Yerba Mate

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Yerba Mate is a flowering tree in which its leaves are commonly consumed as a stimulant tea in varying parts of the Middle East and Southern America. It is a cocktail consisting of xanthines (like Caffeine), flavonoids (like Quercetin), saponins (like Ursolic Acid), and cinnamic acid compounds (like Chlorogenic Acid). It also contains some 'matenosides' which seem to be unique compounds to Yerba Mate, but they in isolation are not well studied.

Yerba Mate is commonly touted for its ability to suppress appetite and burn fat, but the former requires a high dose (if that) and the latter seems to be solely due to Caffeine. It has not really proven itself to be a more effective fat burner than other compounds, like Green Tea Catechins. It seems to be pretty good at partially reversing some of the adverse health effects seen with obesity, and reducing the rate of weight gain during an obesogenic (obesity causing) diet.

Yerba Mate, however, is sufficiently anti-inflammatory and anti-oxidant. It seems to be able to reduce LDL cholesterol fairly quickly (within 20 days) and is cardioprotective like many plants.

It is a tea, it is healthy, it does not appear to be sufficiently healthier than other teas of plant-based drinks (like coffee) although it does have its own unique nutrient composition.

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It is thought that a good conversion dose from animal studies to humans is that 1g/kg bodyweight in rats equals about 1.5 liters of Yerba Mate tea

Human studies that note benefit on lipid and glucose metabolism use 3 cups (each cup being 330mL) of Yerba Mate tea daily, for a period of up to 60 days. Tea up to 1.5 liters daily has been shown to be well tolerated in humans, although toxicity has not been seen in animals at higher dosages either.

Isolated Yerba Mate in supplemental form tends to be around 1,000 to 1,500mg of Yerba Mate leaf.

Although the notion that "Yerba Mate is a better stimulation than coffee" cannot be ruled out at this time, there is no evidence to support it either. The Matenosides are underresearched but may play a role (being unique to Yerba Mate consumption)

Kurtis Frank

The Human Effect Matrix looks at human studies (excluding animal/petri-dish studies) to tell you what effect Yerba Mate has in your body, and how strong these effects are.

Level of Evidence	Effect	Change	Magnitude of Effect Size	Scientific Consensus	Comments
C	Metabolic Rate			100% See study	No significant influence on metabolic rate has been noted
C	Fat Oxidation		Minor	100% See study	An increase in fat oxidation assessed via a lower respiratory quotient has been noted
C	Heart Rate		Minor	100% See study	A decrease has been noted with Yerba Mate consumption, which is somewhat notable as stimulants tend to increase heart rate
C	Blood Pressure			100% See study	No significant influences on blood pressure have been noted (although this may be due to it being underresearched; Mate may follow the same motifs as caffeine ingestion)
D	General Oxidation		Minor	100% See study	A decrease in serum oxidative parameters tends to be noted following Mate consumption
D	Anti-oxidant Enzyme Profile		Minor	100% See 2 studies	Appears to increase the primary three antioxidant enzymes (glutathione, catalase, and SOD) in both healthy and diseased persons
D	LDL-C		Minor	100% See all 3 studies	Decreases in LDL cholesterol have been noted in metabolically unwell persons following moderate Mate consumption (as brewed tea)
D	Apolipoprotein B		Minor	100% See study	Somewhat of a decrease in hyperlipidemic patients consuming Mate tea
D	HDL-C		Minor	100% See study	An increase in HDL-C has been noted with Mate consumption
D	Total Cholesterol		Minor	100% See study	A decrease of total cholesterol has been noted with Mate consumption
D	Lipid Peroxidation		Minor	100% See study	A decrease in lipid peroxidation has been noted with Mate consumption over 7 days
D	HbA1c		Minor	100% See study	A decrease in HbA1c levels has been detected in type II diabetics consuming Mate tea, although not to a remarkable degree
D	Blood glucose		Minor	100% See study	A slight decrease in blood glucose has been noted with Mate consumption in type II diabetics; no evidence in otherwise healthy persons
D	Bone Mineral Density			0% See study	An association has been noted with increased bone mineral density and Mate consumption; insufficient evidence to suggest a causative role
D	Esophageal Cancer Risk			0% See study	The association between Mate and esophageal cancer is due to the temperature of which it is traditionally drunk (scalding to the back of the throat), and applies to any... show hot beverage yet not to chilled Mate or capsules

Studies Excluded from Consideration

• Excluded due to being confounded with Guarana and Damiana Leaf (as YGD capsules)^[3]

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Edit1. Sources and Composition

1.1. Sources

Yerba Mate is a commonly used tea also known as Ilex paraguariensis, in which Ilex refers to the genus. Yerba Mate is a small shrub that grows up to 15 feet as a tree when aged, and bears small white flowers and red fruits. While the tree is the 'Mate' tree, the leaves are commonly referred to as Yerba; hence 'Yerba Mate' tends to be composed of the leaves from this plant.^[4][5] The main producers and consumers of Yerba Mate tea are the countries of Argentina, Paraguay and Brazil.^[5]

It is possible that crude yerba mate is more effective than commercial yerba mate, as one animal study investigating crude (drying the plant) against commercial (blanching, drying, milling, and aging) found the crude extract more potent.^[6] This may be due to significantly higher levels of Caffeine and theobromine in the crude extract relative to commercial (1075.04±29.7ug/mL crude; 959.57±12.6 commercial) and saponin content (386.81±1.6ug/mL crude; 102.98±0.6 commercial).

In addition to the lower bioactive component quantities, the processing of Yerba Mate may also produce Polyaromatic Hydrocarbons; compounds formed from heating some molecules that are seen as carcinogenic.^[7][8]

Its a plant that people make tea from the leaves. Some of the bioactives can be destroyed in processing though

1.2. Composition

As a herbal supplement, yerba leaves contains a variety of molecules including:

• Flavonoids such as Quercetin, Kaempferol and Rutin, the latter at 6.10 ± 0.21mg/g dry weight,^[9] although it varies on extraction^[10]
• Various (5+) cinnamic acids such as Caffeic, 3,4-dicaffeoylquinic acid, feruloylquinic acid, and Chlorogenic Acid, in which amounts of the latter can degrade by half through freeze drying (10.4 to 5.6mg/g dry weight)^[9][11]
• Caffeine (at around 17.5mg/g fresh weight Yerba Mate) and related xanthines^[12]
• 27+ different saponins, of which are combinations of Ursolic Acid, acetyl-ursolic acid, oleanolic acid as well as pomolic acid^[13] These three in varying glycosides make up the majority of the saponin content^[11] and make up about 3-10mg/g dry weight of the leaves.^[14]
• Megastigmane compounds, sometimes referred to as Matenosides^[15]
• Vitamin C^[16]
• Vitamin B1^[16]
• Vitamin B2^[16]

The fruit of the Yerba Mate tree (not commonly used in teas) includes:

• Matesaponins, usually ursolic acid and oleanolic acid although Ilexoside II (glycoside of pomolic acid) and brevicuspisaponin-1 (another pomolic acid compound) are also present in the fruit^[17]

It should be noted that Yerba Mate is frequently referred to as possessing 'Matesaponins'; these are usually glycosides of ursolic acid (ursolic acid bound to sugars).^[13][18] Matenosides also exist, and Matenoside A and B appear to refer to another class of Megastigmane compounds.^[15]

The two classes of compounds above are referred to as the 'active' ingredients, although all classes found in Yerba appear to be significantly bioactive.

The fresh leaves of Yerba Mate have the highest polyphenolic and saponin content when compared to leaf extract of dried leaves, but still less overall phenols than Camellia Sinensis (Green Tea).^[19] These two plants, however, have more polyphenols than a wide variety of other plants.^[20] During Yerba Mate processing (consisting of blanching, drying, milling, and aging) saponin and xanthine content both appear to be significantly reduced (xanthines to 89% of original values, saponins to 27% of original value).^[6]

In general, it would be good to think of Yerba Mate as the five compounds pictured above. Each compound represents a class (and there are most likely hundreds of compounds in Yerba Mate belonging to these classes), and each class tends to have similar biological effects

Edit2. Interactions with Body Fat

2.1. Adipogenesis

Yerba Mate appears to be able to inhibit adipocyte differentiation in vitro, and the compounds rutin (100ug/mL) and Chlorogenic Acid (300ug/mL) appear to contribute most potently to this effect.^[9] Suppression was also noted on genes associated with adipogenesis (C/EBPα, PPARγ2, TNF-α) in which both rutin and CA were again the most potent.^[9] These isolated compounds were more effective than leaf extracts (fresh and dried), suggesting that synergy between nutrients in Yerba Mate do not exist or apply to adipogenesis.^[9]

A study in C57BL/6J mice using Yerba Mate at three doses (0.5, 1, and 2g/kg bodyweight) for 6 weeks significantly reduced food and water intake (seemingly dose dependent, but differences between doses not significant) ^[21]

Sounds nice, and may contribute to some of the soon-to-be-mentioned anti-obesity effects.

2.2. Metabolic Rate and Inducing Fat Loss

A study investigating 1.5g of Yerba Mate powder in a blinded manner found that there was no significant effect of Yerba Mate on the Metabolic Rate, although the respiratory quotient dropped indicating more fatty acids burnt for metabolic purposes over glucose.^[22] A decrease in heart rate alongside no influences on blood pressure were noted.^[22]

A rat study using high dose Yerba Mata (1g/kg bodyweight; human equivalent dose of 160mg/kg) found that after obesity was induced, consumption of Yerba Mate was able to reduce the state of obesity without influencing food intake.^[23] Yerba Mate was able to greatly attenuate changes in adipose mRNA associated with obesity, including an attentuation of TNF-α, IL-6, Leptin, and CCR2 and CCL2. A significant rise in anti-obesity mRNA including PPARy², Adiponectin, PCG-1α and UCP1 was noted, as well as a decreased macrophage infiltration of adipose.^[24][23] Another rat study using 0.24%w/w Yerba Mate in the food during inducing obesity in rats was able to reduce final body weight by 10.7%, and food intake appeared to be reduced by 4.32%,^[24] and attenuation of body weight gain and reversing of some negative health effects of obesity has been seen at lower dosages of 100mg/kg bodyweight as well (16mg/kg bodyweight human equivalent).^[25]

Possibly related to improvements in mRNA of PGC-1α and PPARy², it was noted that Yerba at 0.24%w/w of the diet was able to negate the suppression of AMPKα induced by obesity and cause a relative increase in protein content of AMPKα in adipose tissue.^[24]

Interestingly, a study using up to 2g/kg bodyweight Yerba Mate in C57BL/6J mice found significant decreases in weight that could not solely be explained by the reduction of food intake noted;^[21] body weight was significantly reduced after 1 week, but declined at a lesser rate beyond that until study cessation at 6 weeks. This curve mimicks the metabolic curve of Caffeine, in which fat burning becomes desensitized to after a week. Another study investigating lipase inhibition noted a similar curve for 1 week after Mate ingestion at similar dosages.^[26]

A case can be made for fat burning effects of Yerba Mate to be due greatly to the xanthine component.^[21] This is not to conflate overall weight loss, however, as Yerba Mate may inhibit nutrient uptake and reduce appetite (both of which would contribute to weight loss independent of metabolic rate)

Only human study using reasonable dosages showed no acute benefit, whereas the rat studies that did show benefit were more 'attenuate weight gain' rather than 'induce weight loss'; high dosages used as well

2.3. Appetite

It is theoretically possible that Yerba Mate can suppress appetite, due to its Caffeine content (a conditional appetite suppressant) and its ability to reduce gastric emptying after meals.^[3] This appetite suppression has been noted in rats fed 50-100mg/kg bodyweight (human equivalent dose of 8-16mg/kg bodyweight), in which GLP-1 and leptin increases via caffeic compounds and the Yerba Mate saponins were credited.^[27]

One human study using YGD capsules (Yerba Mate, Guarana, and Damiana) found that after 10 days of using 3 YGD capsules before major meals (3 capsules totalling 336mg Yerba, 285mg Guarana, 108mg Damiana) that placebo group lost 0.3+/-0.03kg and YGD lost 0.8+/-0.05kg.^[3] When the study was extended to 45 days, the difference were a loss of 0.3+/-0.08kg (placebo) and 5.1+/-0.5kg (YGD).^[3]

A 12 month maintenance period was done in an unblinded manner and without placebo, but it was found that continual ingestion of YGD capsules was able to maintain this weight loss.^[3] No dietary records or excretory measures were taken (not even total dose of YGD daily), so a suppression in food intake or food absorption cannot be ruled out.

Other studies looking at the possibility of appetite suppression have varied. One study investigating HDL oxidation rates that did not instruct dietary changes found that, after 15 days supplementation, dietary intake was significant reduced from an average of 1706.9+/-414.8kcal daily to 1470.8+/-446.5kcal in a sample of 15 women; suggesting appetite suppression from 3 servings of 330mL yerba mate tea.^[28] A larger scale study investigating Yerba Mate where diet was recorded, however, did not find statistically significant differences; the group instructed to 'eat more fruits, veggies and less bad fats' ate about 100kcal more than the group simply told to drink 1 liter of yerba mate tea daily.^[29] A study on men (half with type II diabetes) also found a non-significant trend of decreased food consumption, but more minor than the previous study and around 50-100kcal with tea intervention.^[30]

Its possible yerba mate suppresses appetite, but the studies aren't of a quality to support this view. The unblinded nature could have just steered participants away from a cookie, or the yerba tea could have made the ice cream taste bad.

Edit3. Interactions with Glucose Metabolism

3.1. Carbohydrate Absorption

Yerba Mate has been shown to decrease SLGT1 gene expression in the intestines after 1g/kg ingestion for 28 days in diabetic and non-diabetic rats.^[31] This effect was hypothesized to be from the flavonoid content (of which includes Quercetin) and Chlorogenic Acid,^[31] with variable degress of downregulation (53.8% and 19.3% reduction in upper small intestine activity of nondiabetic and diabetic rats, respectively; 26.6% and 46.2% reduction in middle small intestine, respectively).^[31]

3.2. Obesity induced Diabetes

A study on C57BL/6J mice indicated that 2g/kg of Yerba Mate daily was able to bring abnormal blood glucose levels (induced by a high (60%) fat diet) to match control, and doses lower than that (0.5, 1g/kg) were able to attenuate the changes over 6 weeks.^[21]

These results are not unanimous, as some studies do note no significant changes in blood glucose. One study using 1g/kg bodyweight Yerba Mate over 28 days noted no significant differences in glucose, insulin, or glucose-6-phosphatase activity in the liver in non-obese alloxan-induced diabetic rats.^[31]

In humans, Yerba Mate tea (3 cups of 330mL daily) over a period of 60 days was able to decrease elevated blood glucose by 25mg/dL and reduce HbA1c by approximately 0.85%.^[30]

Edit4. Interactions with Lipid Metabolism

4.1. Mechanisms

Yerba Mate, at 1-2g/kg bodyweight, has been shown to inhibit pancreatic lipase in mice.^[26] In vitro analysis showed a dose-dependent increase in inhibition until Yerba Mate hit 3mg/mL, corresponding to 9mg of Yerba Mate extract per gram of enzyme substrate (in this case, fatty acids) and with a 79+/-1.3% inhibition.^[26] Weight gain was attenuated with Mate, but fecal fat analysis was not conducted to assess fat malabsorption.^[26] This lipase inhibition appears to be related to the matesaponins, and a pure water extract of yerba mate seems to be less effective in vitro (58%) than other extracts (88-95%) as the most potent lipase inhibitor are fat soluble.^[32]

4.2. Anti-oxidation of Lipoproteins

An ex vivo study using blood from volunteers found that ingestion of Yerba Mate tea was able to reduce the rate of forced oxidation of LDL induced by copper, but was apparently ineffective at protecting LDL from oxidation induced by lipoxygenase or peroxynitrate.^[33] This protection has also been seen in vivo with the HDL molecule in vitro^[34] and after consumption of 5g instantized Yerba Mate in adult men.^[28]

This protection from lipid peroxidation extends to polyunsaturated fatty acids, as a study in mice livers found reduced rates of PUFA oxidation with Yerba Mate at dosages starting at 0.5g/kg bodyweight and up to 2g/kg bodyweight.^[35]

4.3. Interventions

An intervention study using 1 liter of Yerba Mate tea daily over a period of 90 days found that LDL cholesterol was significantly decreased (160mg/dL to 150mg/dL) in dyslipidemic women without any dietary changes needed.^[29] This same study design was carried out in diabetic and pre-diabetic men to much the same effects, decreasing LDL-C and also improving parameters of glucose metabolism.^[30] In both cases, the tea itself did not influence diet significantly yet the other groups fed yerba and given new diets fared better than the groups given yerba in isolation.^[29][30]

The effects seen with Yerba Mate also appear to be additive to statin therapy, and may offer hope as a adjunct therapy.^[36]

Studies that measure lipids over time (usually 20, 40, and 60 days after the start of the study) note a statistically significant improvement in parameters by 20 days, but no further significant improvements over time. Yerba's benefits on lipid parameters appear to manifest fast but may not culminate over time.^[36][29][30]

Edit5. Interactions with Immunology and Inflammation

5.1. Mechanisms

Cinnamic compounds in Yerba Mate, the dicaffeoylquinic acids, suppress inflammation and NO release from macrophages (immune cells) by preventing nF-kB from translocating into the nucleus; particularly subunits p50 and p65.^[37] The effect seen here (preventing iNOS activation in macrophages) is also seen with both the saponin fraction and the flavonoid fraction, synergistically.^[38] The bioactive saponins appear to be oleanolic acid and perhaps pomolic acid, as ursolic acid shows little anti-inflammatory effects.^[38]

Yerba Mate extract may also protect macrophages from cytotoxicity (death) induced by nitrosylation, with a potency greater than Green Tea and Red Wine.^[39] Nitrosylation is a process by which superoxide radicals bind with Nitric Oxide (NO) to form peroxynitrate (OONO-) and damages cells that tend to form Nitric Oxide such as Macrophages or the endothelium.^[40][41]

5.2. In vivo

When preloaded at a dose of 150mg/kg daily (225mL Yerba Mate tea human equivalent) Yerba Mate appears to be effective in reducing the inflammatory insult on lung tissue from cigarette smoke;^[42] less immune cells are recruited and less pro-inflammatory cytokines (TNF-α) are seen when Yerba Mate is consumed.

Yerba Mate, at 1g/kg bodyweight in mice, also reduces the presence of macrophages in adipose tissue; of which their presence is correlated with the state of obesity.^[23] This same dose has also been shown to reduce transcloation of nF-kB in mouse liver and skeletal muscle, which promotes anti-inflammatory effects and may ameliorate the state of insulin resistance associated with obesity.^[43] Both studies note a decreased level of circulating pro-inflammatory factors IL-6 and TNF-α.^[23][43]

Yerba Mate possesses anti-inflammatory effects, and its locations of action appear to be promising. Too soon to make conclusions on its effects in the body, however.

Edit6. Interactions with Cancer Metabolism

6.1. Epidemiology

A meta-analysis of four epidemiological studies on the association between Yerba Mate tea consumption and oro-pharyngeal and oral cancers found a weak but significant OR of 2.11 with a CI of 1.39–3.19.^[44] Individual studies tend to show ORs around 1.5-3.^[45][46]

The carcinogenicity of Mate is usually given to Hot Mate, and the thermal injury associated with drinking hot beverages to upper digestive tissue.^[47][48][49] This is heavily based upon one case-control survey noting no associated with Yerba Mate per se and cancer, but an association with temperature.^[50] This designation seems to be tentative waiting for further studies.^[47]

Yerba Mate has been associated with cancers beyond the oral cavity (implicating factors beyond thermal trauma), being connected once to lung cancer in a case-control study of 996 persons over 6 years^[51] with a 1.6-fold increase in lung risk associated with heavy mate drinking. It has once been implicated in bladder cancer with an OR of 2.2,^[52] which extended to coffee and other teas as well; a case-control study from a population with high rats of bladder cancer, however, reported no association.^[53]

This small increase in cancers beyond the upper digestive tract implies chemical carcinogens, and may be due to carcinogens (benzo(a)pyrene and Polyaromatic hydrocarbon compounds) produced as a heat by-product during Yerba Mate processing and preparation.^[54][55] The content of heavy metals such as aluminum does not appear to be significant enough to warrant concern.^[56][57]

Yerba Mate is repeatedly associated with upper digestive tract cancers, although the severity of this association is not overly alarming. It is most likely due to the heat at which Yerba Mate is traditionally consumed causing thermal damage, but chemical carcinogens cannot be ruled out right now

Edit7. Nutrient-Nutrient Interactions

7.1. Quercetin

Saponins from Yerba Mate, particularly oleanolic acid, have the ability to prevent iNOS activation and to inhibit COX-2 in macrophages in the presence of a pro-inflammatory insult; exerting an anti-inflammatory effect. This reaction is synergistically enhanced by Quercetin.^[38] Luckily, there is a Quercetin component in Yerba Mate tea.

7.2. Caffeine

One study investigating learning in mice found that as it pertains to social memory, something in Yerba Mate (possibly rutin or kaempferol) is able to synergistically potentiate caffeine and make non-effective dosages of caffeine effective.^[58]

Edit8. Safety and Toxicology

In a acute and chronic study using research animals (rats and rabbits), Yerba Mate at a dose of 2g/kg bodyweight in both species was not associated with any toxicological or biochemical changes of toxicity.^[59]

References

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3. Andersen T, Fogh J. Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients. J Hum Nutr Diet. (2001)
4. Bracesco N, et al. Recent advances on Ilex paraguariensis research: minireview. J Ethnopharmacol. (2011)
5. Heck CI, de Mejia EG. Yerba Mate Tea (Ilex paraguariensis): a comprehensive review on chemistry, health implications, and technological considerations. J Food Sci. (2007)
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37. Puangpraphant S, et al. Dicaffeoylquinic acids in Yerba mate (Ilex paraguariensis St. Hilaire) inhibit NF-κB nucleus translocation in macrophages and induce apoptosis by activating caspases-8 and -3 in human colon cancer cells. Mol Nutr Food Res. (2011)
38. Puangpraphant S, de Mejia EG. Saponins in yerba mate tea ( Ilex paraguariensis A. St.-Hil) and quercetin synergistically inhibit iNOS and COX-2 in lipopolysaccharide-induced macrophages through NFkappaB pathways. J Agric Food Chem. (2009)
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40. Cantoni O, et al. Survival pathways triggered by peroxynitrite in cells belonging to the monocyte/macrophage lineage. Comp Biochem Physiol A Mol Integr Physiol. (2005)
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43. Arçari DP, et al. Anti-inflammatory effects of yerba maté extract (Ilex paraguariensis) ameliorate insulin resistance in mice with high fat diet-induced obesity. Mol Cell Endocrinol. (2011)
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45. De Stefani E, et al. Risk factors for laryngeal cancer. Cancer. (1987)
46. Castelletto R, et al. Alcohol, tobacco, diet, mate drinking, and esophageal cancer in Argentina. Cancer Epidemiol Biomarkers Prev. (1994)
47. Coffee, Tea, Mate, Methylxanthines and Methylglyoxal
48. De Stefani E, et al. Mate drinking, alcohol, tobacco, diet, and esophageal cancer in Uruguay. Cancer Res. (1990)
49. Victora CG, et al. Hot beverages and oesophageal cancer in southern Brazil: a case-control study. Int J Cancer. (1987)
50. Rolón PA, et al. Hot and cold mate drinking and esophageal cancer in Paraguay. Cancer Epidemiol Biomarkers Prev. (1995)
51. De Stefani E, et al. Mate drinking and risk of lung cancer in males: a case-control study from Uruguay. Cancer Epidemiol Biomarkers Prev. (1996)
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