Low Dose Silymarin (Milk Thistle) Boosts Reduction in Body Fat % W/ Both, Strength (-9%) & Endurance Training (-11%)

The "classic" user of silymarin supplements is either fat, sick and suffering from NAFLD, or big, buffed and taking oral steroids. Athletic women like the ones in the photos above, on the other hand, have not yet been very likely to buy and use silymarin supplements... well, unless they were (ab-)using oral, hepatoxic steroids, as well, obviously.

When bros talk about Silymarin, the active ingredient in milk thistle, they usually do that in the context of "cycle support", i.e. the use of supplements to buffer the negative effects of (oral pro-)hormones on organ- and, specifically, liver-health. A recent study from the Ahvaz Jundishapur University of Medical Sciences in Iran, however, the "bro-talk" may change that, though.

In the study, which was meant to test, whether silymarin a scientifically proven (Dixit. 2007; Saller. 2009; Surai. 2015) "powerful antioxidant" (Shirali. 2016), will also affect athletic performance, N = 45 (unfortunately) previously untrained men were randomly assigned to one out of the following five groups: (a) endurance training with placebo (ET + P), (b) endurance training with 140 mg of silymarin/day (ET+S), (c) strength training with placebo (ST+P), (d) strength training with 140 mg of silymarin/day (ST + S) and (e) a placebo (C) to identify both, the effects of exercise and supplementation.

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Anthropometrical and VO2max measurements and ELISA assay for paraoxonase (PON), leptin and adiponectin levels were performed at the beginning and after the 4-week of the study. Of these, the latter were meant to identify the mechanism behind the effects of exercise + silymarin supplementation.

Figure 1: Changes in body composition and physical fitness over four weeks of exercise training plus/minus 140mg/day of silymarin (ethanol extract from dried Silybum marianum seeds | Shirali. 2016)

Effects such as those I have plotted for you in Figure 1, namely significant improvements in body composition - not only the often falsely overvalued BMI / body weight with its very limited health-significance. Effects that were more (albeit not sign. more) pronounced in the silymarin groups; and effects that also involved a non-significantly more pronounced increase in VO2max in the placebo- vs. silymarin-supplemented endurance training group - a difference of which one could argue that it supports the hormesis hypothesis, i.e. the hypothesis that it's the exposure of your mitochondria to mito-hormetic stress that will have them adapt to the stress with the very cellular growth and functional improvements which drive the adaptational response to exercise.

Paraoxonoases are enzymes that are associated with HDL molecules. In our bodies, they appear to be responsible for the antioxidant effects of high- (HDL) on the oxidation of low-density lipoproteins (LDL) - a hypothesis that is confirmed by the above data from Mackness et al. 1993.

What are paraoxonases (PONs)? Paraoxonase enzymes have been found to perform a number of biological functions (the primary role of this group of enzymes is still a topic of speculation, though | Wikipedia. 2016), including anti-inflammatory, anti-oxidative, anti-atherogenic, anti-diabetic, anti-microbial and organophosphate-hydrolyzing effects. "These properties provide a promising potential for development of new therapeutic interventions to combat a number of health conditions" (Wikipedia. 2016). They are synthesized in the liver and appear to be responsible for the antioxidant properties of HDL on LDL particles, with the paraoxonases (PON) that are associated with high-density lipoproteins protecting the lipids in the LDL shuttles from oxidation (Mackness. 1993).

We have to be careful, though. Neither the additive effect of silymarin on VO2max in the strength training group, in which the subjects did a standardized supervised circuit training workout (3 circuits per workout) involving exercises for all large muscle groups (3 sets of 10-15 reps for each muscle group) thrice a week, nor the disadvantage(s) the subjects in the ET+S group, who participated in three supervised 50 minute running workouts (60% - 80% of maximal heart rate), was statistically significant. It is thus speculative to argue that

• the additive beneficial effect of silymarin on VO2max in the strength training (ST + S) and
• the subtractive negative effect on VO2max in the endurance training (ET) group

are a result of optimized / too low "stress" / oxidation levels - that's speculative, but it appears to be supported by the relative pre-/post-changes in paraoxonase, leptin and adiponectin levels (remember: leptin, just like insulin, is usually increased w/ increasing inflammation, while adiponectin is decreased) I've plotted in Figure 2:

Figure 2: %-changes in plasma PON, adiponectin and leptin levels in resp. to 4 wks of exercise +/- silymarin (Shirali. 2016).

Previous studies by Cakmak et al. (2010), show that PON activity is increased in adolescent athletes, suggesting that the cardioprotective effect of regular exercise might be mediated by increased PON activity. On the other hand, Romani et al. (2009) reported that physical stress, such as acute exercise, by altering membrane composition, may impair PON release from liver membranes and can decrease the level of PON in serum - an effect of which the study at hand appears to show that it is blunted by the provision of small amounts of the 'liver tonic' silymarin.

Addendum: What else do we know?

From previous studies, we also know that silymarin appears to increase the use of fat / trigs during exercise while sparing muscle glycogen (Choi. 2016). The latter may be one, yet certainly not the only reason why the study at hand and a previous study by Barari et al. (2014), both suggest that silymarin can help you lose body fat in the absence of energy systemic restriction... speaking of wich: the lack of dietary control is not necessarily a weakness of the study at hand; after all, a study without dietary control provides evidence that a given supplement will work in the real world, where people often fail to adhere to energy restricted diets - plus: the mood improving effects of silymarin Nazarali et al. (2015) observed in 40 female athletes may be an added bonus I haven't even mentioned yet.

Last question: Do I have to pay extra for "super-bioavailable" silymarin

As Angelo points out in response to the publication of the article at hand, silymarin has a suboptimal bioavailability - meaning: not all the silymarin you ingest will actually make it into your blood. Now, that's correct, but supplement producers abuse the notion of a low bioavailability to make money on allegedly "superior" silymarin products.

Figure 3: Primary reasons for poor oral bioavailability of Silymarin (Javed. 2011)

With a mean bioavailability of 20-50%, regular silymarin is yet far from being as quasi-useless as resveratrol with a 1%-ish absorption rate (note: silybin, the main active substance in silymarin, is not fat soluble, so having it with a fatty meal is not going to increase its bioavailability).

Figure 4: Unlike the endurance-training-induced increases in VO2max, the strength-training-induced increases in lean mass (4-5%) I've calculated for you based on the body fat% and weight changes were not checked for their statistical significance by the authors - I am pretty sure, though, they are not statistically significant.

Bottom line - Mechanism(s) and perspective(s): Whether and to which degree either of these previously discussed changes in PON, leptin and adiponectin is causally involved in the effects on body composition and physical fitness (Figure 1) and not just a corollary effect of the overall antioxidant prowess of silymarin is questionable.

What we can say with some certainty, the latter, i.e. the antioxidant effects silymarin will exert even at dosages as low as those that were administered in the study at hand, appear to have differential effects on physique and fitness depending on whether it is added on top of resistance (rel. high oxidative load) or medium intensity endurance (rel. low ox. l.) training: an augmentation of the ben. effects on fitness + body composition w/ the former, a non-sign. ame-lioration of the VO2 increase with the latter form of training.

What exactly it is that causes this exercise-specific difference will have to be the object of future research - research into the previously addressed issue of (mito-)hormesis. That both, the benefits and detriments are not exactly huge (esp. in absolute terms), on the other hand, is something we can tell today, already. Accordingly, we will have to wait for Shirali et al. or other researchers to do longer lasting (>4 weeks; better 8-12 weeks) follow-up studies with subjects who are more representative of the average SuppVersity reader than the untrained young men from Saeed Shirali's study at hand. Before those studies have not been done and are showing higher and/or long-term reductions in absolute body fat levels than the study at hand, I cannot recommend silymarin as a "weight loss drug" or a "cutter", as bros would call it. What I can do however, is to say that it appears to be a promising agent to improve both your health and your ability to maintain a healthy weight in the long(er) run | Leave a comment on Facebook!

References:

• Barari, A., And A. Eftekhari. "Exercise And Silymarin On Clotting Factors." (2014): 88-88.
• Cakmak, Alpay, et al. "Paraoxonase activity in athletic adolescents." Pediatric exercise science 22.1 (2010): 93.
• Choi, Eun-Ju, et al. "Effect of silymarin on gluconeogenesis and lactate production in exercising rats." Food Science and Biotechnology 25.1 (2016): 119-124.
• Dixit, Nitin, et al. "Silymarin: A review of pharmacological aspects and bioavailability enhancement approaches." Indian journal of pharmacology 39.4 (2007): 172.
• Javed, Shamama, Kanchan Kohli, and Mushir Ali. "Reassessing bioavailability of silymarin." Altern Med Rev 16.3 (2011): 239-49.
• Mackness, Michael I., et al. "Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase." Atherosclerosis 104.1 (1993): 129-135.
• Nazarali, Parvaneh, Ahdiyeh Pormphamadi, and Parichehr Hanachi. "Effect of Six Weeks of Resistance Training (RT) and Silymarin Supplement On the Changes in the Inflammation Marker Interleukin 6 and Psychological Profile in Elite Female Taekwondo Players in Alborz Province." International Journal of Sport Studies. Vol., 5 (1), 57-61, 2015
• Romani, Rita, et al. "Modulation of paraoxonase 1 and 3 expression after moderate exercise training in the rat." Journal of lipid research 50.10 (2009): 2036-2045.
• Saller, Reinhard, et al. "An updated systematic review with meta-analysis for the clinical evidence of silymarin." Forschende Komplementärmedizin/Research in Complementary Medicine 15.1 (2009): 9-20.
• Shirali, Saeed, et al. "Effects of Silymarin Supplementation on Leptin, Adiponectin and Paraoxanase Levels and Body Composition During Exercise: A Randomized Double-Blind Placebo Controlled Clinical Trial." (2016).
• Surai, Peter F. "Silymarin as a natural antioxidant: An overview of the current evidence and perspectives." Antioxidants 4.1 (2015): 204-247.
• Wikipedia contributors. "Paraoxonase." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 15 Jul. 2016. Web. 15 Jul. 2016.

Overtrained or in the Zone? Tests & Analyses of Samples of Athletes' Saliva Shall Help Determine Objective Criteria

Could something as simple as a saliva test tell you if you or your clients are overtraining? I mean, common sense would dictate that cortisol, free T and IL-6 should tell us something.

Salivary testosterone, cortisol, and interleukin-6, those are the three parameters Travis Anderson and colleagues had on their list of candidates when they conducted their latest study at the University of North Carolina (Anderson. 2016).

As you will remember from previous articles I wrote about overtraining. The only decently reliable method of seeing it coming is to assess you heart rate variability. On the other hand, athletes who are complaining of general fatigue and decreasing performances in the latter phase of their overtraining, when the symptoms become often almost unbearable, will also show high cortisol, low free testosterone and increased IL-6 levels.

If you want to mess with your cortisol rhythm overtraining is exactly what you "need"!

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It is thus only logical that the scientists assumed that it would be possible to evaluate the (overtraining) response of 20 moderate-to-highly trained young men to a standardized 6-week pre-season workout by the means of the said three parameters.

For this purpose, each subject was assessed at six separate sessions, next to their body composition, the scientists also measured the subjects' individual Recovery-Stress by the means of the standardized Recovery-Stress Questionnaire. In conjunction with the orally administered hormone / cytokine tests (always at 15:00-17:00 h) and the independently recorded training intensities and volumes (that was done by the researchers, not the subjects) on the bench, the back squat and the Olympic-style clean (+ auxiliary movements, see Table 1 | total session length including warm-up 45-60 minutes) these measurements were the basis for the scientists analysis.

Table 1: Overview of the primary and auxiliary exercises in the std. RT protocol (Anderson. 2016).

To make the subjects more overtraining-prone, the scientists kept gradually increasing the training load and began adding in conditioning runs to the workouts from week two on. The latter were done immediately after the RT workouts and consisted of 100 or 300m runs, of which the latter were replaced in week five with a speed/agility circuit that lasted another whopping 45 minutes.

Figure 1: Cortisol, IL-6 and free testosterone (left axes) and body weight (blue, right axis) development (Anderson. 2016).

As you may see with some surprise, the subjects' weight knew only one direction. Unfortunately, the body fat and lean muscle data was either only measured at baseline or simply omitted from the respective table, which holds nothing but the weight information.

Since the subjects' performance on all the prime movers increased significantly, though, we can assume that at least some of these gains were muscle - and that in spite of the significant reduction of the free testosterone / cortisol ratio and the skyrocketing IL-6 levels.

Table 2: REST-Q score by affective category (Anderson. 2016); * denotes sign. difference from baseline (p < 0.05); values for the score range from 1 = low anger, depression, etc. to 5 = high anger, depression, etc.

For the latter, it is, by the way, easy to see that the thing that "hurt" the trainees the most was the late addition of the agility work (another 45 minutes of intense aerobic workouts | -20% free T, +110% cortisol, +600% IL-6 |  note: this is in line with previous studies showing that aerobic exercise is more likely to result in overtraining than anaerobic training). Strength training alone (week 1) and combined with the sprints (weeks 2-4), on the other hand, didn't affect the alleged anabolism gauge, the testosterone / cortisol ratio, significantly.

Based on both the accepted physiological (weight, performance) and psychological (REST-Q) the subjects were, as the authors rightly point out "not symptomatic of overtraining". A conclusion that leaves us with the question...

No overtraining and still sign. markers of overtraining in the saliva? As the authors point out, there's little doubt (based on previous studies) that their workout routines should have brought the subjects - even though they were experienced weight with the performance of elite American Football athletes - to the verge of overtraining. Moreover, the hormonal changes and sign. cytokine increases in weeks 5-6, clearly indicate that the exercise regimen was taxing.

Hormonal Response to Exercise, Revisited: A Consequence, not a Determinant of Your Mood, Effort & Performance | more

The fact that the typical signs of overtraining still didn't occur (unless you count the psychological effects, which appear to be generally emotionally suppressive as signi-ficant symptoms of overtraining), is difficult to interpret. Anderson et al., however, still believe that they were on the right track. At least with IL-6, of which previous studies such as Robson-Ansley (2007) indicate(d) that it, or rather, the overall cytokine response will be sign. elevated in overtrained athletes, the scientists still believe that they've backed the right horse - albeit without knowing the magic numbers, i.e. how much does IL-6 end up over baseline to serve as a viable predictor of overtraining. Testosterone and cortisol, on the other hand, turn out to be rather useless alleged markers of anabolism and I would love if the bros would finally acknowledge that | Comment!

References:

• Anderson, Travis, Et Al. "Changes in Resting Salivary Testosterone, Cortisol and Interleukin-6 as Biomarkers of Overtraining." Sport And Health (2016): 2.
• Robson-Ansley, Paula J., Andrew Blannin, and Michael Gleeson. "Elevated plasma interleukin-6 levels in trained male triathletes following an acute period of intense interval training." European journal of applied physiology 99.4 (2007): 353-360.

Hitting it After Weights - Nothing but Benefits? Not Exactly, but Systemically Impaired Strength & Size Gains are a Myth

Has your cardio-addiction held you back in the past? That does not mean that a short HIIT training after an RT workout will do the same, does it?

Right from the University of Athens comes new paper by Tsitkanou et al. (2016). In their study the Greek scientists investigated whether high-intensity interval cycling performed immediately after resistance training would inhibit muscle hypertrophy and strength improvements induced by resistance training per se.

Based upon previous studies utilizing low-intensity cycling as well as acute studies investigating molecular pathways it was hypothesized that high-intensity interval cycling performed immediately after resistance training would not hinder muscle strength and hypertrophy but would negatively affect the rate of force development. So, no effect on muscle but on strength gains.

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The subjects, twenty-two male university students (age 21.8 0.6 years, body height 177.4 1.5 cm, body mass 74.2 2.1 kg, estimated VO2peak on a cycle ergometer 38.2 0.9 ml/kg/min) who had not been involved in systematic training (resistance or endurance) for at least 6 months before the initiation of the study but participated in recreational activities such as basketball, soccer, and jogging, 2–3 h per week, were assigned into two experimental groups according to their initial 1-RM leg press strength:

"One group of participants (RE, n = 11) performed resistance training only and the other group (REC, n = 11) performed the same resistance training but each session was followed by high-intensity interval cycling. [...] Training was performed two times per week for 8 weeks. Warm-up was the same for both training groups and included 5-min cycling at 50–75 W, lower body muscle stretching and 2 sets 9 - 10 repetitions of three exercises for the trunk (abdominal crunches, lateral crunches, dorsal raises) aiming to strengthen the lumbar spine area for injury prevention. The inclined leg press (45° angle) and the half-squat (knee angle 90°) Smith machine were used for the strength training of the lower extremities. The RE group performed four sets of 6-RM for each exercise (Zaras et al., 2014; approximately 85% of 1-RM: 220 14 kg and 127 +/- 7 kg in leg press and in halfsquat, respectively). In the first week, the training load was set at 80% of 6-RM (176 +/- 11 kg and 102 +/- 6 kg in leg press and half-squat, respectively). Thereafter, the resistance training load was set at 6-RM and it was increased by 2.0–2.5% in every training session so as to maintain at 6-RM until the last week of training intervention" (Tsitkanou. 2016).

Unlike the previously described resistance training protocol with rest periods of 3 minutes and between sets and 5 minutes between exercises, HIIT cycling was performed only by the subjects in the REC group. 10 minutes after the completion of the resistance exercises, the participants performed 10 sets of 60-s duration on a stationary bicycle with 100% of maximal aerobic power and 55–60 revolutions/min. The cycling workload was being increased (~2%) in every training session. The passive recovery between sets was static and amounted to 60 s.

Figure 1:  Δ Physical performance (%) before and after the training period; *: p < 0.05, §: p < 0.001 (Tsitkanou. 2016).

The authors of the study estimate the extra energy cost of performing high-intensity cycling in REC was less than 50 Kcal per day, for the whole training period. "Therefore, the participants of the REC group did not receive any extra nutritional direction in order to compensate for this extra energy loss
compared to RE," the authors argue and are probably right: it is very unlikely that those 50kcal would have a sign. effect on the lean mass and/or strength gains.

What the data in Figure 1 does tell you, however, is that there was a non-significant effect of the training type; albeit with a practically hardly relevant "advantage" for either of the workout protocols. If anything you may argue that the increase in maximal aerobic power of the subjects in the REC group, though it's likewise not statistically significant compared to the RE group, provides evidence of potentially relevant training benefits that would be confirmed by the significant improvements in heart rate at four submaximal workloads you can see in Figure 2.

Figure 2: Heart Rate at four submaximal workloads before and after 8 weeks of resistance training only (RE, a), and resistance plus aerobic training (REC, b). *P < 0.05, difference before and after 8-week training period (Tsitkanou. 2016).

For resistance trainees that may not be the most important benefit, but in view of the fact that the main muscle size increase, i.e. in the quads, did not differ and considering the fact that the vastus lateralis (VL) and rectus femoris (RF) size gains virtually cancel each other out, a significant systemic impairment of muscle hypertrophy as it is often cited as potential side effect of concomitant training.

Figure 3: Cross-sectional area of the right quadriceps and its’ four heads, and architectural characteristics of vastus lateralis before and after 8 weeks of resistance training per se and resistance plus high-intensity aerobic cycling | †P < 0.05 difference in percentage changes between two groups (RE > REC). ‡P < 0.05 difference in percentage changes between two groups (RE < REC). VL = vastus lateralis; RF = rectus femoris; VI = vastus intermedius; VM = vastus medialis; CSA = cross-sectional area; Quad = whole quadriceps (Tsitkanou. 2016).

Rather than that, the data in Figure 3 suggests an activity-dependent selective hypertrophy of the rectus femoris; whether the vastus lateralis simply gets too much exercise (previous studies show a steep inline in VL activity as the intensity of cycling increases / in running, the EMG activity is many times lower | Bijker. 2002) or if there's another reason for the lack of CSA increases, will have to be investigated in future studies
Since the type of training didn't affect the fiber composition of the subjects, either (both groups seeing similar increases in Type IIA and IIX - without sign. inter-group differences), the study at does indeed confirmed the authors' research hypothesis: "[H]igh-intensity interval cycling performed immediately after lower body resistance training did not inhibit muscle hypertrophy induced by chronic resistance training, in moderately trained individuals" (Tsitkanou. 2016). In fact, the additional increase in muscle capillarization and previously discussed beneficial effects on conditioning would even argue in favor of doing HIIT after every workout if...

A study by Kazior, et al. found sign. increases in muscle anabolism with "cardio" before resistance training.,For both studies it may be an important that we are dealing with cycling, not sprinting in the study at hand. After all, a recent review suggests cycling is the least likely to affect your gains (Murach. 2016).

... this study would suggest that doing HIIT after resistance training is a hit, but there are things we shouldn't forget. There's the potential difference between trained and more-or-less untrained individuals as they were recruited for the study at hand. Especially in individuals with a higher training volume and frequency, for example, adding a HIIT session towards the end of every resistance training workout may simply be too taxing.

Furthermore, the existing non-significant inter-group differences may accumulate over time with both the small decrements in strength and size gains having the potential to achieve statistical significance after another 8 weeks - previous studies, such as Häkkinen, et al. 2003, appear to confirm just that.

In their 21-week, study the scientists came close to a sign. difference with larger increases in the CSA of all muscle fiber types in response to strength training per se (I: 46%, IIA: 26%, IIX: 39%) compared with concurrent training (I: 13%, IIA: 23%, IIX: 31%). On the other hand, there are studies like Kazior et al (2016) that seem to provide reliable evidence of an increased muscle anabolic response - albeit with "pre-lifting" cardio training which, in turn, could make a significant difference to the "post-lifting" cardio applied in the study at hand. And then, there's the lack of data on upper body muscles and different types of cardio... ah, so many things we still don't know

Eventually, the best advice I can give you is thus still: try it, judge if it appears to impair your performance and recovery, evaluate your training logs every two weeks and - if possible - do your "cardio" on separate days, anyway | Comment on Facebook!

References:

• Bijker, K., G. De Groot, and A. Hollander. "Differences in leg muscle activity during running and cycling in humans." European journal of applied physiology 87.6 (2002): 556-561.
• Häkkinen, K., et al. "Neuromuscular adaptations during concurrent strength and endurance training versus strength training." European journal of applied physiology 89.1 (2003): 42-52.
• Kazior, Zuzanna, et al. "Endurance Exercise Enhances the Effect of Strength Training on Muscle Fiber Size and Protein Expression of Akt and mTOR." PloS one 11.2 (2016): e0149082.
• Murach, Kevin A., and James R. Bagley. "Skeletal Muscle Hypertrophy with Concurrent Exercise Training: Contrary Evidence for an Interference Effect." Sports Medicine (2016): 1-11.
• Tsitkanou, S., et al. "Effects of high‐intensity interval cycling performed after resistance training on muscle strength and hypertrophy." Scandinavian Journal of Medicine & Science in Sports (2016).
• Zaras, Nikolaos D., et al. "Rate of force development, muscle architecture, and performance in young competitive track and field throwers." The Journal of Strength & Conditioning Research 30.1 (2016): 81-92.

Licorice Flavonoid Oil - More Muscle, Less Fat in 16-Week RCT W/ Human Subjects W/ Only 300 mg of LFO per Day

I know this will disappoint you, but as of now, it seems as if licorice would help you burn the invisible visceral fat, only. That's healthy(-ier) than subcutaneous fat loss, but probably not how you get from lean 15% to ripped 5% body fat.

In the fitness industry, licorice doesn't have a good reputation. While many report astonishing benefits of licorice extract when they recover from stimulant abuse, everyone appears to be afraid of their potential detrimental effects on testosterone; effects that are everything but well-proven (all studies from a single group of scientists, for example, i.e. Armanini, 1999, 2002, 2003 & 2004 and even the latter admit that their initial "results were not confirmed in another study, where the same amounts of licorice did not decrease salivary testosterone values" (Armanini, 2002)... For people with heart problems, the pro-cortisol effect may be an issue and many of the traditional uses, e.g. to reduce abnormal levels of the hormone prolactin, high cholesterol or cramping are likewise only supported by insufficient evidence.

If you want to mess with your cortisol rhythm overtraining is exactly what you "need"!

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The reason Tetsu Kinoshita et al.'s latest study still made the SuppVersity "cut". Why's that? Well, firstly, the aforementioned lack of certainty is rather a reason than an argument against addressing recent licorice research. Secondly, Kinoshita's study is one of the few adequately powered human studies we have. And thirdly, scientists have been dabbling with the idea to use licorice to reduce visceral fat accumulation and improve blood glucose management has gotten some attention, anyway.

In the study at hand, all participants were undergoing rehabilitation treatment for knee osteoarthritis. Overall, fifty patients (7 males and 43 females, 54-90 years), none of which had sarcopenia or other health issues besides their knee osteoarthritis.

"The 50 participants were divided into either the LFO (n=26) or placebo (n=24) group by block randomization within the strata of sex, age, and muscle mass in agreement with an SAS program survey-select procedure. [...] Both of the participants and physical therapists were blinded to the results of random allocation. The LFO group consumed capsules containing 300mg of LFO per day after meals for 16 weeks. The placebo group consumed placebo capsules daily for 16 weeks. Participants were directed not to change their lifestyles during this trial, and [the scientists] confirmed this by monitoring their daily study diaries. All participants undertook nearly the same type of mild exercise, with eight participants of the LFO group and ten of the placebo group using ergometer exercise and the other participants undertaking even milder exercise. Between the groups, there was no significant difference in the intensity of their exercise" (Kinoshita, 2016).

Statistical analysis was performed for each measurement at five time points (week 0 = baseline, week 4, week 8, week 12, and week 16) during the intervention period.

Figure 1: Changes in body composition (LFO = black; PLA = white circles) as assessed with DXA and CT scans over the 16-week study on 300mg/day of licorice flavonoid oil in otherwise healthy subjects with osteoarthritis (Kinoshita. 2016)

Additionally, the results were subjected to a stratification analysis in which the participants divided into older participants (aged 75 and older | n=24; LFO 13, placebo 11) and younger participants (aged under 75 | n=24; LFO 12, placebo 11) to investigate whether the effects of LFO would differ
between the two age groups; and, for the osteoarthritis severity and the trunk fat there was an age effect with potential implications for the practical usefulness of LFO:

• 

  Table 1: Relative percentage of volatile compounds in licorice species root essential oils using gas chromatorgraphy–flame ionization detection measurements (n=3 | Quirós-Sauceda. 2016)

  the osteoarthritis score decreased age-dependently with significant reductions only in the young(er) subjects,
• the trunk fat percentage decreased sign. only in the older subjects (p = 0.04), while the effect in the younger individuals was there, but (potentially due to the lower # of subjects) non-significant (p = 0.08)

Ah, and no: There were no side effects. I have to admit that the study population is not exactly full of people who would note that their libido is dropping or any other low T symptoms begin to surface, but the fact that the authors didn't observe any other of the often-heard side-effects (increased blood pressure, lowered potassium, etc.) is still a relevant information.

Table 2: In vivo biological functions of compounds in licorice (Kao. 2014).

Since we don't know for sure which of the bioactive substances in licorice is to blame for the purported anti-testosterone effect, it is yet not even clear if this / these substance(s) can be found in sign. dosages in the average licorice oil.

For the same reason(s), it's yet not just difficult to assess the potential side effects. It's likewise difficult to predict potential additive bonuses. Let's take Licochalcone-A, for example. It's a flavonoid isolated from licorice root (Glycyrrhiza glabra) with potent anti-prostate cancer effects (Fu, 2004). Or, the anti h. pylori (and thus anti-gut cancer) effect of the sweet licorice root (Fukai, 2002). And the list of these health benefits is, as Table 2 goes to show you, long.  

Figure 2: Changes in body composition in 56 males, 28 females after 8 weeks of different doses of LFO, namely 300 mg, 600 mg and 900 mg; total body fat = DXA data visceral fat = CT scan (Tominaga, 2009).

So what? The study at hand, may be the first one that combined licorice with a physical exercise component, the results are yet consistent with previous studies which likewise found decreasing body fat levels (Tominaga, 2006, 2009, 2014 | see Figure 2) - observations of which Kinoshita et al. rightly point out that their sum indeed "suggests a general effect of the supplementation" (Kinoshita, 2016) that occurs in both Asian and US subjects (cf. results in Tominaga, 2014, a study with US participants). In contrast to age which appears to have at least a small effect, race does therefore not appear to affect the efficacy of licorice flavonoid oil as body composition modulator | Comment!

References:

• Armanini, Decio, Guglielmo Bonanni, and Mario Palermo. "Reduction of serum testosterone in men by licorice." New England Journal of Medicine 341.15 (1999): 1158-1158.
• Armanini, D., et al. "History of the endocrine effects of licorice." Experimental and clinical endocrinology & diabetes 110.06 (2002): 257-261.
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• Armanini, Decio, et al. "Licorice reduces serum testosterone in healthy women." Steroids 69.11 (2004): 763-766.
• Fu, Yue, et al. "Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells." Biochemical and biophysical research communications 322.1 (2004): 263-270.
• Fukai, Toshio, et al. "Anti-Helicobacter pylori flavonoids from licorice extract." Life sciences 71.12 (2002): 1449-1463.
• Kao, Tzu-Chien, Chi-Hao Wu, and Gow-Chin Yen. "Bioactivity and potential health benefits of licorice." Journal of agricultural and food chemistry 62.3 (2014): 542-553.
• Kinoshita, Tetsu, et al. "The Effects of Licorice Flavonoid Oil on Increasing Muscle Mass: A Randomized, Double‐Blind, Placebo‐Controlled Trial." Journal of the Science of Food and Agriculture (2016).
• Quirós-Sauceda, A. E., et al. "Licorice (Glycyrrhiza glabra Linn.) Oils." (2016).
• Tominaga, Yuji, et al. "Licorice flavonoid oil effects body weight loss by reduction of body fat mass in overweight subjects." Journal of health science 52.6 (2006): 672-683.
• Tominaga, Yuji, et al. "Licorice flavonoid oil reduces total body fat and visceral fat in overweight subjects: A randomized, double-blind, placebo-controlled study." Obesity Research & Clinical Practice 3.3 (2009): 169-178.
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Synergistic vs. Antagonistic Supersetting - Is One a Better Fat Burner? Rather NOT, Data From New Study Shows

Superset or not? The research question here is a different one...

I have to admit. I've recommended super setting during fat loss phases before, too. It simply appears too logical to assume that with the decreased rest times you'd burn more energy and - as you, as a SuppVersity reader know - it's your energy deficit that determines your weight loss.

Unfortunately, a recent study from Brazil has recently disillusioned me within less than one second - the title was enough: "Supersets do not change energy expenditure during strength training sessions in physically active individuals" (Brentano. 2016)... until I realized that it fooled me to believe that we were talking about a comparison of super setting to super setting... synergistic and non-synergistic that is.

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What? Yeah, the scientists from the Federal University of Rio Grande do Sul measured the energy expenditure (EE) during standardized strength training (ST) of 20 subjects who were assigned to either a "grouped exercise" (GE: 26.6 ± 3.4 years) or a "separated exercise" (SE: 24.9 ± 2.6 years) - both of them superset protocols, albeit one with synergistic (grouped) and one with antagonistic (separate | actually, this was rather "non-synergistic", as you will learn in minute.

Figure 1: Illustration of energy expenditure data acquisition. EPOC = excess postexercise oxygen consumption;
ST: strength training; VO2: oxygen uptake (Brentano. 2016).

From previous SuppVersity articles, you will know that the number of studies that investigate the physiological response to super setting is very limited - information about the influence of how you combine your sets is simply non-existent. Thus, Brentano, et al. (2016) aimed to determine whether supersets of ST exercises influenced EE during and after one strength exercise session, even doesn't exist - at all.

Intra- and post-workout aerobic energy expenditure with super setting and traditional resistance training (Kelleher. 2009).

Yes, I fully agree... this study lacks a "non-supersetting" group: I personally would rather have preferred to learn whether super setting increases intra- and post-workout EE compared to regular training. Luckily, this study has been done before. 7 years ago, when Kelleher et al. published their paper "The Metabolic Costs of Reciprocal Supersets vs. Traditional Resistance Exercise in Young Recreationally Active Adults " in Journal of Strength & Conditioning Research - a study that shows no sign. differences in aerobic EE during super setting vs. traditional exercise (SUPER 1,009.99 ± 71.42 kJ; TRAD 954. ± 83.31 kJ), p = 0.371 - despite what appears to be a consistent elevation in oxygen consumption for SUPER above TRAD in Figure 1 (top).

A sign. effect was observed, however, for the post-exercise excess energy consumption (EPOC), which increased by a whopping 33% - sounds like much, but with an absolute difference of only ~4.78 kcal per workout (SUPER 79.36 ± 7.49 kJ; TRAD 59.67 ± 8.37 kJ) that's as irrelevant as the non-sign. 7% (= 0,25 kcal/kg body weight) difference in the total metabolic cost of the two workouts, i.e. SUPER (15.52 ± 1.13 kJ/kg body weight) and TRAD (14.52 ± 1.17 kJ/kg; p = 0.265). 

In the study Brentano et al. (2016) had their subjects do four exercises (5 sets of 8 à 10 maximum repetitions) for knee extensor muscles and shoulder horizontal flexor muscles were executed in both training sessions:

• Hypertrophy oriented - All exercises were performed at the load obtained during the 10 RM tests; therefore, both sessions were conducted with loads equivalent to 85% of 10 RM.
• Grouped exercises (GE) - During GE, the participants performed one set of the leg press exercise, immediately followed by one set of the knee extension exercise, with no rest between each exercise. After five sets, the participants performed one set of the bench press exercise, immediately followed by one set of the pec deck exercise, with no rest between each exercise. 
• Separated exercises (SE) - During SE, the participants performed one set of the bench press exercise, immediately followed by one set of the knee extension exercise, with no rest between each exercise. After five sets, the participants performed one set of the leg press exercise, immediately followed by one set of the pec deck exercise, with no rest between each exercise. 
• Standardized rest - In both GE and SE, there were 3 minutes of rest between every two exercises (superset) to minimize the decrease in total work for subsequent sets.

To get accurate data, the scientists measured the actual oxygen uptake during and after exercise (60 minutes post-session). And what they found is ... well, neither what the title would suggest, nor what common sense would dictate:

"Total work during the session and increases in lactate concentrations were similar between the GE and SE Groups. During exercise, EE was greater in the SE Group when compared with the GE Group (GE: 123.8 ± 14.36 kcal vs. SE: 131.77 ± 20.91 kcal). During the postexercise period, GE induced greater EE when compared with SE (GE: 25.12 ± 7.86 kcal vs. SE: 19.76 ± 5.53 kcal)" (Brentano. 2016).

What? Doesn't that mean that the EE did differ? Yes, it does, but the exercise sequence did not influence the previously cited, most relevant parameter, the overall EE (GE: 148.92 ± 18.72 kcal vs. SE: 151.53 ± 17.97 kcal, p = 0.920). Accordingly, the scientists rightly say that "in physically active men, ST supersets do not influence total EE during and 60 minutes after a single session" (Brentano. 2016).

Supersetting is fun, time-efficient, exhausting and based on the reasonable assumption that you can benefit from training agonist + antagonist together, but does it build size & strength? I knew that this is what you were about to ask on Facebook... luckily, I've answered this question before - in this 2015 article!

So what? Eventually, it takes the Kelleher study discussed to draw a practically relevant conclusion because most of you will probably be interested in an answer to the question "Should I or shouldn't I superset?"

Now, it should be obvious that you shouldn't base this decision solely on the amount of energy you can spend during a workout, but if that is an important criterion for you, because, e.g., you want to shed some body fat and could use the extra 100kcal of energy expenditure many people will believe super setting may entail, I have to disappoint you: In conjunction the studies by Brentano (2016) and Kellehrer (2009) clearly indicate - a practically relevant difference between the intra-, post- and total-workout energy expenditure of traditional and superset training does not exist... or do you consider 4kcal significant? | Comment on Facebook!"

References:

• Brentano, M. A., et al. "Supersets do not change energy expenditure during strength training sessions in physically active individuals." Journal of Exercise Science & Fitness 14.2 (2016): 41-46.
• Brennecke, Allan, et al. "Neuromuscular activity during bench press exercise performed with and without the preexhaustion method." The Journal of Strength & Conditioning Research 23.7 (2009): 1933-1940.
• Kelleher, Andrew R., et al. "The metabolic costs of reciprocal supersets vs. traditional resistance exercise in young recreationally active adults." The Journal of Strength & Conditioning Research 24.4 (2010): 1043-1051.