Green Tea Lipids + Statins, PWO CHO + Glycogen, Visceral Fat, Heart Health + Anthrax - Research Update July '17

Matcha releases more antioxidants than tea leaves (Fujioka. 2016).

Only recently, you've read the "Caffeine June 2017 Research Update" [(re-)read it] here at the SuppVersity. Some of the effects of green tea have thus already been discussed. After all, caffeine is one of the health-relevant ingredients of tea; it is, however, not the most important one.

As Yuan Fen et al. explain in their latest meta-analysis of the effects of green tea on blood lipids, tea can be classified as green tea, oolong tea or black tea depending on the manufacturing process" (Fen 2017). What exactly it is that mediates the various health benefits of tea (inflammation, hypertension/heart disease, and cancer | Serafini 2011) and their potency may thus differ slightly from tea to tea.

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For example, "green tea is abundant with kaempferol glycosides, while oolong tea contains more quercetin and myricetin glycosides and black tea is rich in quercetin glycosides" (Fen 2017). Most importantly, however, teas contain substances we call catechins, e.g. epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), and epicatechin (EC). EGCG is considered to be is the major and functional component (Fen 2017). Accordingly, hitherto published studies tested or ascribed the health effects of green tea to the high relative amount of EGCG. I have thus chosen both studies using real tea and EGCG/catechin supplements for this SuppVersity Research Update:

• Green tea improves your blood lipids like a statin, but without the side-effect-prone mechanism of blocking cholesterol completely (Fen 2017) -- The effects of green tea consumption on lipid metabolism in people with overweight or obesity was the research interest of the previously cited study by Fen et al. in "Molecular Nutrition & Food Research". Based on 21 published RCTs, the scientists calculated that ...

  

  Figure 1: No clear effect on HDL was observed (Fen 2017).

  "[...] green tea significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) levels in overweight or obese people[, in form of a] 3.38mg/dl [reduction] for TC (95% CI: -6.42, -0.33mg/dl) and -5.29mg/dl [reduction] for LDL (95% CI: -7.92, -2.66mg/dl), respectively" (Fen 2017).

  That sounds great, but the absolute change in LDL is small in comparison to the average statin, which achieves reductions of 69.6 mg/dl (Law 2003).

Warning! EGCG may mess with the efficacy of your statins (and other medications): It's important to note, that EGCG acutely reduces the pharmacokinetics of statins. This has been proven only recently (Kim 2017) for rosuvastatin in healthy volunteers, whose systemic exposure to the drug was reduced by a whopping 19% when EGCG and rosuvastatin were co-administered only once. Interestingly enough, though, two weeks of chronic EGCG supplementation abolished this inhibitory effect. Green tea does that by interacting with a range of intestinal and hepatic organic anion transport peptides (OATPs) and we're yet far from understanding all its drug interactions. Proven have been the previously mentioned interaction with rosuvastatin, as well as interactions with the blood pressure medication (beta blocker) nadolol, and another statin, namely simvastatin, where it had, paradoxically, opposing effects and increased the plasma concentration by inhibiting both, intestinal CYP3A4 and P-gp and hepatic OATP1B1 (Werba 2015).

And there's more. In rodents on high cholesterol diets, scientists from the Hebrew University in Jerusalem have recently been able to demonstrate that the effect of green tea polyphenols on bile acid will overload your livers ability to get rid of cholesterol and thus promote non-alcoholic fatty liver disease (Tirosh 2017) - a phenomenon that has already been observed in human beings, too.

• Accordingly, people who actually need statin drugs because they have a genetically high risk of heart disease would be ill advised to try and replace their medications with green tea - not just, but also because "green tea's effect on plasma TG and HDL must be further evaluated by additional high-quality and large-scale RCTs" (Fen 2017) - also to answer, among others, the following question.
  • the differential effects of caffeinated and decaffeinated green tea on triglycerides (↕ for regular ↘ for decaffeinated green tea)
  • differences in health effects in healthy overweight or obese individuals vs. unhealthy overweight or obese individuals (in whom the scientists' subgroup analyses, for example, showed sign. reductions in triglycerides that were not observed in healthy subjects)
  • age-effects that couldn't be analyzed in the current meta-analysis of studies in which people from all age groups (from children to the elderly) participated
  • the seriousness and root cause of side effects, which were transient, but were still reported in four of the twenty-one trials
  For (lean and obese) individuals who are interested in overall heart health and don't have a genetically determined increased risk of heart disease, the 2-4 cups of green tea (or 300-1500mg green tea extract) the subjects in the 21 RCTs certainly are the better choice for cholesterol control - after all, the reduction in total (TC) and low-density cholesterol/lipoproteins (LDL) occurs in the absence of headaches, flushing, weakened and impaired skeletal muscle, diabetes, and liver injury - all repeatedly reported side effects of statin therapy (Mancini 2011; Chaipichit 2015; Castro 2016).

600mg/day Anything Beyond That and EGCG May Mess W/ Your Liver Health! Scientists Propose 300mg/day Limit for EGCS in Food Supplements (read the SuppVersity Facebook News Post from July 2nd, 2017). While evidence that the real deal, i.e. green tea can damage your liver, things look different for supplements with isolated catechins, esp. EGCG.

Dekant et al. recently reviewed the existing literature and came to the conclusion that EGCG has the potential to induce hepatic damage. Based on the finding that "[i]n clinical intervention studies, liver effects were not observed after intakes below 600mg EGCG/person/day," the researchers propose a "tolerable upper intake level of 300mg EGCG/person/day" which would give you "a twofold safety margin" (Dekant 2017).

• New study questions previously reported beneficial effects of green tea on post-exercise glycogen resynthesis, but... (Tsai 2017) -- You will remember my article from last October in which I outlined that "Green Tea Extract Reduces the Amount of Insulin You Need to Store Your PWO Carbs by ~20%" (read it). A recent study in the British Journal of Nutrition does now suggest that these effects may at least be dose-dependent.
  
  Unlike the previously cited study by Martin et al. (2016) used 3x350mg of green tea extract (GTE) for one week, Tsai et al. administered a significantly lower dose of GTE (500 mg/d) for 8 weeks. Furthermore, the scientists used a low-intensity workout and a carbohydrate-enriched meal, instead of a graded exercise and 75g of pure glucose as post-workout (PWO) nutrition.
  

  

  Figure 2: While the study did not confirm the beneficial effects on PWO glucose metabolism, it found a sign. reduced PWO RER (a), i.e. ratio of CHO:FAT oxidation, due to higher fat oxidation rates w/ GTE (Tsai 2017).

  In all honesty, it is thus not surprising that Tsai et al. observed only one significant benefit of GTE supplementation: it increased exercise-induced muscle GLUT type 4 (GLUT4) protein content of the vastus lateralis and the energy reliance on fat oxidation compared with the placebo trial (P<0·05). That there were no differences in blood glucose and insulin responses between the two trials may simply be a function of the comparatively slow rise in blood glucose in response to the test meal with a GI of "only" 76.6 (23.4% lower than glucose).
• Even on a normal diet, green tea prevents visceral adiposity (Raso 2017) -- While we do have dozens of studies showing that green tea alleviates the (visceral) body fat accumulation in response to unhealthy, hypercaloric diets, the latest rodent study by Raso et al. is the first study to investigated the effects of administering green tea as the main source of hydration on visceral fat accumulation in the long run - in human terms 45 years!
  

  

  Figure 3: Changes in relative (per kg body weight) and absolute visceral fat over the course of what would be 45 years in human beings with either water or green tea as the main source of hydration (Raso 2017).

  And the results are, as you can see in Figure 3, quite significant: While all animals, which were young at the beginning of the study, showed a sign. increase in weight and visceral fat over the course of the 18-week study, the visceral fat gains proportional to the weight of the animals were different between the groups. In that, the green tea group had a significantly smaller gain in visceral fat compared to body weight, resulting in a smaller area of visceral fat per kilogram body weight at the end of the experiment compared to the control group (p < 0.01).

Table 1: Research overview (Oz 2017 | free full text)

SuppVersity Suggested Read: "Chronic Inflam-matory Diseases and Green Tea Polyphenols" (free full-text). It is well known that green tea polyphenols (GrTPs) are potent antioxidants with important roles in regulating vital signaling pathways. This review summarizes how they act on transcription nuclear factor-kappa B and related proteins to ameliorate the surge of inflammatory markers like cytokines and production ofcyclooxygenase-2.

• Anthrax? Green tea can kill Bacillus anthracis the etiologic agent of the infamous infective disease anthrax that has been used to threaten people and governments by terrorists before (Falcinelli 2017) -- 10 days, that's the time that you have left on earth if you're infected with anthrax spores, spores that can infect you if you touch infected meat or breath in anthrax spores. The corresponding ease of infection is one the reasons that politicians and researchers fear the possible future use of B. anthracis as a bioterrorism agent.
  

  

  Figure 4: Green tea inhibits growth and kills Bacillus anthracis in Luria Broth. CFU/ml of bacilli grown for 4 h in the presence of 10% black tea or 10% green tea. n = 3. p = 0.08, black tea. *p < 0.01, green tea (Falcinelli 2017)

  This fear has resulted in an impetus to develop more effective protective measures and therapeutics. In their latest study, Falcinelli, et al. show that green tea inhibits the growth of B. anthracis - albeit yet only in vitro.
  
  As you probably already expected, it's epigallocatechin-3-gallate (EGCG) that was shown to be responsible for this activity. Yet even though EGCG was clearly bactericidal against both the attenuated B. anthracis ANR and the virulent, encapsulated strain B. anthracis Ames strain, future studies will have to show if and how green tea and EGCG can be used in human beings to prevent or battle anthrax infections... which reminds me to remind you, that GTE has also been shown to be a useful natural disinfectant able to limit enteric viral contaminations conveyed by food and food-contact surface (Randazzo 2017).

Can green tea "fix" Alzheimer's? Latest review of the efficacy of Epigallocatechin-3-gallate (EGCG from green tea) in the treatment of Alzheimer’s disease says that even though "in recent years, natural compounds, due their antioxidants and anti-inflammatory properties have been largely studied and identified as promising agents for the prevention and treatment of neurodegenerative diseases, including AD," the authors highlight that the "promising results" come exclusively from "pre-clinical" studies, so that "drawn clinical trials are extremely needed" (Cascella 2017) before we can tell how useful EGCG is whether it has preventive effects, only or can also be used to ameliorate if not curative Alzheimer's when someone is already experiencing symptoms.

• Part of the heart health benefits of green tea are not about EGCG and green tea extracts don't help with blood flow either, while real tea does (Lorenz 2017) -- In a randomized crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD.
  
  

  

  Figure 5: Only green tea increased flow-mediated dilation (FMD). Subjects consumed 200 mg of EGCG as isolated EGCG, GTE, or green tea after fasting overnight. An equal volume of hot water served as control. Green tea significantly increased FMD compared to GTE, EGCG, and water as control. Water slightly decreased FMD, whereas EGCG and GTE had little effects. Data are means ± SEM from n = 50 subjects. All p-values by repeated measures ANOVA followed by post hoc Bonferroni (Lorenz 2017).

  FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea.
  
  Even though the plasma levels of caffeine increased after green tea consumption, caffeine is not exactly the most likely among the various candidate ingredients that could take EGCG's place as an active ingredient responsible for green tea's (drink) ability to improve flow-mediated dilation. After all, previous studies suggest that coffee rather decreases than increases FMD (Papamichael 2005). Since similar effects have been observed by Heiss et al. in 2007 for a high-flavanol cocoa drink, other phenolic constituents of green tea, which obviously cannot be found in green tea extracts are much likelier candidates.

Hot or not? That could be a matter of health or ah... well almost death ;-) Learn why in my previous article "To Boil or Not to Boil? What's Going to Make Your Tea the Healthiest? Recent Study: It Depends on the Type of Tea"

How do I prepare the healthiest green tea? Now that you've learned that a DIY water-extract from green tea is better than commercially available extracts in pills or capsules (at least for FMD), this question is probably preying on your minds.

The answer to this important question comes from a study that will not be officially published before November this year. A study that shows that increasing the extraction temperature will also increase the polyphenol content of your tea. Thi sin turn enhances not just the antioxidant activity of the brew, it will also boost its ability to inhibit α-glucosidase and α-amylase, in vitro. In vivo, however, green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (p<0.05) than green tea that was prepared at 100°C.

The answer to the previously raised question "Hot to brew the perfect tea?" is thus both, context- and, as previously discussed research suggested, also type-dependent | Comment.

References:

• Chaipichit, Nataporn, et al. "Statin adverse effects: patients’ experiences and laboratory monitoring of muscle and liver injuries." International Journal of Clinical Pharmacy 37.2 (2015): 355-364.
• Cascella, Marco, et al. "The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer’s disease: an overview of pre-clinical studies and translational perspectives in clinical practice." Infectious Agents and Cancer 12.1 (2017): 36.
• Castro, M. Regina, et al. "Statin use, diabetes incidence and overall mortality in normoglycemic and impaired fasting glucose patients." Journal of general internal medicine 31.5 (2016): 502-508.
• Dekant, et al. "Safety assessment of green tea based beverages and dried green tea extracts as nutritional supplements." Toxicol Lett. 2017 Jun 24. pii: S0378-4274(17)30233-3. doi: 10.1016/j.toxlet.2017.06.008. [Epub ahead of print]
• Falcinelli, S.D. et al. "Green tea and epigallocatechin-3-gallate are bactericidal against Bacillus anthracis." FEMS Microbiol Lett. 2017 Jun 12. doi: 10.1093/femsle/fnx127. 
• Fujioka K, et al. "The Powdering Process with a Set of Ceramic Mills for Green Tea Promoted Catechin Extraction and the ROS Inhibition Effect." Molecules. 2016 Apr 11;21(4):474. doi: 10.3390/molecules21040474.
• Heiss, Christian, et al. "Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week." Journal of cardiovascular pharmacology 49.2 (2007): 74-80.
• Kim, Tae-eun, et al. "effect of epigallocatechin-3-gallate, major ingredient of green tea, on the pharmacokinetics of rosuvastatin in healthy volunteers." Drug design, development and therapy 11 (2017): 1409.
• Lorenz, Mario, et al. "Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG)." Scientific Reports 7 (2017).
• Mancini, GB John, et al. "Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference." Canadian Journal of Cardiology 27.5 (2011): 635-662.
• Papamichael, Chris M., et al. "Effect of coffee on endothelial function in healthy subjects: the role of caffeine." Clinical Science 109.1 (2005): 55-60.
• Randazzo, W. et al. "Effect of green tea extract on enteric viruses and its application as natural sanitizer." Food Microbiol. 2017 Sep;66:150-156. doi: 10.1016/j.fm.2017.04.018. Epub 2017 May 3.
• Raso, et al. "Effects of chronic consumption of green tea on weight and body fat distribution of Wistar rats evaluated by computed tomography." Acta Cir Bras. 2017 May;32(5):342-349. doi: 10.1590/s0102-865020170050000003.
• Serafini, Mauro et al. "Health Benefits of Tea" in Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Benzie IFF, Wachtel-Galor S, editors. Boca Raton (FL): CRC Press/Taylor & Francis; 2011.
• Shahid, Saleem Ullah, et al. "Effect of SORT1, APOB and APOE polymorphisms on LDL-C and coronary heart disease in Pakistani subjects and their comparison with Northwick Park Heart Study II." Lipids in health and disease 15.1 (2016): 83.
• Tehrani, H.G. et al.  "Effect of green tea on metabolic and hormonal aspect of polycystic ovarian syndrome in overweight and obese women suffering from polycystic ovarian syndrome: A clinical trial." J Educ Health Promot. 2017 May 5;6:36. doi: 10.4103/jehp.jehp_67_15. eCollection 2017.
• Tirosh, Oren, et al. "OP-17-Tea Extracts-induced Liver Injury: Lipotoxic Interaction Between Lipids and Polyphenols." Free Radical Biology and Medicine 108 (2017): S8.
• Tsai, et al. "Effect of green tea extract supplementation on glycogen replenishment in exercised human skeletal muscle." Br J Nutr. 2017 Jun 20:1-8. doi: 10.1017/S0007114517001374. [Epub ahead of print]
• Werba, Jose, P et al. "Overview of green tea interaction with cardiovascular drugs." Current pharmaceutical design 21.9 (2015): 1213-1219.

May I Salt & Roast My Nuts? Plus: If Catechins Boost One's Energy Expenditure by 400% Why Don't They Work for Me?

One article, two questions, two science-based answers.

If you're like me I bet that you've been asking yourself previously, whether the cheap roasted nuts at the supermarket have the same health benefits as the expensive "raw" nuts from the health-food store... guess what: a recent study by scientists from the Singapore Institute for Clinical Sciences and the University of Otago confirms: "Dry roasting and lightly salting nuts do[es] not appear to negate the cardioprotective effects observed with raw nut consumption, and both forms of nuts are resistant to [dietary] monotony" and thus similarly recommendable health-foods.

Along with the latest "green tea for thermogenesis"-study, which finally answers the important question "If Catechins Boost One's Energy Expenditure by 400% Why Don't They Work for Me?", the Chinese-New-Zealand co-production is one of the two studies in today's SuppVersity article.

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• You can roast and salt your nuts (all puns intended) and still see health benefits (Tey 2016): Unless you're like the average seventh-grader and misunderstand the previous statement, roasted and salted nuts display no health risk whatsoever.
  
  In fact, Siew Ling Tey and colleagues were recently able to show in a randomized crossover study with 72 perfectly healthy participants, who were asked to consume 30 g/day of either raw or dry roasted, lightly salted hazelnuts for 28 days, each that the CVD risk factors the scientists assessed still improved significantly (sign. changes in body composition were not recorded - just for the record: body fat declined by 100-200g, muscle mass increased by ca. 100g).
  

  

  Figure 1: Changes in biochemical parameters in the two groups; only the change in triglycerides (trigs) showed a probably random, yet statistically significant inter-group difference (in favor of the roasted nuts | Tey 2016)

  Furthermore, neither the "raw" nor the "roasted nut"-group saw a decline in their "desire to consume" and "overall liking" of the hazelnuts, which constitute, due to their relatively high omega-6 and extremely high PUFA content, an excellent study object for the potentially negative effects of roasting (one would expect a potential oxidation of PUFAs and downstream ill health effects). Moreover, studies "examining the health effects of consuming hazelnuts are", as the authors point out "relatively sparse despite the fact that hazelnuts are the second most common nut produced worldwide" (Tey 2016).
  
  One downside of roasted nuts I do not want to withhold, though, is the slight decrease in alpha-tocopherol during the roasting process, of which the results of the study do, however, indicate that it had no health-relevant consequences.
• Human study confirms: Green tea + caffeine set your brown fat on fire... assuming that you do have functional brown fat (Yoneshiro 2017) -- In rodents, it's not news that the combination of catechins and caffeine will promote brown adipose tissue thermogenesis. In humans, however, the effect has rarely been observed directly and is, as Yoneshiro et al. point out, "poorly understood".
  
  Reason enough for the Japanese scientists to recruit 15 healthy male volunteers, subject them to fluorodeoxyglucosepositron emission tomography and thus assess their BAT activity before and after a single oral ingestion of a beverage containing 615 mg catechin and 77 mg caffeine, as well as after the chronic ingestion of the same beverage 2 times/d for 5 wk in 10 of the subjects.
  

  

  Figure 2: (A) Study protocol of the acute trial. (B) Study protocol chronic trial. Both of the trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies (Yoneshiro 2017).

  To complicate, ah... I mean to make the study more comprehensive the scientists also evaluated the cold-induced thermogenesis (CIT) after 2 h of "cold" exposure at cozy 19°C. Both the acute and chronic trials were single-blinded, randomized, placebo-controlled, season-matched crossover studies.
  

  

  Figure 3: Change in energy expenditure (adj. for FFM) after the ingestion of the test beverages (left). Thermogenic effects of the catechin or placebo beverage expressed as iAUC of EE (right | Yoneshiro 2017).

  What the authors found was in line with the observations in rodent studies - the effect size, however, was, as it was to be expected, magnitudes smaller; and, more importantly, occurred only in those subjects who were blessed with highly active brown fat depots:
  • A single ingestion of the catechin beverage increased EE in 9 subjects who had metabolically active BAT (mean ± SEM: +15.24 6 1.48 kcal, P < 0.01) but not in 6 subjects who had negligible activities (mean ± SEM: +3.42 6 2.68 kcal).
  • The ingestion of a placebo beverage containing 82 mg caffeine produced a smaller and comparative EE response in the 2 subject groups.
  The scientists multivariate regression analysis revealed a significant interaction between BAT and catechin on EE (b = 0.496, P = 0.003). In other words: The acute effects on your energy expenditure depend on the presence and activity of brown fat cells (see Figure 4).
  

  

  Figure 4: (A) Representative FDG-PET/CT images of the high- and low-BAT subjects. (B) Quantitative BAT activity as the SUV of the high- (n = 9) and low-BAT (n = 6) subjects (Yoneshiro 2017).

  Unfortunately, these fat cells which are already scarce in normal-weight human beings are quasi-non-existent (or dysfunctional, that's not 100% clear) in those people who'd need the fat-burning effects of green tea the most: the obese.
  
  Accordingly, it is important to point out that the beneficial effects of chronic GTE + caffeine intake on the thermogenic response to "cold" (19°C) exposure in the 10 normal-weight Japanese subjects may (and I would dare say that it "will") turn out poorly in the average obese individual.

This FDG-PET image shows where the average (lean) human has active BAT stores (van der Lans 2014).

So what's the verdict? While it is nice to know that roasting and (lightly) salting doesn't turn a health-food like nuts to poisonous trash, I guess that Yoneshiro's study sends the more important message to the fitness community. After all, they finally demonstrated that the answer to the question why green tea extracts don't work for you could be as simple as this: "That's because you don't have the brown fat that's responsive to the effects of the catechins."

That's huge because it shows that (a) the usefulness of green tea catechin supplements depends on the individuals and that (b) those who need "fat burners" the most, i.e. those who are still obese or struggling with their weight, are least likely to benefit from it.

After all, previous studies clearly indicate that the majority of morbidly obese (and older | Sacks 2013) subjects have virtually no brown fat/adipose tissue (Vijgen 2011 | or if they have it, it doesn't respond even to treatment w/ cold, insulin or ephedrine | Orava 2013; Carey 2013). In conjunction with the observation that there's a clear correlation between having active brown fat and having no weight problems (ibid.), as well as the realization that the activity of brown fat in the obese only increases after weight loss (Vijgen 2012), it is thus not surprising that many catechin users are disappointed | Comment on Facebook!

References:

• Carey, Andrew L., et al. "Ephedrine activates brown adipose tissue in lean but not obese humans." Diabetologia 56.1 (2013): 147-155.
• van der Lans, Anouk AJJ, et al. "Cold-activated brown adipose tissue in human adults: methodological issues." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 307.2 (2014): R103-R113.
• Orava, Janne, et al. "Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans." Obesity 21.11 (2013): 2279-2287.
• Sacks, Harold, and Michael E. Symonds. "Anatomical Locations of Human Brown Adipose Tissue." Diabetes 62.6 (2013): 1783-1790.
• Tey, Siew Ling, et al. "Do dry roasting, lightly salting nuts affect their cardioprotective properties and acceptability?." European journal of nutrition (2016): 1-12.
• Vijgen, Guy HEJ, et al. "Brown adipose tissue in morbidly obese subjects." PloS one 6.2 (2011): e17247.
• Vosselman, Maarten J., Wouter D. van Marken Lichtenbelt, and Patrick Schrauwen. "Energy dissipation in brown adipose tissue: from mice to men." Molecular and cellular endocrinology 379.1 (2013): 43-50.
• Yoneshiro, Takeshi, et al. "Tea catechin and caffeine activate brown adipose tissue and increase cold-induced thermogenic capacity in humans." The American Journal of Clinical Nutrition (2017): ajcn144972.

26% Body Fat, Zero Lean Mass Loss W/ HIIT + 3x500mg Green Tea Supp in 10Wks | Is EGCG Liver-Toxic?

Lean, not skinny: In the long run HIIT + GTE could take you there, but there's one caveat... at least w/ the green tea.

The social networks are full of women complaining that they are not losing fat. If you ask them what they have tried to ignite body fat loss, the answer usually is: reduced energy, fat/carb intakes and, if any sport at all, endless cardio sessions... now, while studies show that this approach to fat loss works, it's (a) mostly the caloric deficit that determines the loss of body weight and (b) is often accompanied by significant lean mass losses.

An attractive alternative would be (i) not having to diet, (ii) not having to do endless cardio sessions and (iii) having a fat loss supplement that actually works.

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Well, guess what, Afzalpour et al. have an ahead-of-print paper they tagged with the keywords "HIIT;
Catechins; SRIT1; PGC-1 "(Afzalpour. 2017) that appears to suggest that this 'attractive alternative' does actually exist - at least for those women who have the most body fat to complain about for whom the scientists speculated that it could be the combination of "green tea consumption along with HIIT training" that "would improve body composition in overweight individuals and would show significantly greater improvements compared green tea consumption or HIIT training alone" (Afzalpour. 2017) - without dieting (or I should say: without prescribed dieting, the scientists did not access the women's food intake over the 10-week period; there was just a baseline reading)!

Table: Anthropometric characteristics of the subjects in the three groups (Afzalpou. 2017); note: there were no significant baseline differences in body composition and fitness between the three groups of young women.

To assess the validity of this hypothesis, the researchers from the University of Birnjad, in Iran, recruited thirty overweight young women (21.07 ± 1.2 years, BMI: 27.5 ± 1.3 kg/m²2 and body fat percentage: 34.1 ± 1.5%) and randomly assigned them to 3 groups (cf. Table 1):

• HIIT plus 1.5g/day green tea in 3x500mg servings with meals (HIIT+G),
• HIIT plus placebo (HIIT), and
• no training and supplementation control group (CON).

Said HIIT training program included 3 sessions of high-intensity interval training (HIIT) performed per week for 10 weeks with the intensity of 85—95% HR max. More specifically, ...

Figure 1: Overview of the HIIT parcours and the periodization scheme (Afzalpour. 2017).

"[t]he protocol of HIIT required the participants to finish a determined path (20 meters) with their maximum speed within 30 seconds. The starting point of the test was exactly in the middle of the obstacles, i.e., 10 meters from each obstacle. 

The training included running from the middle line to the first obstacle and then returning a 20-meter path to the second obstacle. After each run, there was an active rest for 30 seconds (Figure 1). 

In the first and second weeks, the training was performed with 4 repeats, in the third and fourth weeks with 5 repeats, in the fifth and sixth weeks with 6 repeats, in the seventh and eight weeks with 7 repeats, and in the ninth and tenth weeks with 8 repeats (Figure 1). In each session before the training protocol, the participants had [to] warm up for 5—10 minutes, and they cooled down for 5—10 minutes at the end of each session." (Afzalpour. 2017).

The intensity of training within the activity was controlled by measuring the heart rate during
the activity by pulse meter and using maximum heart rate formula (220-age). Besides, the Borg scale (6—20) was used to ensure greater control over the intensity of training.

Rodent studies clearly confirm the hepatoxicity of high doses of green tea; with the often-hailed EGCG having the most significant impact on the liver health of mice - with death being a consequence of the injection of a human-equivalent-dose of "only" 12mg/kg, or 850mg - luckily, the oral bioavailability of EGCG is low (Galati. 2006).

Weren't there recent studies showing ill-health effects of green tea? Well, "recent" is relative. I guess it all started w/ the testosterone-reducing effects of green tea I discussed back in 2011, already.

More recently, however, there have 24 case-reports of liver problems in response to the consumption of green tea supplements in man from 1999 to 2009, only (Mazzanti. 2009) - a response of which scientists say that it is due to (-)-epigallocatechin gallate (EGCG) or its metabolites "which, under particular conditions related to the patient’s metabolism, can induce oxidative stress in the liver" (Mazzanti. 2009).

Whether that's actually the case in the human case studies is particularly difficult to tell (Molinari. 2006), because it is well possible that "[i]n a few cases, toxicity related to concomitant medications could also be involved" (Mazzanti. 2009) - especially because EGCG messes significantly with the cytochrome P450 cascade, inhibiting, CYP1A2, CYP2D6, CYP2C9, and CYP3A4, which metabolizes not just all sorts of anti-depressive drugs, but also estrogen and could potentially explain the T-reductions in the previously mentioned 2011 study. In addition to that, a more recent series of studies (James. 2016) suggests that

"EGCG treatment induced hepatotoxicity [is dose dependent] and it induced oxidative stress by inhibiting antioxidant response. Mitochondrial function was impaired based on reduced biogenesis and inhibition of complexes following EGCG treatment." (James. 2016)

As bad as it may sound, this can (a) explain why it worked in the study at hand - practically speaking it did the opposite of what the anti-oxidants which hampered the gains in Bjornson et al. (2015 | discussed in detail, here), did it added to the pressure to adapt - and (b) and must be reconciled with the already low and chronically decreasing bioavailability of EGCG with chronic administration.

One important advice I want to give you at this point is still: do not fall for the notion that 'more helps more' (toxicity of really high doses of GTE in rodents has been proven multiple times), do not buy a pure EGCG product and stop using your green tea supplements if you notice the first symptoms of liver problems (usually otherwise inexplicable fatigue).

An intensity that yielded impressive effects, not only, but especially in terms of the subjects' body at loss that was not unreliably assessed with BIA, but - assuming the authors of the study knew what they did - with body fat calipers (I calculated the more meaningful absolute body fat and lean mass values based on the body fat % from the study). A 26% body fat loss and a 7% improvement in body fat percentage - without dieting - that's quite huge... isn't it?

Figure 2: Total changes (kg) in body fat and total lean mass and corresponding relative changes (in %) above the bars.

Yes, it is, but the way these beneficial effects on the women's body composition relates to their SIRT-1 and PGC-1alpha level is a putative one. Yes, the levels increased significantly in both the HIIT and the HIIT+G group, but the study design does not allow for statements about a causal link between the two: body fat and SIRT-1 and PGC-1a expression. In the end, I guess most women will say that it doesn't really matter, the fact that the PGC-1A expression was another 31% higher in the green tea group (HIIT+G) and went hand in hand with an exclusively significant increase in VO2-max (for the other treatments, the changes were non-significant) would yet argue in favor of an independent or interactive effect of green tea on the expression of these regulatory proteins that could have triggered the additional benefits.

Figure 3: Relative changes in SIRT1, PGC-1A activity and physical fitness as measured by the women's VO2-max.

What does matter, however, is the potential hepatoxicity (see red box), especially green tea products with a high EGCG content appear to have for some, but not all individuals. Against that background it is very unfortunate that (a) the product in the study at hand was either not standardized or the standardization was not reported, and that (b) any effect would have gone unobserved, in the study at hand, simply because no relevant parameters were measured... reason enough to re-address the issue in (a) the red box (general discussion) and the bottom line (weight loss adjuvant specific discussion).

Don't get me wrong: There are a lot of studies showing beneficial effects of green tea extracts, including the recently discussed study showing that "Green Tea Extract Reduces the Amount of Insulin You Need to Store Your PWO Carbs by ~20%". Unfor-tunately, its probably individual liver-damaging effects are being observed in more and more studies, too. 

What do I have to know: The concomitant use of 3x500 mg green tea supplements ingested with all three main meals accelerates the already impressive body fat loss a 10-week HIIT (3x per week) regimen produces in otherwise healthy overweight young women.

Now, the question remains: Is it worth taking the (probably small, but existing) risk of putting your liver health in jeopardy? You got to answer this question for yourself, but if you're having liver problems already, high dose EGCG supplements should IMHO be a no-go... the good news is: since the authors didn't report any EGCG standardization for their supplement, it is very likely that they are also not necessary and drinking green tea, which is a way of preparing your own hot water extract from tea, alone, with every meal could boost your fat loss and is associated w/ a reduced risk of liver cancer (Ni. 2017) |  Comment!

References:

• Afzalpour, M. E., E. Ghasemi, and A. Zarban. "Effects of 10 weeks of high intensity interval training and green tea supplementation on serum levels of Sirtuin-1 and peroxisome proliferator-activated receptor gamma co-activator 1-alpha in overweight women." Science & Sports (2017).
• Galati, Giuseppe, et al. "Cellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins." Free Radical Biology and Medicine 40.4 (2006): 570-580.
• James, Karma. Effect of dietary pretreatment and obesity on (-)-epigallocatechin-3-gallate (EGCG) mediated hepatotoxicity and the underlying mechanism. Diss. The Pennsylvania State University, 2016.
• Mazzanti, Gabriela, et al. "Hepatotoxicity from green tea: a review of the literature and two unpublished cases." European journal of clinical pharmacology 65.4 (2009): 331-341.
• Molinari, Michele, et al. "Acute liver failure induced by green tea extracts: case report and review of the literature." Liver transplantation 12.12 (2006): 1892-1895.
• Ni, Chen-Xu, et al. "Green Tea Consumption and the Risk of Liver Cancer: A Meta-Analysis." Nutrition and Cancer (2017): 1-10.

Green Tea Extract Reduces the Amount of Insulin You Need to Store Your PWO Carbs by ~20% + Discussed: What are the Potential Benefits During Bulking and Cutting?

The beneficial effects of green tea won't occur if you just put some GTE into your post-workout shake... well, at least they didn't occur in response to acute supplementation in the study at hand, where 3x350mg/d consumed for 7 days before a std. exercise + oral glucose tolerance test did the insulin lowering trick.

While green tea has a record of promoting the metabolic and overall health of the obese and sick, its benefits in healthy individuals are still an object of ongoing research. Research such as the latest study from the McMaster University, in which Brian J. Martin et al. (2016) evaluated the effect of supplementation with green tea extract (GTE) on the plasma glucose kinetics of eleven healthy, sedentary men (21±2 y; BMI=23±4 kg/m², VO2peak=38±7 ml/kg/min; mean±SD).

Now, this alone would probably not be SuppVersity newsworthy, but unlike other studies that assessed the effects of GTE on glucose management, Martin's study tested the effects specifically during the post-workout window - a fact that makes the study particularly interesting for SuppVersity readers.

Another important determinant of your 24h insulin levels is your meal frequency:

Grazin' Bad For the Obese!

Largest Meal For Lunch = Winner!?

Regularity is Key to Leanness

Optimal Meal Freq. 4 Kids?

8 Meals = Stable, But High Insulin

Are 6 Meals Better Than 2?

In contrast to what the study's title, "Green tea extract does not affect exogenous glucose appearance but reduces insulinemia with glucose ingestion in exercise recovery", suggests, we are not talking about an acute response study, here.

Simply adding some green tea extract to your PWO drink, alone, is thus unlikely to produce the same results. Rather than that you'd  better mirror the study protocol by consuming 350 mg of a standardized green tea extract thrice daily. After 7 days, which was the timespan after which Martin et al. conducted their oral glucose tolerance test, you should then be able to stash away a significantly larger amount of glucose with a given insulin load than before.

Figure 1: Post-workout glucose kinematics in response to a beverage containing 75g of glucose after 7 days of thrice daily green tea extract supplementation at a dosage of 3x350 mg (Martin. 2016).

As you can see in Figure 1 the chronic intake of GTE decreased the amount of insulin that was required to stash away the 75g of glucose the subjects consumed after participating in a graded exercise test (=cycling to exhaustion at ever-increasing intensities) was reduced by a statistically significant and practically relevant ~20%.

Why did GTE not improve the glucose AUC and the rates of glucose appearance and disappearance? Even though the experiment was not designed to elucidate this hypothesis, it is very likely that the lack of decreases of the amount of glucose in the blood, as well as its absorption kinetics, is probably the logical consequence of the fact that the uptake and storage already took place at the maximal physiological pace - though at sign. lower insulin levels w/ GTE.

Even though neither the glucose AUC, i.e. the amount of glucose that appeared in the blood, nor the glucose rate of appearance and disappearance decreased / increased significantly, said reduction in insulin is a clear indicator of a significantly improved insulin sensitivity - and that during a time-window where your cells' ability to take up and store glucose is already especially high, anyway.

Figure 2: Insulin is the most potent anabolic hormone known, and promotes the synthesis and storage of carbohydrates, lipids and proteins, while inhibiting their degradation and release into the circulation. Insulin stimulates the uptake of glucose, amino acids and fatty acids into cells, and increases the expression or activity of enzymes that catalyse glycogen, lipid and protein synthesis, while inhibiting the activity or expression of those that catalyse degradation (Saltiel. 2001).

In conjunction with the likewise improved oxidation of fatty acids during the workout, said reduction in insulin requirements may be an advantage during both cutting and bulking:

• cutting - during the former part of a "get jacked"-cycle, the reduced insulin excursions could shorten the time period during which elevated insulin levels suppress the release and oxidation of fatty acids from your fat stores while being in a caloric deficit
• bulking - during the latter part of the cycle, a reduced level of insulin could reduce the risk of fat storage while being in a caloric surplus

Eventually, it is important to note the italicization of "could" in the previously outlined hypotheses. Until their accuracy will have been proven in future studies, you better don't overestimate the results you may see from taking GTE supplements. Insulin is, after all, not half as obesogenic as Gary Taubes and co would have it... speaking of insulin: you probably don't have to be afraid to miss out on its beneficial effects on satiety and its ability to inhibit skeletal muscle protein breakdown - if the glucose AUC didn't change, it is after all very unlikely that the efficacy of insulin on other target organs wasn't increased to a similar degree so that you will experience the same satiety improving anti-catabolic effects with 20% less insulin; and yes, this means that, eventually, you could also experience the same degree of fat storage (luckily, though, PWO lipogenesis is → ZERO, anyway).

It may sound boring, but the classic combination of GTE and caffeine is probably the best fat burner left on the OTC supplement market | more

Bottom line: While future studies are, as so often, highly warranted, the study at hand provides initial evidence of the potential usefulness of green tea supplements in people who exercise regularly.

Whether the potential benefits, i.e. increased fat loss during cuts and decreased fat storage during bulks will actually occur in the everyday practice of athletic training and bodybuilding, however, is something that needs further research - research of which I'd hope that the guys at the McMaster University conduct it in the not all-too-distant future. After all, most of you will probably be more interested in the real world results than the mechanism of which Martin et al. write in the conclusion of the study at hand that it warrants further study | Comment on Facebook!

References:

• Martin, B.J. et al. "Green tea extract does not affect exogenous glucose appearance but reduces insulinemia with glucose ingestion in exercise recovery." Journal of Applied Physiology Published ahead of print on October 7, 2016 - DOI: 10.1152/japplphysiol.00657.2016
• Saltiel, Alan R., and C. Ronald Kahn. "Insulin signalling and the regulation of glucose and lipid metabolism." Nature 414.6865 (2001): 799-806.