen in the liver.
  • Glucagon is the hormone that pushes glycogen out into the bloodstream as blood glucose.
  • Insulin is the opposing hormone that keeps glycogen stored in our liver.

When it comes to getting glucose out of the liver, glucagon is like the accelerator pedal while insulin is the brake.

When our blood glucose is elevated, or we have external sources of glucose, the pancreas secretes insulin to shut off the release of glycogen from the liver until we have used up or stored the excess energy.

Insulin helps to turn off the flow of glucose from our liver and store some of the excess glucose in the blood as glycogen and, to a much lesser extent, fat (via de novo lipogenesis).  It also tells the body to start using glucose as its primary energy source to decrease it to normal levels.

We can push the glucagon pedal to extract the glycogen stores in our liver by eating less carbohydrate (i.e. low carb or keto diets), eating less, or not eating at all (aka fasting)!

High insulin levels effectively mean that we have enough fuel in our blood stream and we need to put down the fork.

While fat typically doesn’t require significant amounts of insulin to metabolise, an excess of energy from any source will cause the body to ramp up insulin to shut off the release of stored energy from the liver and the fat stores.

Glucose, insulin and glucagon response to a high carbohydrate meal

At the risk of getting a little bit geeky, let’s look at how our hormones respond to different types of meals.

As shown in the chart below, when we eat a high carbohydrate meal insulin rises to stop the release of glycogen.  Meanwhile, glucagon drops to stop stimulating the release of glycogen from the liver.  When we have enough incoming glucose via our mouth, we don’t need any more glucose from the liver.[11]

Glucose, insulin and glucagon response to a high protein meal

When we eat a high protein meal, both glucagon and insulin rise to maintain steady blood glucose levels while promoting the storage and use of protein to repair our muscles and organs and make neurotransmitters, etc. (i.e. important stuff!).

In someone with a healthy metabolism, we get a nice balance between the insulin (brake) and the glucagon (accelerator).  Hence, we don’t get any glycogen released from the liver into the bloodstream to raise our blood sugar because the insulin from the protein is turning off the glucose from the liver.

This is why metabolically healthy people see a flat line blood sugar response to protein.

Insulin response to protein for people with diabetes

Things are different if you have diabetes.

Insulin resistance means that between our fatty liver and insulin resistant adipose tissue, things don’t work as smoothly.

While your blood sugar may rise or fall in response to protein, needs to rise a lot more while you metabolise the protein to build muscle and repair your organs.

Unfortunately, people who are insulin resistant may struggle to build muscle effectively due to insulin resistance.  Then the higher levels of insulin may drive them to store more fat in the process.[12]  Becoming insulin sensitive is important!

The chart below shows the difference in the blood glucose and insulin response to protein in a group of people who are metabolically healthy (white lines) versus people who have type 2 diabetes (yellow lines).[13]

People with diabetes may see their glucose levels drop from a high level after a large protein meal and will have a much greater insulin response due to their insulin resistance.  People with more advanced diabetes (i.e. beta cell burn out or Type 1 diabetes) may even see their blood sugar rise.  Their ability to produce insulin to metabolise the protein and keep glycogen in storage cannot keep up with the demand.

Drawing on the brake/accelerator analogy, it’s not necessarily protein turning into glucose in the blood stream via gluconeogenesis, but rather the glucagon kicking in and a sluggish insulin response that isn’t able to balance out the glucagon response to keep the glycogen locked away in the liver.

Healthy people will be able to balance the opposing hormonal forces of the insulin (brake) and the glucagon (accelerator), but if we are insulin resistant and/or don’t have a properly functioning pancreas (brake), we won’t be able to produce as much insulin to balance the glucagon response.

Someone who is insulin resistant has normally functioning accelerator pedal (glucagon stimulating glucose release in the blood) but a faulty brake (insulin).

Real life example

To unpack this further, let’s look at an example close to home.

The picture below is of a family meal (i.e. steak, sauerkraut, beans and broccoli) that we had when my wife Monica (who has Type 1 Diabetes) was wearing a continuous glucose meter.

The photo of the continuous glucose monitor below shows Monica’s blood sugar response after the meal which we had at about 5:30 pm.  Her blood sugar rises in response to the veggies and then comes back down as the insulin kicks in.

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The process to bring her blood sugars back under control from a few carbs in the veggies takes about two hours.

But over the next twelve hours, Monica’s blood sugar level drifts up as the insulin dose goes to work as she metabolises the protein.  For all intents and purposes though it looks like the protein is turning to glucose in her blood!

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This is not a one off.  We’ve seen this blood glucose response regularly.  The advent of continuous glucose meters makes this more evident as you can watch blood sugars rise over a long period after a high protein meal.

Many people with type 1 diabetes know they need to dose with adequate insulin for protein.  Once you work out how to reduce simple carbs, working out how to dose for protein is the next frontier of good insulin management.

It’s complicated and sometimes confusing.

More insulin or less protein?

So, what is the problem here?

Why are Monica’s blood sugars rising?

Is it too much protein?

Or not enough insulin?

I think the best way to explain the rise in blood sugars is that there is not enough insulin to keep the glycogen locked away in her liver and metabolise the protein to build muscle and repair her organs at the same time.

Meanwhile, the glycogen pedal is pushed down as it normally would be in response to a protein which is driving the glucose up in her bloodstream.

There is just not enough insulin in the gas tank (pancreas) to do everything that needs to be done.

So, if Monica had a choice, should she:

  • A. Keep her blood sugars stable and stop metabolising protein to repair her muscles and organs,
  • B.  Metabolise protein to build her muscles and repair her organs while letting her blood sugars drift up, or
  • C. Both of the above.

Personally, I think the correct answer is C.

While it’s probably not wise to go hog-wild with protein supplements and powders if you have diabetes, swinging to the other extreme to target minimal protein levels is a sure way to end up with a poor nutritional outcome.

According to Simpson and Raubenheimer in Obesity: the protein leverage hypothesis (2005), people with diabetes may actually need to eat more protein to ensure that they have adequate amounts to build lean muscle mass given that higher levels of gluconeogenesis may cause more protein loss to glucose due to their insulin resistance.

One source of protein loss is hepatic gluconeogenesis, whereby amino acids are used to produce glucose. This is inhibited by insulin, as is the breakdown of muscle proteins to release amino acids, and therefore occurs mainly during periods of fasting (or low carb).

However, inhibition of gluconeogenesis and protein catabolism is impaired when insulin release is abnormal, insulin resistance occurs, or when circulating levels of free fatty acids in the blood are high. These are interdependent conditions that are associated with overweight and obesity, and are especially pronounced in type 2 diabetes (12,34).

It might be predicted that the result of higher rates of hepatic gluconeogenesis will be an INCREASED requirement for protein in the diet.

A lot of my early motivation in developing the Optimising Nutrition blog was to understand which foods provoked the least insulin response and how to more accurately calculate insulin dosing for people with diabetes to help Monica get off the blood glucose roller coaster.

Like Ted Naiman, I thought if we reduced the insulin load from our food (including minimising protein) we would have a pretty good chance of losing a lot of weight (just like someone with uncontrolled type 1 diabetes).

I no longer think we need to restrict or avoid protein to manage insulin resistance.  However, there’s no need to go to the other extreme and binge on protein if you are injecting insulin.

Worrying about getting too little or too much protein is largely irrelevant.  We will get enough protein when we eat a nutritious diet.  Left to its own devices, our appetite typically does a good job of seeking out adequate protein to suit our current needs.

Meanwhile actively aiming to minimise protein will make it harder to maintain lean muscle mass which is critical to glucose disposal and insulin sensitivity.

If you see your blood sugar levels rise due to protein, it is likely due to inability to produce enough insulin rather than too much protein.  If you are injecting insulin you may need to dose with more insulin to allow you to utilise the protein in your diet to build and repair your body.

Basal and bolus insulin

One option to minimise the adverse effects of excess insulin is to focus on reducing the insulin load of our diet and eat only high-fat foods that have a low proportion of insulinogenic calories (i.e. ones towards the bottom left of this chart).

If you are highly insulin resistant and obese, this will work like magic, at least for a little while.

People who suddenly stop eating processed junk carbs and eat more fat often find that their appetite plummets as the insulin demand of their food drops and they are more easily able to access their own body fat.[14] [15]

But this is only part of the story.  Again, we can learn a lot about insulin from people with Type 1 diabetes who have to manually manage their insulin dose.

In diabetes management there are two kinds of insulin doses:

  1. basal insulin, and
  2. bolus insulin.

The bolus insulin is the insulin for the food we eat.

The basal insulin is a steady flow of insulin that is required throughout the day and night.

Without the basal insulin, we would disintegrate into uncontrolled gluconeogenesis and ketoacidosis (e.g. uncontrolled type 1 diabetes).

In a person eating a typical western diet around half the insulin given in a day is for the food and half is basal insulin. The chart below shows the daily insulin dose of a person with type 1 diabetes eating a standard diet.  The white component is the basal, and the black is the bolus for their food.

In someone following a low carb diet only around 30% of the insulin is for the food and 70% is basal insulin as shown below in my wife Monica’s daily insulin dose shown below.

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We can only reduce our insulin requirements marginally by changing our diet.   We always need basal insulin.  If we’re insulin resistant, we’ll need more.

Like caffeine or alcohol, we become more sensitive to insulin when we are exposed to less of it.  As we reduce the insulin load of our diet, our insulin sensitivity will improve.

But not everyone who follows a low carb diet instantly turns into a super athlete.  There has to be more to the story.

How to improve your basal insulin sensitivity

In addition to modifying our diet, we can also improve our blood glucose control by maximizing our body’s ability to dispose of glucose without relying on insulin (i.e. non-insulin mediated glucose uptake).  We enhance our insulin sensitivity and our ability to use glucose by building more lean muscle mass.

I used to think that if we just dropped the insulin load of our diet down far enough, we would be able to lose weight, a bit like someone with uncontrolled type 1 diabetes.  But now I understand that there will always be enough basal insulin in our system to store excess energy (regardless of the source) and stop our liver from releasing stored energy.

While a diabetic can reduce their insulin requirements for food by eating food with lots of fat, they can actually end up insulin resistant and need more basal insulin if they drive over abundance of energy, regardless of whether it’s from protein, fat or carbs.[16]

While ketones can rise to quite high levels when fasting (which is great), I fear that some people are chasing high ketone levels with lots of dietary fat and the excess energy may lead to insulin resistance in the long term.

Dr Bernstein’s approach

The method recommended by Dr Bernstein (who has type 1 diabetes himself) is typically lower in carbs, adequate protein (depending on whether you are a growing child) and moderate in fat.

Even at 83, Dr B feels it is important to maintain lean muscle mass through regular exercise to maximise his insulin sensitivity.

Will too much protein “kick me out of ketosis”?

While the ketogenic diet is becoming popular, I think most people who are interested in it do not necessarily require therapeutic ketosis, but rather are chasing weight loss or blood sugar control/diabetes management.

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If you are managing a condition that benefits from high levels of ketosis (e.g. epilepsy, dementia, cancer, traumatic brain injury, Alzheimer’s) then limiting protein may be necessary to ensure continuously elevated ketone levels and reduce insulin to avoid driving growth in tumour cells and cancer.  

Giving the burgeoning interest in the ketogenic dietary approach, I think it’s important to understand the difference between exogenous ketosis and endogenous ketosis.

  • Endogenous ketosis occurs when a person eats less than the body needs to maintain energy homeostasis and we are forced to up the glycogen in our liver and then our body fat to make up the difference.
  • Exogenous ketosis (or nutritional ketosis) occurs when we eat lots of dietary fat (or take exogenous ketones), and we see blood ketones (beta hydroxybutyrate) build up in the blood. We are burning dietary fat for fuel.

Higher levels of ketones in the blood are an indication that you are eating more fat than you are burning.  Having some level of blood ketones is an indication that your insulin is low, but whether your blood ketones are high or low should not be a major cause for concern as long as your blood glucose levels are also low.  Unless we are doing a long term fast, we will all be somewhere on the spectrum between exogenous and endogenous ketosis.

Keep in mind though that most of the beneficial things we attribute to “ketosis” and the “ketogenic diet” occurs when we are in endogenous ketosis (i.e.  when fat is coming from our body, not our plate or coffee cup).

As detailed in the popular article What are Optimal Ketone and Blood Sugar Levels in Ketosis? it seems that lower levels of total energy (i.e. towards the left of this the chart below) is a better place to be, particularly if we are chasing weight loss or diabetes management.

Our blood ketones may not be as high when we are in endogenous ketosis, but that’s OK because most of the good stuff happens in a low energy state.  

Endogenous ketosis Exogenous ketosis
Low total energy (i.e. blood glucose + blood ketones + free fatty acids) High total energy (i.e. blood glucose + blood ketones + free fatty acids)
Stored energy taken from body fat for fuel Ingested energy used preferentially as fuel
Stable ketone production all day Sharp rise of ketones for a short duration.  Need to keep adding fat or exogenous ketones to maintain elevated ketones.
Insulin levels are low which allows release of glycogen from our liver and fat stores Insulin levels increase to hold glycogen in liver and fat in adipose tissue
Mitochondrial biogenesis, autophagy, increase in NAD+, increase in SIRT1 Mitochondrial energy overload, autophagy turned off, decrease in NAD+
Body fat and liver glycogen used for fuel Liver glycogen refilled and excess energy in the bloodstream stored as fat.

Summary

  • Gluconeogenesis is the creation of new glucose (generally from protein).
  • Protein requires about half as much insulin as carbohydrate to metabolise.
  • Increasing protein intake will generally improve our blood glucose and insulin levels.  Protein forces out processed carbohydrates, increasing the nutritional quality of our diet and helps us to build muscle which in turn burns glucose more efficiently.
  • In a metabolically healthy person glucagon balances the insulin response to protein, so we see a flat line blood sugar response to even a large protein meal.
  • If you cannot produce enough insulin, you may see glucose rise as your body tries to metabolise the protein and keep the energy stored in the liver at the same time.
  • The insulin for the food we eat (bolus) represents less than half of our daily insulin demand. We can improve our basal insulin sensitivity by building lean muscle mass and improving mitochondrial function via a nutrient dense diet.
  • If we are aiming for weight loss and health, then low blood sugars and low ketones will be more desirable rather than chasing high ketone levels via exogenous ketosis.

references

[1] http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002116

[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636610/

[3] https://optimisingnutrition.com/2015/06/04/the-goldilocks-glucose-zone/

[4] https://ses.library.usyd.edu.au/handle/2123/11945

[5] https://optimisingnutrition.com/2015/03/23/most-ketogenic-diet-foods/

[6] https://optimisingnutrition.com/2015/03/30/food_insulin_index/

[7] https://optimisingnutrition.com/2017/05/27/is-there-a-relationship-between-macronutrients-and-diet-quality/

[8] https://www.ncbi.nlm.nih.gov/pubmed/16694439

[9] http://caloriesproper.com/dietary-protein-does-not-negatively-impact-blood-glucose-control/beef-vs-glucose/

[10] http://www.ketotic.org/2013/01/protein-gluconeogenesis-and-blood-sugar.html#¹

[11] https://books.google.com.au/books?id=3FNYdShrCwIC&printsec=frontcover&dq=marks+basic+medical+biochemistry&hl=en&sa=X&ei=-ctaVcivOJfq8AXL84CAAw&redir_esc=y#v=onepage&q=glucagon&f=false

[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997013/

[13] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC524031/

[14] https://docmuscles.com/

[15] https://optimisingnutrition.com/2017/01/15/how-optimize-your-diet-for-your-insulin-resistance/

[16] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-11-23

 

 

post last updated August 2017

the blood glucose, glucagon and insulin response to protein

  • The food insulin index data indicates that there is both a blood sugar and an insulin response to the glucogenic component of protein. [1]
  • A higher protein intake tends to lead to better blood sugar control, increased satiety and reduced caloric intake.
  • Digested amino acids from protein circulate in the bloodstream until they are required for protein synthesis, gluconeogenesis or the production of ketones.
  • The release of glucose from protein via gluconeogenesis is a demand-driven process that is smoother and slower compared to carbohydrate.
  • Someone who is insulin resistant and/or whose pancreas is not producing adequate insulin may benefit from higher protein with lower carbohydrate (LCHP) to smooth out the blood sugar response while still obtaining adequate protein.

background

Protein doesn’t significantly raise blood sugars, at least compared to carbohydrates.

At the same time, it is generally acknowledged (at least by people with Type 1 Diabetes) that protein requires insulin to metabolise.  Managing the blood glucose response to protein is a challenge for diabetics, particularly if they are minimising carbohydrates and hence may have a higher protein intake.

Recently, an increasing number of people trying to achieve nutritional ketosis have found that they need to moderate protein in addition to limiting carbohydrates to reduce insulin to the point where significant levels of ketones can be measured in the blood.

My aim here is not to criticise protein, but rather to better understand the insulin and glucose response to protein in light of the food insulin index data.

My wife Monica has Type 1 Diabetes, anything information that can help refine insulin dosing or help inform food choices that will lead to more stable blood sugars is of interest to me.

Personally, I have a family tendency towards obesity and pre-diabetes (based on my 23andMe testing and a lifetime of personal experience trying to keep the weight off), so I am also interested in how I can optimise my blood sugars and insulin levels.  I would also love to dodge the weight creep that seems to come with middle age for most people.

This has been a challenging topic to get my head around.  It is complex, and there is a lack of definitive research to provide clear guidance.  Hopefully, more data and discussion can help to progress the understanding and the practical application of the theory.

I do not claim to have all the answers, but rather plenty of observations and questions.  I hope that by documenting some of these, I can help move this discussion forward.

the blood glucose response to protein

The food insulin index data contained in Clinical Application of the Food Insulin Index to Diabetes Mellitus by Kirstine Bell (Sept 2014) [2] intrigues me.  There is a lot to be learned from looking at the body’s insulin response to food and the interrelationship to other parameters such as fat, protein, carbohydrates, fibre or blood glucose.

The data points on the right-hand side of the chart below [3] indicate that high protein foods (e.g. fish, tuna and steak) cause a small rise in blood glucose.  However, the blood sugar response to protein is still small relative to the high carbohydrate foods on the left-hand side of the plot.

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For most people, the discussion ends there.  Protein does not raise blood sugar much, therefore it is a non-issue. !

But is it really that simple?  What does the expanded food insulin index data set tell us?

the insulin response to protein

One of the challenges I see for type 1 diabetics is that, even if they eat a low carbohydrate diet, they still struggle with blood sugar control after a high protein meal.

Type 1s who have a continuous glucose monitor know that they need to watch out for a rise in their blood glucose three or four hours after a high protein meal and apply correcting doses of insulin to keep their blood sugar from going too high.

Looking at the plot of protein versus insulin index below, we can see that the insulin response to protein is more significant than the blood glucose response to protein.

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For instance, the insulin index score for whitefish is 42%, however, it only receives a 20% glucose score (note: the percentage scores are relative to pure glucose which has a glucose score and a food insulin index score of 100%).

Maybe there is something going on that can’t simply be explained by the blood sugar response alone?

If we plot the glucose score versus the insulin index we see that glucose and insulin are not directly proportional.

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Low carbohydrate high protein foods such as chicken, cheese, tuna and bacon require a lot more insulin than would be anticipated if insulin was directly proportional to the blood glucose response.

On the lower side of the trend line, we have high carbohydrate foods from whole food sources such as raisins, wholemeal pasta, brown rice and water crackers having less of an insulin response than would be anticipated from the blood glucose response.

diabetic versus normal response to protein

The figure below compares the blood sugar and insulin response to 50g of protein (200 calories) in type 2 diabetics (yellow lines) and healthy non-diabetics (white lines). [4]  We can see that:

  • Blood glucose remains relatively stable for healthy people after eating 50g of protein. However when someone with Type 2 Diabetes eats a high protein meal the insulin secreted seems to bring the blood sugar down from elevated levels!
  • Insulin is elevated for more than five hours after ingestion of protein, particularly for the insulin resistant type 2 diabetic. There’s definitely something going on with insulin in response to high protein foods, even if we don’t see a sharp increase in blood sugar.
  • The diabetic requires a lot more insulin to deal with the same quantity of protein and it takes a lot longer for the insulin levels to peak and comes down.

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We can also see from the insulin response that protein takes more than three hours to digest and metabolise.  It is possible that the food insulin index data (which is based on the measurement of insulin over only three hours) underestimates the insulin response to protein-containing foods and that the insulinogenic demand of protein is actually higher than predicted by the food insulin index data (i.e. protein requires more than 56% of the insulin relative to carbohydrate).

what happens when we eat a lot of protein?

The question of what happens to ‘excess’ protein that is not required for muscle growth and repair is controversial, and the science is not exactly clear.

Does the energy from unused protein magically disappear?  If it did, then protein would be the ultimate macro nutrient that everyone should eat to lose weight.  We could effectively ignore calories from protein.

Does it turn into nitrogen and get excreted in the urine?

Or does it turn into glucose ‘like chocolate cake’?

There is limited authoritative information on this topic. However, some helpful guidance that I’ve found on the subject is outlined below:

  • Richard Feinman says that “…after digestion and absorption, amino acids not used for protein synthesis may be trashed.  The nitrogen is converted to ammonia which is converted to urea and excreted.  The remaining carbon skeleton can be utilized for energy either directly or converted to ketone bodies, particularly on a very low carbohydrate diet.” [5]
  • Richard Bernstein says “Dietary protein is not the only source of amino acids.  The proteins of your muscles continually receive amino acids from and return them to the bloodstream.  This constant flux ensures that amino acids are always available in the blood for conversion to glucose (gluconeogenesis) by the liver or to protein by the muscles and vital organs.” [6]
  • According to David Bender “In fasting and on a low carbohydrate diet as much of the amino acid carbon as possible will be used for gluconeogenesis – an ATP-expensive, and hence thermogenic, process.” [7]

So it appears that amino acids circulate in the bloodstream and can be used as required for protein synthesis or to stabilise blood glucose levels.

The figure below [8] shows a comparison of the blood glucose response to ingestion of glucose and 600g of lean beef (i.e. a huge serving of steak!).

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During the more than eight hour period that the steak takes to digest you can see the nitrogen levels continue to rise.  Meanwhile, blood glucose rises only slightly until around four hours after the meal and comes back down.

tbonesteakongrill

What appears to be happening here is that the amino acids from digestion are being progressively released into the bloodstream (over a period of digestion of more than eight hours) but are not immediately converted to blood glucose.  Thus the digestion of protein does not cause a sharp rise in blood glucose.

It is said that gluconeogenesis is a demand-driven process, not a supply-driven process.  What I think this means is that the body can draw on the amino acids circulating in the bloodstream for muscle growth and repair (protein synthesis) or to balance the blood sugar (via gluconeogenesis) depending on requirements from moment to moment.

The fact that we don’t see a sharp rise in blood glucose in response to protein indicates that excess protein does not immediately turn into glucose.  Gluconeogenesis occurs slowly over time with the amino acids being used up as required.

However as noted by David Bender above, if we are fasting or minimising carbohydrates then our body will maximise the use of protein to produce glucose via gluconeogenesis.  Conversely, if we eating more carbs and less protein the body doesn’t need to rely on protein as much for glucose.

do amino acids spill over into glucose in the bloodstream?

Most people aren’t eating so much protein that their amino acid stores in their blood are full to overflowing like peoples’ livers and are typically overflowing with glucose from a higher carbohydrate diet.

It would be interesting to see what happens in someone whose bloodstream became saturated with amino acids from long-term consistently high protein consumption.

Would we see more protein excreted or perhaps a larger amount removed from the blood via gluconeogenesis with subsequent conversion to fat using insulin?

By comparison, when carbohydrate is eaten we typically see glucose causing an immediate rise in blood sugar because the liver is often already full.

glucagon response

A healthy non-diabetic person will release both insulin and glucagon in response to a high protein meal.

Insulin helps to metabolise the protein and grow and repair muscles (i.e. insulin is ‘anabolic’).   Glucagon helps to keep blood sugar stable and prevent it from going too low due to the action of the insulin used in the muscle growth and repair process.

The body secretes both glucagon and insulin in response to a high protein meal (as shown in the figure below [9]).  In a healthy insulin-sensitive non-diabetic person the glucagon will cancel out the insulin response to the protein used for protein synthesis.  Hence we see a flat line blood glucose response in the insulin-sensitive non-diabetic.

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In a diabetic, particularly type 1s, we often see blood sugar rising after a high protein meal due to the initial glucagon response and then gluconeogenesis as some of the protein converts to glucose.  In the diabetic, the insulin response is either inadequate (due to poor pancreas function) or ineffective (due to high insulin resistance) and therefore the blood sugar does not remain stable as it would in a metabolically healthy person.

By contrast, after we eat a high carbohydrate meal glucagon decreases as the insulin increases and the body moves into fat storage mode as shown in the following figure. [10]  The primary thesis of Protein Power is that we want to do whatever we can to maximise glucagon which promotes fat burning rather than insulin which leads to fat storage.

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Even though glucagon offsets the insulinogenic effect of protein used for protein synthesis, it seems that the glucogenic portion of protein requires insulin.

I haven’t found any data on the subject, but I wonder if the body does not secrete glucagon to negate the effect of the ‘excess’ protein over and above the body’s requirement for protein synthesis (say 7 to 10% of calories)?

If this were the case, then the glucogenic proportion of excess protein will behave largely like a carbohydrate with no glucagon to counteract the insulin?

glucagon, the antidote to insulin?

The observation that glucose does not rise significantly in response to protein is often taken to mean that protein is a non-issue.  [11]  [12]

This may be largely true for someone who is insulin sensitive. However, diabetics with impaired pancreatic function may not be able to secrete adequate insulin to offset the effects of glucagon and keep their blood sugars stable.

If you are a type 2 diabetic or someone with impaired insulin sensitivity I suggest that it would be better to keep your carbohydrate AND protein intake to the point where your body can keep up and maintain normal blood sugars?

The image below shows the continuous glucose monitor (CGM) plot of a type 1 diabetic after ingestion of a protein shake (46.8g protein and  5.6g of carbs).

Without insulin, there is a blood sugar rise over a period of more than eight hours, not dissimilar to what you would see from carbohydrates.

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Is this blood glucose rise from gluconeogenesis of the protein or is the blood glucose rise from glucagon in response to the ingested protein or a bit of each?  It’s hard to know.

What we do know is that there is a rise in blood glucose that needs to be managed if we are going to achieve optimal blood sugar control.

letting your pancreas keep up

For a diabetic who is insulin resistant and/or whose pancreas is not producing adequate insulin, the issue is that the total insulin load of their diet (from carbohydrates and the glucogenic component of protein) is more than their body’s ability to keep blood glucose under control.

From the insulin index data, we know that the body’s blood sugar and insulin response are proportionate to carbohydrate plus about half of the ingested protein.

So potentially we can balance our blood glucose response by managing the glucogenic inputs, that is, by moderating protein and keeping carbohydrates adequately low.  And by doing this, we can minimise, or perhaps eliminate, the need for insulin or other medications.

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the high protein ‘hack’ for diabetics

To some extent, obtaining glucose from protein rather than carbohydrate is a beneficial ‘hack’ for someone who is not able to manage their blood sugars given:

  • eating higher levels of protein will ensure that the body’s needs for essential amino acids are met or exceeded;
  • the blood sugar rise from protein is much slower than it is for carbohydrate foods and hence it is easier to keep blood sugars under control;
  • protein takes more energy to convert to glucose than using carbohydrate directly. Hence there is additional energy lost in the process (i.e. a calorie of protein is not really a calorie if you have to convert it to glucose before it can be used), [13] and
  • protein is more satiating than carbohydrates.

Paul Jaminet argues that obtaining glucose from protein is not ideal given that it’s not as energy efficient as getting it directly from carbohydrates.

However, I think that the optimal approach is to ensure that you maximise vitamins, minerals, fibre and amino acids from carbohydrate and protein containing foods while at the same time not overwhelming your body’s ability to maintain optimal blood sugars due to excess glucose from either carbohydrates or excess protein.

To some extent, it’s a balancing act between gaining adequate nutrition from things that will raise blood glucose while at the same time not overwhelming the ability of your pancreas to produce insulin to keep blood sugars in the ideal range.

The food ranking and meal ranking systems have been designed around this approach.

what is the optimum amount of protein and carbohydrates?

I find Steve Phinney’s well formulated ketogenic diet chart helpful when it comes to understanding how to optimise protein and carbohydrate intake.

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  • The minimum protein intake is around 10% of calories or 0.8g/kg body weight. [14] At this point the vast majority of the protein will go to muscle growth and repair.  Based on the guidance given by the WFKD triangle you might even be able to tolerate up to 20% carbohydrates and stay in nutritional ketosis if you were to keep your protein levels low.  At this point, you won’t have to worry too much about gluconeogenesis messing up your blood sugars because all of the protein will be used up in protein synthesis.
  • If you are active, then you will likely want higher levels of protein, with 1.2 to 1.7g/kg body weight recommended for athletic performance. [15] Higher levels of protein will ensure that you have enough amino acids for optimal physical and mental function rather than just being adequate.
  • As we move to higher levels of protein above the minimum 10% of calories we should consider also reducing carbohydrate and increasing fat, due to the fact that the glucogenic portion of the protein that is over and above the basic needs for growth and repair will likely be turned into glucose, requiring increased levels of insulin which will work against you if your goals are reducing your insulin load in order to stabilise blood sugars or to lose weight.

I have discussed the concept of balancing glucose load from protein and carbohydrates with your body’s ability to produce insulin in more detail in the article the Goldilocks glucose zone.  However, if you are keeping track of your food intake you can use the formula below to calculate and track your insulin load.

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If you are not yet achieving normal blood sugar levels you could try winding back your insulin load.  Most people find that they will achieve stable blood sugars and nutritional ketosis with an insulin load of around 125g, however, your mileage may vary, and you will likely have to tweak this level to find your optimum based on your goals and your situation.

What do you think of all this?  I would love to hear your response in the comments below.

 

 

 

references

[1] See http://en.wikipedia.org/wiki/Glucogenic_amino_acid,   https://www.dropbox.com/s/4dkl03mz2fci71v/The%20metabolism%20of%20%E2%80%9Csurplus%E2%80%9D%20amino%20acids.pdf?dl=0 and http://www.medschool.lsuhsc.edu/biochemistry/Courses/Biochemistry201/Desai/Amino%20Acid%20Metabolism%20I%2010-14-08.pdf

[2] http://ses.library.usyd.edu.au/handle/2123/11945

[3] Glucose score is the area under the curve of the rise in blood glucose response over three hours relative to pure glucose tested in healthy non-diabetics.

[4] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC524031/

[5] Chapter 5 of The World Turned Upside Down: The Second Low Carbohydrate Revolution.

[6] Dr Bernstein’s Diabetes Solution, page 96.

[7] https://www.dropbox.com/s/4dkl03mz2fci71v/The%20metabolism%20of%20%E2%80%9Csurplus%E2%80%9D%20amino%20acids.pdf?dl=0

[8] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC424828/pdf/jcinvest00541-0071.pdf

[9] https://books.google.com.au/books?id=3FNYdShrCwIC&printsec=frontcover&dq=marks+basic+medical+biochemistry&hl=en&sa=X&ei=-ctaVcivOJfq8AXL84CAAw&redir_esc=y#v=onepage&q=glucagon&f=false

[10] https://books.google.com.au/books?id=3FNYdShrCwIC&printsec=frontcover&dq=marks+basic+medical+biochemistry&hl=en&sa=X&ei=-ctaVcivOJfq8AXL84CAAw&redir_esc=y#v=onepage&q=glucagon&f=false

[11] http://caloriesproper.com/dietary-protein-does-not-negatively-impact-blood-glucose-control/

[12] http://www.ketotic.org/2013/01/protein-gluconeogenesis-and-blood-sugar.html

[13] See chapter 15 of Richard Feinman’s The World Turned Upside Down: The Second Low Carbohydrate Revolution for an in depth discussion of this topic.

[14] This is based on the point where at least half of the population has adequate protein!  Not exactly an ideal goal to be shooting for!

[15] https://www.dropbox.com/s/zelfo3n0q8kvtfx/Paoli%20et%20al.%20(2015)%20The%20Ketogenic%20Diet%20and%20Sport%20A%20Possible%20Marriage.pdf?dl=0

 

post updated July 2017