Ketone bodies mimic the life span extending properties of caloric restriction

[Todd Allen]

Al Pater posted the abstract for this paper in his updates thread but I thought it merited the attention of having the full text link posted.

http://onlinelibrary.wiley.com/doi/10.1002/iub.1627/full

 

Although some are opposed to the idea of carbohydrate restriction to achieve nutritional ketosis because of the increased need for dietary fat to maintain weight, one can also on a limited basis achieve elevated ketones through fasting.

[Sibiriak]

Thanks.   Definitely worth reading.   I'm looking forward to comments.

[Burak]

Ok, but where is the study that compares ad-lib ketogenic rats against calorie restricted rats so that we can see which group lives longer? Because I am also curious about long term effects of ketogenic diet. At least they should do that as a next step, right?

[Michael R]

This is a mixture of mechanistic make-the-case arguments and a lifespan study in the roundworm C. elegans. As I've written many times before one should ignore studies on interventions in aging in nematode worms (C. elegans), fruitflies (Drosophila), and all other non-mammalian species until they are replicated in full in mammals (see additional reasons for skepticism about roundworm studies here and more recently here).

 

Additionally, amongst their make-the-case mechanistic arguments is the stimulation of the nicotinic acid receptor Gpr109a/PUMA-G. But activation of that same receptor results in suppression of insulin release and is thought to be the (or a) mechanism of niacin-associated diabetes.

 

And, finally, two rodent lifespan studies of ketogenic diets have been done, and it failed in both.(1,2) An important caution, however, is that one of them used the F3666 ketogenic rodent chow, which provides only 5% of Calories from protein, resulting in some studies in kwashiorkor with fatty liver and insulin resistance. But absent supportive mammalian evidence as counterweight, the balance of evidence can't be said to support ketogenic diets as an anti-aging strategy at this time. (If you're overweight and find keto to be the diet that works best for you, of course, have at).

 

References

1: Douris N, Melman T, Pecherer JM, Pissios P, Flier JS, Cantley LC, Locasale JW, Maratos-Flier E. Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet. Biochim Biophys Acta. 2015 Oct;1852(10 Pt A):2056-65. doi: 10.1016/j.bbadis.2015.07.009. Epub 2015 Jul 11. PubMed PMID: 26170063; PubMed Central PMCID: PMC4862866.

 

2: Muller AP, Dietrich Mde O, Martimbianco de Assis A, Souza DO, Portela LV. High saturated fat and low carbohydrate diet decreases lifespan independent of body weight in mice. Longev Healthspan. 2013 Jun 3;2(1):10. doi: 10.1186/2046-2395-2-10. PubMed PMID: 24472284; PubMed Central PMCID: PMC3922950.

[Todd Allen]

There are some who believe hyperinsulinemia is a contributing factor to insulin resistance and the eventual resulting hyperglycemia. And that much of the pathology of diabetes is directly attributable to the hyperinsulinemia. Niacin lowering the insulin response might aggravate hyperglycemia in a high carbohydrate environment but in the context of a ketogenic diet reducing hyperinsulinemia might help reverse insulin resistance and Type 2 diabetes.

[mccoy]

There  has been some debate recently in the internet about the NuSi study, which was designed to outline the metabolic difference between a 2700 kCal d-1 SAD, complete with simple sugars, and an isocaloric Keto diet. Controlled clinical trial, n=17, no possibility to cheat on the food. The results were surprising, in that there wasn't much difference in the caloric balance between the two diets, at least, the difference, in favour of the keto diet (it burned 40-100 kCal more) was far lesser than expected. Also, the keto diet appeared to burn muscle tissue preferentially and not fat. As long as we want to discuss it, the two diets representing two extremes, the differences turned out to be amazingly small. 

 

Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men¹,²

 

 

 

Abstract

Background: The carbohydrate–insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that “a calorie is a calorie” predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat.

Objective: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition.

Design: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EE_chamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EE_DLW).

Results: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EE_chamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (−0.111 ± 0.003, P < 0.0001). EE_DLWincreased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass.

Conclusion: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.

[mccoy]

The study was not related to people with low BMI so its usefulness in the CR context is dubious.

 

One issue which is occurring to me: a real keto diet, with moderate protein, is able to lower drastically serum insulin and consequently IGF-1.

So, at least theoretically, insofar as such a keto diet (or even low-carb)  is made up of healthy food, it should be well suited to a CR regime (of course other issues such as too many fats may overwhelm the benefits).

 

A vegetarian keto or low-carb diet poses no problems, whereas a vegan keto/LC might be too restrictive for some: above ground vegetables, a few berries, all nuts and seeds (barring cashews maybe), avocados, all fats, soymilk and tofu...not much else .

[randyf]

Saul wrote in another post:

*********

Also unclear is the optimal macronutrient (carb/protein/fat) ratios:  I used t think that I was on a high carbohydrate diet -- since I, like most of us, eat mostly raw vegetables.  While (technically) I was correct -- soluble and insoluble fiber are complex carbohydrates -- what is meant by "carbohydrates" in these ratios is understood to be simple carbs (such as sugar, starch, sugar alcohols, etc.).  By this more correct, definition, my diet is actually low carb, low protein, high fat -- a ketotic diet.  This was verified with bloodwork -- my serum ketone measurement showed that I have "ketosis" (this is because the test is usually performed on diabetics, for which it is a serious complication).

**********

 

Low calorie diets irrespective of carbs, fats, protein significanly increase serum keytone bodies.

In fact rodents on Low Calorie High Carb Low Fat diet produce More keytones than rodents on full calore classic ketogenic diets (high fat, very low carb low protein diets)

 

http://www.nutrition.../content/1/1/11

See figure 4 below. Four diets were compared:

1. Standard diet - calorie unrestricted
    
2. Standard diet - calorie restricted
    
3. Ketogenic diet - calorie unrestricted
    
4. Ketogenic diet - calorie restricted

Note that the Standard diet (high carb/low fat) with Restricted calories produced More hydroxybutyrate than the Ketogenic (low carb/high fat) Unrestricted calorie diet.

 

 

Figure 4

 

[Saul]

Interesting Randy.

 

What isn't clear is what level of keytone bodies in rodents would correspond to "ketosis" in humans?

 

Also, whatever that is (if even well defined), it remains true that my own personal diet is very low in simple carbs (but high in soluble fiber and moderate in insoluble fiber -- which are definitely carbs); so my diet, I think. is a "ketotic diet".

 

(Also, I'm considering adding raw purple sweet potatoes to my diet --that would add a lot of resistant starch.  More "carbs" -- but not much simple carbs.)

 

  --  Saul

[randyf]

Interesting Randy.

 

What isn't clear is what level of keytone bodies in rodents would correspond to "ketosis" in humans?

 

But what the results do show is that rodents on a Low calorie High carb low Fat diet increase keytones by 4x.

Also the low calorie high carb group produced 33% more keytones than the group eating a higher calorie ketogenic diet..

 

 

 

 

 

 

 

 

Also, whatever that is (if even well defined), it remains true that my own personal diet is very low in simple carbs (but high in soluble fiber and moderate in insoluble fiber -- which are definitely carbs); so my diet, I think. is a "ketotic diet".

 

(Also, I'm considering adding raw purple sweet potatoes to my diet --that would add a lot of resistant starch.  More "carbs" -- but not much simple carbs.)

 

  --  Saul

 

I don't know your diet other than your descriptions over the years. But you know CFP rations of what you eat. This shouldn't be a mystery. And keep in mind that the 

soluble fiber is partially digested to fat, insoluble fiber is 0 calories (I think?).

 

From what I've seen simple carbs, even in a full calorie healty, balanced diet, are nothing to worry about. 

Even less so in a health balanced low calorie diet

[Saul]

Randy,

 

Rodents aren't people.  Many things are similar; and many are different. I wouldn't take rodent data as definitive.

If you want to find out if you're burning keytones rather than glucose (in the areas of your body other than

your brain), have your serum keytones tested. I did. (The test said "ketosis". :)

 

-- Saul

[randyf]

Randy,

 

Rodents aren't people.  Many things are similar; and many are different. I wouldn't take rodent data as definitive.

If you want to find out if you're burning keytones rather than glucose (in the areas of your body other than

your brain), have your serum keytones tested. I did. (The test said "ketosis". :)

 

-- Saul

Saul - I'm not doubting that you are in keytosis. In fact I'm fascinated. Your experience is consistent with the rat data.    

Remember the rats eating a high carb diet produced 30% more keytones than the rats not on CR but eating a classic keytotic diet. Rats eating a CR keytotic diets even produce more

 

I thought this research finding in rats was really interesting. Folks could greatly increasse keytones (and hopefully with the associated neuro benefits) without having to eat a low carb diet.

 

What I am interested in, if you care to tell, is what your macronutrient profile is?

 

Thanks

Randy