In my continuing obsession with cold exposure, I did some more research into compounds that can activate brown adipose tissue (BAT), in addition to metformin and capsaicin discussed in the previous post.
It turns out that caffeine  and especially caffeinated green tea , also activates BAT! Of course all these studies except for  were performed in rodents, which naturally possess significant amounts of BAT, particularly when housed at chilly (for them) typical lab temperatures. Study  was in humans, and showed that caffeinated green tea promoted more thermogenesis than its caffeine content would predict. Study  is from 1999, a decade before it was discovered that (some) humans have BAT, so they weren't even in a position to speculate that the increased thermogenesis was likely a result of activating BAT. But we know now that is probably the mechanism.
Of course, like with metformin and capsaicin, you need to have brown adipose tissue before green tea can activate it - which again probably requires cold exposure.
I find it really intriguing (and encouraging) that three compounds known to promote health and possibly lifespan, metformin, capsaicin, and green tea, all seem to have their effect, at least in part, via activating brown adipose tissue.
 J Nutr Sci Vitaminol (Tokyo). 1990 Apr;36(2):173-8.
Caffeine activates brown adipose tissue thermogenesis and metabolic rate in mice.
Yoshioka K(1), Yoshida T, Kamanaru K, Hiraoka N, Kondo M.
(1)First Department of Internal Medicine, Kyoto Prefectural University of
To clarify the effect of caffeine on brown adipose tissue (BAT) thermogenesis, we
measured guanosine-5'-diphosphate (GDP) binding, a thermogenic indicator of BAT,
and oxygen consumption in BAT mitochondria as well as BAT temperature and resting
metabolic rate (RMR) in mice. Intraperitoneal injection of caffeine (60 mg/kg)
significantly elevated BAT temperature with less effect on core temperature, and
increased significantly GDP binding and oxygen consumption in BAT mitochondria,
and RMR. These results suggest that caffeine activates BAT thermogenesis, which
may contribute to the increase of RMR.
 Int J Obes. 1991 May;15(5):317-26.
Peripheral mechanisms of thermogenesis induced by ephedrine and caffeine in brown
Dulloo AG(1), Seydoux J, Girardier L.
(1)Centre Medical Universitaire, Department of Physiology, University of Geneva,
The peripheral mechanisms by which ephedrine and caffeine influence thermogenesis
were investigated in innervated rat interscapular brown adipose tissue (IBAT) by
assessing its rate of oxygen consumption (MO2) in vitro. Dose-response
measurements with tissues from intact or sympathectomized (6-OHDA) animals
indicate that the thermogenic effects of low concentrations of ephedrine and also
of caffeine are entirely dependent upon the presence of intact sympathetic nerve
endings, and thus depend on presynaptic mechanisms. Direct postsynaptic
stimulation of thermogenesis is only apparent at much higher concentrations,
namely greater than 1 microM for ephedrine and greater than 2mM for caffeine. At
subminimal concentrations that neither ephedrine nor caffeine influenced basal
tissue respiration, they induced a 4-5-fold increase in basal MO2 when
administered in combination, a synergistic response prevented by pre-treatment of
the rat with 6-OHDA. Synergistic increases in IBAT respiration were also obtained
when subminimal concentration of ephedrine was added to 3-propylxanthine (a
specific inhibitor of phosphodiesterase), to 8-phenyltheophylline (a potent
adenosine receptor antagonist) or to adenosine deaminase (for enzymatic
inactivation of endogenous adenosine). Conversely, the marked synergism in
thermogenic response with ephedrine + caffeine was reduced in the presence of
2-chloroadenosine (an adenosine analogue). In tissues from fasted rats, the
ephedrine + caffeine synergism in thermogenic response, although attenuated, was
nevertheless present. These studies therefore demonstrate that ephedrine, at
doses comparable with therapeutic use, stimulates thermogenesis in BAT via
sympathetically released NA. In addition, a synergistic interaction between
caffeine and ephedrine on BAT thermogenesis is explained by ephedrine's
enhancement of sympathetic neuronal release of NA, together with caffeine's dual
ability to antagonize adenosine and to inhibit cellular phosphodiesterase
 Int J Obes Relat Metab Disord. 2000 Feb;24(2):252-8.
Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine
and sympathetic activity.
Dulloo AG(1), Seydoux J, Girardier L, Chantre P, Vandermander J.
(1)Institute of Physiology, University of Fribourg, Fribourg, Switzerland.
The thermogenic effect of tea is generally attributed to its caffeine content. We
report here that a green tea extract stimulates brown adipose tissue
thermogenesis to an extent which is much greater than can be attributed to its
caffeine content per se, and that its thermogenic properties could reside
primarily in an interaction between its high content in catechin-polyphenols and
caffeine with sympathetically released noradrenaline (NA). Since
catechin-polyphenols are known to be capable of inhibiting
catechol-O-methyl-transferase (the enzyme that degrades NA), and caffeine to
inhibit trancellular phosphodiesterases (enzymes that break down NA-induced
cAMP), it is proposed that the green tea extract, via its catechin-polyphenols
and caffeine, is effective in stimulating thermogenesis by relieving inhibition
at different control points along the NA-cAMP axis. Such a synergistic
interaction between catechin-polyphenols and caffeine to augment and prolong
sympathetic stimulation of thermogenesis could be of value in assisting the
management of obesity. International Journal of Obesity (2000) 24, 252-258
 Am J Clin Nutr. 1999 Dec;70(6):1040-5.
Efficacy of a green tea extract rich in catechin polyphenols and caffeine in
increasing 24-h energy expenditure and fat oxidation in humans.
Dulloo AG(1), Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P,
(1)Department of Physiology, Faculty of Medicine, University of Geneva.
BACKGROUND: Current interest in the role of functional foods in weight control
has focused on plant ingredients capable of interfering with the sympathoadrenal
OBJECTIVE: We investigated whether a green tea extract, by virtue of its high
content of caffeine and catechin polyphenols, could increase 24-h energy
expenditure (EE) and fat oxidation in humans.
DESIGN: Twenty-four-hour EE, the respiratory quotient (RQ), and the urinary
excretion of nitrogen and catecholamines were measured in a respiratory chamber
in 10 healthy men. On 3 separate occasions, subjects were randomly assigned among
3 treatments: green tea extract (50 mg caffeine and 90 mg epigallocatechin
gallate), caffeine (50 mg), and placebo, which they ingested at breakfast, lunch,
RESULTS: Relative to placebo, treatment with the green tea extract resulted in a
significant increase in 24-h EE (4%; P < 0.01) and a significant decrease in 24-h
RQ (from 0.88 to 0.85; P < 0.001) without any change in urinary nitrogen.
Twenty-four-hour urinary norepinephrine excretion was higher during treatment
with the green tea extract than with the placebo (40%, P < 0.05). Treatment with
caffeine in amounts equivalent to those found in the green tea extract had no
effect on EE and RQ nor on urinary nitrogen or catecholamines.
CONCLUSIONS: Green tea has thermogenic properties and promotes fat oxidation
beyond that explained by its caffeine content per se. The green tea extract may
play a role in the control of body composition via sympathetic activation of
thermogenesis, fat oxidation, or both.
 J Nutr Biochem. 2003 Nov;14(11):671-6.
Green tea reduces body fat accretion caused by high-fat diet in rats through
beta-adrenoceptor activation of thermogenesis in brown adipose tissue.
(1)Department of Foods and Nutrition, Kunsan National University, Kunsan,
Cheollabuk-do 573-701, South Korea. email@example.com
The aim of the present study was to investigate body fat-suppressive effects of
green tea in rats fed on a high-fat diet and to determine whether the effect is
associated with beta-adrenoceptor activation of thermogenesis in brown adipose
tissue. Feeding a high-fat diet containing water extract of green tea at the
concentration of 20g/kg diet prevented the increase in body fat gain caused by
high-fat diet without affecting energy intake. Energy expenditure was increased
by green tea extract which was associated with an increase in protein content of
interscapular brown adipose tissue. The simultaneous administration of the
beta-adrenoceptor antagonist propranolol(500 mg/kg diet) inhibited the body
fat-suppressive effect of green tea extract. Propranolol also prevented the
increase in protein content of interscapular brown adipose tissue caused by green
tea extract. Digestibility was slightly reduced by green tea extract and this
effect was not affected by propranolol. Therefore it appeared that green tea
exerts potent body fat-suppressive effects in rats fed on a high-fat diet and the
effect was resulted in part from reduction in digestibility and to much greater
extent from increase in brown adipose tissue thermogenesis through
There will never be peace in the world while there are animals in our bellies.