480mg/day Polypodium Leucotomos Reduce Infection Rates in High Performance Athletes by 75%! Plus: Extract Protects Against UV Radiation, Cancer, Trauma & Could Be Ergogenic

Don't worry if you have not heard of Polypodium leucotomos before. After all, that's why you're here! To get your daily dose of SuppVersity news and learn, right?

It's starting to get cold and wet outside and aside from my always healthy self, everyone around is getting sick... sounds familiar? Or are you one of those ailing people who always wonder how the others beard the common cold and did not have a single flu in their whole life? I can assure you, it's not just zinc + vitamin C ;-)

That said, I honestly don't believe that the supplement today's news is about will get the job done, if you don't have your diet and workout regimen in check, but if it reduces the incidence of infections in high performance athletes by 75% it can hardly be useless when it comes to protecting yourself from the sniffers and nose blowers all around, can it?

Dear SuppVersity reader, meet Polypodium leucotomos your immune systems best friend!?

Assuming that I've now gotten your attention, let's get right to the facts. The said supplement is an extract from Polypodium leucotomos a fern that is native to the tropical and subtropical regions of the Americas and has a long history as a folk remedy in Honduras, where it is used for a wide variety of ailments. Interestingly, respective extracts have been sold under the label "anapsos" ever since the 1970s. Nevertheless, I am not sure if anybody who does not know the LEF product catalog by heart has ever heard of Polypodim (if you did, probably in relation to skin health) -- specifically not in the context of infectious diseases in high performance athletes, which was what Bartolomé Marí Solivellas and Teo Cabanes Martín were interested in, when they conducted their 3 months study on the effects 480 mg/day Polypodium leucotomos extract (Armaya fuerte; Centrum laboratories, Alicante, Spain / researchers report no conflict of interest) on the onset of infectious processes and relapses during an 8-month follow up from June 2010 to January 2011 (Solivellas. 2011).

The study participants were all athletes who took part in competitive activity, trained or competed for 20 hours per week and had and still were periodically monitored in a sports medicine clinics. Overall, a total of 116 athletes (58 men and 58 women, aged 18-30 years) were included. 63 of them in the Polypodium leucotomos extract-treated group (PL) and 53 in the control group (C), with 58 males and
58 females aged 18–30 years (subjects with autoimmune or chronic disease were excluded; 14 additional athletes were excluded during the trial, either because they left or were non compliant, i.e. didn't take their supps). Most of them were competitive volleyballers, football players, track & field athletes and cyclists.

The protocol: A 2x 240mg/day preload from June to August

The participants in the active arm of the trial had to consume their daily dose of 480mg in two 240 mg servings, one in the morning and one at night, while the the control group did not take Polypodium
leucotomos extract (no question: The fact that the study was not placebo controlled is a bummer!). This means that the acute supplementation did not coincide with the aforementioned period of sniffing and nose blowing, and any effect that would be seen over the whole 8-months follow-up must be due to permanent benefits in response to the supplementation in those first three months (it also reduces the influence of the placebo effect, after all we are quite forgetful and don't really think about the pills we popped in the summer, when we are getting sick in autumn).

The results: 75%! less infections in the treatment group

Table 1: Prevalence of infectious processes in the control group and study group (Solivellas. 2013)

Even at a very cursory glance at the data in table 1 you should notice the two most important figures: "28" and "7", as in 28 infections in the control (=unsupplemented group) and only 7 infections in the treatment (=480mg/day Polypodium leucotomos extract) group - that's a pretty impressive number. Since, both study arms had been of the same size (n = 50), after a couple of athletes had been excluded from the active arm due to non-compliance, this is a 75% reduced risk of catching any type of infection (see table 1 for detailed breakdown). According to the authors, of those, ...

"[...] the cases of pharyngoamygdalitis were the most noteworthy – 12 patients (24%) in the control group compared to three patients (6%) in the Polypodium leucotomos extract"-treated group." (Solivellas. 2011)

The incidence of infections was yet not the only thing that was reduced. What's probably about as important as the number / rate of infections are the facts that

• the "symptomatic improvement was more favorable" (Solivellas. 2011) in patients from the study and 
• the number of relapses, i.e. a 1/7 vs. 12/28 in the active and passive arm of the study, were significantly lower (-66%)

Since the SuppVersity user stats tell me that most of you are living in the Northern Hemisphere and that it stands out of question that all of you work out (right? ;-), these results alone would be reason enough to take a closer look at Polypodium leucotomos, Calaguala, Anapsos, Heliocare, Kalawalla, Polypodiaceae or whatever other funky name the herb may go, where you are currently living.

Anapsos can do more than render athletes 'infectious disease proof', much more!

This would not be the SuppVersity, though, if I would not tell you "the whole story" about what turns out to be quite an outstanding fern species with beneficial health effects that go well beyond giving your immune system a major boost. And though I have to admit that I did not go back into the 1970s, when the first commercially available extract that goes, as I've mentioned before, by the name Anapsos hit the market. Even the research that has been done in the 21st century only did suffice to compile a pretty impressive list of scientifically backed beneficial health effects, of which I have selected only those, I thought you may be interested in:

• Protection against skin cancer  and related pathologies - PL protects the melanocytic nevi in your skin from forming sporadic melanoma in response to UV radioation, dark eyed patients with higher UVR sensibility (lower basal minimal erythematous dose) would benefit most (dosage 1080mg of PL; Aguilera. 2013). Similar results in rodents, where 300mg/kg of PL 5 days before UVR exposure "reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres" (Rodríguez-Yanes. 2013). Also helps against photo aging, polymorphic light eruption, idiopathic photodermatosis, UV-B induced immuno-suppression in the skin,
• Prevention of hyperpigmentation (and psoriasis) - Hydroquinone has been a cornerstone for the treatment of hyperpigmentation; however, concerns regarding adverse effects have prompted a search for alternative agents, one that was suggeted only recently is Polypodium leucotomos (Konda. 2013). Ameliorative effects have also been observed in psoriasis patients, although it appears that more research would be necessary to make any recommendations (Middelkamp-Hup. 2004)
• Remission of subacute cutaneous lupus erythematosus (SCLE) - SCLE is an uncommon autoimmune disease that results in substantial photosensitivity of affected patients. Eruptions often are triggered or exacerbated by UV light (UVL) exposure and a recent case in Cutis shows that while the disease was at best "moderately controlled" with hydroxychloroquine sulfate, "near total remission of disease" was achieved after the addition of oral Polypodium leucotomos supplement (Breithaupt. 2013).
• Amelioration of atopic dermatitis, reduction of antihistamine requirements - Scientists have only shown recently in a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis that PL administered for 6 months led to a statistical significant reduction in oral histamine use of  4.5% (for those interested, patients received Anapsos 120 mg manufactured by Especialidades Farmacéuticas; Ramirez-Bosca. 2013).
• Prevention of the shift in Th1/Th2 (immune characteristics) in response to trauma - In 2007 already researchers from the University of Zaragzoa found that PL blocked the postoperative (day 1) increases in IL-6 and IL-10 in rats undergoing fracture..On postoperative day 7, "rats undergoing fracture showed an increase of IL-6 levels", the latter was not observed in the PL supplemented rats who had increased levels of the "good" inflammatory cytokine IL-12 on postoperative day 7, instead (Navarro-Zorraquino. 2007)

"Hold on, but didn't you say on SHR and in a couple of blogposts that ROS are necessary?" True, ROS (radical oxygen species) are necessary, as they are a signalling molecule and 'toxic junk', both at a time. Whenever your body is however, figuratively speaking, unable to 'read the signals for the signals' -- which happens to be the case for unfortunate majority of the sedentary Western society -- you better cut back on the forest of signs than have them accumulate in the form of toxic metabolic waste and damage (oxidize) your tissue. Always keep in mind: Whenever we are talking about physiological processes it's all about balance and simply about good or bad and black and white.

The list above did already skip a couple of skin related benefits and still: As I mentioned before, there is probably lots more you could find once you start digging deeper and going further back in the archives. What the hitherto elucidated and probably also all future benefits do have in common is that they are in one way or another related to the potent antioxidant effects of certain not exactly specified molecules the (sub-)tropical fern apparently contains.

Whatever antioxidant (I rather suppose it's a synergistic cocktail) Polypodium leucotomos may contain, it must -- contrary to many other antioxidants which fall victim to their own kamikaze tactics (aka "free radical scavenging") often way before they make it to the target tissue-- actually get to where it is needed and can thus exert its potent antioxidant effects right in the skin, the wound, the broken bone,... and maybe the strained muscle!?

If the latter was the case, and the antioxidants in this peculiar American farn had similar effects in muscle tissue as they were observed by Navarro-Zorraqino et. al. in their rodent model -- namely the induction of an increase in IL-12 and a faster decrease in IL-10 expression -- the concerns about 'too much of a good thing' I addressed in the red box to the right, would not just have been unwarranted; in view of the established pro-anabolic effect of IL-10 (cf. Argilé. 2001) they would actually be absurd (just as the common understanding that all cytokines were "bad", by the way).

Bottom line: I guess, you will agree: This stuff is interesting. However, there have been plenty of "interesting" supplements in the past, which did not deliver. So, if you are merely interested in the last mentioned ergogenic effects, which could obviously be present, you better wait for a respective trial and the corresponding SuppVersity news, before you fill your supplement rack with tons of Polypodium leucotomos. If you are supplement fanatic, got some money to spare and are interested in the immune boosting or UV protective effects, you may want to give it a try.

References:

• Aguilera P, Carrera C, Puig-Butille JA, Badenas C, Lecha M, González S, Malvehy J, Puig S. Benefits of oral Polypodium Leucotomos extract in MM high-risk patients. J Eur Acad Dermatol Venereol. 2013 Jul 31.
• Argilés JM, Meijsing SH, Pallarés-Trujillo J, Guirao X, López-Soriano FJ. Cancer cachexia: a therapeutic approach. Med Res Rev. 2001 Jan;21(1):83-101.
• Breithaupt AD, Jacob SE. Subacute cutaneous lupus erythematosus: a case report of Polypodium leucotomos as an adjuvant therapy. Cutis. 2013 Apr;89(4):183-4.
• Konda S, Geria AN, Halder RM. New horizons in treating disorders of hyperpigmentation in skin of color. Semin Cutan Med Surg. 2013 Jun;31(2):133-9.
• Middelkamp-Hup MA, Pathak MA, Parrado C, Garcia-Caballero T, Rius-Díaz F, Fitzpatrick TB, González S. Orally administered Polypodium leucotomos extract decreases psoralen-UVA-induced phototoxicity, pigmentation, and damage of human skin. J Am Acad Dermatol. 2004 Jan;50(1):41-9.
• Navarro-Zorraquino M, García-Alvarez F, Martínez-Fernández AR, Pastor C, Larrad L, Salinas JC, Lozano R. Pharmacological immunomodulation of surgical trauma. J Invest Surg. 2007 Sep-Oct;20(5):283-9. 
• Ramírez-Bosca A, Zapater P, Betlloch I, Albero F, Martínez A, Díaz-Alperi J, Horga JF; Grupo de Anapsos en Dermatitis Atópica y centros de realización del estudio. Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial. Actas Dermosifiliogr. 2013 Sep;103(7):599-607. Epub 2013 May 3.
• Rodríguez-Yanes E, Juarranz Á, Cuevas J, Gonzalez S, Mallol J. Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice. Exp Dermatol. 2013 Aug;21(8):638-40.
• Solivellas B, Martin TC. Polypodium leucotomos Extract use to prevent and reduce the risk of infectious diseases in high performance athlete. Infection and Drug Resistance. 2013 Oct 15.

Double Your Workout Volume With 3,4-DA - Chlorogenic Acid Metabolite, Dihydroxycinnamic Acid, Makes Rats Run 60% Longer, 30% Faster 90% Further!

Image 1 (sodahead.com): Another reason to supersize your cup of coffee; no not the girl, or ... well ;-)

Those of you who can no longer be without their well-deserved daily dose of SuppVersity news will probably remember the amazing weight loss effects an extract from green coffee beans yielded in a 2013 trial by Vinson et al. (cf. "GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks"; Vinson. 2013) and while I am still not convinced that you would see similar results in non-obese individuals, another recently published study by Novaes et al. does suggest that even those of you who don't think that they have another lbs of body fat to spare, could largely benefit not just from the caffeine, but also from the 0.5-1.0g of chlorogenic acid and the subsequent conversion of the latter into 250-500mg of 3,4-Dihydroxycinnamic acid (3,4-DA) even 400ml of regular coffee do contain (Chung. 2004; Novaes. 2013).

3,4-DA is like legal gear from the brown brew

Compared to placebo and vitamin C (25mg/kg), the hydrolyzed chlorogenic acid molecule, of which the 8-week-old male Wistar rats in the Noves study received either 5mg or 25mg per kg body weight (HED for 80kg human being: 65mg or 324mg) had almost incredibly potent "ergogenic" effects:

Figure 1: Time to fatigue (TTF), speed, workload and total distance covered (secondary axis) during exhaustive treadmill running after oral supplementation with placebo (control), vitamin C or 4,5 DA at doses of 5mg/kg and 25m/kg (based on Novaes. 2013)

As you can see in figure 1 the rodents in the high dose group ran 60% longer, 30% faster, 90% further and performed overall twice as much work (42 vs. 21 kg*m) than the rodents who had received the human equivalent of ~325mg vitamin C before a forced running test on a motor-driven treadmill.

Less ROS = Increased efficacy?!

Interestingly, the lactate levels of the 3,4-DA rodents were significantly lower and the remaining liver glycogen levels were significantly higher than in the placebo and vitamin C group (see figure 2).

Figure 2: Serum triglyceride (group effects non-significant) and lactate levels, hepatic glycogen content and protein arbonyl and malondialdehyde levels after the exercise (based on Novaes. 2013)

As Novaes et al. point out this suggests that the effect is partly mediated by a higher metabolic efficiency. The latter is probably a direct result of the profound reduction in reactive oxygen specimen, which have been associated with impairments of the cellular metabolism and subsequently reduced aerobic energy production (Atalay. 2002) - a hypothesis that would be supported by the reduced levels of protein carbonyl and malondialdehyde in the liver of the 3,4-DA treated rodents.

But don't we need ROS?

Image 2: Don't worry those love handles will go away - rather with the antioxidant + caffeine power of coffee than without it!

These observations are also quite revealing as the offer an alternative explanation for the previously mentioned possibly negative effects of antioxidants on the exercise-induced improvements in glucose metabolism (cf. "Update on Antioxidants & Exercise - Neither Vitamin C Nor E Have ANY Effect on the Response to Intense Exercise"): If high doses of other anti-oxidants have the same beneficial effects on metabolic efficacy, it stands to reason that even weaker antioxidants than 3,4-DA would spare liver (and muscle) glycogen and thus reduce the exercise-induced expression of AMPK of which you may remember from posts like "AMPK II/III: Leucine, HMB and a Glimpse on Other AMPK Modulators" that it is expressed in response to intracellular glucose, or more specifically ATP depletion, and the subsequent increase in glucose (re-uptake).

A huge cup of coffee before your workout will therefore neither hamper the weight loss, nor the health effects of your workout, as long as you do actually make use of its ergogenic effect and train 60% longer, 30% faster, 90% further and perform overall twice as much work... just kiddin', if you train regularly you should be more concerned about keeping the amount of inflammation at bay - some is probably necessary, too much counter-productive, but that would the topic of another SuppVersity post. I for one am now going to get myself a nice cup of coffee...yummy!

Suggested reads on coffee:

• GCB Another Fatloss Acronym: Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 weeks.
• Warding Off Holiday Weight Gain 2.0: The Anti-Diabesity Effect of Coffee Goes Beyond its Caffeine Content.
• Only "Real", Not Decaffeinated Instant Coffee Increases Fatty Acid Oxidation. Revisited: Caffeine's Dose-Dependent Effects on Testosterone & Cortisol Response to Exercise
• Study Identifies Caffeic Acid Induced AMPK-α2 Activity Behind the Fat Burning, Insulin-Sensitizing & Life-Extending Effects of Coffee. Plus: Why Creatine & Coffee Don't Mix!

• all about coffee

References:

1. Atalay M, Laaksonen DE. Diabetes, oxidative stress and training. Journal of Sports Science and Medicine 2002 Jan; 1 - 14.
2. Chung TW, Moon SK, Chang YC, Ko JH, Lee YC, Cho G, Kim SH, Kim JG, Kim CH. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. FASEB J. 2004 Nov;18(14):1670-81.
3. Novaes RD, Gonçalves RV, Peluzio Mdo C, Natali AJ, Maldonado IR. 3,4-dihydroxycinnamic Acid attenuates the fatigue and improves exercise tolerance in rats. Biosci Biotechnol Biochem. 2013 May 23;76(5):1025-7.
4. Vinson JA, Burnham BR, Nagendran MV. Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes. 2013;5:21-7. Epub 2013 Jan 18.

Exercise Intensity, Oxidative Damage, Glycogen Depletion and Supercompensation. Plus: Optimal 0-12h Post Workout Glycogen Repletion Protocol For Performance Athletes

Do they train at the right intensity and what is the right intensity? What's right, anyway? Lot's of questions, tons of words, a couple of answers and some interesting revelations in today's 2nd article of the SuppVersity Exercise Science Week.

This is day 2 of the SuppVersity Exercise Science Week -- another day, another news. After you've learned about the various mechanisms by which exercise will induce structural changes to your beer belly, lover handles and other problem and non-problem areas, in yesterday's first article of the SuppVersity Exercise Science Week, today's post does actually pick up on the notion of the superiority of high intensity exercise and takes a look at how low vs. high(er) intensity endurance exercise effects the antioxidant defense system of the body. This will lead us to an issue that was once considered to be a downside of high intensity workouts: their notoriousness to deplete muscle glycogen, of which we now know that it is actually one of their fundamental strengths. When we are done with that, it's about time for the sweet dessert. The latter is going to have three courses and will help you achieve maximal muscle glycogen supercompensation after a workout.

Where does the idea that you better work out at low intensities come from?

I have made it a (enervating?) habit to include a small reminder of the "dark side" the same beneficial exercise stress that elicits muscle gains, fat loss, and improvements in conditioning and overall health can have, whenever you don't allow for adequate recovery and nutrient supply, in almost every of the articles pointing to the superiority of high intensity training vs. training in the comfort zone (click here to read up on a couple of these articles).

Figure 1: A comprehensive study by Carey revealed that the increase in ratio of fat-calories to total energy ependiture, when you train in the "fat burning zone" is 3% for men, 5% for women. The total amount of fat is yet higher above the "zone" and, most importantly, the current research suggests that the glycolytic effect, which is inversely related to the relative fat oxidation, is what triggers most of the beneficial metabolic effects.

The question, how pronounced the differences actually are, on the other hand, is not just rarely addressed here at the SuppVersity, it's also something scientists are still trying to elucidate. Usually you will see creatine kinase, an accepted marker of skeletal muscle damage being accessed before and after a workout, but as I have pointed out in previous articles, my personal experience tells me that an intense strength workout is - despite its ability to increase CK levels in training noops by up to 10,000% (x100, no typo - eg. Sewright. 2008) less prone to send you down into the abyss of the Athlete's Triad, than working out for hours (worst on a daily basis) in the purported fat burning zone, i.e. the target heart rate where you'll satisfy the greatest part of your metabolic demands from body fat and of which Carey has been able to show in "relatively fit" male and female runners that it is at least 30% below the anaerobic threshold (AT: 155Hb/min; Fat Burning Zone: 105Hb/min; cf. Carey. 2009).

Aside from that, Carey's results also support the observation Wilson et al. formulate in their recent review of concurrent training, namely that "most dramatic loss in fat mass occurr[s] from moderately high to very high intensities" (Wilson. 2013). In this context, the scientists' definition of "moderately high" is already way beyond the alleged zone of maximal fat loss. "Dramatic" is by the way also an excellent attribute for the 4.5x higher fat loss effect Wilson et al. computed for the highest vs. medium exercise intensities  (91-100% vs. 61-80% HRMax) based on the data they collected for their review.

"Better fat loss, w/ high intensity, aha... but isn't that at the cost of increased oxidation?"

In view of the fact that will be coming back to the issue of "optimal fat loss" later this week, anyway, I guess it's best we get back to the topic at hand and take a look at the toll endurance workouts at different exercise intensities actually take on your antioxidant defense system. As mentioned before, it is still far from being certain which markers you would actually have to measure to get a clear picture of how much stress and damage a given exercise regimen is inflicting. Compared to the creatine kinase levels, the measurement of markers of the activity and status of the anti-oxidant defense system, which was the main outcome variable in a study by Takahasi et al. does yet appear to be more relevant - if not with respect to exercise performance than certainly with respect to overall and metabolic health.

Figure 2: Changes in myeloperoxidase, heart rate, rate of perceived exertion and trolox equivalent antioxidant capacity (TAEC) in eight healthy and untrained males aged 22.6 ± 1.4 years (mean ± SD), with 67.7 ± 4.1 kg body mass, 175.2 ± 3.7 cm height, and 15.1 ± 2.2% body fat after 20min of exercise at 70%, 100% or 130% of the anaerobic threshold.

On three separate occasions, the Japanese researchers studied the effect of different exercise intensities. The latter ranged from 70% over 100% to 130% of the anaerobic threshold and would thus represent exercising in the "fat burning zone" at moderately high intensities and high intensities.

The first thing the scientists registered was that the pre to post increase in oxidative stress at the low and medium intensities did not even reach statistical significance. The "pro-oxidative" effects of the high intensity trial, on the other hand, were statistically significant. Yet, if you look at the actual data in figure 2, I'd guess that you will - just like me - ask yourselves what all the hoopla was about: The absolute differences are mediocre, at best and their physical not statistical significance is highly questionable; and that's not just because the trolox equivalent antioxidant capacity (TEAC) actually increased from pre to post exercise (from allegedly lower pre levels in the 130% trial than before the other exercise tests.

Training at higher intensities is demanding, yeah... but not overtly demanding!

Now, all these statistical significances were calculated on a pre vs. post basis. Intensity-specific differences on the other hand were not observed. We do therefore have to be cautious not to misinterpret the scientists very own and actually non-judgmental conclusion ...

"We found that plasma concentrations of d-ROMs increased as a result of 20 min of exercise above AT. Exercise above AT also increased enzymatic and nonenzymatic antioxidant capacity. On the other hand, there was no effect after 20 min of exercise at 70–100% AT, suggesting that exercise under the AT level does not produce oxidative stress damage." (Takahashi. 2013)

... as an advice to stick to "exercise under the AT [anaerobic threshold]". There are already way too many people wasting their time on the cross-trainers of this word - don't join them, but don't overexert yourself either.

The "Iranian HIIT Solution" has already proven that a minimalist HIIT regimen in the form of 3x200m sprint sessions per week can make all the difference esp. for someone who has never participated in regular activity before (read more).

A single bout of intense exercise leads to significant improvements in glucose and lipid metabolism in obese individuals, that's the latest result of another very recent study that was conducted at the University of Glasgow (Whyte. 2013). The protocol consisted of nothing more than " four maximal 30-s sprints, with 4.5min recovery between each (HIIT), or a single maximal extended sprint (HIT) matched with HIIT for work done". With 20% higher mean power during the sprints the temporary intensity was higher, in view of the fact that the overall exercise duration was longer and there was no time for in-between sprint glycogen replenishment. Thu it's actually not surprising that the acute increase in insulin sensitivity did reach statistical significance only after the extended sprint session. The overall metabolic benefits (non-significant improvements in glucose and lipid metabolism) on the day after, of which we can assume that they were not brought about by the immediate reduction of muscle glycogen, were identical for both conditions, while the the total and relative increase in fasting fatty oxidation was more pronounced after the HIIT protocol (total: 63% and 38%; relative, based on RER: 11% and 8% ).

Figure 3: Oxidative stress and glycogen depletion are important triggers of the beneficial effects of exercise on glucose metabolism ( (based on Kawanaka. 2013).

If we go a step further and think about whether or not oxidative stress is actually something you would want to avoid at all costs, the figure from Kentaro Kawanaka's recently published alongside review of the regulation of glucose transport in skeletal muscle during and after exercise (see figure 3) can help us make up our minds. If you take a look at my mark-ups it's plain to see that ROS production and the increase in AMP (quasi "used ATP") and decreases in ATP and phosphocreatine (PCr) are major signals for the activation of a hitherto incompletely understood signaling cascade that results in increased glucose uptake by the muscle. That's the same glucose uptake, by the way that makes the most significant difference between the "normal" and, insulin-intolerant individual and makes an ideal stepping stone to full-blown diabesity (=obesity + diabetes type II).

"So, what exactly is the effect size of these improvements? Are the worth the sweating?"

To illustrate the quantity of these effects, Kawanaka uses data from a 2009 study by Koshinaka et al. who subjected rats to an acute bout of 3x20s "high-intensity sprint interal swimming" and measured muscle glycogen levels and glucose transport at different timepoints in the 16h window after the workout.

Figure 4: Insulin and non-insulin stimulated glucose transport in rat epitrochlearis muscle at rest and 4 hours after cessation of HIIT exercise (left); muscle glycogen repletion and supercompensation after a workout (from Kawanaka. 2013 based on Koshinaka. 2009)

If we take into account that 3h(!) of continuous swimming elicited the exact same improvement in glycogen uptake as those 3x20s all out "sprints", I probably don't have to say it "appears" as if the synergistic combination of brief HI(I)T training and an appropriate diet will be more productive than the endless hours on an elliptical way too many (often unfortunately female) trainees are still performing in the desperate hope to finally shed the fat from whatever problem areas they have or believe they'd have.

Glycogen supercompensation: This is how it's done

There is yet more to the Koshinika study than another confirmation of the usefulness of HI(I)T exercise for fat loss, fitness and fabulous health. The data Koshinaka et al. collected does also tell us something about post workout glycogen repletion. Most importantly (at least in my humble opinion) that the first, immediate post-exercise phase is characterized by a rapid non-insulin dependent increase in glucose uptake. The latter is actually just as high (>5µmol/g/20min; respective data is not shown in figure 4) as the maximally measured glucose uptake in phase II, in the course of which the presence of insulin has a dose-dependent beneficial effect on the total amount of glucose that's going to be shuttled into the muscle (see figure 4, left). With phase III being characterized by saturated (in fact more than saturated) glycogen stores, these observations would suggest that an "optimal" glycogen replenishment protocol would look somewhat like this:

When you increase your calorie intake on a bulk, you better go really high carb + low fat, if lean gains are what you're looking for. This is at least what a 2011 study by Mendes-Netto suggests (read more)

1. phase I: immediately post > fast absorbing carbohydrate source -- what's important during the immediate post-workout phase is exclusively the availability of glucose, insulin the presence of extra high insulin levels is more or less unnecessary
2. phase II: post workout phase (<8h) > high GI carbohydrate source -- once the glycogen levels have reached a certain level the supercompensation process requires the presence of additional insulin, therefore your post-workout meal should not be carb-free or extremely low GI
3. phase III: recovery phase (>8h) > low GI carbohydrate source -- the glycogen stores have already reached higher than baseline levels, the presence of high levels of insulin in this phase would be counterproductive as it would actually drive glucose uptake by the adipose, not the muscle tissue

Whether this maximum glycogen repletion protocol does in fact make sense for everyone is yet another question, though. For someone who trains twice a day, like Arnold, it certainly does. The same goes for endurance athletes looking for maximal performance. If Lance Armstrong, for example, would ever be allowed to compete again, he would best go for a fast absorbing carbohydrate source like Vitargo right after the race, a huge bowl of pasta and some sugary grape juice as his first meal after the race and some slow digesting carbs like a couple of bowls of oats later that day to ensure optimal glycogen levels on the next day of the Tour -- what neither Lance nor you should not forget, though, is to add some protein to the equation, even if building muscle is not your goal, the protein will speed up the replenishment of muscle glycogen (Zawadski. 1992)

"But how important is muscle glycogen, anyway?"

For the average trainee it does yet remain questionable whether or not this protocol will actually yield noticeable benefits. While it is important to replete the glycogen stores, the advantages of doing this as fast as possible are actually not really relevant for someone who trains 3-4 times per week in order to promote health, well-being and a leaner, more muscular (but not freakish) physique. Especially with respect to the latter, the majority of the more recent studies clearly suggests that muscle protein synthesis is, in the short run, not impaired by low levels of muscle glycogen (click here to learn more).

What you should never forget, though, is that your body will interpret chronically low muscle and liver glycogen levels as a clear-cut indicator that you're starving. The results are a reduced metabolic rate and the shut down of "auxilliary" and costly bodily functions such as the reproductive machinery, etc. - and we don't want that to happen, right?


References:

• Kawanaka K. Regulation of glucose transport in skeletal muscle during and after exercise. 2013. J Phys Fitness Sports Med, 1(4): 563-572.
• Koshinaka K, Kawasaki E, Hokari F, Kawanaka K. Effect of acute high intensity intermittent swimming on postexercise insulin responsiveness in epitrochlearis of fed rats. Metabolism. 2009; 58: 246-253.
• Takahashi M, Suzuki K, Matoba H, Sakamoto S, Obara S. Effects of different intensities of endurance exercise on oxidative stress and antioxidant capacity. J Phys Fitness Sports Med. 2013 1(1): 183-189.
• Sewright KA, Hubal MJ, Kearns A, Holbrook MT, Clarkson PM. Sex differences in response to maximal eccentric exercise. Med Sci Sports Exerc. 2008 Feb;40(2):242-51.
• Whyte LJ, Ferguson C, Wilson J, Scott RA, Gill JM. Effects of single bout of very high-intensity exercise on metabolic health biomarkers in overweight/obese sedentary men. Metabolism. 2013 Feb;62(2):212-9.
• Wilson JM, Marin PJ, Rhea MR, Wilson SM, Loenneke JP, Anderson JC. Concurrent training: a meta-analysis examining interference of aerobic and resistance exercises. J Strength Cond Res. 2013 Aug;26(8):2293-307. 
• Zawadzki KM, Yaspelkis BB 3rd, Ivy JL. Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise. J Appl Physiol. 1992 May;72(5):1854-9.