aarr
19 Blood
lipids, diabetes, & obesity: clinical
queries recklessly thrown at the Doc Who Lifts.
Interview with Spencer Nadolsky
Copyright © January 1st, 2018 by Alan Aragon
Home: www.alanaragon.com
Correspondence: support@alanaragon.com
2
Musculoskeletal optimization: Exploring the
impact of nutrition and exercise strategies on
tendon and ligament health.
By Alexander Ketterer & Sten Van Aken
10 The three-month effects of a ketogenic diet on
body composition, blood parameters, and
performance metrics in crossfit trainees: a pilot
study.
Kephart WC, et al. Sports 2018, 6(1), 1;
doi:10.3390/sports6010001 [MDPI - Sports]
12 Nutritional
strategies of high level natural
bodybuilders during competition preparation.
Chappel AJ, et al. Journal of the International Society of
Sports Nutrition (2018) 15:4 DOI 10.1186/s12970-0180209-z [JISSN]
14 Induced and controlled dietary ketosis as a
regulator of obesity and metabolic syndrome
pathologies.
Gibas MK, Gibas KJ. Diabetes Metab Syndr. 2017
Nov;11 Suppl 1:S385-S390. [PubMed]
17 10 years and counting: inception and legacy of
AARR – and a big thanks to the contributors.
By Alan Aragon
Alan Aragon’s Research Review – January 2018
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Page 1
Musculoskeletal optimization: Exploring the impact
of nutrition and exercise strategies on tendon and
ligament health.
By Alexander Ketterer & Sten Van Aken
_________________________________________________
Introduction
For decades, exercise biologists have focused on the
mechanisms in which our musculoskeletal system,
specifically the skeletal muscle, functions, acts and responds
both inside and out, all the way to the bottom layer that
addresses the very specific individual muscle cells. This
foundation of knowledge has provided us with many clues as
to what‘s best for ensuring optimal health and performance.
As a result, we‘ve come to understand that there‘s a range of
hypotheses and theories that benefit the skeletal muscle, such
as a set amount of protein to support optimal growth and
repair and a sufficient training stimulus.
The same thing applies to our bone tissue, also part of the
musculoskeletal system, where scientific research has led to
recommendations such as opting for a sufficient amount of
Vitamin D and calcium from our diet, as well as sufficient
exercise, all favoring the optimization of bone health.
There is no doubt that both nutrition and exercise play a
pivotal role in supporting these parts of the musculoskeletal
system. Yet there is something in the musculoskeletal system
that hasn‘t received the proper attention that might be
warranted. It is mostly associated with sports injuries and is
known to take quite the effort to recover from. You‘ve also
possibly encountered it on a piece of bone like chicken and
had trouble tearing and cutting it with your teeth. I‘m talking
of course about the tendons and ligaments, something we
often refer to as our being connective tissue. But before we
jump into what tendons and ligaments are, what do we mean
if we refer to our ligaments and tendons as connective tissue?
Fundamentals of connective tissue
Connective tissue is a type of tissue that serves a structural
purpose, like keeping your organs in place and preventing
your eyes from popping out during a 1RM record attempt
squat. It‘s the difference being a structure that is both strong,
flexible and that can withstand an impact, compared to being
a loose blob of curry on the ground. To answer why we refer
to our tendons and ligaments as our connective tissue and
what prevents us from being a loose blob on the ground in the
first place is to also understand what makes connective tissue
unique.
Alan Aragon’s Research Review – January 2018
First, there are three things that all connective tissues have in
common that set them apart from other tissues in our body.
The first is that they all originate from the mesenchyme, a
loose fluid of embryonic tissue that can transform into many
different tissues. Think of this tissue fluid like the layers of
paint being applied to a skeleton in a Sci-Fi movie or TV
show (like Westworld) where eventually the layers add up to
transforming the skeleton into a real human being. The
second difference is that these cells originating from the
mesenchyme, called the mesenchymal cells, can be situated
any-which-way and are able to move from place to place. The
third and final thing that separates connective tissue from
other tissues is that literally all of it is composed of nonliving material, called the extracellular matrix (ECM). In this
particular case, the cells that reside in the matrix are actually
LESS important than the matrix itself. You can think of the
matrix as representing a piece of dessert jello with flowing
pieces of goodies inside that are protected.
To expand on the analogy of the jello, the jello can be
considered to be buildup of two components: The first is the
ground structure, which fills up the space between cells and
acts as a form of protection. It is flexible because it consists
of tons of starchy protein molecules mixed with water. The
anchors of this framework are made up of proteins called
proteoglycans. These anchor points have long starchy strands
connected to them like ropes called glycosaminoglycans, or
GAGs, that clump together in water like the gluten in flour
that makes it firm and stretchy. The second part and running
throughout the jelly are the fibers, which provide support and
structure to an otherwise shapeless ground structure.
Elastin is one of those fibers and as the name slightly implies,
has the property of being elastic. It allows tissues to ''snap
back'' to their original shape after being stretched or
contracted like your skin or pulling on your ear. Another
good example of where to find elastin is silverskin, that is the
white fibrous tissue that you sometimes find on the surface of
a muscle. Elastin can mostly found in the artery walls, lungs
and intestines, not forgetting the skin.
Another class of fibers are the reticular fibers. Reticular fibers
are sponge-like fibers that form delicate sponge-like networks
that cradle and support your organs.
Lastly, collagen is by far the strongest and most abundant
type of fiber in our body making up for at least 30% of our
total body protein [1]. Collagen differs from elastin in a way
that it is slightly less stretchy and can actually be softened
and melted away if it‘s cooked in say, the muscle of an
animal - which makes the muscle taste moist.
Taking these different fibers into consideration, the
distribution of fibers determines if they‘re considered a form
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of loose connective tissue that is characterized with having
less fibers, more cells and more ground substance, or dense
connective tissue, which is characterized by being either more
tight, irregular and/or flexible tissue. Our focus in this article
is going to be on the dense connective tissue, that is the
regular type, which is characterized by tight bundles of
collagen running parallel and relate to our central question
about tendon and ligament health.
The composition of tendons and ligaments
Now that we‘ve got a general understanding of connective
tissue and what characterizes the different tissues, we can
start taking a closer look at the composition of tendons and
ligaments. Although they differ in functionality, they share a
basic framework and molecular composition, making them
suitable for concerted discussion [2]. As discussed earlier,
what makes up the ECM largely characterizes their structure
and thus their function. Embedded in the ECM are the
fibroblasts that are responsible for synthesizing the ECM‘s
components (collagen, elastin, proteoglycans) and by that,
determining its composition. Furthermore, the fibroblasts are
interconnected across the tendon/ligament via gap junctions
[3], allowing the cells to communicate and respond in a
uniform fashion to internal stimuli like growth factors and
external stimuli like loading.
Collagen is the major type of fiber found in the ECM, making
up around 80% of dry weight of ligaments and tendons [3][4],
and is responsible for most tensile strength in this particular
connective tissue. Just like type I, IIa and IIb muscle fibers,
collagen comes in different isotypes as well. The vast
majority of collagen is composed of collagen isotype I
molecules that are arranged in a parallel, wave-like fashion
and form composites within the ECM, allowing the
tendon/ligament to withstand tension [5]. Another similarity
between muscles and tendons/ligaments is their hierarchical
structure, starting at the smallest functional unit and forming
increasingly large composites all the way to the complete
muscle/tendon/ligament.
Other components of the ECM synthesized by the fibroblasts
include elastin (2%) which we‘ve addressed earlier and
proteoglycans (1-5%)[6], which are proteins with attached
sugar groups, that are responsible for the crosslinking of
collagen fibrils [7].
Now that we‘ve come to understand what makes up tendons
and ligaments and how these characterizations shape the
ECM, we can now understand the crucial role collagen
synthesis plays in providing structural integrity for tendons
and ligaments.
Collagen synthesis and recovery
As discussed earlier, the fibroblast are responsible for
synthesizing the ECM including collagen, the main
component of tendons and ligaments. Collagen synthesis can
be considered a classic protein biosynthesis mechanism and
thus also being concordant in its basic sequence with muscle
protein synthesis. When stimulated, peptide chains called
‗‘preprocollagens‘‘ are synthesized by ribosomes inside the
fibroblast. Preprocollagen is mostly comprised of the
repeated amino acid sequence glycine-X-Y, resulting in
glycine being the predominant amino acid of collagen. This
abundance of glycine makes collagen a notable exception to
the rest of the proteins inside the body, which usually contain
only small amounts of glycine. Inside the ribosome, proline,
the second most common amino acid in collagen, and lysine
are hydroxylated by enzymes that require vitamin C as a
cofactor.
Besides hydroxylation, further modifications like cleaving
and glycosylation take place, allowing the peptide chains to
form a triple helix (procollagen) that gets secreted into the
extracellular matrix. Outside the fibroblast, procollagen gets
cleaved another time, resulting in the finished triple helix
collagen molecule (tropocollagen). Lastly, the lysine and the
hydroxylysine parts of the collagen molecule are oxidized by
lysyl oxidase, allowing the collagen molecules to aggregate to
collagen fibrils.
Now that we understand how collagen is formed, we can start
addressing the way in which tendons adapt to internal and
external stimuli - but in order to do so, we have to understand
their function first.
Tendon and ligament function
Ligaments connect bone to bone and are key structures for
joint stability by blocking certain displacements of the joint
and restrict movements within their physiological range [8].
While the function and properties of ligaments are pretty
basic in nature, the functionality of tendons is a little more
intricate and requires thorough explanation.
Alan Aragon’s Research Review – January 2018
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injury but also more effective in transmitting high forces from
muscle to bone [9].
Tendon and ligament adaptation
The main function of a tendon is to transmit forces exerted by
the muscle to the skeleton and shows two distinct mechanical
properties: non-linear elasticity and viscoelasticity [9]. The
tendon‘s non-linear elasticity, which differs depending on the
tendon, can be observed in its non-linear stress/strain curve as
shown in the top image. The toe region represents the
„straightening ―of the wave-like collagen structure, leading to
a non-linear slope. With increasing stress, the tendon‘s
collagen fibrils orient themselves in the direction of the
mechanical load and stretch, thus leading to the linear part of
the stress/strain curve. This linear part of the stress/strain
curve can be considered a representation of the tendon‘s
elasticity, which means that when the loading is discontinued,
the tendon will revert back to its original length. When the
applied stress on the tendon results in tendon strain that
exceeds approximately 4%, plastic deformation of the tendon
starts to occur, and the tendon is lengthened irreversibly due
to failure of crosslinks between collagen fibrils, consequently
damaging the tendon. This irreversible lengthening of the
tendon continues with increasing stress until the applied
stress causes a strain of 8-10%, the point at which the tendon
ruptures [9].
For a long time, tendons and ligaments were considered static
tissues that show no adaptation to loading and act merely as
structural components of the musculoskeletal framework.
This widely held assumption among scientists and
practitioners alike lead to the disregard of tendon
strengthening protocols as a reasonable approach to injury
prevention and rehabilitation. As more research on tendon
health and development was performed, it turned out that
these connective tissues are in fact highly dynamic and
adaptable to training stimuli [10]. While the optimal training
stimuli to elicit tendon adaptation are still not convincingly
specified, the adaptations themselves and the adaptation
process have been well established [10].
The tendon‘s second distinctive mechanical property is its
viscoelastic behavior, which means the strain of the tendon is
not exclusively dependent on the amount of stress that is
applied to it but also on the rate at which the strain occurs,
resulting in a non-constant relationship between stress and
strain of a tendon. This behavior can be illustrated by
comparing a slow, near maximum squat to a depth jump. In
general, tendons at low strain rates, like those during a slow
squat, are more deformable and less likely to rupture but
absorb more mechanical energy and thus are less effective in
carrying mechanical loads. In contrast, depth jumping
exposes the tendons to a tremendously high rate of strain,
resulting in the tendon being less deformable, more prone to
Research has currently established two possible mechanisms
that allow a tendon to adapt to increasing mechanical
demands: the first is an increase of the tendon‘s crosssectional area (i.e. hypertrophy), with the second being a
change of the tendon‘s mechanical properties (i.e. an increase
in tendon stiffness). The first postulated mechanism is tendon
hypertrophy induced by load-induced strain of the
extracellular matrix [10]. This load-dependent strain is
transmitted to the cytoskeleton of the embedded fibroblast,
activating a signaling cascade that ultimately leads to an upregulation of collagen and matrix protein synthesis, allowing
the tendon to increase in size. Furthermore, research
demonstrated a second adaptive mechanism: mechanical
loading increased the production of enzymes that are
responsible for collagen crosslinking, thus leading to an
increase in tendon stiffness associated with a lower
electromechanical delay, greater rate of force development
and jump height [10]. It is noteworthy that although tendons
can adapt to mechanical loading via an increase in stiffness,
healthy tendons are variable in their mechanical properties
along their length. This makes sense, considering that the
connection of two mechanically different tissues, like muscle
and tendon or bone and tendon, can cause high stresses at the
interface, possibly leading to injury. In order to align the
mechanical properties of the connecting tissues, collagen
crosslinking along the length of the tendon from bone to
muscle decreases, leading to a stiffer tendon towards the bone
and a more pliable tendon towards the muscle [11]. What
happens when this mechanical variability is lost can be
observed as a result of immobilization: preventing a joint to
move causes an increase of tendon stiffness in the pliable
region and an increase in ultimate tensile strength, likely due
to increased collagen crosslinking [12]. Although ultimate
Alan Aragon’s Research Review – January 2018
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tensile strength of the tendon increases, this reduction of
pliability near the muscle increases the probability of
damaging lengthening contractions. These damaging
contractions are a result of the tendon‘s stiffness exceeding
the isometric strength of the muscle, thus increasing injury
risk post-immobilization [11]. Although an adaptation of
tendon stiffness can be considered a good thing for dealing
with higher mechanical loads, it is of vital importance that the
tendon remains mechanically variable.
Now that we have established the mechanisms by which
tendons adapt, we can start taking a look at the temporal
dynamics involving tendon adaptation compared to muscle
tissue.
Temporal dynamic of tendon adaptation
Tendon tissue is characterized by a lower cell to overall dry
mass ratio, vascularization, and metabolism compared to
muscle tissue and research shows that the half-life of tendon
collagen is almost tenfold higher compared to actin and
myosin part of muscle tissue [10]. Furthermore, it has been
postulated that tendon remodeling almost exclusively occurs
in the outside regions of the tendon with the core of the
tendon showing no significant collagen turnover [10]. These
tendon properties combined with findings of heavy resistance
training intervention studies, where changes of muscle
morphology and architecture occurred as early as 3-4 weeks
with no significant alterations of the tendons [10], can lead to
the assumption that meaningful tendon adaptation occurs with
a significant delay compared to muscle morphology and
strength. That assumption is substantiated by exercise
intervention studies that observed a 1-2 month delay in
tendon adaptation in comparison to gains in muscle strength.
What further underpins these findings is the fact that an
increase in muscle strength can be achieved by neuronal
adaptations that precede morphological changes of the muscle
[10]. In contrast to that, adaptations in tendon resilience rely
exclusively on the adaptation of the tissue structure, which
tends to be a slower process due to the lesser rate of effective
tissue renewal compared to muscle [10]. As a result of these
hypotheses, it‘s possible that imbalances between muscle and
tendon development might occur during the training process,
which brings us to our next aspect of the tendon‘s adaptive
process: which loading strategy is optimal for tendon health
and development?
How different loading patterns influence tendon development
First off, this aspect of tendon adaptation has not been
conclusively researched and needs further investigation. That
being said, research and the aforementioned mechanism of
fibroblast stimulation via deformation suggest that slow
Alan Aragon’s Research Review – January 2018
repetitive high-magnitude (at about 90% isometric maximum
voluntary muscle contraction) tendon strain might be the best
approach to elicit the greatest adaptations in healthy tendons
[10]. It is noteworthy that the specific muscle contraction
type (isometric, concentric, eccentric) seems to be of little
relevance for triggering the adaptation process. Research that
incorporated other loading schemes like plyometric loading
(i.e. a high-magnitude, high-frequency tendon strain loading
protocol) failed to elicit significant adaptive changes in
tendon structure, although improving muscle strength [10].
This finding might provide at least some insight concerning
the high prevalence of tendon overuse injuries in sports with
a plyometric loading profile like basketball or athletic
jumping and warrants additional research. Furthermore,
research suggests that fatiguing training with moderate
loading, like classic muscle hypertrophy training, effectively
triggers adaptations in muscle strength and size, yet doesn‘t
provide sufficient stimulus for meaningful tendon adaptations
to occur [10]. This lack of tendon adaptation could result in
an increase in tendon strain as a result of increased muscle
strength without the appropriate tendon adaptations, causing a
possible risk for injury [10]. With that in mind, a compelling
case might be made for implementing strength focused
training phases from time to time, even for athletes that
exclusively train for muscle size.
While collectively these findings might indicate an
appropriate strategy to promote tendon strength in healthy
tendons, a different approach might be necessary for
promoting recovery in injured tendons and ligaments.
Research that used an in vitro tendon/ligament model, which
properties more closely resemble developing/recovering
tendons/ligaments (i.e. higher cell count, less matrix, higher
expression of developmental collagen isotypes), provides
findings that deviate from the findings concerning healthy
tendons. Study of those engineered ligaments showed that the
molecular response was independent of loading intensity and
frequency [13]. Interestingly, it could be observed that the
duration of the applied loading played a significant role in
determining the molecular response. After about ten minutes
of loading, the molecular response reached its maximum and
additional time under load did not increase the molecular
response any further. Moreover, it took six hours for the
engineered ligaments to become responsive to loading again.
These findings suggest that short bouts of lightly loaded
exercise with potentially limited range of motion and
extensive breaks between bouts might be the best way to aid
tendon/ligament recovery.
Hormonal influence on tendons and ligaments
Lastly, although the specifics are not understood yet,
hormonal status plays a role in influencing tendon and
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ligament integrity. One hormonal effect that has been well
established is estrogen‘s influence on ligament laxity [11].
Research showed that the degree of knee laxity and higher
incidence of ACL rupture in female athletes compared to
their male counterparts seems to be related to circulating
estrogen levels [11]. In an attempt to confirm this, the
researchers using the engineered ligaments exposed those
ligaments to a physiologically high estrogen level that mimics
the estrogen surge leading up to ovulation [14]. After 48
hours of exposure, they observed a decrease in ligament
stiffness although the collagen content did not decrease,
which hints at a decrease of collagen crosslinking. To test this
hypothesis, the researchers measured the activity of the
primary collagen crosslinking enzyme, lysyloxidase, under
the aforementioned estrogen exposure of the ligaments. They
observed that the activity of lysyl oxidase dropped as much as
80% after 48 hours of physiologically high estrogen
exposure. Consequently, it seems reasonable to consider
estrogen an influential factor for tendon and ligament
integrity, especially in female athletes.
In contrast to estrogen, little is known about the effects of
testosterone on tendon and ligament properties. Research
only suggest that the use of androgenic and anabolic steroids
in supraphysiological doses stimulate collagen synthesis and
tendon stiffness, yet reduces tissue remodeling ultimate stress
and strain, which might warrant some implications for longterm drug users [10]. That being said, little is known about
the effects of physiological levels of testosterone on tendon
and ligament development.
Another interesting observation was made when engineered
ligaments were grown in media that was infused with isolated
sera from human test subjects pre- and post-exercise. The
ligaments that were grown in the media containing postexercise sera showed a significant increase in collagen
content and mechanics compared to the ligaments grown in
pre-exercise sera [15]. Furthermore, the same study showed
that this stimulation of connective tissue was not mediated by
growth hormone and IGF-1 but used the mTORC1 pathway,
hinting at a global signal that improves connective tissue
integrity in response to exercise. Finally, this study showed
that the treatment of engineered ligaments with high doses of
recombinant growth hormone had no effect on collagen
content or ligament mechanics. Yet, IGF-1 dose-dependently
stimulated collagen synthesis and affected ligament
mechanics. This observation substantiates the idea that
physiological levels of growth hormone have an indirect
effect on tendons and ligaments via regulation of IGF-1.
Now that we have briefly elaborated on the physiological and
mechanical properties of tendons and ligaments and how they
Alan Aragon’s Research Review – January 2018
respond to loading and hormonal status, it‗s time to discuss
how we might improve tendon and ligament development via
nutrition and supplementation.
Nutrition and supplement considerations for optimizing
tendon and ligament health
Regarding everyday nutrition, consuming a leucine-rich diet
seems to be beneficial for improving tendon and ligament
health. Researchers observed that consumption of whey
protein, which is rich in leucine, can increase tendon
hypertrophy in response to strength training. This observation
could possibly be explained by the fact that leucine activates
the mTORC1 pathway, a pathway that was also activated in
engineered ligaments after treating them with sera that were
collected from human subjects post-exercise. In spite of this
hypothetical connection, it is not clear whether the study‗s
result is based on a direct effect of whey protein intake on
tendons or a byproduct of increased muscle hypertrophy and
strength gains caused by whey protein consumption [16].
With no conclusive evidence for a direct effect of whey
protein on tendon health and the fact that the diet of most
fitness enthusiasts is rich in leucine for muscle building
purposes anyway, we can take a look at a more interesting
aspect: intake of actual collagen and its processed derivatives.
Research suggests that ingestion of collagen peptides has a
plethora of effects on the human body. Besides their
potentially beneficial effects on skin, osteoporosis, the
immune system and precursor cell differentiation to only
name a few [17] [18], research also suggest that ingestion of
collagen peptides has beneficial effects on both collagen
synthesis and tendon mechanics [19]. While measuring the
plasma concentration of amino acids after oral collagen
peptide ingestion, researchers observed high concentrations
of
oligopeptides,
like
proline-hydroxyproline
and
hydroxyproline-glycine, two hours after ingestion [18]. With
collagen molecules heavily featuring the repeated amino acid
sequence glycine-X-Y, with X and Y frequently occupied by
proline and hydroxyproline, collagens high bio-availability
and the fact that oligopeptides containing hydroxyproline are
highly resistant to blood proteases [17], this observation
seems comprehensible. Aside from collagen peptides
providing the necessary amino acids for collagen synthesis,
several studies also suggest that these stable hydroxyproline
containing oligopeptides act as signaling molecules and thus
being partly responsible for mediating the effects of collagen
peptide ingestion [18]. Although the actual mechanism hasn‘t
been established yet, this might make a compelling case for
increasing collagen intake considering the fact that
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hydroxyproline is almost exclusively found in collagen as a
nutritional source
.
What further substantiates these hypotheses is a study on
engineered ligaments [20]. During this double-blind
crossover study, the researchers administered different
doses(0g, 5g, 15g) of gelatin, a hydrolyzed form of collagen,
to human test subjects along with a small dose (48 mg) of
vitamin C, one hour prior to six minutes of jumping rope. The
researchers collected blood samples of the participants at
different time points and added the sera to the growth media
of the engineered ligaments. They found a dose-dependent
increase in collagen deposition with 15g of gelatin doubling
the collagen synthesis rate in engineered ligaments.
In another study performed on osteoarthritis patients, around
10 grams of collagen hydrolysate a day was significantly able
to thicken the cartilage [21]. The same 10 grams of collagen
hydrolysate in another study led to improvements in joint
pain in athletes over a 24-week period [22].
Having these promising findings in mind, we have to take a
look at actual collagen intake. Since collagen is the single
most abundant class of proteins of the vertebrate body
making up about one-third of an animals total protein content,
it can‘t be found in non-animal products [17]. Despite this
abundance of collagen in vertebrates, the average collagen
intake is presumably pretty low among non-meat-eaters and
meat-eaters alike.
One of the reasons for low collagen intake might be that
collagen is missing an essential amino acid, tryptophan, thus
being considered a low-quality protein that doesn‘t get much
attention. Further possible reasons include that cuts of meat
high in collagen, like pork chitterlings or chicken gizzard
[18], tend to be less desirable to the general population‘s
palate or that the more chewy, fibrous parts of meats get
trimmed off.
Beef vs. fish and shellfish (adopted from [24] and modified from [18])
That being said, there are alternatives to eating fibrous meats
to reap the beneficial effects of nutritional collagen. Collagen
can be extracted from collagen-rich animal tissues like skin,
bone and tendons. After extracting the collagen, it gets
processed via hydrolysis. Depending on the degree of
hydrolysis, you either get the partially hydrolyzed collagen
product gelatin or the fully hydrolyzed collagen hydrolysate.
While both being tasteless and available in powdered form,
the main differences between the two products are price,
availability, molecular weight and usage. Gelatin is higher in
molecular weight, relatively cheap, found at any convenience
store and can be dispersed in liquids or used as a gelling
agent for jellos and such. Collagen hydrolysate on the other
hand is more expensive, cannot be used as a gelling agent due
to its lower molecular weight and is usually purchased at
supplement stores.
At this point in time, there are no studies demonstrating a
meaningful difference in bio-availability although collagen
hydrolysate is claimed to be easier to digest. Both products
seem to be sufficiently absorbed by the intestines as free form
amino acids and oligopeptides [17][18][23], making them
equally suitable for increasing your collagen intake.
Putting it all together – a proposed protocol for tendon
and ligament prehab and rehab
Preface: With research on influencing tendon and ligament
development still in its infancy, these recommendations
should be considered speculative and non-definitive. If you
suffer from tendon or ligament injuries, please consult with
your physician or physiotherapist first before implementing
such a protocol.
Protocol for strengthening healthy tendons
Beef vs. fish and shellfish (adopted from [24] and modified from [18])
This protocol should be used for strengthening healthy
tendons and ligaments that are particularly stressed during
Alan Aragon’s Research Review – January 2018
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Page 7
your preferred movements in order to reduce their chance of
injury. First, pick a movement that targets the tendon or
ligament you intend to strengthen. You can either choose an
eccentric-concentric movement, like the squat for
strengthening the patellar tendon, or opt for isometric
exercise like knee extension against a non-elastic band.
Research suggests that the chosen exercise should be
performed for 5 sets of 4 repetitions with each repetition
consisting of three seconds of high intensity contraction (8590% iMVC) followed by three seconds of relaxation and two
minute inter-set rest intervals [10]. It is important that these
exercises are performed at a joint angle that is close to
optimal for force production, for example 60° knee flexion
for patellar tendon training, in order for high tendon forces to
occur. While performing isometric exercises at a certain angle
is relatively easy to achieve, eccentric-concentric movements
like the squat move through a wide range of angles during its
full range of motion. To account for that and allow for
sufficient time at which high tendon forces occur, the
duration of a repetition is doubled from three to six seconds
for dynamic movements [10].
This proposed set and rep scheme should be implemented
three times per week along with your regular training for at
least twelve weeks and can be applied to multiple exercises to
strengthen different tendons and ligaments concurrently.
To optimize training results, athletes are encouraged to ingest
15 g of gelatin or collagen hydrolysate with a small dose of
vitamin C one hour prior to tendon training [11]. This can be
done by dispersing the collagen product in a liquid that
contains vitamin C (like juice) or by preparing a jello made
from gelatin that also contains vitamin C. Moreover, it might
be worth mentioning why the collagen product should be
consumed one hour prior to training: while blood flow to
inactive tendons is limited, suggesting limited nutrient uptake
into the tendon post exercise, glucose uptake into active
tendons is increased during exercise [25]. Thus, in
concordance with the absorption rate of collagen peptides,
taking the collagen product one hour prior to exercise seems
reasonable to optimize nutrient uptake into the tendon.
Lastly, leucine-rich protein should be consumed as part of
training to reap the potential benefits of mTORC1 activation
on tendon and ligament development [11].
rich protein remain the same, this protocol follows a different
approach to training and is inferred from the observations
regarding engineered ligaments, as they more closely
resemble regenerating ligaments and tendons. Following
injury, athletes should start their recovery training protocol as
soon as possible by picking movements that target the injured
tendon or ligament. Depending on the severity of injury, these
movements can consist of weight supported exercises with
limited range of motion if necessary. To maximally stimulate
collagen synthesis, training bouts can be performed multiple
times per day but should not exceed ten minutes of activity
per single session. Furthermore, each training bout should be
followed by at least six hours of rest to allow the connective
tissue to become responsive to loading again and yield
optimal results [11].
Training and supplementing for tendon and ligament
health - the verdict
Although research provides some insight regarding training
and supplementing for tendon and ligament health, these
observations are far from warranting definitive protocols and
should be treated as such. To close in on best practices for
tendon and ligament health, extensive research has to be
conducted, including the role of hydroxyproline
oligopeptides, overall training volume, rest intervals and in
vivo studies of recovering tendons and ligaments. It also
remains unclear to what degree the total amount of protein
matters in a diet that already contains the required contains
sufficient protein to stimulate maximum protein and if
adding additional protein with specific amino acids might
yield more optimal results on top of muscle growth. Despite
this rudimentary understanding of training and supplementing
for tendon and ligament health, the proposed protocols
represent our ―best guesses‖ and might be worth a shot since
they can be considered time- and cost-effective plus offering
a desirable risk-reward ratio.
References
1.
2.
Protocol for accelerating the rehabilitation process after
tendon and ligament injury
This protocol can be implemented to potentially speed up the
recovery process after tendon and ligament injury. While the
recommendations for collagen supplementation and leucineAlan Aragon’s Research Review – January 2018
3.
Di Lullo GA, Sweeney SM, Korkko J, Ala-Kokko L, San
Antonio JD. Mapping the ligand-binding sites and diseaseassociated mutations on the most abundant protein in the
human, type I collagen. J Biol Chem. 2002 Feb
8;277(6):4223-31. Epub 2001 Nov 9.[PubMed]
Rumian AP, Wallace AL, Birch HL. Tendons and ligaments
are anatomically distinct but overlap in molecular and
morphological features--a comparative study in an ovine
model. J Orthop Res. 2007 Apr;25(4):458-64. [PubMed]
Massoud EI. Healing of subcutaneous tendons: Influence of
the mechanical environment at the suture line on the healing
process. World J Orthop. 2013 Oct 18;4(4):229-40.
[PubMed]
[Back to Contents]
Page 8
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
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17.
Liu SH, Yang RS, al-Shaikh R, Lane JM. Collagen in
tendon, ligament, and bone healing. A current review.
ClinOrthopRelat Res. 1995 Sep;(318):265-78.[PubMed]
Raspanti M, Congiu T, Guizzardi S. Structural aspects of
the extracellular matrix of the tendon: an atomic force and
scanning electron microscopy study. Arch Histol Cytol.
2002 Mar;65(1):37-43. [PubMed]
Kleiner DM. Human Tendons: Anatomy, Physiology and
Pathology. Journal of Athletic Training. 1998;33(2):185186. [PubMed]
Scott JE. Elasticity in extracellular matrix 'shape modules'
of tendon,cartilage, etc. A sliding proteoglycan-filament
model. J Physiol. 2003 Dec1;553(Pt 2):335-43. Epub 2003
Aug 15. Review. [PubMed]
Lorda-Diez CI, Canga-Villegas A, Cerezal L, Plaza S, Hurlé
JM, García-Porrero JA, Montero JA. Comparative
transcriptional analysis of three human ligaments with
distinct biomechanical properties. J Anat. 2013
Dec;223(6):593-602.[PubMed]
Wang JH, Guo Q, Li B. Tendon biomechanics and
mechanobiology--a minireview of basic concepts and recent
advancements. J Hand Ther. 2012 Apr-Jun;25(2):133-40.
[PubMed]
Mersmann F, Bohm S, Arampatzis A. Imbalances in the
Development of Muscle and Tendon as Risk Factor for
Tendinopathies in Youth Athletes: A Review of Current
Evidence and Concepts of Prevention. Front Physiol. 2017
Dec 1;8:987. [PubMed]
Baar K. Minimizing Injury and Maximizing Return to Play:
Lessons from Engineered Ligaments. Sports Med. 2017
Mar;47(Suppl 1):5-11. [PubMed]
Eliasson P, Fahlgren A, Pasternak B, Aspenberg P.
Unloaded rat Achilles tendons continue to grow, but lose
viscoelasticity.
J
ApplPhysiol
(1985).
2007
Aug;103(2):459-63. [PubMed]
Paxton JZ, Hagerty P, Andrick JJ, Baar K. Optimizing an
intermittent
stretch
paradigm
using
ERK1/2
phosphorylation results in increased collagen synthesis in
engineered ligaments. Tissue Eng Part A. 2012 Feb;18(34):277-84. [PubMed]
Lee CA, Lee-Barthel A, Marquino L, Sandoval N, Marcotte
GR, Baar K. Estrogen inhibits lysyl oxidase and decreases
mechanical function in engineered ligaments. J Appl
Physiol (1985). 2015 May 15;118(10):1250-7. [PubMed]
West DW, Lee-Barthel A, McIntyre T, Shamim B, Lee CA,
Baar K. The exercise-induced biochemical milieu enhances
collagen content and tensile strength of engineered
ligaments. J Physiol. 2015 Oct 15;593(20):4665-75.
[PubMed]
Farup J, Rahbek SK, Vendelbo MH, Matzon A, Hindhede J,
Bejder A, RinggardS,Vissing K. Whey protein hydrolysate
augments tendon and muscle hypertrophy independent of
resistance exercise contraction mode. Scand J Med Sci
Sports. 2014 Oct;24(5):788-98. [PubMed]
Wang L, Wang Q, Qian J, Liang Q, Wang Z, Xu J, He S,
Ma H. Bioavailability and bioavailable forms of collagen
after oral administration to rats. J Agric Food Chem. 2015
Apr 15;63(14):3752-6. [PubMed]
Alan Aragon’s Research Review – January 2018
18. Koyama Y. Effects of Collagen Ingestion and their
Biological Significance. J Nutr Food Sci 2016, 6:3.
[PubMed]
19. Minaguchi J, Koyama Y, Meguri N, Hosaka Y, Ueda H,
Kusubata M, Hirota A, Irie S, Mafune N, Takehana K.
Effects of ingestion of collagen peptide on collagen fibrils
and glycosaminoglycans in Achilles tendon. J Nutr Sci
Vitaminol (Tokyo).2005 Jun;51(3):169-74. [PubMed]
20. Shaw G, Lee-Barthel A, Ross ML, Wang B, Baar K.
Vitamin C-enriched gelatin supplementation before
intermittent activity augments collagen synthesis. Am J
ClinNutr. 2017 Jan;105(1):136-143. [PubMed]
21. Bohm S, Mersmann F, Arampatzis A. Human tendon
adaptation in response to mechanical loading: a systematic
review and meta-analysis of exercise intervention studies on
healthy adults. Sports Med Open. 2015 Dec;1(1):7.
[PubMed]
22. Clark KL, Sebastianelli W, Flechsenhar KR, Aukermann
DF, Meza F, Millard RL,Deitch JR, Sherbondy PS, Albert
A. 24-Week study on the use of collagen hydrolysate as a
dietary supplement in athletes with activity-related joint
pain.Curr Med Res Opin. 2008 May;24(5):1485-96.
[PubMed]
23. Watanabe-Kamiyama M, Shimizu M, Kamiyama S, Taguchi
Y, Sone H, MorimatsuF,Shirakawa H, Furukawa Y, Komai
M. Absorption and effectiveness of orally administered low
molecular weight collagen hydrolysate in rats. J Agric Food
Chem. 2010 Jan 27;58(2):835-41. [PubMed]
24. Noguchi C, Kobayashi M, Koyama Y (2012) Amount of
collagen ingested by Japanese adult women from their diet.
Jpn J Nutr Diet 70:120-128. [PubMed]
25. Bojsen-Møller J, Kalliokoski KK, Seppänen M, Kjaer M,
Magnusson SP.Low-intensity tensile loading increases
intratendinous glucose uptake in the Achilles tendon. J
ApplPhysiol (1985). 2006 Jul;101(1):196-201. [PubMed]
____________________________________________________
Dipl. pharm. Alexander Ketterer is a
pharmaceutical scientist, powerlifting coach and
personal trainer, operating his company Fortius
Per Scientiam out of Constance, Germany
____________________________________________________
Sten van Aken is dietitian in training at the Hague
University of Applied Sciences. He has a passion for
research intertwined with nutrition and training
and has previously written for Fit Zonder Fabels, a
Dutch myth-busting lifestyle platform and worked
as an associate researcher for Bayesian
Bodybuilding.
[Back to Contents]
Page 9
Study strengths
The three-month effects of a ketogenic diet on body
composition, blood parameters, and performance
metrics in crossfit trainees: a pilot study.
Kephart WC,
et al.
Sports 2018,
doi:10.3390/sports6010001 [MDPI - Sports]
6(1),
1;
BACKGROUND: Adopting low carbohydrate, ketogenic
diets remains a controversial issue for individuals who
resistance train given that this form of dieting has been
speculated to reduce skeletal muscle glycogen levels and
stifle muscle anabolism. PURPOSE: We sought to
characterize the effects of a 12-week ketogenic diet (KD) on
body composition, metabolic, and performance parameters in
participants who trained recreationally at a local CrossFit
facility. DESIGN: Twelve participants (nine males and three
females, 31 ± 2 years of age, 80.3 ± 5.1 kg body mass, 22.9 ±
2.3% body fat, 1.37 back squat: body mass ratio) were
divided into a control group (CTL; n = 5) and a KD group
(n = 7). KD participants were given dietary guidelines to
follow over 12 weeks while CTL participants were instructed
to continue their normal diet throughout the study, and all
participants continued their CrossFit training routine for 12
weeks. Pre, 2.5-week, and 12-week anaerobic performance
tests were conducted, and pre- and 12-week tests were
performed for body composition using dual X-ray
absorptiometry (DXA) and ultrasound, resting energy
expenditure (REE), blood-serum health markers, and aerobic
capacity. Additionally, blood beta hydroxybutyrate (BHB)
levels were measured weekly. RESULTS: Blood BHB levels
were 2.8- to 9.5-fold higher in KD versus CTL throughout
confirming a state of nutritional ketosis. DXA fat mass
decreased by 12.4% in KD (p = 0.053). DXA total lean body
mass changes were not different between groups, although
DXA dual-leg lean mass decreased in the KD group by 1.4%
(p = 0.068), and vastus lateralis thickness values decreased in
the KD group by ~8% (p = 0.065). Changes in fasting
glucose, HDL cholesterol, and triglycerides were similar
between groups, although LDL cholesterol increased ~35% in
KD (p = 0.048). Between-group changes in REE, onerepetition maximum (1-RM) back squat, 400 m run times,
and VO2peak were similar between groups. CONCLUSIONS:
While our n-sizes were limited, these preliminary data
suggest that adopting a ketogenic diet causes marked
reductions in whole-body adiposity while not impacting
performance measures in recreationally-trained CrossFit
trainees. Whether decrements in dual-leg muscle mass and
vastus lateralis thickness in KD participants were due to fluid
shifts remain unresolved, and increased LDL-C in these
individuals warrants further investigation. SPONSORSHIP:
The only costs herein were the serum analyses, which were
funded through residual funds provided to Michael D.
Roberts through a prior grant awarded to him by the Applied
Sports Performance Institute (ASPI).
Alan Aragon’s Research Review – January 2018
With scant exceptions,1-3 the performance studies on
ketogenic dieting are typically 4-6 weeks (or less). The
present study was 12-weeks, which presumably is sufficient
for accommodating an initial keto-adaptation period. Subjects
were required to have a minimal strength-to-mass ratio of at
least 1:1 (bodymass: back squat) and a minimum of 3 months
of gym activity. This weeded out untrained/newbie trainees.
Dual X-ray absorptiometry (DXA) was used to assess body
composition. Blood ketone levels (beta-hydrodybutyrate;
BHB) were measured weekly, this provided an objective
marker of compliance to the ketogenic diet.
Study limitations
The authors acknowledged several limitations, the first being
the small number of subjects. Instead of random allocation,
the subjects were given volitional choice of whether they
wanted to try the ketogenic diet (KD) or keep their habitual
diet. This introduces the possibility of expectation bias for
favorable outcomes in the keto group. In light of this, the
authors
diligently
acknowledged
the
following:
―Additionally, there is the real chance that individuals in the
KD group may have experienced a placebo effect in relation
to performance outcomes. Alternatively stated, given that
many of the KD participants experienced improvements in
body composition and (anecdotally) many of these
participants perceived themselves having more energy
throughout the day, these phenomena could have motivated
them to perform the exercise tests with more vigor relative to
the CTL [control] group.‖ I would add to these limitations
that there was no standardization of dietary intake prior to
performance testing, which leaves open the confounding
potential of variable levels of fuel availability. The control
group was not required to track their dietary intake, which is
a shame since this data would have been valuable in drawing
inferences as to the results. Although the KD group was
required to track intake, only 4 out of the 7 subjects submitted
a food log at the 12-week point (food records for the other 3
subjects in KD were limited to baseline and 2.5 weeks).
Comment/application
The main findings were a lack of significant differences
between groups in the performance tests. Performance was
preserved in 1RM squat, 1RM power clean, and 400-meter
run. The only performance parameter that showed
improvement from baseline was push-ups to failure – but no
between-group differences were seen. Individual performance
data were reported (here), and it‘s always interesting to see
the variability of responses. As for body composition
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Page 10
(complete graphical data here), KD lost a significant amount
of bodyweight (3 kg) and body fat (2.5 kg) while the control
group did not lose a significant amount of bodyweight (0.3
kg) or body fat (0.3 kg). Total lean body mass (LBM) was
preserved and not significantly different between groups.
However, when viewed segmentally, decreases in dual-leg
lean mass and lateralis thickness approached statistical
significance in KD, but the effects sizes for each decrease
were large. Resting energy expenditure and respiratory
quotient (an indicator of substrate utilization; the proportion
of fat/carb utilization) were not significantly changed or
different between groups. Expectedly, blood ketone levels
were significantly higher in KD compared to control. I found
it interesting that over time, blood BHB levels appeared to be
on a downward trend, which suggests the potential for a
decrease in adherence over time to the KD:
An additional factor is a potential decrease in food reward via
lower hedonic contribution to food intake.7 So, with the nearelimination of carbohydrate-containing foods, this lowers the
probability of consuming hyperpalatable foods – many of
which are comprised of combinations of fat and refined
carbohydrate.
But once again, the question is whether or not the KD is
sustainable in the long-term, and what potential adverse
effects might manifest as a result of long-term adherence.
Definitive answers to these questions are still under
investigation. The present study shows that for a 3-month
period, going keto is fine for recreationally trained crossfitters seeking to decrease body fat without significant
performance decreases (keep in mind that these were not elite
athletes). However, the effects of keto dieting on highly
trained endurance competitors has thus far been equivocal,
with a mix of positive and negative results – not necessarily
worth rolling the dice when the stakes are high.
References
1.
2.
Zinn C, Wood M, Williden M, Chatterton S, Maunder E.
Ketogenic diet benefits body composition and well-being
but not performance in a pilot case study of New Zealand
endurance athletes. J Int Soc Sports Nutr. 2017 Jul 12;14:22.
[PubMed]
McSwiney FT, Wardrop B, Hyde PN, Lafountain RA,
Volek JS, Doyle L Keto-adaptation enhances exercise
performance and body composition responses to training in
endurance athletes. Metabolism. 2017 Dec 5. pii: S00260495(17)30328-1. [PubMed]
Wilson JM, Lowery RP, Roberts MD, Sharp MH, Joy JM,
Shields KA, Partl J, Volek JS, D'Agostino D. The effects of
ketogenic dieting on body composition, strength, power, and
hormonal profiles in resistance training males. J Strength
Cond
Res.
2017
Apr
7.
doi:
10.1519/JSC.0000000000001935. [PubMed]
Aragon AA, Schoenfeld BJ, Wildman R, Kleiner S,
VanDusseldorp T, Taylor L, Earnest CP, Arciero PJ,
Wilborn C, Kalman DS, Stout JR, Willoughby DS,
Campbell B, Arent SM, Bannock L, Smith-Ryan AE,
Antonio J. International society of sports nutrition position
stand: diets and body composition. J Int Soc Sports Nutr.
2017 Jun 14;14:16. [PubMed]
Paoli A, Grimaldi K, D'Agostino D, Cenci L, Moro T,
Bianco A, Palma A. Ketogenic diet does not affect strength
performance in elite artistic gymnasts. J Int Soc Sports Nutr.
2012 Jul 26;9(1):34. [PubMed]
Heatherly AJ, Killen LG, Smith AF, Waldman HS,
Hollingsworth A, Seltmann CL, O‘Neal EK. Effects of ad
libitum low carbohydrate high-fat dieting in middle-age
male runners. Med Sci Sports Exerc. 2017 Nov 6. doi:
10.1249/MSS.0000000000001477 [Epub ahead of print]
[PubMed]
Alonso-Alonso M, Woods SC2, Pelchat M, Grigson PS2,
Stice E, Farooqi S, Khoo CS, Mattes RD2, Beauchamp GK.
Food reward system: current perspectives and future
research needs. Nutr Rev. 2015 May;73(5):296-307.
[PubMed]
One of the most interesting aspects of this study was the
reported decrease in protein intake from baseline in the KD
group (remember, the control group was not required to
report intake); 114 vs 89 g from baseline to the 12-week
point. Again, this figure is based on only 4 out of the 7
subjects in the KD group who provided dietary intake reports
at the final 12-week data collection point. Thus, it may or
may not be an accurate representation of the mean intake.
This is in contrast to Paoli et al,5 whose subjects‘ KD protein
intake was 200.8 g versus their habitual intake of 83.5 g.
3.
Another interesting result was that, despite an apparent
decrease in protein intake, total energy intake in the KD
group decreased by 551 kcal from baseline. This
‗spontaneous‘ decrease in energy intake as a result of going
on a ketogenic diet has been seen repeatedly in the literature.5
The most dramatic case of this that I‘m aware of is a recent
study by Heatherly et al,5 whose subjects had a rather massive
934 kcal decrease on a ketogenic diet without purposely
restricting calories. The mechanistic basis of this
phenomenon is not definitively understood. It could be either
a function of the elevation of circulating ketones themselves,
or it could be the increase in protein, or both.
5.
Alan Aragon’s Research Review – January 2018
[Back to Contents]
4.
6.
7.
Page 11
Nutritional strategies of high level natural
bodybuilders during competition preparation.
Chappel AJ, et al. Journal of the International Society of
Sports Nutrition (2018) 15:4 DOI 10.1186/s12970-018-0209z [JISSN]
BACKGROUND: Competitive bodybuilders employ a
combination of resistance training, cardiovascular exercise,
calorie reduction, supplementation regimes and peaking
strategies in order to lose fat mass and maintain fat free mass.
Although recommendations exist for contest preparation,
applied research is limited and data on the contest preparation
regimes of bodybuilders are restricted to case studies or small
cohorts. Moreover, the influence of different nutritional
strategies on competitive outcome is unknown METHODS:
Fifty-one competitors (35 male and 16 female) volunteered to
take part in this project. The British Natural Bodybuilding
Federation (BNBF) runs an annual national competition for
high level bodybuilders; competitors must qualify by winning
at a qualifying events or may be invited at the judge‘s
discretion. Competitors are subject to stringent drug testing
and have to undergo a polygraph test. Study of this cohort
provides an opportunity to examine the dietary practices of
high level natural bodybuilders. We report the results of a
cross-sectional study of bodybuilders competing at the BNBF
finals. Volunteers completed a 34-item questionnaire
assessing diet at three time points. At each time point
participants recorded food intake over a 24-h period in grams
and/or portions. Competitors were categorised according to
contest placing. A ―placed‖ competitor finished in the top 5,
and a ―Non-placed‖ (DNP) competitor finished outside the
top 5. Nutrient analysis was performed using Nutritics
software. Repeated measures ANOVA and effect sizes
(Cohen‘s d) were used to test if nutrient intake changed over
time and if placing was associated with intake. RESULTS:
Mean preparation time for a competitor was 22 ± 9 weeks.
Nutrient intake of bodybuilders reflected a high-protein, highcarbohydrate, low-fat diet. Total carbohydrate, protein and fat
intakes decreased over time in both male and female cohorts
(P < 0.05). Placed male competitors had a greater
carbohydrate intake at the start of contest preparation (5.1 vs
3.7 g/kg BW) than DNP competitors (d = 1.02, 95% CI [0.22,
1.80]). CONCLUSIONS: Greater carbohydrate intake in the
placed competitors could theoretically have contributed
towards greater maintenance of muscle mass during
competition preparation compared to DNP competitors.
These findings require corroboration, but will likely be of
interest to bodybuilders and coaches. SPONSORSHIP: No
funding was received for this study.
intakes of drug-free bodybuilding competitors during contest
preparation while stratifying subjects according to having
placed within the top-5, and those did not place within the
top-5 (DNP). This was an important parameter to assess since
it provides hints toward the relative effectiveness of the
dietary strategies employed. The cohort studied here were
competing ‗finals‘ type of contest where winners of regional
contests were the overall winner earns professional status. As
such, this sample is reliably representative of high-level
competitive natural bodybuilders.
It was pretty cool seeing the paper I did with Eric Helms and
Peter Fitschen referenced throughout this manuscript.2
Furthermore, our work was put into context as such:
“The strategies employed by the most successful natural
bodybuilders can be compared to recommendations [11],
which include protein intake of between 2.3 and 3.1 g/kg of
LBM, fat intake of 15 to 30% of total calories, with the
remaining calories from carbohydrate and a weekly weight
loss of 0.5 to 1% of bodyweight (BW) [11]. Here we report
the results of a recent cross-sectional study investigating the
nutritional strategies of natural bodybuilding competitors at
the BNBF finals.”
The above excerpt accurately relays the recommendations in
our paper, and I was eager to see how the results of the study
lined up.
Interesting odds & ends
35 men and 16 women volunteered to do the survey-based
study, one male subject was excluded from the study due to
failing a polygraph test, and ultimately, 32 men and 15
women were included in the analysis. The majority of the
competitors used a coach for contest prep. Interestingly, there
was a lack of difference in the use of a coach (versus not
using a coach) in those who placed and those who did not.
100% of the women who placed used a coach, and 78% of the
women who did not place used a coach. 60 & 59.1% of men
who placed and did not place used a coach, respectively.
Looking at Table 1, I also found it interesting that although
this lacked statistical significance, men who placed had a
higher mean age than those who did not place (36.1 vs 31.8
yrs), while this was the opposite for women who placed
versus those who did not (33.7 vs 34.7 yrs).
As an observational study, cause-and-effect cannot be
established, but the findings are useful and thoughtprovoking. This was the first study to examine the dietary
Another interesting finding was that among the 15
competitors who were able to provide body composition data
(5M, 10F), fat-free mass index (FFMI) exceeded 25 in 2 men
who placed. The relevance of this finding is that a FFMI is
generally known (but not necessarily accepted) as the ―natty
Alan Aragon’s Research Review – January 2018
[Back to Contents]
This is an observational study, so…
Page 12
 The rate of weight loss in males who placed was 0.46%
per week. This is really close to the lower end of our
recommended weekly weight loss recommendations2 as
well as a recent case study of a female physique
competitor in contest prep.3 Slower rates of weight loss
(0.7 vs 1.4%/wk) have also been seen to better preserve
lean mass in an assortment of elite competitive athletes.4
limit‖ beyond which the likelihood of being drug-free drops
precipitously. For an in-depth discussion of this topic, refer
to Eric Helms‘ guest article in the August 2014 issue of
AARR, which is accessible here.
Dietary findings
In Table 2, the mean macronutrient intakes at the start and
end of contest preparation (22 weeks on average) in those
who placed and did not place as follows:
Here are the notable tidbits:
 Protein intake was higher in men who placed. Intake at
the start & end of prep was 3.0 & 3.3 g/kg respectively.
In men who didn‘t place, protein intake at the start and
end of prep was 2.7 g/kg at both the start and end of
prep. This difference was not seen among women.
 Carbohydrate intake was higher in men who placed.
Intake at the start & end of prep was 5.1 & 4.6 g/kg
respectively. In men who didn‘t place, intake at the start
and end of prep was 3.7 & 3.6 g/kg at the start and end
of prep. This difference was not seen among women,
although it‘s interesting that in terms of absolute
numbers, the slight opposite was seen.
 Differences in fat intake across groups and time points
were less marked than differences in protein and
carbohydrate. The latter differences were reflected in the
differences in total caloric intake (more total kcal was
consumed by men who placed).
 In Table 3 (here), absolute gram amounts of the
macronutrients are listed. Total carbohydrate, fat and
energy intakes significantly declined over time in both
men and women, while there was a non-significant
decrease in protein intake in men.
 The macronutrient recommendations in my paper with
Helms & Fitschen2 encompassed the practices of the
competitors in this study, with the exception of our
protein recommendations (2.3-3.1 g/kg of lean body
mass) being exceeded, most markedly by men who
placed (consuming 3.0-3.3 g kg of total body mass).
Alan Aragon’s Research Review – January 2018
Supplement use
Here is the full table ranking the supplements used by the
competitors. The top-5
supplements used collectively (starting from #1)
were
protein powder,
multivitamin, BCAA (),
creatine, and fat burners.
Interestingly, pre-workout
supplements just missed
the top-5. Use of the top4 among these subjects
is in line with previous
research on bodybuilders.5
The authors of the present
study noted that several
competitors exceeded 400 mg supplemental caffeine per day,
which is the limit of safety put forth by the European Food
Safety Agency. In my observations, caffeine use (and abuse)
is rampant among not just physique athletes, but athletes in
general – both competitive and recreational.
Concluding thoughts
The authors acknowledge that misreporting (under-reporting
carbohydrate & over-reporting protein) is a persistent
confounder. Even with a meticulous population such as
competitive bodybuilders, the accuracy of infrequent recall
data is inherently challenged. Nevertheless, the findings of
this study represent a thorough examination of the dietary
habits of successfully competitive drug-free bodybuilders.
References
1.
2.
3.
4.
5.
Henselmans M, Schoenfeld BJ. The effect of inter-set rest intervals
on resistance exercise-induced muscle hypertrophy. Sports Med.
2014 Dec;44(12):1635-43. [PubMed]
Helms ER, Aragon AA, Fitschen PJ. Evidence-based
recommendations for natural bodybuilding contest preparation:
nutrition and supplementation. JISSN. 2014;11:20. [PubMed]
Rohrig BJ, Pettitt RW, Pettitt CD, Kanzenbach TL.
Psychophysiological tracking of a female physique competitor
through competition preparation. Int J Exerc Sci. 2017 Mar
1;10(2):301-311. [PubMed]
Garthe I, Raastad T, Refsnes PE, Koivisto A, Sundgot-Borgen J.
Effect of two different weight-loss rates on body composition and
strength and power-related performance in elite athletes. Int J Sport
Nutr Exerc Metab. 2011 Apr;21(2):97-104. [PubMed]
Hackett DA, Johnson NA, Chow CM. Training practices and
ergogenic aids used by male bodybuilders. J Strength Cond Res.
2013;27:1609–17. [PubMed]
[Back to Contents]
Page 13
Study limitations
Induced and controlled dietary ketosis as a
regulator of obesity and metabolic syndrome
pathologies.
Gibas MK, Gibas KJ. Diabetes Metab Syndr. 2017 Nov;11
Suppl 1:S385-S390. [PubMed]
BACKGROUND: A worsening epidemic of diabetes and its
precursor, metabolic syndrome (MetS) is engulfing America.
A healthy individual, with proper glucose regulation has an
ability to switch between burning fat and carbohydrates. It
has been suggested that signaling errors within this
homeostatic system, characterized by impaired switching of
substrate oxidation from glucose to fat in response to insulin,
can contribute to the etiology of metabolic syndrome and
occurs before the development of type II diabetes. Glucose
regulation with restored insulin sensitivity facilitated through
clinically regulated, benign dietary ketosis (BDK), may
significantly reduce, regulate and reverse the adverse
pathologies common to MetS and obesity. PURPOSE: The
study assessed if prolonged maintenance of induced and
controlled physiological, dietary ketosis, would reverse
pathological processes induced by MetS including a reduction
in fasting triglycerides, BMI (body mass index) and body fat
mass (BFM), weight, a significant decrease and/or
normalization of hemoglobin A1c (HgA1c) and an increase in
resting metabolic rate (RMR) and blood ketones. DESIGN:
A group of 30 adults, previously diagnosed with MetS by
their primary care physician, were randomly prescribed to
one of three groups: a sustained ketogenic diet with no
exercise, standard American diet (SAD) with no exercise or
SAD with 3-5 days per week of exercise (30 min.).
RESULTS: The results demonstrated that the change over
time from week 0 to week 10 was significant (p=0.001) in the
ketogenic group for weight, body fat percentage, BMI,
HgA1c and ketones. CONCLUSIONS: All variables for the
ketogenic group out-performed those of the exercise and nonexercise groups, with five of the seven demonstrating
statistical significance. SPONSORSHIP: This research
received no specific grant from any funding agency in the
public, commercial, or not-for-profit sectors.
Study strengths
A strength of this study was a 3rd group aside from the keto
and control, which involved habitual diet plus exercise. In
addition to the usual parameters, blood ketone levels & body
fat were assessed at weeks 0, 3, 6, & 10. Note that there are
issues with the chosen method of body composition
assessment, as well as the exercise protocol, which I‘ll get to.
Subjects met in small groups modeled after Clevelend
Clinic‘s Share Medical Appointment (SMA) format, which
presumably could have contributed to program
troubleshooting and adherence.
Alan Aragon’s Research Review – January 2018
There were a small number of subjects (10 per treatment –
this is assumed since it was not explicitly stated in the
manuscript, nor were any drop-outs reported). The reporting
of important details was missing in this study, particularly the
specifics of dietary intake. Energy and macronutritional
intake were not specified for either the ketogenic or control
groups. What was the nature of the subjects‘ habitual diet
prior to undergoing the ketogenic diet? Who knows, but
given that the subjects were diagnosed with the metabolic
syndrome, there‘s a good chance that their dietary habits were
crappy. But again, there‘s no way to know the nature of the
total caloric decrease or the shift in macronutrition
distribution from baseline/habitual diet to the ketogenic diet
since none of this was reported in the manuscript.
Adverse/side-effects? Nothing was reported. Furthermore, no
details are reported about the group assigned 3-5 days per
week of 30 minutes of exercise. What was the nature of the
30-minute bouts in terms of type and intensity? How well did
they comply (how was adherence tracked)? The authors did
not report this either.
Body fat was assessed via hand-held bioelectrical impedance
analysis (BIA). Although hand-held BIA is convenient and
easy to use, it has repeatedly shown to have poor consilience
with criterion (benchmark) methods. Esco et al4 found handto-hand BIA to significantly underestimate fat mass and
overestimate lean mass in college-age female athletes when
compared with the criterion method, duel X-ray
absorptiometry (DXA). Varady et al5 found that hand-held
BIA used on overweight women significantly underestimated
fat mass and overestimated lean mass when compared to the
criterion method, magnetic resonance imaging (MRI).
It should be noted that the body composition assessment
method used in the present study was single-frequency BIA,
where the electrical current can pass through extracellular
water (ECW), but cannot penetrate cell membranes. On the
other hand, the more recently developed multi-frequency BIA
(MF-BIA) divides the body into segments, and independently
measures them at a range of frequencies, thus allowing the
measurement of ECW, intracellular water (ICW), and total
body water (TBW), which are then used to estimate body
composition. MF-BIA has been shown to be more accurate
than single-frequency BIA, having closer agreement with
DXA.5,6
A little rant about the melodramatic tone of the paper
I rarely encounter this in the peer reviewed literature (at least
to this degree), but the tone of this manuscript is strongly
indicative of bias. The manuscript oozes absolute fanfare for
carbohydrate restriction. The unbridled fawning over an anticarbohydrate approach is palpable and cringe-worthy. I read
it wondering how certain elements passed peer review. For
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Page 14
example, when discussing Feinman et al‘s review to tout the
supremacy of aggressive carbohydrate restriction for
diabetes,1 they went as far as appealing to the academic
credentials of the paper: “Twelve points of clinical evidence
were derived from the 26 researchers who are a combination
of MD’s and/or PhD’s,”
Furthermore, in the discussion section of their paper, two
studies by Hall et al2,3 are falsely cited in attempt to bolster
their case. The first one is a 2016 study2 where they reported
Hall et al‘s finding of “increased EE, increased SEE and
decreased RQ (Hall et al., 2016), which are correlates of
glucose regulation with restored insulin sensitivity.” What
they neglected to report was the most relevant finding of this
study, which was that after switching to ketogenic diet (after
4 weeks on a conventional diet), body fat loss slowed, and
this was accompanied by an increased loss of nitrogen,
indicating a utilization/loss of bodily protein. The second by
Hall et al they cited was a 2015 study3 where a 30% deficit
(822 kcal) was imposed via either dietary fat or carbohydrate
removal from the maintenance diet. The spotlight was put on
the greater fat oxidation and lesser carbohydrate oxidation in
the carb-restricted treatment. No mention was made of the
primary finding, which was that the fat-restricted diet led to a
significantly lower net fat balance throughout the study,
leading to significantly greater body fat loss than the carbrestricted diet.
Comment/application
Oddly, it appears that bodyweight is reported in pounds
instead of kilograms (judging by the high values in the range;
120-320 who-knows-whats), so who really knows what units
of measurement were used to express the rest of the
endpoints. The ketogenic diet showed statistically significant
changes in all of those parameters except for two – TG and
RMR – but the authors note that the changes in these markers
were clinically meaningful despite not reaching statistical
significance. The significant improvements seen in the
ketogenic treatment are not surprising. As I discussed in my
review of Kephart et al (earlier in this issue),7 a spontaneous
decrease in energy intake as a result of going on a ketogenic
diet has been seen repeatedly in the literature.
The big question & challenge to ketogenic diet proponents is
whether it‘s a sustainable long-term solution. Thus far, the
literature collectively shows that adherence to a ketogenic
diet (with a max of 50 g carbohydrate per day) diet
diminishes over time. Non-ketogenic carbohydrate levels;
roughly double the originally targeted intake or greater are
consumed by the end of the most studies.8
An interesting finding was the lack of significant effect of
exercise on any of the parameters. But to reiterate, no details
about the nature of the exercise were reported. A target of 30
minutes 3-5 days per week could have been as insignificant
as 3 moonlit walks, which could optimistically amount to
about 300-500 kcal per week (easily negated by an extra few
bites of food or an energy-dense snack in a single sitting). It‘s
important to note that despite popular claims of exercise
being useless for weight loss, a meta-analysis by Wu et al9
showed that that diet plus exercise caused significantly
greater weight loss than diet alone. Importantly, this weight
loss was greater in trials lasting a year or longer, indicating
that exercise has a beneficial long-term effect on weight loss
& weight loss maintenance.
References
As shown above as individual data points as well as the mean
value as the thicker line (larger image here), the ketogenic
diet treatment in red (compared to habitual diet and habitual
diet plus exercise in blue and green, respectively) was the
superior performer. Seven parameters were assessed:
bodyweight, body fat, body mass index (BMI), glycated
hemoglobin (HbA1c, a marker of glycemic control, in this
study abbreviated as A1c), triglycerides (TG), resting
metabolic rate (RMR), and ketones. Unfortunately, the units
of measurement are not specified anywhere in the manuscript.
1. Feinman RD, et al. Dietary carbohydrate restriction as
the first approach in diabetes management: critical
review and evidence base. Nutrition. 2015 Jan;31(1):113. [PubMed]
2. Hall KD, et al. Energy expenditure and body composition
changes after an isocaloric ketogenic diet in overweight
and obese men. Am J Clin Nutr. Am J Clin Nutr. 2016
Aug;104(2):324-33. [PubMed]
3. Hall KD, et al. Calorie for Calorie, Dietary Fat
Restriction Results in More Body Fat Loss than
Carbohydrate Restriction in People with Obesity. Cell
Metab. 2015 Sep 1;22(3):427-36. [PubMed]
4. Esco MR, Olson MS, Williford HN, Lizana SN, Russell
AR. The accuracy of hand-to-hand bioelectrical
Alan Aragon’s Research Review – January 2018
[Back to Contents]
Page 15
5.
6.
7.
8.
9.
impedance analysis in predicting body composition in
college-age female athletes. J Strength Cond Res. 2011
Apr;25(4):1040-5. [PubMed]
Gába A, Kapuš O, Cuberek R, Botek M. Comparison of
multi- and single-frequency bioelectrical impedance
analysis with dual-energy X-ray absorptiometry for
assessment of body composition in post-menopausal
women: effects of body mass index and accelerometerdetermined physical activity. J Hum Nutr Diet. 2015
Aug;28(4):390-400. [PubMed]
Thomson R, Brinkworth GD, Buckley JD, Noakes M,
Clifton PM. Good agreement between bioelectrical
impedance and dual-energy X-ray absorptiometry for
estimating changes in body composition during weight
loss in overweight young women. Clin Nutr. 2007
Dec;26(6):771-7. Epub 2007 Oct 23. [PubMed]
Kephart WC, et al. The three-month effects of a
ketogenic diet on body composition, blood parameters,
and performance metrics in crossfit trainees: a pilot
study. Sports 2018, 6(1), 1; doi:10.3390/sports6010001
[MDPI - Sports]
Huntriss R, Campbell M, Bedwell C. The interpretation
and effect of a low-carbohydrate diet in the management
of type 2 diabetes: a systematic review and meta-analysis
of randomised controlled trials. Eur J Clin Nutr. 2017
Dec 21. doi: 10.1038/s41430-017-0019-4. [PubMed]
Wu T, Gao X, Chen M, van Dam RM. Long-term
effectiveness of diet-plus-exercise interventions vs. dietonly interventions for weight loss: a meta-analysis. Obes
Rev. 2009 May;10(3):313-23. [PubMed]
Alan Aragon’s Research Review – January 2018
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Page 16
Acknowledging the AARR contributors
10 years and counting: inception and legacy of AARR
– and a big thanks to the contributors.
By Alan Aragon
_________________________________________________
The alpha and the omega
In the beginning, AARR was an idea born from me spending
roughly 3-6 hours a day answering questions and engaging in
debates and discussions on the bodybuilding.com forums for
approximately 5 years (2003-2008). Near the end of this
period, in 2007, I gained the impetus to create a medium
where I could better answer these questions and organize my
ideas. There was no subscription-based research review that
focused on nutrition and fitness, so I didn‘t have a solid sense
of security about the idea.
I chewed on the idea of doing AARR for a whole year before
I actually launched it. This was a year of me worrying about
whether or not it would succeed or fail, so I let fear keep me
from going forward with releasing it. I eventually gained the
courage to launch AARR at the start of 2008, and it has been
going strong ever since then. In retrospect, it‘s pretty funny
that I was afraid that the idea might flop, since at least 7 other
research review subscription services were launched after
AARR. At least 5 of these are still active, and all of them
were directly inspired by AARR. Most of them cover
research from the same allied fields in nutrition & exercise.
All of this has profound implications in terms of AARR‘s
impact and reach. AARR was instrumental in making
research reviews a ―thing‖ – it started the domino effect of
the brightest people in the allied fields starting their own
research reviews. Did AARR make fitness-related research
more appealing to practitioners and enthusiasts? Did AARR
make science cool? I would like to think that it at least played
a role in that, especially within the fitness industry. It‘s
extremely gratifying that the impact has been positive, and it
continues to grow through not just my work, but the work of
others who have been inspired and influenced by AARR.
While the other research reviews can be viewed as direct
competitors, they can also be viewed as fraternal entities
joined with me in the challenge of raising the educational bar
of the industry. Collectively, we can empower practitioners
and enthusiasts to achieve better results and better lives.
Here‘s to the next 10 years of AARR. But before I forge
ahead, I‘d like to thank the real heroes of of the publication.
Alan Aragon’s Research Review – January 2018
The following list is comprised of all of the illustrious AARR
guest authors since the beginning in 2008. The list is in
alphabetical order of the author‘s last name, and the
accompanying number is the number of times the person
contributed (interviews, roundtables, and articles). Where
possible, the name is linked to the person‘s website. A scant
few of you are on ―stealth‖ mode from the rest of the world
despite having written for my journal, and I can respect that.
If your your name has no link, or a link that‘s not current,
please contact me (support@alanaragon.com) with your
updated connection to the planet, and I‘ll edit this article
accordingly. Without further ado, here are the 109 heroes of
AARR. Thank you all.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
Andrew Abbate (3)
Joseph Agu (1)
Ryan Andrew (1)
Jay Ashman (1)
Anoop Balachandran (1)
Chris Bell (1)
Miguel Blacutt (2)
Adam Bornstein (1)
Ian Capulet (2)
Paul Carter (1)
Andrew Chappell (1)
Chi L. Chiu (2)
James Clear (1)
Sarah Conomacos (2)
Bret Contreras (7)
Christine Crumbley (1)
JC Deen (2)
Antony Dexmier (1)
Brad Dieter (2)
Aman Duggal (1)
Steinar Ekren (3)
Anya Ellerbroek (1)
Sivan Fagan (1)
Dell Farrell (1)
Georgie Fear (1)
James Fell (3)
Peter Fitschen (2)
Sergio Fontinhas (4)
Kurtis Frank (2)
Dan Garner (1)
Evan Godbee (2)
Chas Gonello (1)
Jon Goodman (1)
Molly Gregas (1)
Louie Guarino (1)
Jamie Hale (10)
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Page 17
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
James Heathers (4)
Eric Helms (10)
Menno Henselmans (6)
Joshua Hockett (2)
Robert Hoenselaar (1)
Anthony Howard-Crow (4)
Mike Howard (2)
Juma Iraki (1)
Mike Israetel (2)
Brian Jones (2)
Alexander Ketterer (1)
Kevin Klatt (2)
Dylan Klein (2)
Chelsea Knox (1)
Evelyn Kocur (3)
Justin Kompf (1)
Bryan Krahn (5)
James Krieger (6)
Kedric Kwan (3)
Adam Lawson (1)
Roger Lawson II (1)
Sohee Lee (2)
Armi Legge (10)
Sarah Lewis (4)
Michael Limon (1)
Martin MacDonald (1)
Chris & Eric Martinez (2)
Jason Maxwell (1)
Lyle McDonald (8)
John Meadows (2)
Greg Mikolap (1)
Joel Minden (2)
Cameron Mochrie (2)
Kasey Nadolsky (1)
Spencer Nadolsky (4)
Susy Natal (1)
Mike T. Nelson (1)
Pauline Nordin (1)
Layne Norton (3)
Greg Nuckols (1)
Sol Orwell (1)
Karen Pendergrass (1)
Matt Perryman (3)
Alex Ritson (1)
Matthew Rizzo (1)
Brandon Roberts (5)
Chester Rockwell (1)
Amber Evengeline Rogers (1)
Tim Rowland (1)
Jacob Schepis (1)
Brad Schoenfeld (17)
Alan Aragon’s Research Review – January 2018
88. Lou Schuler (2)
89. Sumi Singh (1)
90. Dean Somerset (1)
91. Brandon Stevens (1)
92. Jordan Syatt (1)
93. Dick Talens (1)
94. Russell Taylor (2)
95. Jason Tremblay (1)
96. Jorn Trommelen (1)
97. Nick Tumminello (2)
98. Adam Tzur (1)
99. Patrick Umphrey (2)
100.
Tom Vachet (1)
101.
Sten Van Aken (2)
102.
Fredrik Tonstad Varvik (1)
103.
Tom Venuto (2)
104.
Jennifer Willett (1)
105.
David A. Wiss (1)
106.
Matt Woodward (1)
107.
Ryan Zielonka (1)
108.
Anastasia Zinchenko (1)
109.
Mike Zourdos (1)
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Page 18
Blood lipids, diabetes, & obesity: clinical queries
recklessly thrown at the Doc Who Lifts.
Interview with Spencer Nadolsky
_________________________________________________
There's a lot of talk amongst the low-carb/keto community
about blood lipids - what's good, what's bad, what's
illuminatti propaganda, etc. I'd like to discuss that. Let's begin
with low-density lipoprotein (LDL) levels in the blood. LDL has
traditionally be regarded as the "bad" cholesterol, while highdensity lipoprotein (HDL) has been called "good" cholesterol.
Now, it seems that the LDL story has been complicated by
claims that LDL particle size is what matters, since low-carb
lore alleges that an increase in the "large, fluffy" LDL is not a
threat to cardiovascular health. Another claim is along the
lines of LDL particle number being what matters, regardless of
type. What's your stance on this, and do you have any advice
on what too look for in terms of lab results regarding HDL &
LDL (in absolute amounts or ratio)?
Hi Alan, the first thing we should do is get some
nomenclature down.
When we discuss LDL-C, we are talking about the
cholesterol being carried by low density lipoproteins. When
we discuss HDL-C, we are discussing the cholesterol being
carried by high density lipoproteins.
Cholesterol is carried by lipoproteins in the blood since it is
not water soluble. Triglycerides are also carried this way.
So for the smart AARR readers, just understanding this will
give you the basics and understanding that most of the
population doesn't have.
Cholesterol is cholesterol. It is the lipoprotein carrying the
cholesterol that makes the difference. Further, there are
apolipoproteins that are bound that make up the lipoproteins.
HDL particles have apolipoprotein A and the LDL particles
and apolipoprotein B. Any particles that contain
apolipoprotein B (also called apoB) are called apoB
containing lipoproteins. All of these particles can cause
atherosclerosis.
So when someone says "bad" cholesterol when referring to
LDL-Cholesterol, it's actually a misnomer. It is only "bad"
due to being carried by a lipoprotein that can penetrate the
artery lining (endothelium), become retained, and start the
atherosclerosis process.
Alan Aragon’s Research Review – January 2018
The story with HDL-Cholesterol being "good" is similar. The
cholesterol contained in an HDL particle is the same as the
LDL particle. It's just that the HDL particle does not cause
atherosclerosis.
Looking at simple pathophysiology would explain the story
behind LDL particle size. Other much larger particles like
chylomicron remnants up to 70 nm in diameter have been
found to still penetrate the endothelium and be retained and
cause atherosclerosis. The biggest fluffiest LDL particles are
less than 40 nm. So why would particles that are about
DOUBLE the size of the largest LDL particles be able to
penetrate the endothelium and not the smaller LDL particles?
That doesn't make too much sense.
When controlling for size, the risk of cardiac events comes
down to the particle number. It's possible that smaller and
denser LDL particles are more readily retained and oxidized,
but it's also true that those who have smaller LDL particles
have insulin resistance which can accelerate atherosclerosis
too.
On a lipid panel that the doctor orders, you will see a total
cholesterol, an HDL cholesterol, a triglyceride level, and
usually a calculated LDL level. This standard test doesn't
actually test the particle number or particle size. It's testing
the cholesterol on each lipoprotein. The cholesterol amount
usually correlates decently with the particle number but it can
be discordant depending on the size of the particles. For
instance, someone can have a lot of cholesterol on each
lipoprotein (large but relatively fewer particles) and another
person can have less cholesterol per particle but more
particles with both of these people having the same
cholesterol in total. If you did a particle test or checked their
apoB levels (another more advanced test), you would see that
the one person actually had more particles and is at a higher
risk of atherosclerosis even though they technically had the
same cholesterol levels.
So when you look at the lipid panel your doctor ordered, you
can actually calculate what is called their "non-HDLcholesterol". This is simply anything that is not HDL.
Anything that isn't HDL is potentially atherogenic. You just
take your total cholesterol and subtract the HDL cholesterol
and you have your number. This cholesterol level has been
found to be better than at predicting risk than just an LDL
cholesterol level. This is of course if you can't check a
particle count or apoB level.
Thanks for going into detail with that. I must really love that
question because I asked you something similar when I
interviewed you in the July 2015 issue (I encourage the reader
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Page 19
to review that issue, Spencer discusses different aspects of this
question). Let's shift gears for a minute and talk about beetus.
I recently became aware of a less-common diagnosis of
diabetes: type 3c. Can you give us the run-down on this - i.e.,
what are the most important aspects of it that academics,
practitioners, and clinicians (basically the AARR readership,
which includes enthusiasts) need to know about type 3c, as
well as aspects that might have flown under the radar of
articles in the lay press?
Nowadays when most people think of diabetes (diabetes
mellitus), they think of type 2 (excess weight, insulin
resistance, etc.) since it accounts for 90-95% of cases. Type 1
diabetes mellitus (autoimmune disease, lack of insulin due to
destruction of pancreas) makes up most of the rest of the
cases. There are other genetic types out there that don't fit
into those categories too. Then there is type 3c, which as you
mentioned has been mentioned due to a relatively new report
out saying it is often misdiagnosed.
Type 3c, also known as pancreatogenic, diabetes occurs due
to inflammation of the pancreas. In medicine this
inflammation in the pancreas is known as pancreatitis to
which there are many causes like alcohol, gallstones, really
high triglycerides, etc. Sometimes those with multiple bouts
of pancreatitis or chronic pancreatitis will have enough
destruction of their pancreas to where they are not producing
enough insulin. Most doctors will assume when they see
these patients that it is type 2 diabetes since it occurs usually
later in life (unless they have cystic fibrosis) and the insulin
requirements may be low (at first). If the doctor starts
thinking about autoimmune type 1 diabetes, the antibodies
will be negative.
When most people think of the pancreas, they think of
insulin. However the pancreas makes digestive enzymes too!
This is the exocrine role of the pancreas. Those with chronic
pancreatitis may have develop some pancreatic insufficiency,
which is where you don't produce enough digestive enzymes
to help with food digestion. So a clue that someone may have
type 3c (pancreatogenic) diabetes is if they have had chronic
pancreatitis in the past and also have pancreatic insufficiency,
which can be tested for if not diagnosed yet.
So if you have someone who has had pancreatitis and doesn't
seen to fit the picture of type 2 diabetes, keep this in mind!
Thanks for the low-down on type 3c. Speaking of diabetes,
type 2 is the most prevalent worldwide, and has been a
growing problem. There is a mountain of literature on type 2
diabetes, but there's also a raging battle going on over how to
treat and manage the disease. I'd like to hear your take on
Alan Aragon’s Research Review – January 2018
how to pull diabetics (and prediabetics) back into normal
glycemic control. One camp - which includes the major public
health organizations - does not delineate a "diabetes diet" per
se.
It
largely
resembles
traditional.
mainstream
recommendations. An opposing camp - the low-carb/keto
proponents view carbohydrate restriction as a first line of
defense, seeing it as not only the most effective solution, but
also the most obvious and logical solution (to the point that
they are collectively furious at the establishment for being
either blind or in willful denial of this). I also see a third camp,
I'll call it the Roy Tayor camp, whose approach involves an
initial very-low-calorie formula diet intervention (~800 kcal for
3-5 months) with the goal of substantial weight reduction (~15
kg if possible), followed by a maintenance phase that
gradually reintroduces solid foods. The interesting thing to me
about Taylor's model is the remission of T2D occurring in a
large percentage of the subjects despite the maintenance
phase not being specifically focused on carbohydrate
restriction. I'd love to hear your take on what's the optimal
approach to take with pre-T2Ds and T2Ds.
I never understand why these camps can't just look at the data
objectively and use it to treat each patient as an individual.
For example, I have had some patients come off insulin and
other diabetes medicines gradually after slowly implementing
a diet and exercise program. I have also had some with great
success with a low carb high fat diet. I have also had amazing
results with the really aggressive very low calorie diet (Roy
Taylor style) getting patients off 100 units of insulin within a
month.
If the camps would take a more patient-centered approach,
they would understand it comes down to patient preferences
in conjunction with working with a doctor to guide them with
evidence-based practice.
Let's say a patient comes in on high doses of insulin and all
you have to offer is a ketogenic diet. I do agree this is an
option, but what if the patient simply hates that style of eating
(most do by the way)? You just keep them on insulin and
send them away with no other options? Maybe a more
moderate approach with them would have been enough to get
the ball rolling. The more aggressive approaches do work
phenomenally, but our patients aren't robots that we just
program to follow a certain diet.
Having said that, I am going to tell you my approach.
If a patient is willing, I go as aggressive as possible. I actually
use a very low calorie protein-sparing modified fast diet
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Page 20
compared to the lower protein version in Dr. Taylor's
protocol. This is because a bro will always be a bro and
protein shakes are life. It's nothing short of amazing what
happens with the patient's blood sugars and insulin
requirements. As mentioned I have been able to quickly take
people off high amounts of insulin. I also don't skimp on the
exercise like they did in the Dr. Taylor protocol.
This first option is extremely hard to follow though. It's not
for everyone. But as you mentioned and from the Direct
study, the patients may be able to back to eating more
carbohydrate than if they just followed a ketogenic diet from
the beginning. I think this is important when looking at the
pathogenesis of type 2 diabetes.
Keto proponents will say they "reverse" or "cure" type 2
diabetes with a ketogenic diet, but really what they are doing
is managing it in a different way. If you gave these patients a
glucose load, they would likely not do well with it. This is
why I reserve a ketogenic diet for patients who have had type
2 diabetes for 10 or more years and are on high amounts of
insulin. Their beta cell function of their pancreas may never
recover even with a very low calorie diet, so in these
instances a very low carb diet may do the trick. Again, if the
patient doesn't want to follow it, it won't matter.
These two approaches aren't usually needed for most patients
though. If I can help a patient get into an energy deficit while
also eating higher quality foods and adding a good exercise
plan, they do very well. Not all patients are on high amounts
of insulin and need an aggressive approach like the very low
calorie or ketogenic diet. This especially goes for those with
prediabetes. They just need some simple changes in their
lifestyle that most of the readers of AARR could help them
do.
I really like the idea of a Taylor-esque protocol whose VLCD
intervention phase is optimized with higher protein (and
exercise). It just makes a ton of sense all the way around.
Especially for patients who require aggressive treatment.
Speaking of clinical interventions, in the November 2008 issue
of AARR, I looked at tesofensine, since it seemed promising,
and at the time, appeared to be the most effective weight loss
drug. I'd like to know how you feel about treating obesity with
such therapies. Are anti-obesity drugs ever necessary beyond
proper diet & exercise -- in your personal observations with
patients? How do you see the landscape looking for antiobesity drugs in general?
Alan Aragon’s Research Review – January 2018
Tesofensine has yet to come to the market, but others have
with decent results.
As an obesity specialist physician, I believe these drugs do
fill a gap between behavioral therapy and surgery for weight
loss. The truth is, most people will fail a diet and exercise
program. I know the readers of AARR may be angry at
hearing that, but it's just a fact and clear in the data.
What do we do then? Just keep telling these patients they
need to try harder or keep doing the same things that have
failed in the past?
When you look at the pathophysiology in obesity, you will
find it's not a simple dysfunction. Individuals may have
excessive hunger when trying to lose weight compared to
others. Some may have more reward center dysfunction,
which leads to being drawn more towards those addictive-like
foods (e.g. cookies, cakes, etc.). Do we tell them they just
need to have more will power and eat more vegetables and
lean protein?
Sure, doing those things will help, but sometimes the patients
need more.
I have had patients who swear up and down that they are
eating 1200 calories, yet have an RMR of about 2000 calories
and absolutely no medical issue that would prevent them
from losing weight (e.g. Cushing's disease etc.). When I put
these individuals on an anti-obesity medicine, they often
times lose at least 10% of their body weight. The medicines
available only work on appetite and not peripherally like an
uncoupler, which would boost metabolism. So clearly these
patients were just eating much more than they knew or were
willing to admit and this came from appetite.
There are several medicines available for long-term obesity
management. Each work at various receptors in the brain to
increase satiety. While some believe you shouldn't need a
medicine for weight loss, the paradigm is shifting to thinking
about obesity as a chronic condition or disease just like
hypertension or type 2 diabetes. You may need a medicine in
those conditions for long-term so why not use medicines
long-term in obesity?
Of course there are responders and non-responders to each
medicine as well. For example one patient may not lose any
weight with one medication and then lose 30-40 pounds with
another. We shouldn't keep patients on these medicines
unless there is a real response, due to possible side effects
(should be true for any medicine).
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With this in mind, I don't want to belittle the behavioral
component of obesity management either. I have had patients
who had gastric bypass surgery (the most powerful tool we
have in obesity management) and are on 3 different
medicines for appetite, and they still say they can't help
themselves from buying candy bars at the store. Clearly the
physiology doesn't matter in these cases.
In order to keep people active, it is very similar to keeping
people on their nutrition. They really have to buy into the
lifestyle. Almost obsessed, but without that negative
connotation. See those initial changes of their body, strength,
and energy and the patients start to love it. That initial barrier
is tough though and getting them comfortable with a good
support system is important.
The medicines are simply a tool to help someone adhere to
their lifestyle plan just like surgery would be too.
________________________________________________________________________________________________________
Agreed that appetite is the issue, along with underestimation
(and of course under-reporting, willful or not) of intake. You
have a unique spot in the fitness space being a doctor who has
one foot in the clinic and another foot in the gym. Knowing
the value of exercise, what's your approach to getting
sedentary patients to become physically active (given that
they have the capacity to do so)? This is a big stumbling block
with a lot of folks, especially those who have no clue what to
do, or are intimidated by gyms. Maytbe a more important
question is, how to you get patients to become physically
active, and STAY physically active? We all are familiar with the
false-start exercise warrior.
Dr. Spencer Nadolsky is a board certified
family and obesity medicine physician. While
earning a BA in exercise science In
undergrad he wrestled heavyweight for the
UNC Tar Heels and was ranked as high as
3rd in the nation at one point while also
garnering Academic All-American status. He
is the author of the fat loss prescription and
now runs an online weight loss program
called the fat loss prescription program More
of Spencer’s stuff can be found at http://drspencer.com
Since exercise is probably the best all-around "drug" or
therapy available, I always ask my patients about how much
and what type they do. As you mentioned, most are sedentary
and the barrier to get started seems high for them.
I always recommend walking, especially after meals to start if
they can. Ideally my patient would all start lifting combined
with some aerobic training. What I found universally is that
most people just don't know what they are doing when it
comes to weights. Not a clue.
Not only that but the gym is a very intimidating place. I can
relate because when I started swimming (really looked like
drowning according to my wife), I was very self conscious at
the pool. Everyone looked like they knew what they were
doing and I was a bit lost. Despite looking great in my
speedo, I was by far the worst swimmer in there. The 80 year
old women were lapping me.
Anyway, since many of my patients were scared to go to the
gym and didn't know what they were doing, I just started
going with them and showing them. I would show them that
the weights weren't scary or too complicated and give them
the simplest of plans. I was even fortunate enough to help set
up a group exercise class at the hospital so that the patients
would be even more comfortable working out with others in
their same stage.
Alan Aragon’s Research Review – January 2018
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―Everyone has biases and everyone has various conflicts of
interest. My biggest conflict of interest: I am paid to work
with elite athletes to try and make them go faster in Olympic
events within the rules of sport, with primary emphasis on
middle to long distance Olympic events. Now if there was
evidence that all I needed to do was change and shift an
athlete‘s macronutrient intake to LCHF [low-carb, high-fat]
to turn them into world beaters do you not think I would
immediately do this? Am I an idiot? (Yes, opening up to
cheap shots here). Do I not follow, read, conduct, publish,
review and edit research? Do I not constantly have my ear to
the elite athlete/coach ground? Am I just completely out of
touch?
A keto intervention is a relatively inexpensive (as one already
needs to buy food) and easier intervention compared to
money spent on various other performance interventions in
technology, engineering, supplements, biomech, training
camps, altitude etc etc etc. In this instance I would take any
form of evidence for keto in elite athletes. Can someone
please show me a definitive study in elite athletes in Olympic
sports featuring sustained energy outputs >2min of duration
where keto works (both training and competition)? Can
someone please introduce me to a keto Olympic medalist in
Olympic sports featuring sustained energy outputs >2min of
duration? My athletes don‘t need to lose weight. My athletes
don‘t need to have better insulin sensitivity. My athletes need
to go faster. That is it. The evidence (literature, anecdotal or
not) is seriously lacking at this point for the elite cohort I
work with. If the evidence changes, I will be very happy to
change and integrate this intervention in my toolkit.‖
— Trent Stellingwerff via Twitter
If you have any questions, comments, suggestions, bones of
contention, cheers, jeers, guest articles you‘d like to submit
for consideration, send it over to support@alanaragon.com.
Alan Aragon’s Research Review – January 2018
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