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Do ketones damage kidneys?

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#1
Injecto

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I can't seem to find anything that backs this up. I know that high BG will damage them over time (duh!!), but what about ketones?

#2
fgummett

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Ketone bodies are water-soluble compounds that are produced as by-products when fatty acids are broken down for energy. They are a vital source of energy during fasting -- such as overnight.

The brain gets its energy from ketone bodies when insufficient glucose is available. In the event of low blood glucose, most other tissues have additional energy sources besides ketone bodies (such as fatty acids), but the brain does not.

Remember that when you are not fasting, the body can use Amino Acids (from dietary Protein) to synthesize Glucose (Gluconeogenesis).

Any production of Ketones is called ketogenesis, and this is necessary in small amounts. When even larger amounts of ketone bodies accumulate such that the blood's pH is lowered to dangerously acidic levels, this state is called ketoacidosis. This happens in untreated Type I diabetes (DKA).

In short, the human body has evolved over the millennia to burn either Glucose or Fatty Acids -- think of these as the short-term fuel and longer-term reserve, respectively.

So if it is normal to burn Fatty Acids and produce Ketones why would they be harmful unless they accumulate to dangerous levels? Yes I know... we always get the "dangerous levels" lecture but consider that BG can be toxic at high enough levels... that does not mean it is bad for us at any level :)

#3
REDLAN

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can we get the production of ketones correct??

The primary cause of ketogenesis in the body is.....

gluconeogenesis from dietary protein, when there is insufficient dietary glucose to fill the body needs, aka the ketogenic diet.

The process of gluconeogenesis utilises a key component of the citric acid cycle (oxaloacetate), which blocks the oxidation of Acetyl CoA. Fatty acid (and glucose oxidation) require their conversion to Acetyl CoA. It is Acetyl CoA which is converted to ketone bodies and this process occurs pretty exclusively in the liver (also happens in the kidney)

Normally oxidation of fatty acids does NOT produce ketone bodies, even during fasting overnight, as usually there are more than sufficient stores of glycogen.

- starvation is an entirely different matter. Fasting for longer than a day or so can be sufficient for ketogenesis to start.

Astrocytes in the brain can produce ketone bodies in response to hypoglycemia, but this will not provide adequate protection in the event of hypoglycemia caused by insulin overdose.

The simple reason why ketogenesis as caused by a ketogenic diet is probably safe is because ketones only transiently rise in response to food, and the levels sustained should not be sufficient to disturb the body's buffer system.

if however you spent long periods without food, or lacking insulin then that is a very different matter.

I can't find anything definitive about ketones and kidney function - the only thing of note is an association with kidney stones for children on ketogenic diets to control epilepsy - but this could be due to the components of the diet (high protein) rather than ketones. There are no long term safety studies on ketogenic diets, but they are though to be safe (probably).

Those on this forum on low carbohydrate diets 50g to 120g of carbs probably do not experience ketogenesis to any significant degree. Significant ketogenesis only occurs at <30g.

#4
fgummett

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can we get the production of ketones correct??

The primary cause of ketogenesis in the body is.....

gluconeogenesis from dietary protein, when there is insufficient dietary glucose to fill the body needs, aka the ketogenic diet.

Are you saying that Ketones (Ketone Bodies) result from Gluconeogenesis rather than from the use (oxidation) of Fatty Acids as fuel?

Has the science changed from everything I have so far found on-line... for example : Fatty Acid Oxidation

During high rates of fatty acid oxidation, primarily in the liver, large amounts of acetyl-CoA are generated. These exceed the capacity of the TCA cycle, and one result is the synthesis of ketone bodies, or ketogenesis. The ketone bodies are acetoacetate, β-hydroxybutyrate, and acetone.


Perhaps my simplified initial explanation was not as detailed as yours but is it substantially incorrect... particularly when taken in context of the OP's question?

#5
REDLAN

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fgummett wrote
Are you saying that Ketones (Ketone Bodies) result from Gluconeogenesis rather than from the use (oxidation) of Fatty Acids as fuel?


yeah pretty much.

There is this misconception that ketogenesis occurs because of oxidation of FFA's. It's repeated many a time, especially by those that follow a low-carb, high fat diet that this results in the production of ketones.

generally it doesn't

Ketone bodies arise because there is more acetyl CoA than the citric acid cycle can handle. The reason the liver can not handle the load of FFA's is because it is busy generating glucose which diminishes the capacity of the citric acid cycle to generate NADH from acetyl CoA. Pretty much all fuels in the body get turned into Acetyl CoA, including glucose, alcohol, FFA's AND ketones.

ergo the cause is not FFA metabolism per se, it is gluconeogenesis which tips the balance... stop the gluconeogenesis, and the production of ketones will shortly stop.

this might well be true

During high rates of fatty acid oxidation, primarily in the liver, large amounts of acetyl-CoA are generated.


however it equally applies during high rates of glucose metabolism, alcohol metabolism, and ketone metabolism. So when do these events occur? Would the liver really have a system where it's citric acid could not handle it's normal energy load? Why indeed would it be deficient in mitochondria?

In humans ketogenesis only normally occurs in response to low glucose levels. Ketogenic diets will do this, and the gluconeogenesis of dietary protein is the driving force behind ketone production. Ketogenesis also occurs during starvation. The most extreme reaction is ketogenesis in the absence if insulin - in effect the body responds as though it's supply of glucose was zero.

ketogenesis is a response to low glucose, rather than a response to FFA oxidation.

#6
fgummett

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There is this misconception that ketogenesis occurs because of oxidation of FFA's. It's repeated many a time, especially by those that follow a low-carb, high fat diet that this results in the production of ketones.

It sounds like you are saying it is a misconception put about by low-carb aficionados... so what about the the many web sites out there such as the one I linked to above?

You also didn't answer my question about whether my first post was "substantially incorrect"... I ask because I found your "can we get the production of ketones correct??" quite patronising, particularly considering this is an open internet forum and not a scientific venue.

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"ketogenesis is a response to low glucose, rather than a response to FFA oxidation." Even if this is true and all the other scientists I have read are wrong... does it really matter in any practical sense..? When we are low on Glucose, we start burning Free Fatty Acids, so both conditions occur at the same time anyway.

#7
REDLAN

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The information about ketogenesis generally relates to starvation + fasting states. However the people posting here are not starving nor fasting (usually).

There is however a general assumption, that

Ketone bodies are water-soluble compounds that are produced as by-products when fatty acids are broken down for energy.


in fact they are only produced in significant quantities in specific situations.

for the purposes of this discussion this means a ketogenic diet - a low carb diet does not necessarily mean that the person is producing significant numbers of ketones, regardless of the amount of fat they might be burning. And to answer Xmenace's question he doesn't need to worry about ketones unless his carbohydrate intake is around 30g a day mark, because he won't be producing ketones in significant amounts.

Also the next time ketones comes up in a low carb diet, and someone says aren't they harmful, it can be countered by explaining that most low carb diets don't result in the production of significant amounts of ketones.

I did go on and read the rest of the article where it explains about how ketogenesis is regulated, and a bit about it's relationship to carbohydrate metabolism - I also had a quick read of a cambridge journal article, which discusses the central role of the citric acid cycle and it's depletion as the driver of ketogenesis - and illustrated how little is known about this process.

#8
Injecto

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So I'd like to get back to my ORIGINAL question before all this side gracking went on. Do ketones damage kidneys in any way?For example, protein spilling into urine means the filter in you nephrons are too big and as such are failing because they let protein through. Is the same true for ketones, or are ketones supposed to be excreted via the urine naturraly, that is, when they are present? And if not then how ARE ketones supposed to exit the body? Or are we just NEVER supposed to see ketones under any circumstances?




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