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April 28, 2012 3:23 PM
Ketogenic Diets Inhibit mTOR, Insulin, IGF-1 and Muscle Growth

Nutrition is arguably the most important component of an athlete or bodybuilder's training regimen. A precise and effective nutritional diet plan produces a biochemical environment that promotes the most efficient muscular adaptations to resistance or endurance exercise. Throughout the years, bodybuilders and athletes have tried to improve their physiques by implementing the ketogenic diet that is high in fat and low in protein and carbohydrate. The fundamental idea behind the ketogenic diet, besides being hypocaloric, is to persuade the body to burn fats rather than carbohydrates or protein due to the lack of carbohydrate and protein in the diet. The excessive fatty acid oxidation in the liver leads to the inevitable conversion of accumulated fatty acid oxidation intermediates into ketone bodies, which were suspected to possess appetite-suppressant properties— thus further facilitating caloric restriction and loss of body fat.

KETOGENIC DIETS DRIVE AN EXTRAORDINARY LOSS OF MUSCLE MASS
While ketogenic diets do tend to stimulate fast weight loss, one of the major drawbacks of the ketogenic diet is that a significant percentage of that bodyweight lost is muscle mass. This negative aspect of the ketogenic diet occurs despite the fact that the body typically prefers to burn either carbohydrates or fat for energy instead of muscle protein, even during times of reduced caloric consumption. For some reason, ketogenic diets generate a greater than normal preference for muscle protein as an energy source during hypocaloric consumption. This phenomenon appears to be partially due to the poor regulation of the all-important nutrient-sensing molecule mTOR from the low-carbohydrate ketogenic diet.

During times of energy surplus, an activated mTOR turns on protein synthesis in muscle cells— leading to enhanced muscle growth and strength. During energy deficits, the inactivated mTOR leads to diminished muscle protein synthesis— leading to muscle atrophy.The consumption of the ketogenic diet has been shown by recent scientific investigation to negatively influence specific hormones and anabolic growth factors that are known to directly or indirectly activate mTOR.This negative influence on mTOR leads to the inhibition of muscle protein synthesis and contributes to the utilization of muscle protein as an energy source.This use of muscle protein as an energy source produces significant loss of muscle mass and strength.

KETOGENIC DIETS INHIBIT INSULIN SIGNALING, PROTEIN SYNTHESIS AND MUSCULAR DEVELOPMENT
Insulin is the primary hormone that responds to increases in blood sugar, causing sugar to be shuttled into the cell for energy consumption or storage. Insulin has also been shown to be one of the most potent activators of mTOR.1 Therefore, the low-carbohydrate feature of the ketogenic diet diminishes insulin signaling and may diminish mTOR signaling. In order to investigate this hypothesis, McDaniel et al.2 investigated the influence of ketogenic diets on insulin signaling. In this study, they showed that low-carbohydrate ketogenic diets significantly diminish insulin action— and this lack of insulin signaling weakens mTOR's ability to stimulate muscle protein synthesis.

GROWTH HORMONE AND IGF-1 FUNCTION ARE DRASTICALLY REDUCED WHILE CONSUMING A KETOGENIC DIET
Growth hormone also integrally participates in mTOR signaling. Since growth hormone is secreted after protein consumption3, the low-protein aspect of the ketogenic diet is further implicated as a potential cause for deficient muscle growth. Consequently, Bielohuby et a1.4 investigated the relationship between growth hormone and ketogenesis. In this study, they demonstrated that the low-carbohydrate aspect of ketogenic diets also leads to a decrease in growth hormone signaling by causing a decrease in the amount of growth hormone receptor levels in the liver. Growth hormone insensitivity in the liver leads to a lack of IGF-1 production, which in turn reduces IGF-1 activation of mTOR, leading to lower protein synthesis levels within muscle cells contributing to muscle atrophy.

HIGH FAT CONSUMPTION FROM THE KETOGENIC DIET ACTIVATES AMPK AND DIMINISHES MUSCLE HYPERTROPHY
Another deleterious consequence that may come from high fat consumption while on a ketogenic diet is the greater amount of fatty acid stored in adipose tissue. The increase in fat storage eventually leads to the release of hormone leptin from the fat cell5, which has been shown to activate the energy-sensing enzyme AMPK in muscle cells and elsewhere.6 AMPK is the cell's master metabolic energy regulator that is typically activated when cellular energy levels are low. However, when high-fat diets— like the ketogenic diet— are consumed, the abundance of fat stored in the fat cell overrides this regulatory principle of AMPK control and triggers AMPK activity, despite the energy status of the cell. AMPK then immediately stimulates fatty acid oxidation. Since AMPK plays such an important role regulating cellular energy, it's no great surprise that AMPK also interacts and regulates mTOR. Moreover, an activated AMPK has been shown to inhibit mTOR function, thus inhibiting muscle protein synthesis and muscle growth. In addition, this increase in adiposity would also lead to a desensitization of the insulin-signaling pathway, which again diminishes the activation of mTOR
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IDEAL DIET CONTAINS A MORE EVEN BALANCE OF MACRONUTRIENTS THAN FOUND IN THE KETOGENIC DIET
The ideal diet for building muscle and burning body fat apparently does not include extreme approaches such as the ketogenic diet, especially for the athlete and bodybuilder who wants to maximize muscle size and strength while losing body fat.The ketogenic diet's low-carbohydrate feature produces a cellular-energy deficit as the human body preferentially and optimally utilizes carbohydrates as an energy source. Carbohydrate depletion reduces the capacity to perform extremely intense resistance and endurance exercise protocols, which will also decrease the capacity to develop muscle mass and remove body fat. Also, the low-protein attribute of the ketogenic diet forces the utilization of muscle protein as an energy source by breaking down muscle protein into amino acids to burn for energy. This, of course, will drive muscle atrophy as well as deplete strength. Finally, the high fat consumption during the ketogenic diet behaves like a molecular monkey wrench within the muscle tissue— wreaking havoc on several biochemical signaling cascades that negatively influence the proper function of mTOR— depleting muscle mass.

In conclusion, a well-balanced diet with plenty of lean protein to drive muscle protein synthesis with complex carbohydrates to supply plenty of energy during resistance training— along with an economic amount of essential fatty acids for long-term energy during endurance work— seems to be the most effective approach to your nutritional routine.

By Michael J. Rudolph, Ph.D.


References:
1. Bolster DR, Jefferson LS, et al. Proc Nutr Soc 2004;63(2), 351-356.
2. McDaniel SS, Reusing NR, et al. Epilepsia 2011;52(3), e7-11.
3. van Vught AJ, Nieuwenhuizen AG, et al. Eur J Endocrinol 2008;159(1), 15-18.
4. Bielohuby M, Sawitzky M, et al. Endocrinology 2011;152(5), 1948-1960.
5. Jazet IM, Pijl H, et al. Neth J Med 2003;61(6), 194-212.
6. MinokoshiY, KimYB, et al. Nature 2002; 415(6869), 339-343.


A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition
  9285851
April 28, 2012 3:38 PM
Nice post, that was a good read.
Thanks!
  18610286
April 28, 2012 4:49 PM
Interesting, I'll have to read through this again, later.
Edited by tigersword On April 28, 2012 4:50 PM
April 28, 2012 4:54 PM
I'll read later - thanks sir flowerforyou
May 23, 2012 12:13 PM
thats for posting this article, its spot on and I wish more people would read it!
May 23, 2012 12:44 PM
Thank you! Very informative. I had never considered following a higher fat than protein diet, I agree with the last statements, about lean protein and complex carbs.
It is the way for me to get stronger and stay fit and healthy.
June 1, 2012 6:37 AM
bump for the keto people trying to build muscle
  9285851
June 1, 2012 6:48 AM
Great read. Thx for posting.
  10992338
December 16, 2012 12:55 PM
bump
December 16, 2012 1:00 PM
I was looking for this the other day - glad it got bumped
  18358448
December 16, 2012 1:02 PM
Tagging to read later- not that it's likely to affect my life. laugh
  20711900
December 16, 2012 1:12 PM
Bumping to read later!
December 16, 2012 1:15 PM
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076631/
December 16, 2012 1:19 PM
Interesting. Jamie Lewis is a proponent of ketogenic with carb backfeeds, and that mother****er is ripped like a parachute cord.
December 16, 2012 1:56 PM
Missed this first time around. Thanks for the bump!
December 16, 2012 1:57 PM
QUOTE:

Interesting. Jamie Lewis is a proponent of ketogenic with carb backfeeds, and that mother****er is ripped like a parachute cord.
Enhancement helps too.

A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition
  9285851
December 16, 2012 2:03 PM
QUOTE:

QUOTE:

Interesting. Jamie Lewis is a proponent of ketogenic with carb backfeeds, and that mother****er is ripped like a parachute cord.
Enhancement helps too.

A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition



Well, I doubt he's on gear. At least he's pretty quiet about it if he is.
December 16, 2012 2:07 PM
Every study I see on pubmed disagrees about losing muscle mass.

http://www.ncbi.nlm.nih.gov/pubmed/22835211
RESULTS:

No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass.
There is just one, I am not bothering with the rest.

What makes some people so angry about keto diets? Seriously.
  3026669
December 16, 2012 2:18 PM
QUOTE:

QUOTE:

QUOTE:

Interesting. Jamie Lewis is a proponent of ketogenic with carb backfeeds, and that mother****er is ripped like a parachute cord.
Enhancement helps too.

A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition



Well, I doubt he's on gear. At least he's pretty quiet about it if he is.
Don't know an elite powerlifter who hasn't used gear. May be "clean" now, but only a bloodtest will tell.

A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition
  9285851
December 16, 2012 2:22 PM
QUOTE:

Every study I see on pubmed disagrees about losing muscle mass.

http://www.ncbi.nlm.nih.gov/pubmed/22835211
RESULTS:

No significant differences were detected between VLCKD and WD in all strength tests. Significant differences were found in body weight and body composition: after VLCKD there was a decrease in body weight (from 69.6 ± 7.3 Kg to 68.0 ± 7.5 Kg) and fat mass (from 5.3 ± 1.3 Kg to 3.4 ± 0.8 Kg p < 0.001) with a non-significant increase in muscle mass.
There is just one, I am not bothering with the rest.

What makes some people so angry about keto diets? Seriously.
This didn't dispute what was posted about keto diets and muscle building being nominal. A "non significant" increase relatively means no increase. So why would you do a keto diet, if muscle gain is not significant from it?

A.C.E. Certified Personal and Group Fitness Trainer
IDEA Fitness member
Kickboxing Certified Instructor
Been in fitness for 28+ years and have studied kinesiology and nutrition
  9285851
December 16, 2012 2:27 PM
QUOTE:

This didn't dispute what was posted about keto diets and muscle building being nominal. A "non significant" increase relatively means no increase. So why would you do a keto diet, if muscle gain is not significant from it?


THIS >KETOGENIC DIETS DRIVE AN EXTRAORDINARY LOSS OF MUSCLE MASS < From OP. Exactly what my first line states. That is all, no more.

EXTRAORDINARY LOSS OF MUSCLE vs A "non significant" increase is a HUGE issue no?

And to be SUPER clear, Keto is not the best way to build muscle, but it seems to be a mighty fine way to lose fat while preserving as much muscle as possible. Stop being so angry and mind your own diets.
Edited by Bakkasan On December 16, 2012 2:38 PM
  3026669
December 16, 2012 2:50 PM
What were the serum beta-hydroxybutyrate levels of the subjects in the six studies cited in support of Dr. Rudolph's article?
Edited by Spartan_Maker On December 16, 2012 2:52 PM
  25147453
December 16, 2012 2:55 PM
Bump.
December 16, 2012 3:07 PM
QUOTE:

What were the serum beta-hydroxybutyrate levels of the subjects in the six studies cited in support of Dr. Rudolph's article?


Perhaps you are thinking what I'm thinking - that its unusual to see an article like this that doesn't quote actual studies in the text to back up what they are saying.

Still, it pretty much goes along with my way of thinking - to have a lot of protein but not actually to go ketogenic.
December 16, 2012 3:22 PM
QUOTE:

QUOTE:

What were the serum beta-hydroxybutyrate levels of the subjects in the six studies cited in support of Dr. Rudolph's article?


Perhaps you are thinking what I'm thinking - that its unusual to see an article like this that doesn't quote actual studies in the text to back up what they are saying.

Still, it pretty much goes along with my way of thinking - to have a lot of protein but not actually to go ketogenic.


Well, in particular, we know as a matter of evolutionary biology that we are all here today because BHB is arguably the most protein (and glucose) sparing compound known to mankind.

It seems more than a little bit bizarre, then, for Dr. Rudolph not to even discuss the BHB levels of the subjects in the studies that he summarily lists as his references.

What's more, how "hypocaloric" were the diets in the studies he cites?

The other thing I'd want to know is if the protein intake of the subjects was between 0.6 and 1.0 grams per pound of lean mass -- generally recommended for those on a ketogenic diet or protein sparing modified fast (PSMF).
  25147453

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