Review: Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks

nerd

Senior Member
Messages
863
Likes
2,537
Crosby L, Davis B, Joshi S, Jardine M, Paul J, Neola M and Barnard ND (2021) Ketogenic Diets and Chronic Disease: Weighing the Benefits Against the Risks. Front. Nutr. 8:702802. doi: 10.3389/fnut.2021.702802

Abstract
Very-low-carbohydrate ketogenic diets have been long been used to reduce seizure frequency and more recently have been promoted for a variety of health conditions, including obesity, diabetes, and liver disease. Ketogenic diets may provide short-term improvement and aid in symptom management for some chronic diseases. Such diets affect diet quality, typically increasing intake of foods linked to chronic disease risk and decreasing intake of foods found to be protective in epidemiological studies. This review examines the effects of ketogenic diets on common chronic diseases, as well as their impact on diet quality and possible risks associated with their use. Given often-temporary improvements, unfavorable effects on dietary intake, and inadequate data demonstrating long-term safety, for most individuals, the risks of ketogenic diets may outweigh the benefits.
 

Shanti1

Moderator
Messages
1,569
Likes
3,892
I can't say I'm surprised given that many people on a ketogenic diet are eating a lot of red meat, cream, butter etc. I personally can't tolerate carbohydrates/sugar and my diet is mostly lots low-carb vegetables, seafood, chicken, eggs, and some dairy. I find myself moving in and out of ketosis (urine strips) and find I feel better when I am in mild ketosis. For those who feel better in ketosis, my take on this study is that is a caution on how we get there rather than being there.
 

Pyrrhus

Senior Member
Messages
4,141
Likes
12,627
Location
U.S., Earth
Excellent find!

This review article is particularly relevant as some patients have reported short-term improvement in ketogenesis/ketosis, perhaps due to the body switching resources away from the immune system and towards basic bodily functions.

Unfortunately, long-term improvement in ketogenesis/ketosis appears to remain elusive...
 
Last edited:

nerd

Senior Member
Messages
863
Likes
2,537
I can't say I'm surprised given that many people on a ketogenic diet are eating a lot of red meat, cream, butter etc. I personally can't tolerate carbohydrates/sugar and my diet is mostly lots low-carb vegetables, seafood, chicken, eggs, and some dairy.
That's why I mentioned it. Unhealthy fats seem to be the main driver for almost all the risks they identified. There's still an argument to be made if a high protein diet can affect the kidneys negatively but it might as well be the cardiovascular vector that affects the kidneys via high blood pressure.

Red meat is one of the greatest concerns for colon cancer. A "cheating" keto diet that doesn't integrate a lot of healthy fats will not improve health. Pushing the ketogenesis margin won't be helpful for insulin sensitivity either. But it's possible that the diabetes risk is somehow confounded by selection or not filtered for sufficient ketogenesis persistence.

I'm still convinced that the keto diet is a very healthy diet if it's done properly with healthy fats, especially olive oil. It's part of the human evolution and leaving fasting or the ketogenesis out of the normal life cycle prevents important metabolic steps to take place.

During summer, humans are supposed to gain weight, build muscle, push growth hormones. In the winter up to spring, this is supposed to inverse, fasting period is supposed to take place, the gained weight is supposed to be lost, apoptosis is supposed to happen, senescent cells are supposed to be cleared out.

That's about the time frame the human organism is supposed to follow. Ketogenesis isn't supposed to happen endlessly. However, it's unclear how long you initially need to basically catch up with all the missed fasting periods. And technically, ketosis is supposed to be starvation, but intermittent fasting might work almost as well, and not everyone has weight to lose, so I try not to fast at all but gain weight that I couldn't gain in gluconeogenesis.

Unfortunately, long-term improvement in ketogenesis appears to remain elusive...
I still feel better than before, but I'm also part of the ME subgroup that generally noticed worsening from sugars, just like @Shanti1. I noticed repetitive improvements of ME symptoms combined with a worsening of pain. I'm not sure if it's a natural reaction because of my high susceptibility to reactive rheumatic autoimmunity or if it's fibromyalgia or reactivation of borreliosis or a zoster virus. It's always either ME or pain, no complete remission. I have never had such a back pain ever before the keto diet.

Once, I have already tried to leave ketosis but it only lead to hyperglycemia, which can become an urgent emergency while being in ketosis. I'll only dare to repeat this in the presence of a physician with an insulin shot at the ready.

It says this article is by "Physicians Committee for Responsible Medicine - Wikipedia" It seems quite possible that they have an agenda to promote eating only vegetables rather than getting to the truth about ketogenic diets for those with health issues.
I agree. I guess it's just like with vitamins. Sometimes, you find meta-reviews that point out all the negatives like there aren't any positives. Ketosis is a natural part of our organism and useful for more people than just epileptics. I think it's a powerful tool for overweight people who want to become healthy and lose weight while still being able to work and think clearly, which isn't possible with these typical low calorie diets. It's also ideal to keep your weight because there's no strong reward mechanism for eating fats without sugars. My personal experience is that it's quite difficult to reach so much fat intake that a gain in weight is even possible. So many people nowadays just overeat everything. The GIS doesn't like that, even if it's vegan only.
 

sb4

Senior Member
Messages
1,577
Likes
2,783
Location
United Kingdom
Once, I have already tried to leave ketosis but it only lead to hyperglycemia, which can become an urgent emergency while being in ketosis. I'll only dare to repeat this in the presence of a physician with an insulin shot at the ready.
I'm still convinced that the keto diet is a very healthy diet if it's done properly with healthy fats, especially olive oil.
You got the hyperglycemia when adding carbs back? Did you add a lot back or go slow? I would expect some level of hyperglycemia when transitioning until your body adjusts.

It is my understanding that the healthy fats you should be eating on ketosis are actually saturated fats as this will lead to better insulin control.
 

Viala

Senior Member
Messages
367
Likes
997
Keto diet doesn't work for me anymore. When I first started keto I felt fantastic, physically, mentally, emotionally. Later on I was on a low carb diet but it gradually made me more and more tired same as ketosis, so finally I decided to go back to high carb and low to moderate fat and felt better, I was on that diet for about a year. Tried keto again two weeks ago, olive oil, some eggs, chicken, seeds, no unhealthy fats, no red meat. No benefits and I quickly started to feel worse, so back to high carb again. Sigh.

Once, I have already tried to leave ketosis but it only lead to hyperglycemia, which can become an urgent emergency while being in ketosis. I'll only dare to repeat this in the presence of a physician with an insulin shot at the ready.
It took me couple of months to readjust to digesting carbs again, I think 3-6 months to fully readjust. I started with little amounts of brown rice, lentils, no sugar, no fruit, no simple carbs and that was about two weeks lower calories and very low fat diet, loads of veggies. Currently I can eat a lot of carbs, some fruit, but still no flours or sugar.
 

nerd

Senior Member
Messages
863
Likes
2,537
Did you add a lot back or go slow?
I went quick with pure glucose, gradually drank more.

It is my understanding that the healthy fats you should be eating on ketosis are actually saturated fats as this will lead to better insulin control.
You mean unsaturated ones? Saturated ones even decrease insulin sensitivity. Saturated ones are also the problem with Alzheimer's, arteriosclerosis, gall stones, etc.
 

sb4

Senior Member
Messages
1,577
Likes
2,783
Location
United Kingdom
You mean unsaturated ones? Saturated ones even decrease insulin sensitivity. Saturated ones are also the problem with Alzheimer's, arteriosclerosis, gall stones, etc.
No I mean saturated. Unsaturated increase insulin sensitivity but that isn't what you want in ketosis. You want most cells to become insulin resistant temporarily post meal to spare glucose for the cells that need it such as brain. Peter @hyperlipid as IMO a really good blog series on it called protons.

I was thinking maybe if you were going out of your way to avoid saturated fats this could have had a negative effect on blood glucose.

As for ketosis, I can no longer enter it without my symptoms increasing significantly, yet my symptoms also increase significantly post carb meals so I am eating lowish carb currently yet still gaining weight.
 

Shanti1

Moderator
Messages
1,569
Likes
3,892
No I mean saturated. Unsaturated increase insulin sensitivity but that isn't what you want in ketosis. You want most cells to become insulin resistant temporarily post meal to spare glucose for the cells that need it such as brain. Peter @hyperlipid as IMO a really good blog series on it called protons.

I was thinking maybe if you were going out of your way to avoid saturated fats this could have had a negative effect on blood glucose.

As for ketosis, I can no longer enter it without my symptoms increasing significantly, yet my symptoms also increase significantly post carb meals so I am eating lowish carb currently yet still gaining weight.
I think we agree that saturated fat increases insulin resistance more than polyunsaturated fat:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951141/

However, insulin resistance will lead to higher insulin levels which would inhibit ketosis:

https://diabetes.diabetesjournals.org/content/69/5/882
"Insulin strongly inhibits ketosis, predominantly by reducing lipolysis in adipocytes and reducing the supply of free fatty acids, the substrate for ketone body production."

My view of the goal of ketosis is to switch the brain over to ketones, not to spare glucose for use by the brain. I think for me, and perhaps others, one of the benefits of having the brain use ketones is that they are calming and may reduce inflammation in the brain.

I'm not saying people shouldn't eat saturated fat, sometimes you do what you have to do to get into ketosis, but it seems insulin resistance is not helpful, and polyunsaturated would be a better choice if it is possible.
 

sb4

Senior Member
Messages
1,577
Likes
2,783
Location
United Kingdom
@Shanti1 As far as I understand it, saturated fat shouldn't lead to ever increasing insulin when in ketosis. It is a temporary insulin resistance where insulin levels are actually quite low due to lack of carbs. Temporary insulin resistance seems to be necessary to signal a cell is "full" and doesn't need more energy.

Peter @Hyperlipids ideas revolve around the NADH/FADH ratio and reverse electron flow. Polyunsaturated fats have more nadh to fadh, which leads to less reverse electron flow in the mitochondria due to less electrons going in at input 2. The reverse electron flow produces ROS which goes on to cause temporary insulin resistance.

So with sat fat you would expect insulin resistance of fat cells to kick in sooner, but this is what you want if IR is the signal for a cell to say it's full.
 

nerd

Senior Member
Messages
863
Likes
2,537
The reverse electron flow produces ROS which goes on to cause temporary insulin resistance.
It's the same issue as with other symptomatic treatments that try to fix one aspect of the condition but while making the sacrifice of creating more oxidative stress.
 

ljimbo423

Senior Member
Messages
4,649
Likes
12,555
Location
United States, New Hampshire
I tried Keto for four months without any improvement. In fact I deteriorated from severe to extremely severe on it.
When I go into ketosis, my immune system seems to get very stimulated. I feel just like I have a bad flu and I've even had severe pink eye from it twice. So it doesn't seem like a typical "keto flu".

I don't know if it's somehow directly stimulating my immune system, or maybe creating a huge amount of toxins from stimulating my mitochondria. But my immune system seems to get very stimulated, making me miserable.

Like you, I'm not sure if I was in full ketosis or maybe moving in and out of it. Therefore getting all these side effects. This lasted for several weeks when I tried a keto diet.
 

nerd

Senior Member
Messages
863
Likes
2,537
When I go into ketosis, my immune system seems to get very stimulated.
It could also be a reactivated virus and this stimulates the immune system. If the immune system is stimulated by ketosis, you'd generally feel better due to improved oxidative capacities.
 

Shanti1

Moderator
Messages
1,569
Likes
3,892
@Shanti1 As far as I understand it, saturated fat shouldn't lead to ever increasing insulin when in ketosis. It is a temporary insulin resistance where insulin levels are actually quite low due to lack of carbs. Temporary insulin resistance seems to be necessary to signal a cell is "full" and doesn't need more energy.

Peter @Hyperlipids ideas revolve around the NADH/FADH ratio and reverse electron flow. Polyunsaturated fats have more nadh to fadh, which leads to less reverse electron flow in the mitochondria due to less electrons going in at input 2. The reverse electron flow produces ROS which goes on to cause temporary insulin resistance.

So with sat fat you would expect insulin resistance of fat cells to kick in sooner, but this is what you want if IR is the signal for a cell to say it's full.
I guess I'm not following how a short burst of IR and a cell saying its full would result in eventual better insulin control. Or how more ROS generation in our already dysfunctional mitochondria could be good. Peter has 65 blog posts called "Protons", was there one in particular the explains what you are mentioning? I'm guessing that reverse electron flow has many more influencers than just NADH vs FADH2 balance from sat and unsat fat and where they imput electrons in the ECT. I'm also thinking that ETC is is just one of many cellular influences fat types have on our cell metabolism and insulin regulation. I try to keep an open mind, but I would need more to convince me that saturated fat is better for you on a keto diet than mono or poly-unsaturated when most data we have from other types of dietary patterns says otherwise.
 

Shanti1

Moderator
Messages
1,569
Likes
3,892
When I go into ketosis, my immune system seems to get very stimulated. I feel just like I have a bad flu and I've even had severe pink eye from it twice. So it doesn't seem like a typical "keto flu".

I don't know if it's somehow directly stimulating my immune system, or maybe creating a huge amount of toxins from stimulating my mitochondria. But my immune system seems to get very stimulated, making me miserable.

Like you, I'm not sure if I was in full ketosis or maybe moving in and out of it. Therefore getting all these side effects. This lasted for several weeks when I tried a keto diet.
There is definitely not a one-size-fits-all when it comes to diet. My husband is vegan and I eat only vegetables and protein- no grains, starches, or fruit. We never eat the same meal together. My favorite dietary advice is to 'eat what your body accepts'.
 

sb4

Senior Member
Messages
1,577
Likes
2,783
Location
United Kingdom
@Shanti1 Whether that approach is better for ME is a valid question and of course I have no idea.
If you are eating ketosis you would have low insulin and you would want the cell to signal as soon as it is "full" to stop taking in food.

As for the blogs maybe the first 10 gives you the gist and the rest are just refining it. Don't let that put you off though as the blogs are generally pretty small, some only a few paragraphs long.
 

pattismith

Senior Member
Messages
3,560
Likes
7,006
one thing that may explain positive effect of this diet on several diseases is by bringing more absorbable iron.

1636007940308.png