Baking Soda For Stressed White Blood Cells: 0.3g/kg NaCO3 90min Before an Anaerobic Workout Protect Your Immune Cells From "Stress" and Oxidative Damage

Image 1: Pure baking soda is not (yet?) a staple of the supplemental arsenal of many athletes. The scientific evidence with regard to its immediate ergogenic effects is ambigious and the mere presence of the word "sodium" in "sodium bicarbonate" scares the hack out of those athletes (bodybuilders and figure competitors) who may benefit most from a few grams of this potent alkalizer.

"Sodium"! This word alone is usually enough to scare bodybuilders and fitness athletes to death. "Sodium!? Isn't that the stuff that makes me look bloated?" The answer is easy: No! While sodium will help you retain enough water in your body to perform in the gym, the amount of sodium you ingest usually has little impact on the amount of water you will be holding, only when you start modulating your sodium intake, your body will react with changes in the renin-andiotensin-aldosterone system and you will be fluctuating "nicely" back and forth from super-bloated to weak and dehydrated... this is yet commonly ignored within the fitness community and thus it is no wonder that most supplement producers are anxious not to include any ingredients in their products that would show up on the label as "sodium" - after all, there are still costumers out there who have not enrolled at the SuppVersity and will thusly run away screaming as soon as they take a closer look on the label of a product they were just about to buy.

It is thusly no wonder that (at least to my knowledge) KreAlkalyn, where NACO3 is the working ingredient of the highly advertised buffering system, is the only product using sodium bicarbonate, or soda ash, as it is also called, as one of its main constituents (more on this topic in the SuppVersity Creatine Special). In medical settings NACO3 was and, in parts, still is still the "drug" of choice to combat acute acidosis. It is thus no wonder that Daniel J. Peart and his colleagues from the University of Hull in the United Kingdom, as well as the Bond University in Queensland, Australia are not the first scientists who speculated that athletes, especially those competing in (primarily) anaerobic sports, could benefit from the alkalizing effects of their grandmothers' secret weapon in the war against fungi and bacteria on her kitchen furnishings (Peart. 2011).

Image 2: "Cholesterol is the devil and sodium is his little brother!" Everyone who still believes everything the medical orthodoxy says, please raise your hands!

A note on the dangers of "salt": Firstly, baking soda is "only" ~28% sodium, which means that for every 4 grams you ingest you get roughly 1 g of sodium. Secondly, it is arguable how much of the sodium is effectively taken up and will be floating around in your blood. As T. Lakhanisky points out in his dossier for the Belgian government: "The uptake of sodium, via exposure to sodium carbonate, is much less than the uptake of sodium via food. Therefore, sodium carbonate is not expected to be systemically available in the body." (Lakhanisky. 2002) And thirdly, there is more and more evidence that suggests that the chloride rather than the sodium content of common table salt (NaCl = NatriumChloride) is the root cause of "sodium induced hypertension" in "sodium sensitive" individuals / animal models. Only recently, a study by Schmidlin et al. showed that chloride loading induced hypertension in the stroke-prone spontaneously hypertensive rat despite profound sodium depletion (Schmidlin. 2010). So, if you asked me, rather than pointing at salt as the #2 on the list of greatest evils (obviously cholesterol is still #1, here) the medical orthodoxy would be better advised to address the imbalances between sodium and potassium, which are so characteristic of the western diet, instead of painting yet another black and white picture where sodium is the bad guy and potassium the dangerous mineral that cannot be sold OTC in dosages >80mg.... but hey, this would be the topic for a whole new blogpost and as gross as it may sound, the chance that you get diarrhea from the baking soda is probably 1000x higher than the remote possibility of increases in blood pressure. A 1990 study by Luft et al. even found that the blood pressure of 10 mildly hypertensive and normal subjects decreased by 5mmHg after 7 days in the course of which they drank 3 liters of sodium bicarbonate containing water per day (Luft. 1990)

In their study, Peart et al. had a group of seven recreationally active men (age 22.3 ± 2.9 years,
height 181.6 ± 4.5 cm, body mass 78.1 ± 8.1 kg, and physical activity 4.2 ± 0.6 h/week) "with no history of supplementing their diet with ergogenic agents" perform a 4-min bout of all-out exercise on an air-brake cycle ergometer on three different occasions (spaced exactly 1 week apart). While the first was an acclimatization session the second and third bout were performed after the ingestion of either 0.3g/kg sodium bicarbonate (trial 2) or plain table salt (trial 3) in "low-energy flavored water" 90 minutes prior to exercise.

Figure 1: Blood ph levels after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

As you can see in figure 1, the ingestion of ~23.4g of baking soda produced a rather slight but significant shift towards a more alkaline blood ph level (compared to placebo), which became much more pronounced after the exercise bout (p<0.003). Interestingly, there was yet no significant difference (p>0.26) in exercise performance as measured by average and peak power (means ± SD; average power 292 ± 43 W vs. 291 ± 50 W; peak power 770 ± 218 W vs. 775 ± 211 W; work completed 71 ± 10 kJ vs. 68 ± 10 kJ) between the groups.

Baking soda: A non-ergogenic ergogenic?

The latter observation, i.e. no or statistically non-significant increases in acute exercise performance upon sodium bicarbonate ingestion, stands in line with ~75% of the previous findings, a recent meta-analysis by Carr et al. summarizes as follows:

The remaining 38 studies and 137 estimates for sodium bicarbonate produced a possibly moderate performance enhancement of 1.7% (90% CL ± 2.0%) with a typical dose of 3.5 mmoL/kg/BM (∼0.3 g/kg/BM) in a single 1-minute sprint, following blinded consumption by male athletes. In the 16 studies and 45 estimates for sodium citrate, a typical dose of 1.5 mmoL/kg/BM (∼0.5 g/kg/BM) had an unclear effect on performance of 0.0% (±1.3%), [...] Study and subject characteristics had the following modifying small effects on the enhancement of performance with sodium bicarbonate: an increase of 0.5% (±0.6%) with a 1 mmoL/kg/BM increase in dose; an increase of 0.6% (±0.4%) with five extra sprint bouts; a reduction of 0.6% (±0.9%) for each 10-fold increase in test duration (e.g. 1-10 minutes); reductions of 1.1% (±1.1%) with nonathletes and 0.7% (±1.4%) with females. Unexplained variation in effects between research settings was typically ±1.2%.

Despite these rather mediocre immediate effects of bicarbonate pre-loading, the main finding of the study at hand hints at hitherto overlooked long(er)-term immune benefits the consumption of sodium bicarbonate might have.

Figure 2: HSP-72 expression in mono- and lymphocytes in response to anaerobic exercise after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

As you can see in figure 2 the stress-induced HSP-72 expression in white blood cells (lymphocytes and monocytes) in response to the HIT exercise was almost completely abolished. Along with the nullification of the already low amount of oxidative stress (cf. T-BARs in figure 3), these results suggest that bicarbonate supplementation has a stress-protective effect on immune cells during anaerobic exercise.

Figure 3: Oxidative stress due to anaerobic exercise as measured by TBAR expression after ingestion of placebo or 0.3g/kg sodium bicarbonate (data adapted from Peart. 2011)

It is yet important to note that the scientists point out that it "is unclear at this stage whether the attenuation was due to a reduced state of acidosis, reduced oxidative stress or a combination of both." Moreover, it is difficult to say which consequences this would have on future bouts of exercise and whether and to which degree athletes would actually benefit - or, if we think of the hormesis hypothesis and the ongoing debate concerning the effects of antioxidants on exercise induced adaptations - maybe even compromise their performance, would yet need further investigations.

We may yet assume that, just as it is the case with antioxidants, the dosage will have to be matched to the individual workload to see optimal results. With people exercising just enough to see any adaptations seeing no and people who do crossfit 2x a day seeing the most beneficial results from (partially) blocking the exercise induced oxidative stress.

1.3g of Grape-Seed Extract Could Protect You From Oxidative Damage, Viral Infections, Obesity and Insulin Resistance, Reduce Your Heart Rate and Blood Pressure and Increase Your Nitric Oxide Production by >25%

Image 1: Bought in bulk, grape-seed extract is actually reasonably cheap... and it does not even taste as awful as some other herb / seed extracts ;-)

After initially being hailed as the yet another anti-oxidant panaceum, grape-seed extract (GSE) has been displaced by newer, fancier "superfoods" from the headlines of the major health and wellness newscasters. Therefore, even you, as a highly self-educated student of the SuppVersity could have missed out on a handful of recently released studies which reported antiviral effects of GSE (Su. 2011) and confirmed its ameliorative effect on diet-induced obesity (Ohyama. 2011) and (high) fructose-induced insulin resistance (Meeprom. 2011). Moreover, a meta-analysis of nine controlled with more than 300 human subjects and daily doses ranging from 250mg to 2,000mg of GSE, which was published in the Journal of the American Dietetic Association (Feringa. 2011), found that ...

[b]ased on the currently available literature, grape seed extract appears to significantly lower systolic blood pressure and heart rate, with no effect on lipid or CRP levels.

These results suggest that we (at least some of) the beneficial health effects that have been observed in rodent studies actually translate to human beings - something  we cannot (yet?) say for some of the next generation "panacea" ;-) This is also important in view of the significance of the results GSE-administration had on exercise-induced oxidative stress in a more recent study by scientists from the universities of Konya and Dicle in Turkey (Belviranli. 2011), which was published in the latest issue of the British Journal of Nutrition.

The experiments were carried out with 64 adult male Sprague Dawley rats who were randomly assigned to one of the following six groups:

• sedentary control (C, n=10), 
• chronic exercise control (CEC, n=11), 
• acute exercise control (AEC, n=11), 
• GSE-supplemented control (GC, n=10), 
• GSE-supplemented chronic exercise (GCE, n=11), and 
• GSE-supplemented acute exercise (GAE, n=11)

The rats in the treatment groups received a standardized GSE extract containing 54% dimeric, 13% trimeric, 7% tetrameric and <5% monomeric proanthocyanidines and undisclosed amounts of cathechines and oligomeric proanthocyanidines, at a daily dose of 100mg/kg body weight in their drinking water for 6 weeks.

Image 2: Click here to learn how to calculate human equivalent doses (HED)

Rat to human equivalent dosage calculation: If you have already read my dissertation on how to calculate the so-called human-equivalent-dose (HED), you will probably already have whipped out your calculator and are just about to type "100mg times the K-value for rats, which is 6; divided by the K-value for humans, which is 37" ... and what does your calculator tell you? Correct! The HED of 100mg/kg GSE in rats is 16.33mg/kg - in other words, if you weigh 80kg you will have to take roughly 1,300mg of grape-seed extract per day to mimic the dosage that was used in the study.

The dosage, according to the scientists, was chosen because it had elicited beneficial anti-oxidant effects in previous studies on alloxan induced diabetes (El-Alfy. 2005) and age-related oxidative damage (Balu. 2006). And, as Belviranli et al. had suspected, it exhibited similar protective effects against the oxidative stress triggered by both chronic, 5x a week treadmill exercise at 25m/min for 45 minutes, as well as, acute running on the treadmill at 30m/min until exhaustion.

Figure 1: Effects of acute or chronic exercise and grape seed extract (GSE) supplementation on plasma malondialdehyde (MDA) levels (data calculated based on Belviranli. 2011).

As you can see in figure 1, administration of 100mg/kg grape-seed extract per day augmented the beneficial effect of 6 weeks of chronic exercise on muscle MDA levels (-37% vs. -18% in the control group) and ameliorated the acute +22% increase in MDA levels due to increased lipid peroxidation during exhaustive treadmill running.

Figure 2: Effects of acute or chronic exercise and grape seed extract (GSE) supplementation on plasma nitric oxide (NO) levels (data calculated based on Belviranli. 2011).

GSE supplementation also increased the expression of nitric oxide (NO in  plasma; on average +25%) in all animals (cf. figure 2). Moreover, GSE ameliorated the increase in xanthine oxidase and adenosine deaminase activities due to acute exercise and triggered an overall increase in antioxidant enzyme activities.

So, even if your favorite anti-aging and health (onilne-)magazine or vendor appears to have forgotten about grape-seed extract. For a physical culturist like you and me, it may yet well be worth to (re-)include the extract from the seeds of the fruits of Vitis vinifera, which are a particularly rich source of vitamin E, linoleic acid and, most importantly, oligomeric proanthocyanidins, into our supplement regimen. And if the current study does not convince you, it may help, if I remind you of the 2006 study by Kijima et al. who were able to show that GSE due to its anti-aromatase activity can suppress tumor growth in a breast cancer model (Kijima. 2006) ... ah, and before I forget: don't be stupid and buy over-priced caps. Use google and find yourself a source of bulk grape-seed extract - don't worry the taste is not all too bad ;-)

Mitohormesis - Suffocated Mitochondria Live Longer: Scientists Probe Longevity-Effect of Low-Level Stressors.

Image 1: Walter Breuning died in April 2011at the biblical age of 114! And you bet that a man who has seen two world wars has had his share of mitohormetic stress in his life.

As a diligent reader of the SuppVersity you will be familiar with the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Jena, here in good old Germany (where not everyone eats Sauerkraut und Weisswurst, even now that the Oktoberfest is in full swing). In previous publications, the scientists have (at least in my mind conclusively) argued against the publicly accepted free-radical hypothesis of aging, which implies that the presence of free radicals is one of the fundamental mechanisms of aging. Now, a few month after the publication of their last review back in May 2011, they are presenting the latest results from their own lab in a paper that is going to be published in the October issue of Hormone and Metabolic Research (Schmeisser. 2011).

Want to live longer? Then you better put another log on the fire

Schmeisser, Zarse, and Ristow used lonidamine (LND), a indazole-3-carboxylic acid derivate, to inhibit cellular respiration in the infamous round-worm (Caenorhabditis elegans) model for aging processes (for a review on the pharmacology, biochemistry and toxicology of lonidamine see Silvestrini. 2008). In essence, they thusly made it more difficult for the cells to "breath", which as you may probably imagine, is a major stressor, which will inevitably increase the formation of purportedly dangerous free radicals (ROS) and should thus increase the aging process, if... yes, if there was any truth to the nonsensical idea that you better sit there, don't eat, don't drink, don't move - in essence - don't live to avoid any potential ROS formation, if you want to extend your lifespan... I guess, you as a self-educated SuppVersity reader won't be surprised that the roundworms did not only survive the "torture" (of life), but - after an initial mitohormetic response, i.e. an adaptational response to the the scientists' effort to suffocate their mitochondria (the initial reduction in oxygen consumption was -37 %!) - thrived on the purportedly life-shortening inhibitor of mitochondrial respiration!

Figure 1: Lifespan of C. elegans treated with 5µM lonidamine, n-acetyl-L-cysteine (NAC) or both (data calculated based on (Schmeisser. 2011)

As you can see in figure 1, the "pro-oxidant" treatment with lonidamine, of which Schmeisser's, Zarse's and Ristow's data shows that it increased respiration and thus mitochodrial ROS formation, increased both median as well as maximal life-expectancy of the nematodes (roundworms) by ~8% - an increase with statistical significance, as the p-value of p<0.001 (= chances that the increased lifespan observed in the study is just coincidence are <0.1%). The latter cannot be said of either the slight increase in maximal lifespan nor the slight decrease in median lifespan in the group of nematodes that was treaded with n-acetyl-L-cysteine (p=0.17; non-significant) or a combination of the anti-oxidant sulfur-amino acid and lonidamine (p=0.95; absolutely non-significant; cf. figure 1).

These observations may be considered further experimental "evidence" for Schmeisser's and Ristow's previously formulated mitohormesis theory ("evidence" in the sense that the results do not falsify their hypothesis - they do yet falsify the ROS hypothesis of aging). A theory that refutes the idea that the aging process is driven by reactive oxygen species and emphasizes (mitochondrial) adaptation processes to (external) stressors that strengthen, not weaken the organism in the long-run - or as the scientists phrase it:

[...] the induction of endogenous defense mechanisms as a secondary response to a stressful condition is assumed to contribute to longevity [...] a lifetime low dose oxidative stress with a subsequent secondary induction of defense mechanisms could delay the aging process

It is thus the interplay of manageable stress and metabolic adaptation which extends life and not an overall reduction of reactive oxygen species, as the vendors of some "super-potent" anti-oxidants would have you believe. What is still missing though, is a tool which would help us to identify the critical point, where the endogenous adaptation processes cannot keep pace with ever-increasing (mainly) exogenous stressors... in case any scientist finds an answer, I guess you will soon be able to download the respective app on your shiny new iPhone - I just hope that this app will account for the significantly (!) decreased glucose metabolism the iPhone itself will induce in the temporoparietal junction and anterior temporal lobe of the right hemisphere of your brain within less than 30 minutes (Kwon. 2011), as well.

Nitrates Work! Even at Low Doses of 300-500mg. Athletes Who Take More or Confuse Nitrates With Nitrites Face Potential Health Risks. First NO2-"Victim" in the ER.

Image 1: With nitrate and nitrite, a
single letter is of literally vital importance.

You probably expected another issue of the famous "Ask Dr. Andro" segment today... ? Well, I have in fact been working on something, but firstly, the topic turned out to be so epic that I could hardly have delivered a post in the usual SuppVersity quality within the next few hours, and secondly, a previous installment of the series on creatine nitrate (cf. Ask Dr. Andro: Is Creatine Nitrate Worth It?), in which I explained why I think that the heavily marketed "revolutionary" creatine supplement probably does not provide any additional benefits beyond supplementing creatine monohydrate and nitrate, individually, urgently needed a follow up.

While the ergogenic potential of creatine monohydrate and its safety are well established (and I do not think I have to recite the whole litany about creatine causing kidney failure, again!? cf. Creatine Save - For Diabetics, As Well!), the studies which show that dietary supplementation with inorganic nitrate (NO3-) reduces whole body oxygen cost during physical exercise (Larson. 2007; Larson. 2010), are pretty recent and have, according to a letter to the editor of the Journal of Applied Physiology by Jon O. Lundberg et al. (Lundberg. 2011), already provoked a case of severe nitrite intoxication in an athlete who obviously wasn't aware of the major difference the "i" which distinguishes the highly reactive nitrite (NO2-) from its harmless precursor nitrate (NO3-) and developed symptoms suggestive of methemoglobinemia (increased oxidation of hemoglobin) after poisoning himself with nitrite salt.

Note! It is unlikely that you will develop methemoglobinemia from reasonable doses of nitrate, even when the lethal dose 50 (LD50 = the dose at which 50% of the subjects / lab rats who ingested the given amount of a chemical die) for nitrite is as low as 100-200mg/kg and thus in the range of cyanide. The reason for that is that, although your body will convert orally ingested nitrates to nitrite, the rate at which this process takes place is limited and this limitation is what avoids the accumulation of nitrite in your blood stream and thus saves the iron-containing oxygen-transport metalloprotein in your red blood cells from being oxidized.

Image 2: Beetroot juice is probably your
safest source of dietary nitrate (NO3-)
(image from planetorganic.com)

This case of unintentional nitrite poisoning goes to show that caution should be exercised, when you are buying and consuming nitrate salts for performance issues. Yet, although salpeter (nitrate salt) is readily available as a food conservative from your local grocery story, I personally would advice against its consumption and tend towards more natural sources of nitrate to elicit the desired ergogenic effects. In fact, the slow controlled release of nitrite from dietary nitrate as it is found in beat root juice (100-200ml would suffice to get into the effective range of 200-300mg nitrate, cf. Ask Dr. Andro: Is Creatine Nitrate Worth It?) may have additional desirable health effects on blood pressure (Larsson. 2006; Lundberg. 2008) and could be used as an adjunct in the treatment and prevention of ischemic conditions such as myocardial infarction and peripheral artery disease.

A final word of caution goes out to the real bros out there: When even nitrite salt can give you hypothension and oxidize your the oxigen carrying metalloprotein in your red blood cells, nitroglycerine and amyl nitrite, both drugs that are prescribed to patients with heart disease, may literally give you the "longest lasting pump of your life" - a pump that lasts until you drop dead to the floor.

Selenium, the Fertility Mineral!? Organic and Inorganic Selenium Ameliorate Reductions in Testosterone, Testicular Damage and Abnormalities in Sperm Quality in Obese Mice

Image 1: With enough selenium in vivo, "in vitro" (-fertilization) may not be necessary.

If you have not heard about it in one of my previous blogposts, you may probably heard about the antioxidant, pro-fertility effects of selenium in the context of Tim Ferris' "selenium experiment" in the 4-Hour-Body. Ferris claimed that by just eating a handful of Brazil nuts (544µg selenium per ounce) every day shot his testosterone levels and libido through the roof. Now, what most people probably overheard, though, was that Ferris was selenium deficient to begin with. Just as every bodybuilder's holy grail, zinc, selenium won't help up your testosterone or fertility if you have already plenty of the potentially toxic trace mineral in your diet. In view of its central role in the antioxidant defense system of our bodies, it is however likely that selenium requirements increase, whenever our bodies are exposed to increasing amounts of oxidative stress.

When your body fat sets your testicles on fire, selenium may come to a rescue...

One of the most common causes of increased oxidative stress, these days, are the increased levels in highly oxidizable very-low density cholesterol and triglyceride levels which appear to be an almost inevitable consequence of the "modern" lifestyle (=sitting on the couch and washing down your fast-food, as well as your low-fat "healthy" cereals, pasta and rice with soda). A recent study from scientists from the Institute of Nutritional and Metabolic Disorders of Domestic in China does now show that an adequate amount of dietary or supplemental selenium, which is, as you may gather from the data in table 1, pretty scarce in everything that was not grown or raised on selenium-rich soil, may not be able to reverse all negative side-effects, but could ameliorate them so that reproduction would still be possible (Ibrahim. 2011).

Table 1: Selenium content of common foods (based on data from the NIS. 2011)

While the basal diet, which had been enriched with cholesterol, lard and cholic acid, so that it would mimic the obesogenic high carb + high fat diet, researchers love to mislabel HFD (high fat diet), contained only 0.04 µg/g of selenium (without the addition the lard, i.e. for the control group, the se-content was 0.05µg/g), both the inorganic selenium HF-diet and the diet of the animals that received a combination of (organic) selenium (75% selenium-methionine) and probiotics (C. utilis and S. thermophilus strains) contained ~6x the amount of selenium (0.3µg/g chow). For humans this would translate to ~1.2µg/kg and 7µg/kg, respectively (since the scientists did not report food intake and body weight of the animals, I based this calculation on the respective data from other HFD feeding studies with mice).

Amelioration? Yes! Reversal / complete prevention? No!

After 75 days on control, high fat, high fat + probiotic only, high fat + inorganic selenium only, and high fat + 90% organic selenium + probiotic diets, the testis of the mice showed histopathological changes even a non-expert as I am one would identify as "probably not healthy" (cf. illustration 1):

Illustration 1: Compilation of the histopathological examination of murine testes (H & E, ×400; based on Ibrahim. 2011)

The evident degenerations, decreases in cell population, and irregularities went hand in hand with a pretty profound changes in the quality of sperm (cf. figure 1), which were ameliorated, yet not prevented in the selenium and selenium + probiotic groups.

Figure 1: Measures of sperm quality - sperm count and motility (left); relative incidence of sperm with abnormal heads and tails (right; data based on Ibrahim. 2011)

In that, it is noteworthy that the selenium + probiotic (SePro) group had an only 1.5x increased amount of sperm with abnormal tails. The latter can thusly hardly be the reason for the -20% reduction in overall sperm motility.

Figure 2: Lipid (left axes) and testosterone (right axes) levels in the different groups (left); HDL to total cholesterol ratio and change in testosterone levels compared to control (right; data calculated based on Ibrahim. 2011)

In view of the fact that the male gonads do not only produce sperm, but also testosterone, it is not surprising that selenium and selenium + probiotic supplementation had a similar ameliorative effect on the diet induced reduction -47% reduction in testosterone (cf. figure 2). The +3% increase in serum testosterone (over the obesogenic diet group) in the probiotic only group, on the other hand, lacked statistical significance.

Image 2: The importance of selenium for thyroid function, specifically the local conversion of the "inactive" T4 to the "active" T3 is not the only reason why women should try to achieve adequate selenium intakes, as well.

Selenium for women? While it appears that research has hitherto focused on the role selenium plays in male health, there is a handful of studies which suggest that adequate levels are just as important for women, as they are for men. The results of a Polish study from 2006, for example, stand in line with the, as of late, controversial anti-carcinogenic effect selenium is supposed to have on prostate cancer. According to the authors, the provision of selenium supplements to women with a genetic disposition for breast and ovarian cancer led to a small, but statistical significant reduction in cancer rates (Huzarski. 2006). In 2009, Hermsdorff et al. observed a statistical significant inverse correlation between selenium intake and serum levels of retinol-binding-protein 4, a marker of whole body inflammation and purported contributer to insulin resistance and diabetes (Yang. 2005), in 74 young (~20y) healthy women (Hermsdorff. 2009). In post-menopausal women, Llaneza et al. found a non-negligible association of low-serum selenium levels and higher LDLc and triglyceride levels (Llaneza. 2009). A 2007 study by Negro et al. underlines the particular importance of adequate selenium levels for thyroid health during and immediately after pregnancy (Negro. 2007). And according to a recent review of the role of selenium in reproductive health, low selenium levels in the follicular fluid are a characteristic feature of "unexplained infertility" in women.

As far as the "potency" of the probiotics is concerned, the study was thusly quite disappointing. That the scientists who were proud to have developed a "Se-enriched probiotic as a new feed additive product for promoting animal industries" do not explicitly state that, is understandable, but won't stop me to repeat my previous recommendation to just add a handful of brazil nuts to your diet on a regular basis to make sure you satisfy your selenium requirements.

Selenium intoxication from Brazil nuts? I don't think so...

Image 3: Eating lots of brazil nuts and other selenium rich foods until they achieve what the US consider "toxic" serum and plasma levels does not seem to impair the health of the inhabitants of the regions around the Tapajós River in Brazil - on the contrary, their cardiovascular health is outstanding (Lemire. 2011)

That this practice is not going to result in selenium toxicity has, by the way, been shown only very recently in one of those studies that analyze traditional diets, which have become so in-vogue, as of late. Lemire et al., who analyzed blood (B-Se) and plasma (P-Se) samples from members of the communities which live along the Tapajós River in Brazil, did not only find that these people had selenium levels well beyond what is "considered toxic" in the US, they also state that their results "support the need to re-assess Se toxicity considering factors such as the chemical form of Se exposure, route of exposure (inhaled versus ingested), co-exposures to toxic elements such as mercury" and hint at "a possible association between high Se status and cardiometabolic health in this study population." (Lemire. 2011) So, men or woman, fertile or infertile, fat or lean... you better make sure you get your share of brazil nuts, today ;-)

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. 2012). 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. 2012).

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. 2012 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. 2012. 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. 2012 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.