is the insulin response to protein dose dependent?

The observation that protein requires insulin initially appears to conflict with a number of studies and anecdotal evidence that suggest protein does not have a significant effect on blood sugar. [1] [2] [3]

I think there are two issues to consider.

Firstly, a healthy non-diabetic will be able to deal with the blood glucose rise caused by gluconeogenesis due to protein, hence the overall blood sugar rise may not be significant.  The extension of this argument is that almost any level of protein intake is a good thing.  I haven’t however seen any real discussion around on the insulin effects of eating a diet high in protein diet.

However type 1 diabetics certainly do see a rise in their blood sugar levels that they need to cover with insulin.  Without insulin to blunt the glucogenic effect of the protein, the blood sugar rise from the fast acting protein is not dissimilar to what you would see  from carbohydrates.

The picture below shows how a well controlled type 1 will give small additional boluses as they see they blood sugar rising due to protein.  This is sometimes called “sugar surfing”.  While this approach provides good blood sugar control wouldn’t it be even better if a type 1 diabetic could better predict the insulin requirements before the meal to proactively predict the blood sugar rise rather than just reacting to the blood sugar roller coaster?

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If you’re metabolically healthy  the blood sugar rise and insulin secretion due to gluconeogenesis after a large protein meal may not be cause for concern.  However if you are not metabolically healthy and / or are aiming for nutritional ketosis moderating protein to manage excessive gluconeogenesis may be something you want to do.

Secondly, the degree of gluconeogenesis appears to be dose dependent.  If you exercise intensely and the amount of protein you eat is moderate then your body will likely shuttle protein to your muscles for growth and repair as the highest priority.

If you are not active, and you eat a large amount of protein then excess protein will be converted to glucose in your blood stream, raise insulin levels and be sorted as fat.

So while the effect of protein on your blood sugars and insulin is dependent on a number of factors, allowing for about half the insulinogenic effect of carbohydrates from protein appears to be a reasonable starting point..

[next article…  is sugar really toxic?]

[this post is part of the insulin index series]

[Like what you’re reading?  Skip to the full story here.]

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

[2] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342171/pdf/IJE2015-216918.pdf

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

14 thoughts on “is the insulin response to protein dose dependent?”

  1. the amount of bcaa leucine will spike insulin and at the same time glucagon is released by ingestion of protein so theres a release of liver glycogen and not gluconeogenesis is the reason for a rise in blood sugar which is offset by insulin release in normal person…gluconeogenesis is a slow demand driven process by the brain which doesnt spike blood sugar….type 2 diabetics have 3 times more glucose from the liver (gluconeogenesis ) due to some unique errors and metformin is the first line of drugs for t2 which controls liver gluconeogenesis …in type one I can only guess that the ingestion of protein and high sugar is the glycogen hormone spike not being offset by insulin release by the body………your use of gluconeogenesis .argument is totally flawed throughout your work as tye 2 large ingestion of protein doesn’t raise my blood sugar without meds and has been proven over and over again……

    1. Larry

      I agree that protein doesn’t “spike” blood sugar given that protein digestion is slow and most people can keep up with adequate insulin to suppress the blood glucose rise.

      What I’m saying is that protein not used by the body for growth and repair can be converted into glucose through GNG and at some point will require insulin to be used for energy or stored as fat.

      If you look at http://en.wikipedia.org/wiki/Glucogenic_amino_acid you will see that the majority of the amino acids that make up protein (74% by weight across the USDA food database) are glucogenic, two are ketogenic (12% by weight) and the other five can be both (14% by weight).

      Unless we believe that the energy from protein magically disappears or is excreted as nitrogen in the urine or something similar then it appears likely that the major of protein not used for growth and repair of the body will be converted to glucose or glycogen and eventually require insulin.

      If we are trying to manage insulin levels for whatever reason (keto dieter, weight loss, diabetic etc) then we need to have some regard for the total protein ingested.

      If you are doing low carb high protein then the protein will have a greater effect on your insulin load than if you were doing high carb low protein.

      Perhaps the rise that type 1s see with a high protein meal occurs once the protein digests, and then the excess not used for muscle repair and filling the liver and muscles with glycogen then flows into the blood stream and shows up as high glucose that requires insulin?

      Cheers

      Marty

  2. I enjoy your blog very much and have gotten very good info here, but as to this particular article, I tend to agree with the first commenter above. You may wish to read Richard Feinman’s recent book about the biochemistry of metabolism, The World Turned Upside Down. Gluconeogenesis (GNG) has been largely misunderstood in the LC community, and even the diabetic and medical communities, and Feinman’s biochemistry teaching helps clear this up. He also blogs at feinmantheother.wordpress.com

    In a nutshell: it is not the AMOUNT of protein available that determines whether GNG occurs. GNG is ongoing all the time. It’s the reason we don’t die in our sleep. GNG, like all other metabolic processes, is based on feedback, and other variables as they exist at any given time, and being a metabolically expensive process, is driven by actual bodily needs at a given moment. It is not a mass-based action (ie how much of something do you have), but a control-based action (ie what controls activate/deactivate the process). Hope this helps.
    I look forward to your continued posts.

    1. Thanks Wendy. I just downloaded The World Turned Upside Down yesterday and have started reading it. Also digging into the biochem a little more to understand this more thoroughly.

    2. Wendy

      I just had another read of chapter 6 of The World Turned Upside. He says that GNG goes on all the time, not just as as last ditch effort in times of starvation.

      My understanding is that in times of starvation GNG will metabolise your muscle for glucose. If you’ve got adequate calories and just enough protein for muscle growth and repair then you won’t get any GNG. If you have adequate calories or excess calories and protein in excess of what is required for growth and repair of the muscles and all the other bodily functions then the majority of that protein will be turned into glucose and potentially stored as fat via insulin if not used for energy.

      In type 1 diabetics who are eating low carb and significant amounts of protein who do not have pancreases that can respond to the glucose from GNG we see blood sugar rises. In most people with working pancreases you don’t see the blood sugar rise because it’s gentle (in comparison to most carbs). For all intents and purposes the excess protein behaves largely as a carb from what I can see.

      If you can point me to a reference that I’m missing I’d be eager to learn more. I think this issue is subtle but important.

      1. Yeah, there’s a comment there from me that I just noticed Amber has replied to saying that GNG is demand driver rather than supply driven. I haven’t yet read the rest of the series, but I will have a look shortly.

        Interestingly, the longest part of this article is an epilogue where they quote a whole pile of people saying the opposite. Even based on the two sides of the article that they paint I find it much easier to believe the opposing argument.

        Just because blood glucose doesn’t rise significantly in healthy normal people doesn’t mean that a large proportion of the protein isn’t being converted to glucose or that it isn’t requiring a lot of insulin to keep the healthy person’s blood sugars in check.

        By analogy, just because something is low GI doesn’t mean it won’t require a significant amount of insulin if you eat a lot of it. Sure it digests slowly and the blood sugar doesn’t go up, but it’s still turning to glucose and that needs insulin to metabolise.

        The majority of proteins are glucogenic rather than ketognic (http://en.wikipedia.org/wiki/Glucogenic_amino_acid). If not used by the body they don’t magically disappear.

      2. Wendy, this is my response to Amber at ketotic.org.

        Thanks for the response Amber.

        I have now read the rest of your posts in this series and from what I can see the essence of your argument is: because ingested protein does not significantly raise blood glucose you have concluded that excess protein does not turn into glucose via gluconeogenesis.

        I think the point you are trying to get across is the concept that eating lots of protein rather than carbs is fine and not unhealthy and it will not raise your blood sugars. I’m fine with that and I think that’s for the most part correct.

        I can also agree that GNG is a demand driven process when it comes to using the body’s own muscle (along with fat) in a calorie restricted state.

        However when your site is called ketotic.org and you’re taken to be an authoritative source on the ketogenic diet I think you need to go a bit deeper than just observing blood sugars which are just a symptom, not the root of the issue.

        Maintaining blood sugars in the normal range is not, to my mind, is not the same thing as being ketogenic. Ketogenesis occurs when our insulin is low enough that we can easily use fat for fuel rather than storing it. It occurs when the glycogen are not overfull and we need to rely on fat for fuel.

        So the discussion needs to be about INSULIN and not blood sugar.

        So moving forward, the testing of the food insulin index shows that protein containing foods generate insulin. Tests in healthy people indicate that protein generates a bit more than half the insulin in normal healthy people as carbohydrate (see https://optimisingnutrition.wordpress.com/2015/03/23/most-ketogenic-diet-foods/). It should be noted that this is AFTER the needs of the body (e.g. growth, repair, brain function etc) are taken into account. Hence it is likely that protein has the potential to create significantly more than half as much insulin as carbohydrate gram for gram.

        My wife is a type 1 diabetic and I hang out diabetes forums. One of the major issues for type 1 diabetics is how to deal with the glucose effect of protein. Due to the slower digestion time of protein what you tend to see is a slower and later rise in blood sugar compared to carbohydrate.

        A normal non-diabetic person would be able to tackle this rise in blood sugar (due to GNG?) with insulin because they have normal pancreatic function, however for a type 1 they have to either calculate a dose up front based on some assumption of how much protein turns to glucose or continually microdose if they have the luxury of a continuous glucose metre to keep the blood sugars in normal range. See https://optimisingnutrition.wordpress.com/2015/04/18/is-the-insulin-reaction-to-protein-dose-dependent/

        If you listen to people like Jimmy More in the keto scene you will hear him continually banging on about is that you have to keep carbs low and MODERATE PROTEIN if you’re going to achieve significant blood ketone readings (due to reduced insulin levels).

        I think managing insulin (not just achieving blood normal blood sugar) is a subtle but important distinction. The ACCORD study recently showed that optimising blood sugar via high levels of insulin were diabolical for health (i.e. it’s the insulin not the blood sugar that is a bigger health concern). Elevated insulin levels are also typical characteristics of the obese. It’s important to be have times of low insulin levels if you’re going to be healthy and normal weight.

        The other question is, if protein in excess of the body’s requirements does not turn into glucose via amino acid, then where does it go? Is it all excreted as ammonia and / or nitrogen? Does it magically disappear because protein a magical macronutrient that does not make you fat? Does it all turn into ketones that are used for energy?

        You’re no doubt aware that some amino acids are ketogenic, some amino acids are glycogenic and some can be both. The vast majority of the amino acids that make up protein are glucogenic and only two are ketogenic. See http://en.wikipedia.org/wiki/Glucogenic_amino_acid

        There’s not a lot written out there so I thought I’d tally up the glucogenic, ketogenic and “both” amino acids in the USDA foods database. I’d love you to check out my numbers (https://www.dropbox.com/s/bxjcoegtlw4l05o/USDA%20foods%20database%20-%20ketogenic%20versus%20glucogenic%20amino%20acids.xlsx?dl=0), but it appears that if you assume that all the “both” aminos are ketogenic we end up with about 78% of the amino acids being glucogenic. If we assume that all the “both” amino acids are glucogenic then we end up with about 90% of the amino acids having the potential to turn into glucose if in excess of the body’s requirements. So it appears to me that about 85% of excess protein will be turned to glucose and eventually require insulin!

        So in sum:

        1. The vast majority of the protein that in excess to the body’s needs will turn into glucose via GNG.
        2. You don’t see a sharp blood sugar rise in most normal healthy people because it is stored as glycogen in the liver and muscle for later use and any excess that spills into the blood over and above what is required for the body’s repair and refilling glycogen stores.
        3. When this glucose from glycogen is used for energy or stored as fat it will require insulin.
        4. Excessive GNG due to high levels of protein ingestion will not lead to a ketogenic state.

        Cheers

        Mary Kendall

  3. I think the difference in perspective simply what is “times of starvation.” This occurs several times a day, when your body needs protein, which is a 24/7 demand but doesn’t happen to have a dietary source of it at the time (only has dietary protein available for how many hours/day? This will vary). It uses its own muscle, and then dietary protein replaces it.
    As to your T1D para… this may be out of my depth to answer. But I believe from what I’ve read that the BG rise that happens is mistaken for GNG, but is actually glycolysis from glycogen stored in the liver. GNG just takes much longer than is compatible with the timing of the blood sugar rise. Why do you think that is NOT the case?
    It may be helpful to put a question like this directly to Feinman, via his blog.
    All best.

  4. Depending on protein source it take between 1-4 hours after meal before BS is raising in a type 1 diabetic. Chicken is one of the fastest to raise BS. And it is a pure simple fact. Research is not any evidence, it is just a piece of sample data that might be correct or wrong.

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