Bustin' Broscience: Leucine and insulinI am going to start some short research articles here called "Bustin Broscience" Most of these will be short using newer research and while they will be far from a complete literature review I want to promote some good discussion and attempt to whittle away at some of the misinformation out there.
While I find anecdotal information interesting, it can be affected by so many things that on the evidence chain I would have it at the bottom. There is a reason we have placebo controlled trials/experiments and blinded subjects and researchers.
Thanks to Joel for the image on the right. Can anyone alter it to put a big red line through it?
If you are looking for much more depth, I would highly recommend Alan Aragon's Research Review. It is only 10 clams a month and I make zero money from recommending it, but he does his homework on all of the topics he covers each month.
Click below for more information
Alan Aragon's Research Review
Bustin' Broscience
What the heck is broscience? Here is the definition from the Urban Dictionary. Not sure where the term started and Alan Aragon was the first I read who had used it.
Broscience is the predominant brand of reasoning in bodybuilding circles where the anecdotal reports of jacked dudes are considered more credible than scientific research.
Broscience in action: "Bro, you gotta slam 40-60 grams of waxy maize plus 20 grams of BCAA within 7 seconds of finishing your last set of squat rack curls. Otherwise, you'll go straight catabolic."
Broscience says "Leucine stimulates insulin"
Is this one about to busted?
Leucine
I am predicting some interesting data on the use of the amino acid leucine coming soon. We know that acutely it stimulates the mTOR receptor which is one of the keys to protein synthesis (build more muscle). Long term data, however, is not as plentiful (although I hear there are several cool studies being conducted now.)
Insulin
While a whole review of the actions of insulin would be volumes, the very very short take away is that insulin is one of the key anabolic hormones in the body. I am using the strict definition of anabolic from the term anaolism.
a·nab·o·lism (-nb-lzm)
n.
The phase of metabolism in which simple substances are synthesized into the complex materials of living tissue.
It is just the fancy term for putting stuff together in the body. Most bodybuilders use this term to exclusively talk about taking amino acids and stuffing them into muscle proteins (which I am all for of course since that will make larger muscles), but it can also apply to taking free fatty acids (FFAs) from the blood and putting them in fat (adipose) tissue.
So insulin is the main anabolic hormone and the basic theory is that more insulin will increase the process of stuffing more fats into adipose tissue.
Do you get get fat by using leucine?
Here is an interesting study where they added leucine to the drinking water of our fury little friends. Let's see if there is an effects on fatness (obesity) and insulin?
Leucine Supplementation of Drinking Water Does Not Alter Susceptibility to Diet-Induced Obesity in Mice,
They stated, "Branched-chain amino acids (BCAA), Leu, and the signaling pathways they regulate have been reported to either improve or worsen adiposity and insulin sensitivity."
They added leucine or BCAAs to the rat's water and fed them lots of food and measured metabolic rate and insulin tolerance.
They found that, "Compared with control, supplementation did not affect body weight, food intake, oxygen consumption, locomotor activity, body composition, insulin tolerance, or total cholesterol."
While this study is limited and done in rats, that is strike one
What else?
Here is another study
Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose
The goal of this study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response.
They used 13 human subjects, which is good as we are not rats; but those little fury guys are much easier to do highly controlled studies on though. The arrived fasted and got some leucine and 25 g of glucose wile they measured serum leucine, glucose, insulin, glucagon, and α-amino nitrogen concentrations over a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak.
Leucine concentrations
Leucine did appear in the blood and acutally REDUCED the 2.5-hour glucose area response by 50%. Leucine, when ingested ALONE, increased the serum insulin area response modestly but glucagon (the antangonist to insulin) also changed.
Think of glucagon as one of the "anti-insulin" hormones and leucine actually increased glucagon!
Shut up and get to the point
2 fold on this study
1) Leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations
2) When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion.
In English please
This shows there is some data that leucine when combined glucose, may increase insulin levels but other hormonal levels change too.
Personal note
If you have ever looked at insulin data (I am currently doing this for a study), it varies much more than you would imagine. Your body is CONSTANTLY adjusting insulin and the "anti-insulin" hormones by the second.
History lesson
As far as I could tell, this below is the first one I can find discussiong leucine and insulin stimulation, published in AJP in 1983.
L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase
The huge downside of this one is that it used perifusion of collagenase-isolated mouse pancreatic islets. In other words, isolated cells in fluid. While ths is a a great START, many many times these data do not translate to whole human (in-vivo) studies.
The final word
I give this one a (drum roll please................)
Plausible
It may happen, but I am not convinced that adding a few grams of leucine or BCAAs to your nutrition is going to dramatically affect insulin levels. Again, this is a supplement, so get your nutrition in line with real food first before you decide to add any fancy supplements.
Comments on this issue of Bustin' Broscience.
Let me know if you this is useful and any feedback you have!
Rock on
Mike T Nelson
REFERENCES
Leucine Supplementation of Drinking Water Does Not Alter Susceptibility to Diet-Induced Obesity in Mice,
Ali Nairizi, Pengxiang She, Thomas C. Vary and Christopher J. Lynch., Penn State Hershey Institute for Diabetes and Obesity and the Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, PA 17033
Branched-chain amino acids (BCAA), Leu, and the signaling pathways they regulate have been reported to either improve or worsen adiposity and insulin sensitivity. Therefore, it is unclear whether dietary supplementation of Leu would be beneficial. To help address this question, we examined the effect of adding Leu (150 mmol/L; Expt. 1 and Expt. 2) or BCAA (109 mmol/L of each; Expt. 3) to the drinking water on diet-induced obesity (induced with a 60-kJ% fat diet) in singly housed C57BL6/J male mice for at least 14 wk. Liquid and solid food intakes were evaluated weekly along with body weight. During the last few weeks, several blood samples were taken at different times for plasma glucose, total cholesterol, or Leu measurements.
Metabolic rate by indirect calorimetry, locomotor activity by light beam breaking, body composition by H1-NMR, and insulin tolerance were also determined. Compared with control, supplementation did not affect body weight, food intake, oxygen consumption, locomotor activity, body composition, insulin tolerance, or total cholesterol. In fed mice, this method of Leu supplementation only increased plasma Leu by 76% when the supplemented group was compared with control. On the other hand, after overnight food deprivation, the plasma Leu did not differ between these 2 groups, even though the mice in the supplemented group had continuous access to Leu-containing water during the solid food deprivation.
CONCLUSION: Taken together, the results do not provide evidence that either Leu or Branched-chain amino acids supplementation of drinking water ameliorates diet-induced obesity in mice, although it may improve glycemia.
Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose
Auteur(s) / Author(s)
KALOGEROPOULOU Dionysia (1 2) ; LAFAVE Laura ; SCHWEIM Kelly ; GANNON Mary C. (1 2 3) ; NUTTALL Frank Q. (1 2) ;
(1) Endocrine, Metabolism and Nutrition Section, VA Medical Center, Minneapolis, MN 55417, ETATS-UNIS
(2) Department of Medicine, University of Minnesota, Minneapolis, MN 55455, ETATS-UNIS
(3) Department of Food Science & Nutrition, University of Minnesota, St. Paul, MN 55108, ETATS-UNIS
Résumé / Abstract
Our laboratory is interested in the metabolic effects of ingested proteins. As part of this research, we currently are investigating the metabolic effects of ingested individual amino acids. The objective of the current study was to determine whether leucine stimulates insulin and/or glucagon secretion and whether, when it is ingested with glucose, it modifies the glucose, insulin, or glucagon response. Thirteen healthy subjects (6 men and 7 women) were studied on 4 different occasions. Subjects were admitted to the special diagnostic and treatment unit after a 12-hour fast. They received test meals at 8:00 AM. On the first occasion, they received water only. Thereafter, they received 25 g glucose or 1 mmol/kg lean body mass leucine or 1 mmol/kg lean body mass leucine plus 25 g glucose in random order. Serum leucine, glucose, insulin, glucagon, and α-amino nitrogen concentrations were measured at various times during a 2.5-hour period after ingestion of the test meal. The amount of leucine provided was equivalent to that present in a high-protein meal, that is, that approximately present in a 350-g steak. After leucine ingestion, the leucine concentration increased 7-fold; and the α-amino nitrogen concentration increased by 16%. Ingested leucine did not affect the serum glucose concentration. When leucine was ingested with glucose, it reduced the 2.5-hour glucose area response by 50%. Leucine, when ingested alone, increased the serum insulin area response modestly. However, it increased the insulin area response to glucose by an additional 66%; that is, it almost doubled the response. Ingested leucine stimulated an increase in glucagon. Ingested glucose decreased it. When ingested together, the net effect was essentially no change in glucagon area. In summary, leucine at a dose equivalent to that present in a high-protein meal, had little effect on serum glucose or insulin concentrations but did increase the glucagon concentration. When leucine was ingested with glucose, it attenuated the serum glucose response and strongly stimulated additional insulin secretion. Leucine also attenuated the decrease in glucagon expected when glucose alone is ingested. The data suggest that a rise in glucose concentration is necessary for leucine to stimulate significant insulin secretion. This in turn reduces the glucose response to ingested glucose.
L-leucine methyl ester stimulates insulin secretion and islet glutamate dehydrogenase
AJP - Endocrinology and Metabolism, Vol 245, Issue 4 338-E346, Copyright © 1983 by American Physiological Society
P. Knudsen, H. Kofod, A. Lernmark and C. J. Hedeskov
Column perifusion of collagenase-isolated mouse pancreatic islets was used to study the dynamics of insulin release in experiments lasting for several hours. The methyl esters of L-leucine and L-arginine were synthesized. Whereas L-arginine methyl ester (L-arginine OMe) had no effect, L-leucine OMe stimulated the release of insulin. The effect of L-leucine OMe was maximal at 5 mmol/liter. Whereas the Km for glucose-stimulated insulin release was unaffected by 1 mmol/liter L-leucine OMe, the maximal release of D-glucose was increased by the amino acid derivative that appeared more effective than L-leucine. L-Leucine OMe was also a potent stimulus of insulin release from the perfused mouse pancreas. In the presence of 10 mmol/liter L-glutamine, 1 mmol/liter L-leucine OMe induced a 50- to 75-fold increase in insulin release. A similar stimulatory effect was also observed in column-perifused RIN 5F cells, a cloned rat islet tumor cell line. A twofold increase in islet glutamate dehydrogenase activity was induced by 5 mmol/liter L-leucine OMe, a larger effect than that of L-leucine (P less than 0.02), whereas L-arginine OMe had a small inhibitory effect. We conclude that L-leucine OMe is a potent stimulus of insulin secretion and that its effect on the beta-cells may be exerted by activating islet glutamate dehydrogenase.
