Sick of Being Sick? 30 High Flavenoid Foods to Reduce the Incidence, Length & Severity of Infections by 40% (Avg.)

Sick of Being Sick? 30 High Flavenoid Foods to Reduce the Incidence, Length & Severity of Infections by 40% (Avg.)

anthocyanins EGCG flavenoids health iimmune health immun system infections infectious diseases proanthocyanidins quercitin theanine URTI

If "that's you" and "that's you" more than four times a year, you better read today's SuppVersity article and learn which Flavenoids may reduce your number of upper respiratory tract infections into the normal range of 2-4 per year.

The number of purported anti-URTI (=anti Upper Respiratory Tract Infection) agents is unquestionable higher than the average number of yearly upper respiratory infections of the average US citizen, which is 2-4. Which of these usually natural agents actually have the ability to protect you from at least one of the previously cited 2-4 infections, however, is far from being obvious.

The scientific evidence is ambiguous and confusing and therefore I am happy that researchers from the University of Auckland and colleagues from the College of Sport and Exercise Science at the Victoria University have recently conducted a large-scale meta-analysis of no less than 387 studies - ok, that's the number they began with, obviously ;-)

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Since the aim of the meta-analysis was not to investigate all possible remedies, but only those that are based on naturally occurring flavenoids and their effects on the immune function in healthy adults, it should not surprise you that not all of those ~400 studies made it into the analysis. After the returned studies were initially screened, and 2 reviewers independently assessed the remaining studies for eligibility against prespecified criteria, only fourteen studies, of 387 initially identified, were included in this review.

Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart. Pop, population; RCT, randomized controlled trial (Somerville. 2016)

The primary outcome measure was the effect of flavonoids on URTI incidence, duration, and severity - outcomes of which not all were measured and every study. This and the differences in dosing, which ranged from 0.2 to 1.2 g/d reduce the significance of the authors' comparison, without making the meaningless, though.

With that being said, the scientists most general finding, i.e. that "[o]verall, flavonoid supplementation decreased URTI incidence by 33% (95% CI: 31%, 36%) compared with control, with no apparent adverse effects" (Somerville. 2016) may give hope to those of you who are way above the initially stated average of 2-4 infections per year.

Eat colorful! I know this advice doesn't sound exactly sexy, but it is - after all, flavenols are the molecules that give our foods (among other things) color... at least the natural foods, obviously not the artificially colored junk from the convenient area in the supermarket. The best way to get a full spectrum of "anti-infectious" flavenols would thus be to always combine differently colored fruits, vegetables, potatoes and grains (if you eat them) in your meals. A 2006 study by Thompson et al. even goes so far to suggest (and prove experimentally) that only a botanical diverse high fruit and vegetable intake will significantly affects reduce oxidative biomarkers in women.

Now, this wouldn't be the SuppVersity if I simply copy and pasted the tabular overviews from the meta-analysis. The latter are nice, but make it difficult for you to grasp which agents actually work and how well they reduced the incidence of URTI. Therefore I decided to take a different approach and to synthesize the most relevant data in a single figure (Figure 2).

Figure 2: Relative risk reduction due to supplementation of the given agents (see bulletpoints below for more legible information) and exemplary data from Niemann et al. (2007).

In that, I dropped all studies with "non-realworld" outcomes and stuck to those that actually measured the incidence of upper respiratory tract infections (URTIs) or rather the URTI risk reduction and supplement the data with some basic information on the individual studies, plus the results of the study with the most significant results (Niemann. 2007 | -91% risk!). Since I couldn't put all that info in the figure, here are the basics:

• 

  Figure 3: Effects of 1g of quercitin on URTI incidence in participants of 160km race in Western States (Hesnon. 2008)

  Henson et al. (2008) conducted a study in 9 healthy participants of the Western States Endurance Run (WSER / 160 km run); a double-blind parallel RCT, with 21-d supplementation of 1000 mg/day quercetin or placebo before the WSER and compared URTI occurrence vs. placebo (Figure 3); a comparison that yielded that had visible, but non-significant effects on the illness rate of the subjects (I would still consider this a success).
• Nantz et al. (2012 & 2013) tested 2.56 g/d aged garlic extract (likewise a major source of quercitin) vs. placebo in 120 healthy subjects (60 per group) for 45 days in 2012 and a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n = 22) or a placebo beverage (n = 23) that was consumed for 10 weeks by 54 healthy subjects (17 men and 37 women), ranging in age from 21 to 50 years in 2013 and found that "aged garlic extract may enhance immune cell function and that this may be responsible, in part, for reduced severity of colds and flu" in Nantz et al. (2012 | -10% URTI risk).
  

  

  Table 1: Chemical characterization of the cranberry treatment and placebo beverages in the 2013 study by Nantz et al. that found a highly sign. 44% reduction in URTI symptoms / risk.

  A sign. more impressive reduction of -44% in URTI symptoms / risk, however, was observed one year later in Nantz et al. (2013) in their study with a cranberry beverage the composition of which you can find in Table 1.

• 

  You're missing the vitamins and aminos? Check out this older SV article and learn if vitamin C, D, E, glutamine, arginine & co promote or hamper immune health!

  Niemann, et al. (2007) investigate the effects of quercetin supplementation on incidence of upper respiratory tract infections (URTI) and exercise-induced changes in immune function in trained male cyclists (N = 40) who were randomized to quercetin (N = 20) or placebo (N = 20) groups and, under double-blind procedures. More specifically, the subjects received 3 wk quercetin (1000 mgIdj1) or placebo before, during, and for 2 wk after a 3-d period in which subjects cycled for 3 h/d at approximately 57% of their maximal wattage. You've seen the results of the study in Figure 2, already - quite impressive with quercetin protecting yielding URTI rates of 1/20 vs placebo = 9/20 (Kaplan–Meier analysis statistic = 8.31).
• Riede et al. (2013) and Rowe et al. (2007) didn't use powders or drinks, but rather commercial immune boosters. Both, RestAid® and ImmuneGuard® worked, but contained very different ingredients.
  

  

  Table 2: Monthly illnesses and symptoms for subjects (healthy, 18-70 years) taking ImmuneGuard®, a combination of EGCG and theanine for three months (Rowe. 2007).

  While the former, i.e. RestAid® as it was used by Riede et al., contains an extract from the larch tree of which the scientists say that its arabinogalactan (a soluble fiber) and bioactive flavonoids are the active ingredients that produced a sign. reduction in common colds (p < 0.040) and the number of participants affected by the infection (p ¼ 0.033), the latter, i.e. ImmuneGuard® (see Table 2) which was used by Rowe et al. in 2007, contains a proprietary Camellia sinensis formulation (CSF) with EGCG standardized decaffeinated green tea and extra L-theanine (Suntheanine®), of which Rowe et al. were able to show that it had 32.1% fewer subjects come down with URTI symptoms (P < 0.035), reduced the number of overall illnesses (not just URTI) of at least 2 days duration by 22.9% (P < 0.092), and the number of days with symptoms by 35.6% (P < 0.002).

If we simply assume that you react similarly to the subjects in said studies, candidate supplements to get you through phases of increased infection risk are:

• quercitin or high quercitin foods like citrus fruits, apples, onions, parsley, sage, tea, and red wine; olive oil, grapes, dark cherries, and dark berries such as blueberries, blackberries, and bilberries,
• cranberry extracts or juices with and/or supplements or other foods containing proanthocyanidins and anthocyanins, like purple corn or sweet potatoes, black rice, aubergines, red cabbage, red onions, radishes or black beans, and - the obvious - red, blue and purple fruits (like cranberry, obviously),
• larch extracts and/or dietary or supplemental arabinogalactan which can be found in very small quantities in a wide variety of foods including carrots, radishes, pears, corn, wheat and tomatoes, as well as
• green tea and/or supplements containing EGCG and theanine, of which you already know that they have various benefits, such as increased fat oxidation with GTE or improved attention and reaction speed(s) with theanine.

So, eventually, the use of the the "right" flavenols (see list above) year-round may thus reduce the number of sick-days significantly. If we go by the numbers Somerville et al. calculated in their meta-analysis by as much as quite impressive 40%! - a reduction of which the meta-analysis suggests that it was not mediated by significant changes in bioimmune markers (e.g., interleukin-6, tumor necrosis factor-a, interferon-g, neutrophils), because those were "trivial between the intervention and control groups during the intervention and after exercise when a postintervention exercise bout was included" (Somerville. 2016).

Don't forget: Cholesterol may also help you recover faster from infections!

Bottom line: Even though the actual mechanism behind the anti-URTI effects of the previously listed flavenoids and the corresponding foods and herbs may not be clear, Somerville et al.'s findings "suggest that flavonoids are a viable supplement to decrease URTI incidence in an otherwise healthy population" (Somerville. 2016), or - in other words - they confirm that at least some of the often well-known remedies actually do what they are supposed to: reduce the risk, number and length of upper respiratory tract aka URTIs (and other infections), significantly.

What would be interesting, now, are head to head comparisons of the agents in the list I've compiled for you, as well as studies that investigate possible synergies and (even if those are unlikely) incompatibilities of  the agents in the list right above this conclusion | Comment!

References:

• Henson, D., et al. "Post-160-km race illness rates and decreases in granulocyte respiratory burst and salivary IgA output are not countered by quercetin ingestion." International journal of sports medicine 29.10 (2008): 856.
• Nantz, Meri P., et al. "Supplementation with aged garlic extract improves both NK and γδ-T cell function and reduces the severity of cold and flu symptoms: a randomized, double-blind, placebo-controlled nutrition intervention." Clinical Nutrition 31.3 (2012): 337-344.
• Nantz, Meri P., et al. "Consumption of cranberry polyphenols enhances human γδ-T cell proliferation and reduces the number of symptoms associated with colds and influenza: a randomized, placebo-controlled intervention study." Nutrition journal 12.1 (2013): 1.
• Nieman, David C., et al. "Quercetin reduces illness but not immune perturbations after intensive exercise." Medicine and science in sports and exercise 39.9 (2007): 1561.
• Riede, L., B. Grube, and J. Gruenwald. "Larch arabinogalactan effects on reducing incidence of upper respiratory infections." Current medical research and opinion 29.3 (2013): 251-258.
• Rowe, Cheryl A., et al. "Specific formulation of Camellia sinensis prevents cold and flu symptoms and enhances γδ T cell function: a randomized, double-blind, placebo-controlled study." Journal of the American College of Nutrition 26.5 (2007): 445-452.
• Somerville, Vaughan S., Andrea J. Braakhuis, and Will G. Hopkins. "Effect of Flavonoids on Upper Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis." Advances in Nutrition: An International Review Journal 7.3 (2016): 488-497.
• Thompson, Henry J., et al. "Dietary botanical diversity affects the reduction of oxidative biomarkers in women due to high vegetable and fruit intake." The Journal of nutrition 136.8 (2006): 2207-2212.

Caffeine + Green Tea = Plus 10% Fat Oxidation & Energy Expenditure at Rest and During Sprint Interval Exercise

Caffeine + Green Tea = Plus 10% Fat Oxidation & Energy Expenditure at Rest and During Sprint Interval Exercise

caffeine coffee EGCG energy expenditure fat burner fat oxidation green tea GTE lose fat metabolic rate REE

From a health perspective it may be good that green tea does not contain all-too much caffeine. From a fat loss perspective, it clearly lacks caffeine.

When it comes to dietary supplements, people like to pay tons of money for unproven ingredients with funky names and dubious or non-existent safety profiles; agents that have been scientifically proven to work, are safe and cheap, on the other hand, are non-sellers or at least considered to be non-effective.

Obviously, I cannot really explain why that is the case (I suspect it is because people effect drug-like effects without drug-like side-effects from supps and are thus always on the lookout for the "next big"... hoax), I can tell you, though, that a recent study that is going to be published in one of the upcoming issues of the Journal of Strength and Conditioning Research (Jo. 2015) shows that caffeine and green tea, two supplements that belong to the previously described category, are everything but useless.

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In said study, Edward Jo and colleagues investigated the effects of a caffeine + green tea polyphenol mix (250mg caffeine + 400mg of a green tea extract with 50% EGCG and 5mg of caffeine per serving) on (a) metabolic rate and fat oxidation at rest, as well as following a bout of sprint interval exercise (SIE) and (b) the performance during a standardized sprint-interval test.

The study was a double-blind, randomized, placebo-controlled, crossover study that involvd 12 subjects (male: n=11; female:1 n=1) whose antroprometric data, i.e "body mass=76.1±2.2 kg; height= 169.8±1.6 cm; BMI= 22.7±3.0 kg/m2; body fat %= 21.6±2.0% [DXA data]" (Jo. 2015), already tell you that they were healthy recreationally active, but not necessarily athletic (it may be worth mentioning that they were relatively stim-naive with an intake of < 201mg of caffeine per day).

Figure 1: Energy expenditure (kcal/h) and fat oxidation (g/day) measure before (at rest) and during (during SIE) the sprint interval exercise 10 and 55 minutes after the ingestion of caffeine + GTE or placebo (Jo. 2015).

During the two testing sessions at the Human Performance Research Laboratory of the California State Polytechnic University, the subjects' resting energy expenditure (REE) was measured for 45 minutes starting 10 minutes after the ingestion of the aforementioned caffeine + polyphenol mix - a mix that was consumed on an empty stomach after an 8-h overnight fast (don't be fooled by the way the scientists report their data in "g/day" and kcal/day - I changed the latter, already but the values for fat in g would have become to small - we are talking about 45 + 30 min and a 24h measurement here).

Don't confuse increases in fat oxidation w/ fat loss: I guess we have to credit the supplement industry for propagating the myth that the ratio of fat to glucose you were burning was in anyway directly related to losing body fat. I am not sure how often I've written this on this blog or told someone in the gym: that is not the case. You can burn 20% more fat and still store more body fat if you increase your energy intake from exactly enough to already too much. The connection between fatty acid oxidation which would actually be a better term for the phenomenon we are talking about is complicated and a decreasing respiratory exchange ratio, i.e. a reduction of the ratio of glucose to fat that's used to fuel your metabolism is not a reliable predictor of fat loss.

After the initial 45-minutes, during which the subjects' resting energy expenditure had been measured, the subjects were placed on a computer-integrated cycle ergometer on which they performed a standardized 30 minute sprint interval exercise (SIE) protocol., the scientists describe as follows:

"Sprint-Interval Exercise Protocol. The SIE protocol was performed on the Velotron DynaFit Pro cycle ergometer and comprised of four 30-second maximal effort intervals each separated by 5 minutes of low-intensity, constant workload cycling (Figure 2). First, the ergometer was properly adjusted for the subject. Adjustment specifications for each subject was recorded during their familiarization visit and repeated for all experimental trials. Subjects initiated the SIE protocol with a 5-minute interval of low-intensity cycling at a constant workload of 75W. Immediately after, subjects cycled with maximal effort for 30 seconds against an added resistance that is 7.5% of BW for males and 7.2% for females. These two intervals were repeated three additional times. After the last 30-second sprint interval, the subjects performed an additional low-intensity 75W interval plus an extra 3 minutes of cool-down at a constant workload of 30W. The total duration of the SIE protocol was 30 minutes" (Jo. 2015).

A workout that had little effect on the effect of the caffeine + green tea combo which did, as you can see, when you compare the "at rest" and "during SIE" values in Figure 1, increase the energy at rest and during sprint interval training to a similar extent. More specifically, the increase in energy expenditure and fat oxidation was - within the margin of inter-individual variability - in the range of +10% during both conditions.

Figure 2: Illustration of the sprint interval exercise test performed 55 min after ingesting the supplement (Jo. 2015).

In view of the fact that we may safely assume that this effect should last for at least 2-3h this can be a practically relevant effect if it is complemented by a reduced energy intake and a caloric deficit. If the latter is not present, even the extremest increases in fat oxidation and energy expenditure will fizzle out and be as irrelevant as the effect of the caffeine + green tea combination on exercise average and peak power (W) during the sprint training, Jo et al. observed in their study... and "Yes!", that is disappointing, but in view of the low dose of caffeine and the non-existent effects of green tea on performance during a test like this not really surprising.

Did you know this SuppVersity Calssic? "Post-Workout Coffee Boosts Glycogen Repletion by Up to 30% and May Even Have Sign. Glucose Partitioning Effects | learn more!

Bottom line: I admit, they certainly sound less exciting as the latest exotic herb from the rain-forest or a substance that is listed only under its funky chemical name on the label, but unlike your average "innovative breakthrough metabolic activator" caffeine and green tea will deliver. The 10% increase in metabolic rate and the accompanying increase in fat oxidation won't make you lose slabs of body fat, but the effects are pronounced enough to expect a measurable effect on the success of your next diet / cut. A cut, by the way, that will still require a significant reduction in energy intake, even if your energy expenditure and fat oxidation. So, don't be a fool and confuse a 10% increase in fat oxidation w/ a 10% increase in fat loss that occurs in the absence of dieting on an ad-libitum diet | Comment!

References:

• Jo et al. "Dietary Caffeine And Polyphenol Supplementation Enhances Overall Metabolic Rate And Lipid Oxidation At Rest And After A Bout Of Sprint Interval Exercise." Journal of Strength & Conditioning Research: Post Acceptance: November 23, 2015. doi: 10.1519/JSC.0000000000001277

Fat-Blocker Effect of Tea Catechins Confirmed (?) in Man - Sign. Abdominal Fat Loss (5-8%) in 12 Weeks W/Out Diet

Fat-Blocker Effect of Tea Catechins Confirmed (?) in Man - Sign. Abdominal Fat Loss (5-8%) in 12 Weeks W/Out Diet

abdominal fat catechins ecg EGCG green tea GTE intra-abdominal fat lose fat lose weight obesity subcutaneous fat tea visceral fat visceral obesity

Tea catechins (which can also be found in black and jasmin tea | see Figure 3) can help you keep particularly unhealthy abdominal fat (Després. 2012) at bay.

It is one thing to have in-vitro and rodent data that green tea can inhibit the digestion of dietary fat (reported previously in the SuppVersity Facebook News); it is another thing, however, to have a human study like the one Makoto Kobayashi and colleagues are about to publish in the peer-reviewed scientific journal Food & Function that shows that the "[i]ngestion of a green tea beverage enriched with catechins with a galloyl moiety (THEA-FLAN 90S) during a high-fat meal reduces body fat in moderately obese adults" (Kobayashi. 2015).

Ok, the abdominal fat loss does not, as the previous quote from the conclusion appears to suggest, occur instantly right after you've consumed your first tea w/ a single meal.

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Rather than that, 124 subjects (two of the initially 126 subjects 2 dropped out for personal reasons unrelated to the trial), 53 men, 71 women, who consumed similar, albeit non-standardized diets (see Figure 1 | note: physical activity was also identical) and began the study with body fat levels of ca. 31-35% had to consume the previously mentioned tea beverage that contained tea catechins (250 mL with 215.3 mg green tea catechins containing 211.0 mg green tea catechins with a galloyl moiety) twice or three times daily during mealtimes for 12 weeks, before the significant reduction in body fat became visible.

Figure 1: Macronutrient composition (in g an % of energy) of the non-energy reduced diets the subjects consumed; the values in the left pie chart represent a group average of all three intervention groups. Since the data is based on food records with photographs, it is probably more reliable than in your average diet study (Kobayashi. 2015).

Now, in view of the fact that this is not the first study to demonstrate weight loss effects in overweight subjects consuming green tea or, as in most other studies, green tea extracts, the word "during" and thus the fact that the green tea beverage was consumed with at least two of the three meals per day should be highlighted as a specific feature of the study at hand that is highly relevant to its interpretation.

Figure 2: Detailed analysis of the rel. change in fat area in the abdominal depot of the subjects (Kobayashi. 2015)

It is after all the requirement that the green tea beverage had to be consumed with a (preferable high fat) meal that allows the authors to conclude that the significant fat loss Kobayashi et al. measured by the means of computer tomography predominantly in the abdominal area are the result of an inhibition or slowing of the intestinal fat absorption and thus warrant the conclusion that "the ingestion of green tea beverages enriched with CGM together with high-fat meals may be an effective strategy for reducing body fat in moderately obese adults" (Kobayashi. 2015) - an observation of which I would like to add that the underlying mechanism is not 100% certain.

What about weight and, even more importantly, muscle loss? No, losing lean mass was not an issue in, because weight loss (-0.6 and -0.8% in the low and high dose group, respectively | measured by bio-electrical impedance vs. computer tomography as it was the case for the abdominal fat area) was actually not an issue, either. If you want to measure your success on the scale, green tea is thus not going to be the "diet tool of choice" (unless you use it alongside an energy-reduced diet)... however, if you take into account that the placebo group actually did what the average Westerner does, these days, i.e. gain weight and body fat over the 12-week study period, you may argue that you can still see the results on the scale which could finally stand still after years of displaying subtle, but eventually relevant increases in body weight.

The authors base their conclusion that it is "unlikely that absorbed green tea CGM leads to increased energy expenditure, followed by reduced abdominal body fat area" (Kobayashi. 2015) on two reasonable, but experimentally (in this study) not confirmed assumptions which are that little to no catechins actually made it into the bloodstream, because ...

1. the low caffeine content of the beverage limits the bioavailability of EGCG & co (caffeine enhances its bioavailability | Nakagawa. 2009) and
2. the ingestion of the beverage with a meal has been shown to significantly reduce the bioavailability of green tea catechins in comparison to the fasted state (Chow. 2005).

The assumption that its just a blockade of the digestion of fat becomes even more questionable, if you (re-)read my 2014 article on the carb blocking effects of tea... Well, eventually, though, you may argue that it does not matter if the reduction in abdominal fat was due to thermogenic effects, thermogenic and fat-blocking effects or, as the scientists believe, mediated exclusively an "inhibit[ion] or slowing [of the subjects'] intestinal fat absorption" (Kobayashi. 2015). And let's be honest, I guess you're right. What matters is that there were significant reduction ins abdominal fat (visceral, subcutaneous and total abdominal fat area). Reduction of which the data in Figure 2 tells you that ...

1. 

   Table 1: Catechin composition of the test beverages.

   the fat loss in the abdominal area was dose dependent - even if the differences between the low and high dose group did not reach statistical significance (for the exact catechin composition see Table 1 on the right) - and that 
2. roughly 50% of the benefits were lost within only 5 weeks when the subjects stopped consuming the green tea beverage, even though their diet didn't change at all (in fact, they consumed minimally less energy in the withdrawal phase from week 12-17).

Now, (b) is obviously good news for green tea lovers, but bad news for those who cannot imagine consuming green tea containing beverages "for the rest of their lives".

Green tea forever, it is then!? Well, as usual we have to consider what limits the generalizability of the results. Firstly, we are dealing with a group of people who have more than a few pounds of extra-weight on their hips. An abdominal fat loss of 8% in 12 weeks is thus not impossible, but not exactly likely to be seen in someone who starts at a body fat percentage of 15% or less (which is half what the subjects in the study at hand began with).

Figure 3: Catechin content (mg/10ml) of black, green and jasmine tea prepared from commercial tea w/ different infusion times (Bronner. 1998).

The second thing we have to keep in mind is the beverage itself. As you've previously read, it has been enhanced with catechins with a galloyl moiety (CGMs | EGCG, ECG, GCG, CG). Does this mean that you cannot achieve similar results if you simply drink green tea? Luckily, data from Bronner, et al. (1998) suggests otherwise. As you can see in Figure 3, it would take only 100 ml of commercially available freshly brewed (infusion time 3 min) green tea and even less black tea to achieve similar concentrations of EGCG and the other catechins with a galloyl moiety in your tea. Accordingly, the second obstacle to the gene- relizability of the study is actually irrelevant.

Third- and lastly, there's yet still the fast reversal of the effects which suggests that it is necessary to become a habitual tea drinker to see long-term / lasting benefits of green tea (or as the data in Figure 3 suggests even catechin containing tea in general) on your body weight and, more importantly, body fat you're carrying around | Comment on Facebook!

References:

• Bronner, W. E., and G. R. Beecher. "Method for determining the content of catechins in tea infusions by high-performance liquid chromatography." Journal of Chromatography A 805.1 (1998): 137-142.
• Chow, HH Sherry, et al. "Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals." Clinical Cancer Research 11.12 (2005): 4627-4633.
• Després, Jean-Pierre. "Body fat distribution and risk of cardiovascular disease an update." Circulation 126.10 (2012): 1301-1313.
• Kobayashi, Makoto, et al. "Green tea beverages enriched with catechins with a galloyl moiety reduce body fat in moderately obese adults: a randomized double-blind placebo-controlled trial." Food & Function (2016).
• Nakagawa, Kiyotaka, et al. "Effects of co-administration of tea epigallocatechin-3-gallate (EGCG) and caffeine on absorption and metabolism of EGCG in humans." Bioscience, biotechnology, and biochemistry 73.9 (2009): 2014-2017.