Leucine + B6: 82% More Weight + Twice As Much Body Fat Loss in First 12 of 24 Weeks on -500kcal/day Diet W/ 2.25g Leucine + 30mg Pyridoxine - To Good to Be True?

Check your nutrition labels, I bet you get 2.25g+ leucine and 30mg of B6 from one of your supps already

I am sorry to say that and actually this is usually something that goes into the bottom line, but I do have serious doubts whether the results reported in this study can be replicated in any of you. Yes, it is a human study, but (a) the subjects, 12 men and 12 women, were obese (34.76 ± 2.57) and (b) if the mere addition of 2.25 g leucine and 30 mg vitamin B6 would have such profound effects, everyone who has ever taken a commercial BCAA product would have noticed a doubling in fat loss, already, as almost all of them contain 2.25g+ of leucine and tons of pyridoxine (B6).

So what are you saying here? Is this study a fraud?

I have no evidence that the study was a fraud and I am certainly not implying this, but you must wonder about the magnitude of the weight loss and fat loss difference between the regular and the NuShape supplemented dieters (-500kcal from baseline energy demands calculated simplistically by  1.3× result of the WHO formula for basal metabolic rate), who ingested 2x 1.125 g leucine and 15 mg pyridoxine per day (whether that's on empty is not disclosed in the paper).

Figure 1: Changes in insulin (μU/ml), HOMA-IR, waist circumference (cm), body weight (kg), fat weight (kg) after 12 (blue) and 24 weeks (orange), relative change from 12-24 weeks is indicated in % below the bars (Zemel. 2013)

According to the researchers, who have published corresponding data for rodents and an analysis of the effects of the same combination of leucine + pyridoxine on total fat oxidation (>30g increase per day in a randomized controlled study; Zemel. 2012), the specific effects on visceral obesity could be a result of the

"reductions of oxidative and inflammatory stress biomarkers, such as plasma malondialdehyde (MDA), 8- isoprostane F-2α, tumor necrosis factor-α, and C-reactive protein, as well as an increase in the anti-inflammatory marker adiponectin" (Zemel. 2013)

they observed in a previous trial after 4 weeks, even in the absence of weight loss (Zemel. 2012). This would certainly be beneficial for both the lean and the fat individual, but with already low levels of CRP, MDA and TNF-alpha as you, as a healthy follower of physical culture should have them, these changes will be so small that they are unlikely to have any visible effects on you.

There decreased weight / waist / fat loss within the 2nd two weeks in the supplement group (see figure 1, yellow arrow for the discussion of waist circumference as an example) does actually provide evidence that the effect size will decrease the learner you are... even "worse", but rather hypothetical: The effect could also be diminishing, because the human body get's used to the new steady influx of leucine and B6 and their beneficial effects on the mitochondria, Sirt-1 and AMPK expression (learn more; note: as stated in this older article of mine, it works also without resveratrol)

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Learn more about leucine, HMB, B6, mitochondrial health and weight / fat loss in a previous post (read more)

Bottom line: You are probably already doing what 50% of the subjects in this (sponsored) study have been randomly assigned to, i.e. consuming an extra 2.25g of leucine and 30mg of vitamin B6 (this is ~3800% of the RDA) per day if you consume either a "sports multi", a "high potency B-vitamin" or simply the next best BCAA or other amino acid / protein product with added B6. So, let me ask you a question, then. Did you get ripped to the shreds from this practice? No? Well, in that case you will probably share my doubts about the relevance of the data and the usefulness of the said supplement.

References:

• Zemel MB, Bruckbauer A. Effects of a leucine and pyridoxine- containing nutraceutical on fat oxidation, and oxidative and inflammatory stress in overweight and obese subjects. Nutrients. 2012;4:529–541
• Zemel MB, Bruckbauer A. Effects of a leucine and pyridoxine-containing nutraceutical on body weight and composition in obese subjects. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 22 August 2013.

Magnesium Round-Up: Know If You Are Deficient, Whether You Need More, Where to Find It, How Dietary Mg Contents Changed & How Magnesium Interacts W/ Vitamin D

24%, 23% and 22% of the DV for magnesium that's what you can find in one serving of sunflower seeds (0.25cup), halibut (4oz) and a large(r) banana - now you tell me it was impossible to get your magnesium from dietary sources.

After having handled half of the Science Round-Up from Thursday yesterday, yesterday, there is still something left to serve: seconds to the seconds, if you will and probably not so "new" as the average SuppVersity news. In order not to bore you, I will yet refrain from telling you how important magnesium is and how it is involved in thousands of enzymatic reactions ... you know the whole magnesium-guru-spiel all too well, anyway. I mean, anyone doing a cursory Google search will have to conclude that there is nothing magnesium cannot cure, right?. Whatever you may suffer from, someone has already found out that it must be related to magnesium deficiency or, even more profitable, taking the wrong form of magnesium supplements.

Apropos deficiency: How do you even know you are deficient?

What sounds like a question that could be answered in one, at best two sentences turns out to be one of the root causes of the whole confusion about magnesium. Based on a standard blood test you can only exclude that your levels are (a) so high or (b) so low that you better head straight to the emergency room. Magnesium is, just as the other electrolytes, simply too important for your body to have them drop below a certain margin in which your heart works optimally. So if there is not enough magnesium around, your body will tap into tissue stores the status of which is obviously not identical to the serum levels on a standard lab test.

Table 1:The lion's share of magnesium to replete your serum levels is not coming from your red blood cells and therefore RBC levels are only a proxy and not a 100% reliable marker of total body mg status (data based on Elin. 1987)

According to Maurice J. Arnaud who wrote a review with the telling title "Update on the assessment of magnesium status" in 2008, the most reliable method to assess the whole body magnesium status would be a metabolic ward study in the course of which a so-called "loading test" would be performed, But...

"[b]alance studies are time consuming, labour intensive and need well trained staff. They are often performed in a metabolic unit and require complete urine and faecal collections; therefore it is not a method that can be applied as a routine test for the evaluation of Mg status. Loading tests are simplified balance studies where absorption is supposed not to be disturbed when Mg is given orally so that body retention is calculated from urine elimination. Mg administration during a loading test can be either oral or intravenous and it is important that the subjects have normal kidney function. Urine is collected for 24 hours following administration of the Mg load as Mg excretion by the kidney has been shown to have a circadian rhythm . Under these conditions, the loading test is supposed to be a reliable indicator of Mg status." (Arnaud. 2008)

With the erythrocyte (red blood cell) test for magnesium, there is however an alternative available, which may not be just as reliable but appears to show a relatively high correlation with whole body magnesium levels in many, but not all studies (Malon. 2004).

How likely is it that you are deficient?

Honestly, I would hope that it is unlikely, because if that is the case for someone who is not taking supplemental magnesium you can almost be sure that her or she is following a healthy whole foods diet.

Table 2: Overview of age groups with more than 5 % of intakes below the lowest recommended intake levels in 7 European countries; T, toddlers (1–3 years (both sexes)); C, children (4–10 years); Y, youth (11–17 years); A, adults (18–60 years); S, seniors (.60 years); capitals, both sexes; lower case, women only; lower case italic, men only (Mensik. 2013)

If you take a look at table 2 you will see that even the average German gets enough magnesium in his diet, irrespective of his age, and much contrary to our neighbors in the East, West and Northwest (I could not resist to mark zinc another of those purported minerals of which conventional wisdom tells you that you simply cannot get enough from your diet).

Knowing that most of you are probably Americans, I can calm you down. You are not worse than your British friends. In fact, the NHANES data from 1999-2000 suggests that the average American Caucasian and Mexican man below 50 gets enough magnesium from his food only! Unfortunately, the same cannot be said for the women, and both male and female African Americans who have trouble meeting their requirements even if one accounts for the additional magnesium from supplements (NHANES).

Magnesium and the athlete

A note on magnesium and cramps: While there is evidence that altered serum osmolality and altered serum electrolyte concentrations, notably hypochloraemia, hyponatraemia, and hypocalcaemia (=not hypomagnesaemia) can cause generalized skeletal muscle cramping at rest in specific clinical settings, "data from well-conducted prospective cohort studies show that athletes with acute EAMC are not hyponatraemic, hypochloraemic, or hypocalcaemic and do not have an abnormal serum osmolality." (Schwellnus. 2008).

For the average athlete, a low magnesium intake is yet rather the exception and can even be problematic for athletes with a high anaerobic-to-aerobic ratio who suffer from increases in blood mg due to an overall reduction on blood volume after intense workouts, anyway (Cordova. 1992; Joborn. 1985; Monteiro. 2005; Monteiro. 2006). It is thus no wonder that not magnesium deficiencies, but high magensium levels are a problem that is commonly observed in athletes. I mean, what are you supposed to do, when even your mother "lies" to you about cramps being caused by magnesium deficiency?

"The most common alterations were higher serum phosphate (29/61, 47%) and magnesium concentrations (28/61, 46%). Abnormalities of serum phosphorus and magnesium concentrations were detected in almost half of the athletes. Hyperphosphataemia and hypermagnesaemia were the most common abnormalities." (Malliaropoulos. 2012)

The data Malliaropoulos et al. analyzed came from 130 elite track and field athletes (65 males and 65 females, age range 20-30 years) from the National Athletics Sports Medicine Center database in Thessaloniki, Greece. And maybe some of them were even on the proven non-ergogenic ZMA (zinc + magnesium + vitamin B6; cf. Wilborn. 2004).

So where do you get your supplemental magnesium from and how much?

I am not going to tell you to stop supplementing with magnesium if you feel that this has done you good in the past. It is after all an important mineral. What I want to remind you of is yet the fact that taking 100% of the RDA is imho the absolute maximum. Even if you don't end up with high levels due to supplementing more and don't care about wasting money, there is one thing that's commonly overlooked about human physiology and that is how the intake and excretion of nutrients are highly inter-related. In other words, if your body switches into a "get rid of magnesium" mode it is likely you are loosing other electrolytes you do not supplement in copious amounts (e.g. salt ;-), as well.

Figure 1: Plasma an bone (primary axis) as well as red blood cell (RBC; 2ndary axis(!)) content after 14 days of supplementation with identical amounts of magnesium in different organic and inorganic forms (Coudray. 2005)

As far as the best forms are concerned the number of studies comparing multiple forms to each other is limited and the inter-comparison of different studies not really legit. Therefore I have simply copied + pasted the figure that went with a previous article on the matter - as you can see, you can generally use whatever form of magnesium you want - even the cheap oxides, which worked wonders for anxiety ridden ladies in a study by De Souza et al. that was published in the Journal of Women's Health & Gender-Based Medicine in March 2000. As long as you take your magnesium supplements in reasonably low doses - the dose in the De Souza study for example was 200mg + 50mg B6 - and over a long enough period, they are going to bring your levels back up - if not sooner, then later.

Magnesium depletion of our foods

A note on topical Epsom salt from the early 20th century: While I did tell you on the show that I could not find peer-reviewed adequately powered studies on the topical absorption of magnesium in the for of mg oil or Epsom salt, I found a comment in a 1915 paper on the potential harm caused by cosmetics quite enlightening, esp. the part on the economic value of respective products, where Martin I. Wilber writes that the ability of respective products to penetrate the "unbroken skin has as yet not been demonstrated" and cautions against the sue "of the now widely advertised lotions containing magnesium sulphate or Epsom salt", of which "the latter preparations serve very well to show the gullability of that portion of the public that is desirous of improving its facial appearance. As Epsom salt, magnesium sulphate can usually be purchased for 5 cents a pound, while in the form of any one of the popular skin or wrinkle lotions it is sold at the rate of from $2 to $4 a pound." (Wilbert. 1915) You see, there were snake,... ah I mean mg oil vendors all over the place even 100 years ago ;-)

Aside from the almost cult-like worship of epsom salt baths and topical ng oils, the notion of a general depletion of mg in the foods we eat is one of the favorites among the bazillion of websites run by people who hoax you to believe they were concerned with your physical health, when all they are concerned with is their own financial health.

Figure 2: Changes in mineral content of selected food types from 1940-2002 (Thomas. 2007)

It is, as the data in figure 2 goes to show you true that the amount of magnesium in many of the foods we consume is lower these days than it was amidst WW2. The mg loss in meats, for example, is  driven by the processing, while corned beef has lost almost 50% of its "original" mg content, the amount of mg in roast beef and steaks is still the same, the one in turkey is even up by ~30% and for chicken it remained 100% stable (Thomas. 2007). It is also a very intriguing coincidence that the same websites will usually also tell you how we are all not just magnesium deficient, but also copper toxic. Strange in view of the fact that the average reduction in copper is -62% and thus >2x higher than that of magnesium.

Magnesium supplementation for special conditions

Before closing this round-up with a bottom line, I am briefly listing a couple of things related to magnesium or rather a deficiency in this important mineral that could be solved by simply upping your dietary and/or supplemental magnesium intake.

• 

  Higher vitamin D levels increase MG uptake from the gut and supplementation with VD has been shown to increase mg in obese, yet not in normal individuals (Farhanghi. 2009). On the other hand, mg has recently been found to be necessary for the production of calcitriol from 25OHD (Matsuzaki. 2013)

  anxiety - mg is the gate-keeper at the NMDA receptor and interacts with the GABA receptors; a deficiency can cause anxiety, the use of extra magnesium will yet not automatically solve the problem if you are not low to begin with
• depression - low cellular mg levels can precipitate if not cause depression(-like) symptoms, 150-300mg of magnesium glycinate or better taurinate can help (Eby. 2006)
• low vitamin D - while it is not yet sure if it helps with upping the storage form of vitamin D (25OHD), it has been recently established that magnesium is necessary for the production of calcitriol the active form of vitamin D; adequate levels of D also facilitate mg absorption very high levels of vitamin D, on the other hand, have been associated with low / imbalanced mg levels - probably due to their effects on calcium homestasis
• constant stress / burnout - initially low mg levels will lead to a hyper activity of the stress-axis within the HPTA; the constantly overtaxed CNS will then give in and you will end up totally burned out (Sartori. 2011); this state cannot be reversed by magnesium supplementation, alone, but it can aid the recovery process which is largely based on taking off of everything that stresses you

Whether or not simply eating more high magnesium foods will be enough or whether you actually have to buy supplements to work on these and other issues will also depend on whether

• you can digest / absorb it, which would be hampered due to vomiting, diarrhea, bowel resection, intestinal and biliary fistulas or hemorrhagic pancreatitis
• lose too much mg over the kidneys, due to chronic parental fluid therapy, osmotic diuiresis, hypercalcemia, diuretics, aminoglycosides, amphotericin B, pentamidine, cisplatin, cyclosporine, alcohol metabolic acidosis (ketosis, starvation, alcoholism), renal diseases, or
• suffer from endocrine disorders like primary or secondary aldosteronism, diabetes, hyperthyroidism or hyperparathyroidism

If anything of these sounds familiar, I would certainly consider testing my mg levels (erythrocyte test) before and while I was supplementing and that's not about wasting money on potentially unnecessary supplements, but much more about making sure that you actually get, absorb and retain enough magnesium.

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Bottom line: Magnesium is certainly an important mineral, but its effects must not be seen in isolation, it should not be supplemented in copious amounts in isolation without medical indication and it may not be misunderstood as a natural pharmacological agent - it works by (a) replacing a deficiency or (b) countering an imbalance. Plus: It is not generally impossible to get your 300-400mg of magnesium from your diet.

References:

• Arnaud MJ. Update on the assessment of magnesium status. Br J Nutr. 2008 Jun;99 Suppl 3:S24-36.  
• Bohl CH, Volpe SL. Magnesium and exercise. Crit Rev Food Sci Nutr. 2002;42(6):533-63. Review.
• Coudray C, Rambeau M, Feillet-Coudray C, Gueux E, Tressol JC, Mazur A, Rayssiguier Y. Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach. Magnes Res. 2005 Dec;18(4):215-23.
• Cordova A. Changes on plasmatic and erythrocytic magnesium levels after high-intensity exercises in men. Physiol Behav1992; 52: 819-21.
• Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. 
• Elin RJ. Assessment of magnesium status. Clin Chem. 1987 Nov;33(11):1965-70. Review.
• Farhanghi MA, Mahboob S, Ostadrahimi A. Obesity induced magnesium deficiency can be treated by vitamin D supplementation. J Pak Med Assoc. 2009 Apr;59(4):258-61. 
• Joborn H, Akerstrom G, Ljunghall S. Effects of exogenous catecholamines and exercise on plasma magnesium concentrations. Clin Endocrinol (Oxf)1985; 23: 219-26; (Oxf).
• Malliaropoulos N, Tsitas K, Porfiriadou A, Papalada A, R Ames P, Del Buono A, Lippi G, Maffulli N. Blood phosphorus and magnesium levels in 130 elite track and field athletes. Asian J Sports Med. 2013 Mar;4(1):49-53.
• Malon A, Brockmann C, Fijalkowska-Morawska J, Rob P, Maj-Zurawska M. Ionized magnesium in erythrocytes--the best magnesium parameter to observe hypo- or hypermagnesemia. Clin Chim Acta. 2004 Nov;349(1-2):67-73.  
• Matsuzaki H, Katsumata S, Kajita Y, Miwa M. Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats. Magnes Res. 2013 May 1;26(2):83-6.
• Mensink GB, Fletcher R, Gurinovic M, Huybrechts I, Lafay L, Serra-Majem L, Szponar L, Tetens I, Verkaik-Kloosterman J, Baka A, Stephen AM. Mapping low intake of micronutrients across Europe. Br J Nutr. 2013 Aug;110(4):755-73.   
• Miriam C. De Souza, Ann F. Walker, Paul A. Robinson, and Kim Bolland. Journal of Women's Health & Gender-Based Medicine. March 2000, 9(2): 131-139.  
• Monteiro CP. Equilíbrio Oxirredutor: um estudo em nadadores e em não atletas, em repouso e em resposta ao exercício [PhD]. Lisboa: Faculdade de Motricidada Humana, Universidade Técnica de Lisboa, 2005.
• Monteiro CP, Santa Clara H, Raposo MF,et al. Effect of training and exercise intensity on magnesium status. In: Alpoim C, Vasconcelos Morais P, Santos MA, Cristóvão AJ,
  Centeno JA, Collery P, eds.Metal Ions in Biology and Medicine. Paris: John Libbey Eurotext, 2006: 546-52 
• Sartori SB, Whittle N, Hetzenauer A, Singewald N. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology. 2012 Jan;62(1):304-12. doi: 10.1016/j.neuropharm.2011.07.027. Epub 2011 Aug 4.
• Schwellnus MP. Cause of exercise associated muscle cramps (EAMC)--altered neuromuscular control, dehydration or electrolyte depletion? Br J Sports Med. 2009 Jun;43(6):401-8. 
• Thomas D. The mineral depletion of foods available to us as a nation (1940-2002)--a review of the 6th Edition of McCance and Widdowson. Nutr Health. 2007;19(1-2):21-55. Review.
• Wilbert MI. Cosmetics as Drugs: A Review of Some of the Reported Harmful Effects of the Ordinary
  Constituents of Widely Used Cosmetics. Public Health Reports. 1896-1970; 30(42): Oct. 15, 1915. 3059-3066.
• Wilborn CD, Kerksick CM, Campbell BI, Taylor LW, Marcello BM, Rasmussen CJ, Greenwood MC, Almada A, Kreider RB. Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism. J Int Soc Sports Nutr. 2004 Dec 31;1(2):12-20.

Caffeine Protects Brain Function Against Stress & SAD Diet; Coffee Withdrawal, Anxiety & Co; Giardia, Messy Subtenant W/ Gusto For Arginine; Vit B6 & n6:n3 PUFA Ratio

19 Billion Euro that's the estimated 2011 financial burden due to lung cancer, alone, here in Europe and the On Short Notice figure of the week (information based on ESMO2012 press release)

Those of you who are also following the SuppVersity facebook news, will probably recognize the figure on the right: 16,000,000,000€ or $24,419,000,000, that's the estimated economical burden due to lung cancer, alone, here in Europe (cf. "Who cares if people are dying as long as the economy is thriving?"). An enormous financial loss, and still not the reason that this is my figure of the week. Rather than the financial damage, itself, it is the tragic fact that only the latter, yet not the fate of the patients and their families, would make a valid argument, when policy makers were debating a long overdue, total and all-encompassing public smoking ban... but now for a couple of more sciency, yet not less intriguing news from the past week.

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Problems thinking straight? Guess what: 3-4 cups of coffee could help :-) According to a soon-to-be-published paper by scientists from the Jordan University of Science and Technology in Irbid, Jordan, the ingestion of the human equivalent of approximately 3.8mg caffeine per kg body weight or 3-4 cups of coffee per day, can inhibit both, the stress, related as well as diet induced (we are talking of the "typical" Western diet (WD), that's both high in carbohydrates and fat) cognitive impairments (Alzoubi. 2012)... well, at least in the researchers 3-months rodent study it worked like a charm

• learning trial: animals in the caffeine/stress, caffeine/WD, and caffeine/stress/WD groups made fewer errors, than non-supplemented stressed or WD animals; overall their performance was comparable to those of the control
• memory tests: treatment reduced the number of error and restored short-term memory and long-term memory during chronic stress and/or WD (P < 0.05) to normal levels

With respect to the underlying mechanisms the scientists speculate that caffeine may "act mainly by inhibiting adenosine receptors" (Alroubi. 2012), which has in turn been shown to to inhibit long term potentiation (LTP) in rat hippocampal slices and disrupt the process of learning and memory at the synaptic level by blocking release of glutamate (de Mendonca. 1994).

Additionally, caffeine has also been shown to increases the expression of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor, which is impaired in response to chronic stress and a hypercaloric Western diet (Aleisa. 2006; Molteni. 2004) and leads to deteriorations in cognitive performance. In the long run those effects could also contribute to the anti-dementia and anti-Parkinson's effects, I mentioned in the recent SuppVersity post on the insulin sensitizing effects of coffee.

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Figure 1: While the Hedonic tone and alertness reduced to baseline on day 5 of caffeine withdrawal, the habitual caffeine consumers had >15% higher anxiety scores on day 7 after giving up on their daily dose of methylxanthine (data calculated based on Smith. 2012).

Don't worry, caffeine will also work for humans. And what's best, upon short-term withdrawl (8 days) your cognitive performance is not going to suck - at least not as much as when you are stressed or living on pizza and French fries, only. All that and a couple of interesting other results have been published ahead of print in the online version of the Journal of Pharmacology (Smith. 2012).

To probe the effects of acute caffeine ingestion on cognitive performance and the influence of previous caffeine consumption and withdrawal, Andrew P Smith, Gary Christopher and David Sutherland recruited 70 volunteers (25 male, 45 female; mean age 22.8 years). The 35 consumers (>100mg caffeine /day, mean 300mg; range 110–600 mg) were put on withdrawal and tested on day 2, alone and without caffeine, and day 8 together with the non-consumers in a double-blind placebo-controlled fashion. During the caffeine challenge, the cognitive performance was tested twice, once before and once 30min after the provision of the caffeinated beverages.

Anxious, but smart: Caffeine gives you the edge

The results of the trial clearly indicate that the ingestion of 2 mg/kg of caffeine, which were served in decaffeinated coffee or tea 30min before the testing procedures, were associated with faster simple reaction times, fewer long responses, greater detection of targets in the cognitive vigilance task, and faster encoding of new information.

"The results confirmed previous findings, with ingestion of caffeine being associated with a faster simple reaction time, fewer long responses, more targets detected and faster encoding of new information. There were no main effects of consumer status, nor were there any significant interactions between caffeine and consumer status." (Smith. 2012)

Notwithstanding, I believe that many of you will probably be more interested in the effects of caffeine withdrawal on overall withdrawal symptoms (figure 1, top), as well as the alertness, hedonic tone and anxiety (figure 1, bottom) and the cognitive performance on day 2 of the withdrawal period (figure 2, left), than in any of the well-established performance cognitive performance boost, right?

Figure 2: Performance on day 2 of withdrawal phase (w/out caffeine) and on day 8 before (w/out caffeine) and after (w/ caffeine)the ingestion of decaffeinated tea or coffee with 2mg/kg caffeine in it (data based on Smith. 2012)

As you can see on the left-hand side of figure 2 there was a minimal performance decline on day 2 of the withdrawal phase, but the latter was statistically not significant and all measured markers of cognitive function had returned to normal on day 8 (remember longer response times = worse performance!), when the resumption or first time provision of caffeine spiked the reaction times and lowered the mistakes in all tests, irrespective of whether the subjects were former habitual consumers on withdrawal, or not.

Outside of controlled experiments "real" coffee and tea do at least as well

Since a large cup of coffee contains about the same amount of caffeine the scientists simply added to decaffeinated beverages, to ensure that the drinks could not be distinguished (by their smell for example), you can simply stick to your regular coffee and if you want to enjoy similar benefits. And to be honest, in view of the plethora of benefits of chronic low dose coffee consumption, I would not even think for a second about whether or not you may be missing out on the occasional boost, when you are not "going on withdrawal" from time to time...

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Figure 3: W/out arginine (Arg-) intestinal epithelial cells can't proliferate (graph based on Stadelmann. 2012)

Giardia eats away your guts arginine supply and makes itself at home within an increasingly morbid digestive tract! As a group of scientists from Sweden and Argentina reports in their latest paper, the protozoan parasite, Giardia intestinalis, feasts on the arginine your gut cells need to proliferate (Stadelmann. 2012). This will lead to reduced polyamine levels and upregulated cell cycle inhibitory genes, which will eventually disrupt the the cell cycle of the intestinal epithelial cells. The reduced intestinal epithelial cell proliferation, on the other hand, allows the gut pathogen to thrive and will, in the long run, disrupt the intestinal tissue homeostasis and thus initiate the decay of the intestinal epithelium  - a central feature of so many of the wide-spread gut pathologies.

Provision of additional arginine + citrulline can help ... in the short run

Now, the good news about all that is that the in-vitro data in figure 3 clearly suggests and anecdotal, as well as the effective therapy of diarrhea patients with arginine/citrulline actually confirm that the provision of supplemental arginine (or citrulline) constitutes a cheap and readily available way to ameliorate the decay, until the bugs have been eradicated by antimicrobial drugs.

A pros pos, antimocrobial drugs, with regard to latter, Noa Tejman-Yarden and Lars Eckmann write in a recent review of the latest drug innovations, that despite the fact that metronidazole and other antimicrobials are usually effective, "treatment failures are common and antimicrobia resistance occurs" (Tejman-Yarden. 2011), so that it would appear as if complex derivatives of 5-nitroimidazole and benzimidazole, which form the core structure of the most widely used antigiardial drugs, will replace them in the short-run. At least for so long, until several new classes of antigiardial drug candidates that have already been identity by high-throughput screening of large compound libraries, will eventually hit the market (Tejman.Yarden. 2011)

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More about vitamin B6: Helps with neurotransmitters synthesis; is involved in nerve function and necessary for normal brain development & function; influences mood, and melatonin production; effects circadian clock; is needed for B12 absorption and thus red blood cell production

When low: "Pins and needles" in extremities, mental disorders, seborrheic dermatitis, estrogenic PMS, dizziness, irritability, kidney stones, abnormal EEG, anemia, convulsions, edema (water retention), hypothyroidism, migraine-headaches, glossitis, lymphopenia

When high: Depression, suicidal tendencies, severe fatigue, mood swings, low blood sugar, migraine-headaches, heart palpitations, thyroid abnormalities (hyper- in the short, hypo in the long term), numbness in hands and/or feet, spinal / nerve degeneration, muscle spasms / cramps, osteoporosis, arthritis, higher blood pressure (short-term suppl.), lower blood pressure (long-term suppl.), mineral imbalances (high phosphor & magnesium vs. low sodium & calcium), restlessness, insomnia, vivid dreams, decreased estrogen & prolactin, depressive PMS.

RDA (adults): 1.3 mg*
*higher for pregnant women & >50y

Upper tolerable limit: 30-100mg*
*depending on the source of information

Food sources: chicken, turkey, tuna, salmon, shrimp, beef liver, milk, cheese, lentils, beans, spinach, carrots, brown rice, bran, sunflower seeds, wheat germ, and whole-grain flour

n6:n3 ratio does not depend on dietary intake alone: A marginal deficiency in vitamin B6 will skew your serum PUFA levels towards the N6-side That's the long and short of the results of a study that's going to be published in the October issue of the Journal of Nutrition.

Mei Zhao and her colleagues analyzed the fatty acid profiles in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC) of healthy men and women who had been fed a low-vitamin B-6 (pyridoxine) diet for 28 days and observed that contrary to the plasma HDL and LDL cholesterol concentrations, the amount of free fatty acids (FFA) in the blood and the erythrocyte and PBMC membrane fatty acid compositions, neither of which showed any statistically significant changes, the amount of all long-chain polyunsaturated fatty acids, i.e. arachidonic acid (n6) and EPA and DHA (n3) decreased from 548 ± 96 to 490 ± 94 μmol/L, 37 ± 13 to 32 ± 13 μmol/L, and 121 ± 28 to 109 ± 28 μmol/L, respectively.

The subsequent 8% increase in the total n6:n3 PUFA ratio from 15.4 to 16.6 is not alarming, but if this trend would continue linearly, it would certainly become problematic, in the long run. Moreover, the decrease in both n6 and n3 long-chain PUFAs (of which people tend to forget that the "inflammatory" arachidonic acid is as vitally important as its "anti-inflammatory" omega-3 counterparts) could provide an alternative / complementary mechanistic explanation for the increased cardiovascular disease risk that has been associated with vitamin B-6 deficiency.

In view of the fact that the RDA is not exactly high and can easily be achieved from dietary sources, along (as long as you follow a diversified whole foods diet), and considering the fact that high levels of B6 have been associated with more negative side-effects than B6 deficiency (see infobox on the right; please note that I collected the information on a couple of trustworthy websites on RDAs & co and did not verify the research on each of them!), I would however caution against the typical Western "more helps more" supplementation mentality.

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Figure 4: Easy come, easy go - the mass you gain and the fat you lose by doing nothing than simply injecting testosterone is lost / regained within 6 months after discontinuation of the "testosterone therapy" (Forbes. 1992); read more about the role of testosterone in skeletal muscle hypertrophy in the Intermittent Thoughts on Building Muscle

In view of the fact that (a) today's short news items are pretty long(ish) and you still got a couple of interesting facebook news to check out, such as...

• health related: "Vitamin D: We probably won't know before 2017, whether supplementation is advisable", "Aromatase inhibitors to treat endometriosis", or 
• muscle related: "The muscle sparing effects of CLA + Omega-3" and a true classic "Muscle mass gained on injectable testosterone is lost, when injections are seized", 

... and a plethora of additional gems from the realms of health, exercise, nutrition & supplementation, I will call it a day for today and save the exercise and a couple of other exciting On Short Notice items for later next week.


References:

• Aleisa AM, Alzoubi KH, Gerges NZ, Alkadhi KA. Chronic psychosocial stress-induced impairment of hippocampal LTP: possible role of BDNF. Neurobiology of Disease 2006;22:453–62. 
• Alzoubi KH, Abdul-Razzak KK, Khabour OF, Al-Tuweiq GM, Alzubi MA, Alkadhi KA. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet. Behav Brain Res. 2012 Sep 20.
• ESMO. Press releases related to the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna.
• Forbes GB, Porta CR, Herr BE, Griggs RC. Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped. JAMA. 1992 Jan 15;267(3):397-9.
• de Mendonca A, Ribeiro JA. Endogenous adenosine modulates long-term potentiation in the hippocampus. Neuroscience 1994;62:385–90.
• Molteni R, Wu A, Vaynman S, Ying Z, Barnard RJ, Gomez-Pinilla F. Exercise reverses the harmful effects of consumption of a high-fat diet on synaptic and behavioral plasticity associated to the action of brain-derived neurotrophic factor. Neuroscience 2004;123:429–40.
• Smith AP, Christopher G, Sutherland D. Acute effects of caffeine on attention: a comparison of non-consumers and withdrawn consumers. J Psychopharmacol. 2012 Sep 19.
• Stadelmann B, Merino MC, Persson L, Svaerd SG. Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells. PLoS ONE. 2012; 7(9): e45325. 
• Tejman-Yarden N, Eckmann L. New approaches to the treatment of giardiasis. Curr Opin Infect Dis. 2011 Oct;24(5):451-6.