TeaCrine®, Tribulus, Cordyceps, ALA, Sesamin, Fish Oil & More - The Latest Supplement Science (November 2016)

Many currently available supplements lack sufficient scientific backup.

It has been a while since I published the last supplement science update - the recent release of the latest edition of the Journal of Dietary Supplements reminded me of that. In issue 1 of volume 14 of this journal that "addresses important issues that meet a broad range of interests from researchers, regulators, marketers, educators, and healthcare professionals" (Aims & Scope according to the publisher) you will find studies on (you already know that from the headline) "TeaCrine®, Tribulus, Guarana, ALA, Sesamin, Fish Oil & More", studies the design and results of which I will briefly summarize for you in the following paragraphs:

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• TeaCrine® performs again: New data on safety, dosing and time course of effects (Ziegenfuss. 2016) -- You've read about theacrine (not to be confused with l-theanine although both are naturally occurring in tea) in previous SuppVersity articles. It's a purported cognitive and physical performance enhancer and its patented variety, which is extracted from Camellia assamica variety kucha tea, is now part of many pre-workout formulas.
  
  In their latest study, Ziegenfuss et al. (2016) who generated most of the currently available TeaCrine® (TC) research examined the "subjective dose–response, daily changes in cognitive and psychometric parameters, and changes in gas exchange and vital signs" (Ziegenfuss. 2016).  As the authors point out, these particular study outcomes "were chosen to better ascertain the previously reported animal and human outcomes involving theacrine administration" (ibid.).
  

  

  Figure 1: Relative changes (calculated based on arithmetic mean of 95% confidence interval) in self-reported fatigue, focus, and willingness to exercise in the chronic administration trial (Ziegenfuss. 2016).

  The study had two parts: Part 1 (chronic administration) was a randomized, open-label, dose–response investigation in nine healthy participants  (3F, 6M) who consumed either 400 mg TC per day or 200 mg TC per day and recorded the subjective changes in cognitive, psychometric, and exercise attributes using 150-mm anchored visual analog scale (VAS) before, and 1, 4, and 6 hours after ingestion every day for 7 consecutive days.
  
  Part 2 (acute administration) had a different design, with 15 healthy subjects (7F, 8M)
  participating in a randomized, double-blind, placebo-controlled, crossover investigation in which all participants ingested a single 200 mg dose of TC or Placebo (PLA).
  Just like in part 1 (results see Figure 1), VAS questionnaires were used to detect subjective changes in various aspects of physical and mental energy along with changes in gas exchange and hemodynamic parameters before, and 1, 2, and 3 hours after acute ingestion.
  
  What the scientists found was a similar increase in energy, focus, and concentration with both dosages of theacrine. Interestingly enough, the subjects' willingness to exercise, anxiety, motivation to train and libido increased only in the low-dose group receiving 200mg/d for 7 days while it was unchanged in the higher-dose group who took 400 mg of the supplement on a daily basis.
  

  

  Figure 2: Graphical summary of the most important take-home messages of the study at hand.

  Now this, i.e. the U-shaped dose-response curve (cf. Figure 1) is yet only one of three important insights into how you should supplement with this natural purine molecule: It can be derived from (a) Ziegenfuss' et al.'s acute administration study that you (A) don't have to take theacrine chronically for a week (or longer) before you see beneficial effects. On the other hand, the results from the long(er)-term study show (B) no habitation effect, i.e. the dreaded decrease in efficacy you see with other stimulants such as caffeine.
  
  Speaking of which, since theacrine does not have any of caffeine's (mild) adverse side effects such as increased heart rate or changes in systemic hemodynamics (more safety data can be found in Hayward. 2015), theacrine could, in fact, make a good adjunct to caffeine in pre-workout supplements or fat loss adjuvants. To award teacrine the "SuppVersity seal of ergogenic approval", it would yet be nice to see independent research on the combination of the two, i.e. caffeine and theacrine - research that would prove that theacrine does, indeed, add meaningfully to the benefits of caffeine when it's co-consumed with the world's favorite stimulant. For l-theanine there's some such evidence, as you've learned earlier this year at the SuppVersity, for theacrine, on the other hand, the one study that investigated the potential nootropic effects of this combination found only subjective, yet no objective benefits (Kuhman. 2015).
• Tribulus disappoints again: No beneficial effects in men with unexplained infertility (Roach. 2016) -- With their latest study, researchers from the Cairo University in Egypt add to the confusion over the efficacy of tribulus terrestris supplements. Unlike the others of other recent studies, Roaiah, et al. didn't find any measurable benefits in the 30–50-year-old patients with unexplained infertility who participated in their three-months study.
  

  

  Figure 3: The relatively low dose of regular tribulus powder didn't have a measurable effect on the hormone levels of the infertile men in the 3-months study at hand (Roaiah. 2016).

  The authors, themselves, attribute the different study outcomes primarily to differences in the dosage regimen with studies yielding positive results using twice the amount that was used in the study at hand (meaning 1,500 mg/day instead of 750 mg/day in three divided doses). Personally, however, I would suspect that the type of the supplement [raw powder vs. saponin extract as it was used in Wilk, et al. (2016)] may better explain the sign. inter-study differences. If that's indeed the case it wouldn't make sense to pick up the next best TT supplement at your local GNC and hope for results. Rather than that, it would be wise for studies to finally settle if it's the product quality and, more specifically, the saponin content and composition that makes all the difference.
• Cordyceps (militaris) surprises again: Study finds performance benefits during high-intensity exercise tests w/ chronic supplementation (Hirsch. 2016) -- Cordyceps is not just the third purported ergogenic in today's installment of the SuppVersity Supplement Research Update, it's also one of those supplements where we simply don't have enough evidence to be sure that it's worth the significant amount of money you have to pay for a monthly supply of 4g/day of this peculiar mushroom.
  
  With the data in Figure 1 and the fact that it is now offered in bulk at prices that would allow you to get a one-month supply for less than $15, cordyceps may be a candidate for your "next supplement to test-drive"-list.
  

  

  Figure 4: Phase II changes in performance measures (A) maximal oxygen consumption (VO2max), (B) ventilatory threshold (VT), and (C) time to exhaustion (TTE) presented as 95% confidence intervals (Mean ± (1.96 × SEM)) | ∗indicates a significant improvement, as determined by 95% CI (Hirsch. 2016).

  You should be aware, though, that it took Hirsch et al. the analysis of 95% confidence intervals and thus some statistical shenanigan to be able to report significant improvements in total time to exhaustion (TTE) after one (+28.1 s) and three weeks (+69.8 s) and three weeks before the small, but measurable increases in VO2max (+4.8 ml/kg/min) and ventilatory threshold (+0.7 l/min) surfaced. If cordyceps does indeed work it is thus, just like creatine, whey and other better-proven ergogenics, a thing that has to be consumed chronically - unlike caffeine and its stimulating cousins' (including theacrine, see above) whose immediate effects are probably the reason why they are so popular.

While it is no longer a popular fat burner ingredient sesamin may be an anti-inflammatory, blood glucose management improving adjunct to the supplement regimen of any type II diabetic according to a new human study (Mohammad. 2016).

What else have we got? Alright, with the three most interesting studies being discussed in detail we can turn to the noteworthy, but not exactly super-interesting studies on guarana, ALA, carnitine, magnesium and fish oil. And no, we're not talking about stacking them. Rather than that, the latest research from scientists all around the world suggests that there are (A) no benefits of 2x50mg /day of guarana in neck cancer patients during chemotherapy (Martins. 20016), (B) potential benefits of carnitine and alpha lipoic acid (ALA) may prevent the onset of diet-induced type II diabetes in humans just like they did in a recent rodent study (Abdelkarem. 2016), (C) significant benefits of sesamin (you may remember this oil from various OTC fat burners) as an anti-inflammatory T2DM supplement (see Figure to the right) and (D) small but significant reductions in muscle soreness in response to resistance training after one week on 6g of fish vs. soybean oil (Tinsley. 2016) | Comment!

References:

• Abdelkarem, Hala M., Laila H. Fadda, and Abeer AG Hassan. "Potential Intervention of α-Lipoic Acid and Carnitine on Insulin Sensitivity and Anti-Inflammatory Cytokines Levels in Fructose-Fed Rats, a Model of Metabolic Syndrome." Journal of Dietary Supplements (2016): 1-11.
• Habowski, S. M., et al. "The effects of Teacrine TM, a nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial." Journal of the International Society of Sports Nutrition 11.1 (2014): 1.
• Hayward, Sara, et al. "Safety of Teacrine®, a Non-Habituating, Naturally-Occurring Purine Alkaloid Over Eight Weeks of Continuous Use." Journal of the International Society of Sports Nutrition 12.Suppl 1 (2015): P59.
• Hirsch, Katie R., et al. "Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation." Journal of Dietary Supplements (2016): 1-13.
• Kuhman, Daniel J., Keanan J. Joyner, and Richard J. Bloomer. "Cognitive performance and mood following ingestion of a theacrine-containing dietary supplement, caffeine, or placebo by young men and women." Nutrients 7.11 (2015): 9618-9632.
• Martins, Suelen Patrícia dos Santos, Cynthia Lemos Ferreira, and Auro del Giglio. "Placebo-Controlled, Double-Blind, Randomized Study of a Dry Guarana Extract in Patients with Head and Neck Tumors Undergoing Chemoradiotherapy: Effects on Fatigue and Quality of Life." Journal of Dietary Supplements (2016): 1-10.
• Mohammad Shahi, Majid, et al. "Effect of Sesamin Supplementation on Glycemic Status, Inflammatory Markers, and Adiponectin Levels in Patients with Type 2 Diabetes Mellitus." Journal of Dietary Supplements (2016): 1-12.
• Roaiah, Mohamed Farid, et al. "Prospective analysis on the effect of botanical medicine (Tribulus terrestris) on Serum testosterone level and semen parameters in males with unexplained infertility." Journal of Dietary Supplements (2016): 1-7.
• Tinsley, Grant M., et al. "Effects of Fish Oil Supplementation on Postresistance Exercise Muscle Soreness." Journal of dietary supplements (2016): 1-12.
• Wilk, Michał, et al. "Endocrine Responses to Phys^ical Training and Tribulus Terrestris Supplememtation in Middle-Age Men." Central European Journal of Sport Sciences and Medicine 13.1 (2016): 65-71.
• Ziegenfuss, Tim N., et al. "A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters." Journal of dietary supplements (2016): 1-15.