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For doctorsNuSI study raises potential concerns about a keto diet
A new study from Kevin Hall, funded by NuSI, suggests that a ketogenic diet worsens lipid, inflammatory and glucose markers and thus may be a health concern.
The study, published in the journal Obesity, enrolled 17 overweight subjects without diabetes and kept them in a metabolic ward for eight weeks. This is an impressive undertaking as it requires the subjects to give up their lives for the study, and it requires that the study provide every single meal that the subjects consume. This is the main strength of the study. There is no question of whether the subjects were following the prescribed diet or not. They had no choice!
For the first four weeks, they ate a control diet of 15% protein, 50% carbohydrates and 35% fat. Then they transitioned to an isocaloric diet of 15% protein, 5% carbohydrates and 80% fat for four weeks. Again another strength. This was a true low-carb diet.
As for the results, weight loss is difficult to assess given the nonrandomized protocol and because the subjects started losing weight right away on the baseline diet. But more interestingly, the authors showed that inflammatory markers CRP and IL-6 increased on a ketogenic diet, as did LDL cholesterol (going from 125 mg/dl to 150) and HDL (44 to 46). Overall insulin levels dropped as did triglycerides.
They also measured the insulin and glucose response to test meals while on a ketogenic diet which showed impaired insulin sensitivity to a “control meal” but improved insulin sensitivity to a keto meal.
There has already been quite a bit of discussion on Twitter regarding the fact that the LDL was calculated rather than directly measured and how this might affect the results. There is no question that direct LDL measurement is a more accurate test, but it’s unclear how much that impacts these findings. The standard calculation of LDL becomes less accurate at low LDL levels (below 70) and higher triglyceride levels (above 200). Neither one was the case in this study, so I am not sure how important that is.
More concerning for me, however, was that this was only a four-week study. As a physician, I am not interested in what happens over a four week period of starting a new diet. At four months I might start to get interested, and at four years you definitely have my attention. But four weeks? That is practically insignificant in my book.
It is well established that the body takes time to transition to a fat-burning metabolism, so we would not expect to see complete metabolic effects of a ketogenic diet within such a short time frame, and the data hints that this is the case. Looking at the inflammatory markers, both CRP and IL-6 decreased from week three to week four on the ketogenic diet. Would this pattern continue in subsequent weeks, months or even years? Would the inflammatory markers eventually equal or go below the baseline diet levels? I would hypothesize yes, but this study doesn’t answer that question. Also, studies have shown that an initially elevated LDL-C can return to normal after 6 or 12-months, and the more important marker of Apo B may not go up at all.1 Again the study does not address this question. (Unfortunately, Apo B was not measured, and LDL-P was not measured, either.)
Last, the insulin and glucose response to sample meals also is likely inadequate to measure after such a short time frame on the keto diet.
In the end, while the authors deserve recognition for meticulously controlling the data, we are left wondering if the data has any meaningful contribution to real life. In the real world, we are concerned about our lifetime health, not just our health in the next four weeks.
For more on cholesterol, please see our guide on cholesterol:
Cholesterol and low-carb diets
Guide Read this guide to learn what cholesterol is, how your body uses it, why low-carb and keto diets may lead to a change in blood cholesterol levels, and whether you should be concerned if your cholesterol increases with a keto or low-carb lifestyle.
Thanks for reading,
Bret Scher, MD, FACC
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Annals of Internal Medicine: Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet [randomized trial; moderate evidence]
Cardiovascular Diabetology: Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study [non-controlled study; weak evidence] ↩
For antidotal evidence, I have been keto (minus a few cheat days 2-3x month - paired with intense exercise for the duration of this) for roughly 5 months. The goal was to reduce information due to Crohn’s.
Initially, my LDL spiked but has lowered (still in a good range), and my inflammatory markers were all perfect. Even had my GI ask me what I was doing.
This stuff worries me - who knows where the funding is coming from and who’s hanging out in the pocket books.
Now, when I went on low carb/keto on 1/1/14, I did not know about CRP or other tests including HbA1c. And I've never had any doctor tell me about these tests. I had to learn about them on my own, and I've had to pay for them myself. So, I can't see what my results were back then to see how they were affected. I was at least a year or more into low carb before I got any relevant tests done.
It's difficult for me to know what to do with a study that's 4 weeks long, when I've been doing this for 5.5 years, have lost around 60 pounds while gaining around 10 pounds of muscle (last based on DEXA scans over about 2 years), and have plenty of blood tests and other markers that contradict the results of this study, reduced my blood pressure, gained too many benefits to list.
Personally, I'm disappointed in NuSi. It seems like every study they've done has left so many unanswered questions.
When I read this study, I wasn't sure what hypothesis was being tested or what the point of it was.
The problem with NuSi is, that they've been sucked into funding studies by hostile experts who know the field well. Hall knows if he stops his study at 4 weeks he will probably get a different result from the result he would get at 6 weeks. Gardner knows that if he extends his study to 12 months and does an ITT analysis the important differences that were obvious at 6 months when most people were still adhering to the protocols will probably become non-significant. Both also know that if they use high-quality unrefined carbohydrate sources they can make their high carb arm results better than they used to be (but the keto arms, of course are still highly dependent on refined fats and still doing even better).
That paper is actually not new. Here's a good article we wrote when it first started to surface. It makes cyclical reappearances.
https://www.dietdoctor.com/all-over-media-low-carb-diets-could-shorte...
Could this be the factor that lead to an increase in inflammatory markers..? Isn’t it well established that high fat coupled with high cabs (in this study 15% protein + 50 % carbs = 65% carbs since excess protein can be converted to glucose) can be a recipe for bad health? Was there any physical activity involved?
How does this study conclude a ketogenic diet could be a concern when insulin sensitivity improved and CRP and IL-6 went down in weeks 3-4, which happened to be the Keto leg of the study?
Am I missing something..?