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Pilar Riobó MD, PhD Endocrinology & Nutrition Madrid www.doctorariobo.com Significance of clinical parameters found so far regarding coffee and diabetes 7th WCPD‐2012

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Page 1: WCPD 2012: Pilar Riobo

Pilar Riobó MD, PhDEndocrinology & Nutrition

Madridwww.doctorariobo.com

Significance of clinical parameters

found so far regarding coffee and

diabetes 7th WCPD‐2012

Page 2: WCPD 2012: Pilar Riobo

Coffee consumption has been linked to poorer health habits, such as smoking and physical inactivity, but…

it also has been associated with a lower risk of type 2 diabetes mellitus in prospective studies

Page 3: WCPD 2012: Pilar Riobo

Data from 18 studies with information on

457 922 participants showed…

...an inverse relationship between coffee consumption and subsequent risk of DM

Every additional cup of coffee consumedin a day was associated with a 7%

reduction in the excess risk of diabetes

Page 4: WCPD 2012: Pilar Riobo

caffeine stimulates the release of adrenaline, an inhibitor of insulin activity, and increases blood pressure and serum homocysteine.

Acute Intake of caffeine impairs glucose metabolism

Page 5: WCPD 2012: Pilar Riobo

Certain components of coffee, such as CGA and other phenolic

compounds, magnesium, and trigonelline, improve glucose

metabolism and reduce inflammation and endothelial

dysfunction.

In the long term, the harmful metabolic and cardiovascular effects

of caffeine would be offset by the beneficial effects of these other

components

Page 6: WCPD 2012: Pilar Riobo

PRCT, 15 volunteers, glucose and insulin after OGTT 12 g decaff coffee, 1 g chlorogenic acid, 500 mg trigonelline, placebo

CGA and trigonelline reduced early glucose and insulin responses, and contribute to the putative beneficial effect of coffee

Page 7: WCPD 2012: Pilar Riobo

Effect on weight

7

Prospective study of 18417 men & 39740 women.

Caffeine intake was assessed every 2–4 y.

Caffeine intake was associated with a smaller weight gain over 12 y of follow-up,

differences were small (but important?) −0.43 kg (95% IC: −0.17, −0.69) in

men −0.35 kg (95% IC: −0.20, −0.62) in

women.

Page 8: WCPD 2012: Pilar Riobo

PRCT to evaluate the efficacy and safety of a green coffee

bean extract (56% CGA) in overweight subjects added to

hypocaloric diet

Significant reductions were observed:

body weight (−8.04 ± 2.31 kg),BMI (−2.92 ± 0.85 kg/m2)

percent body fat (−4.44% ± 2.00%)

Vinson JA, Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2012;5:21-7.

Effect on weight

Page 9: WCPD 2012: Pilar Riobo

cross-sectional survey enrolled 1514 men and 1528 women

Compared with coffee nondrinkers, (all P<0.05) 50% higher interleukin 6 (IL-6), 30% higher C-reactive protein (CRP), 12% higher serum amyloid-A (SAA), 28% higher tumor necrosis factor (TNF-)

concentrations

Moderate-to-highcoffee consumption is associated witn increased inflammation process

(unfiltered coffee was included)

Page 10: WCPD 2012: Pilar Riobo

Effect on inflammation & endothelial dysfunction

In women with 2DM, coffee was associated with lower plasma concentrations of E-selectin: a

soluble vascular adhesion molecule, overexpressed when the endothelium encounters inflammatory stimuli, found to predict CVD)

Lower C-reactive protein (adjusted percentage change 10.2%)

Lopez García E. Coffee consumption and markers of inflammation and endothelial dysfunction in healthy and diabetic women. Am J Clin Nutr.2006;84(4):888-93.

cross-sectional study of 730 healthy women and 663 women with type 2 diabetes from the NHS I

Page 11: WCPD 2012: Pilar Riobo

Kempf K et al. Influence of insulin resistance on the effect of coffee consumption on subclinical inflammation and lipids

Am J Clin Nutr 2010;91:950-957

Changes were observed for:8-isoprostane (-216%)

interleukin-18 (-8%) ,adiponectin (+6%) total cholesterol(+ 12%) HDL cholesterol, (+7%) apolipoprotein A-I (+4%)

No effects on fasting glucose, fasting insulin, and HOMA-IR, IL-6, leptin, LDL-C

8 cups compared with 0 cups coffee/d

An intervention trial in coffee drinkers to investigatethe antiinflammatory effect

Coffee-mediated effects were more

pronounced ininsulin-resistant

individuals

Page 12: WCPD 2012: Pilar Riobo

Japanese women, (N= 459), aged 23-83 years Clinical data included age, BMI, BP, HbA1c, serum hsCRP) and lifestyle habits

Significantly lower levels of hsCRP were observed in the group who drank >1 cup/day so confirming the benefits of coffee consumption, on serum hsCRP in Japanese women, following similarly to other ethnic data.

Kotani K. The relationship between usual coffee consumption and serum C-reactive protein level in a Japanese female population. Clin Chem Lab Med. 2008;46(10):1434-7.

Effect on CRP

Page 13: WCPD 2012: Pilar Riobo

Effect on adiponectin

Williams K. Coffee Consumption Is Associated With Higher Plasma Adiponectin Concentrations in Women With or Without Type 2 Diabetes. Diabetes Care 31:504–507, 2008

982 diabetic and 1,058 nondiabetic women without CVD from NHS

Women with and without diabetes who drank4 cups of coffee/day had higher adiponectin concentrations

Inverse associations of coffee consumption with inflammatory markers, C-reactive protein, & TNF

Page 14: WCPD 2012: Pilar Riobo

Effect of coffee on insulin sensitivity

Inverse association between coffee and HOMA-

IR

(- 8.8% for ≥ 3 cups/day versus never; P =

0.007)

Singapore Prospective study-2 (SP2), 5163 participants,

Rebelllo Coffee and tea consumption in relation to inflammation and basalglucose metabolism in a multi-ethnic Asian population: a cross-sectionalstudy. Nutr . 2011;10:61.

Page 15: WCPD 2012: Pilar Riobo

Consumption of unfiltered coffee increases serum levels of total & LDL cholesterol

Increases in serum lipids were greater

in studies of patients with

hyperlipidemia Jee SH. Am J Epidemiol 2001;153:353

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Metanalysis;12 studies , 1017 subjects

Drinking coffee for 45 days was associated with increase of total -C 8.1 mg/dl (95% CI: 4.5, 11.6;

P<0.001) LDL –C 5.4 mg/dl (95% CI: 1.4, 9.5;

P=0.009) TG 12.6 mg/dl (95% CI: 3.5, 12.6;

P=0.007)

The increase was greater in trials using unfiltered coffee

Those who had hyperlipidemia were more sensitive to the cholesterol-raising effect of coffee

Cai L et al. The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2012 ;66(8):872-7

Effect of coffee consumption on serum lipids

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No effect on LDL levels Phenolic acids are incorporated into LDL Ex vivo oxidation of LDL was significantly

reduced

Natella F.. Am J Clin Nutr 2007

Effect of coffee consumption on LDL

Effect of coffee on the susceptibility of LDL to oxidative modification

Page 18: WCPD 2012: Pilar Riobo

Cross sectional study, 554 adults Consumption of coffee and green tea was assessedMetabolic syndrome was diagnosed using NCEP ATP III Greater coffee consumption was associated with

- lower prevalence of Met-S - lower OR for high serum triglycerides

No significant correlation was found between coffee consumption and either waist circumference or BMI

Takami H. Journal of Epidemiology 2012

Coffee & Metabolic Syndrome

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Observational longitudinal (1976) with 450 children 13.1 ± 0.8 y.o at baseline; 30-year follow-upAt 42 years, Met-S was measured in 344 subjects & coffee consumption was measured at 5 ages

The Amsterdam Growth and Health Longitudinal Study

Moderate and high (>2 cups/day) coffee consumption was associated with lower HDL in women. For men, coffee consumption was not associated with any of the components of the Met-S

Balk L. Eur J Epidemiol.. 2009;24(4):203-9.

Coffee & Metabolic Syndrome

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A rise of 2.04 mmHg in SBP and 0.73 mmHg in DBP

When coffee trials and caffeine trials were analysed separately, BP elevations appeared to be larger for caffeine than for coffee

caffeine:systolic: 4.16 mmHg ; diastolic: 2.41 mmHg coffee: systolic: 1.22 mmHg; diastolic: 0.49 mmHg.

Although regular caffeine intake increases BP, when ingested through coffee, the effect of caffeine is smaller

Blood pressure response to chronic intake of coffee and

caffeine: a meta-analysis

Noordzij M J Hypertens.2005;23(5):921

Page 21: WCPD 2012: Pilar Riobo

Habitual coffee consumption and risk of hypertension systematic review:6 prospective

studies

Habitual coffee consumption of >3

cups/d was not associated with an increased risk of hypertension.

A slightly elevated risk (9%) appeared to be

associated with consumption of 1-3

cups/d

Zhang Z. Am J Clin Nutr 2011

Compared with the lowest consumption ,RRs for

hypertension were 1.09 for 1–3 cups/d, 1.07 for

3–5 cups/d, and 1.08 for 5 cups/d

follow-up : 6.4 to 33.0 y.

Page 22: WCPD 2012: Pilar Riobo

Dose-response meta-analysis of cohort study results of coffee consumption and hypertension risk (shown by first author and year of publication).

Zhang Z et al. Am J Clin Nutr 2011;93:1212-1219©2011 by American Society for Nutrition

Page 23: WCPD 2012: Pilar Riobo

Mesas et al. Am J Clin Nutr 2011;94:1113–26.

Meta-analysis of the acute effects of caffeine on SBP and DBP in hypertensive individuals, by time after caffeine intake.

Caffeine raises BP for ≥3 h after ingestion in hypertensives

Page 24: WCPD 2012: Pilar Riobo

Mesas A E et al. Am J Clin Nutr 2011;94:1113-1126

Administration of 200–300 mg caffeine produced a mean increase of : 8.1 mm Hg in SBP and

5.7 mm Hg in DBP, and lasted 3 h

Acute effects of caffeine on BP in hypertensive individuals

Page 25: WCPD 2012: Pilar Riobo

Mesas A E et al. Am J Clin Nutr 2011;94:1113-1126

 No increase in BP was observed after coffee (compared with a caffeine-free beverage).

No association between habitual coffee consumption and a higher risk of CVD.

No evidence to justify avoidance of coffee consumption in well-controlled hypertensives

Nonetheless, more studies are needed about influence of coffee on the degree of BP control and its possible variation with antihypertensive drugs

Long-term effects of coffee consumption on BP in hypertensive subjects

Page 26: WCPD 2012: Pilar Riobo

Greenberg JA. Caffeinated coffee consumption, cardiovascular disease, and heart valve disease in the elderly . Am J Cardiol

2008;102(11):1502

1354 subjects, Framingham Heart Study, 10 years of follow-up 210 deaths from CVD 118 from CHD.

Coffee consumption was associated with lower risk of CHD mortality in older subjects without hypertension.

 Coffee and CVD

Page 27: WCPD 2012: Pilar Riobo

Coffee and risk of CVD in diabetics

prospective cohort (NHS) study including 7,170 diabetic women with T2D, but free of CVD Coffee consumption was assessed every 2 to 4/y 658 incident cardiovascular events (434 CHD and

224 stroke) RRs for CVD & for all-cause mortality were:

≥ 4 cups/day 0.76 & 0.80 ≥ 2 cups/day decaffeinated coffee , 0.96 & 0.76

higher decaffeinated coffee consumption was associated with lower HbA1c levels (more health-concerned?)

habitual coffee consumption is not associated

with increased risk for CVD or premature mortality among diabetic

womenZhang W. Diabetologia. 2009 May ; 52(5): 810–817

Page 28: WCPD 2012: Pilar Riobo

Is coffee detrimental for persons with CVD?

NHS: Cumulative consumption was calculated with all available FFQs from the diagnosis of CVD to the end of the follow-up in 2004

Coffee intake was not associated with

total or CVD mortality. E. Lopez. Am J Clin Nutr. 2011;94(1): 218–224.

Page 29: WCPD 2012: Pilar Riobo

Post-AMI patients can drink coffee?

No association between moderate coffee intake and cardiovascular events was observed in post–MI

patients after 3.5 years follow-upSilleta MG. Circulation. 2007;116:2944-2951

Page 30: WCPD 2012: Pilar Riobo

Coffee and Risk of heart failure

This study does not support the hypothesis that high coffee consumption is associated with increased rates of HF

Ahmed H. Coffee Consumption and Risk of Heart Failure in Men: an Analysis from the Cohort of Swedish MenAm Heart J. 2009; 158(4): 667–672

Over 9 years of follow-up, 784 men experienced a HF event. Compared to men who drank ≤ 1 cup of coffee per day, RR were: 0.87 for 2 cups/day, 0.89 for 3 cups/day, 0.89 for 4 cups/day, 0.89 (for ≥ 5 cups/day (p for trend in RR = 0.61).

Page 31: WCPD 2012: Pilar Riobo

Coffee consumption and risk of heart failure: Systematic review and a

dose-response meta-analysis

Five prospective studies , including 6522 heart failure events

Moderate coffee consumption is inversely

associated with risk of heart failure,

with a J-shaped relationship

The strongest inverse association was seen

for 4 servings/day and a potentially higher

risk at higher levels of consumption.

Mostofsky E. Circ Heart Fail 2012;5(4):401-5.

Page 32: WCPD 2012: Pilar Riobo

Coffee consumption and risk of stroke

a dose-response meta-analysis of prospective studies

11 prospective studies, with 10,003 cases of stroke and 479,689 participants

Compared with no coffee consumption, the relative risks of stroke were: 0.86 (95% CI: 0.78, 0.94) for 2 cups

of coffee per day, 0.83 (95% CI: 0.74, 0.92) for 3-4 cups/day, 0.87 (95% CI: 0.77, 0.97) for 6 cups/day, 0.93 (95% CI: 0.79, 1.08) for 8 cups/day.

Moderate coffee consumption may be weakly inversely associated with risk of stroke.Larsson SC .Am J Epidemiol

2011;174(9):993

Page 33: WCPD 2012: Pilar Riobo

Risk of AMI, Stroke or Cancer?

Data from 40000 participants in the (EPIC)–Germany study. Intake was assessed by FFQ

During 8.9 y of follow-up, 1432 cases of T2D, 394 of AMI, 310 of stroke,,

1801 of cancer.

Neither caffeinated, nor decaff was associated with the overall risk of chronic diseases

(HR: 0.94; 95% CI: 0.84, 1.05, caff)(HR: 1.05; 95% CI: 0.84, 1.31, decaff)

Lower risk of T2D associated with coffee and decaff

(HR: 0.77; 95% CI: 0.63, 0.94; P-trend 0.009) (HR: 0.70; 95% CI: 0.46, 1.06; P-trend: 0.043)

Floegel A. Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)–German study Am J Clin Nutr 2012 95: 901

Page 34: WCPD 2012: Pilar Riobo

Coffee consumption is

inversely associated with

the risk of bladder, breast,

buccal cavity and pharynx,

colorectum, endometrium,

esophagus, hepatocellular,

leukemia, pancreas, and

prostate cancers

Coffee and cancer risk

Page 35: WCPD 2012: Pilar Riobo

Coffee and mortality

The inverse association was mainly due to a

reduced risk for CVD mortality and was

independent of caffeine

E. Lopez Garcia. Ann Intern Med. 2008;148:904

High coffee consumption

was not related to increased mortality and may even be

associated with lower total and cardiovascular

mortality.

2 large cohorts : NHS and HPFS followed over 2 decades.

Page 36: WCPD 2012: Pilar Riobo

 Coffee and total & cause-specific mortality

Freedman ND. N Engl J Med. 2012;366(20):1891

Health–AARP Diet & Health Study (229,119 men & 173,141 women)

dose-dependent inverse association between coffee drinking and total mortality. Men who drank 6 or more cups of

coffee per day had a 10% lower risk of death, whereas women had a 15% lower risk.

Similar associations were observed for caffeinated or decaff

Inverse associations persisted among diabetics

Page 37: WCPD 2012: Pilar Riobo

Freedman ND. Association of coffee drinking with total and cause-specific mortality. N Engl J Med. 2012;366:1891

  Subgroup Analysis of Associations between the Consumption of 4 or More Cups of Coffee per Day

and Total Mortality.

Page 38: WCPD 2012: Pilar Riobo

What about subjects With Impaired Glucose Tolerance?

The Rancho Bernardo Study

Current or past coffee drinkers who did not have diabetes at baseline had a 60% reduced risk of type 2 diabetes during the next 8 years

The 317 participants with impaired glucose at baseline were similarly protected against diabetes. Smith B. Does coffee consumption reduce the risk of type 2

diabetes in individuals with impaired glucose? Diabetes Care. 2006 ;29(11):2385

Page 39: WCPD 2012: Pilar Riobo

Mechanisms of action of coffee and its constituents responsible for reduce the

risk of the DM2

Pimentel G. Does long-term coffee intake reduce type 2 diabetes mellitus risk? Diabetol Metab Syndr. 2009; 1: 6.

Page 40: WCPD 2012: Pilar Riobo

Women’s Health Study

follow-up of 10 years (n 700) Coffee intake

was positively associated with plasma SHBG.

OR of DM2 for women consuming 4 cups/day of coffee was 0.47

GotoA. Coffee and Caffeine Consumption in Relation to Sex Hormone–Binding Globulin and Risk of Type 2 Diabetes in Postmenopausal Women. Diabetes 60: 269–275, 2011

may it account for the potential protective effect?Strong inverse association between SHBG levels and T2D risk

SHBG

Page 41: WCPD 2012: Pilar Riobo

Effect on gastrointestinal peptides

Higher GLP-1 production after the intake of chlorogenic acid, (the chief polyphenol on coffee) or coffee

Johnston KL, Clifford MN, Morgan LM: Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance: glycemic effects of chlorogenic & caffeine. Am J Clin Nutr 2003, 78:728

McCarty MF: A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Med Hypotheses 2005, 64(4):848-853.

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Fetuin A hepatic secretory protein that binds the insulin receptor in muscle and fat and inhibits insulin action, in vitro. In cross-sectional studies in humans,

higher fetuin-A was associated with insulin resistance

8-week PRCT

Adiponectin and IL-6 levels increased for the

caffeinated coffee group as compared

with the group receiving no coffee.

Ix JH. Fetuin-A and incident diabetes mellitus in older persons. JAMA.2008;300(2):182–188.Wedick et al.: Effects of caffeinated and decaffeinated coffee on biological risk factors for type 2 diabetes: a randomized controlled trial. Nutrition Journal 2011 10:93.

Adiponectin

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Page 44: WCPD 2012: Pilar Riobo

Take home message Coffee consumption increases insulin

sensitivity It may actually decrease an individual’s risk

for T2D Is associated with 20% higher adiponectin Lower levels of inflammatory markers and

fetuin-A Lower levels of markers of liver damage Does not result in worsening of diabetic

control, and it does not increase the risk for diabetic complications

Does not increase cancer risk: It is inversely associated with the risk of bladder, breast, buccal cavity and pharynx, colorectum, endometrium, esophagus, hepatocellular, leukemia, pancreas, and prostate cancers

Page 45: WCPD 2012: Pilar Riobo

Coffee consumption does not cause hypertension.

Coffee consumption causes only minor increases in BP in individuals who do not drink coffee regularly; and this increase disappears when coffee is consumed regularly.

Coffee consumption does not cause CVD Coffee consumption does not cause MI in

patients CVD; Coffee is safe in post AMI patients Moderate coffee consumption is

inversely associated with risk of heart failure, with a J-shaped relationship

Moderate coffee consumption may be weakly inversely associated with risk of stroke

Take home message

Page 46: WCPD 2012: Pilar Riobo

Coffee does not increase the risk of chronic disease

Exists a dose-dependent inverse association between coffee drinking and total mortality in general population, and also in diabetics

Coffee CC is associated with a significant reduction in risk of fibrosis among NASH patients.

Caffeinated coffee consumption can cause mild sleep disturbances, but habitual coffee consumers usually develop tolerance

Although more research on the effect of coffee in health is yet needed, current

information suggests that….coffee is not as bad as previously considered¡¡¡¡

Take home message

Page 47: WCPD 2012: Pilar Riobo

“It is proper at the

present time to devote

time not alone to

treatment but still

more to prevention of

diabetes. The results

may not be so striking

or immediate, but

they are sure to come

and to be important.”

Elliot P. Joslin, 1921

Page 48: WCPD 2012: Pilar Riobo

“It is proper at the

present time to devote

time not alone to

treatment but still

more to prevention of

diabetes. The results

may not be so striking

or immediate, but

they are sure to come

and to be important.”

Elliot P. Joslin, 1921

Thank you for your attention

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Fetuin-A

a biomarker for inflammation and liver function, is a glycoprotein secreted by the hepatocytes with effects on insulin signaling via inhibition of the insulin receptor tyrosine kinase in both liver and skeletal tissue .

Higher fetuin-A levels have been associated with insulin resistance and a higher risk of T2DM

Mori K. Association of serum fetuin-A with insulin resistance in type 2 diabetic and nondiabetic subjects. Diabetes Care. 2006;29(2):468.

Ix JH. Fetuin-A and incident diabetes mellitus in older persons. JAMA.2008;300(2):182–188.

Page 52: WCPD 2012: Pilar Riobo

In cross-sectional studies, coffee consumption has been associated with:

higher adiponectin concentrations,

Williams CJ. Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: a prospective cohort study. Diabetes Care. 2008;31(3):504–507.

lower concentrations of inflammatory markers

Kempf K. Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr. pp. 950–957.

and lower levels of markers of liver damage.

Homan DJ. Coffee: good, bad, or just fun? A critical review of coffee's effects on liver enzymes. Nutr Rev. 2006;64(1):43–46.

Page 53: WCPD 2012: Pilar Riobo

Plasma concentrations of total GLP-1, intact GLP-1 (B)

and GIP (C) before and throughout an OGTT, following ingestion of

chlorogenic acid, decaffeinated coffee,

trigonelline and placebo in 15 healthy overweight men

Decaffeinated coffee slightly increased total

GLP-1 concentration 30 minutes after ingestion (before the OGTT) relative to placebo

(2.7 pmol/L, p = 0.03), butthis change did not correspond

with changes in glucose or insulin secretion

Olthof et al. Nutrition & Metabolism 2011, 8:10

Page 54: WCPD 2012: Pilar Riobo

Fetuin A:

54

hepatic secretory protein that binds the insulin receptor in muscle and fat and inhibits insulin action, in vitro. In cross-sectional studies in humans, higher fetuin-A was associated with insulin resistance

case-cohort study,fetuin-A in baseline serum

was measured among 406 randomly

selected participants and all participants who developed diabetes

during 6-years

fetuin-A levels within the highest tertile had more

than two timeshigher risk of incident

diabetes (HR 2.41; 95% CI 1.28–4.53; P<0.01)

compared to subjects in the lowest tertile

JAMA. 2008 July 9; 300(2): 182–188.

Page 55: WCPD 2012: Pilar Riobo

Keijzers GB, De Galan BE, Tack CJ, Smits P. Caffeine can decrease insulin sensitivity in humans . Diabetes Care. 2002 25(2):364-9.

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Caffeine metabolism

takes place in the liver removal of the methyl 1 and 7

groups in a reaction catalyzed by cytochrome P450, enabling the formation of three methylxanthine groups: paraxantine (84%) increases lypolisis, theobromine (12%) stimulates blood

vessels dilatation and increases the urine volume

theophylline (4%) controls the glucose metabolism

56

Page 57: WCPD 2012: Pilar Riobo

Coffee consumption and CRP levels in postmenopausal overweight/obese women:

importance of hormone replacement therapy use

Plasma CRP was positively associated with BMI and negatively associated with coffee consumption.

Coffee consumption appears to attenuate the association between BMI and CRP, but only in women not using HRT

European Journal of Clinical Nutrition (2009), 1–6