Green Tea and Thermogenesis (long)

As posted by Brooklynjuice:

Green Tea and Thermogenesis
The color (green, oolong, and black) of tea (Camellia sinensis) is determined by how it is manufactured. Green tea is prepared in such a way as to avoid the oxidation of the polyphenols; oolong tea is partially oxidized; black tea is largely oxidized.

The composition of tea is determined by soil conditions, the season the leaves are harvested, and the method used to process the tea. As a rough guide, green tea contains 2.9 to 4.2% caffeine, 0.02 to 0.04% theophylline, and 0.15 to 0.2% theobromine. Green tea also contains theanine, an important water-soluble amino acid that is converted to catechin by sun light. The greatest theanine content is found in the highest grade green tea, Gyokuro, which is cultivated without direct sunlight.

Green tea also contains a number of polyphenolic compounds. The catechin epigallocatechin gallate (EGCG) is the most abundant (> 50% of total tea catechins). It is also believed to be the most pharmacologically active. The other main catechins are epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin (EGC). You can view the chemical structures in a new window.

In addition to stimulating thermogenesis, green tea has a variety of well documented health benefits. Green tea is an antioxidant that has a strong anticancer effects in skin, stomach, colon, etc. Green tea protects against free radicals and it is a logical addition to any supplement program designed to prevent heart disease. In fact, green tea has so many health benefits that this post will have to focus on its ability to stimulate thermogenesis.

Quick facts: The Dulloo et al. studies (1, 2) used an alcohol extract of green tea that is sold in capsule form under the name EXOLISE (Arkopharma Laboratories, Nice, France). This extract is standardized to 24.7% catechins (70% as EGCG), and 8.35% caffeine.
How Powerful Is Green Tea Thermogenesis?
Scientists have found that green tea stimulates thermogenesis and this effect cannot be completely attributed to its caffeine content because the thermogenic effect of green tea is greater than an equivalent amount of caffeine. An in vitro study by Dulloo et al (2) found that a catechin that is abundant in green tea, EGCG, increased the respiration rate of brown fat (stimulated thermogenesis). Dulloo et al. have also done an in vivo study (1) that involved "10 healthy men" who received (with each meal during a 24 hour test period) on three separate occasions:

Test 1: 50 mg caffeine and 90 mg EGCG (total catechins: 125 mg).

Test 2: 50 mg caffeine.

Test 3: Placebo.

There was a "5-10 day interval between successive 24-h trials for each subject." The conditions were controlled and the study was double blind. However, given the fact that obese people respond differently to sympathetic stimuli, it is unfortunate that these tests were performed on "healthy" subjects. The study accepted people described as ranging from "lean to mildly obese" (8-30% bodyfat). But the responses varied widely nonetheless: 24 hour energy expenditure increased "in 6 of the 10 subjects after treatment with the green tea extract, ranging from 266 to 836 kJ" They did not find a correlation between the magnitude of thermogenic response and the degree of fatness of the subjects. That's not too surprising given the number of subjects and the selection criteria. It's a shame that they didn't include more subjects and some fat people in these tests.


Energy Expenditure
Diurnal and 24 hour energy expenditure was increased significantly during treatment with green tea extract. Nocturnal energy expenditure increased, but not significantly. Here's the numbers:

Diurnal: Green tea 4.5% > placebo; Green tea 3.2% > caffeine.
24 hour: Green tea 3.5 % > placebo; Green tea 2.8 % > caffeine.
Perhaps even more interesting is the fact that the green tea extract produced lower respiratory quotients (helped normalize FAT burning):

"Significant differences across treatments were found during the diurnal, nocturnal, and 24-h periods . . . The contribution of fat oxidation [fat burning] to 24-h EE [energy expenditure] during treatment with the green tea extract (41.5%) was significantly higher (p<0.001) than during placebo [31.6%] treatment" (1).

In addition, urinary nitrogen losses showed no significant differences across treatments during all three periods. Clearly, the increased energy expenditure reflects increased FAT burning. This is worth exploring in greater detail.

Written
Dec 2000
Last Update
Dec 2000
Respiratory Quotient
Now we are getting to the interesting stuff. The lower the respiratory quotient, the more fat you are burning. You will often see this referred to as substrate utilization, substrate oxidation (burning), or fuel mix. It is very encouraging that such a small dose of green tea had such an impressive effect on the RQ: The contribution of fat oxidation [fat burning] to 24-h EE [energy expenditure] during treatment with the green tea extract (41.5%) was significantly higher (p<0.001) than during placebo [31.6%] treatment" [emphasis added] (1). Outside of medical journals, fat oxidation and the respiratory quotient are usually only discussed in relation to aerobic exercise (I'm sure you have been told to do low intensity aerobics to burn more fat). However, as usual, the interesting stuff (the stuff that proves obesity is a REAL disease) is ignored.

You see, obese people tend to burn more carbohydrate (glucose) and less fat (fatty acids) than normal people. The Astrup/Toubro team of obesity researchers have studied this defect (4-NA, 5-NA). In fact, a growing number of scientists believe that this part of the thermogenic defect may be more important than energy expenditure. Why do we burn relatively less fat? This is caused be a number of genetic (22) and biochemical defects including insufficient release of noradrenaline and adrenaline. Arne Astrup et al. (5-NA, 22) have written about this genetic defect:

"Direct evidence for a genetic influence on RQ [respiratory quotient] was delivered by Deriaz et al., who studied the relationship between DNA variation at the genes coding for the Na,K-ATPase peptides, RQ, and body fat. Postabsorptive [after a meal] RQ was found to be associated with the alpha2-gene and linked with the beta-gene of the Na,K-ATPase, which suggests that these, or neighboring genes, influence RQ. Twin studies also support the heritability of RQ." [emphasis added] (5-NA).

Based on this study by Dulloo et al. (1), it looks like green tea can help correct this respiratory quotient defect. Of course, ephedrine/caffeine normalizes the release of noradrenaline and adrenaline and corrects the respiratory quotient:

"The respiratory quotient (RQ) indicate that relatively more lipid [fat] was oxidized during chronic ephedrine treatment than in the control study. This change was observed in the fasting state as well as after glucose administration. Certain effects of ephedrine seems to be appropriate to a thermogenic drug for the treatment of obesity: A single dose of ephedrine stimulates thermogenesis, an effect that is enhanced during chronic treatment; Chronic treatment elevates the metabolic rate; and the substrate utilization is changed in favor of lipid [fat] oxidation" [emphasis added] (6).

Is it not curious that doctors tell obese people to eat an abnormally small amount of fat rather than tell us to take thermogenic supplements to correct this genetic fat burning defect? I mean, imagine if your car was having engine trouble and your mechanic refused to fix it and told you to "just drive less." Of course, you would immediately realize that this was a bogus 'solution' and go to another mechanic. But what if they ALL ignored the problem and told you to change your driving habits? Eventually you would realize that you need to read some repair manuals so you can fix the car yourself, right? Fortunately, there is no FDA-type organization trying to pass laws against nonprofessional car repairs.

Obese people who do not want to be mislead by prejudice, ignorance, or political/financial agendas should keep this fuel mix defect in mind when they hear "experts" questioning the importance of thermogenesis. Typically, these "experts" will rattle off a bunch of energy expenditure numbers and tell you that thermogenesis is not very important and thermogenic supplements don't do much. If you want to have some fun, remind the "expert" that there is direct evidence for a genetic influence on respiratory quotient and one of the ways that thermogenic supplements help obese people is by normalizing their defective substrate utilization. Ask the "expert" if he is aware of the fact that a growing number of obesity scientists believe correcting this genetic fat burning defect is more important than those archaic energy expenditure numbers. After all, if you don't BURN fat, you BECOME fat.


Noradrenaline Storage & Release
In order to understand how green tea works we need to take a quick look at noradrenaline storage, release, and metabolism. Noradrenaline is synthesized in the sympathetic nerves and stored in storage vesicles. When sufficiently stimulated, the vesicles migrate to the end of the nerve and release noradrenaline into the synaptic cleft. As you probably already know, the noradrenaline binds to the adrenergic receptors and stimulates thermogenesis. Next in the chain of events is noradrenaline metabolism, which involves two uptake mechanisms.

General references for Noradrenaline Storage, Release, and Metabolism: 3-BK, 20-BK, 21-BK.

Advanced readers should check out "Principles of Neuropsychopharmacology" (3-BK) -- it's an excellent book!






Noradrenaline Metabolism
Uptake 1: After stimulating the adrenergic receptors, 85-90% of the noradrenaline is taken back up into the sympathetic nerves (uptake 1) and stored in vesicles or metabolized by monoamine oxidase (specifically, MAO-A) in the mitochondria. The importance of uptake 1 (neuronal uptake) is reflected by the warnings against combining sympathomimetics (ephedrine, phentermine, etc.) that increase noradrenaline release with MAO inhibitors -- the risk of overstimulation would be much too high.

Uptake 2: Some of the noradrenaline diffuses away from the receptors and is transported by extra-neuronal cells (uptake 2) and metabolized by catechol-O-methyl-transferase (COMT). Green tea increases noradrenaline in the synaptic cleft and safely increases thermogenesis because of its ability to prevent COMT from metabolizing noradrenaline. This is safe because COMT plays a much smaller role in catecholamine dynamics than MAO.

COMT exists in both a soluble and a membrane-bound form. The soluble form of COMT is found in organs and it does not have as high of an affinity for catecholamines as the membrane-bound form.

Quick facts: Uptake 1 of noradrenaline is blocked by cocaine, amphetamines, and tricyclic antidepressants. Progesterone increases MAO and estrogen inhibits MAO.


* There is more information on how caffeine enhances thermogenesis in the following posts: How ECA Works has illustrations and there is referenced information in The "A" in ECA and my Thermogenic FAQ.
How Green Tea Stimulates Thermogenesis
The thermogenic effect of green tea involves two mechanisms: I.) green tea contains a catechin, EGCG, which inhibits catechol O-methyltransferase (COMT), an enzyme that degrades noradrenaline II.) the caffeine in green tea increases intracellular cAMP accumulation by inhibiting the enzyme, phosphodiesterase. See "How ECA Works" for more info on the importance of caffeine.

I have already discussed the effects of caffeine in several posts, so I will focus on COMT. Interestingly, the medical literature showing that green tea inhibits COMT dates back over two decades (7-NA). By inhibiting COMT, green tea prolongs the life of noradrenaline in the synaptic cleft. (This lets noradrenaline stimulate the receptors for a longer time before it is metabolized). The in vivo (human) study by Dulloo et al. (1) found that, compared to placebo and caffeine, green tea significantly increased total 24 hour urinary noradrenaline excretion. The researchers commented on the significance of this:

"This observation is consistent with the inhibiting effect of green tea on COMT, the consequential reduction in norepinephrine [noradrenaline] degradation, and hence, the spillover of norepinephrine into circulation, thereby accounting for the higher urinary excretion of norepinephrine. Such effects, resulting in a prolonged life of norepinephrine in the sympathetic synaptic cleft, could explain the observed effects of the extract in stimulating thermogenesis and fat oxidation" (1).

Written
Dec 2000
Last Update
Dec 2000
Discussion
Although this research is exciting, the fact remains that green tea does NOT normalize the release of noradrenaline (the primary obesity-causing defect) -- it prolongs the action of whatever amount of noradrenaline that your body is able to release. For this reason, Dulloo concluded that the thermogenic effect of green tea is "likely to be highly dependent upon the release of endogenous NA [noradrenaline]." Clearly, green tea (by itself) is going to be a "your mileage may vary" situation. However, tissue studies performed by Dulloo et al. showed that green tea produced a significant synergistic effect when it was combined with ephedrine or ephedrine/caffeine (2).

Since green tea prolongs the action of noradrenaline, you would think that it would have a stimulatory effect. However, Dulloo et al. noted that green tea caused no significant differences in heart rate. The most logical explanation for this is that the stimulatory effect of increased noradrenaline action is being countered by other mechanisms. For example, green tea contains the amino acid, theanine, which has been found to lower blood pressure (. Green tea also has a vasorelaxing effect (9, 10). One recent study found that regular tea consumption had no significant effect on blood pressure (11), but it is difficult to achieve a therapeutic dose without taking concentrated supplements. Further complicating the picture, however, is the fact that they also found that green and black tea caused a short term increase in blood pressure (11).

I hope there will be further research aimed at determining the optimal dosage for the ephedrine/caffeine/green tea combination. It seems likely that the addition of green tea will make it possible to normalize sympathetic tone with a less stimulating stack. In addition, green tea (without ephedrine/caffeine) may permit people with hypertension to obtain a mild increase in fat oxidation and thermogenesis. Clearly, additional research is needed to expand our understanding of the effect of green tea on blood pressure. Hypertensives that want to take green tea should definitely work with a doctor and monitor their blood pressure.

Green tea is an extremely logical supplement for obese people. In addition to its weight loss effect, green tea protects against a number of conditions that are VERY common among the obese:

Green tea has been found to reduce the risk of having a stroke (12, 13).
Green tea has anti-cancer and anti-tumor effects (14, 15).
Green tea can improve glucose/insulin levels and your blood lipid profile (16, 17, 18-NA, 19).
However, it is difficult to obtain all of these health benefits if one does not take green tea supplements -- without supplements, you would have to drink at least ten cups of green tea every day!


Green Tea Products
Green tea has so many health benefits that it's impossible to pick a single best product. The only logical way to evaluate green tea products is to separate them according to their suitability for specific purposes such as weight loss, blood pressure reduction, etc. If you are interested in green tea for cancer prevention and health enhancement, I would shoot for at least 10 cups of tea per day. That's a lot of tea! Perhaps a combination of supplements and drinking tea is the easiest way to consume enough tea.

For the price comparison, whenever possible, I calculated the price per 100 mg of polyphenols and the price per 100 mg of EGCG. These calculations make it easy to compare products with different size capsules and extracts that are standardized to different potencies. I was surprised to find that, based on polyphenol and EGCG content, there were huge price differences between products. For example, Natrol Green Tea Extract is only 3.6 cents per 100 mg of polyphenols; Natures Way Green Tea Extract is a whopping 28.21 cents.

Green Tea For Weight Loss
Research suggests that EGCG is the most important catechin for weight loss. Although most products specify the amount of polyphenols, only a few list the EGCG content. For weight loss purposes, the most powerful Green Tea extract is the standardized Green Tea Extract by NSI -- it contains a whopping 220 mg of EGCG per capsule. The second most powerful green tea extract is the Life Extension Super Green Tea Extract, which contains 122 mg of EGCG per capsule.

Apparently, all of these green tea extracts that are standardized to extremely high levels of EGCG contain very little caffeine. This is good if you are adding green tea to win ECA stack; however, if you are interested in using one of these high EGCG green tea supplements by itself, you'll get much better results if you take some caffeine with it.

Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J "Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans" Am J Clin Nutr 1999, Vol 70 (6), Pg 1040-5. PMID: 0010584049.

2.) Dulloo AG, Seydoux J, Girardier L, Chantre P, Vandermander J "Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity" Int J Obes Relat Metab Disord 2000, Vol 24 (2), Pg 252-8. PMID: 0010702779.

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13.) Uchida S, Ozaki M, Akashi T, Yama****a K, Niwa M, Taniyama K "Effects of (-)-epigallocatechin-3-O-gallate (green tea tannin) on the life span of stroke-prone spontaneously hypertensive rats" Clin Exp Pharmacol Physiol Suppl 1995, Vol 1 Pg S302-3. PMID: 0009072402.

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22.) Deriaz O, Dionne F, Perusse L, Tremblay A, Vohl MC, Cote G, Bouchard C "DNA variation in the genes of the Na,K-adenosine triphosphatase and its relation with resting metabolic rate, respiratory quotient, and body fat" J Clin Invest 1994, Vol 93 (2), Pg 838-43. PMID: 0007509349.