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Chocolate: My Favorite Vegetable Beatrice A. Golomb, MD, PhD with Eric Brown

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.

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Chocolate: My Favorite Vegetable Beatrice A. Golomb, MD, PhD with Eric Brown

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  1. Chocolate: My Favorite VegetableBeatrice A. Golomb, MD, PhDwithEric Brown

  2. "Nine out of ten people like chocolate… "The tenth person always lies." - John Q. Tullius

  3. Till recently, popular perceptions negative – taking your life in your hands

  4. 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

  5. Obesity / “BMI”

  6. Slothful

  7. Blood Sugar…

  8. 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

  9. But mindful of putative benefits to mood "Chocolate makes everyone smile - even bankers." ~ Chocolatier Benneville Strohecker

  10. Emerging Alternative View: Chocolate provides any number of important dietary elements

  11. 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.

  12. Chocolate “Types”

  13. 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

  14. 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"

  15. 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-3-ols [90mg epicatechin] & 100mg isoflavones [aglycone equivalents)]/d) Curtis 2012 Diabetes Care 35: 226 (Flavonol enriched chocolate…)

  16. 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: CholesterolEffect of Enriched vs Regular Chocolate TC:HDL -0.2 ± 0.1 P = 0.01 LDL -3.9 +/- 3.9mg/dL P = 0.04 *27 g/day (split dose) flavonoid-enriched chocolate (with 850 mg flavan-3- Curtis 2012 Diabetes Care 35: 226 (Flavonol enriched chocolate…)

  17. Obesity / “BMI” • Comes with fat and sugar • Indulgence

  18. 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

  19. Finding: Better than wt neutral. Might Chocolate Make you Thinner? Golomb et al 2012. Arch Intern Med 172: 519-21

  20. 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.

  21. “What you see before you is the result of a lifetime of chocolate” -Katherine Hepburn

  22. 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.

  23. If chocolate is an exercise mimetic, putting chocolate in your mouth might actually work in lieu of exercise

  24. 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

  25. 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

  26. 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

  27. 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: DoseHeart Deaths (compared to no choc.) 0 1.0 <1/mo 0.73 (.3-1.3) 1/wk 0.56 (.32-.99) 2+/wk 0.34 (.17-.70) 1 Janszky 2009 J Intern Med 266: 248-57. "Chocolate consumption and mortality following a first acute myocardial infarction: the Stockholm Heart Epidemiology Program."

  28. 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

  29. 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

  30. Stroke Stroke TypeRisk, 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."

  31. 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

  32. 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

  33. Mood • BG add here from choc chapter All Men Women Within Panels: Times/wk, Times/mo (FFQ), Servings/mo

  34. Mood CHICKEN OR EGG? Rose, Koperski, Golomb 2010 Arch Intern Med 170(8) : 699-703

  35. Short term – mood benefits* *Macht 2007 Appetite 49: 667

  36. 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.

  37. 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 . *

  38. Mood Mechanisms (MM) Anandamine, N-oleoylethanolamine N-linoleoylethanolamine* 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 and Health Springer Science+Business Media, LLC • *Fatty acid cannabinoid agonists

  39. Biogenic Amines?

  40. 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

  41. Aggression Golomb et al 2011. "Chocolate consumption is linked to aggression." Circulation suppl 173 P53

  42. Aggression

  43. 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:A16156More Frequent Chocolate Consumption is Linked to Better Word Memory

  44. Chocolate-MemoryImprovement per chocolatex/wk NO tested covariate approached similar significance as a predictor "Food for Thought"? Golomb et al 2012: Circulation 126:A16156More Frequent Chocolate Consumption is Linked to Better Word Memory

  45. 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

  46. 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

  47. 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

  48. 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"

  49. 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

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