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Research Digest
Greg Nuckols
The Examine.com
Research Digest is
my go-to resource for
nutrition information.
It helps keep up
up to date on the
latest studies that
are relevant to my
clients and I, and its
presentation and
readability make it
beneficial for both the
seasoned researcher
and the layman.
- Greg Nuckols
Table of Contents
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Not-so-safe supplements
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By Spencer Nadolsky, DO
More body weight means more risk for metabolic syndrome. But the question of
whether more fat (and especially saturated fat) impacts insulin sensitivity hasnt
been adequately addressed until now.
Studies have shown that supplement buyers generally trust the supplements
they buy. That might not be the safest assumption, as dietary supplements that
are presumed helpful or neutral may sometimes cause serious side effects, as
quantified by this study.
The DASH diet is frequently tested in clinical trials, and often performs well. But the
diets formulation includes strong limitations on red meat, which may be based on
outdated evidence. This study compared animal-protein rich diets with a typical
DASH diet.
Contributors
Researchers
Margaret Wertheim
M.S., RD
Alex Leaf
M.S(c)
Anders Nedergaard
Ph.D.
Jeff Rothschild
M.Sc., RD
Katherine Rizzone
M.D.
Spencer Nadolsky
D.O.
Greg Palcziewski
Ph.D. (c)
Editors
Gregory Lopez
Pharm.D.
Reviewers
Arya Sharma
Ph.D., M.D.
Natalie Muth
M.D., M.P.H., RD
Stephan Guyenet
Ph.D.
Mark Kern
Ph.D., RD
Gillian Mandich
Ph.D(c)
Adel Moussa
Ph.D(c)
Sarah Ballantyne
Ph.D.
clinicians and researchers that dont specialize in obesity treatment is providing advice along the lines of
eating fewer calories and/or burning more calories.
Obesity is not thought of as a disease, but as a sequelae of laziness and lack of willpower. Many people say
put the fork down or push yourself away from the
table, implying that these are ways to manage obesity. Unfortunately, following this advice has a very low
success rate, which is why we need to shift the way we
think about obesity management.
To shift our perception of how to manage obesity, we
must first change our views of obesity itself. Instead of
being a result of sheer laziness, the pathophysiology
of obesity is actually quite complex. Sure, there is an
energy imbalance, leading to more energy stored as
opposed to burned, but the complexities go much deeper than this. Why does this happen? Does it happen the
same way in every person? Why cant people just lose
weight and keep it off? These questions are a good start-
Obesity as a disease
There was an uproar in the fitness community in 2013,
when the American Medical Association declared obesity a disease. Many people questioned why someone
who eats too much and moves too little should be classified as having a disease. I can understand where this
sentiment comes from, when it is said by someone that
does not understand obesity. However, the term disease
describes obesity very well.
A disease is defined as a condition of the living animal
or plant body or of one of its parts that impairs normal
functioning and is typically manifested by distinguishing signs and symptoms. In what ways does obesity not
fit this? How do other chronic diseases like hypertension and type 2 diabetes differ from obesity? You dont
die from hypertension, you die from the end result
of hypertension (e.g. myocardial infarction (MI) or a
cerebrovascular accident). Same with type 2 diabetes.
People
with central
obesity and
the metabolic
derangements
that result from
this condition
are said to have
adiposopathy,
or sick fat.
cant do anything about our genetics. Even more annoying, we dont have control over what our parents and
grandparents did, which may have had a large effect on
our weight, too. Epigenetics, another fun ERD topic,
has been studied more recently in the context of obesity.
Turns out the effect our parents had on us in utero was
stronger than we once thought, and we may be more
likely to store fat than if our parents had chosen different lifestyles.
by itself is not very successful. This is due to the factors described above.
Lets face it, dieting is not fun and often our hunger
and cravings get the best of us. The forces that drive us
combat them.
for life, making sure they are not on any medicines that
style over the long term and have a much higher chance
biome, etc). No matter the reason they work, they are the
move more?
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11
Introduction
Insulin is a hormone that regulates several physiological
functions, such as promoting glucose uptake from the
blood, inhibiting glucose release by the liver, and inhibiting fatty acid release from fat tissue. Insulins role is so
central to our survival that nearly every cell in the body
contains insulin receptors. When these cells become
less sensitive to insulins signal, more insulin must be
secreted by the body to compensate. This combination
of insulin resistance and compensatory hyperinsulinemia may be a fundamental driver of metabolic
syndrome and non-alcoholic fatty liver disease.
As depicted in Figure 1, typical insulin resistance is
thought to be caused in part by excessive inflammation
brought about by an abundance and dysfunction of fat
cells. The last few decades has seen an accumulation of
evidence showing that fat surrounding organs (visceral
or intra-abdominal) is particularly detrimental in this
regard. However, the traditional view that fat beneath
the skin (subcutaneous) is less detrimental or even
protective when compared to visceral fat has been challenged recently. In either case, the commonality is that
there is an excess amount of fat tissue.
Weight loss has been shown to reduce inflammation
and increase insulin sensitivity. Moreover, improvements in insulin sensitivity have been shown to
correlate most strongly with the magnitude of change
in visceral fat. Indeed, fat loss appears to be the primary determinant of improvements in insulin sensitivity
regardless of whether the individual is consuming a
low-fat or low-carbohydrate diet. However, not everyone who is over-fat and insulin resistant is actively
seeking to lose weight.
The study under review sought to examine the effects
of diets differing in their total and saturated fat content on measures of insulin sensitivity and glucose
tolerance during weight-stable conditions. Researchers
also investigated whether these changes were mediated
through changes in body fat distribution.
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far more accurate than just asking people what they ate
weight-stable conditions.
twice weekly.
with 35% calories from total fat, 12% from saturated fat,
13
intervention period.
14
to be primarily attributable to reduced insulin sensitivity in tissues other than the liver, since liver insulin
sensitivity wasnt different between the two intervention
diets (according to measures of endogenous glucose
production and hepatic insulin resistance).
The IVGTT data largely support the hyperinsulinemic-euglycemic clamp data. Glucose tolerance was
Both of these have been shown to reflect the fat composition of the diet. As such, consuming a high saturated
fatty acids, but above which all fatty acids are similarly
20% total fat, compared to the 55% total fat of the HFD.
men, and this may explain why higher glycemic carboHowever, we cannot make any definitive conclusions.
17
18
19
Introduction
resistance training.
20
Healthy men were randomized to take either placebo or 300 milligrams of ashwagandha twice a day
during eight weeks of resistance training. Strength
gains before and after were measured as the primary
outcome, along with a host of secondary outcomes,
including muscle size, body fat, testosterone levels,
and serum creatinine kinase.
pound gain). The 1RM gains for the leg extension exer-
bo group.
between the two groups after the eight weeks was much
after working out in both groups dropped around 100fold over the eight weeks. But the difference between
the two groups at the end of the study was only about
significant difference.
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23
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reported any adverse effects. A third study with participants under chronic stress reported that adverse events
25
This is the the first study to examine ashwagandhas effects on strength training. However, previous
studies have noted safety in most people over short
time periods, as well as increased testosterone plus
improved cardiovascular and muscle performance in
untrained or cardiovascularly trained populations.
Longer-term and larger studies are needed to con-
While this
study fits
well with the
literature on
ashwagandha,
the literature
currently
consists of only
a few shortterm studies of
small sample
sizes.
the other hand, has had much longer term safety stud-
this point.
If the results of this study are to be taken at face value, ashwagandha has a stronger effect. Thats a big if
gandha entry.
Before you drop your creatine and run for the ashwa-
This is the first study to examine the effects of ashwagandha on participants undergoing resistance training.
The researchers found that ashwagandha supplementation combined with training over eight weeks improved
strength quite significantly, as well as muscle size, in
untrained healthy men with no reported side effects.
While these results are promising, they would be
unprecedented if replicable. The sheer magnitude of the
effects (which are more similar to steroid-influenced
gains than that of a normal supplement) definitely
warrants further research. Longer-term, larger studies
are needed to confirm both the safety and the beneficial
effects of ashwagandha.
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Not-so-safe
supplements
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Introduction
Dietary supplements are sometimes erroneously perceived as inherently healthy. And because of the way
many supplements are advertised, its easy to overlook that
improper administration can lead to adverse outcomes.
The classification of a supplement is defined in
the United States Dietary Supplement Health and
Education Act of 1994 (DSHEA) as a vitamin, mineral, herb or botanical, amino acid, and any concentrate,
metabolite, constituent, or extract of these substances.
In the U.S., the Food and Drug Administration (FDA)
is the governing body that oversees the regulation of
dietary supplements. If a supplement has been reported to be causing serious adverse events or reactions,
the FDA has the authority to pull it from the market.
However, no safety testing or FDA approval is required
before a company can market their supplement. The
YouTube video.
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ucts to be safe and effective, but the present data does not
support this notion (ERD readers excluded. We think
About 23,000 people go to the ER for supplement-related visits every year. The biggest contributors to
this are herbal or complementary nutritional products like weight loss and energy supplements, which
largely affect people between the ages of five to 34.
Females are more likely than males to end up in the
ER due to adverse supplement reactions. Those over
the age of 65 are most at risk for an ER visit due to
micronutrient supplements such as iron, calcium,
and potassium.
Proprietary Blends
The FDA has established labeling standards dictating what must appear on a supplements
packaging. Manufacturers must list out each ingredient, and are required to display the amount
or percentage of daily value of those ingredients.
A proprietary blend falls under a slightly different set of regulations. Blends are a unique mixture of ingredients that are typically developed by the manufacturer. The FDA requires that all
ingredients of a proprietary blend be listed on the label in descending order according to predominance of weight. While the amount of the blend as a whole must be listed, the amount of
each ingredient included in the blend does not.
Blends are used to help prevent the competition from knowing what the specific formulation is.
But it can also hide the fact that very little of an active ingredient may be in the bottle. So while
a proven performance enhancing ingredient like creatine may be listed in a proprietary blend, it
could be well below what is considered to be an effective dose.
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sample population.
While 23,000 annual supplement-related emergency visits may not be a large contributor to ER
visits in the larger scheme of things, it does provide
a counter-narrative to the marketing that often
portrays supplements as always health promoting. Supplements are not required to come with
supplement-related ER visits.
supplement??
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34
Throwdown: plant vs
animal protein for
metabolic syndrome
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Introduction
Metabolic syndrome is a cluster of risk factors that
greatly increases the risk of dying from any cause (1.5fold) and especially cardiovascular disease (CVD)
specific causes (2.4-fold). This condition is diagnosed
as either having or being on medications to treat at least
three of the five following criteria:
Abdominal obesity (waist circumference greater
than 40 inches (men) or 35 inches (women)),
Elevated fasting blood glucose (more than 110 mg/
dL),
Elevated fasting triglycerides (more than 150 mg/
dL),
Low HDL-c (less than 40 (men) or 50 (women)
mg/dL), and
than 85 mmHg).
ic syndrome criteria.
in ERD Issue #6 (April, 2015), some dietary approaches may benefit people with metabolic syndrome more
than other approaches.
One currently accepted dietary pattern to reduce
CVD risk factors is the Dietary Approaches to Stop
Hypertension (DASH) diet, which is high in vegetables,
fruit, low-fat dairy products, whole grains, poultry, fish,
and nuts. The diet is low in sweets, sugar-sweetened
beverages, and red meats. The DASH diet is designed
to be low in saturated fat, total fat, and cholesterol, and
rich in fiber, potassium, magnesium, and calcium.
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WM, and WL phases, but only one meal per day was
consumed under the supervision of research personnel.
participant.
2. A five-week weight maintenance (WM) phase following one of three experimental diets.
3. A six-week weight loss (WL) phase consuming
4. A 12-week free living (FL) phase where participants were asked to continue their assigned
hypocaloric diets and physical activity, but without the provision of food and drinks. To prepare
These diets were matched for total fat (as seen in Figure
37
Table 1: Examples of the four study diets: Menus for the test diets
Breakfast
Lunch
Dinner
Snack
HAD
Pancakes with butter
and light syrup
Peaches, canned
in juice
Cottage cheese (1%)
Apple Juice
M-DASH
Pancakes with butter
and light syrup
Blueberries
Skim Milk
Orange Juice
Spinach/baby greens
salad with cherry
Turkey, provolone
tomatoes, mandarin,
cheese, and lettuce
oranges, grilled chicken
sandwich on white
breast, and dressing
bread with mayonnaise
Edamame beans
Granola bar
Whole-wheat dinner
roll with butter
Pistachios
Szechuan stir-fry entr Ratatouille (eggplant/
with pork and white rice
peppers) with pasta
White dinner roll
Spinach salad
with butter
with carrots, cherry
Romaine lettuce
tomatoes, red bell
salad with carrots
pepper, chickpeas,
and italian dressing
and dressing
Light yogurt
High-fiber cereal
Almonds
BOLD
Bran flakes with
raisins and skim milk
Whole-wheat minibagel and margarine
Orange Juice
Banana
Barbeque beef
sandwich on wholewheat bun
Spinach salad with
cherry tomatoes
and dressing
Thin pretzels
Pear
BOLD+
Bran Flakes with
raisins and skim milk
Cottage cheese (1%)
Orange Juice
Note: ranges are based on average changes across all the diets.
None of the diets effects were statistically different from one another.
39
healthy diet.
compared to a diet supplying mainly plant-based prointervention trials (1, 2, 3, 4, 5, 6) showing no differ-
composition.
calcium intake.
poultry. This change was based on observational evidence suggesting a link between red meat and CVD.
41
Observational evidence is important for noticing potential links between diet and health, but it
serves only as a starting point that requires further
and more rigorous testing. It is not uncommon for
dietary recommendations to incorporate observational evidence that is later shown to be incorrect
Ultimately, any diet that results in fat loss will help with
metabolic syndrome. However, some dietary patterns
may better facilitate the necessary caloric deficit. For
instance, a paleolithic diet excluding cereal grains, dairy,
and legumes in favor of lean meats, fruit, fibrous and
starchy vegetables, and nuts has been shown to result
in more favorable health outcomes than a healthy reference diet, as discussed in ERD Issue #6 (April, 2015).
The paleo diet referenced above is unique in that it promotes the consumption of lean unprocessed meats. This
is in contrast to observational evidence that suggests
protective dietary patterns are low in red and processed
meats, providing yet more evidence that the exclusion
of lean red meat is not what makes these other dietary
patterns beneficial.
Ultimately,
any diet that
results in fat
loss will help
with metabolic
syndrome.
However,
some dietary
patterns may
better facilitate
the necessary
caloric deficit.
42
but there are also many types of lean red meat such as
bison and beef steak cut from the round of the cow. Red
differences.
thenic acid.
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In closing...
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