12 The health benefits of dairy protein.

By Armi Legge

14 Bulletproof Coffee & concerning bloodwork:

questions for 2 doctors who actually lift.
Alan Aragon interviews Spencer & Kasey Nadolsky

Copyright July 1st, 2013 by Alan Aragon

Home: www.alanaragon.com/researchreview
Correspondence: [email protected]

Clearing up common misunderstandings that

plague the calorie debate, part 1.
By Alan Aragon

High Caloric intake at breakfast vs. dinner

differentially influences weight loss of overweight
and obese women.
Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity
(Silver Spring). 2013 Mar 20. doi: 10.1002/oby.20460.
[Epub ahead of print] [PubMed]

Effects of a low- or a high-carbohydrate diet on

performance, energy system contribution, and
metabolic
responses
during
supramaximal
exercise.
Lima-Silva AE, Pires FO, Bertuzzi R, Silva-Cavalcante
MD, Oliveira RSF, Kiss MA, Bishop D. Appl Phys Nutr
Metab. 38: 928934 (2013) dx.doi.org/10.1139/apnm-20120467. [APNM]

The effects of anatabine on non-invasive

indicators of muscle damage: a randomized,
double-blind, placebo-controlled, crossover study.
Jenkins ND, Housh TJ, Johnson GO, Traylor DA,
Bergstrom HC, Cochrane KC, Lewis RW Jr, Schmidt RJ,
Cramer JT. J Int Soc Sports Nutr. 2013 Jul 22;10(1):33.
[Epub ahead of print] [PubMed]

10 Blood type diets lack supporting evidence: a

systematic review.
Cusack L, De Buck E, Compernolle V, Vandekerckhove P.
Am J Clin Nutr. 2013 Jul;98(1):99-104. [PubMed]
Alan Aragons Research Review July 2013

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Page 1

Clearing up common misunderstandings that plague

the calorie debate, part 1.
By Alan Aragon
____________________________________________________
Introduction
Anyone involved with the health and fitness sphere has observed
a never-ending battle between the calories-in/calories-out
(CICO) camp and the calories dont matter (CDM) camp, which
might be more accurately called the calories dont matter,
hormones and other stuff do (CDMHOSD) camp. In its most
pure form, CICO is a relatively well-known acronym for the
philosophy that weight loss or gain is determined by a caloric
deficit or surplus, regardless of diet composition. The CICO
camps call to eat less, move more as a solution to obesity
sends the CDM camp into a frothy rage. They believe that this is
not only incorrect, but failed advice, as indicated by the nations
high prevalence of obesity.

However, even in peer-reviewed papers, the non-capitalized

term is common when referring to food energy in the general
sense.
With that detail out of the way, perhaps the more important
problem with discussing calories as units of energy is that the
manifestation of energy is rarely specified. In the context of food
and nutrition, there are distinct differences between the energy
liberated through combustion, and the energy thats
physiologically available.3 In other words, gross energy is what
the foodstuff contains before it enters the body, and
metabolizable energy is what the body is able to use for
physiological processes.
Oddly enough, a helpful model for understanding types of
energy has been used in cattle production, which relies upon the
tracking of energy in order to maintain health, growth, and
reproduction.4 Obviously, humans differ from ruminants in
certain aspects of digestion, among other things. However, the
general framework of food-derived energy use is surprisingly
similar. Heres a graphic of the various fates of energy as it
flows from the food source through the body of the animal:5

Let me state from the outset that there is a range of beliefs

spanning the continuum between the two extreme ends of CICO
and CDM. However, comparing these starkly different
philosophies is the best way to expose which aspects of each are
rooted in scientific evidence, and which are not. In the following
discussion, Ill attempt to clarify the misunderstandings
perpetuated by both sides.
Getting the definitions straight
At the heart of the disagreement is a neglect to adequately
establish operational definitions. Without doing so, its
impossible to have clear, productive communication, so chaos
inevitably continues. The first term that needs defining is the
calorie itself, particularly as it pertains to the CICO mantra that
a calorie is a calorie. Ill first go over the smaller, more
immaterial stuff, then move on to the meatier definitions that
hold the more profound implications.
A Calorie is the amount of heat required to raise the temperature
of 1 kilogram of water by 1C. The term Calorie is synonymous
with kilocalorie (abbreviated as kcal). Less commonly, its
referred to as a kilogram-calorie, or large calorie.1 When the
term is not capitalized, it technically represents one-thousandth
of the value of a kcal. In other words, its the amount of heat
required to raise the temperature of 1 gram of water by 1C. The
non-capitalized term is less commonly called a gram-calorie.

Starting from the top of the chart above, gross energy is the
starting point before ingestion; its the energy that the food
contains, as calculated by combustion in a bomb calorimeter.
Whats left after fecal loss is considered digestible energy. What
remains after energy losses through feces, urine, and gas is
metabolizable energy. Finally, net energy is whats available for
use (or storage) after losses through feces, urine, gas, and heat
increment.

Heres the amusing part. Neglecting to capitalize the word

calorie when discussing kilocalories is so commonplace, that the
non-capitalized term has replaced the capitalized term nearly
everywhere its used especially in the nutritional context.
Kcals and calories have become interchangeable in the press,
with the understanding that the term calorie is not actually
referring to its original definition as a gram-calorie. There are
some rare instances (usually in the academic literature) where
care is taken to capitalize the term. A recent example is the title
of Jakubowicz et als recent study reviewed in this issue.2

Regarding the heat increment, macronutrients vary in their

thermic effect, which ultimately influences the net yield of
energy available to the body. As reported by Jquier, the thermic
effect protein (expressed as a percentage of energy content) is
25-30%, carbohydrate is 6-8%, and fat is 2-3%.6 Take note that
not all of the literature is in precise agreement. Halton and Hu
reported greater variability,7 with the thermic effect of protein
being 20-35%, carbohydrate at 5-15%, and fat being subject to
debate since some investigators found a lower thermic effect
than carbohydrate while others found no difference. In any case,
protein has consistently shown a higher thermic effect than
carbohydrate or fat.

Alan Aragons Research Review July 2013

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The thermic effect of food (TEF) is also called diet-induced

thermogenesis (DIT). This is largely determined by the
macronutrient composition of foods (or meals). However, other
factors can influence DIT even when macronutrition is similar.
A memorable example is by Barr and Wright, who found a DIT
of 137 kcal for a whole food meal, and 73 kcal for the
processed food meal.8 The whole food meal had 5% more
protein, and 2.5 g more fiber, but these factors are too small to
plausibly account for the substantial difference in postprandial
energy expenditure. The authors speculated that the greater
mechanized preparation of the processed food caused less
peristalsis and greater loss of bioactive compounds, resulting in
fewer metabolites, thus requiring less enzyme production. This
would collectively result in more efficient absorption and
metabolism.
By the way, Ive seen articles in the lay press use Barr and
Wrights study to support the idea that processed foods are
prime enemies of weight loss compared to whole foods. While
its understandable how the short-term outcomes would spark
this assumption, chronic studies have not supported it. Theres a
substantial body of controlled interventions showing the robust
weight-reducing effectiveness of highly processed meal
replacement products such as bars, shakes, and powders.9-15 It
therefore is false to assume that the diet needs to be solely
composed of whole and unprocessed foods in order to achieve
weight loss.
So yes, a calorie is a calorie when viewed as a unit of
measurement just like a gram is a gram or a liter is a liter.
However, saying that a calorie is a calorie can evoke the false
idea that the macronutrients all have the same energetic cost of
processing within the body. It also neglects to make the
distinction between gross energy and physiologically available
energy. It goes without saying that the macronutrients have
different physiological and morphological roles aside from their
common role of providing energy. So the problem with saying
a calorie is a calorie boils down to the ability of that
catchphrase to mislead through its oversimplicity.
Thermodynamics & bodyweight
This oversimplification has bothered some academics enough to
address it in the peer-reviewed literature. Feinman and Fine
criticized a calorie is a calorie for being a misunderstanding of
the laws of thermodynamics.16 What inspired them to write this
was a paper by Bucholz and Schoeller, who maintained the
position that a calorie is a calorie since energy cannot be created
nor destroyed; only converted from one form to another.17
Feinman and Fine countered that this position focuses on the
first law of thermodynamics, while neglecting the integral role
of the second law. Specifically, the first law describes the
conservation of energy, while the second law deals with the
dissipation of energy.

championing the so-called metabolic advantage of lowcarbohydrate diets compared to low-fat diets.18 They propose
that carbohydrate restriction per se imparts inherent weight loss
benefits explainable by nonequilibrium thermodynamics.19
Ironically, while Bucholz and Schoeller were criticized for
focusing on the first law of thermodynamics and neglecting the
second law, Feinman and Fine are committing the error of
focusing on differences in dietary carbohydrate instead of
differences in dietary protein. The folly of this assumption was
recently exposed in an elegant study by Soenen et al,20 who did
an isocaloric comparison of four diets: 1) normal-protein, normalcarbohydrate;
2) normal-protein, low-carbohydrate; 3) highprotein, low-carbohydrate; 4) high-protein, normal-carbohydrate.
The two higher protein conditions caused the greatest decreases in
fat mass, while no significant relationship was seen between body
composition change and the varying proportion of dietary fat and
carbohydrate. The authors thus concluded: Body-weight loss and
weight-maintenance depends on the high-protein, but not on the
low-carb component of the diet.

But humans are not bomb calorimeters (well duh...and?)

For those whove been reading this and itching to yell out that
humans are not bomb calorimeters, thats rather obvious no
disagreement there. However, some folks claim that since
humans are not static/closed systems (like bomb calorimeters),
tracking of caloric intake and expenditure in order to alter
bodyweight is a futile endeavor. This is a denial-based cop-out,
since aside from temporary water shifts, theres quite literally no
way to lose or gain weight in the long-term except via sustained
energy deficit or surplus.
The aforementioned conditions of energy balance must be in
place regardless of how loose or meticulous the tracking of
energy is. For example, a focus on choosing good/clean foods
over bad/dirty foods merely serves to impose a deficit by
default. This typically occurs through either satiety-mediated
energy intake reductions, the consumption of foods with less
metabolizable energy, an increase in DIT & lean mass
preservation via consuming enough protein, or a combination of
those factors. The same principle applies to avoiding foods not
on the approved list of the fad diet of the moment.

The second law describes energetic inefficiency, which in the

context of diets goes right back to the varying thermic effect of
macronutrients. As discussed earlier, protein metabolism the
least efficient since its more energetically expensive (evidenced
by a higher DIT) than the metabolism of carbohydrate or fat.
This is well and good, but Feinman and Fine are famous for

It needs to be recognized that involuntary adaptive shifts

separate humans from machines. We unconsciously ramp-up
energy expenditure in the face of increased intake, and downshift energy expenditure in the face of decreased intake. These
adaptations are a good thing, since the survival of our species
would not be possible without it. This is the genius of Mother
Nature at work. We humans differ energetically from bomb
calorimeters primarily due to our dynamic nature, which is based
on homeostatic drive. In other words, the body strives to protect
itself against changes, which it tends to perceive as threats to
survival. It attempts at all times to preserve the physiological
status quo. So, when hypocaloric conditions are imposed, energy
expenditure (EE) has a tendency to decrease. Conversely, when
a caloric surplus is imposed, EE has a tendency to increase. This
is why weight loss and weight gain typically fall short of whats
expected from the respective caloric deficit or surplus initially
imposed.

Alan Aragons Research Review July 2013

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This observation spawned the term adaptive thermogenesis

(AT), which Lowell and Spiegel defined as the regulated
production of heat, influenced by environmental temperature and
diet.21 Keep in mind that this is the broad/general definition. AT
has another definition that pertains specifically to the mystery
of weight loss energetics, which Ill discuss next.

between Bryner et als results and those of Liebel et al (who also

used an 800 kcal liquid diet) can be explained by you guessed
it better macronutrition and the implementation of resistance
exercise. Bryner et als liquid diet was composed of 40%
protein, while Liebel et als was 15%. Bryners subjects
underwent full-body resistance training 3 times per week, while
Liebels design neglected exercise programming altogether.

Adaptive thermogenesis in weight loss

While the mechanisms underlying AT resulting from weight loss

are largely unknown, Dullo and Jacquet have proposed 2 control
systems.26 In what they call non-specific thermogenesis, the
sympathetic nervous system (SNS) responds to environmental
changes and stressors, causing uncoupling proteins to influence
the manifestation of AT. Adipose-specific thermogenesis is the
bodys response to changes in fat mass. Refer to the Oct 2009
issue for more discussion of the potential mechanisms of AT.

The changes in EE are not always completely accounted for by

changes in lean mass and fat mass. Therefore, in the context of
hypocaloric dieting, AT is a term used to describe the gray area
where reduced EE cannot be simply explained by losses in
metabolic tissue or reductions in the energetic cost of movement.
For example, tightly controlled research by Liebel et al showed
that in obese subjects, a 10% or greater weight loss resulted in a
15% greater EE reduction than predicted by body composition
change.22 However, bear in mind that these subjects were put on
an 800 kcal liquid diet composed of 15% protein, 45%
carbohydrate, and 40% fat. It should be painfully obvious that
dieting hard on 30 g protein per day within an 800 kcal diet is far
from optimal. Reductions in EE via the typical research
protocols do not reflect whats possible under conditions
involving better macronutrient targets and proper training.
Camps et al recently found that after significant weight loss,
reduced EE beyond what was predicted was still present after a
year.23 While some see this as evidence of the permanence of
weight loss-induced AT, I would contend that the actual EE
reduction was minor (79 kcal/day). Once again, optimizing
macronutrition and training would very likely eliminate this
impairment. As it stands, the subjects were not engaged in
structured exercise at any point, and the details of their
maintenance diet were not tracked or reported.
The most dramatic case of AT to-date was seen in recent work
by Johannsen et al,24 who examined the effects of morbidly
obese subjects participating in a nationally televised 30-week
weight loss contest. The caloric deficit was targeted at 30%
below maintenance, but since dietary intake was not monitored,
so its likely that subjects did not adhere to this, instead opting
for more aggressive measures. Exercise was supervised 6 days
per week, 90 minutes per session. An additional 3 hours per day
of exercise was encouraged. Expectedly, the majority of weight
lost was fat mass (47.1 kg), and the minority lost was lean mass
(10.5 kg). Resting metabolic rate (RMR) at baseline was 2679
kcal, and this decreased to 1890 kcal by the end of the trial. This
789 kcal decrease represents a 29.4% drop in RMR. Significant
AT was apparent since this was 504 kcal greater than what the
loss of lean mass predicted, making it an 18.8% greater EE
reduction than predicted. This is not too surprising. It makes
sense that an extraordinarily high speed of weight loss (4.22 lb
per week on average for 30 weeks) and high amount of weight
loss (126.7 lb total) would correspond with a stronger
physiological survival defense response than typically seen.
Once again, it should be emphasized that Johanssen et als study
had massive reporting gaps in dietary intake. Therefore, it cannot
be viewed as ironclad proof that dieters are doomed to an
impaired metabolism after substantial weight loss. To illustrate
this, Bryner et al observed an increased RMR by the end of 12
weeks in subjects on an 800 liquid kcal diet.25 The discrepancy
Alan Aragons Research Review July 2013

Adaptive thermogenesis in weight gain

AT (in the broad sense) also applies to weight gain. However,
its not clear whether or not the same mysteriously
unaccountable thermogenesis occurs in weight gain with the
consistency that thermic decreases occur in substantial weight
loss. In attempt to answer this, Joosen and Westerterp combed
the literature and found 5 studies showing evidence of AT
resulting from overfeeding.27 In other words, AT was apparent
based on smaller than expected weight gain or unaccounted
increases in thermogenesis that exceeded obligatory costs.
However, they also found 11 studies that failed to detect AT,
since weight gains corresponded with the amount of
overfeeding, and the increased thermogenesis was proportional
to the theoretical energy costs of increased body mass and
greater dietary intake. To quote them:
These results show that in humans, evidence for adaptive
thermogenesis is still inconsistent. However, they do not rule
out the existence, but emphasize that if present, adaptive
changes in energy expenditure may be too small to measure
considering measurement errors, errors in assumptions made
andsmall(daytoday)differencesinphysicalactivity.

A question relevant to fitness, sports nutrition, and body

composition-oriented goals is whether hardgainers have a
legitimate metabolic impairment against weight gain, or whether
this is a lack of discipline to maintain eating habits that sustain a
caloric surplus. It turns out that conscious and unconscious
increases in non-exercise activity thermogenesis (NEAT) in
response to overfeeding can pose a significant challenge to
expected weight gain. A prime illustration of this was a study by
Levine et al, who fed non-obese adults 1000 kcal above their
maintenance needs for 8 weeks.28 On average, 432 kcal was
stored, and 531 kcal was burned. Nearly two-thirds of the latter
(336 kcal) was attributable to NEAT, which on the upper end of
the range was as high as 692 kcal/day. This finding explains why
some folks can increase their daily intake by 500-600 kcal and
still experience a lack of weight gain. Unbeknownst to them,
their ramped-up NEAT gobbled up their caloric surplus.
Summing up
When the term calories is capitalized, it represents kilocalories.
Non-capitalized calories represent gram-calories, which are
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Page 4

Hargrove JL. History of the calorie in nutrition. J Nutr. 2006

Dec;136(12):2957-61. [PubMed]
2. Jakubowicz D, Barnea M, Wainstein J, Froy O. High Caloric
intake at breakfast vs. dinner differentially influences weight
loss of overweight and obese women. Obesity (Silver Spring).
2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of print]
[PubMed]
3. Buchholz AC, Schoeller DA. Is a calorie a calorie? Am J Clin
Nutr. 2004 May;79(5):899S-906S. [PubMed]
4. AgroMedia, Inc. Energy Partitioning. Accessed July 2013.
http://www.agromedia.ca/ADM_Articles/content/f1r1e1.pdf
5. This is my modified version of a schematic created for an
animal science course at Purdue University (author not
specified). The original PPT presentation is accessible here:
http://www.ansc.purdue.edu/courses/ansc221v/energy.ppt
6. Jquier E. Pathways to obesity. Int J Obes Relat Metab Disord.
2002 Sep;26 Suppl 2:S12-7. [PubMed]
7. Halton TL, Hu FB. The effects of high protein diets on
thermogenesis, satiety and weight loss: a critical review. J Am
Coll Nutr. 2004 Oct;23(5):373-85. [PubMed]
8. Barr SB, Wright JC. Postprandial energy expenditure in wholefood and processed-food meals: implications for daily energy
expenditure. Food Nutr Res. 2010 Jul 2;54. [PubMed]
9. Kroeger CM, Klempel MC, Bhutani S, Trepanowski JF,
Tangney CC, Varady KA. Improvement in coronary heart
disease risk factors during an intermittent fasting/calorie
restriction regimen: Relationship to adipokine modulations.
Nutr Metab (Lond). 2012 Oct 31;9(1):98. [PubMed]
10. Davis LM, Coleman C, Kiel J, Rampolla J, Hutchisen T, Ford
L, Andersen WS, Hanlon-Mitola A. Efficacy of a meal
replacement diet plan compared to a food-based diet plan after
a period of weight loss and weight maintenance: a randomized
controlled trial. Nutr J. 2010 Mar 11;9:11. [PubMed]

11. Cheskin LJ, Mitchell AM, Jhaveri AD, Mitola AH, Davis LM,
Lewis RA, Yep MA, Lycan TW. Efficacy of meal
replacements versus a standard food-based diet for weight loss
in type 2 diabetes: a controlled clinical trial. Diabetes Educ.
2008 Jan-Feb;34(1):118-27. [PubMed]
12. Ashley JM, Herzog H, Clodfelter S, Bovee V, Schrage J,
Pritsos C. Nutrient adequacy during weight loss interventions:
a randomized study in women comparing the dietary intake in a
meal replacement group with a traditional food group. Nutr J.
2007 Jun 25;6:12. [PubMed]
13. Noakes M, Foster PR, Keogh JB, Clifton PM. Meal
replacements are as effective as structured weight-loss diets for
treating obesity in adults with features of metabolic syndrome.
J Nutr. 2004 Aug;134(8):1894-9. [PubMed]
14. Heymsfield SB, van Mierlo CA, van der Knaap HC, Heo M,
Frier HI. Weight management using a meal replacement
strategy: meta and pooling analysis from six studies. Int J Obes
Relat Metab Disord. 2003 May;27(5):537-49. [PubMed]
15. Ditschuneit HH, Flechtner-Mors M, Johnson TD, Adler G.
Metabolic and weight-loss effects of a long-term dietary
intervention in obese patients. Am J Clin Nutr. 1999
Feb;69(2):198-204. [PubMed]
16. Feinman RD, Fine EJ. "A calorie is a calorie" violates the
second law of thermodynamics. Nutr J. 2004 Jul 28;3:9.
[PubMed]
17. Buchholz AC, Schoeller DA. Is a calorie a calorie? Am J Clin
Nutr. 2004 May;79(5):899S-906S. [PubMed]
18. Feinman RD, Fine EJ. Thermodynamics and metabolic
advantage of weight loss diets. Metab Syndr Relat Disord.
2003 Sep;1(3):209-19. [PubMed]
19. Feinman RD, Fine EJ. Nonequilibrium thermodynamics and
energy efficiency in weight loss diets. Theor Biol Med Model.
2007 Jul 30;4:27. [PubMed]
20. Soenen S, Bonomi AG, Lemmens SG, Scholte J, Thijssen MA,
van Berkum F, Westerterp-Plantenga MS. Relatively highprotein or 'low-carb' energy-restricted diets for body weight
loss and body weight maintenance? Physiol Behav. 2012 Oct
10;107(3):374-80. [PubMed]
21. Lowell BB, Spiegelman BM. Towards a molecular
understanding of adaptive thermogenesis. Nature. 2000 Apr
6;404(6778):652-60. [PubMed]
22. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy
expenditure resulting from altered body weight. N Engl J Med.
1995 Mar 9;332(10):621-8. [PubMed]
23. Camps SG, Verhoef SP, Westerterp KR. Weight loss, weight
maintenance, and adaptive thermogenesis. Am J Clin Nutr.
2013 May;97(5):990-4. [Epub ahead of print] [PubMed]
24. Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E,
Hall KD. Metabolic slowing with massive weight loss despite
preservation of fat-free mass. J Clin Endocrinol Metab. 2012
Jul;97(7):2489-96. [PubMed]
25. Bryner RW, Ullrich IH, Sauers J, Donley D, Hornsby G, Kolar
M, Yeater R. Effects of resistance vs. aerobic training
combined with an 800 calorie liquid diet on lean body mass and
resting metabolic rate. J Am Coll Nutr. 1999 Apr;18(2):115-21.
[PubMed]
26. Dulloo AG, Seydoux J, Jacquet J. Adaptive thermogenesis and
uncoupling proteins: a reappraisal of their roles in fat
metabolism and energy balance. Physiol Behav. 2004 Dec
30;83(4):587-602. [PubMed]
27. Joosen AM, Westerterp KR. Energy expenditure during
overfeeding. Nutr Metab (Lond). 2006 Jul 12;3:25. [PubMed]
28. Levine JA, et al. Role of nonexercise activity thermogenesis in
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8;283(5399):212-4. [Pubmed]
29. Taubes G. The science of obesity: what do we really know
about what makes us fat? An essay by Gary Taubes. BMJ. 2013
Apr 15;346:f1050. [PubMed]

Alan Aragons Research Review July 2013

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1000th the value of kilocalories. In the broad scheme, calories

can mean either one, depending on the context of how theyre
presented. Is a calorie a calorie? As a static unit of energy, yes.
Is a macronutrient a macronutrient? Of course not. Theres a
tendency to get caught in the semantic mess of whether or not
a calorie is a calorie is referring to a static unit of energy or the
influence different macronutrients (and foods) have on the
partitioning of energy. Its therefore best to avoid using that
oversimplistic catchphrase. AT can occur in both weight loss
and weight gain scenarios. But just because it exists does not
mean that calories dont matter when manipulating body mass or
composition. As the research evidence indicates, AT comprises
only a minority of the diet-induced reductions in EE, which for
the most part are either preventable or reversible by smart
programming.
Coming up
In part 2 of this article series, Ill examine the controversies
surrounding the eat less, move more mantra. Ill tie this in
with Gary Taubes recent essay in the British Medical Journal,29
which poses several arguments against the focus on calories as
opposed to hormonal response to diet. Ill also discuss the
neuroendocrine factors that influence bodyweight regulation,
and how these can be reconciled with the classic caloric balance
model. This might not all be covered in the next installment due
to the breadth of information Im anticipating, but Ill be sure to
cover it in as many parts as necessary.
References
1.

Page 5

High Caloric intake at breakfast vs. dinner

differentially influences weight loss of overweight and
obese women.
Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity (Silver
Spring). 2013 Mar 20. doi: 10.1002/oby.20460. [Epub ahead of
print] [PubMed]
PURPOSE: Few studies examined the association between
time-of-day of nutrient intake and the metabolic syndrome. Our
goal was to compare a weight loss diet with high caloric intake
during breakfast to an isocaloric diet with high caloric intake at
dinner. METHODS: Overweight and obese women (BMI 32.4
1.8 kg/m2 ) with metabolic syndrome were randomized into
two isocaloric (1400 kcal) weight loss groups, a breakfast (BF)
(700 kcal breakfast, 500 kcal lunch, 200 kcal dinner) or a dinner
(D) group (200 kcal breakfast, 500 kcal lunch, 700 kcal dinner)
for 12 weeks. RESULTS: The BF group showed greater weight
loss and waist circumference reduction. Although fasting
glucose, insulin, and ghrelin were reduced in both groups,
fasting glucose, insulin, and HOMA-IR decreased significantly
to a greater extent in the BF group. Mean triglyceride levels
decreased by 33.6% in the BF group, but increased by 14.6% in
the D group. Oral glucose tolerance test led to a greater decrease
of glucose and insulin in the BF group. In response to meal
challenges, the overall daily glucose, insulin, ghrelin, and mean
hunger scores were significantly lower, whereas mean satiety
scores
were
significantly
higher
in
the
BF
group.CONCLUSIONS: High-calorie breakfast with reduced
intake at dinner is beneficial and might be a useful alternative for
the management of obesity and metabolic syndrome.
SPONSORSHIP: None specified.
Study strengths
This study is strong in concept since very little investigation has
been done in the area of within-day meal timing on bodyweight,
anthropometry, insulin sensitivity, and appetite. Even if the
focus is on the smaller details rather than the big picture, its
interesting nonetheless (especially if there happens to be
something to it). A more concrete strength was the matching of
total energy and macronutrition between conditions. This might
seem like a well duh aspect of the design, but a neglect for
matching these variables is common in studies aiming to
compare temporal effects of nutrients or meals. 74 subjects
completed the study. The authors mentioned that larger cohorts
in future studies are needed, but this sample size was larger than
whats typically used in diet research. A dietitian met with the
subjects on a bi-weekly basis to assess & bolster compliance.
Subjects whose noncompliance exceeded 42.9% were ejected
from the study.

suppressed in self-reported/self-administered diet designs.

Another limitation Id add is that the outcomes might only apply
to the lifestyle profile of the subjects (obese/overweight women
with the metabolic syndrome). Finally, there was no
formal/structured exercise program imposed. I realize that this
can introduce complexity, but programs optimized to alleviate
problems associated with the metabolic syndrome include an
exercise component. Exercise is known to improve a range of
parameters that characterize the metabolic syndrome.1
Comment/application
The primary findings of this study were a significantly greater
weight and waist girth reduction in the large breakfast group
(BF) compared to the large dinner group (D). Specifically, BF
decreased bodyweight 8.7 kg (-11%), while D decreased
bodyweight by 3.6 kg (-4%) over the course of 12 weeks.
Secondary findings were significantly greater improvements in
measures of glucose control in BF, as well as significantly
greater satiety scores and lower hunger scores in BF.
Corroborating the subjective ratings of better appetite control
were the lower ghrelin levels in BF. In sum, BF outperformed D
in all measures.
So, this study supports the traditional recommendation to taper
down caloric intake through the day. However, an important
question is, how do these results compare with the existing body
of evidence? I mentioned in a previous issue that theres no such
thing as a single study that closes the case on any topic; its the
evidence as a whole that matters. Indeed, this body of research is
equivocal. Lets skip over the rodent-based, short-term, and
observational research and look at the chronic human
intervention trials.
To my knowledge, the first to ever compare a larger evening
intake with a larger daytime intake were Sensi and Capani, who
found no significant differences in weight loss between a meal
(684 kcal/day) consumed at 10 am vs 6 pm over either a 3-day or
18-day period.2 However, they detected significantly greater fat
oxidation and lower carbohydrate oxidation in the later-meal
conditions.
Subsequently, Schlundt et al compared the 12-week effects of a
2-meal/day (breakfast-skipped) with a 3-meal/day regimen.3
Despite the isocaloric conditions, no significant differences were
seen in fat loss or weight loss the end of the 12-week trial or the
6-month follow-up.

The authors acknowledge that this 12-week trial was a short

period of time, which diminishes the power to detect follow-up
differences between the groups. Importantly, they also
conceded that lab supervision (and provision) of the dietary
intake would have made for tighter control. Confounders such
over-reporting and under-reporting intake are never completely

Next we have Keim et al, who compared the 6-week effects of

eating 70% of daily calories in the morning versus the evening.4
Unlike the lesser control of the present study, Subjects lived in
the research centers metabolic suite throughout the length of the
study. Unlike the present study, physical activity (including
resistance & aerobic training) was standardized. The larger
evening intake condition retained more lean mass, without any
remarkable difference in fat mass reduction (there was actually a
slight advantage to the larger evening intake). Furthermore, the
present study did not measure body composition, which leaves
an important question unanswered, although one could argue
that the greater waist girth reduction in BF indicates greater
body fat decrease.

Alan Aragons Research Review July 2013

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Study limitations

Page 6

Since Keim et als work in 1997, this area of study stayed

dormant until almost a decade and a half later when Sofer et al
dropped a bombshell on everyone with a 6-month study
finding that all of the anthropometric improvements (weight
loss, waist girth reduction, & body fat reduction) were greater in
the treatment with most of the days carbohydrates eaten at
dinner.5 The control diet where carbs were evenly spread
through each meal was also outperformed for improving glucose
control, inflammation reduction, lipid profile, and satiety ratings.
Interestingly, satiety was rated higher than baseline in the
experimental group by the end of the trial. These results are
almost across-the-board contrary to what was seen in the present
study.
Keim et als inclusion of a structured exercise program could
potentially explain the discrepant outcomes compared to those of
the present study (although that still doesnt account for all of
the differences). But what could explain the diametrically
discrepant outcomes between the present study and Sofer et al?
The present studys subjects had the metabolic syndrome
whereas Sofer et als did not. Total kcals were similar, but
macronutrient composition between diets differed mainly in that
Sofer et al used a higher proportion of carbohydrate & fat, and
lower proportion of protein. Design strengths Sofer et al had
over the present study were the longer duration (6 months vs 12
weeks) and also the measurement of body composition instead
of merely bodyweight and waist circumference.
Sofer et al hypothesized that the superior outcomes from
scooting the majority of the days carbs at dinner were due to a
better manipulation of the bodys leptin-mediated appetite
control, ultimately leading to more favorable body composition:3
It is proposed that the smaller reduction in averaged 12h
leptinconcentration,inducedbytheexperimentaldiet,maybe
an important factor in the higher levels of satiety reported
during the day. [...] Thus, dietary manipulations that will
maintain higher daytime leptin concentrations during daylight
hours in weight loss process may be beneficial. Our
experimental diet might manipulate daily leptin secretion,
leading to higher relative concentrations throughout the day.
Weproposethatthismodificationofhormonesecretionhelped
participants experience greater satiety during waking hours,
enhance diet maintenance over time and have better
anthropometricoutcomes.

In contrast, the authors of the present study offer the following

speculations involving the greater diet-induced thermogenesis of
the morning meal associated with the circadian clock:
Our findings also support a strong correlation between the
timing of food intake and body weight. The association with
feedingtimehasbeenshowninvariousorganismsasastrong
time giver for the circadian clock (6,16). As the circadian clock
and metabolism are tightly linked (12), and disruption of
circadian rhythms leads to obesity (13), it is plausible that
energyintakeandcontentatdifferenttimes,i.e.,breakfastvs.
dinner, may affect the clock differently. Indeed, morning diet
induced thermogenesis (DIT) was significantly higher than
afternoon and night DIT and afternoon DIT was higher than
night DIT, suggesting that the time when a meal is consumed
Alan Aragons Research Review July 2013

affects the thermogenic response and must be considered in

theenergybalance(40).

The present study is at least partially supported by a recent study

led by the same author. In a trial immediately preceding this one,
Jakubowicz et al found that a high-carbohydrate breakfast
resulted in the prevention of weight regain in overweight but
otherwise healthy subjects, while a low-carbohydrate, proteinmatched breakfast did not.6 In fact, the latter group regained 11.6
kg in the 16-week uncontrolled follow-up phase, while the highcarb breakfast group lost additional 6.9 kg. However, unlike the
present study, there were no significant differences in weight
loss or waist girth reduction between conditions during the 16week controlled hypocaloric phase.
In the most recent study in this vein, Garaulet et al found that 20
weeks on a regimen with a later lunch resulted in less weight
loss than an earlier lunch.7 However, the latter studys results
were not nearly as robust as those of the present study, which are
perhaps the most dramatic to-date in terms of weight loss
differences between conditions.
So, in summing up the 7 chronic human intervention studies
(including the present study), 1 shows a fat oxidation advantage
of eating later in the day,2 1 shows no significant difference in
weight or fat loss,3 1 shows a greater preservation of lean mass
mass from eating more calories later in the day,4 1 shows a
greater weight loss, fat loss, and waist reduction from eating
more carbs later in the day.5 3 studies show essentially the
opposite (a favorable effect of front-loading caloric intake), but
none of the latter measured body composition.6-8 Another
notable detail is that only 1 of these 7 studies included a
structured training program (and it happened to show a slight
body composition advantage to eating more later in the day).4
The overall body of evidence is clearly equivocal, so its not
prudent at this time to latch on to a you must eat breakfast or a
breakfast is bad approach to weight or fat loss. Let me
reiterate a conclusion I drew in the December 2012 issue of
AARR, which closely applies here:
AsIseeit,theresahierarchyofimportanceforcarbohydrate
timingthroughtheday.Firstoff,makesurethetotalfortheday
isconsumed.Secondly,timetheconstituentdosessothatthey
maximize, and do not hinder training performance. Tied for
second, on nontraining days, position carb intake to suit your
personally preferred distribution pattern (regardless of what
opposinglinesofresearchmightsuggest).Thirdandloweston
the hierarchy of importance is the option to experiment with
hypothetical optimization techniques currently under scientific
investigation.

Adding to that, Id say that the individuals personal preference

should ultimately dictate the distribution of calories through the
day. If someone simply prefers having a larger evening meal (or
the converse of that), then this should be honored, since
constantly fighting this preference can compromise long-term
adherence. The evidence simply isnt compelling enough to
recommend an attempt at battling personal preference for the
purpose of adopting a particular meal pattern. The focus instead
should be on total daily targets. Individual preference and
training schedule should dictate how these totals are configured.
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Page 7

Effects of a low- or a high-carbohydrate diet on

performance, energy system contribution, and
metabolic responses during supramaximal exercise.
Lima-Silva AE, Pires FO, Bertuzzi R, Silva-Cavalcante MD,
Oliveira RSF, Kiss MA, Bishop D. Appl Phys Nutr Metab. 38:
928934 (2013) dx.doi.org/10.1139/apnm-2012-0467. [APNM]
PURPOSE: The purpose of the present study was to examine the
effects of a high- or low-carbohydrate (CHO) diet on performance,
aerobic and anaerobic contribution, and metabolic responses during
supramaximal exercise. METHODS: Six physically-active men
first performed a cycling exercise bout at 115% maximal oxygen
uptake to exhaustion after following their normal diet for 48 h (
50% of CHO, control test). Seventy-two hours after, participants
performed a muscle glycogen depletion exercise protocol, followed
by either a high- or low-CHO diet ( 70 and 25% of CHO,
respectively) for 48 h, in a random, counterbalanced order. After the
assigned diet period (48 h), the supramaximal cycling exercise bout
(115% maximal oxygen consumption) to exhaustion was
repeated. RESULTS: The low-CHO diet reduced time to
exhaustion when compared with both the control and the high-CHO
diet (19 and 32%, respectively, p < 0.05). The reduced time to
exhaustion following the low-CHO diet was accompanied by a
lower total aerobic energy contribution (39%) compared with the
high-CHO diet (p < 0.05). However, the aerobic and anaerobic
energy contribution at the shortest time to exhaustion (isotime) was
similar among conditions (p > 0.05). The low-CHO diet was
associated with a lower blood lactate concentration (p < 0.05), with
no effect on the plasma concentration of insulin, glucose and
K+ (p > 0.05). CONCLUSION: In conclusion, a low-CHO diet
reduces both performance and total aerobic energy provision during
supramaximal exercise. As peak K+ concentration was similar, but
time to exhaustion shorter, the low-CHO diet was associated with an
earlier
attainment
of
peak
plasma
K+ concentration.
SPONSORSHIP: None specified.

Study strengths
This study is innovative since its the first to ever examine the
effects of a high-carbohydrate (HC) versus a low-carbohydrate
(LC) diet on time-to-exhaustion (TTE), as well as compare the
aerobic versus anaerobic contributions of these diets during
supramaximal-intensity exercise. The subjects were described as
physically active, and they happened to be relatively lean (13%
body fat). This reduces the confounding potential of newbie
status, which can often mask treatment effects. A third condition
(moderate-carb control) was included, as opposed to merely
testing the two extremes. A crossover was implemented, which
helped alleviate the low statistical power of the small sample (6
subjects).
Study limitations
Its possible that the outcomes of this study are confined to the
protocol used. A TTE model was used, as opposed to a time trial
which either measured the work done over a fixed time period or
the time it took to complete a fixed amount of work. TTE
models are not necessarily reflective of real-world race
conditions, and have been found to have greater variability than
time trials,9,10 although this idea has been recently challenged.11
To add an important disclaimer, the present studys TTE test was
done at supramaximal intensity (115% of VO2max), as opposed
Alan Aragons Research Review July 2013

to submaximal intensity taken to exhaustion, so the traditional

criticisms might not apply. Another limitation was the length of
time that the diets were imposed (48 hours prior to testing).
Although this was enough to establish a steady state of glycogen
storage prior to testing, some might argue that it was not enough
time to allow the subjects to adapt to the LC condition. A
counterpoint to this would be that the testing was not conducive
to a critical reliance on fat oxidation due to its supramaximal
intensity.
Comment/application

The primary finding was that the LC diet (25% carb, 30% prot,
45% fat) caused significantly lower supramaximal exercise
endurance compared to the HC diet (70% carb, 10% prot, 20%
fat), resulting in a TTE of 3.0 & 3.7 minutes, respectively. No
significant performance difference was seen between the HC diet
and the moderate (50% carb) control diet. As seen above, the LC
diet had a lower aerobic energy contribution than HC. The
control diet trended toward a lower aerobic contribution than HC
(p = 0.08), but higher aerobic contribution than LC (p = 0.09).
Blood lactate was significantly higher in the HC than LC, but
there were no differences between HC and control or between
LC and control.
The lower TTE in the LC condition is perhaps not too surprising,
given that LC diets have a generally poor track record for
optimizing performance that involves sustained high-intensity
exercise above the lactate threshold.12 Even the noted low-carb
advocate Steven Phinney (who is typically mentioned in the
same breath as Jeff Volek) admitted to observing constrained
sprinting capability in cyclists on a ketogenic diet.13 The
problem with compromised supramaximal performance even
in endurance events is eloquently put by Burke & Kiens:14
Itistemptingtoclassifyenduranceandultraendurancesports
assubmaximalexercise,whichmightbenefitfromincreasedfat
utilization and a conservation of limited endogenous
carbohydrate stores. However, the strategic activities that
occurinsuchsports,thebreakaway,thesurgeduringanuphill
stage,orthesprinttothefinishline,arealldependentonthe
athlete's ability to work at high intensities. With growing
evidence that this critical ability is impaired by dietary fat
adaptation strategies and a failure to find clear evidence of
benefits to prolonged exercise involving selfpacing, it seems
thatweareneartoclosingthedoorononeapplicationofthis
dietaryprotocol.

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Page 8

Study limitations
The effects of anatabine on non-invasive indicators of
muscle damage: a randomized, double-blind, placebocontrolled, crossover study.
Jenkins ND, Housh TJ, Johnson GO, Traylor DA, Bergstrom
HC, Cochrane KC, Lewis RW Jr, Schmidt RJ, Cramer JT. J Int
Soc Sports Nutr. 2013 Jul 22;10(1):33. [Epub ahead of print]
[PubMed]
BACKGROUND: Anatabine (ANA), a minor tobacco alkaloid
found in the Solanaceae family of plants, may exhibit antiinflammatory activity, which may be useful to aid in recovery
from exercise-induced muscle damage. The purpose of this
study, therefore, was to examine the effects of ANA
supplementation on the recovery of isometric strength and
selected non-invasive indicators of muscle damage.
METHODS: A double-blinded, placebo-controlled, crossover
design was used to study eighteen men (mean +/- SD age = 22.2
+/- 3.1 yrs; body mass = 80.3 +/- 15.7 kg) who participated in
two randomly-ordered conditions separated by a washout period.
The ANA condition consisted of consuming 6--12 mg anatabine
per day for 10 days, while testing took place during days 7--10.
The placebo (PLA) condition was identical except that the PLA
supplement contained no ANA. Maximal voluntary isometric
peak torque (PT) of the forearm flexors, arm circumference,
hanging joint angle, and subjective pain ratings were measured
before (PRE), immediately after (POST), and 24, 48, and 72 h
after six sets of 10 maximal, eccentric isokinetic forearm flexion
muscle actions. Resting heart rate and blood pressure were
measured at PRE and 72 h in each condition. RESULTS: For
PT, hanging joint angle, arm circumference, and subjective pain
ratings, there were no condition x time (p > 0.05) interactions,
there were no main effects for condition (p > 0.05), but there
were main effects for time (p < 0.001). There were no condition
x time (p > 0.05) interactions and no main effects for condition
(p > 0.05) or time (p > 0.05) for blood pressure or resting heart
rate. CONCLUSIONS: ANA supplementation had no effect on
the recovery of muscle strength, hanging joint angle, arm
swelling, or subjective pain ratings after a bout of maximal
eccentric exercise in the forearm flexors. Therefore, ANA may
not be beneficial for those seeking to improve recovery from
heavy eccentric exercise. Future studies should examine the
effects of ANA on the pro-inflammatory cytokine responses to
exercise-induced muscle damage and the chronic low-grade
inflammation observed in obese and elderly individuals.
SPONSORSHIP: This study was funded by a research grant
from Rock Creek Pharmaceuticals, Inc.

The supplementation period was 10 days, with days 7-10

involving testing. Its possible that a longer supplementation
period and/or a higher antabine dose than 6-12 g was required to
be effective. Another potential limitation was the inclusion of
other nutrients in both treatments (834 IU vitamin A, and 66 IU
vitamin D3). Although its not likely, the possibility of
confounding/masking effects from these nutrients cant be
completely dismissed. Although the subjects were instructed to
maintain their habitual dietary intake, there was no reporting or
analysis of it. Average compliance was high, at 95.3%, but it
ranged between 74% and 104%, which is unexpected for a small
number of subjects and a short supplementation period. A final
limitation was that non-invasive means of measuring muscle
damage (with the exception of strength testing) are more
subjective than direct measurement of serum biomarkers such as
creatine kinase, myoglobin, or 3-methylhistidine.
Comment/application
The main findings were a lack of significant effects on peak
torque, hanging joint angle, subjective pain ratings, and arm
circumference. These findings were contrary to the authors
hypothesis that antabine would attenuate losses in muscular
strength and improve the recovery of the hanging joint angle,
relaxed arm circumference, and subjective pain ratings due to its
potential anti-inflammatory properties. They additionally
hypothesized antabine would also decrease blood pressure and
increase heart rate due to its similar chemical structure (see the
charts here & here) yet this didnt happen either.
The authors speculate that despite their null findings, its still
possible that antabine could be useful for counteracting the
baseline systemic inflammation associated with obesity and
aging. Previous research in mice showed its ability to inhibit the
phosphorylation of signal transducer and activator of
transcription 3 (STAT3) and nuclear factor-kappa-B (NFkB).15,16
This in addition to its reduction of inflammatory cytokines
render antabine subject to further research seeking to mitigate
conditions of chronic, low-grade inflammation.
What I found particularly interesting was the apparent lack of
sponsor bias. Rock Creek Pharmaceuticals, Inc. funded the
study, and they happen to sell Antabloc, which was the same
formula tested in this study. The supplements failure to show
significant effects on any of the tested parameters lends
confidence in the authors statement that, Rock Creek
Pharmaceuticals, Inc. had no involvement in the data collection,
analysis and interpretation of the data, writing of the manuscript,
or in the decision to submit the manuscript for publication.

This was the first study to test the ergogenic effects of antabine
in human subjects. Previous research has either been in mice, or
in vitro, measuring inflammatory effects or preventive potential
against alzheimers disease.15,16 The present study has specific
relevance to competitive and recreational athletes. Subjects were
blinded as to the placebo versus antabine supplementation via
delivery through mint-flavored lozenges in both groups. A
crossover was implemented in order to alleviate the lowered
statistical power of the small sample (18 subjects total).

Bourgeois et al examined safety and efficacy trials of drugs

registered in ClinicalTrials.gov,17 and found that industry-funded
drug trials reported positive outcomes in 85.4% of the
publications, which contrasted most strongly with governmentfunded trials reporting positive outcomes in 50.0% of the
publications. Interestingly, a systematic review by Golder and
Loke did not find any significant bias against the reporting of
adverse effects in pharmaceutical industry-funded studies.18
However, they did find that authors with industry funding were
more likely to interpret the data as supportive of the drugs
safety, despite the presence of adverse outcomes.

Alan Aragons Research Review July 2013

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Study strengths

Page 9

Blood type diets

systematic review.

lack

supporting

evidence:

Cusack L, De Buck E, Compernolle V, Vandekerckhove P. Am

J Clin Nutr. 2013 Jul;98(1):99-104. [PubMed]
BACKGROUND: Diets that are based on the ABO blood group
system have been promoted over the past decade and claim to
improve health and decrease risk of disease. To our knowledge,
the evidence to support the effectiveness of blood type diets has
not previously been assessed in the scientific literature.
OBJECTIVE: In this current systematic review, published
studies that presented data related to blood type diets were
identified and critically appraised by using the Grading of
Recommendations, Assessment, Development and Evaluation
(GRADE). DESIGN: A systematic search was performed to
answer the following question: In humans grouped according to
blood type, does adherence to a specific diet improve health
and/or decrease risk of disease compared with nonadherence to
the diet? The Cochrane Library, MEDLINE, and Embase were
systematically searched by using sensitive search strategies.
RESULTS: Sixteen articles were identified from a total of 1415
screened references, with only one article that was considered
eligible according to the selection criteria. The identified article
studied the variation between LDL-cholesterol responses of
different MNS blood types to a low-fat diet. However, the study
did not directly answer the current question. No studies that
showed the health effects of ABO blood type diets were
identified. CONCLUSIONS: No evidence currently exists to
validate the purported health benefits of blood type diets. To
validate these claims, studies are required that compare the
health outcomes between participants adhering to a particular
blood type diet (experimental group) and participants continuing
a standard diet (control group) within a particular blood type
population. SPONSORSHIP: There was no funding source for
this project.
Study strengths
This is analysis is conceptually strong because the practice of
blood typing has received widespread popularity since the 1996
publication of naturopath Peter D'Adamos best-selling book Eat
Right 4 Your Type. Theres even a Blood Type Diet
Certification headed by Peter Malia, a naturopath who was
trained by D'Adamo. The far reach of this diet paradigm makes
the present analysis particularly relevant, especially since a wide
range of allied health practitioners have either dabbled in it,
practice it, or have been confronted with client/patient questions
about its evidence basis. As for the technical strengths of the
meta-analysis, all languages were included. The Grading of
Recommendations, Assessment, Development, and Evaluation
(GRADE) method was used to judge the quality of the studies.
Study limitations
Observational as well as controlled studies were included. While
this relatively loose allowance might be construed as a flaw in
the design, in this case it didnt end up mattering due to the lack
of data not to mention lack of support for the diet to begin
with. The single study that fulfilled all of the inclusion criteria
Alan Aragons Research Review July 2013

was somewhat of a mess. It was a controlled interruption time

series, with participants drawn from another study. There was a
lack of participant blinding and an incomplete accounting of
subject outcomes (Only 254 out of the 315 randomly assigned
patients were analyzed). Furthermore, the study did not provide
a direct answer to the PICO (population, intervention,
comparison, and outcome) question. The study thus received a C
grade based on the GRADE standards (C = low, D = very low
evidence quality).
Comment/application

As seen above, out of 1415 studies initially considered for the

analysis, only 1 fulfilled all of the inclusion criteria. This solitary
study did not directly answer the question of whether or not
adherence to a specific diet based on blood type improves health
or lowers disease risk compared to nonadherence. Specifically,
Birley et al compared the variation in LDL-c levels between
different MNS blood types in response to a low-fat diet.18 As
pointed out by the authors, aside from the PICO question not
directly answered, MNS blood types are functionally discinct
from ABO blood types, which comprise the basis of D'Adamos
hypotheses. Furthermore, a systematic review by Masson et al
(published after Birley et als study) which analyzed 74 studies
concluded that in terms of lipid response to dietary intervention,
...the effects of genetic variation are not consistently seen and
are sometimes conflicting.19 Back to the present study, the
authors concluded that based on their meta-analysis, no evidence
currently exists to support the validity of blood type diets. To
quote them:
However,thereiscurrentlynoevidencethatanadherenceto
blood type diets will provide health benefits, despite the
substantial presence and perseverance of blood type diets
withinthehealthindustry.Untilthehealtheffectsofbloodtype
dietshavebeensubstantiated,thewidespreadclaimsshouldbe
clarified so that consumers are aware that the advertised
health benefits are theoretical and not supported by scientific
evidence.

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Page 10

\
1.

2.
3.

4.

5.

6.

7.

8.

9.
10.
11.

12.
13.
14.
15.

Pattyn N, Cornelissen VA, Eshghi SR, Vanhees L. The

effect of exercise on the cardiovascular risk factors
constituting the metabolic syndrome: a meta-analysis of
controlled trials. Sports Med. 2013 Feb;43(2):121-33.
[PubMed]
Sensi S, Capani F. Chronobiological aspects of weight loss
in obesity: effects of different meal timing regimens.
Chronobiol Int. 1987;4(2):251-61. [PubMed]
Schlundt DG, Hill JO, Sbrocco T, Pope-Cordle J, Sharp T.
The role of breakfast in the treatment of obesity: a
randomized clinical trial. Am J Clin Nutr. 1992
Mar;55(3):645-51. [PubMed]
Keim NL, Van Loan MD, Horn WF, Barbieri TF, Mayclin
PL. Weight loss is greater with consumption of large
morning meals and fat-free mass is preserved with large
evening meals in women on a controlled weight reduction
regimen. J Nutr. 1997 Jan;127(1):75-82. [PubMed]
Sofer S, Eliraz A, Kaplan S, Voet H, Fink G, Kima T,
Madar Z. Greater weight loss and hormonal changes after 6
months diet with carbohydrates eaten mostly at dinner.
Obesity (Silver Spring). 2011 Oct;19(10):2006-14.
[PubMed]
Jakubowicz D, Froy O, Wainstein J, Boaz M. Meal timing
and composition influence ghrelin levels, appetite scores
and weight loss maintenance in overweight and obese
adults. Steroids. 2012 Mar 10;77(4):323-31. [PubMed]
Garaulet M, Gmez-Abelln P, Alburquerque-Bjar JJ, Lee
YC, Ordovs JM, Scheer FA. Timing of food intake predicts
weight loss effectiveness. Int J Obes (Lond). 2013
Apr;37(4):604-11. [PubMed]
Jakubowicz D, Barnea M, Wainstein J, Froy O. Obesity
(Silver Spring). High Caloric intake at breakfast vs. dinner
differentially influences weight loss of overweight and
obese women. 2013 Mar 20. doi: 10.1002/oby.20460. [Epub
ahead of print] [PubMed]
Jeukendrup A, Saris WH, Brouns F, Kester AD. A new
validated endurance performance test. Med Sci Sports
Exerc. 1996 Feb;28(2):266-70. [PubMed]
Hopkins WG, Schabort EJ, Hawley JA. Reliability of power
in physical performance tests. Sports Med. 2001;31(3):21134. [PubMed]
Laursen PB, Francis GT, Abbiss CR, Newton MJ, Nosaka
K. Reliability of time-to-exhaustion versus time-trial
running tests in runners.Med Sci Sports Exerc. 2007
Aug;39(8):1374-9. [PubMed]
Cook CM, Haub MD. Low-carbohydrate diets and
performance. Curr Sports Med Rep. 2007 Jul;6(4):225-9.
[PubMed]
Phinney SD. Ketogenic diets and physical performance.
Nutr Metab (Lond). 2004 Aug 17;1(1):2. [PubMed]
Burke LM, Kiens B. "Fat adaptation" for athletic
performance: the nail in the coffin? J Appl Physiol. 2006
Jan;100(1):7-8. [PubMed]
Paris D, Beaulieu-Abdelahad D, Abdullah L, Bachmeier C,
Ait-Ghezala G, Reed J, Verma M, Crawford F, Mullan M.
Anti-inflammatory activity of anatabine via inhibition of
STAT3 phosphorylation. Eur J Pharmacol. 2013 Jan
5;698(1-3):145-53. [PubMed]

Alan Aragons Research Review July 2013

16. Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, AitGhezala G, Bishop A, Chao J, Mathura V, Crawford F,
Mullan M. Anatabine lowers Alzheimer's A production in
vitro and in vivo. Eur J Pharmacol. 2011 Nov 30;670(23):384-91. [PubMed]
17. Bourgeois FT, Murthy S, Mandl KD. Outcome reporting
among drug trials registered in ClinicalTrials.gov. Ann
Intern Med. 2010 Aug 3;153(3):158-66. [PubMed]
18. Birley AJ, MacLennan R, Wahlqvist M, Gerns L, Pangan T,
Martin NG. MN blood group affects response of serum LDL
cholesterol level to a low fat diet. Clin Genet. 1997
May;51(5):291-5. [PubMed]
19. Masson LF, McNeill G, Avenell A. Genetic variation and
the lipid response to dietary intervention: a systematic
review. Am J Clin Nutr. 2003 May;77(5):1098-111.
[PubMed]

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Page 11

The health benefits of dairy protein.

By Armi Legge
____________________________________________________

wasnt focused on getting big and freaky, just maintaining

overall health and decent body composition which is what most
people are after. The researchers identified several potential
health problems dairy protein may be able to combat:
1. The cluster of symptoms called metabolic syndrome which
includes imbalanced blood lipids, poor glucose control,
hypertension, impaired endothelial function, inflammation,
overweight, and obesity is a growing problem around the
world.
2. Sarcobesity is another growing problem where people
are gaining body fat and losing muscle mass, especially as
they age.
Poor eating habits, aging, and physical inactivity are considered
the main culprits of these problems.

Editors note: I thought this piece might serve as a refreshing,

science-based contrast to all of the silly anti-dairy alarmism that
perpetually pervades the lay media.
____________________________________________________
Introduction
Its funny to think theres something that vegans and paleos
agree on. Its even funnier to think theyre both wrong.
Dairy has been getting a pretty bad rep for a while. Its blamed
for causing cancer, inflammation, acne, and pretty much
everything else you can think of. Granted, many health
authorities get a little too worked up about the benefits of dairy.
Its easy to think that if you dont drink it at every meal, youre
basically guaranteed to get osteoporosis.
Others are a little more conservative, and simply claim that
theres no need to eat dairy. Thats true, but you generally dont
need to eat any specific food as long as youre able to hit your
macro- and micronutrient targets.
Some take things even further and claim that consuming dairy
has no benefit and thus should be avoided. If you ignore the fact
that dairy is delicious, this argument might seem to hold some
water (or whey) at first. However, a new review published in
The Journal of Nutrition and Metabolism (free full text here)
gives a nice summary of the potential benefits of consuming
dairy protein.1
Alan already debunked the idea that dairy isnt helpful in terms
of bone growth in the November 2008 issue of AARR.2
While going through all of the claims against dairy would be
fun, it would also take a while (and I have some cookies in the
oven, so time is an issue).Toady, were going to take a look at
the other side of the equation some of the benefits of dairy.
More specifically, dairy protein.
The review
The review, Milk protein for improved metabolic health: a
review of the evidence, mainly focused on how consuming
dairy protein could improve glucose control and muscle mass. It
Alan Aragons Research Review July 2013

Eating less and exercising more to correct energy imbalance is

the best way to correct or prevent obesity. When people lose
weight, however, about 25% of the weight they lose is often lean
mass, much of which is muscle. (Dont worry, this number can
be much lower if you consume adequate protein, lift weights,
and dont diet too aggressively. See AARR January 2011, April
2008, and April/May 2013 for more on this). Luckily, some
researchers think our bovine friends can help with this.
The dairy solution
People who consume dairy tend to have a lower risk of
metabolic disorders and cardiovascular disease. Virtually all of
the proteins in dairy have the potential to improve metabolic
health. Dairy also tends to be high in minerals and
micronutrients. This seems like a good argument for consuming
whole protein sources rather than just supplements.
Whey and casein, the two primary proteins in dairy, are both
extremely high quality protein sources, thanks to their wide
range of essential amino acids and ease of digestion. Theres
evidence that whey and casein can help improve insulin action,
increase satiety, reduce blood pressure, and increase muscle
protein synthesis. They may also improve immune function.
Lets start by looking at how dairy affects metabolic health.
Glucose control
Several studies have shown that dairy protein can help reduce
post-meal glucose levels. It doesnt seem to take much dairy to
cause these effects somewhere around 10-40 grams,
depending on the study. These effects occur in healthy people
and those with type-2 diabetes. Whey seems to be superior to
casein in this regard, though theres still some evidence casein
may also improve glucose control as well.
While dairy protein seems to reduce post-meal glucose, its not
clear if this is true for fasting glucose levels. The only study thus
far thats tested this found that dairy did reduce fasting insulin
levels, but not glucose levels. (Another hit to the dairy raises
insulin which makes you fat, theory).
Blood lipids & blood pressure
Dairy tends to reduce the level of triglycerides and other fats in
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Page 12

the blood after a meal, though not all studies have found this to
be the case. Its also not clear if these results are maintained over
the long-term, if they have any real impact on health over time,
or if theyre generalizable to everyone.
One study found that consuming 15 grams per day of a whey
protein supplement helped reduce fasting triglycerides, but only
in people with a high risk of metabolic syndrome. There is also
some animal evidence that dairy protein might help reduce fatty
liver disease in rodents.
Most trials have found that whey protein can reduce blood
pressure in people with hypertension and improve arterial
function, although not all have found this to be the case. The
reason for this discrepancy isnt clear. Based on the totality of
evidence, the authors believe that people with poor blood lipids
and/or high blood pressure may benefit from consuming a
moderate amount of dairy.

cases (got milk?). Incidentally, there is an emerging body of

evidence pointing to the superiority of protein blends over single
sources (even whey alone).3,4
Consuming both casein and whey protein post-exercise tends to
increase myofibrillar muscle protein synthesis. Short-term
studies have generally shown that dairy protein supplements
have little effect on muscle growth, while longer term studies
have generally shown positive trends.
Many of these studies didnt include exercise of any kind. When
they did, it wasnt always progressive, so we dont know what
effect it might have on muscle growth or weight loss with a
reasonable strength training program. Once again, there was
little dietary control in most of these studies which throws a
huge monkey wrench into the results.
As always, we need more research.

Inflammation and immune function

The bottom line

In-vitro studies have shown that whey protein can suppress

immune activation and lower inflammation, but in-vivo studies
have not all found this to be the case. At this point, there isnt
enough evidence to say for sure that dairy proteins help reduce
inflammation or improve immune function, but the research is
promising.

While consuming dairy is far from a guarantee of health, the

claims that it offers no additional benefit over other protein
sources are also dubious. Theres some evidence that dairy
protein may improve insulin action and glucose control, lower
blood lipids and blood pressure, aid fat loss, and assist in muscle
growth. Of course, other protein sources also have benefits over
dairy protein, so it seems wise to have a balance of both.

Appetite control
Dairy proteins generally enhance satiety and reduce food intake
more than other foods, and in some cases more than other
proteins such as soy. One study also found that whey suppressed
food intake more than casein, at least in the short-term. Dairy
proteins do alter levels of satiety-related gut hormones, but at
this point were mostly in the dark as to how dairy proteins
suppress appetite more than other protein sources.
Weight loss
Some data indicates that adding whey protein to the diet under
ad libitum conditions can reduce food intake and cause weight
loss, while others have not. Interestingly, in one study where
people did not lose weight after eating more dairy protein, they
still had lower blood lipids and insulin levels.
Controlled weight loss studies where people eat more dairy
protein have generally found mixed results in terms of body
composition. Some have found adding dairy protein improves fat
loss and spares muscle mass while others have not. These
inconsistent results are largely due to poor overall dietary control
especially not matching total protein intake between groups.
At this point, its not clear if whey or casein is better for sparing
muscle mass during weight loss.
Muscle growth

Both whey and casein have pros and cons, so a mixture of both
is probably a wise choice like most whole dairy sources. You
also have to consider that whole dairy foods are high in
micronutrients and fairly cheap much cheaper than most
protein supplements.
If you dont like dairy, avoiding it wont kill you. If you like
dairy, adding it to your diet in moderate amounts may give you
some small benefits over other protein sources. The key here is
that you have options, and theres no reason to restrict your
intake to one protein source.
Of course, all of this evidence pales in comparison to the simple
fact that avoiding dairy means giving up ice cream which is
simply unacceptable.
References
1.
2.
3.

4.

McGregor RA, Poppitt SD. Milk protein for improved metabolic health: a
review of the evidence. Nutr Metab (Lond). 2013 Jul 3;10(1):46. [PubMed]
Aragon AA. Milk-bashing: a sport for the ignorant. The Alan Aragon
Research Review. Nov 2008:12. [AARR]
Reidy PT, Walker DK, Dickinson JM, Gundermann DM, Drummond MJ,
Timmerman KL, Fry CS, Borack MS, Cope MB, Mukherjea R, Jennings K,
Volpi E, Rasmussen BB. Protein blend ingestion following resistance
exercise promotes human muscle protein synthesis. J Nutr. 2013
Apr;143(4):410-6. [PubMed]
Paul GL. The rationale for consuming protein blends in sports nutrition. J
Am Coll Nutr. 2009 Aug;28 Suppl:464S-472S. [PubMed]

____________________________________________________

Whey protein seems to stimulate protein synthesis, while casein

seems to be more effective at preventing muscle protein
breakdown. Casein seems to cause a more sustained release of
amino acids with a lower spike in amino acids levels, while
whey protein has a more immediate spike with a shorter
duration. It seems like a mix of both would be optimal in most

Armi Legge is the editor and founder of Imprvism.com, a website that

uses science to help people become more awesome. He is also the cofounder and product manager of Imprvr, an app that helps people
track their workouts with as little effort as possible.... He also likes ice
cream and cookies.

Alan Aragons Research Review July 2013

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Page 13

Bulletproof Coffee & concerning bloodwork: questions

for 2 doctors who actually lift.
Kasey & Spencer Nadolsky interviewed by alan Aragon
____________________________________________________
First off, I want to thank you both for doing this interview.
Lets get right to it. Some of your patients with concerning
bloodwork happened to be consuming Dave Asprey's recipe
(special coffee with generous helpings of butter and MCT
oil). Can you please elaborate on this?
SN: Yep definitely. I am currently listed as a healthcare provider
in the Primaldocs.com and Paleophysiciansnetwork.com
directories. I've listed myself in these because you tend to get
more compliant patients this way. I am also a provider for
WellnessFx.com where you can get your blood drawn without
having to see a doctor and then you can consult over the phone
with me as I look over the lab report. Many of the people who
sign up for WellnessFx.com are Paleo followers as well.
Well, I started noticing a trend with the blood work. Many of
these "super healthy" folks had sky high numbers on their
cholesterol panels!
When doing the dietary recalls for the patients with these high
numbers, the most consistent variable I found was that they were
drinking this "Bulletproof Coffee." My brother in law had
actually told me about this special coffee/fat mixture so I was
slightly familiar. It didn't make too much sense to me why Paleo
people would be drinking large quantities of fat in their coffee
but they are always down for some self-experimentation so I am
okay with that as long as it isn't dangerous.
Now most of these guys are well educated in the context of
Paleo bloggers so when I told them to cut out their BP coffee
they were reluctant. They told me, "but cholesterol doesn't
matter!" The only problem was that I didn't check just "Total
Cholesterol," which we now understand not to be that great of a
risk factor for heart disease. I checked the most advanced lipid
testing available with LDL particle numbers and also
apolipoprotein B.
KN: This situation became apparent to me after I had a few
patients specifically referred to me in order to evaluate their
advanced lipid tests (VAP or NMR) which they requested upon
their primary care physicians explaining to them that their LDL
cholesterol had risen and was now high enough to warrant
medication. There turned out to be one significant thing in
common for all these patients, which I will explain after I give
just one case presentation of an otherwise healthy adult male
who had very normal lipid levels in previous years but suddenly
reasonably elevated levels.
Case: The most recent case I had was a consult for a 39 year old
male without any known past medical history but was sent to me
for further evaluation of his lipids after screening showed
significantly elevated total and LDL-c compared to previous
Alan Aragons Research Review July 2013

screening. He had no complaints, felt well and was without any

history chest pain, dyspnea(shortness of breath), fatigue,
hair/skin changes, goiter (enlarged thyroid), weight changes,
libido
change,
sexual
dysfunction,
GI
(abdominal
pain/nausea/diarrhea) complaints nor urinary changes. He states
he has exercised regularly for most of his life and includes
resistance training without any problems. No concerning family
history of coronary artery disease (heart disease), diabetes, or
other significant problems. His only change in lifestyle over the
past couple of years was going from a "moderately low carb
diet" to a "Paleo diet" and recently started "Bulletproof Coffee"
just a few months ago. His diet has otherwise been high in meats
including poultry/beef/fish and some veggies but rare fruit. He
denied any changes in weight or body composition during this
time frame, does not use tobacco, and sleeps 8 hours nightly.
Exam was without any concerning findings, reasonable blood
pressure, no thyroid enlargement and waist circumference 34".
The important components from his recent labs included total
cholesterol of 282, directly measured LDL-c 198, HDL-c 66,
non-HDL 216, and most importantly an apoB 136. He also had
a low-normal hsCRP, normal Lp(a) and pattern "A" with his
VAP test.
For comparison, here are his previous basic lab results:
3 months prior: total cholesterol 248, HDL 59, non-HDL 189,
LDL 181, trig 41; normal thyroid function tests; normal fasting
glucose and electrolytes.
2010 (3 years ago): TC 203, HDL-c 48, non-HDL 155,
LDL-c 143, trigs 58
2005 (8 years ago): TC 219, HDL-c 43, non-HDL 176,
LDL-c 139, trigs 185 (this was prior to his "moderately
low carb diet" consisting of basic changes such as
increasing veggies, decreasing processed carbohydrates).
My assessment was that this is an otherwise very healthy adult
male with no known atherosclerotic disease and no concerning
family history or other risk factors for heart disease but now with
newly elevated non-HDL and apoB which are both well above
goals for a low risk patient even though the pattern is nonatherogenic. The interesting part, of course, is the that they
recently increased now statistically putting him at increased
atherosclerotic risk. I advised him to cut out the excessive butter
and medium-chain triglyceride oil, increase his veggies,
consume more of his fat from nuts and "Mediterranean" type fats
and recheck his lipids in 6-8 weeks.
This case was actually not as extreme as a case I had previously,
and
there
was
a
similar
case
reported
with
impeccable timing published in the Journal of Clinical
Lipidology for which to compare: They reported a case about
a 52 year old female who recently started supplementing with
daily coconut oil and was found to have significantly elevated
TC (303), LDL-c (178), HDL-c (106), trigs (94), and non-HDL
(197) before stopping and rechecking 6 weeks later showing TC
of 201, LDL-c of 127, HDL-c 58, trigs 77, and non-HDL 143. [i]
[i] J Clin Lipid 2013;7(3)151
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As discussed in the AARR from April, 2011, the evidence

demonizing SFAs directly in regards to cardiovascular disease
has turned out to be weak, specifically when comparing to
processed trans-fatty acids and processed carbohydrates. But
there is still evidence suggesting adding excessive amounts of
SFAs may be detrimental and certainly so when compared to
other fatty acids such as omega-3 & omega-6 PUFAs from fish,
nuts, seeds, etc and MUFAs from olives/avocados, and
nuts/seeds. Obviously those sources of fatty acids have other
beneficial components like fiber, lignans, and anti-oxidant
properties which may contribute to the observed cardiovascular
benefits shown in their studies vs SFAs. Weve also seen the
body of evidence grow revealing benefits from cocoa, which is
high in SFA, but perhaps is also confounded by the other
components similar to those mentioned above. The problem I
have seen, as witnessed by evaluating patients similar to the one
I presented above, is that consuming what I would consider
excessive amounts of SFAs from items such as butter and
coconut oil (which, by the way, are processed to some degree
and extracted from their whole food sources) has adverse effects
on increasing atherogenic lipoproteins which are directly
involved in the process of forming atherosclerotic plaques within
coronary arteries (otherwise known as coronary artery disease)
and the rest of our vasculature.
That said, SFA intake is associated with increased apoB1 even
though systematic reviews have questioned the pure association
of SFA consumption and CVD.23 Dairy as a whole has evidence
to support its beneficial role in dietary health including risk of
heart disease and diabetes4 but not necessarily the high-fat forms
such as butter and cream.5 The effects or benefits of MCT oil in
regards to lipids is more convoluted. A review of MCT studies
in 2002 concluded that there may be a mild improved energy
expenditure plus a potential caloric deficit from improved satiety
when MCT isocalorically replace LCTs.6
i.

ii.
iii.

iv.

Study of MLCT vs LCT (25-30gm/d) showed better

weight,
waist,
and
triglyceride
lowering
in
hypertriglyceridemic patients with bmi 24-28 but not in
other bmi categories.7
30ml of coconut oil vs soybean oil in viscerally obese
women during hypocaloric diet appeared superior for
lipoprotein patterns and decreased waist circumference.8
It has been mentioned that MCTs or coconut oil do not
contribute to hypertriglyceridemia due to ability to forego
chylomicron transfer to lymphatic system and deliver
directly to portal system but coconut oil has been shown to
cause increased post-prandial hypertriglyceridemia in
diabetics compared to normal controls.9
Study comparing coconut oil, butter, and safflower oil
showed butter leading to elevated TC, LDL-c, and apoB
compared to the others while safflower oil had lowest
LDL-c and apoB while coconut oil group was
intermediate.10

Can you please explain the significance of measuring LDL-c,

non-HDL, LDL-p & apo B?
KN: We like to look beyond the tradition LDL-c (the amount of
measured cholesterol in low-density lipoproteins) because there
are now ways to more accurately measure the risk associated
Alan Aragons Research Review July 2013

with more specific lipoproteins. The easiest way to measure

atherogenic lipoproteins is something called non-HDL,
which is just total cholesterol minus the HDL-c (giving you just
measurement of atherogenic cholesterol lipoproteins), and is
much stronger at predicting cardiovascular events than LDL-c as
shown in multiple studies11 because it accounts for the increased
risk due to other atherogenic lipoproteins12 including VLDL-c,
apoB, and apoCIII. It additionally showed superiority even in
statin treatment trials as revealed in the Emerging Risk Factor
Collaboration meta-analysis.13 The Framingham Offspring
Cohort14 and Multi-Ethnic Study15 of Atherosclerosis have
clearly shown a stronger correlation of LDL-p16 (low-density
lipid particle number) and apoB (the specific protein attached to
atherogenic lipoproteins), respectively, to incident of coronary
artery disease and subsequent heart attacks and the like than
measurement of LDL-c (though incidence of bad events is
closely related17). This becomes even more important when
correlations may be discordant (one measure high while the
other is low) which is prevalent specifically in insulin resistance
(metabolic syndrome) or diabetes.18 The body of evidence has
grown considerably to include the Copenhagen study,19 Health
Professionals Study,20 and EPIC-NORFOLK.21 While using
advanced lipid testing in the general population is not
universally agreed upon at this time, non-HDL may serve as a
nearly optimal test with the option for checking apoB or LDL-p
when concern for discordance is high.22
Many of the Paleo and Bulletproof Coffee disciples claim
that even having significantly elevated levels of these strong
correlating lipoproteins dont matter without the inflammation
associated with metabolic syndrome. But in addition to the
evidence mentioned above (especially Framingham which
showed LDL-p to outperform even non-HDL in metabolic
syndrome and diabetes), other studies (Nurses Health23 and
Cardiovascular Health Study24 have shown even stronger
correlation of apoB and LDL-p compared to LDL-c while
adjusting for diabetes, hypertension, hsCRP (marker of
inflammation and cardiovascular risk), smoking, physical
inactivity, and weight thus essentially accounting for
inflammation.
SN: Heres an overview of the difference between the standard
lipid panel and advanced lipid testing and why it
matters. Cholesterol cannot travel through the blood stream by
itself so it attaches to these proteins called apolipoproteins to
form what are called lipoproteins. It's almost like cholesterol is
the cargo and the apolipoprotein is the boat - together they make
a cargo ship traveling through your arteries like a river. This is
important to understand because it is an apolipoprotein (in
particular, apolipoprotein B or apo B) and not the cholesterol
that gets "stuck" in the inside of blood vessels and starts the
atherosclerosis cascade. So you see it isn't the cargo that is the
problem, it is the ship that crashes into the sides of the river (the
inner walls of your arteries) and causes damage. This is a super
simplified version, but hopefully you get the gist.
Standard lipid panels look at cholesterol concentrations in the
various lipoproteins (e.g. low density lipoproteins or LDL-C).
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Page 15

This more or less gives an estimate of all of those

aforementioned apo B particles, which I mentioned are a large
part of atherosclerosis. However, this estimation CAN be off for
various reasons that is beyond the scope of this article. Either
way, the LDL-C (which isn't even directly measured in a lipid
panel) does a decent job at estimating the risk and is why you
see it listed as "bad cholesterol." To even better estimate the apo
B particles with a standard lipid panel, you can calculate what is
called Non-HDL Cholesterol. High Density Lipoproteins contain
apo A particles, which DO NOT cause atherosclerosis and are
actually protective and anti-atherogenic. This is why HDL is
called "good cholesterol." So the thinking is that anything that
isn't HDL (apo A containing) cholesterol, is bad (atherogenic).
With this you can calculate the Non-HDL by just subtracting
HDL from Total Cholesterol. This gives you an even better
estimation of the apo B containing particles.
With advanced lipid testing, you can actually measure the
amount of apo B and/or the lipoprotein particle number. It isn't
an estimation like the standard lipid panel. So now you are
looking at the true problem (apo B particles) and not the
innocent bystander cholesterol (cholesterol is still involved in
the process though).
Any concluding thoughts?
SN: After I explain to these BP coffee drinkers that it is the
lipoprotein particles / apo B and not necessarily the cholesterol
that matters more, they start to understand. I then go on to
explain that while saturated fat is not likely dangerous in whole
food sources (see AARRapril 12' I think), the highly
concentrated saturated fat bomb that is BP coffee is likely the
culprit for their high apo B / LDL - Particle levels.
What I then find is that when these folks stop the BP coffee and
then go back to their protein based breakfast (eggs, protein
shake, etc) their levels come back down. While they generally
don't have any weight changes or noticeable body composition
changes when using the BP coffee, the common theme is these
higher LDL-Particles and/or apo B levels. Maybe they are just
getting extra calories but it is my feeling that they are getting
unneeded extra saturated fat that is driving these high levels.
KN: From a clinical perspective, I feel that excessive added
calories from what is essentially processed, or at least extracted
SFAs, from potentially healthful whole foods such as milk and
coconuts for a significant lipemic load may be hazardous to
cardiometabolic health. I would consider comparing
macronutrient profiles of other basic coffee preparations and
consider your options wisely. Compare macronutrient profiles:
Bulletproof coffee:
456 kcal; 22g fat (42 sat); 0 carb; 0 protein
2 tbsp. & :
40 kcal; 3g fat (2 sat); 1g carb; 1g protein
1oz whole milk:
18 kcal; 1g fat (1 sat); 2g carb; 1g protein
Lean Latte* (1 serving)
150 kcal; 3.5g fat (2 sat); 9g carb (6 fiber); 21 g protein
*Disclaimer for conflict of interest
Alan Aragons Research Review July 2013

While natural SFAs are unlikely to be problematic in reasonable

amounts from their natural whole food sources and perhaps even
with some benefit, our experience suggests that these
disproportionately added quantities of processed fats leads to
elevation in atherogenic lipoprotein levels which is consistent
with the body of evidence and of concern for potentially
increased cardiovascular atherosclerotic disease. Conceivably
this will open the door to more research on the subject.
_________________________________________________

Kasey Nadolsky (left): BA in kinesiology at Michigan State University,

captainofthevarsitywrestlingteamand4xNCAAqualifierrankedas
high as #4 nationally and academic allAmerican. Attended Nova
SoutheasterCollegeofOsteopathicMedicinebeforeresidencytraining
in internal medicine at the Naval Medical Center, Portsmouth, Va.
Board certified in internal medicine and obesity medicine following
residency,currentlytraininginendocrinologyfellowshipattheNational
Capital Consortium, Bethesda, MD. Memberships: American
Association of Clinical Endocrinology, The Endocrine Society, National
Lipid Association, The Obesity Society, American Society of Bariatric
Physicians, and American Thyroid Association. Cofounded
www.leanerliving.comwithSpencerwhileinmedicalschool.

Spencer Nadolsky (right): Dr. Spencer Nadolsky is an osteopathic

physician who specializes in weight loss (bariatric medicine) and
cholesterol (lipidology). 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
AcademicAllAmericanstatus.

_________________________________________________
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Who doesnt love open access to scientific research? Heres a

directory of open access journals: http://www.doaj.org/

If you have any questions, comments, suggestions, bones of

contention, cheers, jeers, guest articles youd like to submit, or
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