Examine.com
Research Digest

Issue 24, Vol 1 o 2 ◆  October 2016

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Table of Contents
0 5  The high cost of high
hig h heat cooking
The delicious browning and crusting of steak or chicken could also be harmful.
This one-year long randomized trial looked at high-heat cooking versus gentler
cooking, and its impact on insulin resistance.

14  INTERVIEW: Courtney Silverthorn, PhD

Are you in the life sciences, but not sure if you want to work in a lab? Courtney
is uniquely qualified to give advice about this.

17   Does being insulin resistant affect weight loss on aa  

low-fat or low-carb diet?
Weight loss is not a simple issue. The impact of a diet could be influenced by
whether or not you’re insulin resistant, as examined by this one-year trial of a
low-fat versus low-carb diet.

 26  Examining the potential for edible sunscreen

Phytochemicals in plants are well known to have positive effects on chronic
conditions, such as heart disease and cancer. But certain ones could also help
you avoid ... sunburn!

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From the Editor
So apparently there’s
there’s a presidential election next month.
Have you heard about this?
Just kidding. I don’t
don’t spend 24 hours a day buried under
nutrition research (only 22 or so). When I emerge out
o my pile o p-values, and observe
obser ve comments about the
presidential election, there
t here’’s always one thing I’m most
surprised by. And no, it doesn’t have to do with either
candidate.
Everybody has a strong opinion on extremely complex
policy issues. All 242 million adults in the US, along
with many younger people as well. How is that possible?
Does everyone know the secret to peace in the Middle
East? And everyone also knows the key to sustainable
economic growth while not up-ending the job situation
o millions o citizens?
Te armchair quarterback has a more insidious relative,
the armchair politician. And the armchair politician
has a second-cousin as well, the
t he armchair nutritionist.
You see, some issues only have a handul o variables
involved. I you want to buy a quality new car, you can
peruse online reviews, try out the car or yoursel, and
ask people you know who are into automobiles. So
there aren’t
aren’t that many (any?) people who
w ho proclaim that
Geo is the greatest car maker o all time, because the
 variables all point to the same answer:
answer: alse.
But or every nutrition and diet related issue, there is
someone on both sides, who staunchly opposes any
 view that conflicts with their own. A large number
number o
people avoid animal products because they’re sure
o the unhealthiness o eating meat or drinking milk.
Some people are low-carb evangelists, and they’ll tell
anyone willing to listen that they’d
they’d be healthier i they
cut out a large chunk o their carb intake. Tese strong
positions don’t
don’t just apply to animal products and carbs
though, there are also people with strong positions on
either side o GMOs, saturated
s aturated at, and pretty much
everything else you can imagine.
People who read research all day long tend to not have
extremely strong views on any particular issue. And
that’s because o three distinct reasons. First, there is
decent research on both sides o many controversial
controversial
issues. Second, research is an ongoing process, given
that our whole field is based on the scientific meth-
od (which is iterative by nature). Tird, “published
research” does not equal “act”. Much o the published
literature has important methodological flaws. And due
to the controlled nature o research, it won’
won’tt ever cap-
ture the ull spectrum o human effects, especially given
the relative lack o unding or certain
cer tain topics.
I’ll take back the first sentence o the last paragraph. I
do have a strong view on nutrition research. And that is
this: there are more unknowns than knowns, and any-
body who pretends otherwise is automatically suspect.
 Kamal Patel, Editor-in-Chief 
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Contributors
Researchers

Margaret Wertheim Alex Leaf  Courtney Silverthorn Zach Bohannan Anders Nedergaard Jeff Rothschild
M.S., RD M.S. Ph.D. M.S. Ph.D. M.Sc., RD

Greg Palcziewski James Graham

Ph.D. Ph.D.
Editors

Gregory Lopez Pablo Sanchez Soria Kamal Patel

Pharm.D. Ph.D. M.B.A., M.P.H.,
Reviewers Ph.D(c)

Arya Sharma Natalie Muth Stephan Guyenet Sarah Ballantyne Katherine Rizzone Mark Kern
Ph.D., M.D. M.D., M.P.H., RD Ph.D. Ph.D. M.D. Ph.D., RD

Gillian Mandich Adel Moussa

Ph.D(c) Ph.D(c)
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The high cost of high

heat cooking
Oral AGE restriction ameliorates insulin
resistance in obese individuals with the
metabolic syndrome: a randomized
controlled trial.

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Introduction Although the accuracy o AGE measurement is debat-

ed within the scientific community, the largest study to
Advanced glycation end products (AGEs) are highly
date to
date to investigate the AGE content o ood showed that
reactive compounds that result rom a chemical reac-
AGE content
content is highly dependent
dep endent both on the ood itsel
tion between reducing sugars and amino acids (also
and the preparation method used. Although high at,
known as a Maillard reaction) and rom the oxidation
high protein oods generally had higher levels o AGEs
o sugars, lipids, and amino acids. Although the or-
compared to oods high in carbohydrate, there was
mation o AGEs within the body is a part o normal
metabolism, a growing 
growing body o  evidence
evidence suggests
 suggests that considerable variability.
variability. By contrast, harsher cooking
methods such as rying, broiling, grilling, and roasting
excessive AGE levels promote oxidative stress and
consistently led to higher AGE levels than gentler cook-
inflammation and may thereore increase the risk o
ing methods such as boiling, poaching, stewing, and
developing type 2 diabetes, cardiovascular disease, atty
steaming, suggesting that high-heat and dry heat cook-
liver, cancer, Alzheimer’s disease, and inertility.
ing lead to higher AGE levels. Some specific levels are
shown in Figure 1.
AGEs were first recognized as being produced with-
in the body under conditions o increased oxidative
A handul o short-term clinical trials have shown that
stress. However,
However, it is now known that dietary
d ietary AGEs are
restricting dietary AGEs results in reduced inflamma-
important contributo
contributors
rs to
 to the
t he body’s total AGE con-
tion and increased insulin sensitivity
s ensitivity among patients
patients  
centration, where they become indistinguishable rom
indistinguishable rom with  type 2 diabetes
with diabetes,, overweight women,
women, and healthy
those AGEs produced within the body itsel. Te most
adults.. Moreover,
adults Moreover, among individuals with
w ith obesity and
widely studied AGE is carboxymethyllysine (CML),
the metabolic syndrome, both dietary and serum AGEs
while another common marker o AGE ormation is
have been significantly correlated
correlated with
 with insulin resis-
methyl-glyoxal (MG).
tance, oxidative stress, and inflammation. However, no
long-term trials have been conducted.

 
Figure 1: Carboxymethyllysine
Carboxymethyllysine content of chicken breast by cooking technique
Harsh techniques Values in AGE kU/100g Gentle techniques

General cooking principles

Deep-fried Broiled Microwaved Boiled

High heat Moisture

9,722 5,828 1,524 1,210

Pan-fried Grilled Acids (lemon, Poached Steamed

Oil
vinegar)

4,938 4,849 1,07 1,058

 
 Reference: Uribarri, J, et al. J Am Diet Assoc. 2010 Jun

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Te study under review was designed to test whether

prolonged (one year) dietary AGE restriction could
improve insulin resistance and other risk actors or
type 2 diabetes in people with metabolic syndrome.
Advanced glycation end products (AGEs) are produced
both within the body and during the cooking and pro-
cessing o ood. Dietary AGEs contribute
contribute to the body’
body ’s
total AGE concentration. Excessive amounts promote
oxidative stress and inflammation. Short-term clinical
trials show that reducing dietary AGEs improves insu
insu--
lin sensitivity and reduces inflammation.
inflammation. Te current
study sought to test i these observations would be
apparent over the long term (one year).
Who and what was studied?
Tis was a randomized controlled trial involving 138
adults age 50 years or older who had at least two o
five criteria or metabolic syndrome, as defined by  
the National Cholesterol Education Program Adult
reatment Panel III. Criteria includes an obese waist
circumerence, high blood pressure, low HDL choles-
terol, high triglycerides, and high asting blood glucose.
However,, none o the participants
However part icipants had type 2 diabetes
di abetes
or kidney disease.
Participants were randomly assigned to ollow a
low-AGE diet or their usual diet or one year under
ree-living conditions. A sample day o one partici-
pant’s low-AGE diet is shown in able 1. Te low-AGE

Table 1: Sample daily diet in the low-AGE group

Meal Baseline high AGE diet Intervention L-AGE diet
Item Portion AGEs* Item Portion AGEs*
Fresh ruit cup 0.12 | (½ cup) 15 Fresh ruit cup 0.12 | (½ cup) 15
Fried eggs 1 1200 Boiled egg 1 75
Toasted bagel 112 g 200 Fresh bagel 112 g 120
Cream cheese 5 ml 500 Cream cheese 5 ml 500
Skimmed milk 240 ml 2 Skimmed milk 240 ml 2
Coffee 240 ml 19 Coffee 240 ml 19
Orange juice 120 m l 3 Orange juice 120 ml 3
Breakast
Grilled chicken breast 84 g 5200 Poached chicken breast 84 g 1000
Green salad 0.24 | (1 cup) 0 Green salad 0.24 | (1 cup) 0
Caesar dressing 30 m l 200 Caesar dressing 30 m l 200
Bread, white 1 slide 10 Bread, white 1 slice 10
Margarine 5 ml 900 Margarine 5 ml 900
Iced tea 360 ml 5 Iced tea 360 ml 5
Apple 1 medium 15 Apple 1 medium 15
Cantaloupe wedge ¼ small 20 Cantaloupe wedge ¼ small 20
Grilled steak 84 g 6600 Bee stew 84 g 2200
Masged Potato 1 20 Mashed Potato 1 20
Dinner
Carrots 0.12 | (½cup) 10 Carrots 0.12 | (½cup) 10
Coffee with milk 240 ml 5 Coffee with milk 240 ml 5

Muffin, bran 1 102 Muffin, bran 1 102

Total AGEs 15, 026 5,221

Total energy, kJ/day 7.94 7.77

* Reproduced from original paper, Table 1

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group received instructions on reducing dietary

dietar y AGEs
through modiying cooking time and temperature
What were the findings?
O the 138 adults who began the study, 100 finished it
without changing the amount or type o ood being
and were included in the final analysis. Te number o
eaten. Tey were instructed to avoid rying, baking, or
dropouts was higher in the low-AGE group (n=25) com-
grilling, and encouraged to boil, poach, stew, or steam
pared to the control (n=12), but no test was perormed
their ood. Participants met with a dietitian every three
to evaluate whether this was statistically significant.
months and were contacted twice per week via tele-

phone to promote dietary compliance. At baseline, the low-AGE group had a significantly low-
er BMI (31.2 vs. 33.3), waist circumerence (106.3 110.4
esting was perormed at baseline and afer the one-
cm), and serum VCAM1 (-15%) than the control group,
year intervention. Te primary outcome was a change
with trends towards significance (all p<0.08) or lower
in HOMA-IR, which is an indirect measure o insulin
bodyweight (84.8 vs. 90.7 kilograms), calorie intake
resistance.. Secondary outcomes
resistance outcomes included metabolic syn-
(-9%), and higher HbA1c (6.0% vs. 5.8%). Tereore,
drome criteria (blood pressure
pressure,, anthropometrics, asting
the groups were not evenly distributed when
w hen the study
glucose, triglycerides, and HDL-c), other type 2 diabetes
began, and there is a possibility that these differences
risk actors (asting insulin, two-hour glucose tolerance
may have influenced the results.
test, and HbA1c), MRI measuremen
measurements
ts (visceral at, sub-
cutaneous at, and carotid wall thickness—a predictor
predictor  
o cardiovascular events), CML and MG concentrations Tree-day ood logs as well as blood and urinary analyses
revealed that the low-AGE intervention was successul
(dietary, serum, intracellular,
intracellular, and urinary), inflamma-
at reducing dietary, serum, and urinary AGE concen-
tory and oxidative
oxidative markers (8-isoprostanes,
(8-isoprostanes, VCAM1,
trations. Compared to the control group, the low-AGE
NF-α, and RAGE), and anti-inflammatory/oxidative
group consumed 65% less dietary AGEs and had approx-
markers (SIR1, AGER1, GLO1, and adiponectin).
imately 40% less serum AGEs, 35-40% less intracellular
AGEs, and 40-50% less urinary excretion o AGEs.
Tis study also had a test tube component, during
which peripheral blood mononuclea
mononuclearr cells (PMNCs)
Both groups significantly reduced caloric intake, but
were collected rom the participants
p articipants beore and afer
the reduction was significantly greater in the low-AGE
the intervention. Tese cells were analyzed or inflam-
matory markers and insulin sensitivity.
sensitivity. group by about 200 kcal per day.
day. As would thereore be
reasonably expected, the low-AGE group also lost sig-
nificantly more bodyweight than the control group (1.4
A group o older (50+ years) adults with metabolic  vs. 0.4 kilograms).
syndrome were randomly assigned to continue with
their usual diet or to use gentler cooking methods in Figure 2 shows some o the main study results.
ood preparation (boil, poach, stew or steam rather Although both groups started the study with similar
than ry, bake, or grill)
gri ll) or one year. Insulin resis- HOMA-IR,
HOMA-IR, the low-AGE group experienced a signi-
tance was assessed beore and afer the intervention. icant 53% reduction in HOMA-IR compared to the
est tube studies were used to determine
d etermine the cellular control group, which remained statistically significant
effects o dietary AGE restriction. afer adjusting or baseline BMI, age, sex, race, and
dietary intake o calories, protein, carbohydrate, and
at. Moreover, the improvement in HOMA-IR was
observed among the 12 participants in the low-AGE

8
 

Figure 2: Changes in insulin resistance

resistance markers and serum CML
HOMA-IR Fasting plasma insulin (pmol/l)

4 120
113.2
3.6 90 95.8 93.8
3 3.1
2.9
60
60.4
2
1.9 30

1
Responsible
change in for 0
Month 0 Month 12 Month 0 Month 12

Fasting plasma glucose (mmol/l) Serum carboxymethyllysine (U/ml)

6 24
23
5.1 4.9
4.5 4.9 4.8 18
17 17
3 12 13

1.5 6

0 0

Month 0 Month 12 Month 0 Month 12

Reg-AGE diet Low-AGE diet

group that didn’t

didn’t lose weight (they actually signifi- were influenced by the presence o a SIR1 activator
cantly gained two kilograms), suggesting weight loss and inhibitor,
inhibitor, suggesting that
t hat SIR1 may play a role in
alone could not explain the finding. o put this reduc- modiying inflammation within the low-AGE group.
tion o HOMA-IR into perspective, the 53% reduction
corresponds
corresponds to
 to about a 50% reduction in the odds o
Consuming an AGE-restricted diet or one year led
le d
experiencing atal cardiovascular diseases, even afer
to significant reductions in HOMA-IR and numerous
adjusting or other metabolic syndrome criteria and
markers o inflammation and oxidative stress with-
liestyle actors.
out affecting other metabolic syndrome criteria. est
est
tube studies supported these findings.
Tere were no significant differences between groups
or any metabolic syndrome criteria or MRI variables.
However,, the low-AGE group did experience significant
However
improvements
improvements in every
ever y variable related to inflammation What does the study really
and oxidative stress compared to the control group. tell us?
Te current study is the longest randomized controlled
Tese results were supported by the test tube studies, trial to date that shows that reducing dietary AGE
which showed that the PMNCs rom
 rom the low-AGE consumption leads to a reduction in insulin resistance
group displayed significantly lower NF-α concentra- among individuals with metabolic syndrome, possibly
tions and significantly greater insulin sensitivity than through reducing inflammation and oxidative stress.
the control group. Additionally, NF-α concentrations

9

Since the participants were ree-living individuals
instructed only to change how they cook their ood,
this finding has important practical consequences.
Te average dietary AGE intake o healthy adults
rom the New York City area was ound to be 14,700
be 14,700
kilounits. Moreover,
Moreover, higher dietary intake o AGEs was
significantly correlated with a higher serum
s erum AGE level,
which in turn was significantly correlated with HOMA-
IR and plasma 8-isoprostane,
8-is oprostane, a marker o oxidative
stress. Dietary AGE consumption was also significantly
sig nificantly
related to higher CRP levels, a marker o inflammation.
Tereore, the finding in the study at hand that reducing
dietary AGEs leads to reduced serum AGE levels and
insulin resistance, possibly through reducing inflamma-
tion and oxidative stress, has a logical basis.
At baseline, the participants in both groups were con-
suming about 18,000 kilounits o AGEs per day.
day. Tis
was significantly reduced to 7,000 kilounits in the
low-AGE group, which was accompanied by a reduc-
The current study is the longest
randomized controlled trial to date
that shows that reducing dietary AGE
consumption leads to a reduction in
insulin resistance
resistance among individuals
with metabolic syndrome, possibly
through reducing inlammation and
oxidative stress.
tion in insulin resistance. However,
However, caloric intake and
bodyweight also significantly decreased, the impact o
which on insulin resistance is uncertain. Still, chang-
es in insulin resistance were independent o BMI and
calorie and nutrient consumption. Moreover,
Moreover, signifi-
cant improvements
improvements were still observed
obser ved in the low-AGE
participants who did not lose bodyweight.
bo dyweight. ogether,
ogether,
these findings strongly support the notion that it was
the reduction in dietary AGEs that led to the reduction
in insulin resistance.
Even so, other metabolic syndrome criteria were not
significantly affected when compared to the con-
trol group. Te reduction in HOMA-IR was large
enough to result in 80% o the low-AGE participants
no longer being classified as insulin resistant based
on their HOMA-IR value. Yet,
Yet, there were no signi-
icant between-group differences in asting glucose,
triglycerides, HDL-c, blood pressure, or HbA1c. Tis
trial lasted one year,
year, so it is unlikely that a longer dura-
tion would lead to changes not observed
obser ved in this study.
study.
10

Rather, it could be that the study was underpowered
under powered to
detect significant differences between the low-AGE and
control groups, especially considering that these were
not primary endpoints. Tis is supported by the act
that many o these variables significantly improved over
time in the low-AGE group but not the control group.
Te idea that dietary AGEs work through inflam-
mation and oxidative stress was supported by this
study.. Plasma 8-isoprostane and VCAM-1, a protein
study
expressed in blood vessels in response to inflammation,
were significantly reduced in the low-AGE group com-
pared to the control. And the test tube studies noted
a reduction in NF-α, an inflammatory molecule, o
cells isolated rom the participants. Additionally, the
low-AGE group experienced significant increases in the
gene expression o SIR1, a regulator o metabolism 
metabolism 
with beneficial effects on insulin sensitivity,
sensitivity, AGER1
(shown in Figure 3), an AGE receptor that neutraliz-
es the AGEs it binds, and GLO1, an AGE degrading
enzyme, while the expression o RAGE, a pro-inflam-
matory molecule,
molecule, was reduced.
Despite the finding that dietary AGE restriction reduc-
es insulin resistance, this study doesn’t tell us whether
dietary AGE restriction would actually impact the
Figure 3: AGER1 protects SIRT1 from AGEs
Low AGE diet
AGER1 restored
Adiponectin
SIRT1
Inflammation
Reference: Cai, W, eett al. Proc Natl Acad Sci U S A. 2012 Sep | Vlassara,
development o type 2 diabetes or related complications,
such as cardiovascular disease.
d isease. Additionally
Additionally,, while
HOMA-IR
HOMA-IR does generally provide an accurate mea-
sure o
sure o insulin resistance, it is not the gold-standard
hyperinsulinemic-euglycemic clamp technique. Tis is
problematic because HOMA-IR relies on asting insu-
lin and glucose values, meaning that something which
affects either could change HOMA-IR without actually
impacting insulin sensitivity. Still, a study  using
 using the
gold-standard hyperinsulinemic-euglycemic clamp in
healthy overweight and obese adults did find that insu-
lin sensitivity increases afer ollowing a low-AGE diet.
Finally,, the use o individuals with metabolic syndrome
Finally
precludes generalizations to healthy
hea lthy populations about
the impact that dietary AGE restriction would have.
Dietary restriction o AGEs through modiying
cooking methods appears to be a easible long-term
method to reduce insulin resistance in people with
metabolic syndrome. Tese effects appear to be
mediated through reductions in inflammation and
oxidative stress. Whether these benefits
b enefits translate
into actual reduced risk o developing type 2 diabetes
remains to be determined.
High AGE diet
AGER1 depleted
Oxidative stress
Insulin Adiponectin Insulin
signaling SIRT1 signaling
Inflammation
  H, Striker, G. Nat Rev Endocrinol. 2011 May
11
 

The big picture Te study under review serves as a gentle reminder that
there is more to nutrition than nutrients or ood. Recent
Several past issues o the
t he ERD have discussed reduc-
years have greatly shifed the ocus rom the ormer to
tionism in nutritional science and how ocusing on
the latter, and perhaps now it is time to consider both in
nutrients
nutrients rather than oods misses part o the nutrition
combination with how ood is prepared and eaten.
puzzle because the ood itsel impacts the health effect o
some nutrients. Te current study points to yet another
layer that cannot be overlooked: how ood is prepared. Nutrition isn’t
isn’t just about specific oods or their
nutrients, but also about how these oods are pre-
Te study at hand, along with others, shows that
t hat mod- pared to be eaten. Clearly how we cook certain oods
iying cooking techniques can have a proound impact impacts their health effects, and this adds a new layer
on health. Yet,
Yet, this variable is almost never addressed in o understanding to nutrition research.
clinical or observational research.
rese arch. It raises many ques-
tions about current associations (or lack o) between
oods and health outcomes. For instance, the consump-
Frequently asked questions
tion o red meat and its relationship to disease is a
What is a maillard reaction?  
controversial topic. Tere is strong and consistent evi-
A maillard reaction is a non-enzymatic reaction
dence linking processed meats to poor health outcomes,
between reducing sugars and amino acids. A reduc-
but the associations with unprocessed red meats are less ing sugar is one that reduces another compound and
clear-cut. What would happen i red meat was urther
ur ther
is itsel oxidized, meaning that it “takes”
“takes” an oxygen
categorized by how it was prepared?
atom rom another molecule (in this case, an amino
acid). Tese sugars include glucose, ructose, galactose,
Similarly,, how can findings rom one population be
Similarly
mannose, ribose, and some intermediates o energy
extrapolated to another when the type o cooking tech-
metabolism. O the reactive amino acids, lysine, argi-
niques used to make the ood they eat may be vastly
nine, and sulur-containing amino acids are particularly  
different? A recent review article addressed
article addressed this very
 vulnerable to
 vulnerable to being reduced.
problem, when the authors argued that the benefits o
a Mediterranean diet may not be owed entirely to the While the study under review shows that excessive

oods being eaten, but also to how the oods are pre- levels o dietary AGEs may be harmul to health, the
pared and consumed.
maillard reaction plays an important role in ood
o od pro-

  Nutrition isn’t just about speciic

oods or their nutrients, but also
about how these oods are prep
prepared
ared
to be eaten.
12
 

cessing by imparting both color and flavor to cooked
oods. Tis reaction is literally responsible or the
golden brown color o bread crust and toast or the
browning o red meat during cooking. As such, anyone
consuming cooked ood in the diet will consume some
maillard reaction products, such as AGEs.
baking, or broiling, have been ound to
ound to produce acryl-
amide, while boiling and microwaving appear less likely
to do so. However, longer cooking times actually reduce
acrylamide production when the cooking temperature
is above 200 degrees Celsius (390 degrees Fahrenheit)
due to greater degradation processes. Similarly, adding
other protein sources or amino acids (such as cooking

What are other harmful compounds produced during alongside meat) and increasing the acidity (like marinat-
cooking, aside from AGEs?   ing with vinegar) reduce acrylamide levels.
Aside rom AGEs, meats may contain several other
potentially harmul compounds, depending on how they When considered alongside the current study
study,, there is
are cooked. Processed meats usually have some orm a strong evidence base supporting a potential health
o nitrite added as a preservative, be it rom a salt
s alt such benefit o reducing consumption o processed meats
as sodium nitrite or rom the “natural” celery powder. (which tend to contain all o these harmul compounds)
When exposed to high heat,
heat, these potentially beneficial 
beneficial  and cooking unprocessed meats gently or shorter peri-
carcinogenic  nitrosamines
nitrites are transormed into carcinogenic nitrosamines.. ods o time.

Polycyclic aromatic hydrocarbons (PAHs) are anoth-

er group o carcinogenic compounds
compounds that
 that orm when What should I know?
Advanced glycation end products (AGEs) are natu-
organic matter burns, such as the burning o wood or
rally occurring compounds ormed within the body
charcoal or the burning (oops) o your dinner. Tey
and ound in most oods, with greater amounts being
can be created in ood directly when burned and also
ormed in meat that is cooked with more harsh meth-
transerred to ood through the smoke that orms rom
ods such as rying, baking, and grilling rather than
cooking over an open flame. For this reason, smoked
more gentle methods such as boiling, poaching, stew-
high in
oods are high  in PAHs.
ing, and steaming.

Heterocyclic amines (HCAs) are a third class o car-

Evidence suggests that dietary AGEs contribute
contribute substan-
cinogenic compounds that
compounds that orm when meat is cooked
on a high temperature, such as during rying or grill- tially to the body’s total AGE pool, and that an excessive
AGE pool causes oxidative stress and insulin resistance.
ing. Generally speaking, well-done and very well-done
Te current study shows that restricting dietary AGE
meats will contain higher levels o
levels o HCAs than less
consumption
consumption through using gentler cooking methods
cooked and more gently cooked meats.
does result in significant reductions in insulin resistance
among individuals with metabolic syndrome. Since the
Acrylamide is yet another potentially harmul com-
participants were ree-living individuals instructed only
pound (carcinogenic
pound  (carcinogenic and neuro, reproductive, and
to change how they cook their oods, this finding has
genotoxic) that is commonly used in the production o
important practical implications.
implications. ◆
paper, dyes, and plastics (including ood packaging). It is
produced rom maillard reactions involving the amino

acid asparagine, which is ound in high concentrations 

concentrations  Te debate on dietary AGEs is really starting to heat
among many plants such as potatoes and cereal grains. up. So put down the hot dog, and head to the Facebook
High-temperature
High-temperature cooking methods, such as rying, ERD orum.
orum.

13
 

INTERVIEW:
Courtney Silverthorn, PhD
Dr. Courtney Silverthorn is the Deputy Director o the Technology Partnerships Office
at the National Institute o Standards and Technology
Technology (NIST) in the Department
o Commerce, ocusing on the coordination o cross-agency technology trans-
er policy and overseeing economic analysis o the impact o ederal research &
development investment. She works with a number o interage
interagency
ncy working groups,
serves as the Host Agency Representative on the Executive Board o the Federal
Laboratory Consortium, and is the Executive Secretariat or the National Science
and Technology Council’s Lab-to-Market subcommittee. Prior to coming to NIST NIST,,
she held tech transer and partnership development roles at the Frederick National
Laboratory or Cancer Research and the National Cancer
C ancer Institute.

Some (or most?) of our readers probably don’t know much about tech transfer. Can you give us an
overview, and tell us how you came into your current position?  
I don’t
don’t think I knew what tech transer was
w as until my last year o grad
g rad school, but it’s
it’s turned out to
be an extremely ascinating career. Te ederal government spends about $140B a year on
year on scientific
research and development. About
About two-thirds o that
t hat money goes out to universities, small business-
es, and other organizations through grants and contracts. Te rest gets spent at approximately 350
ederal laboratories across the country - what we reer to as ‘intramural’ research. Sometimes those
government scientists invent things - but the government isn’t
isn’t going to manuacture products or sell
things to the public. So we rely on tech transer proessionals at the labs to help find partners to devel-
op the technology, sometimes in collaboration with the government or sometimes through
t hrough a license,
and eventually bring a new drug or battery technology or other invention to the market.

I was looking or alternatives to lab science as I was wrapping up my PhD, and stumbled into tech
transer at a career services workshop. My postdoctoral ellowship was actually in a tech transer
office at the National Cancer Institute, where I worked directly with the scientists
s cientists on their inven-
tions and collaborations. I later had the opportunity to move into a tech transer policy position
p osition at
the National Institute o Standards and echnology,
echnology, where I’ve been or almost three years. So
S o now I
can assist the entire ederal government on ways to make their tech transer efforts better - through

14

sharing best practices, writing
wr iting regulations, developing
interagency tools, and overseeing economic research on
the impacts o our efforts.
You’re starting school yet again soon. Which begs the
question ... why??
A ew people do wonder i I’m crazy! I’ve just started
a program, which is offered through a partnership
between Washington
Washington University in St. Louis and Te
Brookings Institution, a nonpartisan think tank in
DC. Te program is designed or higher level govern-
ment employees who want to transition into the Senior
Executive Service (SES), and the course material covers
all o the Office o Personnel Management’s Executive
Core Qualifications. All o my previous degrees have
been in hard sciences, but most o my day job now is in
‘sof skills’
skills’ - so the opportunity to have ormal training
and education in the skills I’m actually using now was
 very attractive to me.
What I really liked about this program is that, unlike
individual agency SES prep classes, I would be exposed
to agencies rom all over the ederal government, which
is really important or my role in tech transer policy. I’m
also able (required!) to start implementing the skills I’m
learning in my current position - so or example, afer
a course on Strategic Tinking, I wrote about using the
processes we learned in the class or our 2017 budget plan.
In my brief contract work with the federal government,
there seemed to be a lot of pros and a lot cons. Like
the work is very impactful for public health, but oh my
 goodness the
the bureaucracy!
bureaucracy! Can
Can you tell us more a
about
bout
how things work over there in DC?   scientific conerences and meetings. Tis really became
Government bureaucracy can be a real hurdle, but
sometimes it’s actually harder or the government to
work internally than it is or us to work with outside
partners. A lot o issues can arise when agencies have
different legislation that applies to them, and/or di-
erent policies in how they interpret that legislation
internally. One o my projects last year was developing a
“tech transer playbook” collecting agency best practices
and compiling them into an online ormat, so that other
agencies had inormation to provide to their internal
legal and policy people when
w hen they ran into pushback
while trying to implement new programs and initiatives.
initiatives.
Having something to point to that says another agency
is doing something can be very powerul.
Tere are a lot o rules,
r ules, and it’s
it’s sometimes easier or
people to say “no”
“no” to something than to find a way to
make it work. Te more we can streamline things, the
better! But at the same time, to some extent the gov-
ernment is slow and reluctant to change by design. It
would be a real challenge to the public and to business-
es i they had completely new rules and regulations to
try to comply with all the time - they’d
they’d never get any-
thing else done. My experience has been that i you can
find the person in any agency who understands what
they can do and how to do it, you can ultimately get
things done.
 Along those
those lines, if you were
were granted three wishes
wishes for
things to change on the federal level, what would you
change?
Te first thing I’d
I’d like to see changed is increased und-
ing or scientific research and development across the
ederal government. $140B sounds like a lot, but as a
GDP and as a percentage o our total
percentage o our GDP and
ederal budget it’s
budget it’s at an all-time low. We are at a real risk
o alling behind other nations as a scientific leader.
Te second thing on my list would be an easing o trav-
el restrictions or government proessionals to attend
an issue a ew years ago with a ew isolated, high-profile
incidents and the spillover into the scientific communi-
ty was incredibly ar-reaching. Government scientists
weren’t
weren’t able to travel to conerences and meetings in
order to present their work, which really hurt both the
science and the tech transer efforts - most agencies
have small to non-existent marketing budgets, so scien-
15
 

tists interacting with their industry counterparts is one
o our best ways to talk about our technologies and find
potential partners.
And the third thing, which is a bit more general, is that
i I’ve learned anything rom
 rom my policy classes it’s
it’s that
gerrymandering has ruined our political system and
degrees in the sciences stay
sciences stay in academic research. It’s
It’s a
tough field to compete or jobs, compete or tenure, and
compete or dwindling ederal grant dollars. Te people
who I know who have been successul at it truly
tr uly,, com-
pletely love what they do and love ocusing on a single
aspect o a single scientific area. But i that ends up not
being you, it’s okay!

made it even more challenging or the government to

get things done. I’m encouraged by some recent efforts
at the state level to have non-partisan committees lead
redistricting efforts, and I’m hoping
hoping more states will
come on board with the idea.
Wow, nice use of “gerrymandering”! How do you bal-
ance a busy job with other commitments, and continued
Toga. 
learning? I have a feeling the answer rhymes with Toga.  existential crisis (speaking rom experience here…) to
oga yoga? For real though,
t hough, having a yoga practice is
a huge help to keeping my sanity. It’s pretty much the
only time in my day where my brain shuts up. I also
run, but tend to have long involved conversations
conversations with
mysel while running - so it’s
it’s nowhere as mentally
relaxing as a yoga practice. In terms o staying orga-
nized, I have detailed, color-coded Google and Outlook
calendars and I make a LO o lists.
For readers with a science degree who are wavering
between pursuing lab work or alternatives, do you have
any advice?
Know that only about 40% o people with advanced
Tere are so many different opportunities available to
use a science degree and I think that graduate schools
are really starting to come around to this act and are
doing a better job o providing inormation about
“alternative
“alternative”” careers in the sciences - which is almost
a misnomer now that they’re the majority o gradu-
ates. It does take a bit o soul-searching,
s oul-searching, and maybe an
figure out what you love doing. ake advantage o any
inormation you can get your hands on, take advantage
o your network connections, and ask people what they
love about their careers in lab work or in another pur-
suit. I afer all that you’re
you’re still not sure - take the lab job.
It
It’’s ar easier to move rom the bench to an office than
to go the other direction. ◆
(Required disclaimer: Te author contributed to this
article in her personal capacity. Te views and opinions
expressed in this article are those of the author, and do not
represent the views and opinions of NIS, the Department
of Commerce, or the United States Government.)

Dr. Silverthorn earned a Ph.D. in Pharmacology rom the Johns Hopkins University School o
Medicine and a B.S. in Biochemistry and Molecular Biology rom Sweet Briar College. She also
has certiicates in Biotechnology Enterprise rom Johns Hopkins and in Policy Strategy rom the
Brookings Institution, and is pursuing a Masters in Public Leadership rom Washington University
in St. Louis. Courtney is a RYT
RYT-200
-200 vinyasa yoga teacher in Northern Virginia and
a nd has written or
the Examine.com Research Digest since November o 2014.20 14.

16
 

Does being insulin

resistant affect weight
loss on a low-fat or
low-carb diet?
loss, 
Effects of diet composition on weight loss, 
metabolic factors and biomarkers in a
1-year weight loss intervention in obese
women examined by baseline insulin
resistance status

17
 

Introduction Still, the question remains as to what

Obesity has recently been called a
called a “single house or
many evils” based on evidence that it increases the risk
or numerous comorbidities, including cardiovascular
disease, cancer, and diabetes. One proposed explana-
tion or
tion  or the link between obesity and other metabolic
diseases is that obesity leads to chronic inflammation in
some people, which in turn leads to a dysregulation o
insulin signaling, also known as insulin resistance.
w hat the optimal mac-
ronutrient distribution or a weight loss diet is. wo
previous short-term
short-term  studies
studies have
 have suggested that insulin
resistance may predict which macronutrient distribu-
tion is most beneficial. Specifically,
Specifically, these two studies
showed that insulin resistant individuals lose more
weight on a low-carbohydrate diet, as opposed to a low-
at diet. However, a more recent study  with
 with a stronger
methodological design did not support these findings.

Aside rom macronutrients, the actual oods includ-

Insulin resistance has widespread effects on health
hea lth
ed in the diet may influence weight loss. For instance,
and is the hallmark  o
 o metabolic syndrome and type 2
“Blast rom the past: a paleo solution or type 2 dia-
diabetes. Weight
Weight loss is a well-established met
method
hod o
betes” rom ERD #8 explored a study that compared
restoring insulin sensitivity among people with obesity
two diets o equal calorie and macronutrient content,
and insulin resistance. Several trials
tr ials have shown that
with the difference being what oods supplied them.
 very low-calorie diets
diets and
 and rapid weight loss are able to
One group ate an American Dietetic Association diet
restore insulin sensitivity  and
 and possibly even reverse type 
type 
while the other ate a Paleo diet. Although both groups
2 diabetes.
diabetes. O course, a very-low calorie diet (less than lost a similar amount o weight and showed similar
1000 calories) is not sustainable over the long term.
improvements
improvements in insulin sensitivity (again suggesting
that weight loss is the most important), the paleo group
Under more modest levels o caloric restriction,
restr iction, weight
showed superior benefits or changes in blood lipids
loss is achievable with a variety o macronutrient (pro-
and glycemic control.
tein, carbohydrate, and at) intakes. Tis was discussed
in “Te best diet is the one you can stick to” in the first
In this regard, walnuts may be o interest because o
issue o the ERD, where 11 popular
p opular name-brand diets
their ability to reduce inflammatory
reduce inflammatory markers and blood
were compared or their ability to produce weight loss
lipids without significantly affecting weight,
weig ht, despite
among individuals with obesity. Te results showed that
t hat
contributing a substantial number o calories to the
while there were some differences between diets, overall diet. And more directly, walnuts may also be o interest
any diet was better than no diet at all.

Several trials have shown that very

low-calorie diets and rapid weight loss
are able to restore insulin sensitivity and
possibly even reverse type 2 diabetes.
18

because the study under review was partially unded by
the Caliornia Walnut Commission. Nonetheless, long-
term walnut trials are still necessary to investigate i the
previously identified benefits are merely transient.
Te current study sought to examine the effect o three
diets (low-carb, low-carb plus walnuts, or high-carb) on
weight loss and other markers o health in overweight
or obese women over a one-year period and determine
whether baseline insulin resistance influenced the effec-
tiveness o the interventions.
Obesity greatly increases the probability o suffer-
ing rom insulin resistance, which in turn serves
as a hallmark o metabolic syndrome and type 2
diabetes. Weight
Weight loss is known to restore insulin
sensitivity,, but the optimal macronutrient distribu-
sensitivity
tion o a weight loss diet has not been established.
Certain oods, such as walnuts, may also have a ben-
eficial impact on health. Te current study sought to
compare three diets differing in macronutrient com-
position and the amount o walnuts in the diet on
their ability to produce weight loss over a one-year
intervention. Tis study also investigated whether
baseline insulin resistance influenced any outcomes.
Figure 1: Diet Composition
High-Carb
15%
20% 56%
Protein
All diet prescriptions limited saturated fat
Who and what was studied?
Tis was a randomized, open-label (non-blinded)
controlled trial in which 245 women were instructed
to ollow one o three dietary
dietar y interventions or one
year,, which are broken down in Figure 1. Te dietar
year dietaryy
interventions were a high-carbohydrate diet (65%
carbohydrate, 20% at, and 15%
15 % protein), a lower-car-
bohydrate diet (45% carbohydrate, 35% at, and 20%
protein), and a lower-carbohydrate diet that included
walnuts (1.5 ounces or 42 grams per day).
Te participants varied widely in age, with a range o
22-72 years and average o 50 years. Te majority o the
women had obesity, as the BMI range was 27-40 with
an average o 33.5. Roughly hal o the participants
were classified as insulin resistant (HOMA-IR o more
than 3), although none o the women had type 2 dia-
betes. Importantly,
Importantly, the participants
p articipants were stratified by
menopausal status and insulin resistance status beore
randomization so that an even number o pre-/post-
menopausal and insulin resistant/sensitive participants
would ollow each diet.
Te participants were ree-living throughout
t hroughout the inter-
 vention and initially provided
provided with a detailed diet
prescription and sample meal plans during an individu-
Lower-Carb Lower-Carb + Walnuts
20% 20%
45% 45%
35%
35%
Fat Carbs
19
 

al counseling session with a dietitian.

d ietitian. Additionally,
Additionally, the All outcomes were assessed at baseline, six months, and
participants were encouraged to use web-based ood one year. Te data or changes at six months was pub-
tracking programs to ensure proper dietary intake and lished previously . In the current study, weight loss was
were provided with a scale,
sca le, pedometer, measuring cups, the primary outcome, with markers o insulin sensitiv-
and exercise videos to acilitate
 acilitate compliance.
compliance. ity and glycemic control (asting glucose and insulin,
HOMA-IR,
HOMA-IR, and HOMA-β), blood lipids (LDL-c,
Te participants had weekly group-based behavioral HDL-c, and triglycerides), inflammatory markers (CRP

meetings or the first our months, biweekly or the next and IL-6), and hormones [estradiol and sex hormone
two months, and monthly thereafer.
thereafer. Tey also had binding globulin (SHBG)] being o secondary interest.
unlimited telephone and email contact with the group
g roup
leaders, who had backgrounds in health science.
Healthy women with obesity were randomly
assigned to ollow a high-carbohydrate diet (65%
Te overall goal o the dietary guidance was to pro-
carbohydrate, 20% at, and 15% protein), a lower-car-
mote a 500-1000 calorie per day reduction in energy
bohydrate diet (45% carbohydrate, 35% at, and 20%
intake using individualized diet plans. Participants in
protein), or a lower-carbohydrate diet that included
the walnut group were also instructed to consume 1.5
walnuts (1.5 ounces or 42 grams per day) or one
ounces (42 grams) o walnuts daily,
daily, and these individu-
 year. Te main outcome o
o interest was weight loss,
als were provided with walnuts at two-week intervals to
with secondary outcomes being changes in insulin
acilitate compliance. Te other groups were instructed
sensitivity and glycemic control, blood lipids, inflam-
to exclude nuts. All participants were also encouraged
matory markers, and hormones.
to aim or an average o at least 60 minutes per day o
moderate-intensity exercise.

  [...] the walnut group experienced

signiicantly greater increases
increases in the
linoleic acid and alpha-linoleic acid
content
cont ent o their serum phospholipids
than the other two groups, indicating
strong compliance
compliance with the walnut
intervention.
20
 

What were the findings? Women classified as insulin sensitive lost 3.6 kilograms
or 7.9 pounds more weight
weig ht on the high-carbohydrate
O the 245 women that began the trial, 31 (13%)
diet compared to the low-carbohydrate diet, although
dropped out, which is notably low or a year-long trial.
this difference was not quite statistically significant
sig nificant
Additionally,, the walnut group experienced significantly
Additionally
(p=0.06). Additionally,
Additionally, the insulin sensitive women
greater increases in the linoleic acid and alpha-linoleic
lost significantly more weight on the walnut
wa lnut diet (4.0
acid content o their serum phospholipids than the oth-
kilograms or 8.8 pounds more) when compared to the
er two groups, indicating strong compliance with the
walnut intervention. low-carbohydrate diet. However,
However, there were no signifi-
cant differences in weight loss between diets or women
who were insulin resistant.
All three diet groups lost a significant amount o weight
compared to baseline, with the high-carbohydrate
hig h-carbohydrate
None o the secondary outcomes differed significantly
group losing non-statistically-significant more weight
between groups afer one year, nor did insulin resis-
(2.3 kilograms or about five pounds; p=0.06) than the
tance status affect the degree o change (as shown in
low-carbohydrate diet. When expressed as a percentage
Figure 2). However, all groups did experience mostly
o baseline weight, there were no significant differences
significant improvements compared to baseline, and
between groups.
30% o the insulin resistant participants were no longer
classified as insulin resistant by study end.

  Figure 2: Results of insulin resistant

resistant vs sensitive subjects
   s 20 160 7 94 75
    t
   c 18
   e 140 6 92 70
    j
    b 16
   u 120 90
14 5 65
    S
   e 100 88
12
   v
    i
4 60
    t
    i 10 80 86
   s 3 55
   n 8
60 84
   e
    S
 
6 2 50
40 82
    i
   n 4
    l
1 45
   u 2 20 80
   s
   n 0
    I 0 0 78 40
Insulin (μIU/mL) Triglycerides (mg/dL) CRP (μg/mL) Weight Change (kg) HDL (mg/dL)

   s 20 160 7 94 75
    t
   c 18
   e
    j
140 6 92 70
    b 16
   u 120 90
14 5 65
    S
    t 100 88
   n 12
4 60
   a
    t 10 80 86
   s
    i 3 55
   s 8
60 84
   e
    R
 
6 2 50
40 82
   n
    i 4
    l
   u 2
20 1 80 45
   s
   n
    I 0 0 0 78 40
Insulin (μIU/mL) Triglycerides (mg/dL) CRP (μg/mL) Weight Change (kg) HDL (mg/dL)

Baseline High Carb Low Carb Low Carb + Walnuts

21
 

All groups, compared to baseline, had significant reduc-

tions in asting triglycerides,
tr iglycerides, LDL-c, CRP,
CRP, and IL-6 and
significant increases in HDL-c. Te high-carbohydrate
group also significantly reduced asting insulin, and both
the high-carbohydrate and low-carbohydrate plus wal-
nut groups significantly reduced asting glucose. In other
words, all groups experienced notable benefits rom
 rom
What does the study really
tell us?
Te current study shows that all three diets were effec-
tive at promoting weight loss and improvements in
insulin sensitivity, blood lipids, and inflammatory mark-
ers. Additionally, the results suggest that the degree

weight loss alone, regardless o dietary

dietar y composition.
All three diet groups lost a significant amount o
bodyweight compared to baseline without signi-
icant difference between groups. Insulin sensitive
individuals lost significantly more weight on a
low-carbohydrate diet with walnuts compared to the
low-carbohydrate diet, but the insulin resistant wom-
en ared equally well on all three diets. None o the
secondary outcomes differed between groups or were
affected by insulin resistance status.
 
o weight loss may depend in part on baseline insulin
sensitivity, although the study wasn’t randomized to
answer this question, meaning this finding is effectively
observational. Overall, this study supports the notion
that weight loss matters more than dietary composition
or improving health markers among women with obe-
sity. Tereore, pick a diet that you can stick with.
In order to directly test whether insulin sensitivity
influences the effectiveness o a diet on weight loss,
we need to have separate groups
g roups o participants that
differ by insulin sensitivity at baseline, rather than
t han
doing within-group analyses afer the results come in.
A recent study  has
 has done just that, and its main results
are shown in Figure 3. Unlike the current study (which

 
Figure 3: Weight Loss on high-carb vs. low-carb diets by
insulin resistance status: No significant difference
-7.5 kg

High-carb diet (n=15)

      d
    e -9.6 kg
    z
     i Insulin Resistant
    m Low-carb diet (n=16)
    o (n=31)
      d
    n
    a -10.4 kg
     R
High-carb diet (n=16)

-8.6 kg
Insulin Sensitive
Low-carb diet (n=14)
(n=30)
Source: Gardner et al. Obesity (Silver Spring). 2016 Jan.
 
22

created three groups o women and analyzed how
insulin resistance status impacted weight loss afer the
act), the primary analysis looked at the influence o
insulin resistance status on weight loss with a low- or
high-carbohydrate diet by first grouping the participant
according to insulin resistance status and then random-
izing them to a low- or high-carbohydrate diet. Tis
study ound no effect o insulin resistance status on
weight loss afer six months.
In the current study
study,, insulin sensitive women lost
about 9% o their initial bodyweight on the walnut
and high-carbohydrate diets, compared to 5.5% on the
low-carbohydrate diet, although only the walnut diet
difference was statistically significant. Te only differ-
ence between the low-carbohydrate and walnut diets
were the inclusion o 1.5 ounces (42 grams) o walnuts
in the walnut diet and instructions to exclude nuts in
the other. Te current
cur rent study doesn’t provide insight into
why walnuts may have a beneficial effect on weight
weig ht loss,
but other research might.
Clinical trials involving a variety o nut types have
shown that they consistently promote satiety  and
 and
compensatory dietary responses that may offset some
o the calories they provide. Additionally,
Additionally, a recent
study showed that walnuts contribute about 21% less
energy  than
 than a calorie label suggests. Combined, it is
possible that the walnut diet group
g roup simply ate less cal-
ories, thereore promoting greater weight loss than the
low-carbohydrate group. However,
However, firm
fir m conclusions
cannot be made without any data on the dietary intake
o the participants.
What then explains the trend towards statistical sig-
nificance or the superiority o the high-carbohydrate
diet among insulin sensitive women compared to the
low-carbohydrate diet? Tese women are still sensitive
to the signal o insulin, meaning that they respond to
its effects. Research has shown that insulin promotes
satiety . Since insulin release with the high-carbohydrate
diet is likely to have been greater than with the low-car-
bohydrate diet, it could be that the women ate less
ood and were more satiated on a high-carbohydrate
compared to a low-carbohydrate diet. But as with the
walnuts, this is purely hypothetical without dietary data.
d ata.
In contrast to the insulin sensitive women, the insulin
resistant women ared similarly regardless o diet.
Support or the satiating effects o the high-carbo-
hydrate diet comes rom “High-carb, high satiety?”
in ERD #18,
# 18, Volume
Volume 2. Tis study investigated how
manipulating macronutrient composition
composition o meals
mea ls
throughout the day would affect satiety and the
t he hedonic
response to a subsequent ood exposure in people who
were overweight or obese. Although we do not know
how insulin resistant these participants were, they con-
sumed about 35-40% more calories ollowing a 56% at
and 30% carbohydrate diet than when ollowing a 63%
carbohydrate and 23% at diet.
Despite differences in weight loss, there were no statis-
tically significant differences in secondary outcomes
between groups. Perhaps the 2-3% difference in weight
loss was not large enough to result in notably different
effects in insulin sensitivity, blood lipids, and inflam-
matory markers. Whatever the reason, this study was
not designed to test or differences in these variables,
meaning that other research will be needed to assess
how insulin resistance status and dietary composition
interact to affect insulin sensitivity,
sensitivity, blood lipids, and
inflammatory markers.
Te low drop-out rate and ree-living design o this
study are strengths, as they increase the generalizability
o these findings to women in the general population.
However,, the lack o dietary
However diet ary control is a limitation that
prevents us rom knowing i the observed outcomes
were owed specifically to the differences in macronutri-
ent composition.
Another limitation was the macronutrient composition
23
 

o the diets. A 30% carbohydrate diet is not considered
a low-carbohydrate diet by some standards, and it is
possible that different outcomes would be observed
with a lower carbohydrate intake. Additionally
Additionally,, protein
was not matched between the high-carbohydrate diet
and other two diets, which contained an extra 5% o
calories rom protein.
weight loss may depend in part on an interaction
between baseline insulin sensitivity and the macronu-
trient composition o the diet. Different
D ifferent populations
have different dietary needs, and what is best or one
group is not necessarily the best
b est or another.
It is also worth noting that the current study adds to

a growing evidence base

bas e showing that carbohydrates
are not responsible or obesity and weight gain. Te
Tere may be differences in weight loss among
idea that carbohydrates drive insulin and thereore
insulin sensitive women depending on macro-
at gain was expanded and promoted by Gary a
aubes
ubes
nutrient composition, possibly due to effects on
and called the carbohydrate-insulin hypothesis
hypothesis o
satiety.. However, we cannot conclude what
satiety w hat mecha-
obesity.. However,
obesity However, two studies, covered in “Te study
nism explains the differences. Regardless, all diets
that didn’t
didn’t end the low-at/low-carb diet wars” o ERD
appeared to acilitate weight loss and have simi-
#11, Volume
Volume 2 and “Quoth the insulin hypothesis,
lar effects on insulin sensitivity, blood lipids, and
Nevermore”” o ERD #22, Volume
Nevermore Volume 2, have directly
d irectly tested
inflammatory markers.
this hypothesis and ailed to support it.

Te above studies showed that a reduction in carbohy-

The big picture
One o the most widely debated topics or the treatment
o obesity and type 2 diabetes is carbohydrate
carbohydrate intake.
raditionally, many health authorities have recommend-
ed diets in which more than 50% o the calories come
rom carbohydrates. However, more recent evidence has
led to some authorities, such as the American Diabetes
Association,, to acknowledge that “evidence is incon-
Association
clusive or an ideal amount o carbohydrate intake or
drate intake and insulin levels was not necessary or at
loss to occur in healthy overweight and obese adults.
Te study under investigation supports these findings by
showing that low- and high-carbohydrate diets promote
a similar amount o weight loss over the long-term.
Tere is no one-size-fits-all diet prescription, and
the study at hand lends support to the notion that

people with diabetes” and “thereore, collaborative

collaborative goals diet plans should be tailored to the individual. Also,
should be developed with the individual with diabetes.”
diabetes.” carbohydrates are not the villain some popular
media would have us believe – you can lose at on a
Te current study lends support to the
t he notion o indi- high-carbohydrate diet.
 vidually tailored nutrition programs
programs by showing that
that

  This study ound no effect o

insulin resist
resistance
loss afer six ance status
status on weight
months.
24
 

Frequently asked questions sity,, that showed no significant differences in weight

How would the glycemic index (GI) of the diets have
affected the results?
Tis question was previously investigated in “Is the gly-
cemic index actually useul or making ood choices?”
rom ERD #4. A group o overweight adults consumed
one o our diets based on the DASH-diet guidelines
that were either low (40% o kcal) or high (60% o kcal)
in carbohydrates and had a low or high
hig h glycemic index.
Each diet was consumed or five weeks each.
Te results showed that glycemic index didn’t really play
a substantial role when it came to triglycerides, LDL-c,
and systolic blood pressure (the primary
primar y outcomes o
this study), but that a low carbohydrate intake did lead
to significantly lower triglycerides compared to a high
carbohydrate intake. In act, in the context o a high-
er-carb diet, certain high-GI oods may be preerable
to low GI oods rom the standpoint o their effects on
insulin sensitivity and LDL-c levels.
Tis finding is supported by a meta-analysis
meta-analysis o
 o 19 RCs
involving 1,577 participants with overweight or obe-
sity
loss between high glycemic index/load diets compared
to low glycemic index/load diets. While it is possible
that the GI o the oods eaten may have impacted the
secondary outcomes o the study under investigation, it
seems unlikely.
What should I know?
Te study under investigation was a random-
ized controlled trial in which women ollowed a
high-carbohydrate diet, a low-carbohydrate diet, or a
low-carbohydrate diet supplemented with walnuts or
one year.
All the groups lost a significant and similar amount
o weight, and similarly improved insulin sensitivity,
blood lipids, and inflammatory markers. Exploratory
analyses suggested that insulin sensitive women lost
more weight on a low-carbohydrate plus walnut diet
compared to the low-carbohydrate diet, while insu-
lin resistant women ared similarly on all three diets.
However,, urther research
However res earch is needed to clariy this
observation. ◆

I know what you’re

you’re thinking. Walnuts? Just remember that the interventions aren’t
aren’t always the most important part
o a paper. Discuss this study at the Facebook ERD orum.
orum.

25
 25

Examining the potential

for edible sunscreen

Skin photoprotective and antiageing effects
of a combi
combination
nation of rosemary (rosemarinus
officinalis) and grapefruit (citrus paradisi)
polyphenols
 26

Introduction that antioxidants could help protect against damage

caused by UV radiation
radiation.. Tis study used malondialde-
Common knowledge tells us that using sunscreen helps
hyde (MDA)
hyde  (MDA) as a marker o oxidative stress in the skin,
prevent sun damage, yet regular application can some-
as it has been shown that MDA can be produced when
produced when
times be cumbersome. Wouldn’t it be great i we could get
ree radicals react with lipids in the skin.
similar skin protection against UV light through our diet?

A previous study  by
 by the same group reported synergis-
UVB rays primarily produce acute effects on the skin
in the orm o sunburns (erythema,
sunburns (erythema, see Figure 1), while tic effects o rosemary and citrus extracts in a skin cell
model, showing a decrease in reactive oxygen species
A rays are primarily responsible or long term effects 
UVA
UV effects 
and reduced DNA damage afer exposure to UVB radi-
on skin quality and appearance, producing wrinkles,
ation. Te same study included a small pilot trial in
dryness, and loss o skin elasticity, collectively
collectively known
humans, showing that the combination o extracts was
as ‘photoaging.’
able to increase the dose o UV radiation necessary to
cause a sunburn. Te study discussed here aimed to
Photoaging and sunburns are both 
both caused
caused,, in part, by
build on those results by using living humans and differ-
inflammation and the ormation o reactive oxygen
ent doses o the extracts. Te supplement tested here was
species or ‘ree radicals’ generated in the skin afer UV
a proprietary blend o plant extracts, including rosemary
light exposure. Tus, it seems reasonable to hypothesize 
hypothesize 
and graperuit, henceorth reerred to as the R-G extract.
 
Figure 1: The effects of ultraviolet
ultraviolet rays A and B (UVA and UVB)

Short Term Effects

Sunburn

Long Term Effects

UVB UVA
Skin Quality Elasticity

Epidermis
Wrinkle Dryness

Dermis Skin Appearance

Hypodermis

Reactive oxygen species have been linked to
UV-induced
UV-induced photoaging, and it is hypothesized that
antioxidants can protect against this damage. Few
studies have investigated the protective properties o
rosemary and citrus extracts, and most o them with
limited relevance to humans. Tis study aimed to
test the effectiveness o varying doses o extracts in a
larger group o women.
Who and what was studied?
Te authors report two treatments here, a short-term,
and a long-term treatment. In both o these, the partic-
ipants were healthy Caucasian women. Te average age
or the group in the short-term treatment was 31, while
the average age in the long-term treatment was 52.
Participants were asked to avoid natural or artificial UV
exposure during the study, as well as ood supplements
with high levels o antioxidants. All o the participants
had very air to medium skin tones, classified as a I-III
(out o six levels) on the Fitzpatrick Scale. Participants
in both studies began their enrollment by having their
Minimal Erythemal Dose (MED) measured, which is
the dose o UV light required to produce a sunburn on
that individual. o determine this
determine this measurement, patch-
es o skin on the participant’s inner arm are exposed to
increasing doses o UV light. Te lowest dose that pro-
duces sunburn symptoms 24-48 hours later is the MED.
Te short-term treatment was structured like a cross-
over study that enrolled five participants or three
three-day periods. In the first three-day period, partici-
pants received either 100 or 250 milligram doses o the
R-G extract, and had skin redness measured at vari-
ous intervals afer exposure to one MED o UV light.
Te R-G extract contained substantial levels o a ew
plant components: 35 gallic acid equivalents/100 g dry
weight, total rosemary phenolic content higher than 7%
7%
dry weight, and total graperuit flavone content higher
than 20% dry weight.
27
One dose o supplement was given 15-30
1 5-30 minutes
beore the UV exposure, ollowed by additional doses
dos es
at 24 and 48 hours. In the second three-day period, all
five participants received the placebo dose and had
the same exposure and measurements taken. Tis also
served to act as a ‘wash-out’ period rom the first dos-
ing period. In the third three-day period, the original
dosing groups were switched, resulting in a combi-
nation pattern where every individual was evaluated
under all three conditions (100 milligrams, 250 milli-
grams, or placebo).
Te long-term treatment involved 90 participants, divid-
ed into three groups o 30, receiving either a placebo,
100, or 250 milligrams o the R-G extract once a day or
two months at breakast. Te measurements in this study
were more extensive. In addition to measuring the MED
over the course o the study, the researchers measured
MDA levels in the top-most layer o skin (the stratum
corneum or “horny layer”) and wrinkle depths as the
primary endpoints or photoprotection and anti-aging,
respectively. A secondary endpoint was skin elasticity.
A short crossover study o five women measured the
effects o the R-G extract on Minimal Erythemal
Er ythemal Dose
(MED), while a larger two month study looked at the
effects o the extract on MED, skin wrinkles and elas-
ticity, and markers o oxidative stress in the skin.
What were the findings?
In the short-term treatment, the 100 and 250 milligram
doses o the R-G extract provided a slight acceleration
in the ading o sunburn redness compared to the pla-
cebo dose. Te difference was most evident at the 25
hour time point, one hour afer the second dose was
given. By 72 hours, the differences in redness were still
statistically significant compared to the placebo but
indistinguishable rom a practical standpoint, and there
were no statistically significant differences between the
two doses.
 28

MED was also a measurement in the long-term treat-
ment, with results shown in Figure 2. Both treatment
groups saw statistically significant
sig nificant improvements
improvements in
their MEDs afer 0.5,
0.5 , one, and two months o supple-
mentation, though there were no statistically significant
differences between the two doses. By two months,
MED had increased by an average o 30% in the 100
cally significant effects between the two doses or either
measurement. Women
Women who took the R-G extract or
two months saw an improvement o about 15% in the
depth o their ‘crows eet’ wrinkles and about a 4-5%
4-5 %
improvement in skin elasticity.
No adverse events were reported, and the study had a

milligram group and by 27% in the 250 milligram 100% compliance rate, so the R-G extract was extremely
group, while the placebo group remained unchanged. well-tolerated at the levels supplemented.

Te MDA content in the skin, both afer UV exposure

Te results o the crossover study showed that
(acute levels) and without UV exposure (basal levels),
post-sunburn redness started to decrease earlier
was reduced in both treatment groups compared to the
when the participants were taking the R-G extract,
placebo group, indicating that the supplementatio
supplementation
n
but that the overall
over all redness wasn
w asn’t
’t that different
likely had a protective effect to background UV expo-
between the treatment and placebo groups. In the
sure. For this measurement, dose-dependent effects
long-term treatment,
treatment, MED was increased
increase d by 27-30%,
were seen. Afer two months o supplementation,
supplementation, the
basal and acute post-exposure levels o oxidative
100 milligram group showed a 20% reduction in acute stress markers in the skin were reduced, and wrinkle
skin oxidative stress and a 19% reduction in basal levels.
depth and skin elasticity were both improved. Other
Te 250 milligram group showed reductions o 22% and
than the oxidative stress markers, there were no
33% in acute and basal levels, respectively.
dose-dependent effects o the R-G extract.

Wrinkle depth and skin elasticity were also improved in

both treatment groups, and again there were no statisti-

 
Figure 2: Results: Natural SPF and wrinkle depth

30% Times (Months)

0.5 1 2
    *
    )
    %
0%
    (
    V
    U
   o
    t 20%     *
    )
   e     %
   c     (
   n     h
   a
   r     t
   e    p
    l    e 10%
   o     D
    T    e
    l     l
   a
   r     k
   u 10%    n
    i
    t    r
   a     W
    N

20%

0%
0.5 1 2
100 mg 250 mg Placebo
Times (Months)
 29

What does the study really saw more or less benefit rom the supplement. While
this would have required a much larger population
p opulation in
tell us? order to achieve study power within each subgroup,
Tis larger study confirmed the results o the prior it would have provided some useul data as people
in vitro and pilot human study , which showed a 34% with a type I skin classification have a greater risk or
increase in the participants
par ticipants’’ MED. It also suggests UV-induced
UV-induced skin damage than
t han people with a type
typ e III
additional potential benefits by showing small improve- skin classification.

ments in skin condition and reductions in oxidative

stress. While MED is correlated to SPF,
SPF, it’s difficult to
Te results o this study are consistent with the
say what exact SPF effect the extract would have (due
group’’s previous in
group i n vitro and pilot human studies,
to variations in skin color among other actors).
 actors). Hence,
but don’t
don’t yet provide any inormation on w
whether
hether
it is not at all recommended to replace your sunblock
different skin types would show different benefits
with a plant extract, rather
r ather than using both together.
rom the extract.

Overall, the short-term data was weaker than the long-

term data, suggesting that the extract may be more useul
when used daily as opposed to just beore exposure.
Te manuacturer o the proprietary plant extract blend
did und the study and provide the study product, as
well as provided input as to the study design,
d esign, but this
company did not have any input
input in the data
d ata analysis or
the final manuscript.
It would have been interesting to see the results clas-
sified by skin tone, to know whether airer people
The big picture
ERD previously covered a somewhat similar study
evaluating the effects o six months o supplemen-
tation with cocoa flavanols on skin photosensitivity
and skin quality measurements (“Chocolate ountain
ountain
o youth”, ERD #15, Volume 1). Both studies showed
similar magnitudes o effects on SPF and skin elastic-
ity,, but wrinkles showed a bigger improvement
ity improvement with
the R-G extract afer only two months, a 15% decrease
 versus cocoa’
cocoa’s 6% when compared to baseline measure-

  The authors o the coco

cocoaa study
suggested that the supplement might
be more effective or preventing
wrinkles rather than or tre
treating
ating them,
so it’s possible that could also be the
case or the R-G extract.

ments. Te authors o the cocoa study suggested that
the supplement might be more effective or preventing
wrinkles rather than
t han or treating them, so it’s possible
that could also be the case or the R-G extract. It is
interesting to note that there were no differences at the
12-week time point o the cocoa study when compared
to placebo, while in this study benefits were statistically
significant at the two-month time point.
As we wrote in the cocoa study, there are a number o
antioxidants that
antioxidants that are being studied or their effects on the
skin, and the components o this supplement are simply
two more to add to the list. Tis study provides more
evidence that regardless o where you get your dietary
antioxidants, they’re likely to provide some benefits.
Te small magnitude o effect is generally to be
expected based on other studies o antioxidants or
skin protection. As in other studies, it’s possible that
antioxidants might be more beneficial to protect skin
rom photodamage rather than to repair it afer the
damage has already occurred.
Frequently asked questions
Do I still need to wear sunscreen?  
Te small increase in participants’ MED doesn’t
doesn’t trans-
late to a lot o extra time in the sun - or example, i you
start to sunburn afer 20 minutes o sun exposure, the
supplement would extend that to about 26
2 6 minutes.
Also, while there was some
s ome modest improvement in
wrinkle appearance, there’s
there’s no data
d ata in this study about
wrinkle prevention. Tus it’s
it’s still prudent to wear sun-
screen whether or not you choose to supplement.
Could I just eat rosemary and grapefruit?
I you like them, go or it. Te supplement used in the
study contains 35 ‘gallic acid equivalents’, a measure o
antioxidant potency.
potency. But a gram o rosemary  (about
 (about a
teaspoon) contains 214 gallic acid equivalents. Most
30
o the graperuit flavones are ound in the peel o the
ruit, but a cup o graperuit juice (or
juice (or an average peeled
graperuit) still contains about 32 gallic acid equiva-
lents. You
You would need to consume them daily in order
to achieve the (small) benefits o this study, but it
wouldn’t
wouldn’t be impossible to do so.
Why didn’t the larger dose of extracts produce greater
effects?
More isn’t always better. For example, the benefits o
higher doses could be limited by the incorporation o
antioxidants into the skin.
But sometimes, longer timerames are better
b etter.. Te pre-
 vious pilot study conducted
conducted by the researchers
researchers showed
a 56% improvement
improvement in MED at three months. It’
It’s very
possible that participants would have continued to
show improvements
improvements in their MED in this study,
study, and
possibly also in their wrinkle and elasticity measure-
ments. A longer study would be needed to determine
the ull extent o the improvements.
improvements.
What should I know?
Middle-aged women who took a daily supplement
containing rosemary and graperuit extracts or two
months saw a small
sm all increase in their ‘natural SPF’,
reductions in oxidative stress markers in the skin, and
a slight improvement in wrinkle depth and skin elastic-
ity. In general, a hig
ity. higher
her dose o the supplement did not
produce greater effects.
Despite these positive results, please do not replace
your sunblock with a supplement or ood consump-
tion (as opposed to using natural plant compounds as
an adjunct). Sunblock is not only more powerul, but
much more highly studied and hence reliable. ◆
First cocoa, now rosemary
rosemar y and graperuit. o discuss
the bounty o potential benefits rom plants, head to the
orum.
ERD Facebook orum.
 31

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Infographics: Antonius Khengdro,
Khengdro, Hieu Nguyen & Calla Lee

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