Sunday, October 9, 2016

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!
  • 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.
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  • 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
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  • 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).
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  • Wikipedia contributors. "Paraoxonase." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 15 Jul. 2016. Web. 15 Jul. 2016.