Does Long Term Ketosis Cause Insulin Resistance?

blindmenandelephant

We’ve never really seen a man or an elephant in ketosis before  . . .

“It’s a snake.”

“It’s a wall.”

“It’s a rope.”

“It’s a fan.”

“It’s a tree.”

“It’s insulin resistance.”

I’ve always been fascinated by those describing a “new finding” in medicine.  I am reminded of the story of 5 men who, never having seen an elephant before, were blindfolded and asked to describe what he discovered. However, each man was introduced to a different part of the elephant.  Each of them had a dramatically different description of the elephant and each made a conclusion that was very different from the others.

What is fascinating, is that we usually make our “blindfolded comparisons” to those things we have seen or about which we have some descriptive understanding.  Observing and describing human physiology is much like examining an elephant while blindfolded for the first time.

This week’s “blind-folded finding” is what has been interpreted by some as “insulin resistance” made worse by a ketogenic diet. Really?  This perked my curiosity, because I’ve personally been following a low-carbohydrate/ketogenic diet for 10 years and have thousands of patients doing the same.  To this day, I’ve never seen insulin resistance “get worse.”  In fact, it gets better.  Clinically, it seems to take about 18-24 months to improve, but, it usually gets better.

THE QUESTION –

I’ve had three people from around the world contact me this week and ask why, after being on a ketogenic diet and “in ketosis,” they suddenly get a notably large blood glucose spike when they cheat.  By notably large, I mean that their blood sugars rise to over 200 mg/dl within 2 hours of a carbohydrate containing meal.  Now, they admit to rapid glucose recovery within an hour or two, and their hemoglobin A1c levels are subjectively normal (less than 5.6%).  The worry is “am I becoming diabetic?”  They also complain that after having been in ketosis for longer than 3-4 months, they cannot get their fasting blood sugars below 100 mg/dl.

Those asking me the question about this anomalous “physiological insulin resistance” referred to a couple of off-the-cuff blogger’s posts from 2-3 years ago referencing a few small studies (some of which were very poorly designed) [here, herehere & here] in the journals from 10-20 years ago.  These articles describe a physiologic response interpreted as worsening “insulin resistance.”  However, if you understand what is actually occurring in the Ketonian (yes, I made that term up – there will soon be a whole village of us), I see it as a normal physiologic response. It is misinterpreted by those who’ve never actually seen long term ketogenic physiology, as  anomalous, in the average human.

Adapt Bar Berry

THE ANSWER – 

I’ve been seeing this slight elevation in fasting blood sugar with normal or low normal HbA1c in myself and many of my patients for quite some time.  However, I never saw it as “insulin resistance” worsening.  Clinically, when I tease out the food logs, it usually ends up being protein intake is too high, the person is using a sweetener or creamer causing rebound morning glucose elevation or, in those with low normal HbA1c’s (4.3-5.6%), it is in actuality a protective mechanism of “glucose sparing” in the keto-adapted individual (1, 2).

It can very easily be explained when one understands how ketones are actually used in the keto-adapted individual.  First, a wonderful figure below (Thank you for pointing me to this one, Dr. Peter Attia) found in Dr. Veech et. al.’s paper (3) gives us an overview of how ketones skirt the TCA cycle within the mitochondria of the cell,  causing inhibition of pyruvate dehydrogenase leading to glucose sparing by the cells of the brain that still require it’s availability (Oh, by the way, this is how we survived harsh winters and famines).

BHB use in the TCA cycle

From the Figure 1 above, you can see that beta-hydroxybuterate [BHB (a ketone)] is converted to acetoacetyl CoA leading to the production of pyruvate, block-aiding additional glycolysis or inhibiting further glucose production at the liver level.  Because the muscle tissues become more adept at using BHB, GLUT receptors are down-regulated at the muscle level as a person becomes more keto-adapted.  Although we still have much to learn about the keto-adapted state, we know that this occurs more prominently in the muscle tissues than in the gut and brain.  This fascinating glucose sparing phenomenon, has been interpreted by some as “worsening insulin resistance.”

Not to worry, glucose sparing is rapidly reversible and transitory within 1-3 days of increasing carbohydrate intake above 100-150 grams per day (1).  It is also why those who become keto-adapted get a carbohydrate hangover including headache, stomach cramps, diarrhea, and malaise lasting 8-24 hours after cheating.

Is this bad? Absolutely not! It is NORMAL! (It’s just that most people, physicians included don’t know what the normal physiology of the Ketonian should look like.)  Is it going to kill you, cause a stroke or give you a heart attack?  Absolutely not.  The elevated BHB actually increases production of adiponectin, leucine & glutathione that have antioxidant properties protecting one from transient inflammatory rises in blood sugar, enhancing insulin’s effect on the muscle, and preserving muscle mass while allowing for fat metabolism (4, 5, 6).

THE TAKE-HOME MESSAGE – 

First, don’t cheat if you don’t want to see transient rises in blood sugar and experience the wonders of a carbohydrate hangover and some mild reactive hypoglycemia (low blood sugar) after the fact.

Second, if you’ve been in ketosis for longer than 3-4 months, and you absolutely must get another two or three hour oral glucose tolerance test (OGTT), you might want to increase your carbohydrate intake to 50-100 grams per day 1-3 days before the test to avoid an anomalous spike in blood glucose.  (One OGTT was enough for me . . . but hey, some of us are gluttons for punishment.)

Third, enjoy your eggs, pass the bacon and stir me up some Keto//OS.

KetoOS

KetoOS – Drinkable Exogenous Ketones

References:

  1. Kinzig KP, Honors MA, Hargrave SL. Insulin sensitivity and glucose tolerance are altered by maintenance on a ketogenic diet. Endocrinology 151: 3105–3114, 2010.
  2. Oliveira Caminhotto R, Lima FB. Impaired glucose tollerance in low-carbohydrate diet: maybe only a physiological state.  
  3. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. Ketone bodies, potential therapeutic uses. IUBMB Life. 2001 Apr;51(4):241-7.
  4. Jarrett SG, Millder JB, Liang LP, Patel M. The ketogenic diet increases mitochondiral glutathione levels. J Neurochem. 2008 Aug; 106(3): 1044-51.
  5. Rauch JT et al. The effects of ketogenic dieting on skeletal muscles and fat mass. J Int Soc Sports Nutr. 2014; 11(Suppl 1): P40
  6. Manninen AH. Very low carbohydrate diets and preservation of muscle mass. Neut Metab (London). 2006; 3:9

12 Comments on “Does Long Term Ketosis Cause Insulin Resistance?

  1. Thanks Doc! I noticed a bs of 128 about 30 minutes after a cheat meal. But then an hour after, I was at 75. I wondered why the spike. This makes since.

    • Yes. I am familiar with refeeding syndrome. Patients on a ketogenic diet, if they are following it correctly, should not experience refeeding syndrome, as a ketogenic diet is not starvation.

      • Hi Doc!
        Great articles!
        I really want to eat a ketogenic diet, and most of the time I do.
        I have one major problem with it though. I get very cold. And when I get that cold I loose My energy, I get constipated, And so on…
        I do have SIBO, and probably might have some additional problem with My gut. I have tresteg with antibiotics, and now I’m trying to SLOWLY add some probiotics.
        I’m thinking I might have low testosterone and/or some problem with My Thyroid.. I have no idea what the root cause is.
        How can I make the ketogenic work For me?
        // Patrik

      • Patrik, you describe three different issues that need to be assessed. A ketogenic diet helps in all the areas you described, however, if you are getting significant symptoms, then a full evaluation of your metabolism should be completed by your doctor if not already. An appropriate lab test looking at your hormones, gut bacteria, insulin loads are an initial start.

  2. Hello Dr. Nally:
    Thank you for all the wonderful information you provide.
    I have been living LCHF for eight months. I am experiencing the FBS creep. My FBS is now usually 100. It had been in the low 90’s. If I fast for 36 hours FBS declines to the 70’s, but returns to 100 the day after I resume eating LCHF. For the most part, BS remains between 95 and 105 throughout the day.
    You say that “this physiological insulin resistance is normal”. My question is, is “normal” healthy? If one is diabetic (I am not.), it is “normal” for blood sugar to soar if a high carbohydrate meal is eaten. In this case normal is not healthy. I “thought” (Uh Oh!! 😊) that the closer one’s fasting blood sugar was to 83, the healthier that individual was, so I am a little concerned that my blood sugar now is always at 100 unless I fast for 36 hours.
    So…… my second question is: Are there any long term negatives to having an elevated (100) BS while eating LCHF. Are there any studies?
    Thank you.
    Bob Griffiths

    • One add on: This morning as usual my FBS was 99. Because I hadn’t eaten in twelve hours I ate one (1) teaspoon of peanut butter (less than two (2) grams of carbs) before a moderate 40 minute workout with weights. Fifteen minutes after my workout, without having eaten anything more, my BS was . Usually BS would be around 100 at this time. I then ate three slices of bacon and a heavy fat shake with less than ten carbs. Fifteen minutes later BS was 106. An hour later BS was still 106.
      Any insight as to why my BS is so high while eating minimum carbs.(body fat % is approximately 12%)
      Thank you.

      • Bob, you are asking me to diagnose specifics regarding your health. That will need to be done face to face in a doctor visit. Please schedule an appointment.

      • Hey Doc:
        Thanks for your reply. I understand.
        Your blogs, your periscopes are outstanding. Thank you. Thank you. Thank you!!
        You are helping many, many people.
        Thanks.

  3. Hi Dr. Nally, HgA1c has gone from 5.9 8yrs ago to 6.1. FBS is 109mg%. BMI is 28, insulin level 15.9. Have been traveling the past few months and eating way too many carbs. Now do aerobic aerobic exercise 30min at least 5x/wk and have started going ketogenic which surprisingly I like. Goal is to loose 10% of current wt (20lbs) and maintain loss, keto and exercise program. Anything else you would recommend to keep insulin levels and resistance down. I see where a intermittent fasting program is recommended by a nephrologist (Jason Fung) who states he has had great success with diabetics on this, the research is scant.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s

%d bloggers like this: