Weight Control and Slimming Ingredients in Food Technology (Cho/Weight Control and Slimming Ingredients in Food Technology) || The Effects of Caffeine and Green Tea on Energy Expenditure,

P1: SFK/UKS P2: SFKc10 BLBS044-Cho October 15, 2009 21:23 Printer Name: Yet to Come

PART III

Functional Components

159

Weight Control and Slimming Ingredients in Food Technology Susan S. Cho© 2010 Blackwell Publishing. ISBN: 978-0-813-81323-3


CHAPTER 10

The Effects of Caffeine andGreen Tea on EnergyExpenditure, Fat Oxidation,Weight Loss, andWeight Maintenance

Rick Hursel, MSc, and Prof. Dr. MargrietWesterterp-Plantenga, PhD

Abstract

Overweight and obesity, caused by an imbalance between energy intake andenergy expenditure, represent a rapidly growing threat to the health of populationsin an increasing number of countries worldwide. Natural food products such ascaffeine and green tea, which also contains caffeine, are being studied as possiblethermogenic agents that have the ability to increase diet-induced thermogenesis.It has been shown that green tea and caffeine enhance energy expenditure and fatoxidation over 24 hours as well as in the long term. In several long-term studies,it was shown that green tea and caffeine contributed to weight loss or helpedmaintaining weight after a period of weight loss. The main mechanism of actionconsists of the inhibition of two key enzymes that help regulate the sympatheticnerve system. Green tea inhibits the catechol-O-methyltransferase, which usuallydegrades noradrenalin, and caffeine inhibits phosphodiesterase that hydrolysescAMP to AMP. Due to the inhibition of these enzymes, the sympathetic nervesystem is constantly activated, and ultimately this leads to an increase in energyexpenditure and fat oxidation. Green tea and caffeine are natural products thatare safe to use and consume, although there is a limit to the amount of caffeine aperson can consume per day.

161Weight Control and Slimming Ingredients in Food Technology Susan S. Cho© 2010 Blackwell Publishing. ISBN: 978-0-813-81323-3


162 Functional Components

Introduction

Overweight and obesity represent a rapidly growing threat to the healthof populations in an increasing number of countries (“Obesity,” 2000).The ultimate cause of obesity is an imbalance between energy intake andenergy expenditure (EE) (Stunkard, 1996). A negative energy balance isneeded to produce weight loss and can be achieved by either decreasingintake or increasing expenditure. Classical weight-loss programs, such aslow-fat diets, behavioral modification, and exercise, often fail to achievea long-term maintenance of weight loss (Pasman et al., 1999; Waddenet al., 1988). Because of these low success rates, the stimulation of EE (orthe prevention of its decline during dieting) by the use of natural herbalnutrients such as green tea and caffeine has attracted interest. Green tea isconsumed primarily in China, Japan, and a few countries in North Africaand the Middle East (Graham, 1992; Weisburger, 1997). Tea is made fromthe leaves of Camellia sinensis L. species of the Theaceae family, green teabeing the nonoxidized, nonfermented product. As a consequence of this,it contains high quantities of several polyphenolic components such asepicatechin, epicatechin gallate, epigallocatechin, and, the most abundantand probably the most pharmacologically active, epigallocatechin gallate(Kao et al., 2000a).

From caffeine, that is also present in green tea, it has been reportedthat it has thermogenic effects and can stimulate fat oxidation in vitro,in part via sympathetic activation of the central nervous system (Dullooet al., 1992). In humans, caffeine has been shown to stimulate thermogene-sis and fat oxidation (Astrup et al., 1990; Bracco et al., 1995; Dulloo et al.,1989). Green tea extracts, containing caffeine and catechin-polyphenols,have been reported to have an effect on body weight (Chantre and Lairon,2002; Kao et al., 2000a) and EE (Dulloo et al., 1999, 2000). The fact thatgreen tea stimulates thermogenesis cannot be completely attributed to itscaffeine content because the thermogenic effect of green tea is greater thanthat of an equivalent amount of caffeine (Dulloo et al., 1999).

Efficacy of Green Tea and Caffeine

Short-Term Experiments

Green Tea

In a short-term human study epigallocatechin gallate plus caffeine(EGCG/caffeine), (90/50 mg), caffeine (50 mg), or placebo capsules were


Effects of Caffeine and Green Tea 163

consumed three times daily on three different occasions (Dulloo et al.,1999). Relative to the placebo and to the caffeine alone, treatment withthe green tea extract resulted in a significant increase in 24-hour EE(4% = 328 kJ) and fat oxidation, suggesting that green tea has ther-mogenic properties beyond that explained by its caffeine content per se(Borchardt and Huber, 1975). Rudelle et al. conducted a similar studyin which 3 servings of a 250 mL thermogenic beverage per day (during3 days), containing 94 mg EGCG and 100 mg caffeine, were consumed.Twenty-four-hour EE was significantly increased with 4.6% (= 445.2 kJ)after the thermogenic beverage (Rudelle et al., 2007). In another short-termstudy, subjects took two capsules of 150 mg EGCG a day, for 3 days. Onday 3, 24-hour EE was measured, which was increased with a magnitudesimilar to the short-term study of Dulloo et al. In a Japanese study byKomatsu et al., subjects increased their EE over 2 hours with 4%(= 49.5 kJ) after a beverage containing 161 mg caffeine and 156 mgEGCG (Komatsu et al., 2003). These observations were confirmed by de-termining 24-hour EE using respiratory chambers and giving the subjectdifferent dosages of green tea (Berube-Parent et al., 2005). No significantdifference was seen between the different doses of EGCG (Berube-Parentet al., 2005). Comparing all short-term studies, the increase in 24-hourEE was doubled in the latter (24-hour EE = 750 kJ), probably due to thedifference in the amount of caffeine (200 vs. 50 and 100 mg three timesdaily) since the amount of EGCG was, besides the Japanese study, thesame (±300 mg daily) (Berube-Parent et al., 2005). Although the pre-vious studies showed a short-term thermogenic effect of green tea andcaffeine, a recent study by Belza et al. could not retrieve similar resultsfor green tea. They did find that caffeine increased the EE over 4 hourswith 6% (= 72 kJ). No significant effects of both thermogenic agents onenergy intake were found (Belza et al., 2009).

Caffeine

While consuming the same breakfast, normal-weight subjects presenteda greater thermic effect over 3 hours, when it was accompanied with acaffeinated coffee (8 mg/kg body weight) in comparison to a decaffeinatedcoffee (Acheson et al., 1980). Moreover, EE was increased by 16% over a2-hour period with caffeinated (100 mg) compared to decaffeinated coffee(Hollands et al., 1981). In accordance with this effect, an increase inbasal metabolic rate by 3–4% was seen after consumption of a single oraldose of 100 mg caffeine in nine lean and nine postobese subjects (Dullooet al., 1989). A linear, dose-dependent stimulation of thermogenesis, whichlasted longer than 3 hours after administration of 100, 200, or 400 mg oral



caffeine, was observed in subjects with a habitual caffeine intake of lessthan 200 mg/day (Astrup et al., 1990). In 20 female subjects (10 lean and10 obese), an increase in thermogenesis was seen with 4 mg/kg caffeinefive times a day but this increase was smaller in the obese (4.9 ± 2.0%)than in the lean subjects (7.6 ± 1.3%). The thermogenic effect of caffeinewas prolonged even overnight, which may suggest a possible long-termeffect of caffeine (Bracco et al., 1995).

Long-Term Experiments

Green Tea

When investigating the effect of a green tea extract (375 mg catechinsfrom which 270 mg EGCG and 150 mg caffeine/day, divided over fourcapsules) on body weight with 70 overweight subjects, body weight wasdecreased by 4.6% and waist circumference by 4.5% after 3 months, whichis substantial since the study had an open uncontrolled design (Chantreand Lairon, 2002). In accordance with this observation, Japanese studiesshowed that the long-term (12 weeks) administration of tea catechins in adose of 400–700 mg/day reduced body fat and body fat parameters (Haseet al., 2001; Kozuma et al., 2005; Nagao et al., 2001, 2005, 2007; Tsuchidaet al., 2002). Harada et al. demonstrated that after a 12-week administra-tion of a 350-mL tea beverage a day (592.2 mg), EE and dietary fat oxida-tion were increased (Harada et al., 2005). Furthermore, a recent Japanesestudy observed that the daily consumption of 340 mL tea containing576 mg catechins for 24 weeks reduced body fat ratio and waist circum-ference compared to the control group, who had a daily consumption of340 mL tea with 75 mg catechins (Matsuyama et al., 2008). In the Nether-lands, 104 overweight/moderately obese subjects were followed after avery-low-energy diet (2.1 MJ/day) of 4 weeks, during a weight mainte-nance period of 13 weeks in which subjects received placebo or green tea(caffeine/catechins: 104/573 mg/day) (Kovacs et al., 2004). Body weightregain and the rate of regain were not significantly different between thegreen tea and placebo group. Significantly, stronger body weight main-tenance after weight loss was shown by post hoc analysis, that is, 16%body weight regain in the habitually low-caffeine consumers versus 39%in the habitually high-caffeine consumers relative to habitual caffeineconsumption (Kovacs et al., 2004). From a follow-up study, it was con-cluded that habitual high caffeine intake was associated with a significantgreater weight loss (6.7 vs. 5.1 kg) and relatively higher thermogenesis



70

75

80

85

90

95BW

0 1 2 3 4 5

time (months)

BW CH, GT

BW CH, P

BW CL, GT

BW CL, P

**

**

Figure 10.1. Body weight (BW) of men (n = 23) and women (n = 53) overtime. Month 1: after the VLED; month 4: after 3-month follow-up; CL, habituallow caffeine intake; CH, habitual high caffeine intake; GT, green tea duringfollow-up; P, placebo during follow-up. * p < 0.01, at month 1: group (pooledhigh caffeine intake groups vs. pooled low caffeine intake groups) × time (two-factor repeated measures ANOVA). * p < 0.01, at month 4: group (low caffeineintake group receiving green tea vs. all other groups) × time (four-factor repeatedmeasures ANOVA). (After Westerterp-Plantenga et al., 2005.)

and fat oxidation, while green tea was associated with greater weightmaintenance in habitual low-caffeine consumers, supported by relativelygreater thermogenesis and fat oxidation (Westerterp-Plantenga et al., 2005)(Figs. 10.1 and 10.2).

Thus, the effect of green tea may partly depend on habitual caffeineintake. In 46 females following a low-energy diet combined with green tea(caffeine/catechins 225/1,125 mg/day) or placebo supplementation during12 weeks, with caffeine intake being standardized at 300 mg/day, restingEE as a function of fat-free mass and fat mass did not decrease significantlyover time when green tea was ingested independently of habitual caffeineintake. On the other hand, the decrease in resting EE was significant in theplacebo group (Diepvens et al., 2005). However, this did not imply a sig-nificant difference in body weight loss between the green tea and placebo



0.75

0.775

0.8

0.825

0.85

0.875RQ

0 1 2 3 4 5

time (months)

RQ CH, GT

RQ CH, P

RQ CL, GT

RQ CL, P

*

*

Figure 10.2. RQ of men (n = 23) and women (n = 53) over time. Month 1,after the VLED; month 4, after 3-month follow-up; CL, habitual low caffeineintake; CH, habitual high caffeine intake; GT, green tea during follow-up; P,placebo during follow-up. * p > 0.01, at month 1: group (pooled high caffeineintake groups vs. pooled low caffeine intake groups) × time (two-factor repeatedmeasures ANOVA). * p > 0.01, at month 4: group (low caffeine intake groupreceiving green tea vs. all other groups) × time (four-factor repeated measuresANOVA). (After Westerterp-Plantenga et al., 2005.)

group (Diepvens et al., 2005). Moderate use of caffeine is likely to makethe green tea supplement ineffective (Westerterp-Plantenga et al., 2005).

In a recent long-term weight-loss study from Thailand, obese peoplethat consumed the green tea intervention (100 mg EGCG and 87 mgcaffeine/day) lost significantly more weight within 12 weeks compared tothe placebo group (2.7 vs. 2.0 kg) that ate the similar standardized mealsduring the entire study. REE was significantly increased after 12 weeksof green tea supplementation, which led to the body weight reduction(Auvichayapat et al., 2008).

Caffeine

Although caffeine seems to increase thermogenesis in the short term,greater weight loss was not achieved when consuming caffeine in compar-ison to a placebo in obese subjects in the long term (Pasman et al., 1997;Tremblay et al., 1988). The observation that a habitually high (>300mg/day) caffeine intake group receiving a green tea–caffeine combinationdid not show greater body weight maintenance after body weight loss than



a habitually high-caffeine group receiving placebo leads to the suggestionthat sensitivity to caffeine may be lost over time (Westerterp-Plantengaet al., 2005). Increased SNS activity has been shown to lead to a decreasein energy intake (Bray, 1993). In men (but not in women), caffeine con-sumption (300 mg) appeared to reduce energy intake (by 22%) (Tremblayet al., 1988). Moreover, a positive relationship between satiety and dailycaffeine intake, in men and women, was shown (Westerterp-Plantengaet al., 2005). Lopez-Garcia et al. studied the effect of caffeine on long-term weight change in a prospective study. In their cohort, they found thatpeople who increased the caffeine consumption over 12 years gained lessweight than those who decreased the caffeine consumption (Lopez-Garciaet al., 2006). Thus, caffeine may influence both EE and energy intake.

Mechanisms of Action

Catechins in green tea inhibit the enzyme catechol-O-methyltransferase(COMT) that is present in almost every tissue and degrades catecholiccompounds such as norepinephrine (NE) (Dulloo et al., 1999; Westerterp-Plantenga et al., 2005). COMT decreases the hydrophilicity by methy-lation, followed by sulfation and glucuronidation to make the excretionin urine and bile possible (Shixian et al., 2006). NE cannot be degradedthrough the inhibition of COMT and consequently the sympathetic nervesystem (SNS) will be stimulated continuously due to the presence of NE,which attaches to β-adrenoceptors and causes an increase in EE and fatoxidation (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006). TheSNS plays an important role in the regulation of energy homeostasis butthe above-described phenomenon does not always appear equally clearin all ethnic groups. For instance, studies with Asian subjects seem toreport more positive results than studies with Caucasian subjects. Thismay be caused by differences in relevant enzyme activity, causing differ-ences in sensitivity for these ingredients. In that respect, Hodgson et al.(2006) stated that there is a wide variability in flavonoid O-methylation,a major pathway of flavonoid metabolism, by the enzyme COMT. Theinterindividual variability of the activity of COMT could vary as much asthreefold (Hodgson et al., 2006). Moreover, there is evidence that there isa difference in COMT enzyme activity between ethnic groups (Palmatieret al., 1999). Asian populations have a higher frequency of the ther-mostable, high-activity enzyme, COMTH allele (Val/Val polymorphism)than the Caucasian populations. The Caucasian populations have ahigher frequency of the thermolabile, low-activity enzyme, COMTL allele



(Met/Met/Val polymorphism) (Palmatier et al., 1999). Fifty percent ofCaucasians are homozygous for the COMTL allele (25%) and COMTH

allele (25%). The other 50% is heterozygous (Met/Met polymorphism)(Palmatier et al., 1999). This may explain the difference in sensitivity tointerventions with green tea–caffeine mixtures, and why, in some studieswith Caucasian subjects, no effect was seen after ingestion of green tea.

As caffeine is also present in green tea, its effect will also take placeafter green tea consumption. Caffeine affects the thermogenesis by in-hibiting the enzyme phosphodiesterase. This enzyme degrades intra-cellular cyclic amino mono phosphate (cAMP) (Diepvens et al., 2007;Westerterp-Plantenga et al., 2006). Phosphodiesterase usually hydrolysescAMP to AMP, but after consumption of caffeine, cAMP concentrationrises and SNS activity will be increased and inactive hormone-sensitivelipase (HSL) will be activated, which promotes lipolysis (Acheson et al.,2004). The SNS activity and lipoysis are dependent on cAMP, becausecAMP activates the protein kinase A (Belza et al., 2007). Besides theinhibition of phosphodiesterase, caffeine also affects the thermogenesisthrough the stimulation of substrate cycles such as the Cori cycle andthe FFA-triglycreride cycle (Diepvens et al., 2007; Westerterp-Plantengaet al., 2006). Caffeine is a methylxanthine, which has a thermogenic im-pact. In the Cori cycle, lactate moves from the muscles to the liver where itwill be converted into pyruvate. The pyruvate will be converted to glucoseby the enzyme lactate dehydrogenase and circulate back to the musclesvia the blood (Diepvens et al., 2007; Westerterp-Plantenga et al., 2006).Acheson et al. showed that FFA turnover and lipid oxidation are increasedafter the consumption of caffeine but that it requires a large increase inFFA turnover to have a small increase in lipid oxidation. Nonoxidativelipid turnover, the hydrolysis and reesterification of triacylglycerol, isgreater than the increase in oxidative lipid disposal (Acheson et al., 2004).They also found that caffeine antagonizes the inhibitory effects of adeno-sine on lipolysis via adenylyl cyclase. Nonadrenergic thermogenic mech-anisms can also be involved, as caffeine antagonizes the ryanodine re-ceptor, the calcium ion release channel of sarcoplasmatic reticulum inskeletal muscle that for instance increases glycolysis and ATP turnoverafter stimulation (Acheson et al., 2004).

Catechins and caffeine inhibit two enzymes, which interrupt the path-way of NE-activated thermogenesis (Kao et al., 2000b). As SNS activityis determined by the concentration of NE, more NE means a higher ac-tivity and increased EE. SNS activity regulates the resting metabolic rate,which is the largest component of the daily EE. NE makes it possibleto increase the usage of ATP through ion pumping and substrate cycling



(Diepvens et al., 2007). The rate of mitochondrial oxidation is also in-volved in the increased thermogenesis due to the poor coupling of ATPsynthesis, which leads to heat production. Catechins also have a directeffect on the gene expression of different uncoupling proteins (UCPs)that influence the thermogenesis with the production of heat (Klaus et al.,2005). Gene expression of the UCPs also increases when cAMP activatesthe protein kinase A, after the inhibition of phophodiesterase by caffeine(Lowell and Spiegelman, 2000). The protein kinase A stimulates HSL,which increases the concentration of free fatty acids by the conversionof triglycerides. UCP activity will be enhanced through this (Lowell andSpiegelman, 2000).

The increase in EE is accompanied by a change in substrate oxidationas Dulloo et al. showed an increase in fat oxidation after the supplemen-tation of green tea (Dulloo et al., 1999). Another mechanism is triggeredby the tea catechins that block the nuclear factor-κ B (NFκB) activationby inhibiting the phosphorylation of IκB (Yang et al., 2001). NFκB isan oxidative stress sensitive transcription factor that regulates the expres-sion of several genes, which are important in cellular responses such asinflammation and growth (Yang et al., 2001). NFκB is no longer able toinhibit the peroxisome proliferator activated receptors (PPARs) that areimportant transcription factors for lipid metabolism (Murase et al., 2002).The mRNA expression of lipid-metabolizing enzymes such as acyl-CoAoxidase (ACO) and medium-chain acyl-CoA dehydrogenase (MCAD) isupregulated. ACO is a peroxisomal β-oxidation enzyme and MCAD isa mitochondrial β-oxidation enzyme in the liver (Murase et al., 2002).The upregulation of these lipid-metabolizing enzymes makes it clear thatβ-oxidation activation after the supplementation of tea catechins is en-hanced followed by an increase in fat oxidation.

Safety of Caffeine and GreenTea Administration

Caffeine appears to be a safe thermogenic agent for weight control. Inadults, the short-term lethal dose for caffeine is estimated at 5–10 g/day(either intravenously or orally), which is equivalent to 75 cups of coffee,125 cups of tea, or 200 cola beverages (Curatolo and Robertson, 1983).Long-term ingestion of caffeine has been suggested to have some minoradverse effects on human health. Astrup et al. (1990) observed only smalland insignificant changes in blood pressure and pulse rate after 100 and



200 mg caffeine. In contrast, 400 mg caffeine significantly increased sys-tolic and diastolic blood pressure by an average value of 6.3 mm Hg.Furthermore, after 400 mg caffeine, significantly more subjects reportedside effects such as palpitation, anxiety, headache, restlessness, and dizzi-ness compared with placebo (Astrup et al., 1990). Robertson et al. (1978)administrated 250 mg oral caffeine to nine subjects who were not used tocoffee. Systolic blood pressure increased 10 mm Hg 1 hour after caffeineconsumption. Heart rate showed a decrease after the first hour followedby an increase above baseline after 2 hours (Robertson et al., 1978). How-ever, in a subsequent study that examined the chronic effects of caffeineingestion (150 mg/day for 7 days), tolerance to these effects was devel-oped after 1–4 days (Robertson et al., 1981). Thus, no long-term effectsof caffeine on blood pressure, heart rate, or plasma rennin activity weredemonstrated. Furthermore, in the short term, Bracco et al. (1995) did notfind a significantly altered heart rate during the day after 4 mg caffeine perkg body weight was consumed five times daily. Accordingly, the use ofcaffeine is relatively safe, as it is quite certain that, although acute caffeineconsumption may alter some cardiovascular variables, chronic ingestionof caffeine has little or no health consequences.

Green tea has been widely consumed in China and Japan for manycenturies and is regarded as safe. A possible side effect of green teaconsumption is a minor increase in blood pressure as seen by Berube-Parent et al. (2005). They observed a nonsignificant increase (7 mm Hg)in 24-hour systolic blood pressure accompanied by a significant increase(5 mm Hg) in 24-hour diastolic blood pressure. No increase in heart ratewas seen (Berube-Parent et al., 2005). This small short-term increase inblood pressure induced by green tea might be neglected since systolicblood pressure, diastolic blood pressure, and heart rate were not affectedby green tea in other short-term (Dulloo et al., 1999) or long-term research(Chantre and Lairon, 2002; Diepvens et al., 2005).

Food/Supplement Applications

Caffeine and green tea are known to enhance fat oxidation and EE,which makes them excellent (slimming) ingredients for people who wantto lose weight or maintain their weight. These ingredients are also knownto have a positive effect on one’s health as the antioxidants protect againstdifferent types of cancer, cardiovascular diseases, and neurodegenera-tive diseases such as Parkinson’s disease and Alzheimer’s. They are also



offered as capsules and powders and for instance used by athletes to en-hance their performances, as they can give them an energy boost.

Patent Activities

1. Document ID: WO2003090673A2Title: COMPOSITIONS AND METHODS FOR PROMOTING

WEIGHT LOSS, THERMOGENESIS, APPETITE SUPPRES-SION, LEAN MUSCLE MASS, INCREASING METABOLISMAND BOOSTING ENERGY LEVELS, AND USE AS A DIETARYSUPPLEMENT IN MAMMALS

Assignee: RTC RES & DEV LLC2. Document ID: WO2007056133A2

Title: HERBAL COMPOSITION FOR WEIGHT MANAGEMENTAssignee: INDFRAG LTD

3. Document ID: WO2007101349A1Title: COMPOSITIONS AND METHODS FOR INCREASING

ADIPOSE METABOLISM, LIPOLYSIS OR LIPOLYTICMETABOLISM VIA THERMOGENESIS

Assignee: HHC FORMULATIONS LTD4. Document ID: WO2008006082A2

Title: ENERGY ENHANCING FORMULATIONAssignee: BARRON JON

5. Document ID: WO2008028268A1Title: DIET SUPPLEMENT FOR CAUSING WEIGHT LOSS COM-

PRISING CISSUS QUANDRANGULANS, GREEN TEA ANDCAFFEINE

Assignee: MULTI FORMULATIONS LTD6. Document ID: US20020192308A1

Title: Method and composition for controlling weight

Information on Global Suppliers

Green tea and caffeine (coffee, soft drinks, energy drinks) are availablein every supermarket worldwide. Capsules and powders are also availablein commercial stores and on the internet. One of the world’s leadingcompanies in green tea is the Japanese Kao Corporation. Nestle is a bigcompany that deals with caffeine as it exploits the world’s largest coffeebrand.



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