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Researched
and Composed by
Jacob Wilson, BSc. (Hons), MSc. CSCS
Address correspondence to:
jwilson@abcbodybuilding.com
Journal of HYPERPLASIA
Research 6(3):
Published August 3, 2006
Abstract
Consistently protein diets rich in leucine have been demonstrated to stimulate
greater fat loss, maintenance of lean tissue mass, higher satiety , lower post
absorptive insulin levels, and lowered plasma triglyceride levels relative to
standard recommended daily allowance diets which recommend low protein intakes.
The purpose of this paper is to review this evidence, and provide explanations
as to why this occurs.
Introduction
According to standard recommendations as of 2000, individuals should be able to
meet their daily protein needs with as little as 50-100 grams of protein or a
mean of 75 grams. The AHA restates the common Mantra: “There is at present no
scientific evidence to support the concepts that high protein diets result in
sustained weight loss, significant changes in metabolism, or improved health.”
Fat intake is recommended to be approximately 60 grams per day (Layman, 2003).
The remainder of calories are encouraged to come in the form of carbohydrates.
When taken together Layman (2003) suggests that standard recommendations allot
for a 3.5 to 1 ratio of carbohydrates to protein.
However, an analysis of the literature demonstrates that this type of ratio
impairs glycemic control (Layman, 2003a, b), causes sustained hyperinsulemia
after food absorption (layman, 2003b), reduces blood glucose levels post
absorbatively (layman, 2003b), reduces fat oxidation due to increased inhibition
of carnitine transferase (Sidossis et al, 1998; Sidossis et al., 1999), if
consumed in a higher GI form stimulates greater hunger , and can lead to greater
increases in blood triglyceride levels (Sidossis et al., 1998).
In
contrast when protein intake is such that the ratio of carbohydrates to protein
is lowered to 1.5, evidence suggests greater fat loss, maintenance of lean
tissue mass , higher satiety , lower post absorptive insulin levels , and
lowered plasma triglyceride levels (each concept will be discussed below).
Evidence suggests that leucine plays a critical role in each of the above
results (layman, 2003a). The purpose of this paper is to analyze recent data on
higher protein, and the effects of leucine on fat metabolism, maintenance of
lean tissue mass, and glycemic control.
Studies comparing the
effects of a 1.5 to 3.5 ratio of carbohydrates to fats on body composition
To
date some of the more notable research has been conduced by Layman and
associates. As an illustration Layman and colleagues (2003a, Layman et al., &
Layman et al., 2003b) conducted two excellent studies in adult women. The first
study consisted of a 10 week intervention, followed by a second 16 week
intervention. Both studies compared a diet consisting of a 1.5 to 3.5 ratio of
carbohydrates to protein. Study one examined the effects without exercise,
while study two examined the effects with exercise.
In study one participants in the high protein group lost 12.5 pounds of fat
compared to 10.4 pounds of fat in the low protein group, while lean body mass
loss was -1.9 in the high protein group compared to -2.7 pounds of lean mass
lost in the high carbohydrate condition.
Results were even more dramatic in study two. Fat loss was nearly double in the
high protein condition relative to the high carbohydrate condition (19.4 vs 12.3
pounds), while lean tissue loss was more than double in the high carbohydrate
group (-0.9 vs. 2.7). It is interesting to note however that during the first
10 weeks the high protein diet had gained lean tissue mass. However they only
consumed 1.5 grams of protein per kg of bodyweight daily with low meal
frequency. Perhaps with higher protein intakes no lean tissue loss would have
occurred.
These
results suggest that a decreased ratio of carbohydrates to protein enhances fat
lost and lean tissue mass spared during a dieting intervention meant to induce a
500 calorie deficit per day.
Studies comparing the
effects of a 1.5 to 3.5 ratio of carbohydrates to fats on glycemic control
In
the above 10 week study, Layman et al. (2003a) also examined resting glucose
levels after an overnight fast, and 2 hours after a meal, along with the plasma
insulin response to a 400 calorie test meal.
Results indicated that the adult women on a higher protein diet had more stable
blood glucose levels following the overnight fast, as well as after the test
meal. What was really intriguing however was that the plasma glucose levels
following an overnight fast became progressively lower in the CHO group compared
to the protein group, which maintained plasma glucose levels the entire study,
indicating a progressive decline in glycemic control.
Layman (2004) also examined the effects of high vs. low protein conditions on
the postprandial to post absorptive transition (PP-PA transition). The PP-PA
transition is a characteristic of feeding which occurs approximately two hours
after feeding. After a meal, glucose levels rise, as well as plasma insulin
levels. Near two hours time glucose levels return to basal and the individual
enters into a post absorptive state. However, insulin levels still remain
elevated, which means that the liver must provide endogenous glucose output to
match the higher insulin levels. More sustained and stable glucose levels, and
lower insulin levels suggest greater glycemic control during the transition.
Figure 1 displays the typical glucose and insulin response during postprandial,
and transition periods, to a standard 400 calorie meal consisting of
approximately 50 carbohydrates..

Figure 1.
Standard glucose
and insulin response to a 400 calorie meal. Adapted
from Layman (2003)
Layman et al.
(2004) had overweight subjects with abnormally high insulin responses at 2 h
after a test meal either consume the higher protein or higher carbohydrate diet
previously described. Results are displayed in figure 2 which graphically
demonstrates the abnormally high insulin response at 2 hours following a 400
calorie test meal. It was found that the protein group had reached a normative
range by week four and continued to improve to week 10 (12 µU/mL). While the
CHO diet improved, most likely due to weight loss they still had abnormally high
transition levels of insulin (38 µU/mL).

Figure 2.
Comparison of
insulin levels 2 hours after a test meal in Protein and CHO conditions. Adaped
from Layman et al. (2004)
Leucine’s Role in
Greater Fat Loss, Lean Tissue Maintenance, and Glycemic Control
Higher protein diets appear to enhance fat loss through a number of mechanisms.
Wilson G. (2004) provided power evidence that protein has a higher satiation
effect then glucose. The mechanism is most likely linked to the glucostatic
theory explained in that paper, which suggests that satiety is closely linked to
blood glucose levels. Because higher protein diets sustain plasma glucose
levels to a greater extent in the post absorptive period, individuals are less
likely to have a need to search out and consume extra food.
A
second factor concerns efficiency of energy use with proteins. For example 1
gram of protein converts to approximately 0.6-0.7 grams of glucose.
Further, muscle tissue is extremely metabolically active. Because leucine is
able to positively enhance lean mass, it is able to maintain an overall higher
metabolic rate for the duration of a dietary intervention.
Leucine is also the major signaling molecule for protein synthesis which is
itself an extremely costly process.
Finally higher protein diets, and in particular leucine are able to enhance
glycemic control. The mechanisms of protein synthesis and leucine were
discussed in article one, and cover maintenance of lean muscle tissue as well,
while Satiation was discussed previously by Wilson G. (2004).
Therefore the remainder of the article will primarily discuss the role of
leucine in improving glycemic control
Leucine’s Effects on
Glycemic Control
Glucose homeostasis is controlled by two primary regulators, including insulin
mediated and hepatic mediated glucose homeostasis (note that a number of
hormones interact in this process, but insulin and hepatic regulation are of
primary concern in this article, for reviews of fast acting hormones and their
effects on glucose homeostasis see Wilson & Wilson, 2005).
During post absorptive periods the liver is the primary regulator of glucose
homesostasis and produces endogenous glucose output proportional to tissue
needs. During this time gluconeogensis provides the majority of endogenous
glucose output (Alborg et al., 1982). The major amino acids used to produce
glucose are alanine and glutamine. One of the major contributors for these
amino acids are the BCAAs. In particular BCAAs donate their amino group to
pyruvate, converting it to alanine. Alanine then circulates to the liver where
it provides substrate for endogenous glucose production.
Therefore a high proportion of BCAAs in the diet during caloric deficit
conditions, when energy is low is able to provide exogenous substrate which
spares muscle tissue, which itself is comprised of over 80 % BCAAs. The greater
substrate is able to also assist in maintenance of stable blood glucose levels.
During postprandial states, particularly when consuming a high carbohydrate meal
there is a rapid rise in glucose which stimulates insulin secretion. Insulin
hinders gluconeogensis and gluconeogenic enzymes (Wilson & Wilson, 2005).
However, during the transition period when glucose levels return to basal and
insulin remains elevated, the liver must balance the higher levels of insulin
with endogenous glucose output. Because insulin inhibits endogenous glucose
output, levels of blood glucose remain low for time periods proportional to the
magnitude of the insulin response.
It
has been well established that proteins consumed orally have a much lower
insulin response than carbohydrates. However when amino acids are administered
by infusion they have the capacity to greatly increase the insulin response (krebs,
2002). The difference between oral and infused administration appears to be
related to absorption patterns (Layman et al., 2004). Amino acids are slowly
absorbed in the gut, and therefore they are able to be slowly metabolized in the
body. In contrast infusion requires rapid handling of the amino acids.
Similarly, consumption of CHO causes rapid rises in substrate relative to amino
acids, and absorption is handled within two hours of consumption, requiring a
rapid handling of the CHO, unlike orally administered protein. This rapid
handling of the CHO therefore requires great increases in insulin to maintain
glucose levels within normative physiological ranges.
A
clear example of the response of a high protein vs. high carbohydrate meal was
again examined by Laymen and colleagues (2003a). They administered subjects a
400 calorie meal consisting of either the 1.5 or 3.5 ratio of carbs to protein.
Results indicated that the high protein condition increased leucine along with
other BCAAs by 80 %, this was paralleled by a rise in plasma alanine levels,
which is reflective of useable substrate for the liver for the maintenance of
plasma glucose levels. In contrast the high carbohydrate condition had an
overall 6 % decrease in plasma BCAA, alanine, and glutamine levels, which not
only would hinder plasma glucose levels in the post absorptive period, but also
would negatively effect protein balance. As indicated in article 1, lowered
BCAAs decreases protein synthesis.
When
examining the transition period which occurred at 2 hours it was found that
plasma glucose levels in the high carbohydrate group was 30 % below fasting, and
30 % below the high protein group! This was reflective of double the insulin
levels seen at fasting in the high carbohydrate group, and corresponded to a 40
% value above the protein condition.
Leucine not only provides substrate, but has metabolic roles in each of these
processes. First leucine hinders the oxidation of pyruvate by inhibiting its
rate limiting enzyme pyruvate dehydrogenase(Chang et al., 1978), and partitions
it towards the glucose alanine cycle. Further, increased leucine concentrations
activate the rate limiting enzyme for BCAA oxidation (energy use) known as
branched-chain
ketoacid dehydrogenase.
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5
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