Insulin vs. Ketones

By December 2, 2016Blog

POST SUMMARY: What this means for you…

Let ketones be your guide to knowing how well you’re controlling your insulin levels (because ketones are easier to measure at home than blood insulin levels). Make an effort to keep insulin low by avoiding the starchy carbohydrates and consuming insulin-friendly fat.

Insulin Resistance and Ketones

If you’ve heard the word “ketone” before, I bet it was in the context of a conversation about someone with diabetes. And rightly so—diabetes (type 1 or 2) is a problem of insulin (not glucose!), and insulin and ketones are, in a way, opposites.

Ketones are an inverse indicator of insulin because insulin inhibits ketone production (i.e. ketogenesis) [1, 2]. In other words, if insulin is high, ketones are low; if insulin is low, the liver breaks down fat into small pieces called ketones (insulin in fact tells the liver to make and store fat) [1]. For this reason, a diet that keeps insulin low is referred to as a “ketogenic diet”—the low insulin levels allows the production of ketones.

You’re invited to attend one of our free, > live lectures to learn more about InsulinIQ™.

Metabolic Garbage?

I used to consider ketones as a simple indicator of insulin—for me they were only relevant insofar as I wanted insulin to be low and increased ketones are a sign of low insulin.

However, ketones are enjoying their day in the sun, but it wasn’t always this way.

Ketones were once considered “metabolic garbage” because scientists were unaware of any role for them. Oh how the times have changed! Not only are ketones recognized as a viable fuel source for almost every cell, including the brain and muscles, but they’re also important signaling molecules that have multiple beneficial effects. Some of the known benefits of ketones include increasing the number of mitochondria in the cell (where fats are broken down) [3], reducing oxidative stress [4], controlling inflammation [5], improving brain/cognitive function [6] and, in the case of some organisms (no evidence in humans), extending lifespan [7].

It’s for these reasons that people have started selling (and buying!) supplements with ketones.

Nutritional vs. Supplemental Ketosis

With evermore evidence supporting the benefits of ketones, several companies have come to life that seek to capitalize on ketones’ new reputation. These companies claim to improve one’s health by providing oral ketone supplements and there is evidence, mentioned above, that supports the benefits of ketones. However, putting ketones in your mouth is a very different state than that created by a diet that induces ketone creation in your liver from your own fats.

Oral ketone supplements may be beneficial, but this is inarguably an artificial condition where ketones may be increased at the same time as insulin. Ketones and insulin are opposites—they are never high at the same time in normal physiology. It just doesn’t happen. If insulin is high, ketone production (i.e., ketogenesis) is blocked. If insulin is low, ketone production is increased.

You’re invited to attend one of our free, > live lectures to learn more about InsulinIQ™.

Doing More Harm Than Good?

The effects of having possibly both insulin (due to diet) and ketones (due to supplements) elevated simultaneously are unknown. But I’ll speculate. The main circulating ketone (and what is ingested with ketone supplements) is β-hydroxybutyrate, which is converted to acetoacetate and then to acetyl-coA. Acetyl-coA is at the crux of multiple important metabolic pathways dictated by the energetic state of the cell and the prevalent mix of hormones. Acetyl-coA, as mentioned, is involved in ketone formation (and use), as well as the formation (and use) of fats and, finally, it can be broken down for the production of chemical energy. When insulin and acetyl-coA are increased, insulin activates an enzyme called acetyl-coA carboxylase (ACC) [8]. ACC is a key enzyme in a process called lipogenesis—the creation of fat. So, taking oral ketones while eating a typical insulin-spiking diet may be doing more harm than good, increasing fat production in the liver.

Again, It’s All About Insulin

In the end, here’s a reminder: it’s the insulin that we really care about. Ketones, in the context of insulin resistance, are mostly useful because they’re an inverse indicator of our insulin levels—they simply tell us how we’re doing keeping our insulin in check. We don’t seek high ketones as much as we seek low insulin. The fact that ketones are themselves beneficial molecules for our health is a bonus.

Should You Be Worried About Ketones?

If you have a functioning pancreas, you’re fine. In the near total absence of insulin (i.e. type 1 diabetes), the amount of ketones produced can be dangerous—a condition called “ketoacidosis”. But a person with a functioning pancreas could avoid carbs completely (I’m not suggesting you do it) and only be in “ketosis”—a level of ketones about a tenth of what’s required for ketoacidosis.

References:

  1. Laffel L: Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes/metabolism research and reviews, 1999, 15:412-426.
  2. Nadal A, Marrero PF, Haro D: Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1. The Biochemical journal 2002, 366:289-297.
  3. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG, Shaw R, Smith Y, Geiger JD, Dingledine RJ: Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Annals of neurology 2006, 60:223-235.
  4. Kim DY, Davis LM, Sullivan PG, Maalouf M, Simeone TA, van Brederode J, Rho JM: Ketone bodies are protective against oxidative stress in neocortical neurons. Journal of neurochemistry 2007, 101:1316-1326.
  5. Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D’Agostino D, Planavsky N, Lupfer C, Kanneganti TD, et al: The ketone metabolite beta-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. Nature medicine 2015, 21:263-269.
  6. Henderson ST, Vogel JL, Barr LJ, Garvin F, Jones JJ, Costantini LC: Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutrition & metabolism 2009, 6:31.
  7. Edwards C, Copes N, Bradshaw PC: D-ss-hydroxybutyrate: an anti-aging ketone body. Oncotarget 2015, 6:3477-3478.
  8. Witters LA, Moriarity D, Martin DB: Regulation of hepatic acetyl coenzyme A carboxylase by insulin and glucagon. The Journal of biological chemistry 1979, 254:6644-6649.

This blog post (and all other posts and content on this website) is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of qualified health providers with questions you may have regarding medical conditions.

Dr Ben Bikman

About Benjamin Bikman, Ph.D. – Ben earned his Ph.D. in Bioenergetics and was a postdoctoral fellow with the Duke-National University of Singapore in metabolic disorders. Currently, his professional focus as a scientist and professor (Brigham Young University) is to better understand chronic modern-day diseases, with special emphasis on the origins and consequences of obesity and diabetes. He frequently publishes his research in peer-reviewed journals and presents at international science meetings.

15 Comments

  • Lois Ketch says:

    Dr. Bikman, how do I measure my ketones? I read your blog post and it is great information, but it does not give me any information about how to measure my ketones. I know there are little gadgets that people with diabetes use where they poke their finger. Is that what I need? If so, where do I buy one? Where do I learn how to poke my finger and what I do after that? And what should the number be? Does it tell me how many ketones I have in my blood? Sorry for all the questions, but I want to monitor my ketones but I don’t know how! Help! Can Lindsay, Cory, or Richard chime in because maybe this is not a question for Dr. Bikman. Thanks!

    • Richard Hart says:

      Barbara, I would stop worrying about glucose and go get a fasting insulin level. That would really tell you where your at in regards to insulin resistance and how well this ketogenic protocol is working.

    • Richard Hart says:

      Lois, I use a ketone meter called nova max plus. You can get them on amazon. You use them the same as a glucose meter. .5 is considered nutritional ketosis and 1.0 is consisderd optimal ketosis for fat loss.

  • Barbara Greenwood says:

    Do higher ketones necessarily mean low insulin in someone with type 2 diabetes?

    I’ve been following a ketogenic diet for 5 months now and have greatly reduced my blood glucose levels. However, it is still somewhat raised compared to a completely healthy person (last HbA1C was 40). So I speculate that my insulin level will still be somewhat raised. I have a blood ketone meter and usually test between 1 and 2, a bit higher when fasting for 24 hours.

  • Nissa says:

    There’s no button for me to repost this on Facebook?

  • JEAN ARNOTT says:

    This post is timely for me right now as I have just been introduced to oral ketones (keto/os). Are you saying that the supplement is okay/beneficial as long as you are on a strictly keto diet vs. taking them while on the normal carb diet? Or do you recommend that oral supplements be avoided in any case?

    • Ben Bikman says:

      Hi Jean. I do not recommend oral ketone supplements. While research certainly suggests a benefit to ketones, so much of the benefit of a LCHF lifestyle is lowering insulin. The fact that ketones increase when insulin is low is a pleasant side effect; it’s not, however, the aim. Ketone supplements seem to blur this line–getting into ketosis for ketosis sake (as opposed to changing a lifestyle to change metabolic health).

  • Linda Peterson says:

    I’m just now seeing your blogs and I have to tell you, this one hit me like a baseball bat between my eyes! LOL! I’ve been eating keto for 8 months and have a very hard time getting my ketones in the range of nutritional ketosis. (.5 – 5.0). I recently had labs done and was surprised at some of my results. My Fasting Insulin was 9.0, but an NMR showed that my Insulin Resistance score was <25, which would imply I'm NOT insulin resistant. My HbA1C was 6.0 and my hsCRP was 12.1! I've never been diagnosed as diabetic or even pre-diabetic, but my morning fasting BG levels usually run just slightly over 100. I've never seen 1 hour post-prandial BG readings of over 110 (not that I know what would be normal, since it's not something my doc is treating me for or training me on.) For 2 hour post-prandial BG readings it's usually in the 90s. (As a side note, last week we went to dinner at a Mexican restaurant and I ran a little experiment. I drank two beers and ate some corn chips. One hour after the meal my BG was 87 and 2 hours later it was 79. Was that an indication of an insulin spike?) The only way to get my ketones to 1.0-2.0 and my BG into the 80s is to do extended fasting (48-72 hrs). Based on this article, it would appear that I'm very insulin resistant since it's so hard to get my ketones up in spite of a low carb (20g or less)/keto diet. IF that's the case, what do I do about it?

    • admin says:

      Hi Linda. Thanks for your comment. Perhaps Dr. Bikman will be able to chime in, but his schedule right now is quite insane! Perhaps you would benefit from asking your question on our Facebook Group. There are a lot of really smart people in our group that could chime in. Are you a member there yet? Here is the link in case you haven’t joined yet. Thanks. LINK: https://www.facebook.com/groups/insuliniq

    • Ben says:

      Hi Linda. Of course, it’s prudent to discuss some of these things with your physician. Nevertheless, I think we get too caught up in measuring ketones. Don’t let ketosis be your goal, but rather trying to control insulin. They’re certainly related, but if you’re feeling good and seeing the health changes you like, don’t let a ketone number discourage you. As you keep eating smart, you’re body will become increasingly insulin sensitive.

  • Sun says:

    Hello Dr Bikman – Thank you for this article.

    I have come to understand that “High blood glucose elicits the release of insulin, which speeds the uptake of glucose by tissues and favors the storage of fuels as glycogen and triglycerides, while inhibiting fatty acid mobilization in adipose tissue.” – Principles of Biochemistry.

    I have a simple question. Assuming that one doesn’t release (or reduce) insulin through reduced carbohydrates and substitutes more fat in the diet, Will the cells get the required energy first from dietary FAT and then mobilize the fatty acids in adipose(for further energy requirement)?

    Thanks for your inputs.:)

    • Ben Bikman says:

      Hi Sun.

      Most certainly, yes. If a diet is providing sufficient glucose to maintain elevated insulin, dietary nutrients will be the first source of energy for the body. Elevated insulin prevents the use of stored fuel by inhibiting the breakdown of fat and the breakdown of glycogen (stored glucose in the liver). Because of this, dietary energy is the only option remaining.

  • Sun says:

    Thank you very much for your message.

    In a state of ketosis, Will the cells get the required energy first from DIETARY FAT and then mobilize the FAT IN ADIPOSE(for further energy requirement if need be)? Or the only metabolic pathway (if that’s the right word) for cells is to derive energy from the fat cells in Ketosis?

    Could you please recommend a book or a published paper to understand this further?

    Thank you for your time 🙂

    • Ben Bikman says:

      The body would use both sources of fuel–dietary and mobilized fat tissue. If insulin is low, lipolysis is active. However, the degree to which the body uses its own stores would certainly partly depend on the amount of fuel provided by the diet.

      You may enjoy reading “the physiology of insulin in man” by George Cahill.

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