February 07, 2007
Leucine Deficiency Emulates Calorie Restriction

Instead of restricting all calorie sources just avoidance of the amino acid leucine delivers many of the same benefits for fat metabolism.

Two biologists at Penn State have discovered a master regulator that controls metabolic responses to a deficiency of essential amino acids in the diet. They also discovered that this regulatory substance, an enzyme named GCN2 eIF2alpha kinase, has an unexpectedly profound impact on fat metabolism. "Some results of our experiments suggest interventions that might help treat obesity, prevent Type II diabetes and heart attacks, or ameliorate protein malnutrition," said Douglas Cavener, professor and head of the Department of Biology, who led the research along with Feifan Guo, a research assistant professor. Their research will appear in the 7 February 2007 issue of the scientific journal Cell Metabolism.

Can one get some of the weight loss benefit on a low leucine diet that has enough leucine for basic needs?

A leucine-free diet is the fast path to big time weight loss?

Organisms adapt metabolically to episodes of malnutrition and starvation by shutting down the synthesis of new proteins and fats and by using stores of these nutrients from muscle, fat, and the liver in order to continue vital functions. Cavener and Guo found that the removal of a single amino acid, leucine, from the diet is sufficient to provoke a starvation response that affects fat metabolism. "These findings are important for treating two major problems in the world," Cavener says. "The starvation response we discovered can repress fat synthesis and induce the body to consume virtually all of its stored fat within a few weeks of leucine deprivation. Because this response causes a striking loss of fatty tissue, we may be able to formulate a powerful new treatment for obesity."

Do any readily available protein sources have no leucine in them? Would one need to stop eating all protein in order to avoid leucine? If you wanted to avoid the amino acid tryptophan then gelatin will serve as a cheap easily available tryptophan-free food. But gelatin is 3.5% leucine. So that's not a solution.

Note that leucine is an essential amino acid. Someone who wants to go on a leucine-free diet could not continue on it indefinitely. Also, ingestion of extra leucine with protein stimulates muscle protein synthesis. So leucine has advantages to bodybuilders. Avoidance of leucine involves trade-offs.

Thanks to Lou Pagnucco for the heads-up.

Share |      Randall Parker, 2007 February 07 11:06 PM  Aging Diet Studies

hamerhokie said at February 8, 2007 10:49 AM:

I guess the key followup question becomes - how might an individual eliminate all leucine from his diet? Sounds like becoming a vegetarian isn't sufficient. Anyone have a master list of 'All Foods Containing Leucine?'

Purenoiz said at February 8, 2007 1:45 PM:

Great, a new way to yo-yo your weight all over the map while not eating sensibly or breaking a sweat.

I wonder how long these mice were on this plan. And how this is going to play out in humans, since we are in effect different creatures than mice, particularly lab mice.

Randall Parker said at February 8, 2007 6:49 PM:

hamerhokie, I think one would need to go on a protein-free diet. I do not see another way unless one assembled individual amino acids into leucine-free protein.

rhodan said at February 9, 2007 2:16 AM:

It seems to be also the case for methionine restriction :


It is also looked at for cancer. Methionine restriction can be tolerated by humans (but there is a limit). This is one good reason to become vegetarian as meat is rich in methionine.

But as you said, limiting proteins is s

hamerhokie said at February 9, 2007 6:50 AM:

"hamerhokie, I think one would need to go on a protein-free diet. I do not see another way unless one assembled individual amino acids into leucine-free protein."

Do all protein-containing foods provide all the branch chain amino acids? I hope not, because to me avoiding all protein foods to eliminate leucine would be like using a nuke to destroy a chipmunk. Google tells me there are a few leucine free protein supplements available commercially. So it might be a matter or assembling a short duration diet using all non-leucine foods plus one of these supplements.

What the article doesn't say is how long the mice could survive without leucine.

Lou Pagnucco said at February 9, 2007 9:31 AM:

The Enfamil product LMD is a source of leucine-free protein used by people who cannot easily metabolize leucine.
See the website:

I would not take it without medical oversight - it is probably ill-advised for the elderly and the ill who are experiencing muscle wasting.

There are some very interesting interrelationships between leucine, mitochondrial activation, aging, mTOR signaling, satiation and neuroendocrine activity.

Doug said at February 9, 2007 4:46 PM:

Here's a link to a page on which a leucine-free "medical food" is offered for sale. I'm not making a recommendation; eat, or not, at your own risk.


Given that leucine supplementation with exercise is reported to boost muscle protein synthesis, while leucine deprivation boosts metabolism of fat stores, it seems intermittent leucine fasts and leucine feasts might be a way to be both muscular and lean, while avoiding undernourishment and hunger pangs. Arthur Devany, please call your office.

Randall Parker said at February 9, 2007 8:17 PM:

Vegetable proteins are incomplete. Anyone know the vegetarian protein matching rules for making amino acids balance out? Is leucine one of the amino acids that one has to worry about getting when a vegetarian?

Soy is short on methionine if memory serves.

hamerhokie said at February 13, 2007 6:40 AM:

Another way to look at this is to consider that the lack of leucine triggers the catalyst enzyme GCN2 eIF2alpha kinase. So maybe ingesting or injecting this enzyme in sufficient quantity would induce the same effect.

Bryan said at March 2, 2007 11:53 AM:

Leucine is the most common amino acid found in proteins, and is essential for optimal growth in infancy and childhood and for nitrogen equilibrium in adults. It is suspected that Leucine plays a part in maintaining muscles by equalizing synthesis and breakdown of proteins. Cutting Leucine out of your diet is really good for you.

Kim Watkins said at March 27, 2007 5:27 AM:

I am a dietitan researching a list of low leucine containing foods for a client (child) with a condition called Isovalkoric acidemia, a rare condition in which she lacks the enzyme to metabolize leucine and it builds up in her system causing a severe acidemia. She is on the Low leucine formula but Mom wants to know what foods her 2 year old can safely eat. A list of leucine content of foods would be helpful to her. Anybody know of a resource list? Kim

drosart said at November 30, 2007 9:58 AM:

Emulates calorie restriction? Did the mice live longer? They lost a lot of fat mass--did they lose a lot of lean mass? I've read elsewhere that the mice lost half their liver weight, as well. I could lose all my fat mass if you were to render me down in a cauldron, too.

steampowered god said at December 11, 2011 8:55 AM:

"it seems intermittent leucine fasts and leucine feasts might be a way to be both muscular and lean, while avoiding undernourishment and hunger pangs. Arthur Devany, please call your office."

Yes, protein cycling like diet. How fast does the leucine deficiency start to rev. up the fat metabolic machinery? Would 30 hour very-low-protein low calorie periods be enough to eliminate fat drastically?. One could alternate with higher protein higher calorie periods with resistance training to generate lean muscle mass.

It is known that alternate day fasting CR can boost lifespan in animal models. That is no food on alternate days, and regular food intake on the other days. Of course protein cycling, would simply lower protein intake while allowing some calories and food on alternate days, making it vastly easier to implement.

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