Chocolate:
My Favorite Vegetable
Beatrice A. Golomb, MD, PhD
with
Eric Brown
"Nine out of ten people like
chocolate…
"The tenth person always lies." - John Q. Tullius
Till recently,
popular
perceptions
negative –
taking your life
in your hands
The Rap
•
•
•
•
•
•
•
•
•
High in saturated fat - Bad for cholesterol
High in sugar - Bad for insulin/ diabetes
High in calories - Makes you fat
Which makes you slothful
Plus, it gives you cavities
These should hurt heart health
And overall health
Flip side: good for your mood
Makes you happier and therefore nicer
Obesity / “BMI”
Slothful
Blood Sugar…
People ate chocolate despite
presumed health effects
My therapist told me the way to achieve true inner
peace is to finish what I start. So far today, I have
finished 2 bags of M&M’s and a chocolate cake. I
feel better already.
– Dave Barry
But mindful of putative
benefits to mood
"Chocolate makes everyone smile - even bankers."
~ Chocolatier Benneville Strohecker
Emerging Alternative View: Chocolate
provides any number of important
dietary elements
Principles
• Prefer outcomes that balance risks &
benefits -- to the patient (e.g. all-cause
mortality; not single cause or class)
• Prefer long-term follow-up.
(Shortterm can be opp. to longterm effects)
• RCT best: 2nd is prospective longitudinal.
• Require Data: but Think Physiologically!
• Beware: Not all chocolate is alike!
• Accompaniments differ, and carry their own
health ramifications: Nuts; dairy; sugar
amount; trans fats; etc.
Chocolate “Types”
Cocoa Butter
+
+ Dark
Cocoa
Chocolate*
- White
chocolate
White
baking bar
*Add milk-> milk chocolate
(or, chocolate milk)
**Add cream -> mousse!
CHOCOLATE is a vegetable
•
•
•
•
•
•
 Antioxidant via phytonutrients1,2
 BP3-5  Insulin resistance3-5,
Improve cholesterol profile6
Inflammation (women)6
Coronary artery diameter7 (on angio)
Supply many interesting compounds
1.Vinson 2006 J Agric Food Chem 54:8071
2. Spadafranca 2010 BrJNutr 103:1008 3.Grassi 2005 AmJClinNutr 81:611
4. Grassi 2005 Hypertension 46:398
5.Grassi 2008 J Nutr 138:1671
6. Hamed 2008 SouthMedJ 101:1203 7 *Flammer 2007 Circulation116:2376
8. Nogueira 2011 J Physiol 589: 4615
Blood pressure: RCT
Design: Meta-analysis of RCTs
Ss: 173 (from 5 studies)
Exposure: Cocoa products
Control: Cocoa-free controls
Duration: Median 2 weeks
Outcome: Blood pressure
Result:(mean pooled)
SBP: -4.7 mm Hg* (95%CI -7.6 to -1.8 mmHg)
DBP: -2.8 mm Hg* (95%CI -4.8 to -0.8 mmHg)
Taubert 2007 Arch Intern Med 1657:626 "Effect of cocoa and tea intake on blood pressure: a
meta-analysis"
Blood sugar/ insulin
Design: Double-blind RCT
Ss: 118 (59/group) diabetic (Type-2) post-menopausal women
(on statin plus glucose-lowering drug)
Exposure: High-Flavonol chocolate*, 27g/d split
Control: Callebaut regular chocolate, 27g/d split
Duration: 1 year
Outcomes: 1. Insulin.
2. Insulin resistance: HOMA (homeostatic assessment of IR)
3. Insulin sensitivity (QUICK-IS: quant IS index)
Result:
Insulin:
-0.8 ± 0.5 mU/L
P=0.02
HOMA-IR:
-0.9 ± 0.2
P=0.004
QUICK-IS:
+0.003 ± 0.00
P=0.04
*27 g/day (split dose) flavonoid-enriched chocolate (with 850 mg flavan-3ols [90mg epicatechin] & 100mg isoflavones [aglycone equivalents)]/d)
Curtis 2012 Diabetes Care 35: 226 (Flavonol enriched chocolate…)
Cholesterol
Design: Double-blind RCT
Ss: 118 (59/group). Post-menopausal women w/ type 2
diabetes, on statin plus glucose-lowering drug
Exposure: Hi-Flavonol chocolate*, 27g/d split
Control: Callebaut regular chocolate, 27g/d split
Duration: 1 year
Outcomes: Ratio of Total chol (TC):HDL; LDL-cholesterol.
Result:
Cholesterol
TC:HDL
LDL
Effect of Enriched vs Regular Chocolate
-0.2 ± 0.1
P = 0.01
-3.9 +/- 3.9mg/dL
P = 0.04
*27 g/day (split dose) flavonoid-enriched chocolate (with 850 mg flavan-3Curtis 2012 Diabetes Care 35: 226 (Flavonol enriched chocolate…)
Obesity / “BMI”
• Comes with fat and sugar • Indulgence
CHOCOLATE vs BMI
Hypothesis: Frequent modest chocolate is
calorie neutral: extend to BMI the metS
benefits of chocolate
Ss: 1018 adults (694 men, 324 women) w/o DM
or CAD, from San Diego
Design: Cross-sectional
Exposure: Chocolate times/week
Outcome: BMI (measured weight & ht)
Covariates: Age, sex, calories, activity, sat fat,
mood
Result: More frequent chocolate eaters: more
calories, no more exercise BUT weigh less!
Golomb et al 2012. "Association Between More Frequent Chocolate
Consumption & Lower Body Mass Index." Arch Intern Med 172: 519-21
Finding: Better than wt neutral.
Might Chocolate Make you Thinner?
Chocolate Frequency
Association to BMI
Adjustment Model
β
p
-0.14
0.01
Unadjusted
-0.13
0.02
Age-sex adjusted
-0.13
0.01
Age-sex-activity
-0.15
0.01
(Age-sex-activity-calories)
-0.19
0.001
Age-sex-activity-sat.fat
-0.20
0.001
Age-sex-activity-sat.fat-CESD
Golomb et al 2012. Arch Intern Med 172: 519-21
CHOCOLATE vs BMI
Can't presume causality BUT:
-- Rationale guided conduct of study
-- No identified "confounders" to explain
-- Rodent studies concordant
-- In humans, benefit to other metabolic
parameters
-- Emailed after study was published by a
researcher who did an RCT of chocolate,
and unexpectedly found sev lbs wt loss in
the chocolate vs control group, among
overwt but not normal wt subjects
SO: there are prospects for causality.
“What you see before you is the result of a
lifetime of chocolate” -Katherine Hepburn
Exercise?
Cocoa derived epicatechin
in mice:
 Lean muscle mass,
 Fat mass,
 "Mitochondrial Biogenesis"
 Muscle "Vascularity"
Exercise mimetic?
Nogueira 2011 J Physiol 589: 4615-31 "(-)-Epicatechin enhances fatigue resistance
and oxidative capacity in mouse muscle"
Villarreal 2010 "Chocolate: an exercise mimetic?" Southwest Chapter American
College of Sports Medicine 2010 Annual Meeting, Oct 22, San Diego.
If chocolate is an exercise mimetic,
putting chocolate in your mouth might
actually work in lieu of exercise
Chocolate Milk & Endurance
Design: Crossover RCT
Subjects: 9 trained male cyclists
Chocolate "intervention": "chocolate milk"
CM: Chocolate milk = Mars Refuel, 459± 53mL, 62.9±7.2g,
FR: Fluid replacement = Gatorade, 526.3±60.4 mL, 30.7±3.5g
CR: carb replacement:Endurox R4, 526.3±60.4 mL, 72.5±8.3g
Outcome: Cycle duration. (3 trials of glyogen depleting, 4hr
recovery, cycle to exhaustion. Intervention @ 0&2hr recovery
Result:
CM: 32 ± 11 min
FR: 23 ± 8 min, p = 0.01
CR: 21 ± 8 min, p = 0.01
CM -> cycled 43% and 51% longer than w/ FR & CR
Thomas 2009 "Improved endurance capacity following chocolate milk consumption
compared with 2 commercially available sport drinks" Appl Physiol Nutr Metab 34: 78-82
Exercise?
"The divine drink which
builds up resistance and
fights fatigue. A cup of
this precious drink
permits a man to walk for
a whole day without
food."
– Hernando Cortés, 1519
Heart Health
Design: Prosp Cohort (Zutphen
Elderly Study) 1
Ss: 470 elderly men
F/U: 15 yrs
Exposure: Top vs bottom third of
Cocoa consumption (estimated
fm cocoa-containing foods)
Result:
 Cardiovascular death:
RR: 0.50 (0.32-0.78) P = .004
1
Buijsse 2006 Arch Intern Med; 166:411.Cocoa intake, blood pressure, and cardiovascular
mortality: the Zutphen Elderly Study
Heart Health
Design: Prosp Cohort 1
Ss: 1169 Swedes 45-70 w/ 1st-MI, no DM
F/U: 8 yrs
Exposure: chocolate in prior 12mo.
Never, <1/mo, 1/wk, 2+/wk
Outcome: cardiac death
Result:
Dose
0
<1/mo
1/wk
2+/wk
1
Heart Deaths (compared to no choc.)
1.0
0.73 (.3-1.3)
0.56 (.32-.99)
0.34 (.17-.70)
Janszky 2009 J Intern Med 266: 248-57. "Chocolate consumption and mortality
following a first acute myocardial infarction: the Stockholm Heart
Epidemiology Program."
Heart Failure
Design: Prospective Cohort
Ss: 31,823 women 48-83 (Sweden)
-- No hx diabetes, heart failure, MI
F/U: 9 years
Chocolate: Consumption by quartiles
Outcome: Heart failure
Analysis: "Survival analysis"
Result: 379 hospitalized + 40 died, of HF
1-2 "servings" per week = optimal
HR: 0.68 (95%CI 0.50-0.93)
More than daily: nothing (trend unfavorable)
1
Mostofsky 2010 Circ Heart Fail 3: 612-6 Chocolate intake and incidence of heart
failure: a population-based prospective study of middle-aged and elderly women
Stroke
Design: Prospective Cohort (mammography cohort)
Subjects: 33,372 Swedish women age 49-83.
Follow-up: 10.4yrs ave.
Chocolate: FFQ 1997, chocolate on ave over prior
year. Quartiles to group chocolate.
Lowest <8.9g/wk. Highest >45g/wk (mean 66.5)
Outcome: Strokes over 1 yr (1998):
Covariates: Many Age, education, smoking, BMI, activity, aspirin
use, hx HTN, dx atrial fibrillation, FH premature heart disease, alcohol,
coffee, tea, total calories, fresh red & processed red meat, fruit,
vegetables,
Larsson 2011 JACC 58 1828-9. Chocolate consumption & risk of stroke in women
Stroke
Stroke Type
Risk, hi vs low chocolate quartile
Only hi quartile benefit:
All
0.8 (0.66-0.99)
p =0.01 (for trend)
Infarction
0.83 (0.66-1.04)
p =0.04
Hemorrhagic
0.58 (0.34-1.00)
p =0.04
Comment: >45g/wkvs <9. Only hi quartile benefited median 66.5
g/week (chocolate equivalent to ~15 “kisses”)
Comment: Same result RR for stroke= 0.8, in 2012 meta-analysis of prospective
studies, men & women, >100,000 people†
Larsson 2011 JACC 58 1828-9. "Chocolate
consumption and risk of stroke in women."
†Larsson 2012 Neurology 79:1223-9.
"Chocolate consumption and risk of
stroke: A prospective cohort of men and
meta-analysis."
Brain - Mood
Popular perception that when people need a pick-me-up,
they pick up chocolate.
~No evidence, hitherto.
Denise Mann 2010 "Study: Chocolate and depression go hand in hand", CNN
Health.com Apr 26
http://www.cnn.com/2010/HEALTH/04/26/chocolate.depression/index.html
Brain - Mood
Design: Cross-Sectional
Subjects: 1018 adult men and women 20-85 years
Chocolate measure:
Times/wk (SSQ). Time/mo (FFQ). Servings/mo (FFQ)
Outcome: Center for Epidemiological studies – Depression
Scale. Cutoff at 16 = used as a screening cutpoint for
depression.
Result:
Higher chocolate linked higher depression
Rose N, Koperski S, Golomb B 2010. "Mood Food: Chocolate and Depressive
Symptoms in a Cross-sectional Analysis." Arch Intern Med 170(8) : 699-703
Mood
16
• BG add here from choc chapter
Chocolate Consumption
12
8
CES-D <16
CES-D 16-21
4
CES-D ≥22
0
FFQ-C
times/mo
FFQ-C
times/mo
SSQ-C
times/week
CES-D Women
FFQ-C
times/mo
FFQ-C
times/mo
SSQ-C
times/week
CES-D Men
FFQ-C
times/mo
FFQ-C
times/mo
SSQ-C
times/week
CES-D All
All
Men
Women
Within Panels: Times/wk, Times/mo (FFQ), Servings/mo
Mood
CESD <16
CESD 16
Chocolate (g)
5.4 (8.8)
8.4 (15)
Fat (g)
68 (40)
75 (46)
KCalories
Rel. Diff P
(%)
56.
.004
1681 (791) 1785 (958)
9.5
.17
6.2
.24
C'hyde (g)
187 (91)
198 (109)
5.9
.28
Caffeine (mg)
148 (147)
158 (155)
1.1
.70
CHICKEN OR EGG?
Rose, Koperski, Golomb 2010 Arch Intern Med 170(8) : 699-703
Short term – mood benefits*
*Macht 2007 Appetite 49: 667
Mood Mechanisms:
Factoid: Chocolate has substances that bind
“cannabinoid receptors” in the brain*
I suggest it is the “chocolate receptor;”
The intended ligand is chocolate, & regular
binding is essential for good neurochemical
health. Some of us see no need for"special" brownies
.
*di
Tomaso 1996. Brain cannabinoids in chocolate. Nature; 382:677-8.
Cannabinoids
"Researchers have discovered that chocolate
produces some of the same reactions in the
brain as marijuana.
“The researchers also discovered other
similarities between the two, but can't
remember what they are."
--Matt Lauer
.
*
Mood Mechanisms (MM)
Anandamine, N-oleoylethanolamine Nlinoleoylethanolamine*
Polyphenols (antioxidation)
Altered copper balance: Copper Fungicides
Methylxanthines (boost mood; anxiogenic in excess)
Theobromine Caffeine (also: Sleep Effects)
Withdrawal: amines, methylxanthines
Tetrahydro-beta carbolines: potential neuroalkaloids
Microflora contamination Magnesium repletion.
Biogenic amines
Phenylethylamine Ethylamine Synephrine
Serotonin Histamine Isobutylamine Tyramine
Normetanephrine Octopamine Tryptamine
• Millen MM, Golomb BA 2012 "Chocolate: Mood" Chapter 30 in Nutrition
Biogenic Amines?
Aggression
Design: Cross-sectional
Subjects: 1018 adults (San Diego), 20-85
Exposure: Chocolate times/week
Outcome:
1. Overt Aggression Scale (a): behavioral aggression
against others, self, or objects in the last week.
2. Road rage: tally of increasingly severe behaviors
engaged in (last 2 weeks) (0-10, max seen=7)
3. Impatience (self-rated, 0-10)
Covariates: age, sex, smoking, alcohol
Golomb et al 2011. "Chocolate consumption is linked to aggression." Circulation
suppl 173 P53
Aggression
Chocolate Effect,
per time/week
βSE
P
OASMa
+0.180.06
0.005
Impatience
+0.090.03
0.004
Road Rage
+0.110.03
<0.001
Ordinal Logistic Regression:
Adj. for age sex smoking alcohol
β = regression coefficient. SE = standard error
P = probability effect could occur by chance
Golomb et al 2011. "Chocolate consumption is linked to aggression." Circulation
suppl 173 P53
Aggression
Memory
Design: Cross-sectional (="slice in time")
Subjects: 1018 men + women (age20-85)
Chocolate: Times/week. Mean 2±2.5 (0-20)
Memory: Word recall test (number correct).
Mean 86±8.
Analysis: Regression
Age-interaction effect: P<0.001 (I.e. relation of
chocolate to memory differs w age)
Covariates: Age, sex, exercise, calories
Trans-fats, LDL-chol, depression (CES-D)
Result: if age< 50, chocolate   memory
Golomb et al 2012: Circulation 126:A16156 More Frequent Chocolate
Chocolate-Memory
Improvement per chocolatex/wk
Unadjusted
Age, sex
Age, sex, exercise
Age, sex, exercise, calories
All Above+transfat, LDL
All above+CES-D* (depression)
NO tested covariate approached
similar significance as a predictor
"Food for Thought"?
Golomb et al 2012: Circulation 126:A16156 More
Frequent Chocolate Consumption is Linked to Better
 (SE)
0.64 (.17)
0.66 (.18)
0.67 (.18)
0.78 (.22)
0.83 (.22)
0.89 (.24)
P
<0.001
<0.001
<0.001
0.001
<0.001
<0.001
Cognitive RCT
Design: Double-blind RCT (1:1:1 randomization)
Subjects: 90 Alzheimer's Unit patients w/ MCI mild cognitive
impairment (Petersen criteria). (Exclude statin users)
Chocolate "intervention": Hi, med, low flavanol chocolate.
High and Med used Cocoapro processed cocoa powder. Low
used highly processed alkalinized cocoa.
HF: 990 mg flavanols
MF: 520mg
LF: 45mg
Duration: 8 weeks
Outcomes: 1 Trails A/B 2.Fluency words/time
Results (HF vs LF chocolate):
Trails A+B time: 38±11 vs 53±18 seconds p<0.05
Verbal fluency: 28 vs 22 words/min p<0.05
Desideri, 2012 "Benefits in Cognitive Function, Blood Pressure, and Insulin
Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild
Cognitive Impairment: The Cocoa, Cognition, and Aging (CoCoA) Study"
Hypertension 60: 794-802
Pre-Carious? Or the opposite?
Cavities form when specific cavity-promoting
bacteria feed on carbohydrates & produce a slime
layer of water-insoluble "glucan" by which they
adhere firmly to the tooth, & produce acid that
leads to local demineralization of the tooth
Cocoa polyphenols significantly  biofilm (slime)
formation & acid production by cavity-forming
bacteria (Streptococcus mutans & S. sanguinis).
Cocoa substances added to water powerfully
 cavity & plaque formation in rats.
Ferrazzano 2009 Fitoterapia 80: 255-62 "Anti-cariogenic effects of polyphenols from
Ooshima 2000 Arch Oral Biol 45: 639-45
Ito 2003 Biosci Biotechnol Biochem 67: 2567-73
Pre-Carious? Or the opposite?
Although killjoy David Beighton (Professor at King's
College, London) stated "Good oral hygiene,
rather than eating lots of chocolate, is the
way to good healthy teeth"
(Quoted in a BBC story on the cavity-fighting
benefits of cocoa products.)
Author Ooshima thinks cocoa substances
should be added to toothpaste,
mouthwash.
Ferrazzano 2009 Fitoterapia 80: 255-62:
Ooshima 2000 Arch Oral Biol 45: 639-45
Ito 2003 Biosci Biotechnol Biochem 67: 2567-73
BBC News Aug 24, 2000 Chocolate 'fights' tooth decay
CHOCOLATE & SKIN
Design: Dbl blind placebo-controlled
Subjects: 30 adults (22women)
Interv: 15 high flavonol Belgian chocolate, chocolate droplets
(Acticoa method, preserves flavonols), 20g/d x 12 wks
Control: 15 conventional chocolate droplets, 20g/d x 12 wks
Outcome: MED=min erythema dose UVB(280-320nm)
Result: Double the min erythema dose w "HF" chocolate
(p=0.005), not placebo (P= 0.5)
Williams 2009 J Cosmet Dermatol 8 : 169-73. "Eating chocolate can significantly protect the skin from UV light"
Survival
“I have this theory that chocolate slows down the
aging process…It may not be true, but do I dare
to take the chance?”
--Unknown
CHOCOLATE & MORTALITY
Design: Prosp Cohort (Zutphen Elderly Study) 1
Ss: 470 elderly men
F/U: 15 yrs
Exposure: Highest vs lowest tertile Cocoa
(estimated fm cocoa-containing foods)
Outcome:All death (314)
Result:
 All Deaths: 0.53 (0.39-0.72)
1
P<.001
Buijsse 2006 Arch Intern Med; 166:411. "Cocoa intake, blood pressure, and
cardiovascular mortality: the Zutphen Elderly Study"
Women and Chocolate
"After about 20 years of marriage, I'm finally
starting to scratch the surface of what
women want. And I think the answer lies
somewhere between conversation and
chocolate."
– Mel Gibson
But benefits extend to men. Rebranding?
Not Just for Women
Caveats
Chocolate comes with
“stuff”
• Dairy (Milk
chocolate)
• Nuts
• Coffee
• Cinnamon (Mexican
chocolate)
• Trans fats
The Rap
•
•
•
•
•
•
•
•
Bad for cholesterol?
Bad for blood sugar?
Makes you fat?
Hinders exercise?
Causes cavities
These should hurt heart health?
And overall health and survival?
Good for your mood?
The R(ec)ap:
•
•
•
•
•
•
•
•
•
•
Mood & aggression: associations unfavorable
Good for blood pressure
Good for insulin sensitivity
Good for cholesterol
Maybe good for BMI (animal exp + human observ’l)
Not “pre-carious” (prevents cavities, apparently)
Good for physical function (exercise)
Good for brain function (e.g. memory)
Favorable link to heart disease & stroke
Associated with longevity
The (almost) perfect vegetable
Concluding Remarks
"The superiority of chocolate, both for
health and nourishment, will soon
give it the same preference over tea
and coffee in America which it has in
Spain."
- Thomas Jefferson
"Chemically speaking, chocolate
really is the world’s perfect food."
• – Michael Levine, nutrition researcher
Or, the Ideal Medicine?
This no longer seems
entirely facetious
As Recognized by our Forebears
"Chocolate is a divine, celestial drink …,
panacea and universal medicine."
-- Geronimo Piperni (1796; quoted by
Spanish army surgeon)
Chocolate
An important food group.
Incorrect. This neglects one other important food,
My other favorite vegetable: Coffee
Thank You!
• Thanks to Eric Brown, who contributed
substantially to this talk
• IF you want us to email any of our articles, let us
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• THANK YOU FOR LISTENING!
Conflict of Interest
The chocolate industry doesn't give
us money; rather, vice versa.