9

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New Study: Low-carb diet linked to increased inflammation, cortisol & CRP?

Commented on January 07, 2016
Created June 27, 2012 at 1:07 PM

A new study just published in the AMA Journal compared three diets: a low-fat diet, a low-glycemic/Mediterranean diet, and a low-carb/Atkins-like diet.

Although participants burned the most energy on the low-carb diet, researchers found that it came at a cost of "increases in cortisol, a stress hormone, and a measure of inflammation called CRP, which can raise the risk of developing heart disease and diabetes."

Original article here

Those who are versed in reading scientific journals, can you comment on this? Why would low-carb increase inflammation? Does it have anything to do with the quality of food the participants were eating?

D33a8d5f095a8532ddf7a0d6c27bfe63

(578)

on September 01, 2013
at 10:21 PM

Seriously, how many people go around here saying fat-burning via ketosis is the preferred form of metabolism? At best it would have been intermittent and was limited to a select group at the extremes of the environment (the Inuits, Lapps), unusual geographic conditions (the buffalo herd, rain forest tribes) or those with unique customs (Masais). I simply don't see that any large populations have resorted to ketosis on a long-term basis. I once believed in this myth. But you don't need any archeological evidence to disprove it; you just need to look at the presence of amylase.

141171c0810650168d82601d85cfa5a3

(415)

on July 31, 2012
at 12:54 PM

It depends on which markers of inflammation you want to cherry-pick. PAI-1, plasminogen activator inhibitor, may be an even more potent biomarker of risk. It improved the most on the low carb regimen. We didn't hear about that though, did we?

E45e707a87ba8d2a5ac79fae42e56c60

(30)

on July 03, 2012
at 05:04 PM

Have you seen Peter Attia´s post on this study? The best and most rigorous interpretation I have seen so far: http://eatingacademy.com/

Af842c68e3d07fa0e35b4274f3acaeec

on July 01, 2012
at 06:17 PM

Actually... http://www.ncbi.nlm.nih.gov/pubmed/11724664 Ever wonder why they're called glucocorticoids? http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/adrenal/gluco.html

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 28, 2012
at 02:50 PM

@Mambo: There isn't a shred of evidence that an adequate low-carb or very-low-carb diet of any duration causes any symptom of hypothyroidism in a healthy person. Anecdotes are not evidence, and you don't do science by taking a poll.

5e92edc5a180787a60a252a8232006e9

(345)

on June 28, 2012
at 02:25 AM

Ok, so we can treat that as a biomarker. But these were done 4 weeks after rotational diets. The common charge is that hypothyroidism doesn't appear 6-9 months after staring VLCing. Matt Stone and others have argued for years that for the first 6-9 months, everything was beautiful. Then, everything went haywire, including hypothyroid symptoms and hormonal problems. The problem is not during the first few weeks but after: on a sustained basis, VLC diets seems to induce undue stress and result in hypothyrid symptoms. That's why this study is no nail in the coffin of the LC/hypothyroid link.

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 08:49 PM

@Mambo: Resting energy expenditure (REE). Scroll down to "Results, Energy Expenditure" here: http://jama.jamanetwork.com/article.aspx?articleid=1199154

5e92edc5a180787a60a252a8232006e9

(345)

on June 27, 2012
at 08:14 PM

And what, may I ask, are you using as a marker of "basal metabolism" to make that conclusion?

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 06:28 PM

Here's a better source: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/glucagon.html It says the same thing. "Glucagon activates hepatic gluconeogenesis."

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 06:25 PM

Gluconeogenesis is up-regulated by glucagon, not cortisol. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm Scroll down to "gluconeogenesis inputs".

A968087cc1dd66d480749c02e4619ef4

(20436)

on June 27, 2012
at 05:34 PM

Can you say bologna and mayo on low-carb tortillas?

F0e558010a2ecb31fa37b7c491596b8e

(3850)

on June 27, 2012
at 04:41 PM

Actually, to be fair, I also ate a lot more vegetables after starting low-carb than I did on my carb-heavy low-fat diet. So my food quality wasn't as bad as I thought. But I ate a LOT of chicken wings fried in god-knows-what oil, and protein bars too.

71af3866ba45915e06061a627b40f31d

(235)

on June 27, 2012
at 04:40 PM

Couldn't find a link to the original in a hurry - thanks Christine M. :)

F0e558010a2ecb31fa37b7c491596b8e

(3850)

on June 27, 2012
at 02:37 PM

They're not always available for free.

1edb06ded9ccf098a4517ca4a7a34ebc

(14952)

on June 27, 2012
at 02:13 PM

haven't we known this?

7dc950fc76a046048e683d2a27dced37

on June 27, 2012
at 01:17 PM

Alright, it's not really a duplicate, but do we really need two questions to discuss the same study?

7dc950fc76a046048e683d2a27dced37

on June 27, 2012
at 01:16 PM

This is a duplicate of this post: http://paleohacks.com/questions/130873/does-this-study-really-show-a-metabolic-advantage-for-low-carb

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16 Answers

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2
A2c38be4c54c91a15071f82f14cac0b3

(12682)

on June 28, 2012
at 05:18 AM

Compared to the other diets, the low carb diet produced the smallest decrease in (resting and total) energy expenditure, a greater decrease in leptin (perhaps indicating a greater decrease in leptin resistance), better insulin sensitivity, lower triglycerides, and lower PAI-1 levels. These are all points in favor of the low carb diet in my mind.

Compared to other diets, CRP levels were higher in the LC group. However, all diets produced a decrease in CRP levels compared to baseline (which was 1.75) and ultimately the difference between the 3 diets was hardly significant (.78, .76, and .87). I'm critical of the author statement that low carb diets may increase CRP; this depends on context. According to the American Heart Association a CRP below 1 is considered "low risk". The low carb diet produced a CRP of .87.

The cortisol reading was interesting because it actually did increase in the LC group both compared to baseline and the other diets. I suspect cortisol increased to support gluconeogenesis; this effect was likely accentuated due to the high protein intake (30% of calories).

And as some have stated, diet quality may have had an effect. I suspect low intakes magnesium, vitamin C, and other nutrients more likely to be lacking in the LC group could have produced such effects on cortisol (and CRP).

Medium avatar

(10611)

on November 01, 2014
at 12:15 PM

Thanks mscott for a balanced assessment. The OP's question needlessly distorts the study's real value.

5
78964c5cc470f86a5897db8e1ce8e6f9

on June 27, 2012
at 04:00 PM

The article (freely available) is here: http://jama.jamanetwork.com/article.aspx?articleid=1199154

First thoughts:

1) The study is too small to draw meaningful conclusions. 21 participants is a ridiculously low number. That said, it was a crossover study (all participants tried all three diets), so that makes it more interesting.

2) The low-carb diet was VLC, 10% calories from carbohydrates. The authors even comment, "Main study limitations are the relatively short duration of the test diets and the difficulty extrapolating findings from a feeding study to a more natural setting, in which individuals consume self-selected diets. In particular, the very low-carbohydrate diet involved more severe carbohydrate restriction than would be feasible for many individuals over the long term. Therefore, the study may overestimate the magnitude of effects that could be obtained by carbohydrate restriction in the context of a behavioral intervention."

3) There is no mention of food quality with regards to the VLC diet. On the other hand, "The low???glycemic index diet aimed to achieve a moderate glycemic load by replacing some grain products and starchy vegetables with sources of healthful fat and low???glycemic index vegetables, legumes, and fruits"

4
68294383ced9a0eafc16133aa80d1905

(5795)

on June 27, 2012
at 02:23 PM

The preface really speaks about food quality, like you said, IMO.

A low-carb, Atkins Diet, in a casual sense, can really improve metabolism, blood sugar regulation and various health markers. That doesn't mean it paid attention at all to other things.

A traditional Atkins low-carb approach puts very little emphasis on quality and advocates a lot of controversial things like artificial sweeteners and refined carbohydrate substitutes like like coconut flour, almond flour, etc. Highly-processed foods are also fine as long as their net carbs are low.

You can eat a Ketogenic diet but if you're doing so by eating a ton of low quality/processed meat, food additives, articial sweeteners and a lot of fake stuff, you might be just as bad off in the long run as eating a SAD outside of being less insulin-resistant and maybe a lower weight.

Medium avatar

(10611)

on November 01, 2014
at 12:09 PM

This study isn't about the long run. 4 weeks of low carb is good. But after 30 years is it still good? Atkins himself looked great at the start, but 30 years later looked like a jowly old man.

4
B348f05b8dee2e4efe08c50525479f88

(100)

on June 27, 2012
at 02:17 PM

If it's improperly done I can see where inflammation may be increased. The metabolism of meats (especially red grain-fed meats, as well as the cooking style: barbecue (char grilling being one destroyer of meat's nutritional value) generates a lot of free radicals and I can see where that could potentially raise levels of inflammation. This study is not specific on the type of low-carb diet followed on the low-carb/Atkin's style diet but I will wager that there were likely participants who were not as careful as they should be about where exactly their proteins came from, as well as how they balanced it with healthy low glycemic root starches (say, sweet potato vs. potato), quinoa, etc... and plenty of vegetables with a smattering of fruit.

The balance of anti-inflammatory and pro-inflammatory fats and oils is altered by animal diet- just like our own bodies are altered when our diets are full of too much corn and sugar. This is a scientifically investigated fact. Can't refer to journals as I have graduated college and don't have access to the databases, but Loren Cordain's speaking and writing on the Paleo Diet is informative. I'd look up whatever resources he cites.

Medium avatar

(10611)

on November 01, 2014
at 12:05 PM

No point in being hypercritical of a short study. Paleos roasted meat, not having access to crock pots to make Neolithic stocks and bone broths. The main point is that LC is advantaged for weight maintenance in a short small controlled study.

A968087cc1dd66d480749c02e4619ef4

(20436)

on June 27, 2012
at 05:34 PM

Can you say bologna and mayo on low-carb tortillas?

3
E45e707a87ba8d2a5ac79fae42e56c60

on June 27, 2012
at 06:21 PM

Could the cortisol response be related to the initial phases of adaptation to a low carb diet? What would happen after the dieters become keto-adapted?

3
21189b5cf0bb5b57e7b82d02717ce265

on June 27, 2012
at 02:07 PM

where is the other question posted?

2
Af842c68e3d07fa0e35b4274f3acaeec

on June 27, 2012
at 05:48 PM

That a low-carb diet increases cortisol should be obvious. Cortisol is one of the main long term blood glucose regulators, and if insufficient amounts of carbohydrates are consumed, gluconeogenesis will be up-regulated through increased cortisol production.

As for the increased inflammation, the low carb diet STILL decreased CRP levels dramatically from baseline, just slightly less so than the low-GI and low-fat diets. The levels of plasminogen activator inhibitor 1 were however lower in the VLC diet, so I don't know whether you can really say inflammation was higher in the VLC condition.

As others have said as well, we don't have information on the types and quality of food consumed, so that could be a big confounding variable.

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 06:28 PM

Here's a better source: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/glucagon.html It says the same thing. "Glucagon activates hepatic gluconeogenesis."

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 06:25 PM

Gluconeogenesis is up-regulated by glucagon, not cortisol. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm Scroll down to "gluconeogenesis inputs".

Af842c68e3d07fa0e35b4274f3acaeec

on July 01, 2012
at 06:17 PM

Actually... http://www.ncbi.nlm.nih.gov/pubmed/11724664 Ever wonder why they're called glucocorticoids? http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/adrenal/gluco.html

1
729868b6457caeb9b5dae69b0edafb48

on September 01, 2013
at 08:35 PM

Low blood sugar raises cortisol. Cortisol increases inflammation and causes bone loss and fat storage.

See the human body runs on glucose. Avoiding glucose just makes the body work harder to get the energy it needs. It does this by raising cortisol levels, this is bad.

The paleo diet is inadequate in that it does not focus on the only thing that matters, which is supporting the metabolism. There is no way to know what a caveman ate as paleolithic ancestors probably ate different things depending on where they lived, and secondly all attempts to recreate this would be impossible.

We are not paleolithic hunter gatherers, our lifestyles and nutritional needs are vastly different. The brain requires lots of energy and it requires that energy in the form of sugar.

If you do some google searches on how the body processes sugar, insulin carries it through the cell membrane. It is theorized that ingestion of the wrong types of fats or perhaps genetic malfunctions alter the state of cell membranes, which make it more difficult and therefore require more insulin to carry sugar into the cell.

322a2783dfe4086591f323c6d2c086d6

on January 07, 2016
at 08:38 PM

Actually, prehistoric man would have gone through almost annual seasonal and extended switches to ketosis, both those who experienced cold winters and those who experienced "dry" seasons. No... this is not a myth.

D33a8d5f095a8532ddf7a0d6c27bfe63

(578)

on September 01, 2013
at 10:21 PM

Seriously, how many people go around here saying fat-burning via ketosis is the preferred form of metabolism? At best it would have been intermittent and was limited to a select group at the extremes of the environment (the Inuits, Lapps), unusual geographic conditions (the buffalo herd, rain forest tribes) or those with unique customs (Masais). I simply don't see that any large populations have resorted to ketosis on a long-term basis. I once believed in this myth. But you don't need any archeological evidence to disprove it; you just need to look at the presence of amylase.

1
5dd50f78f47b8848d93724d6eb38d4c1

on June 28, 2012
at 11:05 AM

It takes cortisol to perform the actions of making glucose out of protein. I wasn't convinced that was a very healthy thing to do but I wasn't sure it increased the risk of heart disease or caused inflammation.

1
F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 07:52 PM

The study also provided another nail in the coffin of the low-carb/thyroid bollocks.

T3 was lowest, but basal metabolism highest, on the low-carb diet.

5e92edc5a180787a60a252a8232006e9

(345)

on June 27, 2012
at 08:14 PM

And what, may I ask, are you using as a marker of "basal metabolism" to make that conclusion?

5e92edc5a180787a60a252a8232006e9

(345)

on June 28, 2012
at 02:25 AM

Ok, so we can treat that as a biomarker. But these were done 4 weeks after rotational diets. The common charge is that hypothyroidism doesn't appear 6-9 months after staring VLCing. Matt Stone and others have argued for years that for the first 6-9 months, everything was beautiful. Then, everything went haywire, including hypothyroid symptoms and hormonal problems. The problem is not during the first few weeks but after: on a sustained basis, VLC diets seems to induce undue stress and result in hypothyrid symptoms. That's why this study is no nail in the coffin of the LC/hypothyroid link.

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 27, 2012
at 08:49 PM

@Mambo: Resting energy expenditure (REE). Scroll down to "Results, Energy Expenditure" here: http://jama.jamanetwork.com/article.aspx?articleid=1199154

F0a3e3f17d9a740810ac37ff2353a9f3

(3804)

on June 28, 2012
at 02:50 PM

@Mambo: There isn't a shred of evidence that an adequate low-carb or very-low-carb diet of any duration causes any symptom of hypothyroidism in a healthy person. Anecdotes are not evidence, and you don't do science by taking a poll.

1
0a0afca93a127c82ec4192a2e99647f4

on June 27, 2012
at 07:48 PM

With Ludwig, the lead guy on the study, I have to wonder if he stacked the deck in low-glycemic diet's favor. If even on an unconscious level. He has long been known as a low glycemic kida guy (as opposed to blatent LC) so I'm not suprised to see his study - or at least his interpertaion it- lend more overall support for a low GI diet than a brute LC diet. In much the same way I'm never surprised to see a study by a vegan lend more support for a vegan diet.

That's why I love the A to Z study. The low-carb diet did best, and the lead author was a vegetarian, but intellectually honest enough to admit the LC diet did better than the Ornish diet. In fact, he says the Ornish diet tended to raise the triglyceride levels of the study participants. Which of course is no big surprise to most of us.

1
F0e558010a2ecb31fa37b7c491596b8e

(3850)

on June 27, 2012
at 02:37 PM

I 100% agree that when I was in my "low-carb" phase, the quality of my food was terrible. High consumption of O6 PUFAs, crap processed meat (not always, but a fair amount). However, I did actually have a significant improvement in my health, including autoimmune/inflammatory conditions. I attribute that to reduced consumption of gluten and grains. My cortisol was so high normally, that any reduction would have been an improvement.

So on that line, I wonder if they compared the coritsol to baseline levels or if it was compared to the people on the other diets. Obese people would generally have higher cortisol levels to begin with.

Fortunately, I have learned that the quality of my food really does matter and now moderately low carb plus paleo eating has made me even better.

F0e558010a2ecb31fa37b7c491596b8e

(3850)

on June 27, 2012
at 04:41 PM

Actually, to be fair, I also ate a lot more vegetables after starting low-carb than I did on my carb-heavy low-fat diet. So my food quality wasn't as bad as I thought. But I ate a LOT of chicken wings fried in god-knows-what oil, and protein bars too.

0
Medium avatar

(10611)

on November 01, 2014
at 11:27 AM

Very interesting article. Rather than dwell on the negatives, the positive effects of low carb on reducing hunger and increasing energy expenditure are huge advantages for maintaining weight loss. This study needs to be done for a much longer period eith a much larger study group to verify though. Years rather than weeks of maintenance.

0
6a44141b4c4280c96471f1ded9226b58

on November 01, 2014
at 09:47 AM

 This guy is an astrazeneca shill, and this study counterdicts every other study out there.

Medium avatar

(10611)

on November 01, 2014
at 12:13 PM

Oh come on. This hit-and-run adds nothing to the discussion.

0
8767a1533a7b3ed96dd3edb70df9bc90

on June 27, 2012
at 05:50 PM

In the article that I read, it actually pointed out that a low-fat diet was the worst.

http://www.ivillage.com/certain-diets-may-help-body-burn-more-calories-study/4-a-468579

...the low-fat diet had the worst effects on metabolic syndrome, a group of heart disease risk factors. Low-fat diets had adverse effects on insulin sensitivity, triglyceride levels and good cholesterol levels...

-1
D979c5c48086fccb8d7bbacc44a59722

(8)

on June 27, 2012
at 02:32 PM

wsj is a new medical journal ? :D

a proper link is beter.

71af3866ba45915e06061a627b40f31d

(235)

on June 27, 2012
at 04:40 PM

Couldn't find a link to the original in a hurry - thanks Christine M. :)

F0e558010a2ecb31fa37b7c491596b8e

(3850)

on June 27, 2012
at 02:37 PM

They're not always available for free.

E45e707a87ba8d2a5ac79fae42e56c60

(30)

on July 03, 2012
at 05:04 PM

Have you seen Peter Attia´s post on this study? The best and most rigorous interpretation I have seen so far: http://eatingacademy.com/

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