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Examine.comResearch Digest
Greg Nuckols ◆ 5 Year Anniversary Edition
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From the EditorFirst, we want to thank you or taking the time to check out the
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Table o Contents0 5 Beyond ‘eat less, move more’: treating obesity in 2016
By Spencer Nadolsky, DO
11 High versus low at diets or insulin sensitivityMore body weight means more risk or metabolic syndrome. But the question o
whether more at (and especially saturated at) impacts insulin sensitivity hasn’t
been adequately addressed until now.
19 Root rage: The impact o ashwagandha on muscleSo called “adaptogens” like ashwagandha are typically studied or stress-easing
potential. A randomized trial looked into this popular herb or a different purpose:
bolstering adaptations to weight training.
28 Not-so-sae supplementsStudies have shown that supplement buyers generally trust the supplements
they buy. That might not be the saest assumption, as dietary supplements that
are presumed helpul or neutral may sometimes cause serious side effects, as
quantiied by this study.
35 Throwdown: plant vs animal protein or metabolic syndromeThe DASH diet is requently tested in clinical trials, and ofen perorms well. But the
diet’s ormulation 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outdated evidence.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.
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Beyond ‘eat less,move more’:
treating obesityin 2016
By Spencer Nadolsky, DO
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Te mainstay therapy or obesity management among
clinicians and researchers that don’t specialize in obe-
sity treatment is providing advice along the lines o
eating ewer calories and/or burning more calories.
Obesity is not thought o as a disease, but as a sequel-
ae o laziness and lack o willpower. Many people say
“put the ork down” or “push yoursel away rom the
table,” implying that these are ways to manage obesi-
ty. Unortunately, ollowing this advice has a very low
success rate, which is why we need to shif the way we
think about obesity management.
o shif our perception o how to manage obesity, we
must first change our views o obesity itsel. Instead o
being a result o sheer laziness, the pathophysiology
o 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 deep-
er than this. Why does this happen? Does it happen the
same way in every person? Why can’t people just lose
weight and keep it off? Tese questions are a good start-
ing point to getting a deeper understanding o obesity.
Obesity as a diseaseTere was an uproar in the fitness community in 2013,
when the American Medical Association declared obe-
sity a disease. Many people questioned why someonewho eats too much and moves too little should be clas-
sified as having a disease. I can understand where this
sentiment comes rom, 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 o the living animal
or plant body or o one o its parts that impairs normal
unctioning and is typically maniested by distinguish-ing signs and symptoms.” In what ways does obesity not
fit this? How do other chronic diseases like hyperten-
sion and type 2 diabetes differ rom obesity? You don’t
die rom hypertension, you die rom the end result
o hypertension (e.g. myocardial inarction (MI) or a
cerebrovascular accident). Same with type 2 diabetes.
Many people say “put the orkdown” or “push yoursel away rom thetable,” implying that these are waysto manage obesity. Unortunately,
ollowing this advice has a very lowsuccess rate, which is why we need toshif the way we think about obesitymanagement.
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Obesity doesn’t kill us through excess adipose tissue.
We die rom the sequelae: obesity leads to hypertension,
which ends with an MI. I we aren’t looking at mor-
tality, but instead quality o lie, then think about type
2 diabetes leading to neuropathy, which causes awul
pain. Obesity also results in a lower quality o lie due
to conditions like obstructive sleep apnea and osteoar-
thritis, not to mention the many other affected aspects
o health and quality o lie.
Obesity is the leading precursor to many o these chronic
diseases. I we want to prevent these diseases, shouldn’t
we be treating the underlying cause? Te answer is yes,
o course. I we wouldn’t hold back giving someone
with type 2 diabetes a medicine, then why would we
not provide someone with obesity effective treatments?
We will get into effective treatment options later.
“But at just sits there as an energy storage depot!” Tis
is where the pathophysiology o obesity gets really
interesting. We used to think o adipose tissue as an
inert substance, basically serving as a warehouse or
energy until when we needed it later. Researchers have
ound that our at is the largest endocrine organ in ourbody! As readers o ERD are aware, there are hormones
called adipokines that our at tissue releases. Tese
adipokines have various effects on our bodies, some
good, some bad. Where we store our at has an effect on
the types o adipokines released as well. People with an
“apple” shape, with at stored centrally (visceral) tend to
have the more deleterious types o adipokines, whereas
people with a “pear” shape (subcutaneous) tend to have
the more benign adipokine profile.
People with central obesity and the metabolic derange-
ments that result rom this condition are said to have
adiposopathy, or sick at. Tis term was coined by obe-
sity researcher and clinician Dr. Harold Bays. Not only
is the at hormonally active, but due to its location (near
the liver and portal vein), a higher flux o ree atty
acids throughout the body is stored in the muscle, heart,
and other area o the body. Te increase in ree atty
acids and adipokines are thought to be the cause o the
metabolic issues we see with obesity, like insulin resis-
tance, dyslipidemia, hypertension, and other conditions.
Te idea o inert at is old and needs to be buried.
What about people with the pear shape and subcutane-
ously stored adipose? Te metabolic issues describedabove may not be as relevant, but these people still have
a condition called at mass disease. Tis is the conse-
quences o having too much body mass, as mentioned
above, and it includes osteoarthritis, obstructive sleep
apnea, and even symptoms like reflux.
Either way, obesity be considered a disease. I we think
issues caused by liestyle shouldn’t be called diseases,
then we should stop calling type 2 diabetes and hyper-
Peoplewith central
obesity andthe metabolicderangementsthat result rom
this conditionare said to haveadiposopathy,or sick at.
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tension diseases too. Yes, there are non-liestyle causes
o the aorementioned diseases, but the same can be
said or obesity.
The cause(s) o obesityMuch to Gary aubes’ dismay, the ault o obesitydoesn’t rest on the shoulders o a single macronutrient
like carbohydrates. While refined carbohydrates play a
role in the disease, there are many other strong actors
pushing us towards larger waistlines.
Obesity researcher and ERD reviewer, Dr. Stephan
Guyenet, ofen discusses ood reward and hyper pal-
atability o ood. What seems as simple as avoiding
certain high caloric oods becomes a much tougher task
when scientists are trying to create oods that cause our
brain wiring to short circuit and crave more o them.
Our appetite regulation also doesn’t rely only on the
volume o ood we eat. Te layers o complexities run
much deeper. Te adipokines mentioned above and the
subsequent inflammation can disrupt our appetite and
ood reward signaling. Tis partially explains why it
might be hard to lose weight once we have gained it.
Te microbiome is also involved (another avorite o
ERD readers). It’s possible the bacteria in our guts con-
trol part o our appetite and cravings. Even viruses have
been implicated in weight gain, like adenovirus-36.
As a physician, I ofen see patients who are taking
multiple medicines that are thought to be helpul or
certain symptoms or disease, but which cause weight
gain as a side effect. Kids are being put on powerul
antipsychotics or an off-label use, without regard that
they will likely experience weight gain and metabol-
ic derangement. Heck, many o my patients use over
the counter antihistamines, which could account or a
ew pounds o weight gain i used chronically. For an
exhaustive list o medicines that cause weight gain, reer
to my book, Te Fat Loss Prescription.
O course, genetics also play a role in our body weight.
Researchers are constantly finding various single nucle-
otide polymorphisms (SNPs) related to our weight. We
can’t do anything about our genetics. Even more annoy-
ing, we don’t have control over what our parents and
grandparents did, which may have had a large effect on
our weight, too. Epigenetics, another un ERD topic,
has been studied more recently in the context o obesity.
urns out the effect our parents had on us in utero was
stronger than we once thought, and we may be more
likely to store at than i our parents had chosen differ-
ent liestyles.
What can we do though?Inevitably when I discuss this topic with someone who
is an “eat less, more more” pusher, they point out that
[...] many o my patients use overthe counter antihistamines, whichcould account or a ew pounds oweight gain i used chronically.
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we still do need to “eat less
and move more.” Tey are
absolutely correct, but we
also need to find out how to
get the individual to be able
to actually do so.
Tere is a reason that weight
regain afer initial weight
loss is so common. Te envi-
ronment, genetic, epigenetic,
biological, physiological, and
psychological drivers all col-
laborate to orce us back the
wrong way. Tink about all
o the people you know that
have obesity. Tink o those
with obesity who have lost
weight. Have most kept it off
successully? I most o the
people you know that have
had obesity in the past have
now lost the weight and kept
it off, then I want you to findout their secret and patent it.
Research shows that unor-
tunately liestyle counseling
by itsel is not very success-
ul. Tis is due to the actors described above.
Let’s ace it, dieting is not un and ofen our hunger
and cravings get the best o us. Te orces that drive us
to regain are strong and we need strong treatments to
combat them.
As an obesity medicine specialist, my goal is to find the
linchpin in a patient’s road map or long-term obesity
success. Tis includes creating a liestyle they can ollow
or lie, making sure they are not on any medicines that
cause weight gain or inhibit weight loss, and deciding
on whether they need a medicine and/or surgery that
will help them with their
liestyle.
Many fitness proessionals
balk at the idea o a medi-
cine that helps with weight
loss. Te truth is that these
medicines work in the brain
to actually help you “eat less
and move more.” Instead
o eeling miserable on a
diet and eeling driven to
eat highly palatable oods,
these medicines work in the
parts o the brain that con-
tain our appetite and ood
reward centers to take the
edge off. As explained above,
our brains may not be unc-
tioning properly due to our
weight and other actors.
Why not use a deemed sae
medicine to push back the
other way, toward weightloss?
Tere are currently our
medicines approved or
long-term weight loss in the U.S. Each work in different
ways in our brain to help with liestyle adherence. Since
saety is a concern, there are long-term trials currently
going on to ensure the adverse effects o these medi-
cines are minimal and that our treatment o obesity is
saving lives and/or improving quality o lie.
While I am a medical bariatrician (nonsurgical weight
loss physician), I do understand that weight loss sur-
gery is actually the most powerul tool we have when
fighting obesity. Just like medicine, the surgery isn’t a
magical procedure that automatically makes someone
lose weight and keep it off orever. Surgical weight loss
Let’s ace it,dieting is not
un and ofenour hunger andcravings get thebest o us. The
orces that driveus to regain arestrong and weneed strong
treatments tocombat them.
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is another method that allows patients to stick to a lie-
style over the long term and have a much higher chance
o success than without (in many cases). In act, weight
regain (bariatric surgery recidivism) is common when
the new liestyle is not adhered to.
Tere are multiple bariatric surgeries available today,
but the most common are the roux en y gastric bypass
and the vertical sleeve gastrectomy. It was thought these
worked by shrinking the size o our stomach and there-
ore our ability to eat large portions, but we are now
finding these procedures also affect the aorementioned
drivers o obesity (adipokines, gut hormones, micro
biome, etc). No matter the reason they work, they are the
most efficacious treatment we have right now or obesity.
So, do we still believe that obesity is just a matter o
“pushing ourselves away rom the table?” As heard
rom ERD reviewer and renowned obesity researcher
Dr. Arya Sharma at an obesity conerence, we wouldn’t
tell someone with depression to just “cheer up.” Why
would we tell someone with obesity to just “eat less and
move more?” ◆
Dr. Spencer Nadolsky is a board certiied Family Medicine Physicianand a Diplomate o the American Board o Obesity Medicine. He is
the medical editor or Examine.com. Dr. Nadolsky is the author o
The Fat Loss Prescript ion, now available on Amazon.com.
His love or liestyle as medicine began in athletics, where he
worked using exercise and nutrition science to succeed in oot-
ball and wrestling. Afer wrestling at UNC Chapel Hill as a Tar Heel
heavyweight and earning a degree in exercise science, he head-ed to Edward Via College o Osteopathic Medicine in Blacksburg.
During medical school, Dr. Nadolsky attended multiple obesity
medicine conerences and realized that he wanted to apply the same nutrition and exercise
inormation he learned during his athletics to the general population and health. Afer medical
school, he attended VCU’s Riverside Family Medicine Residency in Newport News to hone his
skills. He is currently practicing in Olney, Maryland. He launched the book Skinny on Slim and
has a blog called Through Thick and Thin.
http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/http://drspencer.com/
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High versus low at diets
or insulin sensitivity A high-fat, high-saturated fat diet decreasesinsulin sensitivity without changing intra-
abdominal fat in weight-stable overweight
and obese adults
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IntroductionInsulin is a hormone that regulates several physiological
unctions, such as promoting glucose uptake rom the
blood, inhibiting glucose release by the liver, and inhib-
iting atty acid release rom at tissue. Insulin’s role is so
central to our survival that nearly every cell in the bodycontains insulin receptors. When these cells become
less sensitive to insulin’s signal, more insulin must be
secreted by the body to compensate. Tis combination
o insulin resistance and compensatory hyperinsu-
linemia may be a undamental driver o metabolic
syndrome and non-alcoholic atty 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 dysunction o at
cells. Te last ew decades has seen an accumulation o
evidence showing that at surrounding organs (visceral
or intra-abdominal) is particularly detrimental in this
regard. However, the traditional view that at beneath
the skin (subcutaneous) is less detrimental or even
protective when compared to visceral at has been chal-
lenged recently. In either case, the commonality is that
there is an excess amount o at tissue.
Weight loss has been shown to reduce inflammation
and increase insulin sensitivity . Moreover, improve-
ments in insulin sensitivity have been shown to
correlate most strongly with the magnitude o change
in visceral at. Indeed, at loss appears to be the prima-
ry determinant o improvements in insulin sensitivity
regardless o whether the individual is consuming a
low-at or low-carbohydrate diet. However, not every-
one who is over-at and insulin resistant is actively
seeking to lose weight.
Te study under review sought to examine the effects
o diets differing in their total and saturated at con-
tent on measures o insulin sensitivity and glucose
tolerance during weight-stable conditions. Researchers
also investigated whether these changes were mediated
through changes in body at distribution.
Figure 1: How inlammation may contribute to the development o diabetes
http://www.ncbi.nlm.nih.gov/pubmed/25724480http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/http://www.ncbi.nlm.nih.gov/pubmed/26650242http://www.ncbi.nlm.nih.gov/pubmed/24063931http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725490/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725490/http://www.ncbi.nlm.nih.gov/pubmed/19087366http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185302/http://diabetes.diabetesjournals.org/content/48/4/839.shorthttp://www.ncbi.nlm.nih.gov/pubmed/21400557http://www.ncbi.nlm.nih.gov/pubmed/21400557http://www.ncbi.nlm.nih.gov/pubmed/21400557http://www.ncbi.nlm.nih.gov/pubmed/21400557http://diabetes.diabetesjournals.org/content/48/4/839.shorthttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185302/http://www.ncbi.nlm.nih.gov/pubmed/19087366http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725490/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725490/http://www.ncbi.nlm.nih.gov/pubmed/24063931http://www.ncbi.nlm.nih.gov/pubmed/26650242http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1483173/http://www.ncbi.nlm.nih.gov/pubmed/25724480
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Insulin resistance is considered a hallmark o met-
abolic syndrome and atty liver. It is commonly
brought about by at cell-mediated inflammation.
Although at loss has been shown to improve insulin
sensitivity and inflammation regardless o dietary
composition, not everyone who is insulin resistant
and inflamed is seeking to lose weight. Tus, the
current study sought to compare the effects o a high-
at diet to a low-at diet on insulin sensitivity during
weight-stable conditions.
Who and what was studied?
Tis was a randomized, controlled, crossover eedingstudy with two our-week intervention periods. Each
intervention period was preceded by a 10-day con-
trol diet and separated by a six-week washout period.
During the control and intervention periods, all ood
was provided to the participants in amounts designed
to maintain bodyweight. Each participant picked up
their ood or off-site consumption and was weighed
twice weekly.
Dietary compliance was monitored with a checklist,
meaning that there was no guarantee that the par-
ticipants actually ate all their assigned oods and no
non-study oods. Still, this design is quite rigorous and
ar more accurate than just asking people what they ate
using a ood requency questionnaire or dietary recall.
Te participants consisted o a small group o mid-
dle-aged obese men (n=10) and women (n=3). Despite
having an average BMI o 33.6, all the participants
had normal glucose tolerance based on asting and
two-hour glucose levels afer a standard oral glucose
tolerance test. However, NAFLD was present in 7 out o
13 participants.
Te two intervention diets (broken down in Figure 2) were:
• A high-at diet (HFD) containing 55% o calories
rom total at, 25% rom saturated at, 27% rom
carbohydrates, and 18% rom protein, and ...
• A low-at diet (LFD) containing 20% calories rom
total at, 8% rom saturated at, 62% rom carbo-
hydrates, and 18% rom protein.
Te control diet mimicked a standard American diet
with 35% calories rom total at, 12% rom saturated at,47% rom carbohydrates, and 18% rom protein.
Figure 2: Kinds o ats in the different diets
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Te major sources o at in all three diets were butter
and high-oleic (meaning high-monounsaturated at)
safflower oil. Additionally, vegetable content between
diets was matched, inulin fiber was added to the HFD
to match the LFD fiber content, and ructose was lim-
ited to less than 15 grams per 1000 kcal in all diets.
However, ructose content was not matched between
diets, being roughly 4.5-old greater in the LFD com-
pared to the HFD. Aside rom knowing that the diets
were based on typical American oods, we don’t know
what specific oods were being eaten by the participants.
Study assessments were perormed at the end o the
control diet and intervention diet phases. Body com-
position was assessed with DXA, abdominal at was
assessed with MRI, and liver at was assessed with
magnetic resonance spectroscopy (MRS). Tese mea-
surement methods are all considered gold standards or
their respective uses in this study.
Whole-body and liver-specific insulin sensitivity were
assessed with the hyperinsulinemic-euglycemic clamp.
Tis method was discussed previously in ERD #8, Blast
from the past: a paleo solution for type 2 diabetes, and iswidely accepted as the gold-standard or directly deter-
mining insulin sensitivity in humans. Te clamp data
was complemented by an intravenous glucose tolerance
test (IVGG), which provided inormation about insu-
lin sensitivity, glucose tolerance, and β-cell unction.
Tis was a randomized, crossover, controlled eeding
study in which 13 middle-aged obese men and wom-
en with normal glucose tolerance consumed a low-at
(20% at, 8% saturated at) or high-at (55% at, 25%
saturated at) diet or our weeks each. Gold stan-
dard measurement methods were used to determine
body composition, abdominal and liver at, insulin
sensitivity, and β-cell unction afer each dietary
intervention period.
What were the indings?Since this was a crossover study, the participants served as
their own controls or analysis. However, only seven par-ticipants completed both the LFD and HFD interventions,
whereas the other six completed only one. Tereore, a
lack o statistical power to detect differences between the
LFD and HFD is a potential limitation o this study.
As intended by the study design, bodyweight remained
stable during the LFD and HFD periods relative to the
respective control periods that preceded them. Despite
a stable bodyweight, the HFD showed a significant 6%increase in subcutaneous at, and the LFD showed a
significant 22% reduction in liver at (absolute change
rom 9.4 to 7.2%).
Figure 3 shows some o the main study results. Te
hyperinsulinemic-euglycemic clamp data suggests that
Figure 3: How the high-at diet compared to the low-at diet
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whole-body insulin sensitivity was reduced by 12-19%
on the HFD only, and this change was significantly
different rom the non-significant increases observed in
the LFD. Tereore, the HFD impaired the body’s ability
to uptake glucose compared to the control diet and LFD.
Te reduction in whole-body insulin sensitivity appears
to be primarily attributable to reduced insulin sensi-
tivity in tissues other than the liver, since liver insulin
sensitivity wasn’t different between the two intervention
diets (according to measures o endogenous glucose
production and hepatic insulin resistance).
Te IVG data largely support the hyperinsuline-
mic-euglycemic clamp data. Glucose tolerance was
significantly greater during the LFD compared to the
control diet and HFD. However, the HFD was not sig-
nificantly different rom the control diet and neither the
LFD or HFD affected beta-cell unction.
Te atty acid composition o VLDL was also assessed
afer each diet, with no significant changes observed or
the HFD. However, the LFD led to significant increases
in the relative proportions o stearic and palmitoleicacid, a trend or an increase in palmitic acid, and a sig-
nificant decrease in linoleic acid.
Finally, correlational analyses revealed that changes in
insulin sensitivity in both diets were positively associ-
ated with changes in subcutaneous at and negatively
associated with changes in VLDL concentrations o
the omega-6 atty acid docosapentaenoic acid (22:5
n6). Additionally, only in the LFD was increased pal-
mitic acid predictive o increased insulin resistance in
the liver. No associations with insulin sensitivity were
observed or visceral at, the subcutaneous to visceral
at ratio, or liver at.
Four weeks on an HFD led to significant reductions
in the insulin sensitivity o tissues other than the liv-
er, whereas the LFD led to significant improvements
in glucose tolerance and reductions in liver at. Tese
changes were not related to changes in visceral or
liver at.
What does the study reallytell us?Tis study suggests that a high-at, high saturated at
diet reduces whole-body insulin sensitivity within a rel-
atively short timerame o our weeks, but that a low-at,
low saturated at diet does not improve insulin sensitiv-
ity compared to a standard American diet.
One possible explanation or the detrimental effect o
the HFD but lack o positive effect in the LFD is that
the effects were mediated by the saturated at content
rather than the total at content o the diets. Insulin
No associations with insulinsensitivity were observed or visceralat, the subcutaneous to visceral atratio, or liver at.
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resistance is directly correlated to the amount o sat-
urated at stored within the muscle (intramuscular
triglycerides), as well as the proportion o saturated
atty acids contained within the muscle cell membranes.
Both o these have been shown to reflect the at compo-
sition o the diet. As such, consuming a high saturated
at diet would be expected to increase the amount o
saturated at within the muscle tissue, which in turn
increases insulin resistance.
Te above is in agreement
with the current study find-
ings. It is possible that the
difference between the 12%
saturated at content o the
control diet compared to the
to 8% o the LFD was not
pronounced enough to have
an effect on skeletal muscle
at composition and insulin
sensitivity. By contrast, the
increase rom the control diet
to the HFD was quite large
(12% to 25%). However, thisstudy was not designed to
investigate the specific effects
o saturated at. Te research-
ers changed two variables at
once, total and saturated at,
and this precludes us rom
determining which mediated
the observed outcomes.
Alternatively, it is possible that the lack o benefit rom
the LFD was owed to an increase in deleterious met-
abolic pathways that counterbalanced any beneficial
effects. Te observed increase in the proportion o pal-
mitic acid within the VLDL particles during the LFD
may reflect an increase in de novo lipogenesis (DNL, or
the synthesis o new lipids in the body), which is also
known to occur with high carbohydrate intakes such as
that o the current study (62% o calories). Additionally,
the proportion o stearic acid was increased, and there
is evidence in mice that this may be involved in insulin
resistance o the liver.
It is tempting to add support to the DNL hypothesis by
noting the disproportionate intake o ructose among
the LFD and HFD. However, this difference amount-
ed to 35 grams per day with a total ructose intake in
the LFD being around the
average intake o Americans.
As discussed in ERD #9,
Fructose: the sweet truth,
ructose use in experimen-
tal trials averaged more
than double this amount,
ofen in isolation. Moreover,
ructose does not appear to
have a detrimental impact
on liver at accumulation
when exchanged or other
carbohydrates with total
caloric intake held constant.
It thereore seems unlikelythat the difference between
the groups in ructose intake
played any substantial role in
the observed outcomes.
As already mentioned, the
small sample size was a
notable limitation o this
study. Many o the effects were large but not statistically
significant. Tis is why uture work with a larger sample
size is needed to corroborate this study.
Another limitation is that the saturated to unsaturat-
ed atty acid ratios o the diets were not matched. It
has been argued that the quality o dietary at is more
important than the quantity o at with regard to insulin
resistance and the development o metabolic syndrome.
[...] the smallsample sizewas a notablelimitation othis study. Manyo the effectswere large butnot statisticallysigniicant.
http://www.metabolismjournal.com/article/S0026-0495(00)91377-5/abstracthttp://www.nejm.org/doi/pdf/10.1056/NEJM199301283280404http://ajcn.nutrition.org/content/76/6/1222.fullhttp://ajcn.nutrition.org/content/76/6/1222.fullhttp://www.jlr.org/content/39/6/1280.fullhttp://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-24http://jn.nutrition.org/content/139/6/1228S.longhttp://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://jn.nutrition.org/content/139/6/1228S.longhttp://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-7-24http://www.jlr.org/content/39/6/1280.fullhttp://ajcn.nutrition.org/content/76/6/1222.fullhttp://ajcn.nutrition.org/content/76/6/1222.fullhttp://www.nejm.org/doi/pdf/10.1056/NEJM199301283280404http://www.metabolismjournal.com/article/S0026-0495(00)91377-5/abstract
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Tere is also evidence to suggest that a threshold or at
intake exists, below which mono- and polyunsaturated
atty acids have a more avorable impact than saturated
atty acids, but above which all atty acids are similarly
detrimental to insulin sensitivity. Tis threshold was
suggested to be 34% o calories. Tus, the different ratios
could have had a different impact on the LFD with its
20% total at, compared to the 55% total at o the HFD.
Despite these limitations, the control diet preceding
each intervention diet was an important strength o
this study as it allowed or a standardization o dietary
parameters beore making changes and eliminat-
ed the possibility that the participants’ habitual diet
conounded the results. Additionally, the methods o
measurement were all considered to be at or near gold
standards, thus lending strong support that the observed
outcomes were not a result o measurement error.
Several questions that remain include the effects o a
very-low carbohydrate or ketogenic diet (with at less
than 10% o daily calories), the effects o consuming
more protein, the effects o physical activity, the effects
o carbohydrate type and quality, the effects o differenttypes o atty acids, and the effects over the long-term.
Tis study suggests that a high-at, high saturated
at diet reduces whole-body insulin sensitivity when
compared to a low-at, low saturated at diet and
standard American diet (control). However, the study
design precludes conclusions about the cause.
The big pictureTe current study supports the notion that a high-at,
high saturated at diet impairs insulin-mediated glucose
uptake into tissues other than the liver. However, not
all experimental evidence does. wo other studies that
utilized the hyperinsulinemic-euglycemic clamp had
overweight and primarily normal-weight men consume
high-at (50-55%) and low-at (20-25%) diets or two to
three weeks with no observed changes in insulin sensi-
tivity. Unortunately, these studies do not indicate how
much o the at was saturated. However, an 11-day study
in healthy men ailed to show a difference in peripher-
al insulin sensitivity they ate diets with zero, 41%, and
83% o calories rom total at when the ratio o saturat-
ed to unsaturated atty acids remained constant.
Te primary difference between these studies and the
current one is the population. Te study under review
was in obese (BMI o 33.6) individuals, while the above
studies were not. It is possible that the reduction in insu-
lin sensitivity is owed to an inability to readily switch
uel sources, ofen reerred to as metabolic flexibility.
Te current study also showed no improvement in
insulin sensitivity with a low-at, low saturated at diet.
Tis is in contrast to a study analyzing 548 participants
across five different dietary interventions that showed
that insulin sensitivity increases when consuming a diet
containing 28% total at and 10% saturated at. Tis
may be owed in part to the type o carbohydrate being
consumed. Te current study modeled the standardAmerican diet in ood choice, while this other study
utilized low-glycemic carbohydrates. Notably, one
o the other five dietary interventions was the same
low-at prescription with high-glycemic index carbohy-
drates, and this dietary group actually worsened their
insulin sensitivity.
In both this and the abovementioned study, the partici-
pants were obese. It does also appear that DNL is more
pronounced in overweight-obese men compared to lean
men, and this may explain why higher glycemic carbo-
hydrates override any potential benefit o a low-at diet.
However, we cannot make any definitive conclusions.
https://www.researchgate.net/profile/Gabriele_Riccardi/publication/12017583_Substituting_dietary_saturated_for_monounsaturated_fat_impairs_insulin_sensitivity_in_healthy_men_and_women_The_KANWU_Study/links/0c96052b08f0388448000000.pdfhttp://press.endocrine.org/doi/full/10.1210/jc.2010-2243http://ajcn.nutrition.org/content/83/4/803.longhttp://ajcn.nutrition.org/content/73/3/554.full.htmlhttp://ajcn.nutrition.org/content/92/4/748.fullhttp://ajcn.nutrition.org/content/73/2/253.fullhttp://ajcn.nutrition.org/content/73/2/253.fullhttp://ajcn.nutrition.org/content/92/4/748.fullhttp://ajcn.nutrition.org/content/73/3/554.full.htmlhttp://ajcn.nutrition.org/content/83/4/803.longhttp://press.endocrine.org/doi/full/10.1210/jc.2010-2243https://www.researchgate.net/profile/Gabriele_Riccardi/publication/12017583_Substituting_dietary_saturated_for_monounsaturated_fat_impairs_insulin_sensitivity_in_healthy_men_and_women_The_KANWU_Study/links/0c96052b08f0388448000000.pdf
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It appears that the effects o high- and low-at diets
on insulin sensitivity are dependent on the carbohy-
drate quality o the diet and the metabolic flexibility
o the individual. High-at diets may be more detri-
mental in overweight-obese individuals because o
an inability to readily switch between using glucose
and at or energy. Low-at diets may only coner
benefits when the increased carbohydrates come
rom low-glycemic sources.
Frequently asked questionsWhat is DNL and why is it seen as detrimental?
A consequence o overconsumption o carbohydratesis increased de novo lipogenesis (DNL), which is a
process that involves the synthesis o atty acids rom
non-lipid sources. Te major end-product o DNL is
the saturated at palmitic acid, which can be desaturat-
ed within the body to orm the monounsaturated at
palmitoleic acid.
Tere are numerous studies showing associations
between higher proportions o palmitoleic acid in
blood and tissue, and adverse health outcomes such as
metabolic syndrome in adults and adolescents, hyper-
triglyceridemia, type-2 diabetes, coronary heart disease,
and prostate cancer. However, since none o these stud-
ies establish causality, it is possible that these conditions
lead to higher proportions o palmitoleic acid.
What should I know?Consuming a high-at, high-saturated at diet may
be detrimental to insulin sensitivity i you are
overweight-obese, and consuming a low-at, low-sat-
urated at diet may be beneficial i you are consuming
low-glycemic carbohydrates. However, there are many
potential conounding variables that prevent drawing
firm conclusions, and this small study does not addressmany o these. ◆
Te most annoying answer to any research question is
“it depends”. Yet that is the answer to many questions,
including the one o at impact on glucose regulation.
alk it over at the ERD Facebook orum.
http://www.jlr.org/content/39/6/1280.longhttp://ajcn.nutrition.org/content/96/5/970.longhttp://ajcn.nutrition.org/content/82/6/1178.longhttp://www.sciencedirect.com/science/article/pii/S0939475307000877http://www.sciencedirect.com/science/article/pii/S0939475307000877http://ajcn.nutrition.org/content/early/2013/10/23/ajcn.113.069740.full.pdf+htmlhttp://-/?-http://aje.oxfordjournals.org/content/early/2013/08/28/aje.kwt136.fullhttps://www.facebook.com/groups/examineERD/permalink/934701639951074/https://www.facebook.com/groups/examineERD/permalink/934701639951074/http://aje.oxfordjournals.org/content/early/2013/08/28/aje.kwt136.fullhttp://-/?-http://ajcn.nutrition.org/content/early/2013/10/23/ajcn.113.069740.full.pdf+htmlhttp://www.sciencedirect.com/science/article/pii/S0939475307000877http://www.sciencedirect.com/science/article/pii/S0939475307000877http://ajcn.nutrition.org/content/82/6/1178.longhttp://ajcn.nutrition.org/content/96/5/970.longhttp://www.jlr.org/content/39/6/1280.long
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Root rage: The impacto ashwagandha on
muscleEx amining the effect of Withania
somnifera supplementation on muscle
strength and recovery: a randomizedcontrolled trial.
http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282http://www.ncbi.nlm.nih.gov/pubmed/26609282
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IntroductionBeing stressed sucks. However, stress has its benefits.
It’s been long-known that a moderate amount o psy-
chological stress can improve physical perormance.
And, as many o our readers probably know, exercise is
a stressor on the body that actually strengthens it in thelong run.
Recently there has been increased interest in a class
o herbal supplements known as “adaptogens” (some
common ones are shown in Figure 1). Adaptogens are
purported to help the body cope with both physical and
mental stressors. Well-known examples o adaptogens
include ginseng and rhodiola.
Another adaptogen that may help in this context is the
root o Withania somnifera, also known as ashwagand-
ha, Indian Ginseng, or Winter Cherry. Ashwagandha
is a perennial shrub that grows primarily in parts
o Asia, and is a member o the nightshade amily.
Ashwagandha root is classified in traditional Indian
Ayurvedic medicine as a rasayana, or a rejuvenator.
Initial research on ashwagandha has indicated that it
may live up to this classification. Supplementation o
ashwagandha in humans may decrease the stress hor-
mone cortisol, increase testosterone, and even improve
cardiovascular perormance. Yet many o these studies
were published in lower-impact journals, which may
somewhat call into question the validity o the results.
With that many effects to its name, it is plausible that
ashwagandha may also be beneficial or strength train-
ing. Tis is the question the authors o the study under
review intended to answer.
Ashwagandha is classified under the loose umbrella
o “adaptogen,” meaning an herbal supplement that
helps the body cope with stressors. Te purpose o
this study was to determine i ashwagandha sup-
plementation could improve strength gains during
resistance training.
Who and what was studied?Healthy men aged 18-50 were recruited or this study.
People were excluded i they took perormance-en-
hancing medications, smoked or drank excessively,
Figure 1: Some common adaptogens
https://en.wikipedia.org/wiki/Yerkes%E2%80%93Dodson_lawhttp://www.jhse.ua.es/jhse/article/view/585http://online.liebertpub.com/doi/abs/10.1089/107628003321536959http://online.liebertpub.com/doi/abs/10.1089/107628003321536959http://examine.com/supplements/Panax%20ginseng/http://examine.com/supplements/Rhodiola%20Rosea/http://www.tandfonline.com/doi/abs/10.3109/13880208209083282http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.ncbi.nlm.nih.gov/pubmed/24371462/http://www.ncbi.nlm.nih.gov/pubmed/21170205/http://www.ncbi.nlm.nih.gov/pubmed/21170205/http://www.ncbi.nlm.nih.gov/pubmed/24371462/http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.tandfonline.com/doi/abs/10.3109/13880208209083282http://examine.com/supplements/Rhodiola%20Rosea/http://examine.com/supplements/Panax%20ginseng/http://online.liebertpub.com/doi/abs/10.1089/107628003321536959http://online.liebertpub.com/doi/abs/10.1089/107628003321536959http://www.jhse.ua.es/jhse/article/view/585https://en.wikipedia.org/wiki/Yerkes%E2%80%93Dodson_law
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had an injury in the past six months. Researchers also
excluded participants i they had medical conditions
deemed problematic or the study. Participants were
also excluded i they engaged in resistance training in
the past 18 months. Fify-seven men who met these
criteria were recruited or the study. Tey were asked
not to take anti-inflammatory medications or the eight
weeks duration o the study.
Te participants were then randomized to receive either
twice-daily placebo (28 people) or 300 milligrams o
KSM-66 twice-daily (29 people). KSM-66 is a com-
mercial high-concentration ashwagandha water extract
standardized to 5% withanolides, one o the primary
active ingredients ound in ashwagandha.
Both groups then began the same resistance training
program. Te program consisted o two weeks o an
acclimation phase consisting o multiple ree weight
and machine exercises done until ailure, with a goal o
15 reps. Tis phase was ollowed by six weeks o a peri-
odization scheme, where the target reps per set rotated
between 5-13 on different days, with the weight also
being adjusted accordingly.
Te main outcome measured or this study was strength
gains as measured by the one repetition maximum
(1RM) or leg extension and a machine bench press.
Similar exercises were part o the training protocol.
Tese were measured on the first day o the acclimation
phase and two days afer the eight-week training proto-
col was complete.
Secondary endpoints were also measured. Tese
included muscle size as measured on the mid-upper
arm, chest, and upper thigh, body at as measured by
bioelectrical impedance, serum testosterone, and serum
creatine kinase (a measure o muscle damage caused
by exertion) 24 and 48 hours afer working out at the
beginning and end o the study. Participants were also
asked to report any side effects.
Healthy men were randomized to take either place-
bo or 300 milligrams o ashwagandha twice a day
during eight weeks o resistance training. Strength
gains beore and afer were measured as the primary
outcome, along with a host o secondary outcomes,
including muscle size, body at, testosterone levels,
and serum creatinine kinase.
What were the indings?Tree people in the placebo group and our people in
the treatment group stopped the resistance training
program beore completing the study, leaving 25 people
in each group who completed the study. Tere were nomajor side effects or adverse events in either group.
Te study findings are summarized in Figure 2. At the
end o the eight weeks, both groups gained strength.
However, the ashwagandha group seemed to out-
perorm the placebo group. Te ashwagandha group
improved their bench press 1RM by a whopping 20
kilograms (or 44 pounds) more than the placebo group
With that many effects to its name,it is plausible that ashwagandha mayalso be beneicial or strength training.
http://www.ncbi.nlm.nih.gov/pubmed/9332168http://www.ncbi.nlm.nih.gov/pubmed/9332168
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(46 kilogram or 101 pound gain vs. 26 kilogram or a 57
pound gain). Te 1RM gains or the leg extension exer-
cise o the treatment group was about 4.5 kilograms
(10 pounds) more than the placebo group’s gains (14.5
kilograms vs. 9.8 kilograms or 32 vs 22 pounds). Each
o the differences between groups were statistically sig-
nificant, and will be discussed urther later.
Both groups also gained muscle size over the eight-week
trial. Te ashwagandha group gained more size in theupper arm. Tey also had an increased chest girth o
about two centimeters more than the placebo group, on
average. Tigh size was not different between the groups.
Both groups also reduced their body at percentage.
Both groups started at around 22% body at. Te pla-
cebo group dropped by 1.5%, while the ashwagandha
group lost about 3.5%, which was also a statistically
significant difference.
Serum testosterone rose in the ashwagandha group by
about 15%, while it remained unchanged in the place-
bo group.
Finally, muscle recovery, as measured by serum creatine
kinase levels ound in the blood 24 and 48 hours afer
working out, improved in both groups over the eight
weeks. Te ashwagandha group improved more, to a
statistically significant degree. However, the difference
between the two groups afer the eight weeks was muchsmaller than the improvement over the eight-week
trial in both groups: the serum creatine kinase levels
afer working out in both groups dropped around 100-
old over the eight weeks. But the difference between
the two groups at the end o the study was only about
five-old. In other words, training over time accounted
or most o the improved muscle recovery seen in this
study, and not supplementation.
Figure 2: Gains over placebo rom ashwagandha
supplementation combined with resistance training
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Te ashwagandha group gained a lot more strength
in the bench press and moderately more strength
in the leg extension compared to the placebo group.
Tey also lost more body at, bulked up a little more,
had a higher testosterone level, and recovered aster.
No side effects were reported.
What does the study reallytell us?Te results o this study seem to be pretty impressive at
first glance, perhaps even unbelievable. Especially the
gains seen in the bench press, which were almost dou-
ble that o the placebo group. In short, this study ound
that ashwagandha supplementation, when combined
with a sensible resistance training program, improves
strength and size in previously untrained men, and
with no reports o side effects to boot.
However impressive these results seem, though, there
are some important limitations.
Firstly, although the gains seen in the bench press and
leg extension 1RM seemed quite large, they also had
a pretty large error associated with them. For instance,
the 95% confidence interval (essentially the range o
values you can be 95% confident the real value lies
within) or the 1RM gain or the ashwagandha group in
the bench press was 36.56-55.54 kg and or the placebo
group 19.52-33.32 kg. Note that the lower estimate o
36.56 or the ashwagandha group is close to the higher
estimate o 33.32 or the placebo group. So, there may
be a difference between groups, but the data rom this
study are consistent with the difference being small. For
the leg extension, the 95% confidence intervals between
ashwagandha and placebo actually overlap, so there
could in theory be no difference in that measurement.In short: the large gains in strength seen in this study
could be in large part just due to chance.
In addition, this was only an eight-week study. Tus,
the saety and efficacy over more extended periods
has not been well-tested. In act, other studies explor-
ing ashwagandha’s saety have been o an even shorter
duration (and one showed an adverse reaction involv-
How does resistance trainingaffect testosterone levels?
In general, serum testosterone rises immediately ollowing resistance training in men, but
returns to baseline, or even below baseline, afer about 30 minutes. Several actors may
affect the speciic testosterone response to working out, however. For instance, high inten-
sity or high volume alone isn’t enough to induce a testosterone response. A response isinduced by meeting a minimum threshold or both.
In women, some studies have also ound short-term increases in serum testosterone, but
others haven’t, so the results are more equivocal.
The measurements o serum testosterone taken in this study were done prior to any activi-
ty, so the act that the placebo group’s levels remained unchanged between the initial and
inal measurements isn’t out o the ordinary, since they were both taken in the morning,
beore resistance training sessions started.
http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.ncbi.nlm.nih.gov/pubmed/21058750http://www.ncbi.nlm.nih.gov/pubmed/21058750http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.ncbi.nlm.nih.gov/pubmed/23125505/
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ing hallucinogenic effects with vertigo at the lowest
dose). So, there’s definitely more work to be done tomake sure that ashwagandha supplementation is sae in
the long term.
Also, muscle recovery was not measured directly
by asking participants about soreness or by testing
strength reductions afer exercise. Instead, serum cre-
atine kinase measures were taken to be a marker o
muscle recover. While there’s some evidence that higher
levels o this correlates well with soreness and reduc-
tions in strength, other studies have ound that creatine
kinase correlates poorly with unctional measures o
recovery. So, we can’t necessarily say that the reductions
in creatine kinase seen in this study would necessarily
translate into better perormance.
Another limitation o this study was that it only recruit-
ed men with “little experience in resistance training,”
according to the authors. Whether or not women or
more experienced lifers would experience similar ben-
efits is an open question since the results rom this study,
which only recruited men, may not generalize to women.
Te at loss measurements should also be taken with
a grain o salt, since the method used (bioelectrical
impedance) is somewhat unreliable.
Tere were also a couple o weird things going on in the
way the study was reported. Te paper had an import-ant omission concerning compliance to the resistance
training protocol. While the authors mention treatment
compliance in terms o pill count, no mention o how
well the participants adhered to the strength training
protocol itsel was mentioned. I, by random chance,
participants in the ashwaganda group adhered better to
the training protocol than those in the placebo group, it
could account or the differences seen between groups.
Since these data weren’t reported, this possibility couldn’t
be ruled out on the basis o the original paper. However,
we contacted the authors, and they indeed tracked the
resistance training protocol between groups and ound
no difference. Tis increases the plausibility that it was
indeed the ashwagandha that lead to the gains.
One other item o note was the exclusion criteria in the
study. One o these criteria was that the authors exclud-
ed people with “any other conditions which [were]
judged problematic or participation in the study.” Tis
is a pretty broad category, and may have skewed the
outcome as well as introduced researcher bias into the
sample used in this study. Tus, there’s a chance the
population studied here may not be representative o
the general population.
I, by random chance, participants inthe ashwaganda group adhered better
to the training protocol than those inthe placebo group, it could account orthe differences seen between groups.
http://www.ncbi.nlm.nih.gov/pubmed/26244131http://www.ncbi.nlm.nih.gov/pubmed/12453160/http://www.ncbi.nlm.nih.gov/pubmed/16770360/http://www.ncbi.nlm.nih.gov/pubmed/11033983http://www.ncbi.nlm.nih.gov/pubmed/11033983http://www.ncbi.nlm.nih.gov/pubmed/16770360/http://www.ncbi.nlm.nih.gov/pubmed/12453160/http://www.ncbi.nlm.nih.gov/pubmed/26244131
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Te results o this study are only over the short-term
and only in relatively untrained men. Te results also
have pretty large errors associated with them, so the
actual effect o ashwagandha may be smaller than
seen in this study. Whether ashwagandha is sae and
effective in experienced strength trainers, women, or
over the long-term is still unknown.
The big pictureTis is the first study to the authors’ (and our) knowl-
edge that took a look at ashwagandha’s effects on
resistance training in particular. However, ashwagand-
ha has been studied in other contexts, many o whichalso show positive results.
Te saety o ashwagandha has been tentatively estab-
lished in the short-term in a ew different studies, with
one exception. One small study reported no side effects
in healthy young people perorming cardio exercise
over eight weeks. Another small study in healthy vol-
unteers reported one adverse event, where a participant
experienced “increased appetite, libido, and halluci-
nogenic effects with vertigo” at the lowest dose, and
was withdrawn rom the study. No other participants
reported any adverse effects. A third study with partici-
pants under chronic stress reported that adverse events
were mild and no different rom placebo.
Ashwagandha’s effect on increasing testosterone has
also been seen in two studies looking at men with
stress-related inertility or low sperm count.
Ashwagandha has also been studied in other athlet-
ic-related contexts and shown benefit, as seen in Figure
3. Te study on healthy volunteers mentioned above
showed mild improvements in back and quad strength
Figure 3: Ashwagandha’s effects on physical perormance in other studies
http://www.ncbi.nlm.nih.gov/pubmed/21170205/http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.ncbi.nlm.nih.gov/pubmed/24371462/http://www.ncbi.nlm.nih.gov/pubmed/19789214http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/19789214http://www.ncbi.nlm.nih.gov/pubmed/24371462/http://www.ncbi.nlm.nih.gov/pubmed/23439798/http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/21170205/
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over 30 days, even though the participants were not
told to train and did not participate in any exercise
program in the month beore enrolling in the study.
Another study in healthy, untrained young people
showed improvements in cardiovascular fitness and
jumping power afer taking 500 milligrams o ashwa-
gandha extract or eight weeks. A third study in trained,
elite cyclists ound improvements in cardiovascular
unction afer eight weeks o 500 milligram supplemen-
tation as well.
While this study fits well with the literature on ashwa-
gandha, the literature currently consists o only a ew
short-term studies o small sample sizes. And in these
respects, the current study is no different. While lon-
ger-term and larger studies are needed to confirm its
effects, the early research on ashwagandha seems
quite promising.
Tis is the the first study to examine ashwagand-
ha’s effects on strength training. However, previous
studies have noted saety in most people over short
time periods, as well as increased testosterone plus
improved cardiovascular and muscle perormance in
untrained or cardiovascularly trained populations.
Longer-term and larger studies are needed to con-
firm these effects.
Frequently asked questionsBy what mechanisms might ashwagandha improve
strength?Nobody is really sure, but the authors o this study offer
one suggestion: ashwagandha improves muscle recov-
ery while also helping muscle development.
Tis study saw improved serum creatine kinase levels
with ashwagandha supplementation, which is sug-
gestive (but not definitive—see above) o improved
muscle recovery afer training. Ashwagandha has some
anti-inflammatory and analgesic properties as well. Te
authors suggest that improved muscle healing alongside
less pain allowed the ashwagandha group to train hard-
er, thereby increasing their gains.
In terms o muscle development, evidence suggests
that supplementation could increase testosterone levels,
which may be one contributing actor. But ashwagand-
ha may also increase the body’s use and/or production
o creatine. A previous study ound increased levels
o the breakdown product o creatine in the blood o
healthy people taking ashwagandha, accompanied by
mild increases in strength. Tus, the authors o the cur-
While thisstudy its
well with theliterature onashwagandha,the literature
currentlyconsists o onlya ew short-term studies o
small samplesizes.
http://www.ncbi.nlm.nih.gov/pubmed/21170205http://www.ncbi.nlm.nih.gov/pubmed/23326093http://www.ncbi.nlm.nih.gov/pubmed/10956379/http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/23125505/http://www.ncbi.nlm.nih.gov/pubmed/10956379/http://www.ncbi.nlm.nih.gov/pubmed/23326093http://www.ncbi.nlm.nih.gov/pubmed/21170205
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rent study suggest that ashwagandha may also stimulate
creatine utilization through an unknown mechanism.
But, again, these mechanisms are mostly speculation at
this point.
Speaking of creatine, how do the gains found in this study
compare to those found with creatine supplementation?
I the results o this study are to be taken at ace val-
ue, ashwagandha has a stronger effect. Tat’s a big “i ”
though. A meta-analysis o creatine supplementation
ound a difference in 1-3RM perormance on the bench
press o about seven kilograms (15 pounds) versus pla-
cebo. In this study, an improvement o 20 kilograms (44
pounds) over placebo on the bench press was seen.
Beore you drop your creatine and run or the ashwa-
gandha, there are some caveats to keep in mind.
First, keep in mind there was some error associated
with the measurements in strength gain, and that the
results o this study are also consistent with smaller
gains. Tis was discussed above.
Second, the meta-analysis mentions that almost all o the
studies included in the calculation to get the seven kilo-
gram number were done on experienced lifers. Recall
that the study under review recruited untrained people.
So, a large part o the difference between creatine and
ashwagandha may be the result o beginner gains.
Also, creatine is a very well-studied supplement at
this point, and its effects and saety are quite estab-
lished (you can check out the nitty-gritty details on
the Examine.com creatine page). While ashwagandha
seems promising, its evidence base is much smaller. Te
great results you see here may diminish or disappear
when urther research is done, or unpublished research
is uncovered. Tis is actually a common phenomenon
in science, known as the decline effect.
Finally, recall that the saety o ashwagandha supple-
mentation has only been evaluated on the time scale o
a month or two at best. Creatine supplementation, on
the other hand, has had much longer term saety stud-
ies in various populations and has ared quite well.
So, it may not be wise to drop creatine in avor o ash-
wagandha just yet.
What other effects is ashwagandha purported to have?
Preliminary evidence suggests that ashwagandha may
improve semen quality and anxiety , and may improve
glycemic control and cholesterol in diabetics as well.
You can check out the details at Examine.com’s ashwa-
gandha entry.
What should I know?Tis is the first study to examine the effects o ashwa-
gandha on participants undergoing resistance training.
Te researchers ound that ashwagandha supplementa-
tion 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 i replicable. Te sheer magnitude o the
effects (which are more similar to steroid-influenced
gains than that o a normal supplement) definitely
warrants urther research. Longer-term, larger studies
are needed to confirm both the saety and the beneficial
effects o ashwagandha. ◆
Pumped up to discuss ashwagandha? Head on over to
the private ERD Facebook orum!
http://www.ncbi.nlm.nih.gov/pubmed/12485548http://examine.com/supplements/Creatine/https://en.wikipedia.org/wiki/Decline_effecthttp://www.ncbi.nlm.nih.gov/pubmed/15795816http://www.ncbi.nlm.nih.gov/pubmed/10449011http://www.ncbi.nlm.nih.gov/pubmed/19083405http://www.ncbi.nlm.nih.gov/pubmed/21399917http://www.ncbi.nlm.nih.gov/pubmed/19789214http://www.ncbi.nlm.nih.gov/pubmed/23439798http://-/?-http://examine.com/supplements/Ashwagandha/https://www.facebook.com/groups/examineERD/permalink/926835777404327/https://www.facebook.com/groups/examineERD/permalink/926835777404327/http://examine.com/supplements/Ashwagandha/http://-/?-http://www.ncbi.nlm.nih.gov/pubmed/23439798http://www.ncbi.nlm.nih.gov/pubmed/19789214http://www.ncbi.nlm.nih.gov/pubmed/21399917http://www.ncbi.nlm.nih.gov/pubmed/19083405http://www.ncbi.nlm.nih.gov/pubmed/10449011http://www.ncbi.nlm.nih.gov/pubmed/15795816https://en.wikipedia.org/wiki/Decline_effecthttp://examine.com/supplements/Creatine/http://www.ncbi.nlm.nih.gov/pubmed/12485548
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Not-so-saesupplements
Emergency Department Visits
for Adverse Events Related to
Dietary Supplements
http://www.ncbi.nlm.nih.gov/pubmed/26465986http://www.ncbi.nlm.nih.gov/pubmed/26465986http://www.ncbi.nlm.nih.gov/pubmed/26465986http://www.ncbi.nlm.nih.gov/pubmed/26465986http://www.ncbi.nlm.nih.gov/pubmed/26465986http://www.ncbi.nlm.nih.gov/pubmed/26465986
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IntroductionDietary supplements are sometimes erroneously per-
ceived as inherently healthy. And because o the way
many supplements are advertised, it’s easy to overlook that
improper administration can lead to adverse outcomes.
Te classification o a supplement is defined in
the United States Dietary Supplement Health and
Education Act o 1994 (DSHEA) as a vitamin, miner-
al, herb or botanical, amino acid, and any concentrate,
metabolite, constituent, or extract o these substances.
In the U.S., the Food and Drug Administration (FDA)
is the governing body that oversees the regulation o
dietary supplements. I a supplement has been report-
ed to be causing serious adverse events or reactions,
the FDA has the authority to pull it rom the market.
However, no saety testing or FDA approval is required
beore a company can market their supplement. Te
lack o oversight authority given to the FDA has even
drawn the attention o late night talk shows hosts like
John Oliver, who humorously covered the issue in this
Youube video.
Many adults are using one or more supplements to
address illnesses or symptoms, and to maintain or
improve health. Hal o all U.S. adults have report-
ed using at least one supplement in the past 30 days.
welve percent o college students have reported taking
five or more supplements a week. Now, more than ever,
there are seemingly endless options to choose rom.
Te number o supplement products currently avail-
able on the market is thought to be in excess o 55,000.
Compare that to the mere 4,000 available in 1994, when
DSHEA was passed.
Furthermore, confidence in the saety and efficacy o
these supplements is very high despite the lack o rigor-
ous oversight by the FDA. A survey conducted by the
trade association, Council or Responsible Nutrition,
ound that “85% o American adults … are confident in
the saety, quality and effectiveness o dietary supple-
ments.” An independent survey has echoed these results,
finding that 67.2% o respondents elt extremely or
somewhat confident in supplement efficacy and 70.8%
elt extremely or somewhat confident about their saety.
While the majority o Americans trust in their sup-
plements, more than one-third have not told their
physician about using them. Tere are numerous docu-
mented drug-supplement interactions ranging rom the
mild to the severe. Te herb St. John’s Wort is thought
to be able to reduce symptoms in people with mild to
moderate depression. But this ‘natural’ supplement also
has 200 documented major drug interactions, including
some with common depression medication. However,
no good data currently exists to document how com-
mon adverse events related to dietary supplements may
be. Te authors o the present study have used surveil-
lance data to try and fill this knowledge gap.
Due to DSHEA, supplements remain largely unreg-
ulated by the FDA. But dietary supplements are
becoming ever more popular, as about hal o U.S.
adults report using one or more in the past 30 days.
rust in the saety and efficacy o these supplements
also remains high. Te authors o this study aimed
to investigate how many annual adverse events are
caused by improper supplement usage.
Who and what was studied?Te researchers looked at 10 years o data (2004-2013) to
estimate the adverse events associated with dietary sup-plements in the United States rom 63 different hospitals.
Te selection o these hospitals was meant to be nation-
ally representative and included locations that had
24-hour emergency departments. rained patient record
abstractors reviewed the reports rom each hospital to
identiy cases where supplements had been implicated
as the likely source o the adverse event. Tese abstrac-
tors have been trained to analyze and compile medical
inormation contained in patient records.
http://www.gpo.gov/fdsys/pkg/STATUTE-108/pdf/STATUTE-108-Pg4325.pdfhttp://www.gpo.gov/fdsys/pkg/STATUTE-108/pdf/STATUTE-108-Pg4325.pdfhttp://www.fda.gov/Food/DietarySupplements/QADietarySupplements/default.htm#FDA_rolehttps://youtu.be/WA0wKeokWUUhttps://youtu.be/WA0wKeokWUUhttp://www.ncbi.nlm.nih.gov/pubmed/23381623http://www.ncbi.nlm.nih.gov/pubmed/23381623http://www.ncbi.nlm.nih.gov/pubmed/23381623http://www.ncbi.nlm.nih.gov/pubmed/25466950http://www.gao.gov/assets/660/653113.pdfhttp://web.health.gov/dietsupp/final.pdfhttp://www.crnusa.org/prpdfs/CRNPR12-ConsumerSurvey100412.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/23051046http://www.ncbi.nlm.nih.gov/pubmed/23403846http://www.ncbi.nlm.nih.gov/pubmed/23403846http://examine.com/supplements/Hypericum+perforatum/http://www.drugs.com/drug-interactions/st-john-s-wort.htmlhttp://www.drugs.com/drug-interactions/st-john-s-wort.htmlhttp://examine.com/supplements/Hypericum+perforatum/http://www.ncbi.nlm.nih.gov/pubmed/23403846http://www.ncbi.nlm.nih.gov/pubmed/23403846http://www.ncbi.nlm.nih.gov/pubmed/23051046http://www.crnusa.org/prpdfs/CRNPR12-ConsumerSurvey100412.pdfhttp://web.health.gov/dietsupp/final.pdfhttp://www.gao.gov/assets/660/653113.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/25466950http://www.ncbi.nlm.nih.gov/pubmed/23381623http://www.ncbi.nlm.nih.gov/pubmed/23381623http://www.ncbi.nlm.nih.gov/pubmed/23381623https://youtu.be/WA0wKeokWUUhttps://youtu.be/WA0wKeokWUUhttp://www.fda.gov/Food/DietarySupplements/QADietarySupplements/default.htm#FDA_rolehttp://www.gpo.gov/fdsys/pkg/STATUTE-108/pdf/STATUTE-108-Pg4325.pdfhttp://www.gpo.gov/fdsys/pkg/STATUTE-108/pdf/STATUTE-108-Pg4325.pdf
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Cases were scanned or emergency room visits where
the treating clinician had explicitly ascribed dietary
supplements as the root cause o the medical issue. Tis
included herbal or complementary nutritional products
such as botanicals, microbial additives, and amino acids,
in addition to micronutrients like vitamins and minerals.
Products that may typically be classified as ood were
excluded, like energy drinks and herbal tea beverages.
opical herbal items and homeopathic products were
included in the analysis even though they do not all
under the regulatory definition o dietary supplements.
Adverse events were classified as anything causing
adverse or allergic reactions, excess doses, unsu-
pervised ingestion by children, or other events like
choking. Due to the non-standard death registration
practices among different hospitals, cases involving a
mortality were not included, as were any cases involv-
ing intentional sel-harm, drug abuse, therapeutic
ailures, nonadherence, and withdrawal.
Researchers examined patient records rom 2004 to
2013 rom 63 different hospitals. Cases where the
treating clinician had identified a supplement asthe cause o the medical emergency were extracted
rom the dataset. However, deaths associated with or
caused by supplements were not included, as hospi-
tals differ in their practice o registering mortalities.
What were the indings?Some o the major findings are summarized in Figure
1. Over 3,600 cases were identified within the prede-
termined 10-year period. Te researchers extrapolated
rom these data that the U.S. experienced an average
Figure 1: Supplement saety by the numbers
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o 23,000 supplement-related emergency department
visits per year, with estimates ranging rom 18,600 to
27,400. O these 23,000 emergency room visits, it was
calculated that about 2,150 (9.4%) o these result in
hospitalization. About 88% o these ER visits were
attributed to a single supplement, as opposed to inter-
actions or mixtures o multiple supplements. Te
average age o patients treated or supplement-related
adverse events was 32 years, and the majority o these
cases were emale.
Figure 2 shows age and supplement category related
results. About a quarter o ER visits involved people
between the ages o 20 to 34, but people older than 65
years old were more likely to have a visit that resulted
in hospitalization. O patients above 65 admitted to the
ER, 16% had to be hospitalized. Surprisingly, one-fifh
o supplement-related ER visits were due to accidental
ingestion by children. When the data covering unsuper-
vised ingestion o dietary supplements by children was
not included, the researchers ound that the majority
o ER visits (65.9%) were due to herbal or complemen-
tary nutritional products. Te top five products in this
category included the ollowing: weight loss (25.5%),
energy (10.0%), sexual enhancement (3.4%), cardiovas-
cular health (3.1%), and sleep, sedation, or anxiolysis
(i.e. anti-anxiety) (2.9%). Multivitamins or unspecified
vitamin products were the biggest contributors to ER
visits under the micronutrient product category.
ER visits also varied according to gender and age.
Weight loss and micronutrient supplements dispro-
portionately landed emales in the ER, while sexual
enhancement and bodybuilding products largely affect-
ed males. Among patients younger than our years old
and adults over 65, micronutrients were the number
one cause o emergency department visits. Tis is in
contrast to the other age groups, where herbal and
complementary nutritional products were the biggest
contributor. In people ages five to 34, weight loss prod-
ucts or energy products were implicated in more than
50% o ER visits. Weight loss products mostly affected
Figure 2: Summary o which types o supplements lead to ER visits by age
Source: Geller AI et al. N Engl J Med. 2015 Oct.
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patients rom 20 to 34 years o age, while the micro-
nutrients iron, calcium, and potassium mostly affected
those older than 65.
About 23,000 people go to the ER or supplement-re-
lated visits every year. Te biggest contributors tothis are herbal or complementary nutritional prod-
ucts like weight loss and energy supplements, which
largely affect people between the ages o five to 34.
Females are more likely than males to end up in the
ER due to adverse supplement reactions. Tose over
the age o 65 are most at risk or an ER visit due to
micronutrient supplements such as iron, calcium,
and potassium.
What does the study reallytell us?While 23,000 annual supplement-related emergency vis-
its may sound high, this is less than 5% o pharmaceutical
product-related ER visits. However, these ER admittance
rates do not line up with the marketing that has promot-
ed dietary supplements as undamentally healthy. Tat is,
the general public overwhelmingly perceives these prod-
ucts to be sae and effective, but the present data does not
support this notion (ERD readers excluded. We think
you are all ahead o the curve on this one).
However, it should also be noted that overall incidences
o supplement-related ER visits have remained con-
stant over time. No significant changes were detected
between 2004 and 2013 when accounting or popu-
lation increases. Te only increase that occurred was
ER visits associated with micronutrient supplements,
which jumped 42.5%, rom 3,212 to 4,578 cases in this
same time rame.
Unlike their highly regulated pharmaceutical coun-
terparts, there are no legal requirements or dietary
supplements to identiy any potential adverse effects or
major drug interactions on their packaging. Te lack o
adequate warning labels may be a contributing actor
to why histories o dietary supplement usage are rarely
obtained by clinicians. Tis can be due to a combina-
tion o clinicians not asking proper patient screening
questions and to a lack o disclosure by the patient.
Proprietary Blends
The FDA has established labeling standards dictating what must appear on a supplement’s
packaging. Manuacturers must list out each ingredient, and are required to display the amount
or percentage o daily value o those ingredients.
A proprietary blend alls under a slightly different set o regulations. Blends are a unique mix-ture o ingredients that are typically developed by the manuacturer. The FDA requires that all
ingredients o a proprietary blend be listed on the label in descending order according to pre-
dominance o weight. While the amount o the blend as a whole must be listed, the amount o
each ingredient included in the blend does not.
Blends are used to help prevent the competition rom knowing what the speciic ormulation is.
But it can also hide the act that very little o an active ingredient may be in the bottle. So while
a proven perormance enhancing ingredient like creatine may be listed in a proprietary blend, it
could be well below what is considered to be an effective dose.
http://www.ncbi.nlm.nih.gov/pubmed/25636694http://www.ncbi.nlm.nih.gov/pubmed/25636694https://ods.od.nih.gov/HealthInformation/dailyvalues.aspxhttp://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/DietarySupplements/ucm070597.htm#4-34http://examine.com/supplements/Creatine/http://examine.com/supplements/Creatine/http://www.fda.gov/Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/DietarySupplements/ucm070597.htm#4-34https://ods.od.nih.gov/HealthInformation/dailyvalues.aspxhttp://www.ncbi.nlm.nih.gov/pubmed/25636694http://www.ncbi.nlm.nih.gov/pubmed/25636694
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Given that there is a tendency to underreport sup-
plement usage, the researchers have noted that their
calculations o emergency department visits attributed
to supplement-related adverse events are probably an
underestimation. A urther limitation was the relative-
ly small sample o hospitals used. But this method o
data collection is likely to yield more accurate results
over voluntary reporting despite the act that volun-
tary reporting would have likely allowed or a larger
sample population.
While 23,000 annual supplement-related emer-
gency visits may not be a large contributor to ER
visits in the larger scheme o things, it does provide
a counter-narrative to the marketing that ofen
portrays supplements as always health promot-
ing. Supplements are not required to come with
labels warning o adverse events or potential drug
interactions, which can be a contributing actor to
supplement-related ER visits.
The big pictureTe supplement industry is the wild west o nutrition.By and large, DSHEA has hampered the ability o the
FDA to adequately regulate supplements. I you have
ever taken a supplement that makes a health claim,
you may have encountered this statement on the label:
“Tese statements have not been evaluated by the Food
and Drug Administration. Tis product is not intended
to diagnose, treat, cure, or prevent any disease.” While
all ingredients must be declared on the label, there is lit-tle oversight to ensure that these ingredients are present
in the supplement, at the doses that are advertised on
the packaging. Under DSHEA, there is no requirement
or companies to provide any data to the FDA showing
that their supplement is sae and effective, unless they
are introducing a new or novel ingredient. It alls on
the FDA to show that a supplement is unsae beore any
action can be taken.
In light o this lack o regulatory oversight, i you are
currently taking or thinking about adding a supplement
to your diet, be sure to notiy your doctor. Supplements
can interact with prescription medication or could
exacerbate certain medical conditions. Wararin
(Coumadin) is a good example. It is a blood-thinning
medication that can be prescribed to people at risk o
orming blood clots. o ensure that the medication
works properly, these patients are usually placed on a
low vitamin K diet, as vitamin K plays an essential role
in orming blood clots. I these patients do not disclose
that they are taking a multivitamin with vitamin K,
multivitamins being one o the most commonly used
supplements, they could be putting themselves at risk
or developing unwanted clots.
Currently, the supplement industry is partially
policed by itsel. Companies that market and sell
supplement products do not have to show the FDA
data o saety or efficacy in the same ashion that
pharmaceutical companies do. Te FDA can step in
when a supplement has been shown to cause harm
and pull it rom the market. It is important to dis-
cuss all supplements you may be taking with your
doctor to avoid unpleasant or dangerous interactions.
Be sure to tell them even i they do not ask during
your screening.
Frequently asked questionsIs there any way to ensure that I’m purchasing a quality
supplement?? Tere are companies out there that do supply third-par-
ty certifications to supplement manuacturers. Tese
companies will veriy that the supplements listed on
the ingredient list are present in the concentrations
claimed. Tere are our major companies that provide
these certifications, which are shown in Figure 3: NSF
International, Inormed Choice, Consumer Lab, and
U.S. Pharmacopeia. With the exception o Consumer
http://inf