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. 2012)

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. 2012). 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. 2012). 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. 2012). 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. 2012).
• 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. 2012).
• 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. 2012 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. 2012 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. 2012 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. 2012 Sep;103(7):599-607. Epub 2012 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. 2012 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. 2012 Oct 15.

Vitamin A Educates T-Cells, Joins Forces With Vitamin D Against Liver Cancer. Milk Better Than Sugary Electrolyte Solutions for Rehydration? Helicobactor Pylori: Probiotics from Breast Milk & Feces Better Than Amoxicillin!

Lactobacilli are hip, vitamin A is not - at the SuppVersity you still get news on both

1kg! That's the amount of weight you could probably lose if you rid yourself of all the microbes in your gut - from the weight of the bacteria alone, of course. Whether this would be a good idea or not, is however very questionable. On the one hand, we do have the still not fully understood studies on obesity-resistant germ free mice and an accumulating amount of evidence that having the "wrong" bacteria in the gut is at least associated with an increased obesity risk (Blaut. 2012). On the other hand, however, we are seeing new studies on the various benefits of having the "right" gut microbiome being published on an almost daily basis. So what?

Before we take a closer look at a definite benefit of having the "right" gut bacteria, though, let's start out with another likewise gut-related news item on the role of retinoic acid in T-cell education. In a way it's funny, it starts right where the bacteria reside, could have immune-modulatory effects that are way more pronounced and far reaching than probiotics and is still hardly discussed.

Vitamin A is of critical importance to (intestinal) T-cell education

If you have ever asked yourself how the immune cells in your body know what they are supposed to do, Catharine Ross' latest paper that was published in the American Journal of Clinical Nutrition and is based on a short talk the researcher from the Department of Nutritional Sciences at the Pennsylvania State University held at a conference earlier this year may provide at least some additional insides into the role a still way underrated molecule plays in this "T cell education" (Ross. 2012): Vitamin A!

Figure 1: Model of T cell differentiation, from uncommitted naive T cells into different T cell subsets that produce different cytokines and thus promote different functional activities (adapted from Ross. 2012)

As you can see in figure 1, retinoic acid does not simply promote the differentiation of regulatory T cells, which help to suppress inflammatory reactions, it also plays a significant role in normal mucosal immunity (in the gut, the airways and elsewhere) by modulating T cell activation and regulating cell trafficking. Moreover, vitamin A promotes antibody responses to T cell–dependent antigens. Needless to say that

"[...] in a state of vitamin A deficiency, inflammatory T cell reactions may be inadequately opposed and therefore become dominant [...] Although data from human studies are still needed, the framework now developed from studies in mice and rat models suggests that adequate vitamin A status, [...] is  important for maintaining a proper balance of well-regulated T cell functions and for preventing excessive or prolonged inflammatory reactions." (Ross. 2012).

Discovery a beta carotene derived vitamin A receptor blocker is only one of a couple of intriguing findings wrt to vitamin A.

One thing that sticks out from the complex interactions (see figure 1), really is the way by which the interaction of vitamin A with the T-cells in the gut crucially determine the efficiency of the 'fist line defenses' and their downstream effects on the whole organism. It is by no means co-incidental that diarrhea is rampant in areas of the "third world", where a large amount of the population is vitamin A deficient (Beaton. 1994). And in fact studies have shown consitently that

"RA is essential for 'imprinting' gut-homing specificity on T cells activated by intestinal DCs [dendritic cells] and suggested that MLN DCs are a source of RA that drives T cell differentiation toward the gut-homing phenotype" (Ross. 2012)

Moreover, oral tolerance to foreign antigens and thus an allergy free live requires a form of immune suppression, which can be proffered or hampered by sufficient and insufficient vitamin A intakes. In that, the exact effects of vitamin A will depend on the cytokine milieu the T-cells are exposed to. Examples are...

• an exaggerated IL-17 response with vitamin A deficiency, on the one hand, and
  
• an increase of the inflammatory response due to high vitamin A in an IL-15 environment 

Based on these observations, Ross rightly points out that "when RA is used for therapeutic purposes, it should be used cautiously in subjects with various inflammatory bowel conditions and sensitivities to dietary antigens." (Ross. 2012) People with gluten intolerance, celiac and other allergic reactions, for example would probably be better off avoiding the consumption of any form of supplemental vitamin A (on top of what's in their regular diet). Someone with high IL-17 and IL-6 levels as they have been observed in non-celiac inflammatory bowel disease, type 1 diabetes, multiple sclerosis and rheumatoid arthritis, on the other hand, could actually benefit from vitamin A's (especially ATRA) presence during activation of CD4⁺ T cells, because it will - even in the presence of IL-6 - "favor the development of the a Treg lineage at the expense of T cells secreting IL-17" and could thus help reduce chronic inflammation and keep autoimmune reactions at bay (Schambach. 2007; also Ramgolam. 2010).

More news

• 

  Figure 2: Who cares about cell viability, the survival time (in days) matters

  Combination therapy with vitamin A and a vitamin D (not D3, but calcitriol) analog EB1089 kills liver cancer cells. And it does so more effectively than any of the two molecules alone. That's the actually unsurprising result of a study that has been conducted at the Beijing Army General Hospital in China. The researchers injected nude mice with molecules that made them develop hepatocellular cancer. Afterwards, the rodents received either 10 μmol/L retinoic acid (vitamin A), 10 nmol/L EB1089 or both as a combination treatment.
  
  Compared to vitamin A or the calcitriol analog alone, the combination treatmend resulted in a significanlty higher reduction of the viability of hepatocellular cancer cells. Based on TUNEL analysis, Zhang et al. did also establish that individual cancer cells had a higher apoptotic ratio in the combined drug group than in the groups for which the drugs were used separately. Most importantly, however, the tumor weight was decreased and the mice on the combination treatment lived significantly longer (see figure 2; Zhang. 2012)

• 

  In the same publication, Pritchett and Pritchett recommend 1.0-1.5ml / kg body weight per hour of chocolate milk as the optimal post-workout drink to be consumed in the 2 h after a workout.

  Skimmed milk, the ideal post-workout rehydration formula? According to L James' paper in Lamprecht's compendium Acute Topics in Sport Nutrition, milk is a way better choice then the standard sugar + electrolyte rehydration formulas. Interestingly this is not due to the minerals in the milk, or the sugar, but, as James argues, a direct consequence of the milk proteins, which help restore "fluid balance after exercise-induced dehydration to a greater extent than a carbohydrate-electrolyte sports drink." As James points out it will yet have to be elucidated, whether the simple addition of whey protein to a standard sugar + electrolyte formula would exert similar effects (James. 2013).
• Probiotics to kill Helicobacter Pylori? While not every bacteria stands a chance against the nasty gut bug H. Pylori, certain Lactobacillus spp. strains obviously do. At least, if the results of a recent in-vitro + in vivo rodent study by Pei-Shan Hsieh can be replicated in human studies.

  

  Figure 3: Urease activity in H. pylpori after co-incubation with the specific probiotic and resulting bacteriostatic ratio (100% = bacteria free; data adapted from Hsieh. 2012)

  Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were the most effective strains the researchers from National Chung Hsing University in Taichung, Taiwan, analyzed. And believe it or not, the latter of these, i.e. L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32, both of which are  by the way found in feces, were even minimally more potent effective than Amoxicillin, a moderate-spectrum, bacteriolytic, β-lactam antibiotic used to treat bacterial infections. L. acidophilus TYCA15, however, steals the show. This probiotic that occurs naturally in breast milk reduced the urease activity of H. Pylori by -97.1% (see figure 3).
  
  In the consecutive rodent study, Hseieh et al. did yet still use 10⁹ CFU/mL of either AP-32 alone, MH-68 alone, or an equal mix of cultures of the two strains and both, "either alone or as a mixture in powder form were effective in reducing H. pylori load in gastric mucosa and help in reducing gastric inflammation and in regulation of gastric acid production." (Hsieh. 2012)

Thats it for today and for this weekend. As mentioned yesterday, there was simply not enough time to do the necessary research for the follow up to the Athlete Triad Series, so that this will have to wait. So don't dig an even deeper whole in the mean time. Maybe you want to do some of the psychomotor tests mentioned in yesterday's news, and check whether you are already overtrained!? How steady are your hands, for example? And whatever the result may be, don't forget to enjoy the rest of the weekend!

References:

• Beaton GH, Martorell R, Aronson KA, Edmonston B. McCabe, G, Ross, AC, Harvey, B. Vitamin A supplementation and child morbidity and mortality in developing countries. Food Nutr Bull 1994;15(4): 282–9.
• Blaut M, Klaus S. Intestinal microbiota and obesity. Handb Exp Pharmacol. 2012;(209):251-73.
• Hsieh PS, Tsai YC, Chen YC, Teh SF, Ou CM, King VA. Eradication of Helicobacter pylori Infection by the Probiotic Strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32. Helicobacter. 2012 Dec;17(6):466-77.
• James L. Milk Protein and the Restoration of Fluid Balance after Exercise. In Lamprecht M (ed): Acute Topics in Sport Nutrition. Med Sport Sci. Basel, Karger, 2013, vol 59, pp 120–126. 
• Pritchett K, Pritchett R. Chocolate Milk: A Post-Exercise Recovery Beverage for Endurance Sports. In Lamprecht M (ed): Acute Topics in Sport Nutrition. Med Sport Sci. Basel, Karger, 2013, vol 59, pp 127–134.
• Ramgolam VS, Markovic-Plese S. Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets. 2010 Jun;10(2):161-7.
• Ross AC. Vitamin A and retinoic acid in T cell-related immunity. Am J Clin Nutr. 2012 Oct 10.  
• Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007 Sep;37(9):2396-9. 
• Zhang J, Zhang H, Zhang X, Yu Z. Synergistic effect of retinoic acid and vitamin D analog EB1089-induced apoptosis of hepatocellular cancer cells. Cytotechnology. 2012 Oct 16.