Ketosis leads to increased methylglyoxal production on the Atkins diet

[Sting]

I read this Abstract and article my English is not great just wondering what others thoughts are re article

Abstract
In the popular and widely used Atkins diet, the body burns fat as its main fuel. This process produces ketosis and hence increased levels of beta-hydroxybutyrate (BOB) acetoacetate (AcAc) and its by-products acetone and acetol. These products are potential precursors of the glycotoxin methylglyoxal. Since methylglyoxal and its byproducts are recognized as a significant cause of blood vessel and tissue damage, we measured methylglyoxal, acetone, and acetol in subjects on the Atkins diet. We found that by 14-28 days, methylghyoxal levels rose 1.67-fold (P = 0.039) and acetol and acetone levels increased 2.7- and 6.12-fold, respectively (P = 0.012 and 0.028). Samples from subjects with ketosis showed even greater increases in methylglyoxal (2.12-fold), as well as acetol and acetone, which increased 4.19- and 7.9-fold, respectively; while no changes were seen in samples from noncompliant, nonketotic subjects. The increase in methylglyoxal implies that potential tissue and vascular damage can occur on the Atkins diet and should be considered when choosing a weight-loss program.

Methylglyoxal on Atkins... Uh oh!
OK, time for a post. Shawn forwarded this this report which is interesting on several fronts.

It includes a specific named weight loss diet in the title of the paper. They omitted the "TM" after "Atkins" but I'm sure that won't offend anyone too much. This is science after all. This is not about ketogenic diets in general, it's got a commercial title. Smells bad to me.

What did they find? Well, ketosis produces ketones and these include acetol and acetone. Acetol is a scary chemical that I know nothing about, except I probably make a bit more now than I did 10 years ago.

Acetone is just acetone and, as these clowns undoubtedly know, acetone is a prime suspect as the candidate molecule which deprives intractable epileptics of their refractory seizures. Obviously something to avoid at all costs. Buy the phenobarbitone instead, even if it doesn't work for you.

But methylglyoxal, now there's a scary chemical. Apparently:

"...beta-hydroxybutyrate, acetoacetate and its by-products acetone and acetol... are potential precursors of the glycotoxin methylglyoxal."

A glycotoxin (gasp) from ketones (extra gasp)! Skip your pasta and you will die, from a glycotoxin. Hmmmmm.

No one (with a few exceptions) doubts that methylglyoxal is Bad Stuff. It does make me wonder why our poor body manufactures it in the first place. Blood concentration certainly increases in pathological ketoacidosis, so it may not have come as a complete surprise to these seekers-after-truth that methylglyoxal is also modestly elevated in benign ketosis.

Methylglyoxal is elevated in ketosis, but the bulk is produced by glycolysis. Why should this be so?

I would just like to speculate that it might actually be related to glycerol metabolism. The glycerol produced by the breakdown of triglycerides in adipocytes is exported to be used for gluconeogenesis or burned for energy production. Glycerol is phosphorylated then dehydrogenated to give DHAP. DHAP can break down spontaneously to give methylglyoxal but, when this method of production is inadequate, metabolism simply uses the enzyme methylglyoxal synthetase to do a better job.

Apart form diet assisted suicide and any career ehancing denigration of the Atkins TM diet, is there any use for methylglyoxal in the body? Methylglyoxal is an inhibitor of glycolysis. Well, it might just be useful to inhibit glycolysis under conditions when glycerol is more freely available than usual. As in lipolysis. It looks very neat to me that a product of lipid breakdown should inhibit the process of glycolysis. I'll bet that the gene for methylglyoxal synthetase is not expressed in neurons, certainly not during ketosis.

An aside. Let's just imagine this group had found that glucose restriction in C elegans worms produced a marked increase in respiration due to the use of fat and a significant increase in the production of free radicals as a result of this. As it does. I can just see the headline:

"Increased fat metabolism might generate excess free radicals. The increase in free radicals implies that potential tissue and vascular damage can occur on the Atkins diet and should be considered when choosing a weight-loss program"

I guess they either would forget to mention the increased longevity in their worms or have been damned sure to have thrown out their worm colonies at two weeks of age!

Another aside. How toxic is methylglyoxal? Compared to what? How about carbon monoxide, nitric oxide or hydrogen sulphide, all essential mammalian signaling molecules that you don't want to inhale in bulk. Well you can drink methylglyoxal. What happens?

It looks like you don't die immediately. Lots of your cancer cells, many of which are glycolysis dependent, might not fare quite so well under inhibited glycolysis.

So I would concur with Beisswenger et al in their Atkins bashing paper. Choose your diet for weight loss with care. Great care.

[margame]

who's papers are you quoting?
can you post a link?

[Sting]

Originally Posted by margame

who's papers are you quoting?
can you post a link?

Petro Dobromylskyj wrote the article on Methylglyoxal on Atkins

[Dottie]

I found the blog easily through google (the author is a veterinarian).

[margame]

thanks.

so the abstract is from a study/report done by a group at the dartmouth medical school and the second quote is from someone's blog.

[Sting]

Originally Posted by margame

thanks.

so the abstract is from a study/report done by a group at the dartmouth medical school and the second quote is from someone's blog.

Yes he had the study abstract linked in his article.

[Taxbane]

I smell bias. Hm... How do the Inuit people who eat their traditional diet have such a low incidence of cardio vascular disease yet practially eat only meat and fat?

[Arctic_Mama]

Peter, himself, follows Kwaniewski's plan quite closely and his entire family eats ketogenically. His blog, Hyperlipid, is excellent and a bit on the sarcastic side. Just an FYI.

You do need to consider that ketone bodies, under certain conditions, can damage tissues. However the body regulates those very tightly, and the question of whether that damage supercedes that of high blood glucose is the real kicker (I have not found that it does, excess sugar in the blood is a far more deleterious condition). Be wise, but for every paper out there with a conclusion there's another two to counter it. The quality of the study matters, as does the body of evidence in general. And that finds the metabolic effects of ketosis to be safe and effective for weight loss and health promoting, in general, over a glucose metabolic pathway. We need ATP somehow, there's a cost to getting it regardless. So as he said, pick your method with care!

(As an aside, what this paper did NOT indicate was if the rise in ketone body levels, which we expect in ketosis, was actually at a level where any harm could be measured. Simply asserting that the chemical is harmful doesn't mean anything - the poison is in the dose, not the mere presence, of a substance).

I realized I didn't actually explain the conclusion - sorry! Essentially the paper is bollocks from a useful perspective, as it concludes that ketosis does indeed create ketone bodies, including those that are used as vehicles for transport of said bodies during fat loss. They made this sound like a bad thing, when anyone with critical thinking skills and a brain in their head would realize that this process is neither deleterious to the vascular system OR brain, and in fact therapeutic and rehabilitative compared to the damage sustained under glycolysis as opposed to ketosis. The paper essentially leaves their 'caution' as an insinuation that such a diet could be dangerous to health, where nothing in their research indicates a causative agent that would do that, or even a quantitative level at which this would happen.

There is a word for this - scare tactics. I would summarily ignore this as both a poorly constructed paper and experiment, that leans more toward diet propaganda than any real research.

[Taxbane]

Originally Posted by Arctic_Mama

(As an aside, what this paper did NOT indicate was if the rise in ketone body levels, which we expect in ketosis, was actually at a level where any harm could be measured. Simply asserting that the chemical is harmful doesn't mean anything - the poison is in the dose, not the mere presence, of a substance).

This is also an excellent point. Kinda like a "scientific paper" concluding that Oxygen is a harmful chemical and then insinuating caution to "BEWARE" of your exposure to it!

[tea cup]

I wonder who paid for the study.

[avid]

interesting.
Looking forward to reading more of this discussion

[jem51]

Dr Kwasniewski doesn't encourage ketosis and his plan adds enough carb to avoid it.
I don't know if Petro follows that close but he has added glucose to ice cream in the past....so maybe?

Groves said the same but I do not know his stance now.

Both believed that ketosis was hard on the bod.

[Arctic_Mama]

For weight loss or weight maintenance? It was my understanding that ketosis long term for weight maintenance was the avoided state, not while still losing, unless ketosis is being maintained for therapeutic reasons. But I confess that isn't one of the plans I've bothered reading up on extensively, so my knowledge is second hand gleaned

[Leo41]

Ketogenic diets for health reasons are long term, and they are particularly used for children with epilepsy, so I doubt that anyone would keep children in ketosis indefinitely if there were any danger at all.

I also saw Dr. Phinney interviewed on television, and he certainly doesn't have to lose weight, but he said that he has been in ketosis for 6 years--continuously. He maintains that it is a very healthful WOE, and he advocates it without reservation.

I stay in ketosis because I am extremely sensitive to carbs, and I've never been healthier in my life--at age 71.

[avid]

I wonder if there are any studies re: long term ketosis.
Has Gary Taubes ever commented on that?
It seems to me that his diet would have him in ketosis.