Cupping for Pain, Health & Performance | Must Be Good, if Phelps Does it, Right? Let's See What the 100+ Studies Say

The "cups" come in various forms and sizes... and no, there's no meta-analysis yet that can tell you what the optimal size and form for the treatment of a given disease / problem would be ;-)

"If Phelps does it, it must be good!" I am pretty sure that SuppVersity readers don't think like that this is why I'd like to invite you to join my brief research review on cupping, i.e. the use of cups that are sucked to specific acupuncture points on your back via a simply physics trick: After being heated with fire, the air in the cup expands rapidly only to decrease by the same extent after the pre-heated cup is placed on your back. The rapid reduction of the volume of air in the cup will will create a vacuum that will not just glue the cup to your skin, but literally suck some of your skin into the cup and the capillaries in the skin to rupture - no wonder Phelp's body was plastered with red "cup marks" during the Olympic games ;-)

With Phelps strongly believing in the practice, it is quite obvious that it would have worked its alleged recovery magic irrespective of whether the increased blood flow to the cupped area has any local or systemic health effects whic allegedly range from anti-viral therapy to blood pressure management - you call that "placebo effect".

Read previous True or False!? Articles at the SuppVersity

You Cannot Consume too Much Whey?!

Caffeine and Creatine Don't Mix, do They?!

Creatine is Better Taken After Workouts!?

Low Fat for Lean, Low Carb for Fat Individuals!?

Protein Timing Really Doesn't Matter!?

Nicotine Gums Will Help Fat Loss!?

From a science perspective, though, there is some preliminary evidence that Phelps' trust is / was not totally misplaced, though - here's an overview of what we know...

• Initial evidence of cupping to treat chronic neck pain (Lauche. 2013) - Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options.
  
  It would thus be great, if the positive results of a 2013 study that tested the efficacy of 12 weeks of a partner-delivered home-based cupping massage, and compared it to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain, could be reproduced in a more tightly controlled  setting.
  

  

  Figure 1: Cupping vs. PMR home-treatment in a 12-week study in patients w/ chronic neck pain (Lauche. 2013).

  Primary outcome measure was the current neck pain intensity (0-100 mm visual analog scale; VAS) after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients (54.1±12.7 years; 73.8%female) were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31).
  
  After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds.
  
  "In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results" (Lauche. 2013), the Lauche and colleagues from the University of Duisburg-Essen conclude.
• Preliminary evidence of a reduction of symptoms of osteoarthritis (Teut. 2012) - Scientists from the Charité University Medical Center in Berlin investigated the effectiveness of cupping in relieving the symptoms of knee osteoarthritis (OA) in a two-group, randomized controlled exploratory pilot study.
  
  

  

  Image 1: Much in contrast to most other studies, the osteoarthritis didn't use "cups" and heating, but this adaptable silicone cup at the knee (Teut. 2012).

  Patients with a clinically and radiological confirmed knee OA (Kellgren-Lawrence Grading Scale: 2-4) and a pain intensity > 40 mm on a 100 mm visual analogue scale (VAS) were included. 40 Patients were randomized to either 8 sessions of pulsatile dry cupping within 4 weeks or no intervention (control). Paracetamol was allowed on demand for both groups. Outcomes were the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score, the pain intensity on a VAS (0 mm = no pain to 100 mm = maximum intensity) and Quality of Life (SF-36) 4 and 12 weeks after randomization.
  
  In addition, the subjects' use of Paracetamol was documented within the 4-week treatment period. Analyses were performed by analysis of covariance adjusting for the baseline value for each outcome.
  

  

  Figure 2: Western Ontario and McMaster Universities Osteoarthritis (WOMAC) score and Visual Analogue Scale (VAS) for pain intensity after 4 and 12 weeks of cupping or control (Teut. 2012).

  21 patients were allocated to the cupping group (5 male; mean age 68 ± SD 7.2) and 19 to the control group (8 male; 69 ± 6.8). After 4 weeks the WOMAC global score improved significantly more in the cupping group with a mean of 27.7 (95% confidence interval 22.1; 33.3) compared to 42.2 (36.3; 48.1) in the control group (p = 0.001). After 12 weeks the WOMAC global score were still significantly different in favor for cupping (31.0 (24.9; 37.2) vs. 40.8 (34.4; 47.3) p = 0.032), however the WOMAC subscores for pain and stiffness were not significant anymore. Significantly better outcomes in the cupping group were also observed for pain intensity on VAS and for the SF-36 Physical Component Scale compared to the control group after 4 and 12 weeks. No significant difference was observed for the SF-36 Mental Component Scale and the total number of consumed Paracetamol tablets between both groups (mean 9.1, SD ± 20.0 vs. 11.5 ± 15.9).
  
  "In this exploratory study dry cupping with a pulsatile cupping device relieved symptoms of knee OA compared to no intervention. Further studies comparing cupping with active treatments are needed," Teut et al. conclude and forget to mention that everything could be placebo... after all, simply not doing anything is not a valid / significant "treatment" to evaluate the effects of cupping. This and the fact that the dosage of pain-killers are things you should keep in mind when evaluating the study results. 

"Wet" = bloody cupping - Geez!

"Wet cupping" is gorier than you'd expect: What doesn't sound like much is in fact a completely different way of cupping. While the previously described procedure (see introduction) may be a bit painful, it is totally non-invasive. That's in contrast to the so-called "wet-cupping" process aka "Hijamat bilshurt" in Unani medicine, which involves "the incising of skin either before the cup is placed or during the process of suctioning with needles placed at the base of the cup being used" (Akhtar. 2008). Overall a rather gory practice as the image to the left is one of the rather harmless photos you will find online.

• Promising effects in chronic low back pain, systematic review says (Huang. 2016) - It's just published as a letter, but the systematic review Huang and colleagues from Taiwan argue that "the research results show that cupping therapy is promising for pain control and improvement of quality of life, and minimises the potential risks of treatment" (ibid.). Huang et al. base this assessment on their review of one randomised controlled trial (RCT, level I evidence), six non-RCTs (level II evidence), 20 case reports (level IV evidence) and two mechanism-based reasoning studies (see Table 1):
  

  

  Table 1: Overview of studies with levels I and II evidence Huang et al. (2016) included in their review.

  In the RCT, the effective rate of the wet-cupping (see red box!) group was similar to that of the waiting-list group (p>0.05). Interventions in both groups decreased pain, disability and acetaminophen dosage, but a significant decrease in pain intensity according to the McGill pain questionnaire (p<0.01) and reduced consumption of acetaminophen (p=0.09) were seen in the wet-cupping group. Similarly promising were the results of the six non-RCTs: one showed that the visual analogue scale (VAS) score and the Oswestry disability index in the balance-cupping group were significantly lower than in the group with cupping with retention and diclofenac (p<0.05), but there was no difference between the cupping with retention group and the diclofenac-only group (p>0.05). The other studies individually showed that the effectiveness of cupping in decreasing VAS,  reducing recurrence rate and improving quality of life, was better than Western medication.
  
  It should not be forgotten, though, that the evidence is rather preliminary than water-tight. Accordingly, Huang et al. are 100% right, when they demand that "further studies are needed to determine the potential role of cupping therapy in the treatment of low back pain" (Huang. 2016).

Table 2: Estimate effect of cupping for pain management (all types of diseases) from 16 included trials (Cao. 2014).

Pain management appears to be the best proven area of application (Cao. 2014) - As the overview of studies from Cao et al.'s 2014 review in Table 2 indicates, the effect of cupping for pain management (regardless of type of diseases) from 16 included trials is mostly, but not exclusively positive (meaning the pain was reduced), albeit not always significant and in many cases potentially influenced by confounding factors / treatments and thus far from being convincing evidence.

• A plethora of additional possible benefits (Cao. 2012) - While pain management appears to be the closest to being a proven benefit of cupping, the literature that was reviewed among others by Cao, Li and Liu lists other purported benefits.
  
  The scientists from the University of Western Sydney and the Beijing University of Chinese Medicine managed to identify the impressive number of 135 RCTs published from 1992 through 2010; studies that were generally of low methodological quality, but investigated diseases ranging from herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, over acne, lumbar disc herniation, to cervical spondylosis.
  

  

  Figure 3: Types of cupping therapy used in the studies in the meta-analysis (Cao. 2012).

  Unlike Phelps, most researchers used the "bloody" wet cupping - when all is said end done, not without negative effects as Cao et al. point out: "Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis" (Cao. 2012 | check out the Figures for free). 

Figure 3: While it turned out to be a failure in this follow up study (data from Aleyeidi. 2015), wet, i.e. bloody, cupping aka "Hijama" is traditionally used in Indian medicine to treat hypertension (=elevated blood pressure), too - and guess what: initial evidence from other studies suggested that it works (Lee. 2010; Zarai. 2012).

Bottom line: Thanks to the placebo effect and its very likely effects on practitioners pain threshold, it does not seem appropriate to laugh about Michael Phelps or anyone else who uses (dry!) cupping to promote recovery and/or control back, knee or whatever other pain (cf. Cao. 2014).

In the absence of bulletproof evidence from sensibly controlled human trials, it would yet be similarly misguided to think of cupping as a decisive factor in Phelps' recent Olympia success and/or a traditional medicine technique that doesn't just cure pain but also high blood lipid levels, which was the goal of an inaccessible doctoral thesis Abeer Mohammed Kawthar announced at the King Abdulaziz University - for blood pressure, Kawthar, this time working with Aleyeidi & Aseri has, after all, only recently failed to replicate the results of previous studies that suggested a blood pressure lowering effect of wet, i.e. bloody, cupping (Aleyeidi. 2015) | Comment!

References:

• Akhtar, Jamal, and M. Khalid Siddiqui. "Utility of cupping therapy Hijamat in Unani medicine." Indian J Trad Knowl 7.4 (2008): 572-4.
• Cao, Huijuan, Xun Li, and Jianping Liu. "An updated review of the efficacy of cupping therapy." PLoS One 7.2 (2012): e31793.
• Cao, Huijuan, et al. "Cupping therapy for acute and chronic pain management: a systematic review of randomized clinical trials." Journal of Traditional Chinese Medical Sciences 1.1 (2014): 49-61.
• Huang, Chia-Yu, Mun-Yau Choong, and Tzong-Shiun Li. "Effectiveness of cupping therapy for low back pain: a systematic review." Acupuncture in Medicine (2013): acupmed-2013.
• Kawthar, Abeer Mohammed. "Effect of compining antilipids drugs with wet cupping on lipid blood level." (2007).
• Lauche, Romy, et al. "Effectiveness of home-based cupping massage compared to progressive muscle relaxation in patients with chronic neck pain—A randomized controlled trial." PloS one 8.6 (2013): e65378 [FFT]
• Lee, Myeong Soo, et al. "Cupping for hypertension: a systematic review." Clinical and experimental hypertension 32.7 (2010): 423-425.
• Teut, Michael, et al. "Pulsatile dry cupping in patients with osteoarthritis of the knee–a randomized controlled exploratory trial." BMC complementary and alternative medicine 12.1 (2012): 1.
• Zarei, Mohammad, et al. "The efficacy of wet cupping in the treatment of hypertension." ARYA Atheroscler (2012): S145-S148.

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

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.

Natural Migraine Prophylaxis & Treatment: Riboflavin, ALA, Magnesium, CoQ10, Feverfew, Melatonin, Butterbur & Co.

Natural migraine protection: Even if supps won't cure it, they can at least reduce the number of "bad days" and the severity of the attacks.

In the last installment of the "Short News" you've learned about the enormous costs chronic pain produces on an annual basis: Roughly $300 billion for its treatment and another $300 billion in form of economic damage. No wonder pain killers, Cox inhibitors and & co are among the top selling and drugs in the world.

Now, migraine is unquestionably among the most debilitating forms of chronic or rather cyclic chronic pain and while women are much often hit by the pain from withing (21.8% v.s 10.0% of the US citizens suffer; NHS 2009). And while I cannot tell you how much of the $2,000 bucks each of you is "spending" on an annual base on treating the pain of his / her fellow citizens, I believe that both of you, my dear mal and female readers, may benefit from the information in today's installment of "On Short Notice" with a comprehensive, but probably not all-encompassing list of promising supplemental agents for migraine prophylaxis and "treatment":

• magnesium: I have actually mentioned that in a previous SuppVersity post already (read more), but I guess it's well worth mentioning it again. Low brain magnesium levels have been reported in a whole host of observational studies in migraineurs. There have also been a couple of respective trials with overall inconclusive, but rather positive results for the acute treatment of patients with aura and, possibly, perimenstrual migraine prophylaxis.
  
  The magnesium formulation that has been used in these trials varied, and there is no large(r) scale comparison of different forms and dosing regimen as of now. Corresponding effects have been observed with 250mg of intravenous and 600mg of oral magnesium chelates (Cady. 1998; Mauskop. 1998), for example. Evans and Taylor additionally cite the following four randomized controlled trials (RCTs; my emphases):

  Take a form that does not give you diarrhea! If you look at the success rates it would appear as if  the organic formulas are superior to the inorganic ones. On the other hand, this may be a simple effect of the increased rates in diarrhea reported by many researchers using non-organic formulations. After all, this does not simply reduce magnesium absorption but will also have negative effects on the overall mineral and water balance. Both, dehydration and mineral imbalances could otherwise increase instead of decrease your risk to suffer from migraine attacks.

  "The first RCT of magnesium for migraine prevention involved only 20 subjects and was positive; the active therapy was 360 mg Mg++ pyrrolidone carboxylic acid divided TID. The second RCT, by Peikert et al, involved 81 adult women and 600 mg magnesium (trimagnesium dicitrate) daily demonstrated a 41.6% improvement with verum versus 15.8% for placebo. The third RCT for migraine prophylaxis, published by Pfafferath et al, involved 69 patients taking 486 mg magnesium; no benefit for magnesium was found; at the end of the 3-month treatment phase, the responder rate was 28.6%in the magnesium group and 29.4% in placebo subjects, according to the primary efficacy endpoint. [...] In a last trial, Wang et al gave magnesium oxide 9 mg/kg divided TID to subjects aged 3 to 17 years. Approximately three-quarters of eligible subjects completed the study, with a significant downward trend in headache days in the active treatment group versus placebo; the lack of any difference in the slope of treatment trends, however, was such that no significant superiority of magnesium over placebo could be documented." (Evans, 2006)

  While magnesium's acute effects are usually ascribed to increases in the circulating levels of Mg++ ions, it's efficacy as a prophylactic treatment is most likely a result of increasing tissue levels and requires a minimum of 3 to 4 months for measurable benefits to occur.
• CoQ10: As a student of the SuppVersity you are well aware of the beneficial (actually vital!) importance of CoQ10 on mitochondrial health. It is an endogenous enzyme cofactor that can be produced by your body. Unfortunately, there are certain conditions and medications that lead to the depletion of CoQ10 and subsequently impair the proton-electron translocation across the mitochondrial membranes.
  
  

  

  No headache, no problem, but not a reason not to consider CoQ10 supplementation. CoQ10 can also help if your exercise performance is what gives you headaches: "300mg CoQ10 Boost Peak Power Increases in Young Elite Athletes. Plus: 140ml of Beet Root Juice, That's all it Takes to Minimize the Oxygen Demands During a Workout" (learn more)

  Against that background and in view of the involvement of mitochondrial malfunction in the etiology of migraine, it is not surprising that Rozen et al. observed in a 2002 open label study in which 61%  of the 31 patients who consumed 150mg CoQ10 daily for 3 months had at least a 50% reduction in migraine days without experiencing any significant adverse events. Interestingly, the supplement took "only" 4 weeks to kick in (a follow up on whether or not it was necessary to stay "on" CoQ10 is not available, but I would consider it likely). In 2005 Sandor et al. conducted one of the few randomized controlled trials: In this particular study, the patients received 100mg of CoQ10 three times daily and saw significant decreases in the attack frequency, the number of headache days, and days with nausea.
  
  Interestingly the highly soluble version of CoQ10 (a liquid formulation of water dispersed nano-particles comprising a supercooled melt of CoQ10 with modified physicochemical properties; GuttaQuinone) that was used in the Sandor study had some side effects (gastrointestinal disturbances and cutaneous allergy that had not been reported in other studies). Overall, CoQ10 is yet perfectly safe (even if it's nano-sized) and may even yield benefits if you don't suffer from migraine.
• Tanacetum parthenium: Also known as Feverfew, the dried chrysanthemum leaves have a long history as an analgesic and one huge problem, according to the only available peer-reviewed report, preparations of feverfew have shown a >400% variation in dosage strength of the known active ingredient parthenolide (Rossi. 2005). According to evens Evans & Taylor, some experts even doubt if it can be generally assumed that parthenolide, which has some very promising research to back up its efficacy even is the active ingredient in the plant leaves.
  

  

  Feverfew does not look exactly, like powerful medicinal plant, right?

  "In a systematic review, Vogler et al reported on randomized controlled trials (RCTs) involving feverfew for migraine prophylaxis conducted prior to 1998. 11-16 Five studies qualified by Jadad score as adequate; 1 has been published in abstract form only, and only 216 subjects in total have been studied. Vogler et al concluded, “In view of the popularity of feverfew, perhaps the most striking finding was the paucity and low average quality of the existing RCTs on the subject.”

  If you wanted to cut it short you could thus say. It's popular, people swear by it, but according to our current knowledge it may as well be the placebo effect that keeps people coming back to this natural remedy for headaches.
  
  The latter would be nasty, since Feverfew does actually have a handful of side effects that range from a sore mouth and tongue (including ulcers), over swollen lips, loss of taste, abdominal pain, and GI disturbances, up to the occasional report of what Evans & Taylor call the "post-feverfew syndrome" of joint stiffness and aches that were accompanied by (guess what) increasing headaches! In the MIG-99 trials, which used an isolated and highly standardized 6.25 mg dose of parthenolide the number of adverse events were similar. It would thus seem very likely that many of the side effects are brought about either by the initially mentioned natural fluctuations in the active or - and this is even more likely - by other agents in the feverfew leaves.
• Riboflavin: Also and probably better known as vitamin B2, riboflavin has only few quality trials to support its efficiency with its importance in the mitochondrial energy chain and its role in the electron transport within the citric acid cycle, it does, however, appear to be likely that the otherwise often overlooked "yellow-green pee"-vitamin may actually help reduce the number of migraine attacks by >50% (that's 35% more than w/ 25mg/day; Schoenen. 1998), when it is consumed in doses of 400mg/day.

  

  This table shows the nutrient combination of a supplement that has been found to optimize mitochondrial function in a 2011 study (learn more) and it has not just riboflavin, but also lipoic acid and coQ10, both of which are also on the list of "anti-migraine supplements" - certainly no coincidence! Migraine is after all about mitochondrial health and disease.

  The only known side effects researchers observed in the few available randomized controlled trials were diarrhea and polyuria - and those were pretty rare. Evans & Taylor do yet point out that despite its non-toxicity and the non-existence of a tolerable upper intake level they wouldn't recommend high-dose riboflavin consumption to pregnant women, simply because the possible health effects on the unborn child are not known yet.
• Alpha lipoic acid: Certainly less known and not well-researched are the potential benefits of ALA (it is thus not necessary to buy R-ALA, which was in the formula of the supplement mentioned on the label of the table above). A double-blind, placebo-controlled trial by Magis et al. from the year 2007 was yet able to show a reduced monthly attack frequency with alpha lipoic acid at dosages of 600 mg daily after 3 months. It must be said, though that these results were not significantly different from those in the placebo group. Within-group analyses did yet reveal a significant reduction in attack frequency, headache days and headache severity in patient treated with alpha lipoic acid, but not in the placebo group (Magis. 2007)
• Buttebur:
  A note of caution: The Butterbur plant contains pyrrolizidine alkaloids which are
  hepatotoxic and carcinogenic, these compounds have to be removed before you can safely use this plant from the genus of Asteraceae  to counter / prevent headaches.
  Petasites hybridus or rather extracts of its root have gotten some attention as a potential migraine treatment, as well. Petasites is thought to act through calcium channel regulation and inhibition of peptideleukotriene biosynthesis. These cells are thought to play an important role in the inflammatory cascade associated with a migraine (Sheftell. 2000; Pearlman. 2001). A randomized, double-blind, placebo-controlled trial by Grossman & Schmidrams (2000) found that the consumption of 50 mg of butterbur twice daily yielded significantly reduced number of migraine attacks and migraine days per month. Similar results with 50mg of Petasites extract were also reported by Lipton et al. (2004). Finally, a multicenter prospective open-label study of butterbur in 109 children and adolescents with migraine resulted in 77% of all patients reporting a reduction in migraine frequency of at least 50% (Pothmann. 2005).
  
  Serious adverse events were not observed in any of the few hitherto published studies. Overall, butterbur was well tolerated and the most frequently reported adverse reactions were mild gastrointestinal events, predominantly eructation (burping). 
• Melatonin: Yep, you will be hard pressed to find anything melatonin the pineal sleep hormone is not good for. So it is probably not very surprising that it is on the list or rather the end of a list potential natural(*) anti-migraine supplements (some critics will probably say that supplementing with melatonin is not "natural").
  

  • 

    Sleep is good for everything and if you look back at the past SuppVersity articles on the pineal hormone this seems to apply to melatonin, as well.

    1999, Leone et al. were among the first to report beneficial effects of 10mg of melatonin on cluster headaches; yet while this worked magically in some, other patients did not appear to benefit at all (Leone. 1999)
  • melatonin appears to be an effective alternative for indomethacine in idiopathic stabbing headache (Rozen. 2003)
  • cluster migraine which often goes hand in hand with a lack of melatonin secretion has been shown to respond to 9 mg melatonin taken at bed time (Peres. 2001)
  In a 2005 review of the literature Peres does yet point out a multitude of mechanisms by which melatonin could help alleviate headaches, including "its anti-inflammatory effect, toxic free radical scavenging, reduction of proinflammatory cytokine up-regulation, nitric oxide synthase activity and dopamine release inhibition, membrane stabilization, GABA and opioid analgesia potentiation, glutamate neurotoxicity protection, neurovascular regulation, serotonin modulation, and the similarity of chemical structure to that of indomethacin" (Peres. 2005). Despite the fact that large(r) scale randomized controlled trials are absent, up to know. I personally would certainly give it a try.

Aside from "real medications" (I wonder where you can make the distinction between a supplement like thiotic acid aka ALA and a medicinal agent like aspirin?), there is also a "consistent level of evidence"for the usefulness of acupuncture, which has proven to be superior to no or placebo treatment and works as an adjunct to conventional treatment (Schiaparelli. 2010).

There is one thing left to mention that may even work better than any of the previously enumerated supplements: Prevention! While many people don't really know the cause of their migraine attacks there are a couple of known food triggers you may want to avoid or even test (Peatfield. 1984; Scharff. 1995):

• 

  MSG in fast food is a problem (learn more about MSG)

  Alcohol -- 29-35% of people with migraine are sensitive to mankind's most consumed poison
• Chocolate -- 19-22% of the migraine sufferers worldwide are sensitive to the sweet superfood
• Cheese -- 9-18% don't tolerate the tyramine which can also be found in other fermented foods
• Caffeine -- 14% of the patients report that the vasoconstrictive effects of caffeine make the headaches significantly worse
• MSG -- 12% of the migraine sufferers report that eating high mono-sodium glutamate foods gives them the "Chinese Restaurant Migraine"

Theoretically, each and every food item could trigger migraine attacks, therefore I would not suggest relying on this list all too much. Instead of just testing those 5 and resigning, when you are unable to trigger/avoid migraines by consuming/abstaining from them, I'd strongly advise to start a food diary, in which you log everything you eat, drink and supplement (nitrates are by the way notorious for triggering headaches, as well) + your migraine symptoms. Once you go through the notes you should be able to identify what causes the problem, if it has any dietary cause at all.

References:

• Cady RK, Farmer K, Altura BT, et al. The effect of magnesium on the responsiveness of migraineurs to a 5-HT1 agonist.Neurology.1998;50(suppl 4):A340. 
• Evans RW, Taylor FR. "Natural" or alternative medications for migraine prevention. Headache. 2006 Jun;46(6):1012-8. Review.
• Grossman M, Schmidrams H. An extract of Petasites hybridus is effective in the prophylaxis of migraine.Int J Clin Pharmacol Ther.2000;38:430–435.
• Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996 Nov;16(7):494-6.  
• Lipton RB, Gobel H, Einhaupl KM, et al. Petsites hybridus root (butterbur) is an effective preventive treatment for migraine.Neurology.2004;63:2240–2244.
• Magis D, Ambrosini A, Sándor P, Jacquy J, Laloux P, Schoenen J. A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis. Headache. 2007 Jan;47(1):52-7.
• Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines.Clin Neurosci.1998;5:24-27.
• Pearlman EM, Fisher S. Preventive treatment for childhood and adolescent headache: role of once-daily montelukast sodium.Cephalalgia.2001;21:461
• Peatfield RC, Glover V, Littlewood JT, et al. The prevalence of diet-induced migraine.Cephalalgia.1984;4:179–183.
• Peres MF, Rozen TD. Melatonin in the preventive treatment of chronic cluster headache. Cephalalgia. 2001 Dec;21(10):993-5.
• Peres MF. Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia. 2005 Jun;25(6):403-11. 
• Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract.Headache.2005;45:196–203.  
• Rossi P, Di Lorenzo G, Malpezzi MG, et al. Prevalence, pattern and predictors of use of complementary and alternative medicine (CAM) in migraine patients attending a headache clinic in Italy.Cephalalgia.2005;25:493-506. 
• Rozen TD, OshinskyML, Gebeline CA, et al. Open label trial of Coenzyme Q10 as a migraine preventive. Cephalalgia. 2002;22:137–141.
• Rozen TD. Melatonin as treatment for idiopathic stabbing headache. Neurology. 2003 Sep 23;61(6):865-6. 
• Sandor PS, DiClemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005;64:713–715.
• Scharff L, Turk DC, Marcus DA. Triggers of headache episodes and coping response of headache diagnostic groups. Headache.1995;35:397–403. 
• Schiapparelli P, Allais G, Castagnoli Gabellari I, Rolando S, Terzi MG, Benedetto C. Non-pharmacological approach to migraine prophylaxis: part II. Neurol Sci. 2010 Jun;31 Suppl 1:S137-9.
• Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial.Neurology.1998;50:466-470 
• Sheftell F, Rapoport A, Weeks R, et al. Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers.Headache.2000;40:158–163. 
• Srivastava KC, Mustafa T. Ginger (Zingziber officinale) in rheumatism and musculoskeletal disorder. Med Hypotheses.1992;33:342–348.
• Sun-Edelstein C, Mauskop A. Foods and supplements in the management of migraine headaches. Clin J Pain. 2009 Jun;25(5):446-52.