Caffeine + quercetin + exercise = enhanced fat loss

Supplements containing quercetin [structural formula shown below] may well increase fat burning during training, especially when combined with good old caffeine [structural formula shown below]. A test tube study carried out at the National University of Singapore as long ago as 1994 suggests this. According to the research, quercetin enhances the effect of adrenalin-like compounds on fat cells.

The researchers did experiments on fat cells from rats, adding adrenalin and quercetin to the cells in test tubes. Then they watched whether this caused the fat cells to release their contents into the bloodstream. Their main interest was to learn more about the effect of quercetin on the PDE enzyme, or phosphodiesterase. This is the enzyme that is blocked by caffeine. If you block PDE then fat cells dump more fatty acids they have stored into the bloodstream. The name for this is lipolysis. When this happens, the body is able to burn the fatty acids.

Well – quercetin doesn’t work like this. The figure below shows that quercetin, alone or in combination with adrenalin, actually increases the activity of that enzyme. But the figure also shows that quercetin does the same with cAMP, a second messenger. CAMP tells the cell that compounds have attached themselves to receptors and that the cell needs to step up its metabolism. Substances that increase the cAMP concentration have a slimming effect.


The researchers also tested fisetin. This flavonoid had the same effect as quercetin.

But the net effect, however, was that the fat cells released fatty acids. Lipolysis as a result of adrenalin increases if the fat cells are exposed to more quercetin, according to the figure below. The curves with the transparent symbols represent lipolysis when the fat cells are submerged in a solution containing only quercetin [squares] or fisetin [triangles]. The curves with the black symbols represent lipolysis when the fluid also contains isoproterenol, an adrenalin analogue. Quercetin seems to improve the performance of the receptor that adrenalin attaches itself to.


The researchers used quercetin with no sugar groups attached in their experiment. When you consume quercetin the digestive system makes sure that sugar molecules get attached to it really fast. The researchers published an article earlier in which they report that a sugared version of quercetin works less well. [Biochem Pharmacol. 1992 Oct 6;44(7):1307-15.] According to recent research, the cells are capable of removing the sugar molecules again, but scientists don’t know to what extent.

Taking caffeine before training increases the amount of fat you burn. So would a hefty dose of quercetin boost this even further? If you know how quercetin works, it’s not such an unlikely idea.

By the way, quercetin is becoming more and more interesting. See the posting on an animal study in which quercetin boosted metabolism, and another posting on a Japanese rat study in which quercetin inhibits the production of cortisol.

Potentiation of beta-adrenoceptor agonist-mediated lipolysis by quercetin and fisetin in isolated rat adipocytes.


Quercetin and fisetin, two naturally occurring bioflavonoids mobilized lipids and enzymes in the absence or presence of epinephrine in intact rat adipocytes. Dose-(0-250 microM) and time-(0-2 hr) course studies, showed that they stimulated phosphodiesterase (PDE) activity and simultaneously exert cyclic AMP accumulation. These bioflavonoids when present either singly or together with epinephrine stimulated the membrane-bound PDE but not the cytosolic PDE. The stimulation may act as a feedback mechanism to terminate the cyclic AMP effects. The action of theophylline, a known lipolytic agent (exerting its effects through antagonism of adenosine A1 receptor as well as PDE inhibition) was not potentiated by either fisetin or quercetin. However, the flavonoids potentiated epinephrine or isoproterenol- (a specific beta-adrenoreceptor agonist) induced lipolysis. Their effects were inhibited by propranolol (a beta-receptor antagonist). These results suggest that the flavonoids act synergistically with epinephrine on beta-adrenergic receptor and not through phosphodiesterase inhibition to stimulate adipocyte lipolysis. Increase in membrane phospholipid methylation occurred as a consequence of the epinephrine and/or quercetin/fisetin actions, and it correlated with the cellular accumulation of cyclic AMP.
PMID: 7906943 [PubMed – indexed for MEDLINE]