Dark chocolate consumption improves blood pressure and

insulin sensitivity in impaired-glucose-tolerance and

hypertensive individuals.
System(s) involved:
Endocrine, cardiovascular

Therapeutic modality used:

Nutrition

Paper title:
Blood Pressure Is Reduced and Insulin Sensitivity Increased in Glucose-Intolerant,
Hypertensive Subjects after 15 Days of Consuming High-Polyphenol Dark Chocolate

Authors:
Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg J, Ferri C

Journal:
The Journal of Nutrition

Year and issue:

2008;138(9):1671-6.

Aim of the study:

A repeated study dealing with the effects of dietary dark chocolate on insulin
sensitivity and hypertension on individuals with impaired glucose tolerance and
hypertension. This study was conducted to corroborate findings from previous
studies in healthy individuals to see if the intervention was applicable to those who
would benefit from it.

Design of the study:

Randomized single-blind cross-over trial

Setting:
Outpatient clinic at the University of L’Aquila, Italy.

Participants:
19 patients (11 male, 8 female) were recruited from a group of 157 sent to the
Division of Internal Medicine and Centre of Hypertension and Cardiovascular
Prevention Outpatient Unit that were screened for hypertension and glucose-related
conditions (eg. diabetes). Excluded were patients with clinically overt diabetes and
patients with very high blood pressure (over 160 mmHg systolic and over 100
mmHg diastolic).

Intervention(s):
1. 100g flavanol-rich dark chocolate bar in a divided dose with breakfast and
lunch for 15 days. Diet was isocaloric with pre-intervention diet through
advice from dieticians and physicians.

Nathan Nicholls BSc Page 1

 2. 100g flavanol-free white chocolate bar administered in the same fashion as
above.

Main outcome measure(s):

The study measured insulin sensitivity (HOMA-IR [homeostatic model assessment of
insulin resistance], QUICKI [quantitative insulin-sensitivity check index] , ISI [insulin
sensitivity index]) and β-cell function (CIR120 [2-hour corrected insulin response]) by
means of an OGTT (oral glucose tolerance test); hematochemical array (serum
electrolytes, HDL cholesterol, total cholesterol, triglycerides); endothelial function
(endothelium-dependent flow –mediated dilation [FMD] of the brachial artery); and
blood pressure (via 24-hour ambulatory blood pressure monitoring device and
traditional stethoscope with sphygmomanometer).

Summary of key findings & results:

• Consumption of dark chocolate increased insulin sensitivity and β-cell
function compared to baseline levels (decreased HOMA-IR, increased QUICKI
and ISI) whereas white chocolate did not.
• Dark chocolate consumption affected insulin and glucose responses to the
OGTT (P < 0.0001).
• Blood pressure decreased after dark chocolate consumption, significantly so
compared to the lack of change recorded after consumption of white
chocolate.
• Flow-mediated dilation of the brachial artery was improved by dark chocolate
consumption but not white chocolate consumption.
• Dark chocolate consumption decreased both serum total cholesterol (-6.5%; P
< 0.0001) and LDL cholesterol (-7.5%; P < 0.0001) yet did not change HDL
cholesterol or triglyceride levels. White chocolate consumption did not impact
lipid levels.
• Notable correlations:
o Insulin resistance decrease was inversely correlated with the
improvement in endothelial function.
o Insulin resistance decrease was directly correlated with the decrease
of blood pressure measured post-intervention.
o Blood pressure decrease was inversely correlated with the increase in
flow-mediated dilation of the brachial artery.
• Treatment order had no effect on any of the recorded parameters.

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(from Grassi D et al. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive
subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 2008; 138(9):1671-6.) (FRDC – flavanol-
rich dark chocolate, FFWC – flavanol-free white chocolate)

Authors Conclusion:
The consumption of dark chocolate in large (100 g) quantities has a beneficial effect
in the short-term by improving insulin sensitivity, vascular function and blood
pressure in individuals with hypertension and impaired glucose tolerance.

Quality of the evidence:

Grade B.

Conflict of interest:
No conflicts of interest were mentioned.

Cost effectiveness:
There was no discussion of cost-effectiveness.

Discussion:
Since impaired glucose tolerance has been associated with hypertension – which is
a known risk factor for cardiovascular disease (1-3) this study shows the ability of
dark chocolate to benefit individuals with both indications but lacking other known
risk factors such as obesity, smoking and dyslipidemia.

From a nutrition standpoint, testing the efficacy of a whole-food supplement instead

of breaking out the constituents is refreshing to see. To compensate for the high-
caloric value of the addition of the 100 g chocolate bars to the diet, patients were
instructed on how to compensate for this with dietary guidelines. Additionally, the
dietary guidelines precluded patients from consuming other foods and beverages
known to contain significant flavanols (eg. wine). How this would translate to a
therapy remains to be seen, considering that the dosage size employed in this
study is fairly large and may not be palatable to most individuals for an extended
duration.

Limitations:

Nathan Nicholls BSc Page 3

 • The duration of the study and power were rather small. Despite this, the
results agree with a previous study done with a much smaller dose of dark
chocolate over a longer period of time (4).
• The interventions were dissimilar enough to preclude placebo control. This is
a common issue with interventions employing whole food supplements.
However, since the control (white chocolate) was a similar food to that of the
test intervention, it is reasonable to conclude that the patients may not have
been able to determine the specific intent of the test intervention with
respect to the control thereby providing sufficient placebo occlusion.
• Since the presumption of the flavanols present in the dark chocolate and
their benefit to CVD markers is the main driving force for this study, it would
have been beneficial to see a direct observation of cocoa flavanols and
polyphenols with metabolites in blood plasma and/or urine along with the
effects of NO.
• Since cocoa (and accordingly, dark chocolate) is known to contain a
significant amount of magnesium (among many other constituents), it is
difficult to attribute the therapeutic effect of dark chocolate solely on the
flavanols as done by the authors of this study (5). Magnesium
supplementation is known to have significant effects on blood pressure and
insulin sensitivity (6).

The data reported in this study was done so in a fashion that was strictly relative;
no specific values were released. Therefore it is not possible to calculate NNT for
this study.

Application of results to patients:

Dark chocolate supplementation may be an additional consideration when
incorporated with a standard low-glycemic index diet for impaired glucose-tolerance
patients. Care should be taken to compensate for such a high-energy food in terms
of caloric intake.

Etiology & prevalence of condition:

As of 2008, wholly one third of the population of the United States is considered
hypertensive (7). Essential hypertension is a condition of kidney pathology with 3
pathways (reduced glomerular filtration rate reducing sodium excretion; excessive
sodium reabsorption in the distal nephron caused by genetic abnormalities; renal
ischemia, oxidative stress and inflammation) (7). Research done in 2007 estimated
that 13% of the US population 20 years or older had type 2 diabetes mellitus and a
further 30% had prediabetes (including impaired glucose tolerance) (8). An
association with obesity and thus diet can be done with both hypertension and
metabolic syndrome (including impaired glucose tolerance) over the past 100 years
(7).

Further work/research needed:

• A comparison of flavanols derived from cocoa and magnesium to determine
independent and synergistic effects of these ingredients.
• A higher power study with a longer duration needs to be completed.
• Variation of dark chocolate cocoa levels to more directly establish correlation.

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 • Variation of quantity administered to determine threshold of beneficial effect.

Date of completion: November 7, 2010

Reviewer: Nathan Nicholls BSc

Supervisor: Heidi Willms ND

References:

1. Amini M et al. People with impaired glucose tolerance and impaired

fasting glucose are similarly susceptible to cardiovascular disease: a study
in first-degree relatives of type 2 diabetic patients. Ann Nutr Metab 2010;
56:267-272.
2. Van Vliet M et al. Differential impact of impaired fasting glucose versus
impaired glucose tolerance on cardiometabolic risk factors in multi-ethnic
overweight/obese children. Eur J Pediatr 2010 October 20 (E-published
ahead of print).
3. Tugrul A, Guldiken S, Ugur-Altun B, Arikan E. An evaluation of glucose
tolerance in essential hypertension. Yonsei Med J 2009; 50(2):195-9.
4. Taubert D et al. Effects of low habitual cocoa intake on blood pressure and
bioactive nitric oxide. JAMA 2007; 298(1):49-60.
5. Meisel P. Hypertension, diabetes: chocolate with a single remedy? Letter
to the editor. Hypertension 2005; 46:e17-e18.
6. Fox C, Mahoney MC, Ramsoomair D, Carter CA. Magnesium deficiency in
African-Americans: does it contribute to increased cardiovascular risk
factors? J Natl Med Assoc 2003; 95:257-262.
7. Johnson RJ et al. Pathogensis of essential hypertension: historical
paradigms and modern insights. J Hypertens 2008; 26(3):381-91.
8. Valdez R. Detecting undiagnosed type 2 diabetes: family history as a risk
factor and screening tool. J Diabetes Sci Technol 2009; 3(4):722-6.

Nathan Nicholls BSc Page 5

RES100 Research Assignment Part 1 – Nathan Nicholls 1015124

Question: Can dark chocolate ingestion be used to increase insulin sensitivity in individuals
diagnosed with impaired glucose tolerance compared to a placebo?

Investigation: The idea of using a food to aid in blood sugar control for diabetics is not new.
Research into specific foodstuffs and the effects they have on insulin sensitivity (among other
symptoms diabetics wish to control) is increasing as we discover how food plays an enormous
role in this disease.1 One concern I have about using dark chocolate therapy in this manner is the
risk/benefit of having a patient intake a fairly large amount of saturated fat, along with the
dietary compensation required to allow for the high caloric value of this food. Since chocolate is
a relatively popular treat, patients will most likely follow through with this treatment – at least at
first – with the potential caveat of saturation (ie. patients may become disinterested in the food
due to the repetitive nature of continuous daily intake). Type 2 diabetes is rapidly becoming an
epidemic so viable treatment options (of any kind) are desperately needed.2 As much as
conventional medicine has made inroads with the availability of injectable insulin and other
drugs3 it seems that there needs to be a much greater focus on lifestyle adjustments like diet and
exercise, with a specific focus on foods that can directly assist in the control of blood glucose
levels. I have a personal tie to diabetes, as the disease exists in my father’s side of the family. As
such, this research is directly relevant to me and how I may practice in the future.

1. Marrero DG. The prevention of type 2 diabetes: an overview. J Diabetes Sci

Technol 2009; 3(4):756-60

2. Colagiuri R. Diabetes: a pandemic, a development issue or both? Expert Rev

Cardiovasc Ther 2010; 8(3):305-9

3. Zinman B et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in
combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4
Met+TZD). Diabetes Care 2009; 32(7):1224-30

Nathan Nicholls BSc Page 6

RES100 Research Assignment Part 2 – Nathan Nicholls 1015124

Question: Can dark chocolate ingestion be used to increase insulin sensitivity (as measured via
an oral glucose tolerance test) in individuals diagnosed with impaired glucose tolerance
compared to a placebo?

1. Search: “dark chocolate” AND “insulin sensitivity”

a. PubMed MeSH: There are no MeSH terms for this search.
b. See above.
2. PubMed and Alt HealthWatch were searched.
3. PubMed yielded 4 results for this search. Three of the four results are clinical trials and
one is a review. Alt HealthWatch yielded one review article.
4. This initial search strategy was designed to determine the breadth of research done
around my question. Unfortunately there doesn’t seem to be a lot of research related
directly to my search query. However, the articles generated are extremely relevant to the
search question.

1. Search: “chocolate” AND “insulin” AND “sensitivity”

a. PubMed MeSH: ("cacao"[Mesh] AND "insulin"[Mesh] AND "sensitivity and
specificity"[Mesh] )
b. “Cacao” had the following trees: Organisms Category > Eukaryota > Plants > Plant
Families and Groups > Angiosperms > Sterculiaceae > Cacao.
“Insulin” had the following tree: Chemicals and Drugs Category > Homones,
Hormone Substitutes, and Hormone Antagonists > Hormones > Peptide Hormones >
Pancreatic Hormones > Proinsulin > Insulin.
Chemicals and Drugs Category > Amino Acids, Peptides, and Proteins > Peptides >
Peptide Hormones > Pancreatic Hormones > Proinsulin > Insulin.
“Sensitivity and specificity” had seven trees (here is the first): Analytical, Diagnostic
and Therapeutic Techniques and Equipment Category > Investigative Techniques >
Epidemiologic Methods > Statistics as Topic > Sensitivity and Specificity.
2. PubMed and Alt HealthWatch were searched.
3. PubMed yielded 10 articles; 6 of which are clinical trials. Alt HealthWatch yielded 3
articles – none of which were clinical trials.
4. This search didn’t seem to yield a great deal of information, but one of the 6 articles from
PubMed happened to be a perfect fit for my question.

1. Search: “chocolate AND “diabetes”

a. PubMed MeSH: ("Cacao"[Mesh] AND "Diabetes Mellitus"[Mesh])
b. PubMed Mesh: “Cacao” had the following tree: Organisms Category > Eukaryota
> Plants > Plant Families and Groups > Angiosperms > Sterculiaceae > Cacao.
“Diabetes Mellitus” had the following trees:

Nathan Nicholls BSc Page 7

 Diseases Category > Nutritional and Metabolic Diseases > Metabolic Diseases >
Glucose Metabolism Disorders > Diabetes Mellitus.
Diseases Category > Endocrine System Disease > Diabetes Mellitus.
2. PubMed and EBSCO were searched.
3. PubMed yielded 53 results. Of these results, 7 are clinical trials. EBSCO yielded 60
results, of which 10 were clinical trials.
4. To observe a more broad-based search result, I decided to employ the least specific terms
that would still emcompass relevant results. Despite the increase in results, there are
actually fewer relevant results when compared to the previous search.

Nathan Nicholls BSc Page 8