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1) Dark Chocolate and Health

a) The purpose of this literature review of the ten articles I have chosen is
to see if there are health benefits related to the consumption of dark
chocolate through randomized clinical trials. Also to see if a cause and
effect association can be determined.
b) The cause and effect benefits of dark chocolate to be evaluated include
improved endothelial function, satiety, lowering blood pressure,
cholesterol, and improved cardiovascular health.
2) 10 Articles
a) Glucan and Dark Chocolate: A Randomized crossover study on
short-tern satiety and energy intake
i) This study was to find out if there is a cause and effect relationship
between glucan and dark chocolate on short term satiety and
energy intake.1 There were 25 subject, all women, who participated
in the randomized crossover design with four products including
milk chocolate-control, oat glucan, dark chocolate, and oat
glucan and dark chocolate together were given to the participants.
After given one of the products they reported a VAS related to
sensory outcomes and satiety for four hours at ones pleasure (ad
libitum) then lunch was served and energy intake of participants
was measured. The VAS scores showed that none of the foods
tested showed an effect on satiety. Energy intake did show that
during lunch at their pleasure, energy intake was lower in the dark
chocolate groups.
ii) This study is not a very detailed, in depth experiment. I feel like it is
kind of vague overall. First, the sample size was 25 and all women.
That is not particularly large enough and is not reliable in that the
only subjects were women therefore the results cannot be applied
to males. Also, the test meals were did not have the same energy
content. I think that each test meal should be the same exact
energy content to make the results the most valid. There was
however sufficient randomization and blinding. Im assuming since
there are four different treatments the experiment took place four
different times and each person got each treatment once but no
details on time besides that it was four days. Was it four days
consecutively, or once a week? Confounding variables were taken
into account but how do they know for sure that the subjects fasted
for 12 hrs before they came each morning before the test? This
study should be performed on a larger sample size, with more
variety in subjects demographics. Overall I would rate this study as
neutral because it did meet a lot of criteria there were just a few
negatives that can result in unreliable results.

b) The effect of poly-phenol rich dark chocolate on fasting capillary whole


blood glucose, total cholesterol, blood pressure and glucocorticoids in
healthy overweight and obese subjects
i) This study used a randomized, single-blind, cross-over design with
14 overweight and obese subjects who were randomized to either
take 20 g of dark chocolate with 500 mg of polyphenols then 20 g of
dark chocolate with 1000 mg of polyphenols or vice versa.2 It aimed
to measure and compare the effect of two different doses of
polyphenols on fasting capillary whole blood glucose levels, total
cholesterol, blood pressure, urinary free cortisol and cortisone
excretion in healthy overweight and obese adults. Each subject was
randomly assigned their first treatment either the dark chocolate
with 500 mg or 1000 mg of polyphenols. It lasted two weeks and
then followed by a 1 week wash out period. Then the opposite mg
was given to each group for two weeks. Subjects were instructed to
eat the dark chocolate through the day, maintain their usual diet,
but refrain from polyphenol rich foods. They completed a three day
diet and physical activity log during the run-in phase and at the end
of each intervention. Interviewing, a questionnaire, diet diaries, and
returning empty chocolate foils was used to manage compliance
with the studys protocol. Measurements included fasting blood
glucose, total cholesterol, waist and hip circumference, BMI, blood
pressure, urine samples for Mg excretion and cortisol levels. All tests
were done at baseline, before and after each intervention. The
results showed that there was a significant reduction in fasting
capillary blood glucose concentrations but no difference in the
effect of 1000 mg and 500 mg of polyphenol dark chocolate. Also a
significant effect on fasting glucose levels from 500 mg polyphenol
dark chocolate.
ii) This study tested numerous effects of dark chocolate but only found
significant results in fasting capillary blood glucose concentrations
and fasting glucose levels. The first flaw I want to point out is the
sample size, its only 14 people. This alone takes away much of the
validity of this study. The article was not very organized and a little
all over the place making it hard to understand. Also, I believe there
might be bias because a chocolate company voluntarily supplied
their chocolate. Theyre diet was not restricted in anyway, they
were just asked to refrain from certain things which did not account
for confounding variables. There was also no blinding mentioned in
this experiment. The measurements seemed accurate but does not
describe how each one is used or the reliability. The methods were
not detailed and it doesnt even say how much dark chocolate they

were eating, only the amount of polyphenols. Overall, I give this


article a weak rating for the previous reasons.
c) A double-blind, placebo-controlled, randomized trial of the effects of
dark chocolate and cocoa on variables associated with
neuropsychological functioning and cardiovascular health: clinical
findings from a sample of healthy, cognitively intact older adults
i) This study was a 6 week long randomized, double-blind, fixed-dose,
placebo-controlled, parallel-group experimental design. 3 The 101
participants were randomly assigned either the dark chocolate and
cocoa group or the placebo group. One dark chocolate bar (37 g)
and one 8 oz cup of the cocoa drink and the same for the placebo
group with similar products were taken on a daily basis. Before the
treatment began the subjects took a questionnaire that assessed
their medical and psychiatric history, and three screening BP and
pulse rate measurements. The subjects who met the first criteria
then underwent a 12 hr fasting hematologic assessments consisting
of a coronary risk panel and an ultrasensitive C-reactive protein
test. Blood was also drawn. Height, weight and body mass index
measurements were also taken. Then participants who met the
hematologic inclusion criteria then went for a baseline assessment.
This involved 3 BP and pulse measurements, and then a numerous
amount of neuropsychological testing. After all testing the final
participants were randomly supplied with either the dependent
variable or the placebo and instructions on product consumption.
After 3 weeks, before assessment they were to eat one of their
products 2 hrs before, BP and pulse measurements were taken and
an assessment of mental energy. After week 6, hematologic, BMI, BP
and pulse, and neurological assessments were taken. Also a followup self-report questionnaire. They were advised again to consume
their product 2 hrs prior to final assessment. In the end 89
participated fully in treatment, 45 who got the treatment and 44
who got the placebo. In conclusion, they was no cause and effect
between the short-term consumption of dark chocolate and cocoa
on neuropsychological, hematologic, or physiologic variables
measured.
ii) This study had an extremely numerous amount of measurements
going on before, during, and after the treatment which made it
seem slightly all over the place, to me. I think that the treatment
should have been longer than 6 weeks and then they maybe would
have seen some significant results. It was stated that more than half
of each treatment group was not fully blinded to the products which
is obviously going to cause bias and conflict within this experiment.
I think that overall the treatment should have been over a longer

period of time, and they shouldve taken a lot more precaution in


making sure subjects did not know which treatment they were
getting, the placebo or the dark chocolate and cocoa. More of a
focus on confounding variables in their diet wouldve been more
effective as well considering they werent restricted from anything.
Overall, I think the study was well put together but the fact that the
participants werent fully unaware of the treatment they got really
makes this experiment lose a lot of validity. I gave it a neutral
rating.
d) Acute dark chocolate and cocoa ingestion and endothelial function: a
randomized controlled crossover trail
i) This study is a randomized, placebo-controlled, single-blind
crossover trail with 45 nonsmoking adults (78% were women) aged
30-75 with a BMI between 25 and 35.4 In phase 1 the subjects were
randomly assigned to get the (22 g of cocoa powder) of solid dark
chocolate or the placebo, then had a 7 day wash out period and
received the opposite of what they just had. In phase 2 subjects
were randomly assigned, all containing 22 g of cocoa powder except
the placebo, sugar-free cocoa, sugared cocoa, or placebo. Then they
had a wash out period of 7 days and got other treatment, and then
again for the last treatment that they hadnt had yet. Epithelial
testing took place after 8 hour overnight fasting and then 2 hour
after each treatment. Weight, height, and blood pressure were
measured at each visit. Theyre baseline data was collected before
the first treatment and then measurements were taken at the end of
each wash out period. Endothelial functions was measured, and
blood pressure. The results found that consumption of dark
chocolate in this study significantly improved endothelial function
and lowered blood pressure. The benefits were greater in the
ingestion of the sugar free cocoa compared to the sugar cocoa.
ii) This study did have some flaws as do many. The first one I noticed
was they didnt say how long this study was overall, all they
accounted for was the 7 day wash out periods. Also, how long was
the period between phase 1 and phase 2? There are also
confounders that arent accounted for like genetic factors, or dietary
intake, physical activity and noncompliance. Also, I think the sample
used should be more diverse if they arent studying the effect on a
specific group. The sample is mostly women and this could have an
effect on the results. Despite a few flaws I gave this article close to
a positive rating because of the way the study was configured. The
sample size was large enough, the measurements were very
precise, and it was blinded and randomized. It is also very detailed
compared to other studies and to me seems to have a lot of validity.

e) Protective Effects of Flavanol-Rich Dark Chocolate on Endothelial


Function and Wave Reflection During Acute Hyperglycemia
i) The purpose of this study was to see the effects of flavanol rich dark
chocolate administration on flow mediated dilation and wave
reflections, blood pressure, endothelin-1 and oxidative stress, before
and after a glucose tolerance test is given.5 The sample size was 12
healthy volunteers, males and females. They randomly received 100
g/d of dark chocolate or flavanol-free white chocolate for a period of
3 days. Then there was a 7 day washout period, and the subjects
were given the opposite treatment of the first one. Evaluation after
each treatment included flow-mediated dilation, stiffness index,
reflection index, peak-to-peak time, blood pressure, endothelin-1
and 8-iso-PGF. Dark chocolate improved flow-mediated dilation,
wave reflections, endothelin-1 and 8-iso-PGF. These results suggest
that there may be vascular health benefits.
ii) This study randomized 12 volunteers, which is not nearly a large
enough sample size. They did do a good job accounting for
confounding variables which adds some validity and subjects were
also provided with dietitians and physicians throughout the study
for diet counseling. There was informed consent but it was not
approved specifically by an IRB, but by the responsible Ethics
Committee which Ive have not seen before. Measurements of the
variables were evaluated before and after each intervention. There
was blinding to the physicians and staff involved for the group
assignment. The short-duration of the study makes the results less
reliable, as in other studies I have read thus far. The subjects were
not blinded to the test and chocolate interventions which is also a
negative to this study. The types of participants were not specific.
There was no detail in the instruments used for measurements,
which in itself is unclear and confusing. The methods section was
vague and not described in sufficient detail making understanding
this study difficult. No statistical tests utilized are mentioned.
Overall I rated this article negative because it is lacking in a lot of
ways and makes the research challenging to evaluate.
f) Short-term administration of dark chocolate is followed by a significant
increase in insulin sensitivity and a decrease in blood pressure in
healthy persons.
i) This study used 15 healthy subjects and an oral-glucose-tolerance
test to compare the effects of dark chocolate and white chocolate
on blood pressure, glucose and insulin.6 After 7 days free of cocoa
the 15 subjects were randomly assigned to receive either 100 g of
dark chocolate or 90 g of white chocolate bars for 15 days. They
then went through a wash out phase for 7 days and were assigned

the opposite treatment. They were instructed not to consume any


flavonoid rich foods or beverages. Oral-glucose-tolerance test were
given at the end of each treatment to calculate the homeostasis
model assessment of insulin resistance and the quantitative insulin
sensitivity check index. Blood pressure was measured every day. It
was concluded that dark chocolate decreases blood pressure and
improves insulin sensitivity in healthy persons.
ii) Once again the sample size is too small for there to be valid results
based off this study. The sample size was 15 healthy subjects, 7
men and 8 women, recruited from their medical staff which is
insufficient in size and also lacking in sample variety. There was
nothing stated that there was informed consent or if it was reviewed
by an IRB. They did take into account confounding diet variables
and controlling them however there was no monitoring besides a
diet dairy. No blinding was mentioned at all between the subjects or
the staff. They did use proper statistical testing for their results. This
study is short-term making the results less valid and reliable
compared to a longer term study. Measurements for insulin
resistance and insulin sensitivity were used on acceptable indexes
and the OGTT values were used making this an accurate
measurement. Blood pressure was measured daily by a physician
who was not aware of the study design, but I feel like it shouldve
been checked at the same time every day, which was not
mentioned. Overall this is not a very thorough and precise study per
say and it does not include some important key factors like informed
consent and a review. But the study itself was simple and the design
although it is lacking in sample size, consent, review from an IRB
and blinding. I gave it a negative rating.
g) Cocoa reduces blood pressure and insulin resistance and improves
endothelium-dependent vasodilation in hypertensives
i) In this study their sample size was 20 subjects with essential
hypertension. They tested the effect of dark chocolate on 24 hour
ambulatory blood pressure, flow mediated dilation, and oral glucose
tolerance tests.7 There first was a 7 day chocolate free period, then
the subjects were randomly assigned to receive either 100 g per
day of dark chocolate or 90 g per day of white chocolate which was
flavanol free. The trail lasted fifteen days then they had another 7
days wash out period free of dark chocolate and were then assigned
the opposite treatment for fifteen days again. Evaluated at the end
of each treatment was blood pressure, flow mediated dilation, oral
glucose tolerance tests, serum cholesterol, and indicators of
vascular inflammation. HOMA-IR, QUICKI, and ISI were calculated
from the subjects oral glucose tolerance test values. They were able

to conclude that after the dark chocolate treatment blood pressure


and HOMA-IR decreased, improvement in QUICKI, ISI, and flow
mediated dilation. There was also a decrease in serum LDL
cholesterol. Theyre findings can suggest that flavanols from dark
chocolate can provide cardiovascular benefits for people with
essential hypertension.
ii) This research article was written very well, first off. There were
however flaws. The first I always notice is the sample size, 20 is not
large enough for the most valid and reliable results. They also dont
elaborate on the demographics of the subjects just gender, age and
their health condition which is essential hypertension. A couple
citations are not from within the past 5 years of the articles
publication date. There was no blinding used in the experiment
besides on a physician who was assessing FMD. Blinding couldve
compensated for the lack of sample size. There was nothing stated
about how exactly the sample size was chosen besides being
recruited and no procedures for sample selection. No statement of
informed consent was written in this article. There was also no
approval from an institutional review board, but it was conducted
according to the Declaration of Helsinki of the World Medical
Association. The methods section thoroughly explains
measurements and instruments used very well. There is a lack of
details in the treatment, however which is important because that it
was the experiments results are based off of. I think I would deem it
more valid if there was more detail in the treatments. They did take
baseline measurements to compare the results of the tests too,
which is a positive. The charts also made it helpful in understanding
the information. Overall, I gave this article a neutral rating because
it really is a well done experiment and article just lacking in areas.
h) Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health:
a systematic review and meta-analysis of randomized trails
i) (I did not realize this was a meta-analysis, I mustve saw
randomized trails and automatically picked it and put it on endnote.
This article was helpful in that it entails all the information Im
reading about in my other articles.) The purpose of this systematic
review was to evaluate the effects of chocolate, cocoa, and flavan3-ols on major cardiovascular risk factors.8 The databases that were
searched for randomized controlled trails or chocolate, cocoa, or
flavan-3-ols were Medline, EMBASE, and Cochrane. After searching
for articles and excluding ones for not meeting inclusion criteria, the
final result was 42 acute or short-term chronic randomized
controlled trials. Important findings included improvement in insulin
resistance, flow mediated dilation, and reductions in diastolic blood

pressure. Using GRADE, the quality of evidence of all the articles


used was low to moderate but no suggestion of negative effects.
ii) This research article was very detailed because of reviewing such a
large amount of articles requiring a lot of information to account for.
It was a little overwhelming to read but I feel thats unavoidable in a
systematic review. There was a well-defined topic searched on
appropriate databases and scaled down to the ones that met their
inclusion criteria. They only used parallel or cross over randomized
controlled trails and ended with a reasonable, reliable amount being
42 articles. Findings on each topic they were focused on had its own
section for example, FMD, glucose and insulin metabolism, and
other cardiovascular disease risk biomarkers were some sections
included. Results were backed up with evidence. A lot of different
analyses were used to compare information and results, which got
confusing but was straight forward. All aspects of the research was
addressed, like bias and limitations. Overall the validity of the
results after reading this does not seem very promising because of
weak characteristics in some of the studies like sample sizes,
duration, industry funding, dosage, and missing data to name a few.
Overall I think the article did a great job analyzing and reviewing the
42 articles because they were very systematic and comprehensive
in all the information. I gave it a positive rating.
i) Flavan-3-ol-enriched dark chocolate and white chocolate improve acute
measures of platelet function in a gender-specific way a randomized
controlled human intervention trial
i) This research article was an observed-blinded randomized acute
intervention trial.9 The sample size was 42 healthy subjects. They
wanted to see if flavan-3-ol-enriched dark chocolate would
positively affect platelet function in the subjects compared to
standard dark and white chocolate and whether this relates to
flavan-3-ol bioavailability. The subjects randomly received an acute
dose of flavan-3-ol-enriched dark, standard dark or white chocolate.
There were 14 day wash out periods in between treatments. Before,
two, and six hours after consumption blood and urine samples were
taken. This was to measure for platelet function and bioavailability
and excretion of flavan-3-ols. It was concluded that flavan-3-ols in
dark chocolate but also compounds in white chocolate can improve
platelet function, dependent on gender, and may affect
atherogenesis.
ii) After reading this article, I decided is the worst one I read. This
article is awful. I do not believe it is from a respected journal. Its
very all over the place. The methods and materials arent included
in this version of the journal it directs you to see the Supporting

Information, wherever that is. So I really know nothing reading this


about the treatments besides that it involved three different types
of chocolate. There are no details on the subjects besides that they
are healthy. There was however written informed consent, and study
reviewed by an institutional review board. There was a lot going on
with the measurements and analyses of the plasma, blood, and
urine like initiating activation and spiking human serum samples
just to give examples. There is detail in how each measurement was
taken and analyzed. There is no discussion on reliability or validity
of instruments being used. The whole study comes off to be very
unnatural. No confounding variables were mentioned in the article.
This information was not easily understood. The results answer the
hypothesis however a lot of justifying and explaining why certain
results happened. The results dont stick to the findings and
continue to theorize in this section about them going away from the
subject information a bit. Overall I gave this article a negative rating
because compared to the others it is structurally and experimentally
vague and all over the place.
j) Dark chocolate or tomato extract for prehypertension: a randomized
controlled trial
i) This study was a randomized controlled trail consisting of 36
prehypertensive healthy adults.10 The sample was randomly split
into three groups, 50 g of dark chocolate, tomato extract capsule
containing 15 mg lycopene, or placebo capsule. The trail consisted
of two phases. Phase 1 being a three group parallel randomized
controlled trial and phase 2 followed with a crossover of the two
active treatments. Each treatment was 12 weeks long with an 8
week intervention period and a 4 week wash out period.
Measurements taken were median blood pressure, weight, and
abdominal circumference. There were also a few assessments
through a questionnaire. The results showed that there is a not a
blood pressure lowering effect on dark chocolate or tomato extract
in prehypertensive adults.
ii) This study although did not find statistically significant results was
decently put together. They at least had a sample size above 30,
and thats even with withdrawals. The article is written in a
systematic way that is detailed enough to deem reliable. They,
unlike other articles I read, explained their sample selection. There
was informed consent and review by an IRB. The control group
getting the placebo was getting attention. One set-back was that
the only blinding was in tomato extract treatment because you cant
use blinding when the two treatments being used are totally
different. I also think it was kind of pointless to do the placebo group

because they only took the placebo then had a washout, they
werent part of the cross over at all. Also there was not much
mention about confounding variables being controlled, when it
comes to diet there should be more restriction in the study. Overall
although there was no correlation between dark chocolate and
tomato extract consumption the study was conducted fairly well
compared to others that I read. I gave it a neutral rating.
k) Summary and Conclusions
i) Out of 10 articles I rated 4 neutral, 2 positive, and 4 negative. The
majority of the articles I read had some significant setbacks that
took away from the studys reliability and validity. However all of
them did have some did have good designs. I grade this research II
fair.
ii) Conclusions
Most of the studies I read for this paper were neutral to negative
and did not deduce very strong significant cause and effects
between dark chocolate consumption and cardiovascular health.
What I can take from this is that there may be positive effects of
dark chocolate in our diet that can improve things like
cardiovascular health, blood glucose levels, and endothelial function
but there is not enough evidence to truly say that there are health
benefits. The studies are too varied in results. More research needs
to be done and conducted for further conclusions.

1. Akyol A, Dasgin H, Ayaz A, Buyuktuncer Z, Besler HT. -Glucan


and dark chocolate: a randomized crossover study on short-term
satiety and energy intake. Nutrients. 2014;6(9):3863-3877.
2. Almoosawi S, Fyfe L, Ho C, Al-Dujaili E. The effect of polyphenolrich dark chocolate on fasting capillary whole blood glucose, total
cholesterol, blood pressure and glucocorticoids in healthy
overweight and obese subjects. Br J Nutr. 2010;103(6):842-850.
3. Crews WD, Harrison DW, Wright JW. A double-blind, placebocontrolled, randomized trial of the effects of dark chocolate and
cocoa on variables associated with neuropsychological functioning
and cardiovascular health: clinical findings from a sample of
healthy, cognitively intact older adults. Am J Clin Nutr.
2008;87(4):872-880.
4. Faridi Z, Njike VY, Dutta S, Ali A, Katz DL. Acute dark chocolate
and cocoa ingestion and endothelial function: a randomized
controlled crossover trial. The American Journal of Clinical Nutrition.
2008;88(1):58-63.
5. Grassi D, Desideri G, Necozione S, et al. Protective effects of
flavanol-rich dark chocolate on endothelial function and wave
reflection during acute hyperglycemia. Hypertension.
2012;60(3):827-832.
6. Grassi D, Lippi C, Necozione S, Desideri G, Ferri C. Short-term
administration of dark chocolate is followed by a significant increase
in insulin sensitivity and a decrease in blood pressure in healthy
persons. Am J Clin Nutr. 2005;81(3):611-614.
7. Grassi D, Necozione S, Lippi C, et al. Cocoa reduces blood
pressure and insulin resistance and improves endotheliumdependent vasodilation in hypertensives. Hypertension.
2005;46(2):398-405.
8. Hooper L, Kay C, Abdelhamid A, et al. Effects of chocolate, cocoa,
and flavan-3-ols on cardiovascular health: a systematic review and
meta-analysis of randomized trials. The American Journal of Clinical
Nutrition. 2012;95(3):740-751.

9. Ostertag LM, Kroon PA, Wood S, et al. Flavan-3-ol-enriched dark


chocolate and white chocolate improve acute measures of platelet
function in a gender-specific way--a randomized-controlled human
intervention trial. Mol Nutr Food Res. 2013;57(2):191-202.
10.
Ried K, Frank OR, Stocks NP. Dark chocolate or tomato
extract for prehypertension: a randomised controlled trial. BMC
Complement Altern Med. 2009;9:22.

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