MSM Cures Exercise Related Joint & Muscle Pain, But May Effect Immunity | Arginine Silicate Delivers, but Practically Relevant Data is Still Missing | ISSN Research Review '15 #5

MSM Cures Exercise Related Joint & Muscle Pain, But May Effect Immunity | Arginine Silicate Delivers, but Practically Relevant Data is Still Missing | ISSN Research Review '15 #5

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Exercise induced joint and muscle pain - Can a few grams MSM help?

In this installment of the SuppVersity ISSN '15 Research Re- or rather Overview I couldn't really find a common theme. With two studies on MSM and one on arginine silicate you could probably best call it the "less researched supplement review".

Many people probably don't even know that MSM stands for "methylsulfonylmethane" and the notion that one could benefit from inositol-stabilized arginine silicate was - I openly admit that - complete news to me, too.

Read more about ISSN and other studies at the SuppVersity

Vitargo, Red Bull, Creatine & More | ISSN'15 #1

Pump Supps & Synephrine & X | ISSN'15 #2

High Protein, Body Comp & X | ISSN'15 #3

Keto Diet Re- search Update | ISSN'15 #4

The Misquantified Self & More | ISSN'15 #5

BCAA, Cholos-trum, Probiotics & Co | ISSN'15 #6

• The benefits of inositol-stabilized arginine silicate as a workout ingredient - Over the past years the way people thought and think about arginine has changed significantly. While it was originally considered a super-supplement that would increase pump, gains and vascularity, most recent studies on its effects on relevant markers of exercise performance and training adaptation yield similarly disappointing results as Gary Cooks honor thesis from 2015 in which he observed that neither arginine supplementation 20 minutes prior to exercise, nor arginine supplementation two hours post exercise had an effect on the increase in strength performance or hypertrophy following a 4-week resistance training regime (Cook. 2015).
  
  

  

  Only few studies show ergogenic effects of plain arginine. This one, however reports a sign. increase in to exhaustion in a group of elite wrestlers.

  With more and more consumers becoming aware of the lack of effect of regular arginine, supplement producers are forced to develop "alternatives" - alternatives that promise to finally do what regular l-arginine supplements promised to do: Boost your nitric oxide levels, exercise performance and overall gym experience. With inositol-stabilized arginine silicate (ASI; Nitrosigine®) there's a true newcomer that is set about revolutionizing the pre-workout supplement scene ... that's at least if we believe in what the patent holders tell us about the "new standard for pumped results" (manufacturer's homepage).
  
  In fact, ASI has been previously shown to enhance blood levels of arginine up to six hours post-dose and increase nitric oxide levels, acutely (Kahlman. 2014). In the long(er) term, Whether that would produce practically relevant increases in perceived intra-workout energy, muscle pump, and stamina, as well as post-workout muscle recovery was now the subject of a new study by Rood-Ojalvo et al. (2015).

Future (independent) research necessary: When it comes to supplement research it is absolutely normal that the effects of new products are initially tested by the ones who invent / produce it. In the long run, however, it would be nice to see the results of the study being reproduced by independent research... research that would also include actually meaningful (=performance or hypertrophy-related), objectively measurable study outcomes instead of subjective levels of perceived energy and (on their own) practically irrelevant increases in blood flow.

• The randomized double-blind placebo-controlled cross-over study study was conducted with 16 male subjects with limited exercise routines prior to participating in the study. The subjects took 1,5g/day of ASI or a placebo supplement daily for 4 days before they completed an intense leg extension exercise protocol to induce muscle soreness. Subjects then returned to the lab after 24, 48, and 72 hours for additional study measurements. After 72 hours, subjects repeated the leg extension exercise protocol to assess whether the provision of ASI (or placebo) had measurable effects on the recovery protocol.
  

  

  Figure 1: In spite of significant changes in blood flow velocity and leg circumference (which is interpreted as increased blood flow / hyperemia by the authors) the study at hand cannot prove practically relevant ergogenic effects of ASI simply because corresponding outcome variables were not assessed (Rood-Ojalvo. 2015).

  The scientists' analysis of the data they got produced two important results: Firstly, the 19-33 year-old subjects felt significantly more energetic and less fatigued (at least based on inertia sub-scores) on the 72 hour retest compared to placebo (p = 0.039). Secondly, the provision of the supplement lead to significant increases in leg circumference. Unfortunately, this increase in leg circumference is not a sudden muscle gain. Rather than that, the increased leg circumference appears to be a result of increased hyperemia (=increase of blood flow).
• In conjunction with the significant decrease in CK levels - a purported, albeit unspecific marker of muscle damage - in the ASI group at 24 (p = 0.040), 48 (p = 0.017) and 72 (p = 0.034) hours, the overall results of the study at hand do thus suggest that short-term supplementation with inositol-stabilized arginine silicate could have ergogenic effects. In the absence of meaningful outcome measures such as the number of reps (=volume) or the maximal weight lifted during the exercise tests, it would yet be premature to say that ASI is a proven ergogenic. 
• MSM for muscle and joint pain in marathoners and other athletes -- As Withee et al. point out in the introduction of the abstract to their poster presentation "[p]articipants in organized running commonly experience muscle and joint pain while training for and competing in distance events" for them a supplement that is able to reduce the pain associated with osteoarthritis could be a true game changer; and methylsulfonylmethane (MSM), a sulfur-based nutritional supplement, could be that supplement.
  
  Several previous studies have shown that MSM has anti-osteoarthritic and anti-inflammatory properties. Whether it would also help managing exercise-induced muscle and joint pain, effectively, was now the research question of a recent study from the National College of Natural Medicine in Portland (Withee. 2015). The design of the study is simple:

  "Twenty-two healthy females (n = 17) and males (n = 5) (33.7 ± 6.9 yrs.) were recruited from the 2014 Portland Half-Marathon registrant pool. Participants were randomized to take either MSM (OptiMSM®) (n = 11), or a placebo (n = 11) at 3g/day for 21 days prior to the race and two days after (23 total). Pain was recorded using a 100 mm Visual Analogue Scale (VAS) for both muscle pain (MP) and joint pain (JP) on a single questionnaire. Participants completed the questionnaire at five time points. Baseline levels (T0) were recorded approximately one month prior to the race. Post-race pain levels were recorded at 15 minutes (T1), 90 minutes (T2), 1 Day (T3), and 2 days (T4) after race finish. Data were analyzed using linear mixed models controlled for baseline, with time point as a repeated factor. Simple contrasts compared post-race time points to baseline, and Student's t-tests assessed between-group time point comparisons" (Withee. 2015)

  Unfortunately, this cannot be said for the study results, which showed nothing but a trend of lower pain levels in the MSM group - with non-significant time-by-treatment effects in either of the groups.
  

  

  Figure 2: Muscle and joint pain  15 minutes (T1), 90 minutes (T2), 1 Day (T3) after half-marathon race with methylsulfonylmethane (MSM | 3g/day) or placebo supplementation (Withee. 2015)

  In view of the fact that the provision of the 3g of MSM did result "in nearly significantly lower MP at T1 (MSM = 27.3mm vs. placebo = 49.8mm, p = 0.063), and lower MP at T2 (27.1mm vs. 40.0mm; p = 0.300), and T3 (30.0mm vs. 41.9mm; p = 0.306)" (my emphasis in Withee. 2015), as well as similar changes in joint pain (see Figure 2), it does still appear warranted to conclude that MSM supplements (3g/day) may be worth trying for anyone suffering from persistent joint and/or muscle pain after workouts.
• MSM as an inflammatory cytokine modulator -- While the previously discussed study by Withee et al. (2015) clearly indicates that MSM supplementation helps managing the level of exercise-induced inflammation, Withee et al. did not investigate the mechanism that was responsible for their observations. A recent study from the University of Memphis, however, did just that: In said study, Godwin et al. determined the effect of MSM on lipopolysaccharide (LPS) - induced inflammatory mediators after a single bout of acute eccentric exercise.
  
  To do so, they had five recreationally active, healthy men consume either 3g/day of MSM or a placebo supplement for 28 days. At the end of the supplementation program, a single bout of acute exercise (10 sets of 10 repetitions of eccentric knee extensions) was performed and blood samples were collected (immediately = 0 h, as well as 24 h, 48 h and 72 h post exercise) and analyzed.
  
  

  

  Do you remember that MSM can also act as a GH booster & bone builder | more

  The most significant results of the analysis are hardly surprising: The supplementation of MSM blunted the increase in the systemic levels of inflammatory cytokines (IL-6 and IL-1β) immediately after exercise.
  
  What is surprising, though, is the fact that the inflammatory response to LPS exposure in an ex-vivo study with blood that had been drawn at various time-points during the study shows a "dramatic increase in inflammatory cytokine secretion (IL-6, IL-1β and TNF-α) only after exercise for samples that was exposed to MSM" (Godwin. 2015).
  
  So what does that mean - practically speaking? Well, the authors are certainly right, when they point out that ...

  "[t]his response is specific to the stimulation with LPS as secretion of LPS-non responsive proteins is not increased, as evident by the stable levels of IL-17a [... and thus suggestive of the fact that] MSM is able to reduce the initial cytokine surge that is induced by acute exercise, while allowing for an efficient response to infectious stimuli after a single bout of acute exercise" (Godwin. 2015).

  On the other hand, this assumption stands in contrast to the 2-3 fold increase in IL-10 production after LPS stimulation for the subjects in the MSM group whose pre-exercise levels of the IL-10 levels before exercise. Previous research did after all suggest that greater IL-10 production my be the motor of the exercise induced "depression of immunity commonly reported in athletes engaged in high training loads" (Handzlik. 2013). Whether the chronic use of MSM supplements entails an increased risk of infection may thus warrant further investigations.

3x 1.3g/day cordiceps synensis can significantly increase time to exhaustion and have (individually different) beneficial effects on the ventilatory threshold (Hirsch. 2015).

Two more to go... two more studies that is: While the total number of ISSN '15 studies I haven't discussed or at least mentioned in this series yet is larger than two, there are only two studies I'd like to single out before the end of this installment of this Suppversity series. The Cordyceps synensis study by Hirsh et al. who were able to show that 4g of the mushroom can improve oxygen kinetics, and peak power non-significantly, as well as time to exhaustion significantly in recreationally active subjects who completed  a maximal graded exercise test, 6 min sub-maximal cycle test, and 3 min all-out cycle test, each separated by at least 24 hrs when the supplement is consumed chronically, i.e. in thee servings of 1.3 g equally spread across the day for three weeks (Hirsch. 2015).

Also worth mentioning, but in the absence of hard evidence of causality hardly worth discussing in much detail is Marc Bubbs' observation that basketball players who are training at high-intensity "seem more likely to have insufficient levels of vitamin 25(OH)D" (Bubbs. 2015) - if a follow up shows that normalizing these levels with supplementation will have performance enhancing effects, though, this would be really news-worthy | Comment on Facebook!

References:

• Bubbs, Marc. "Observational case study-Vitamin 25 (OH) D status of professional basketball players and its impact on athletic performance and recovery." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P55.
• Cook, Gary. The Effects of Chronic Arginine Supplementation on Muscle Strength and Hypertrophy Following Resistance Training. Diss. Ohio Dominican University, 2015.
• Godwin, Simone, et al. "MSM enhances LPS-induced inflammatory response after exercise." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P48.
• Handzlik, Michal K., et al. "The influence of exercise training status on antigen-stimulated IL-10 production in whole blood culture and numbers of circulating regulatory T cells." European journal of applied physiology 113.7 (2013): 1839-1848.
• Hirsch, Katie R., et al. "Chronic supplementation of a mushroom blend on oxygen kinetics, peak power, and time to exhaustion." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P45.
• Kalman, Douglas, et al. "A clinical evaluation to determine the safety, pharmacokinetics and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males.(LB418)." The FASEB Journal 28.1 Supplement (2014): LB418.
• Rood-Ojalvo, S., et al. "The benefits of inositol-stabilized arginine silicate as a workout ingredient." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P14.

Synephrine More Ergogenic, Than Thermogenic? Pump Supps Revisited - L-Arginine, L-Citrulline and Respective Whey-Peptides & -Nitrates | ISSN Research Review '15 #2

Synephrine More Ergogenic, Than Thermogenic? Pump Supps Revisited - L-Arginine, L-Citrulline and Respective Whey-Peptides & -Nitrates | ISSN Research Review '15 #2

arginine arginine nitrate citrulline ISSN15 ISSN2015 l-arginine l-citrulline nitrate nitrates performance pump pump supplements supplements vasolidation whey peptides

Synephrine, arginine, citrulline - Which pre-workout ensures that you're "on fire"?

As I pointed out previously, my initial idea to cherry pick only the most interesting study results that were presented in form of of poster presentations at the Twelfth International Society of Sports Nutrition (ISSN) Conference and Expo in 2015 didn't work out. The number of interesting studies is is simply too much for a single SuppVersity article to discuss them all.

Accordingly, I am now posting the 2nd serving of what is going to be a multi-part series of articles with brief discussions of the most significant results of the >20 studies and short references to those that didn't make the SuppVersity cut in this, previous and future installments of this series for one reason or another.

Read more about ISSN and other studies at the SuppVersity

Vitargo, Red Bull, Creatine & More | ISSN'15 #1

Pump Supps & Synephrine & X | ISSN'15 #2

High Protein, Body Comp & X | ISSN'15 #3

Keto Diet Re- search Update | ISSN'15 #4

The Misquantified Self & More | ISSN'15 #5

BCAA, Cholos-trum, Probiotics & Co | ISSN'15 #6

• Synephrine More Ergogenic Than Thermogenic? There was not just one, but two poster presentations and a full paper that has been published only days ago on synephrine containing supplements at the ISSN meeting and on the ISSN website, respectively. Synephrine? Yes, that's the supplemental non-starter, ah... I mean allegedly powerful fat burner from orange peels. The one with promising fat loss results in rodents, but discouraging results in practice.
  
  Luckily, the studies that were presented in form of posters by scientists from the Texas A&M University (Jung. 2015 & Dalton. 2015) at the ISSN meeting did not deal with synephrine as fat burner. Rather than that, Jung et al. and Dalton et al. took a look at the short- and long-term safety of synephrine as a pre-workout. A pre-workout that contained either 3g beta alanine, 2g creatine nitrate, 2g arginine AKG, 300mg N-acetyl tyrosine, 270mg caffeine, and 15mg Mucuna pruriens, alone (PLA) or the same baseline ingredients and synephrine.
  

  

  Figure 1: Number of reps on sets 1-3 & 4-6 in the control and treatment conditions (Ratamess. 2015)

  Now, the fact that some synephrine in your preworkout won't kill you is not really exciting. I have to admit that. What is exciting... at least sort of, though is the fact that the questionable thermogenic turned out to be an effective ergogenic in the already published and thematically related study by Ratamess and colleagues (Ratamess. 2015). A study that shows that p-synephrine of which previous studies indicate that it is a potent, but highly selective β-3 adrenoreceptor may nor be the best fat burner (the good old ephedrine was a pan-receptor activator and clenbuterol & co target the β-3 receptor, maybe that's also why the fat loss results are rather disappointing) , but at least an underestimated ergogenic.

Is p-synephrine different from synephrine? That's a good question without a clear question. Most supplements that list synephrine on the label actually contain P-hydroxy-α-{methylaminomethyl}-benzylalcohol aka p-synephrine, a protoalkaloid compound that differs from m-synephrine and o-synephrine structurally and comes in form of to stereoisomers in most supplements - the l-enantiomer and the d-enantiomer as the racemate d,l-synephrine. While the latter have been shown to be present in bitter orange, other forms, like the m,s-isomer may are suspected to be adulterations from synthetic phenylephrine supplement producers use to "spike" (Allison. 2005) their products (I assume this was not the case with the samples the researchers in the study at hand used, but the chaos wrt to the types of synephrine puts a huge "?" behind the assumption that you'll see the same effects from any given synephrine or synephrine + caffeine supplement. 

• As the data in Figure 1 goes to show you, the p-synephrine supplement, which was administered to twelve healthy, college-aged men at a dosage of 100mg either alone (S) or in conjunction with 100 mg caffeine (SCF) for three days. On the day on which the subjects participated in a standardized resistance exercise protocol consisting of 6 sets of squats for up to 10 repetitions per set using 80 % of their one repetition-maximum (1RM) with 2 min of rest in between sets, the supplement was ingested 45 minutes before the workout. In comparison to the placebo treatment synephrine alone triggered a significant increase in total repetitions and volume load. When synephrine was combined with 200 mg of caffeine, it also increased the mean power and velocity of squat performance. What did not change in response to either synephrine alone or caffeine and synephrine, though, were the blood lactate levels or the rate of perceived (RPE) exertion the subjects reported on the usual visual analogue scales.
  
  For me personally, that's a surprising result. For the scientists it "indicate[s that] supplementation with S and SCF can enhance local muscle endurance during resistance exercise" (Ratamess. 2015); and I have to admit: They are right. One thing you should keep in mind, though, is that unlike caffeine, where you often see reductions in RPE and thus an effect you will feel, synephrine will - even if it works - do its purported "magic" more subtly.
• The Latest on "Pump Supplements" - Creatine, Arginine, Citrulline, Nitrates -- To make sure that this series is not turning into a 12-part article, I will address the results of Moon's, Suzuki's and Vogel's results in one item (since Moon's paper basically summarizes the results of studies by Falcone and Joy, I won't discuss those separately) .
  
  

  

  Figure 2: Increases in blood flow volume (BFV) 33 minutes after the ingestion of 1.87g of RC, 3.67g of CP (citrulline content 1.87g), 1.87g of RA, or 3.07g of AP (arginine content 1.87g) before 3 sets of 15 arm curls (Moon. 2015).

  Moon et al.'s comparison of citrulline's and arginine's ability to increase the exercise-induced vasodilation and blood flow yielded unsurprising results that confirm that citrulline-based ingredients are more effective than arginine-based ingredients for modulating vasodilation and blood flow. Now that alone wouldn't be news-worthy if the scientists had not tested the effects of both, rawe L-citrulline (RC) and raw L-arginine (RA) and, citrulline and arginine bound to a whey peptide (CP and AP, respectively).
  
  I guess I am not going to surprise you, when I tell you that regular arginine was the worst vasodilator in this quartet. What is more surprising, though, is the extent to which the peptide bonding increased the vasodilating effects of regular citrulline and even arginine. With the the former producing 2x higher increases in vessel diameter and 9% higher increases in blood glow volume than regular citrulline (let's not even mention regular arginine | see Figure 2) the effects are pronounced enough to be potentially "feelable" and "visible" during a workout.
  
  

  

  Citrulline & Glutathione - GSH Amplifies & Prolongs CIT's NO Boosting Effects During + After Biceps Workout | learn more.

  Against that background I would be curious to see, whether the likewise recently reported performance enhancing effects of citrulline Suzuki et al.'s observed in twenty two well-trained young men who consumed 2.4 g / day of L-citrulline or placebo for 7 days and they took 2.4 g of L-citrulline or placebo 1 hour before 4 km cycling time trial on day 8 would be enhanced by bonding citrulline to whey peptides.
  
  I mean, if citrulline-whey-peptides appear to offer the same effects citrulline does, but at a higher efficacy, their beneficial effect on cycling time trial performance of which the Suzuki et al. argue that it was mediated by an up-regulation of plasma NO availability should be superior to that of raw citrulline, as well, right?
  
  And now that we are already talking about what really matters, i.e. performance enhancements, not increases in blood flow, it would also be interesting to see a follow up on the last "pump supplement" study to be mentioned in this installment of the ISSN Research Review: A study by Vogel et al.'s on the vasolidating effects of an arginine-nitrate based pre-workout supplements that shows significant increases in brachial artery diameter. Increases that are quantitatively similar to those Moon et al. observed for citrulline-whey-peptides in the previously discussed study. That does not mean, though that they are equally effective, though. To be able to say that we would need a study in which both agents are compared head-to-head. Unless this study is done and a follow up on Vogel's study proves that the increases in blood flow will actually produce significant performance gains, the only thing I can say about arginine nitrate is: It's interesting, but with respect to its ergogenic effects more studies have to be done.

You don't believe citrulline can do anything for you? Check this out: 8g/day Citrulline Increase Leg Workout Performance - More Reps on Leg Press, Hack Squat & Leg Ext. in Exp. Gymrats (more)! It is thus by no means useful for "cosmetic pumps", only 

Studies that didn't make the cut in this issue are Brooke Bouza et al.'s study on the exercise and calorie information on menus (Bouza. 2015) as well as O'Conner et al.'s tart-cherry study (O'Connor. 2015). That's not because there were methodological issues or something. It's much simpler: The notion that "exercise and calorie information on menus is not enough to improve food choices in Hispanic adults" (Bouza. 2015) is about as unsurprising as the word "potentially" (O'Connor. 2015) in the conclusion of O'Connor's study is daunting. And by the way, now that you know that tart cherry "potentially increases running performance and attenuates post-race markers of inflammation" you actually know the most relevant finding of O'Connor's study, right? | Comment on Facebook!

References:

• Allison, D. B., et al. "Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?." International journal of obesity 29.4 (2005): 443-446.
• Bouza, Brooke, et al. "Exercise and calorie information on menus is not enough to improve food choices in Hispanic adults." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P3.
• Dalton, R., et al. "Safety and efficacy of a pre-wrkout dietary supplement with and without synephrine." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P5.
• Falcone, Paul H., et al. "Acute hemodynamic effects of L-arginine, arginine nitrate, and arginine peptide on exercise-induced vasodilation and blood flow in healthy men." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P10.
• Joy, Jordan M., et al. "A comparison of raw citrulline and citrulline peptide for increasing exercise-induced vasodilation and blood flow." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P18.
• Jung, Y. P., et al. "Effects of 8 weeks pre-workout dietary supplement ingestion with and without synephrine on blood chemistry panel." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P4.
• Moon, Jordan R., et al. "A comparison of citrulline and arginine for increasing exercise-induced vasolidation and blood flow." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P6.
• O'Connor, A., et al. "Short-term powdered tart cherry supplementation encircling an acute endurance challenge potentially increases running performance and attenuates post-race markers of inflammation." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P7.
• Suzuki, Takashi, et al. "Oral L-citrulline supplementation enhances cycling time trial performance in healthy well-trained males." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P52.
• Vogel, Roxanne M., et al. "Acute hemodynamic effects of a multi-ingredient performance supplement on brachial artery vasodilation and blood flow volume following elbow flexion exercise in healthy young men." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P28.