Following a Ketogenic Diet for 5 Years, the Story of Glucose Transporter 1 Deficiency Syndrome

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hose of us advocating an ultra-low carb™ diet struggle with the question of the long term effects of following such a prescription. The flak from high-carb (or balanced diet, as they call it) advocates originates in this basic premise: there is no long term research. Their answer to the problem: Stay the course (which we already know is NOT working).

The current norm for many controlled nutritional studies is 12 weeks to a year. Clearly, this span of time in relation to the human lifespan is too short. Basing life-long recommendations on such short-lived studies could easily end up being a case of misrepresentation. As for myself, I believe it’s the strategic reintroduction of carbs at specific times that is the healthiest approach—the topics in both Carb Backloading™ and Carb Nite®.

Lack of research also allows people to post opinion pieces about supposed effects of long-term ketogenic diets, effects that we don’t actually see in practice. But there’s still the elephant in the room:

What really happens with long-term adherence to an ultra-low carb diet?

Long-term ultra-low carbohydrate research?

We can look to clinical populations with certain diseases who are enrolled in studies that are generally longer in duration, stronger in design and much stricter with adherence. We must be careful when extrapolating, however—i.e. generalizing the results to the entire population—but it offers good insights and opens up areas of new research.

Some of the most important insights into various fields of human study come from looking at diseased or injured populations—looking at such cases literally exploded the field of cognitive research and transformed the science of the mind from speculation to fact. Such research can do the same in the realm of diet and health.

A recent work published by Bertoli et al (2014) looked at the ketogenic diet over a 5 year period in the treatment of glucose transporter 1 deficiency syndrome (GLUT-1 DS). This is a genetic disorder where patients are unable to express proper levels of the GLUT1 protein that is used to transport glucose across the blood–brain barrier. Therefore less glucose is available to the brain causing a whole host of neural and developmental problems when those suffering continue to eat a carb-based diet. This can lead to seizures, developmental delay, microcephaly (essentially a small cranium) and neurologic manifestations including spasticity, hypotonia, and ataxia (Brockman, 2009). Like in the field of epilepsy, researchers have called for using ketogenic diets for this group which provides the brain with an alternative fuel in the form of ketones rather than glucose.

For over 5 years of ketogenic adherence this group saw no negative effects.

A concern the authors mentioned with using the ketogenic diet was the possibility of progressive loss of bone mineral content. They believed this could be manifested by a more acidic environment caused by following a ketogenic diet. The informed readers of Body.io know there is a distinct difference between “ketosis” and “ketoacidosis”. Remember ketoacidosis almost always occurs in a type I diabetic state where ketone levels increase WITHOUT sufficient insulin to help pull them into the tissue. This leads to a decrease in the pH of the blood (an increase in acidity), thus we get the term “ketoacidosis”. This almost never happens in people that don’t have major issues with insulin secretion (although isolated cases can occur in extreme alcoholics).

The aim of Bertoli was to determine the long-term effects of a ketogenic diet on body composition and bone mineral status of patients with GLUT-1 DS. Changes in body composition and bone mineral status were observed in adult patients with GLUT-1 DS who have been treated with a ketogenic diet for more than 5 years.

So what did they discover?

The ketogenic diet did not produce any negative appreciable changes in weight, body composition or any adverse effects on bone health. For over 5 years of ketogenic adherence this group saw no major negative effects.
Obviously we would love to see such studies expanded to a broader population looking at an array of metrics but this is a step in the right direction. What makes this study significant is the length and adherence in following a true ultra-low carb diet.

It appears we may be able to start dismissing the folklore about long-term ultra-low carb diets and evolve the conversation to one of facts, application and life-long health.

References (click the reference to access the resource):
1. Bertoli, S., Trentani, C., Ferraris, C., De Giorgis, V., Veggiotti, P., & Tagliabue, A. (2014). Long-term effects of a ketogenic diet on body composition and bone mineralization in GLUT-1 deficiency syndrome: a case series. Nutrition, 30(6), 726-728.
2. Brockmann, K. (2009). The expanding phenotype of GLUT1-deficiency syndrome. Brain and Development, 31(7), 545-552.

Kiefer

KIEFER

Physicist turned nutrition and performance scientist. Currently considered one of the industry’s leading experts on human metabolism.

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  • “literally” exploded the field? How many people were injured? 😉

    Otherwise, great article as usual!

  • Great article as always, however where does this leave cns which I’m using now? Could we just go l.c continuously even though we exercise? So Dr.Volek & Dr.Attia could be right? I do calisthenics & on occasions k.b, could I do strict u.l.c? Hope to hear from you soon

    • I do not think Peter Attia or Jeff Volek are correct about long-term strictly ketogenic diets. Neither have studied, nor do they seem to take seriously the role of carbohydrate cycling. Carbs do have a place in the diet and when used appropriately, can have greater benefits (health, fat loss, performance) than a strict ketogenic diet or a high-carb diet.

      • Thanks for the comment Kiefer. In defence of Peter (who in my opinion is one of the most measured on this topic other than yourself), he has never suggested people should do what he does, he just puts out there the results of his own experiments. He has always strongly urged others not to copy him but to experiment for themselves.

        I have also seen him make positive comments re: periodic re-introduction of carbs as a potential strategy.

  • Awesome stuff, as usual, Kiefer.
    *One correction though: “This leads to an increase in the pH of the blood, thus we get the term ‘ketoacidosis'” — I think you meant to say a *decrease* in the pH of the blood. (An increase in *acidity,* but a decrease in pH.) An *increase* would be alkalosis, rather than acidosis. Just an oversight. You know this stuff. This is what happens when you’re busy churning out books & other great stuff. 🙂

  • Great information Kiefer.
    I’ve been doing Carb Nite for about 5 months and am down 50 pounds, but I have more to go. As a perennial dieter, I thought I knew everything about losing weight, but just didn’t have the self discipline to be successful long term. I was wrong!
    I love the Carb Nite plan and have learned so much more about what “healthy” eating really means. I won’t be stopping it any time soon and I can easily see myself doing some form of ultra-low carb diet the rest of my life.
    Thank you!!!

    • Great diet I second that Dana s. I started at 245 pounds at 29 % fat and now down to 10% at 206 and just a few weeks out from doing my first bodybuilding show after 15 years out. Looking at the diet side of things I am able to build strength,muscle while dropping weight but from a leverage and water in joints point of view I am better gradually increasing carbs but working backwards and finding the point where I am not losing weight but got max nutrishan. But got to say I look pumped and well vascular with this diet,it seems like the first time that I can control my weight ect

  • I’ve heard Dr Dominic D’Agostino say that ketogenic diet does put a mild acid load on the body. I’ve seen my HCO3 levels drop during a strict ketogenic diet and low-normal range pH on blood gas with respiratory compensation.

    I’m now back loading 3-4 times a week with rice and tubers and occasional desserts and it seems to have corrected itself.

  • Researchers spent money efforts in the wrong topics, diet that actually works like ketogenic has existed since Atkins it’s incredible the lost of time focusing in other nonsense diets like zone, instead of ketogenic diets, nice one Kiefer doing what most people refuse to belive

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