ERD Gnuckols

8/18/2019 ERD Gnuckols

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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

Examine.com Research Digest (ERD). We eel a connection to those

who love to get their hands dirty, wading through interesting and

complex topics in nutrition and supplementation.

Examine.com was ounded five years ago to help cut through the

massive amount o misinormation on the web and everywhere else.

o make sure we stay unbiased, we have a strict policy o accept-

ing no advertising, sponsorship, product samples, or pretty much

anything else that could even slightly skew our research. Tere’s a

reason why over 50,000 people visit us every day.

As our reputation grew, health proessionals started asking i they

could get continuing education credits rom reading our reviews.

We responded with ERD, which covers new research in depth,

using editors and reviewers rom academic fields ranging rom neu-

roscience to immunology. Each month, ERD looks at eight recent

papers that are both interesting and practical, and presents them

in an easy-to-read and graphically pleasing manner. We are now

approved or CECs rom NSCA, NASM, Te Academy, and more.

Greg has always been a big supporter o ERD, so

we made this special anniversary issue or his

readers, containing five ERD articles he thought

you would find interesting.

For 72 hours only, we are offering ERD at a sale price o 20% off .

Click here to buy ERD

(on sale only until March 17 midnight EST)

Click here to learn more about how Examine.com

evolved over the past ive years.

Kamal Patel, Editor-in-Chief

The Examine.comResearch Digest is

my go-to resource for

nutrition information.

It helps keep up

up to date on the

latest studies thatare relevant to my

clients and I, and its

presentation and

readability make it

beneficial for both the

seasoned researcher

and the layman.

- Greg Nuckols

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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

http://ajpendo.physiology.org/content/294/1/E15.longhttp://ajpendo.physiology.org/content/294/1/E15.long


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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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23

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