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Lack of Blood Pressure-lowering Effects of Cocoa with Natural or High-dose Theobromine
Date 01-14-2011
HC# 101032-416
Cocoa (Theobroma cacao)
Blood Pressure
Re:  Lack of Blood Pressure-lowering Effects of Cocoa with Natural or High-dose Theobromine

van den Bogaard B, Draijer R, Westerhof BE, van den Meiracker AH, van Montfrans GA, van den Born BJ. Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial. Hypertension. November 2010;56(5):839-846.

Consuming foods and beverages rich in flavanols may decrease the risk for cardiovascular morbidity and mortality. Cocoa (Theobroma cacao) and cocoa-containing products, which are rich in flavanols, are presumed to help prevent cardiovascular disease by lowering blood pressure (BP). Theobromine, which is present in cocoa in high concentrations, is thought to have vasodilating properties, thus contributing to cocoa's antihypertensive effect. In this double-blind, placebo-controlled, 3-period crossover study, the authors examined the effects of flavanol-rich cocoa drinks (Unilever; The Netherlands) with natural dose or additional added theobromine versus placebo on peripheral and central BP in subjects with high-normal BP or stage 1 hypertension and low added risk for cardiovascular disease.

Included in the study were healthy male or postmenopausal female volunteers aged 40 to 70 years with high-normal BP (130 to 139/85 to 89 mm Hg) or stage 1 hypertension (140 to 159/90 to 99 mm Hg) with low added risk for cardiovascular disease and not taking BP-affecting medication. Eighty-five prospective subjects took part in 2 screening visits, where a medical history was recorded, physical examination was conducted, and a fasting blood sample was drawn. Of those persons, 42 eligible subjects were recruited.

The study was conducted between November 2008 and October 2009. After baseline measurements were recorded, the subjects were assigned to a random treatment sequence of acidified milk-based drinks containing the following:

  1. Placebo,
  2. Flavanol-rich cocoa powder with natural-dose (106 mg) theobromine (NTC), or
  3. Theobromine-enriched flavanol-rich cocoa powder with high-dose (979 mg) theobromine (TEC).

Treatment duration was 3 weeks, with a 2-week washout period.

The subjects were instructed to drink 200 mL of 1 test drink daily after fasting in the morning. They were allowed to have breakfast 1 hour after consuming the drink. Subjects could maintain their normal diet except that coffee intake had to be less than 4 cups, only milk chocolate could be consumed, and, on the day prior to measurements, coffee, tea, and alcohol could not be consumed.

Study outcome data were collected before the first treatment and after each treatment period. The primary outcome was the difference in 24-hour ambulatory systolic BP (SBP) between placebo and active cocoa products after 3 weeks of treatment. Secondary outcomes were differences between placebo and active treatment in 24-hour ambulatory diastolic BP (DBP), central BP, and systemic hemodynamics after 3 weeks of treatment.

The authors report that except for a 1.2 mm Hg higher 24-hour mean DBP in the NTC group, there were no significant differences between placebo and NTC treatment in ambulatory SBP or DBP for all time periods. In the group receiving TEC, however, mean 24-hour ambulatory SBP and DBP were 3.2 ± 1.1/1.3 ± 0.6 mm Hg higher compared with placebo (P<0.01 and P=0.04, respectively).

Central hemodynamic measurements were taken 2 hours after intake of the test drink, coinciding with the peak plasma levels of the flavanols. Compared with placebo, central SBP and DBP were 4.3 ± 1.4/1.1 ± 0.8 mm Hg lower in the TEC group (P=0.003 and P=0.19, respectively), whereas there were no significant differences between the NTC group and placebo.

Mean arterial pressure was not different between the treatment groups.

Two subjects withdrew from the study due to adverse events: nausea (1) and headache (1), which were both resolved immediately upon cessation of intake.

The authors conclude that flavanol-rich cocoa drinks enriched with theobromine significantly increased 24-hour ambulatory SBP compared with placebo. In contrast, 2 hours after theobromine-enriched cocoa, laboratory peripheral SBP was not different from placebo, whereas central SBP was lower. "Treatment with flavanol-rich cocoa drinks with natural theobromine content did not significantly change either ambulatory or central SBP compared with placebo in these middle-aged individuals with high-normal BP or grade I hypertension and at low added risk for cardiovascular disease," write the authors.

The authors noted that the lack of a BP-lowering effect after consumption of flavanol-rich cocoa drinks could be explained by the content and bioavailability of the flavanols. They include a bioavailability study as a supplement to this article, which revealed significantly increased plasma concentrations of epicatechin and (-)-catechin 1 hour after cocoa consumption and a more gradual increase of the catechins 5-(3,4-dihydroxyphenyl)-y-valerolactone and 5-(3-methoxy-4-hydroxyphenyl)-y-valerolactone, still rising 8 hours after cocoa consumption. The study confirmed the uptake of flavanols under similar conditions as in this trial. The amount of catechin used was 25 mg with NTC and 24 mg with TEC treatment. "We cannot exclude that the amount of epicatechin and the treatment period may have contributed to the lack of a BP-lowering effect observed in our study," write the authors. Lastly, the authors note that flavanol intake was not controlled except for refraining from intake of dark chocolate.

Shari Henson