ERD

Examine.com
Research Digest

Issue 24, Vol 1 of 2  ◆  October 2016

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Table of Contents
05 The high cost of high 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 a

   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!

2
From the Editor
So apparently there’s a presidential election next month.
Have you heard about this?
Just kidding. I don’t spend 24 hours a day buried under
nutrition research (only 22 or so). When I emerge out
of my pile of p-values, and observe comments about the
presidential election, there’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
of millions of citizens?
The armchair quarterback has a more insidious relative,
the armchair politician. And the armchair politician
has a second-cousin as well, the armchair nutritionist.
You see, some issues only have a handful of variables
involved. If you want to buy a quality new car, you can
peruse online reviews, try out the car for yourself, and
ask people you know who are into automobiles. So
there aren’t that many (any?) people who proclaim that
Geo is the greatest car maker of all time, because the
variables all point to the same answer: false.
But for 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 of
people avoid animal products because they’re sure
of the unhealthiness of eating meat or drinking milk.
Some people are low-carb evangelists, and they’ll tell
anyone willing to listen that they’d be healthier if they
cut out a large chunk of their carb intake. These strong
positions don’t just apply to animal products and carbs
though, there are also people with strong positions on
either side of GMOs, saturated fat, 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 of three distinct reasons. First, there is
decent research on both sides of many 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). Third, “published
research” does not equal “fact”. Much of the published
literature has important methodological flaws. And due
to the controlled nature of research, it won’t ever cap-
ture the full spectrum of human effects, especially given
the relative lack of funding for certain topics.
I’ll take back the first sentence of 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)
4
The high cost of high
heat cooking
Oral AGE restriction ameliorates insulin
resistance in obese individuals with the
metabolic syndrome: a randomized
controlled trial.

5
Introduction Although the accuracy of AGE measurement is debat-
ed within the scientific community, the largest study to
Advanced glycation end products (AGEs) are highly
date to investigate the AGE content of food showed that
reactive compounds that result from a chemical reac-
AGE content is highly dependent both on the food itself
tion between reducing sugars and amino acids (also
and the preparation method used. Although high fat,
known as a Maillard reaction) and from the oxidation
high protein foods generally had higher levels of AGEs
of sugars, lipids, and amino acids. Although the for-
compared to foods high in carbohydrate, there was
mation of AGEs within the body is a part of normal
considerable variability. By contrast, harsher cooking
metabolism, a growing body of evidence suggests that
methods such as frying, broiling, grilling, and roasting
excessive AGE levels promote oxidative stress and
consistently led to higher AGE levels than gentler cook-
inflammation and may therefore increase the risk of
ing methods such as boiling, poaching, stewing, and
developing type 2 diabetes, cardiovascular disease, fatty
steaming, suggesting that high-heat and dry heat cook-
liver, cancer, Alzheimer’s disease, and infertility.
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 of increased oxidative
A handful of short-term clinical trials have shown that
stress. However, it is now known that dietary AGEs are
restricting dietary AGEs results in reduced inflamma-
important contributors to the body’s total AGE con-
tion and increased insulin sensitivity among patients
centration, where they become indistinguishable from
with type 2 diabetes, overweight women, and healthy
those AGEs produced within the body itself. The most
adults. Moreover, among individuals with obesity and
widely studied AGE is carboxymethyllysine (CML),
the metabolic syndrome, both dietary and serum AGEs
while another common marker of AGE formation is
have been significantly correlated with insulin resis-
methyl-glyoxal (MG).
tance, oxidative stress, and inflammation. However, no
long-term trials have been conducted.

Figure 1: Carboxymethyllysine content of chicken

Figure 1: Carboxymethyllysine content of technique
breast by cooking 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
Reference: Uribarri, J, et al. J Am Diet Assoc. 2010 Jun

6
The study under review was designed to test whether
prolonged (one year) dietary AGE restriction could
improve insulin resistance and other risk factors for
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 of food. Dietary AGEs contribute to the body’s
total AGE concentration. Excessive amounts promote
oxidative stress and inflammation. Short-term clinical
trials show that reducing dietary AGEs improves insu-
lin sensitivity and reduces inflammation. The current
study sought to test if these observations would be
apparent over the long term (one year).
Who and what was studied?
This was a randomized controlled trial involving 138
adults age 50 years or older who had at least two of
five criteria for metabolic syndrome, as defined by
the National Cholesterol Education Program Adult
Treatment Panel III. Criteria includes an obese waist
circumference, high blood pressure, low HDL choles-
terol, high triglycerides, and high fasting blood glucose.
However, none of the participants had type 2 diabetes
or kidney disease.
Participants were randomly assigned to follow a
low-AGE diet or their usual diet for one year under
free-living conditions. A sample day of one partici-
pant’s low-AGE diet is shown in Table 1. The 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 fruit cup 0.12 | (½ cup) 15 Fresh fruit 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 ml 3 Orange juice 120 ml 3
Breakfast
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 ml 200 Caesar dressing 30 ml 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 Beef 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

7
group received instructions on reducing dietary AGEs
through modifying cooking time and temperature
What were the findings?
Of the 138 adults who began the study, 100 finished it
without changing the amount or type of food being
and were included in the final analysis. The number of
eaten. They were instructed to avoid frying, 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 performed
their food. 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 circumference (106.3 110.4
Testing was performed at baseline and after the one-
cm), and serum VCAM1 (-15%) than the control group,
year intervention. The primary outcome was a change
with trends towards significance (all p<0.08) for lower
in HOMA-IR, which is an indirect measure of insulin
bodyweight (84.8 vs. 90.7 kilograms), calorie intake
resistance. Secondary outcomes included metabolic syn-
(-9%), and higher HbA1c (6.0% vs. 5.8%). Therefore,
drome criteria (blood pressure, anthropometrics, fasting
the groups were not evenly distributed when the study
glucose, triglycerides, and HDL-c), other type 2 diabetes
began, and there is a possibility that these differences
risk factors (fasting insulin, two-hour glucose tolerance
may have influenced the results.
test, and HbA1c), MRI measurements (visceral fat, sub-
cutaneous fat, and carotid wall thickness—a predictor
Three-day food logs as well as blood and urinary analyses
of cardiovascular events), CML and MG concentrations
revealed that the low-AGE intervention was successful
(dietary, serum, intracellular, and urinary), inflamma-
at reducing dietary, serum, and urinary AGE concen-
tory and oxidative markers (8-isoprostanes, VCAM1,
trations. Compared to the control group, the low-AGE
TNF-α, and RAGE), and anti-inflammatory/oxidative
group consumed 65% less dietary AGEs and had approx-
markers (SIRT1, AGER1, GLO1, and adiponectin).
imately 40% less serum AGEs, 35-40% less intracellular
AGEs, and 40-50% less urinary excretion of AGEs.
This study also had a test tube component, during
which peripheral blood mononuclear cells (PMNCs)
Both groups significantly reduced caloric intake, but
were collected from the participants before and after
the reduction was significantly greater in the low-AGE
the intervention. These cells were analyzed for inflam-
group by about 200 kcal per day. As would therefore be
matory markers and insulin sensitivity.
reasonably expected, the low-AGE group also lost sig-
nificantly more bodyweight than the control group (1.4
A group of 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 of the main study results.
food preparation (boil, poach, stew or steam rather Although both groups started the study with similar
than fry, bake, or grill) for one year. Insulin resis- HOMA-IR, the low-AGE group experienced a signif-
tance was assessed before and after the intervention. icant 53% reduction in HOMA-IR compared to the
Test tube studies were used to determine the cellular control group, which remained statistically significant
effects of dietary AGE restriction. after adjusting for baseline BMI, age, sex, race, and
dietary intake of calories, protein, carbohydrate, and
fat. Moreover, the improvement in HOMA-IR was
observed among the 12 participants in the low-AGE

8
 Figure 2: Changes in insulin resistance
markers and serum CML

Figure 2: Changes in insulin 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
Responsible for
1 change in 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 lose weight (they actually signifi-
cantly gained two kilograms), suggesting weight loss
alone could not explain the finding. To put this reduc-
tion of HOMA-IR into perspective, the 53% reduction
corresponds to about a 50% reduction in the odds of
experiencing fatal cardiovascular diseases, even after
adjusting for other metabolic syndrome criteria and
lifestyle factors.
There were no significant differences between groups
for any metabolic syndrome criteria or MRI variables.
However, the low-AGE group did experience significant
improvements in every variable related to inflammation
and oxidative stress compared to the control group.
These results were supported by the test tube studies,
which showed that the PMNCs from the low-AGE
group displayed significantly lower TNF-α concentra-
tions and significantly greater insulin sensitivity than
the control group. Additionally, TNF-α concentrations
were influenced by the presence of a SIRT1 activator
and inhibitor, suggesting that SIRT1 may play a role in
modifying inflammation within the low-AGE group.
Consuming an AGE-restricted diet for one year led
to significant reductions in HOMA-IR and numerous
markers of inflammation and oxidative stress with-
out affecting other metabolic syndrome criteria. Test
tube studies supported these findings.
What does the study really
tell us?
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
among individuals with metabolic syndrome, possibly
through reducing inflammation and oxidative stress.

9
Since the participants were free-living individuals
instructed only to change how they cook their food,
this finding has important practical consequences.
The average dietary AGE intake of healthy adults
from the New York City area was found to be 14,700
kilounits. Moreover, higher dietary intake of AGEs was
significantly correlated with a higher serum AGE level,
which in turn was significantly correlated with HOMA-
IR and plasma 8-isoprostane, a marker of oxidative
stress. Dietary AGE consumption was also significantly
related to higher CRP levels, a marker of inflammation.
Therefore, 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 of AGEs per day. This
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 among individuals
with metabolic syndrome, possibly
through reducing inflammation and
oxidative stress.
tion in insulin resistance. However, caloric intake and
bodyweight also significantly decreased, the impact of
which on insulin resistance is uncertain. Still, chang-
es in insulin resistance were independent of BMI and
calorie and nutrient consumption. Moreover, signifi-
cant improvements were still observed in the low-AGE
participants who did not lose bodyweight. Together,
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. The reduction in HOMA-IR was large
enough to result in 80% of the low-AGE participants
no longer being classified as insulin resistant based
on their HOMA-IR value. Yet, there were no signif-
icant between-group differences in fasting glucose,
triglycerides, HDL-c, blood pressure, or HbA1c. This
trial lasted one year, so it is unlikely that a longer dura-
tion would lead to changes not observed in this study.
10
Rather, it could be that the study was underpowered to
detect significant differences between the low-AGE and
control groups, especially considering that these were
not primary endpoints. This is supported by the fact
that many of these variables significantly improved over
time in the low-AGE group but not the control group.
The idea that dietary AGEs work through inflam-
mation and oxidative stress was supported by this
study. Plasma 8-isoprostane and VCAM-1, a protein
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 TNF-α, an inflammatory molecule, of
cells isolated from the participants. Additionally, the
low-AGE group experienced significant increases in the
gene expression of SIRT1, a regulator of metabolism
with beneficial effects on insulin 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 of RAGE, a pro-inflam-
matory 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
Figure 3: AGER1 protects SIRT1 from AGEs
Low AGE diet
AGER1 restored
Adiponectin SIRT1
Inflammation
Reference:
Reference: Cai, W, et al. Proc Natl Acad Sci U S A. 2012 Sep  Cai, W, et
development of type 2 diabetes or related complications,
such as cardiovascular disease. Additionally, while
HOMA-IR does generally provide an accurate mea-
sure of insulin resistance, it is not the gold-standard
hyperinsulinemic-euglycemic clamp technique. This is
problematic because HOMA-IR relies on fasting insu-
lin and glucose values, meaning that something which
affects either could change HOMA-IR without actually
impacting insulin sensitivity. Still, a study using the
gold-standard hyperinsulinemic-euglycemic clamp in
healthy overweight and obese adults did find that insu-
lin sensitivity increases after following a low-AGE diet.
Finally, the use of individuals with metabolic syndrome
precludes generalizations to healthy populations about
the impact that dietary AGE restriction would have.
Dietary restriction of AGEs through modifying
cooking methods appears to be a feasible long-term
method to reduce insulin resistance in people with
metabolic syndrome. These effects appear to be
mediated through reductions in inflammation and
oxidative stress. Whether these benefits translate
into actual reduced risk of developing type 2 diabetes
remains to be determined.
protects SIRT1 from AGEs
High AGE diet
AGER1 depleted
Oxidative stress
Insulin Insulin
signaling
Adiponectin SIRT1 signaling
Inflammation
|  Vlassara, H,al. Proc Natl
Striker, AcadRev
G. Nat Sci Endocrinol.
U S A. 2012 Sep
2011 May
Vlassara, H, Striker, G. Nat Rev Endocrinol. 2011 May
11
The big picture
Several past issues of the ERD have discussed reduc-
tionism in nutritional science and how focusing on
nutrients rather than foods misses part of the nutrition
puzzle because the food itself impacts the health effect of
some nutrients. The current study points to yet another
layer that cannot be overlooked: how food is prepared.
The study at hand, along with others, shows that mod-
ifying cooking techniques can have a profound impact
on health. Yet, this variable is almost never addressed in
clinical or observational research. It raises many ques-
tions about current associations (or lack of) between
foods and health outcomes. For instance, the consump-
tion of red meat and its relationship to disease is a
controversial topic. There is strong and consistent evi-
dence linking processed meats to poor health outcomes,
but the associations with unprocessed red meats are less
clear-cut. What would happen if red meat was further
categorized by how it was prepared?
Similarly, how can findings from one population be
extrapolated to another when the type of cooking tech-
niques used to make the food they eat may be vastly
different? A recent review article addressed this very
problem, when the authors argued that the benefits of
a Mediterranean diet may not be owed entirely to the
foods being eaten, but also to how the foods are pre-
pared and consumed.
  Nutrition isn’t just about specific
foods or their nutrients, but also
about how these foods are prepared
to be eaten.
The study under review serves as a gentle reminder that
there is more to nutrition than nutrients or food. Recent
years have greatly shifted the focus from the former to
the latter, and perhaps now it is time to consider both in
combination with how food is prepared and eaten.
Nutrition isn’t just about specific foods or their
nutrients, but also about how these foods are pre-
pared to be eaten. Clearly how we cook certain foods
impacts their health effects, and this adds a new layer
of understanding to nutrition research.
Frequently asked questions
What is a maillard reaction?
A maillard reaction is a non-enzymatic reaction
between reducing sugars and amino acids. A reduc-
ing sugar is one that reduces another compound and
is itself oxidized, meaning that it “takes” an oxygen
atom from another molecule (in this case, an amino
acid). These sugars include glucose, fructose, galactose,
mannose, ribose, and some intermediates of energy
metabolism. Of the reactive amino acids, lysine, argi-
nine, and sulfur-containing amino acids are particularly
vulnerable to being reduced.
While the study under review shows that excessive
levels of dietary AGEs may be harmful to health, the
maillard reaction plays an important role in food pro-
12
cessing by imparting both color and flavor to cooked
foods. This reaction is literally responsible for the
golden brown color of bread crust and toast or the
browning of red meat during cooking. As such, anyone
consuming cooked food in the diet will consume some
maillard reaction products, such as AGEs.
What are other harmful compounds produced during
cooking, aside from AGEs?
Aside from AGEs, meats may contain several other
potentially harmful compounds, depending on how they
are cooked. Processed meats usually have some form
of nitrite added as a preservative, be it from a salt such
as sodium nitrite or from the “natural” celery powder.
When exposed to high heat, these potentially beneficial
nitrites are transformed into carcinogenic nitrosamines.
Polycyclic aromatic hydrocarbons (PAHs) are anoth-
er group of carcinogenic compounds that form when
organic matter burns, such as the burning of wood or
charcoal or the burning (oops) of your dinner. They
can be created in food directly when burned and also
transferred to food through the smoke that forms from
cooking over an open flame. For this reason, smoked
foods are high in PAHs.
Heterocyclic amines (HCAs) are a third class of car-
cinogenic compounds that form when meat is cooked
on a high temperature, such as during frying or grill-
ing. Generally speaking, well-done and very well-done
meats will contain higher levels of HCAs than less
cooked and more gently cooked meats.
Acrylamide is yet another potentially harmful com-
pound (carcinogenic and neuro, reproductive, and
genotoxic) that is commonly used in the production of
paper, dyes, and plastics (including food packaging). It is
produced from maillard reactions involving the amino
acid asparagine, which is found in high concentrations
among many plants such as potatoes and cereal grains.
High-temperature cooking methods, such as frying,
baking, or broiling, have been found 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
alongside meat) and increasing the acidity (like marinat-
ing with vinegar) reduce acrylamide levels.
When considered alongside the current study, there is
a strong evidence base supporting a potential health
benefit of reducing consumption of processed meats
(which tend to contain all of these harmful compounds)
and cooking unprocessed meats gently for shorter peri-
ods of time.
What should I know?
Advanced glycation end products (AGEs) are natu-
rally occurring compounds formed within the body
and found in most foods, with greater amounts being
formed in meat that is cooked with more harsh meth-
ods such as frying, baking, and grilling rather than
more gentle methods such as boiling, poaching, stew-
ing, and steaming.
Evidence suggests that dietary AGEs contribute substan-
tially to the body’s total AGE pool, and that an excessive
AGE pool causes oxidative stress and insulin resistance.
The current study shows that restricting dietary AGE
consumption through using gentler cooking methods
does result in significant reductions in insulin resistance
among individuals with metabolic syndrome. Since the
participants were free-living individuals instructed only
to change how they cook their foods, this finding has
important practical implications. ◆
The debate on dietary AGEs is really starting to heat
up. So put down the hot dog, and head to the Facebook
ERD forum.
13
 INTERVIEW:
Courtney Silverthorn, PhD
Dr. Courtney Silverthorn is the Deputy Director of the Technology Partnerships Office
at the National Institute of Standards and Technology (NIST) in the Department
of Commerce, focusing on the coordination of cross-agency technology trans-
fer policy and overseeing economic analysis of the impact of federal research &
development investment. She works with a number of interagency working groups,
serves as the Host Agency Representative on the Executive Board of the Federal
Laboratory Consortium, and is the Executive Secretariat for the National Science
and Technology Council’s Lab-to-Market subcommittee. Prior to coming to NIST,
she held tech transfer and partnership development roles at the Frederick National
Laboratory for Cancer Research and the National Cancer 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 think I knew what tech transfer was until my last year of grad school, but it’s turned out to
be an extremely fascinating career. The federal government spends about $140B a year on scientific
research and development. About two-thirds of that money goes out to universities, small business-
es, and other organizations through grants and contracts. The rest gets spent at approximately 350
federal laboratories across the country - what we refer to as ‘intramural’ research. Sometimes those
government scientists invent things - but the government isn’t going to manufacture products or sell
things to the public. So we rely on tech transfer professionals at the labs to help find partners to devel-
op the technology, sometimes in collaboration with the government or sometimes through a license,
and eventually bring a new drug or battery technology or other invention to the market.

I was looking for alternatives to lab science as I was wrapping up my PhD, and stumbled into tech
transfer at a career services workshop. My postdoctoral fellowship was actually in a tech transfer
office at the National Cancer Institute, where I worked directly with the scientists on their inven-
tions and collaborations. I later had the opportunity to move into a tech transfer policy position at
the National Institute of Standards and Technology, where I’ve been for almost three years. So now I
can assist the entire federal government on ways to make their tech transfer efforts better - through

14
sharing best practices, writing regulations, developing
interagency tools, and overseeing economic research on
the impacts of our efforts.
You’re starting school yet again soon. Which begs the
question ... why??
A few people do wonder if I’m crazy! I’ve just started
a program, which is offered through a partnership
between Washington University in St. Louis and The
Brookings Institution, a nonpartisan think tank in
DC. The program is designed for higher level govern-
ment employees who want to transition into the Senior
Executive Service (SES), and the course material covers
all of the Office of Personnel Management’s Executive
Core Qualifications. All of my previous degrees have
been in hard sciences, but most of my day job now is in
‘soft skills’ - so the opportunity to have formal 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 from all over the federal government, which
is really important for my role in tech transfer policy. I’m
also able (required!) to start implementing the skills I’m
learning in my current position - so for example, after
a course on Strategic Thinking, I wrote about using the
processes we learned in the class for 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 bureaucracy! Can you tell us more about
how things work over there in DC?
Government bureaucracy can be a real hurdle, but
sometimes it’s actually harder for the government to
work internally than it is for us to work with outside
partners. A lot of issues can arise when agencies have
different legislation that applies to them, and/or dif-
ferent policies in how they interpret that legislation
internally. One of my projects last year was developing a
“tech transfer playbook” collecting agency best practices
and compiling them into an online format, so that other
agencies had information to provide to their internal
legal and policy people when they ran into pushback
while trying to implement new programs and initiatives.
Having something to point to that says another agency
is doing something can be very powerful.
There are a lot of rules, and it’s sometimes easier for
people to say “no” to something than to find a way to
make it work. The 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 if they had completely new rules and regulations to
try to comply with all the time - they’d never get any-
thing else done. My experience has been that if 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 lines, if you were granted three wishes for
things to change on the federal level, what would you
change?
The first thing I’d like to see changed is increased fund-
ing for scientific research and development across the
federal government. $140B sounds like a lot, but as a
percentage of our GDP and as a percentage of our total
federal budget it’s at an all-time low. We are at a real risk
of falling behind other nations as a scientific leader.
The second thing on my list would be an easing of trav-
el restrictions for government professionals to attend
scientific conferences and meetings. This really became
an issue a few years ago with a few isolated, high-profile
incidents and the spillover into the scientific communi-
ty was incredibly far-reaching. Government scientists
weren’t able to travel to conferences and meetings in
order to present their work, which really hurt both the
science and the tech transfer efforts - most agencies
have small to non-existent marketing budgets, so scien-
15
tists interacting with their industry counterparts is one
of our best ways to talk about our technologies and find
potential partners.
And the third thing, which is a bit more general, is that
if I’ve learned anything from my policy classes it’s that
gerrymandering has ruined our political system and
made it even more challenging for 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 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
learning? I have a feeling the answer rhymes with Toga.
Toga yoga? For real though, 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 with
myself while running - so it’s nowhere as mentally
relaxing as a yoga practice. In terms of staying orga-
nized, I have detailed, color-coded Google and Outlook
calendars and I make a LOT of 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% of people with advanced
degrees in the sciences stay in academic research. It’s a
tough field to compete for jobs, compete for tenure, and
compete for dwindling federal grant dollars. The people
who I know who have been successful at it truly, com-
pletely love what they do and love focusing on a single
aspect of a single scientific area. But if that ends up not
being you, it’s okay!
There 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 fact and are
doing a better job of providing information about
“alternative” careers in the sciences - which is almost
a misnomer now that they’re the majority of gradu-
ates. It does take a bit of soul-searching, and maybe an
existential crisis (speaking from experience here…) to
figure out what you love doing. Take advantage of any
information you can get your hands on, take advantage
of your network connections, and ask people what they
love about their careers in lab work or in another pur-
suit. If after all that you’re still not sure - take the lab job.
It’s far easier to move from the bench to an office than
to go the other direction. ◆
(Required disclaimer: The author contributed to this
article in her personal capacity. The views and opinions
expressed in this article are those of the author, and do not
represent the views and opinions of NIST, the Department
of Commerce, or the United States Government.)

Dr. Silverthorn earned a Ph.D. in Pharmacology from the Johns Hopkins University School of
Medicine and a B.S. in Biochemistry and Molecular Biology from Sweet Briar College. She also
has certificates in Biotechnology Enterprise from Johns Hopkins and in Policy Strategy from the
Brookings Institution, and is pursuing a Masters in Public Leadership from Washington University
in St. Louis. Courtney is a RYT-200 vinyasa yoga teacher in Northern Virginia and has written for
the Examine.com Research Digest since November of 2014.

16
 Does being insulin
resistant affect weight
loss on a low-fat or
low-carb diet?
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 the optimal mac-
ronutrient distribution for a weight loss diet is. Two
Obesity has recently been called a “single house for
previous short-term studies have suggested that insulin
many evils” based on evidence that it increases the risk
resistance may predict which macronutrient distribu-
for numerous comorbidities, including cardiovascular
tion is most beneficial. Specifically, these two studies
disease, cancer, and diabetes. One proposed explana-
showed that insulin resistant individuals lose more
tion for the link between obesity and other metabolic
weight on a low-carbohydrate diet, as opposed to a low-
diseases is that obesity leads to chronic inflammation in
fat diet. However, a more recent study with a stronger
some people, which in turn leads to a dysregulation of
methodological design did not support these findings.
insulin signaling, also known as insulin resistance.

Aside from macronutrients, the actual foods includ-

Insulin resistance has widespread effects on health
ed in the diet may influence weight loss. For instance,
and is the hallmark of metabolic syndrome and type 2
“Blast from the past: a paleo solution for type 2 dia-
diabetes. Weight loss is a well-established method of
betes” from ERD #8 explored a study that compared
restoring insulin sensitivity among people with obesity
two diets of equal calorie and macronutrient content,
and insulin resistance. Several trials have shown that
with the difference being what foods supplied them.
very low-calorie diets and rapid weight loss are able to
One group ate an American Dietetic Association diet
restore insulin sensitivity and possibly even reverse type
while the other ate a Paleo diet. Although both groups
2 diabetes. Of course, a very-low calorie diet (less than
lost a similar amount of weight and showed similar
1000 calories) is not sustainable over the long term.
improvements in insulin sensitivity (again suggesting
that weight loss is the most important), the paleo group
Under more modest levels of caloric restriction, weight
showed superior benefits for changes in blood lipids
loss is achievable with a variety of macronutrient (pro-
and glycemic control.
tein, carbohydrate, and fat) intakes. This was discussed
in “The best diet is the one you can stick to” in the first
In this regard, walnuts may be of interest because of
issue of the ERD, where 11 popular name-brand diets
their ability to reduce inflammatory markers and blood
were compared for their ability to produce weight loss
lipids without significantly affecting weight, despite
among individuals with obesity. The results showed that
contributing a substantial number of calories to the
while there were some differences between diets, overall
diet. And more directly, walnuts may also be of 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 funded by
the California Walnut Commission. Nonetheless, long-
term walnut trials are still necessary to investigate if the
previously identified benefits are merely transient.
The current study sought to examine the effect of three
diets (low-carb, low-carb plus walnuts, or high-carb) on
weight loss and other markers of health in overweight
or obese women over a one-year period and determine
whether baseline insulin resistance influenced the effec-
tiveness of the interventions.
Obesity greatly increases the probability of suffer-
ing from insulin resistance, which in turn serves
as a hallmark of metabolic syndrome and type 2
diabetes. Weight loss is known to restore insulin
sensitivity, but the optimal macronutrient distribu-
tion of a weight loss diet has not been established.
Certain foods, such as walnuts, may also have a ben-
eficial impact on health. The current study sought to
compare three diets differing in macronutrient com-
position and the amount of walnuts in the diet on
their ability to produce weight loss over a one-year
intervention. This study also investigated whether
baseline insulin resistance influenced any outcomes.
Figure
Figure 1: Diet Composition
1: Diet Composition
High-Carb Lower-Carb
15% 20%
20% 56%
35%
Protein
All diet prescriptions limited saturated fat
Who and what was studied?
This was a randomized, open-label (non-blinded)
controlled trial in which 245 women were instructed
to follow one of three dietary interventions for one
year, which are broken down in Figure 1. The dietary
interventions were a high-carbohydrate diet (65%
carbohydrate, 20% fat, and 15% protein), a lower-car-
bohydrate diet (45% carbohydrate, 35% fat, and 20%
protein), and a lower-carbohydrate diet that included
walnuts (1.5 ounces or 42 grams per day).
The participants varied widely in age, with a range of
22-72 years and average of 50 years. The majority of the
women had obesity, as the BMI range was 27-40 with
an average of 33.5. Roughly half of the participants
were classified as insulin resistant (HOMA-IR of more
than 3), although none of the women had type 2 dia-
betes. Importantly, the participants were stratified by
menopausal status and insulin resistance status before
randomization so that an even number of pre-/post-
menopausal and insulin resistant/sensitive participants
would follow each diet.
The participants were free-living throughout the inter-
vention and initially provided with a detailed diet
prescription and sample meal plans during an individu-
Lower-Carb + Walnuts
20%
45% 45%
35%
Fat Carbs
19
al counseling session with a dietitian. Additionally, the
participants were encouraged to use web-based food
tracking programs to ensure proper dietary intake and
were provided with a scale, pedometer, measuring cups,
and exercise videos to facilitate compliance.
The participants had weekly group-based behavioral
meetings for the first four months, biweekly for the next
two months, and monthly thereafter. They also had
unlimited telephone and email contact with the group
leaders, who had backgrounds in health science.
The overall goal of the dietary guidance was to pro-
mote a 500-1000 calorie per day reduction in energy
intake using individualized diet plans. Participants in
the walnut group were also instructed to consume 1.5
ounces (42 grams) of walnuts daily, and these individu-
als were provided with walnuts at two-week intervals to
facilitate compliance. The other groups were instructed
to exclude nuts. All participants were also encouraged
to aim for an average of at least 60 minutes per day of
moderate-intensity exercise.
All outcomes were assessed at baseline, six months, and
one year. The data for changes at six months was pub-
lished previously. In the current study, weight loss was
the primary outcome, with markers of insulin sensitiv-
ity and glycemic control (fasting glucose and insulin,
HOMA-IR, and HOMA-β), blood lipids (LDL-c,
HDL-c, and triglycerides), inflammatory markers (CRP
and IL-6), and hormones [estradiol and sex hormone
binding globulin (SHBG)] being of secondary interest.
Healthy women with obesity were randomly
assigned to follow a high-carbohydrate diet (65%
carbohydrate, 20% fat, and 15% protein), a lower-car-
bohydrate diet (45% carbohydrate, 35% fat, and 20%
protein), or a lower-carbohydrate diet that included
walnuts (1.5 ounces or 42 grams per day) for one
year. The main outcome of interest was weight loss,
with secondary outcomes being changes in insulin
sensitivity and glycemic control, blood lipids, inflam-
matory markers, and hormones.

  [...] the walnut group experienced

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

Figure 2: Results of insulin

Figure 2: Results of insulinresistant vs sensitive
resistant vs sensitive subjects subjects
20 160 7 94 75
Insulin Sensitive Subjects

18
140 6 92 70
16
120 90
14 5 65
100 88
12
4 60
10 80 86
3 55
8
60 84
6 2 50
40 82
4
20 1 80 45
2

0 0 0 78 40
Insulin (μIU/mL) Triglycerides (mg/dL) CRP (μg/mL) Weight Change (kg) HDL (mg/dL)

20 160 7 94 75
Insulin Resistant Subjects

18
140 6 92 70
16
120 90
14 5 65
100 88
12
4 60
10 80 86
3 55
8
60 84
6 2 50
40 82
4
20 1 80 45
2

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 fasting triglycerides, LDL-c, CRP, and IL-6 and
significant increases in HDL-c. The high-carbohydrate
group also significantly reduced fasting insulin, and both
the high-carbohydrate and low-carbohydrate plus wal-
nut groups significantly reduced fasting glucose. In other
words, all groups experienced notable benefits from
weight loss alone, regardless of dietary composition.
All three diet groups lost a significant amount of
bodyweight compared to baseline without signif-
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 fared equally well on all three diets. None of the
secondary outcomes differed between groups or were
affected by insulin resistance status.
What does the study really
tell us?
The 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
of 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
for improving health markers among women with obe-
sity. Therefore, pick a diet that you can stick with.
In order to directly test whether insulin sensitivity
influences the effectiveness of a diet on weight loss,
we need to have separate groups of participants that
differ by insulin sensitivity at baseline, rather than
doing within-group analyses after the results come in.
A recent study 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

Figure 3: Weight Loss on high-carb vs. low-carb diets by
resistance status: No significant difference
insulin resistance status: No significant difference
-7.5 kg
High-carb diet (n=15)
Randomized

-9.6 kg
Insulin Resistant Low-carb diet (n=16)
(n=31)

-10.4 kg
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.
Source: Gardner et al. Obesity (Silver Spring). 2016 Jan.
22
created three groups of women and analyzed how
insulin resistance status impacted weight loss after the
fact), the primary analysis looked at the influence of
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. This
study found no effect of insulin resistance status on
weight loss after six months.
In the current study, insulin sensitive women lost
about 9% of 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. The only differ-
ence between the low-carbohydrate and walnut diets
were the inclusion of 1.5 ounces (42 grams) of walnuts
in the walnut diet and instructions to exclude nuts in
the other. The current study doesn’t provide insight into
why walnuts may have a beneficial effect on weight loss,
but other research might.
Clinical trials involving a variety of nut types have
shown that they consistently promote satiety and
compensatory dietary responses that may offset some
of the calories they provide. Additionally, a recent
study showed that walnuts contribute about 21% less
energy than a calorie label suggests. Combined, it is
possible that the walnut diet group simply ate less cal-
ories, therefore promoting greater weight loss than the
low-carbohydrate group. However, firm conclusions
cannot be made without any data on the dietary intake
of the participants.
What then explains the trend towards statistical sig-
nificance for the superiority of the high-carbohydrate
diet among insulin sensitive women compared to the
low-carbohydrate diet? These women are still sensitive
to the signal of 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
food 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.
In contrast to the insulin sensitive women, the insulin
resistant women fared similarly regardless of diet.
Support for the satiating effects of the high-carbo-
hydrate diet comes from “High-carb, high satiety?”
in ERD #18, Volume 2. This study investigated how
manipulating macronutrient composition of meals
throughout the day would affect satiety and the hedonic
response to a subsequent food 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 following a 56% fat
and 30% carbohydrate diet than when following a 63%
carbohydrate and 23% fat 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 for 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, blood lipids, and
inflammatory markers.
The low drop-out rate and free-living design of this
study are strengths, as they increase the generalizability
of these findings to women in the general population.
However, the lack of dietary control is a limitation that
prevents us from knowing if the observed outcomes
were owed specifically to the differences in macronutri-
ent composition.
Another limitation was the macronutrient composition
23
of 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, protein
was not matched between the high-carbohydrate diet
and other two diets, which contained an extra 5% of
calories from protein.
There may be differences in weight loss among
insulin sensitive women depending on macro-
nutrient composition, possibly due to effects on
satiety. However, we cannot conclude what mecha-
nism explains the differences. Regardless, all diets
appeared to facilitate weight loss and have simi-
lar effects on insulin sensitivity, blood lipids, and
inflammatory markers.
The big picture
One of the most widely debated topics for the treatment
of obesity and type 2 diabetes is carbohydrate intake.
Traditionally, many health authorities have recommend-
ed diets in which more than 50% of the calories come
from carbohydrates. However, more recent evidence has
led to some authorities, such as the American Diabetes
Association, to acknowledge that “evidence is incon-
clusive for an ideal amount of carbohydrate intake for
people with diabetes” and “therefore, collaborative goals
should be developed with the individual with diabetes.”
The current study lends support to the notion of indi-
vidually tailored nutrition programs by showing that
  This study found no effect of
insulin resistance status on weight
loss after six months.
weight loss may depend in part on an interaction
between baseline insulin sensitivity and the macronu-
trient composition of the diet. Different populations
have different dietary needs, and what is best for one
group is not necessarily the best for another.
It is also worth noting that the current study adds to
a growing evidence base showing that carbohydrates
are not responsible for obesity and weight gain. The
idea that carbohydrates drive insulin and therefore
fat gain was expanded and promoted by Gary Taubes
and called the carbohydrate-insulin hypothesis of
obesity. However, two studies, covered in “The study
that didn’t end the low-fat/low-carb diet wars” of ERD
#11, Volume 2 and “Quoth the insulin hypothesis,
Nevermore” of ERD #22, Volume 2, have directly tested
this hypothesis and failed to support it.
The above studies showed that a reduction in carbohy-
drate intake and insulin levels was not necessary for fat
loss to occur in healthy overweight and obese adults.
The study under investigation supports these findings by
showing that low- and high-carbohydrate diets promote
a similar amount of weight loss over the long-term.
There is no one-size-fits-all diet prescription, and
the study at hand lends support to the notion that
diet plans should be tailored to the individual. Also,
carbohydrates are not the villain some popular
media would have us believe – you can lose fat on a
high-carbohydrate diet.
24
Frequently asked questions
How would the glycemic index (GI) of the diets have
affected the results?
This question was previously investigated in “Is the gly-
cemic index actually useful for making food choices?”
from ERD #4. A group of overweight adults consumed
one of four diets based on the DASH-diet guidelines
that were either low (40% of kcal) or high (60% of kcal)
in carbohydrates and had a low or high glycemic index.
Each diet was consumed for five weeks each.
The 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 outcomes of
this study), but that a low carbohydrate intake did lead
to significantly lower triglycerides compared to a high
carbohydrate intake. In fact, in the context of a high-
er-carb diet, certain high-GI foods may be preferable
to low GI foods from the standpoint of their effects on
insulin sensitivity and LDL-c levels.
This finding is supported by a meta-analysis of 19 RCTs
involving 1,577 participants with overweight or obe-
I know what you’re thinking. Walnuts? Just remember that the interventions aren’t always the most important part
of a paper. Discuss this study at the Facebook ERD forum.
sity, that showed no significant differences in weight
loss between high glycemic index/load diets compared
to low glycemic index/load diets. While it is possible
that the GI of the foods eaten may have impacted the
secondary outcomes of the study under investigation, it
seems unlikely.
What should I know?
The study under investigation was a random-
ized controlled trial in which women followed a
high-carbohydrate diet, a low-carbohydrate diet, or a
low-carbohydrate diet supplemented with walnuts for
one year.
All the groups lost a significant and similar amount
of 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 fared similarly on all three diets.
However, further research is needed to clarify this
observation. ◆
25
Examining the potential
for edible sunscreen
Skin photoprotective and antiageing effects
of a combination of rosemary (rosemarinus
officinalis) and grapefruit (citrus paradisi)
polyphenols

26
Introduction that antioxidants could help protect against damage
caused by UV radiation. This study used malondialde-
Common knowledge tells us that using sunscreen helps
hyde (MDA) as a marker of oxidative stress in the skin,
prevent sun damage, yet regular application can some-
as it has been shown that MDA can be produced when
times be cumbersome. Wouldn’t it be great if we could get
free radicals react with lipids in the skin.
similar skin protection against UV light through our diet?

A previous study by the same group reported synergis-

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

27

Reactive oxygen species have been linked to
UV-induced photoaging, and it is hypothesized that
antioxidants can protect against this damage. Few
studies have investigated the protective properties of
rosemary and citrus extracts, and most of them with
limited relevance to humans. This study aimed to
test the effectiveness of varying doses of extracts in a
larger group of women.
Who and what was studied?
The authors report two treatments here, a short-term,
and a long-term treatment. In both of these, the partic-
ipants were healthy Caucasian women. The average age
for 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 food supplements
with high levels of antioxidants. All of the participants
had very fair to medium skin tones, classified as a I-III
(out of 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 of UV light required to produce a sunburn on
that individual. To determine this measurement, patch-
es of skin on the participant’s inner arm are exposed to
increasing doses of UV light. The lowest dose that pro-
duces sunburn symptoms 24-48 hours later is the MED.
The short-term treatment was structured like a cross-
over study that enrolled five participants for three
three-day periods. In the first three-day period, partici-
pants received either 100 or 250 milligram doses of the
R-G extract, and had skin redness measured at vari-
ous intervals after exposure to one MED of UV light.
The R-G extract contained substantial levels of a few
plant components: 35 gallic acid equivalents/100 g dry
weight, total rosemary phenolic content higher than 7%
dry weight, and total grapefruit flavone content higher
than 20% dry weight.
One dose of supplement was given 15-30 minutes
before the UV exposure, followed by additional doses
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. This also
served to act as a ‘wash-out’ period from 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).
The long-term treatment involved 90 participants, divid-
ed into three groups of 30, receiving either a placebo,
100, or 250 milligrams of the R-G extract once a day for
two months at breakfast. The measurements in this study
were more extensive. In addition to measuring the MED
over the course of the study, the researchers measured
MDA levels in the top-most layer of skin (the stratum
corneum or “horny layer”) and wrinkle depths as the
primary endpoints for photoprotection and anti-aging,
respectively. A secondary endpoint was skin elasticity.
A short crossover study of five women measured the
effects of the R-G extract on Minimal Erythemal Dose
(MED), while a larger two month study looked at the
effects of the extract on MED, skin wrinkles and elas-
ticity, and markers of oxidative stress in the skin.
What were the findings?
In the short-term treatment, the 100 and 250 milligram
doses of the R-G extract provided a slight acceleration
in the fading of sunburn redness compared to the pla-
cebo dose. The difference was most evident at the 25
hour time point, one hour after the second dose was
given. By 72 hours, the differences in redness were still
statistically significant compared to the placebo but
indistinguishable from a practical standpoint, and there
were no statistically significant differences between the
two doses.
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MED was also a measurement in the long-term treat-
ment, with results shown in Figure 2. Both treatment
groups saw statistically significant improvements in
their MEDs after 0.5, one, and two months of supple-
mentation, though there were no statistically significant
differences between the two doses. By two months,
MED had increased by an average of 30% in the 100
milligram group and by 27% in the 250 milligram
group, while the placebo group remained unchanged.
cally significant effects between the two doses for either
measurement. Women who took the R-G extract for
two months saw an improvement of about 15% in the
depth of their ‘crows feet’ wrinkles and about a 4-5%
improvement in skin elasticity.
No adverse events were reported, and the study had a
100% compliance rate, so the R-G extract was extremely
well-tolerated at the levels supplemented.

The MDA content in the skin, both after UV exposure

The results of 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 supplementation
but that the overall redness wasn’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, MED was increased by 27-30%,
were seen. After two months of supplementation, the
basal and acute post-exposure levels of 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
The 250 milligram group showed reductions of 22% and
than the oxidative stress markers, there were no
33% in acute and basal levels, respectively.
dose-dependent effects of 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

Figure 2: Results: Natural SPF and wrinkle depth
30% Times (Months)
0.5 1 2
Natural Tolerance to UV (%)*

0%

20%
Wrinkle Depth (%)*

10%

10%

20%

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

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What does the study really
tell us?
This larger study confirmed the results of the prior
in vitro and pilot human study, which showed a 34%
increase in the participants’ MED. It also suggests
additional potential benefits by showing small improve-
ments in skin condition and reductions in oxidative
stress. While MED is correlated to SPF, it’s difficult to
say what exact SPF effect the extract would have (due
to variations in skin color among other factors). Hence,
it is not at all recommended to replace your sunblock
with a plant extract, rather than using both together.
Overall, the short-term data was weaker than the long-
term data, suggesting that the extract may be more useful
when used daily as opposed to just before exposure.
The manufacturer of the proprietary plant extract blend
did fund the study and provide the study product, as
well as provided input as to the study design, but this
company did not have any input in the data analysis or
the final manuscript.
It would have been interesting to see the results clas-
sified by skin tone, to know whether fairer people
  The authors of the cocoa study
suggested that the supplement might
be more effective for preventing
wrinkles rather than for treating them,
so it’s possible that could also be the
case for the R-G extract.
saw more or less benefit from the supplement. While
this would have required a much larger population in
order to achieve study power within each subgroup,
it would have provided some useful data as people
with a type I skin classification have a greater risk for
UV-induced skin damage than people with a type III
skin classification.
The results of this study are consistent with the
group’s previous in vitro and pilot human studies,
but don’t yet provide any information on whether
different skin types would show different benefits
from the extract.
The big picture
ERD previously covered a somewhat similar study
evaluating the effects of six months of supplemen-
tation with cocoa flavanols on skin photosensitivity
and skin quality measurements (“Chocolate fountain
of youth”, ERD #15, Volume 1). Both studies showed
similar magnitudes of effects on SPF and skin elastic-
ity, but wrinkles showed a bigger improvement with
the R-G extract after only two months, a 15% decrease
versus cocoa’s 6% when compared to baseline measure-
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ments. The authors of the cocoa study suggested that
the supplement might be more effective for preventing
wrinkles rather than for treating them, so it’s possible
that could also be the case for the R-G extract. It is
interesting to note that there were no differences at the
12-week time point of 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 of
antioxidants that are being studied for their effects on the
skin, and the components of this supplement are simply
two more to add to the list. This study provides more
evidence that regardless of where you get your dietary
antioxidants, they’re likely to provide some benefits.
The small magnitude of effect is generally to be
expected based on other studies of antioxidants for
skin protection. As in other studies, it’s possible that
antioxidants might be more beneficial to protect skin
from photodamage rather than to repair it after the
damage has already occurred.
Frequently asked questions
Do I still need to wear sunscreen?
The small increase in participants’ MED doesn’t trans-
late to a lot of extra time in the sun - for example, if you
start to sunburn after 20 minutes of sun exposure, the
supplement would extend that to about 26 minutes.
Also, while there was some modest improvement in
wrinkle appearance, there’s no data in this study about
wrinkle prevention. Thus it’s still prudent to wear sun-
screen whether or not you choose to supplement.
Could I just eat rosemary and grapefruit?
If you like them, go for it. The supplement used in the
study contains 35 ‘gallic acid equivalents’, a measure of
antioxidant potency. But a gram of rosemary (about a
teaspoon) contains 214 gallic acid equivalents. Most
of the grapefruit flavones are found in the peel of the
fruit, but a cup of grapefruit juice (or an average peeled
grapefruit) still contains about 32 gallic acid equiva-
lents. You would need to consume them daily in order
to achieve the (small) benefits of this study, but it
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 of
higher doses could be limited by the incorporation of
antioxidants into the skin.
But sometimes, longer timeframes are better. The pre-
vious pilot study conducted by the researchers showed
a 56% improvement in MED at three months. It’s very
possible that participants would have continued to
show improvements in their MED in this study, and
possibly also in their wrinkle and elasticity measure-
ments. A longer study would be needed to determine
the full extent of the improvements.
What should I know?
Middle-aged women who took a daily supplement
containing rosemary and grapefruit extracts for two
months saw a small 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 higher dose of the supplement did not
produce greater effects.
Despite these positive results, please do not replace
your sunblock with a supplement or food consump-
tion (as opposed to using natural plant compounds as
an adjunct). Sunblock is not only more powerful, but
much more highly studied and hence reliable. ◆
First cocoa, now rosemary and grapefruit. To discuss
the bounty of potential benefits from plants, head to the
ERD Facebook forum.
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Credits
Copy Editor: Dmitri Barvinok
Infographics: Antonius Khengdro, Hieu Nguyen & Calla Lee

©iStock.com/Michael Phillips
©iStock.com/Serghei Platonov
©iStock.com/sveta_zarzamora

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