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From a physiological perspective NO is not primarily there to make you look vascular and pumped, boys.

If you've read the headline and are asking yourselves "Why on earth would I even want to spend money on cosmetic pump?", you probably need a reminder of the multiple important functions nitric oxide (NO) serves in your body: (1) With their ability to relax the musculature of your blood vessels to increase the blood flow through your veins, normal NO levels are required to guarantee optimal blood flow to every body part; (2) since this includes your sexual organs, normal NO levels are also a prerequisite for normal / optimal sexual function; (3) having enough NO is also required to keep your immune defenses up, because the white blood cells need it in their fight against intruders; and if heart disease, sexual dysfunction and immune health are all things you don't care about (4) you may be interested to hear that your brain and metabolic health critically depend on normal NO levels, as well.
Now that you've got the primer on "nitric oxide beyond the pump" you may be happy to hear that a very common NO supplement, i.e. citrulline, actually delivers. But there's more: In a very recent study, scientists from the Baylor University demonstrated for KYOWA HAKKO BIO CO (so this is sponsored research) that a combined treatment with citrulline and glutathione leads to significant increases in the levels of cGMP, nitrite, and NOx (nitric oxide metabolite) in cells, rodents and humans.

Figure 1: Overview of the design of the "human part" of the study (McKinley-Barnard. 2015).

In the latter part of the study (the human part), the researchers had sixty six participants randomly assigned (in a double-blind fashion) to one of four groups (n = 15 per group) involving 7 days of the oral ingestion of four capsules containing a total daily dose of either: cellulose placebo (2.52 g/day), L-citrulline (2 g/day), GSH (1 g/day), or L-citrulline (2 g/day) + GSH (200 mg/day). Supplementation compliance was monitored by participants returning empty containers of their supplement on day 7, and also by completing a supplement compliance questionnaire.
Each participant ingested all four capsules containing their respective daily supplement dose each evening for six consecutive days until at Visit 3 (Day 7), participants were provided the final daily dose of their respective supplement ingested one hour prior to performing a previously familiarized biceps training program consisting of  3 sets of 15 repetitions with as much weight as they could lift per set (typically 70–75 % of 1RM | 10s rest between sets, only) on a selectorized weight machine (Body Master, Rayne, LA).

Figure 2: Nitrate concentration and change in plasma NOx in rodents (NO metabolites | McKinley-Barnard. 2015).

Figure 2, which depicts data from the rodent study, already suggests that only citrulline or citrulline and glutathione would trigger significant increases in NO production in the 20-22 year-old healthy, well-trained (at least three resistance training sessions per week) participants, while GSH alone would trigger only a minor increases of the nitric oxide levels.

Figure 3: Changes in NO metabolites (NOx) and cGMP levels (McKinley-Barnard. 2015) in the human study.

The data in Figure 3 (left) which tells you that the increase in stable NO metabolites (NOx) in the blood of the subjects in the citrulline + GSH group was the highest. What may surprise you, though, is that the increase in nitric oxide that is obviously partly mediated by an increase in c-GMP (Figure 3, right) levels was not only maintained after the workout, the levels even kept increasing.
This is in contrast to your regular "pump" formula (using only citrulline), where the levels drop back to baseline ( and potentially even lower - after all only 30 min were monitored) after the workout.

Why is that important? Well, if you look back at the "nitric oxide beyond the pump" list from the introductory paragraph, you will notice that almost all of these "beyond the pump" effects are health-relevant during, but also and even more so after the workout.
References:

• Ghigo, D., et al. "Correlation between nitric oxide synthase activity and reduced glutathione level in human and murine endothelial cells." Amino acids 10.3 (1996): 277-281.
• Hofmann, Heinrich, and Harald HHW Schmidt. "Thiol dependence of nitric oxide synthase." Biochemistry 34.41 (1995): 13443-13452. 
• McKinley-Barnard, Sarah, et al. "Combined L-citrulline and glutathione supplementation increases the concentration of markers indicative of nitric oxide synthesis." Journal of the International Society of Sports Nutrition 12.1 (2015): 27.

Does the vasodilatory effect of nitrates have a direct ergogenic effect that correlates with increases in blood flow?

If you are someone who actually reads the "product write-ups" (=ads) for NO boosters you will have heard the claim that the NO-induced vasodilation and the subsequent increase in blood flow will have significant performance enhancing effects. If you are a critical thinker, you will yet also have noticed that a "[citation]" (=reference) that would prove this claim is missing... with the publication of a recent study from the Université Droit et Santé Lille this may change in future write-ups.

In said study, Julien Aucouturier et al. tried to determine whether 3 days on NO3-rich beetroot juice would boost the tolerance to supra-maximal intermittent exercise.
To this ends, the French researchers had their subjects, who were not previously engaged in any form of intense endurance exercise perform a standardized exercise test, which consisted of 15-second exercise periods at 170% of the maximal aerobic power interspersed with 30-second passive recovery
periods, to failure.

Figure 1: Overview of the study design (Aucouturier. 2015).

All subjects performed the standardized testing procedure twice - at the same time of the day, but seperated by at least one, maximally two weeks. Once without after ingesting 680mg of NO3- for three days from beetroot juice, once after ingesting the low nitrate (<5mg/L) apple-black currant juice that was used as a placebo.

Figure 2: Individual data points for the increase in reps (=number of intervals to exhaustion) and markers of potential mechanisms that trigger this increase, i.e. ventilation (right, top) & oxygen uptake (right, bottom | Aucouturier. 2015)

The individual data points in Figure 2 (which are much more meaningful than group averages) show that the majority of the subjects experienced a measurable, some of them even a significant increase in exercise tolerance in response to the ingestion of 680mg of NO3- from beetroot juice over a three-day period.

Before we get back to the mechanism I hinted at in the introduction, already, I want to highlight one last thing that follows from the previously highlighted result: If "only" more than 50% of the subjects benefited from the NO3- almost 50% of them didn't benefit and that's not exactly news when it comes to beetroot juice and nitrate supplementation. Previous studies showed similarly conflicting results with some suggesting that the training status of the subjects may be a significant modifier (athletes may benefit less than couch potatoes), but the reason for the differentials response of the subjects is something to investigate in another study.
References:

• Aucouturier, Julien, et al. "Effect of dietary nitrate supplementation on tolerance to supramaximal intensity intermittent exercise." Nitric Oxide (2015).

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

In this installment of the waredownloadsoft 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.

• 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).

• 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.