A "Question of Faith": Do Multivitamins, Antioxidants and Mineralsupplements Improve Your Quality of Life?

Image 1: Do you believe that you could solve this profound imbalance by randomly adding more people to both sides of the seesaw? No? Well, why are you taking a high-dose multivitamin then?

As the name of this website already implies, I am an outspoken believer in the usefulness of "supplements" (as in "to supplement" = to add to something, where it makes sense). There is however a particular group of "supplements", which is a real thorn in my side... Yes, I am talking about those one-size-fits-it-all-multivitamin-multimineral-multi-whatever products with "high quality ingredients" the ratios of which are based on either the "recommended dietary allowances" of the omniscient USDA (actually a way better name would be "random dietary allowances") or the even more idiotic maxime that "if some is good, then more is probably even better". These days every major supplement company has at least one of these formulas in their line-up and obvoiusly they all will claim that only their product will provide you "with all the vital nutrients you need".

Wtf!? How do those guys know which nutrients I need? 

Even if those formulas were perfectly balanced - which they certainly are not, because we simply don't know what the "perfect balance" is, yet - the chances that anyone of you, my educated, well-nourished whole-food eating readers, has a full-blown, all across the board nutrient deficiency that would be fixed by any of those products are probably one in a million. What is much more likely, though is that you have a small or (oftentimes due to "healthy supplements") profound nutrient imbalance.

Let's say you are an aspiring male fitness athlete and have been taking your ZMA religiously for years. At the same time you have heard that copper is not only bad for you, but that "we all" would get way too much copper in our diet, anyways. So you have been avoiding copper like a plague and ingesting 30mg of zinc from your ZMA everyday... now chances are that you have already set off the natural (and optimal) ratio of copper to zinc in your body. Let's say the optimal ratio was 1:12 (copper to zinc, and again - we do not even know what the optimal ratio would be). With your high zinc and low copper intake you are now at 1:20, i.e. 60% off! Now the nice guy from your local GNC convinces you that it would be prudent to add the brand new "Male Super-Power Vitamin" to you supplement regimen if you wanted to live a long and healthy life. Chances are that the guy who designed that product will also have heard that zinc is good for men and that we all get way too much copper (and even if he knew better, he will be aware that his formula won't sell if it does not follow conventional stupidity... ah, I mean wisdom). So, the product will have 200mcg of copper and 30mg of highly bioavailable zinc - I mean it's a "high quality product"! What is going to happen now? What? Right! The well-formulated product will exasperate you existing imbalance... Your multi does not do that? How come you think so?

"Ever since I take my multi, I have not become sick and feel way better!"

Right, you feel better... and you are not alone! In fact many of the 8112 participants in a well-controlled randomized, double-blind, placebo-controlled, primary human intervention trial which was conducted by a group of scientists from Paris (Briancon. 2011), also felt that the capsule with 120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 µg selenium and 20mg zinc, they had been taking for 76 months(!) improved their overall well-being.

Warning! I suggest you don't continue reading the following paragraphs if you do feel that your vitamin product works and do not want to take the risk that it will stop working as soon as you have finished reading this blogpost ;-)

What is pretty strange, though, is that this effect did not depend on whether the subjects actually received the anti-oxidant + mineral combination, or not. Rather, the main determinant of the the results of the health-related quality of life (HRQoL) questionnaire in this sample of healthy French adults was whether the subjects, who, as it is right and proper for a "placebo-controlled" trial, obviously did not know whether they were ingesting a capsule with the active ingredients or the placebo (it had been established in a previous study that the two capsules were indistinguishable; cf. Hercberg. 1998), believed that they were in the active arm of the study (cf. figure 1, believers vs. non-believers):

Figure 1: Perceived effect on global health (VAS) in subjects who had "no idea" whether they received the active or the placebo treatment and subjects who thought they received the active ("believers") or placebo ("non-believers") treatment (data adapted from Briancon. 2011)

What is also interesting, is that women were slightly more susceptible to placebo effect than men (not to the nocebo effect though), although this difference did not reach statistical significance.

Multivitamins are like religion: Believe in it and it works!

A pros pos statistical significance, as far as the "real" markers of health and disease are concerned, the "key message" (I use the words of the scientists ;-) of the SU.VI.MAX was that "long-term supplementation with antioxidant vitamins and minerals has no effect on quality of life" - in other words, although there were not measurable improvements, the study did not provide further evidence for the hypothesis that long term supplementation with anti-oxidant supplements, selenium and vitamin E in particular, had any negative effect on objectively measurable health markers (if you want to read more about the flawed analysis of and biased media reports on the data from the SELECT trial, read my previous blogpost on this issue).

Image 2: Add a body made of animal products to this guy and you have all the nutrients you need ;-)

It should be mentioned here that in a previous analysis of other data from the same cohort, the scientists had found a small, but statistically significant decrease in cancer and all-cause mortality among the male study participants of the active arm of the SU.VI.MAX trial (Hercberg. 2004). So, while the quality of life did not improve, the miserable life of some of the male subjects was at least extended by a few years ;-) All sarcastic jokes aside, even the scientists realize that in the presence of conflicting evidence, the "major implication for public health of the present findings is that a lifelong diet rich enough in vitamins and min-erals may be preferable to supplementation that is likely not to be efficacious and has the potential to be harmful." - sound advice!

Those of you for whom this is not the first visit, here at the SuppVersity, will be aware, that, as a trained scientist, I don't content myself with the conclusions my "colleagues" (from another branch of science) draw. Therefore, I dug a little deeper into the actual data that comes with the study and - alas! - I was able to find a statistically significant (p<0.014) increase in the reported "vitality" among the women who actually received the vitamin + mineral supplement (cf. figure 2):

Figure 2: Real (difference between treatment and placebo) and perceived (difference between "believers" and "non-believers") of antioxidant + mineral supplement (data calculated based on  Briancon. 2011)

What is strange though, is that of all statistically significant differences between women who believed they received the supplement and those who did not, just this one is the least distinct. Moreover, in all the other variables, where there was a statistically significant difference between believers and non-believers, the "real" data (meaning the comparison of subjects who actually received the treatment vs. the placebo group) could not confirm the positive self-assessment of the believers. Among the male subjects, there was even a trend toward reduced quality of life measures in the real data, where the "believers" thought that it was the "supplement" they were taking that soothed their bodily pain, improved their general health or overall physical performance (physical summary scale).

So what? Am I wasting my money?

These additional observations do yet not falsify any of the three main conclusions, Serge Briacon and his five colleagues from Nancy University, the Metz University, the University Paris Descartes, the University hospital of Nancy and the French Department of Public Health draw based on their interpretation of the data:

1. [t]here is no proof that supplementation with these vitamins and minerals is beneficial in participants whose dietary intakes are already sufficient
    
2. [t]he perception that supplementation improves general well-being is not supported by this trial.
    
3. [a] reverse causal pathway may even be advocated (healthier participants may have been more likely to believe they were in the supplement group).

What this means for you is that if your multivitamin "works", chances are that you are doing something right as far as your general lifestyle, your diet and your exercise regimen are concerned. If despite taking your multi religiously, you still feel miserable, you better take a closer look at what your real problems are instead of switching from one band-aid-fits-it-all "solution" to the next one.

The A to Z of Effective & Less Effective Immuno-Nutrients to Prevent and Combat Respiratory Tract & Other Infections

Teddy bears are like vitamin C and zinc. They can help you when you are already sick, but what are supplements athletes and gymrats take in advance to survive the flu season without getting sick at all?

Specifically during the winter time, hard working athlete and manic gymrats can be particularly susceptible to all sorts of infections. To help you having to work out with a handkerchief in your hand all winter long, I have compiled a non-comprehensive list of supplements that may help you to maintain and even improve your immune defenses and thus to survive the cold and dark winter times without catching a cold or even the flu.

In their recent review in the Journal of the International Society of Sports Nutrition Vinicius Fernandes Cruzat, Maurício Krause and Philip Newsholme reviewed the extensive literature on nutritional supplements that act as immuno-nutrients, may to reduce immunosuppression and excessive inflammation in hard-training athletes and gymrats like yourself (or yourself in 2015 ;-)

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In said paper, the researchers from the CHIRI Biosciences Research Precinct at the Curtin University in Perth and the Laboratory of Cellular Physiology at the Federal University of Rio Grande do Sul in Porto Alegre focus what they call the "key immuno-nutrients" L-glutamine, L-arginine, branched chain amino acids (BCAA) and whey protein. Now this would not be the SuppVersity if I didn't go beyond this list and added a few more or less promising extra supplements to the list. Before we get to any of those extras, let's briefly recap what Cruzat et al. (2014) found:

"Although a balanced diet with high quality and sufficient quantity of nutrients is essential, there is growing evidence that some non-synthetic supplements can assist optimal nutrition. In fact, the use of nutritional supplements especially the provision of amino acids, has grown year-on-year. [...]

The use of proteins and amino acids for supplementation deserves special attention, since these molecules are critical for anti-oxidant and fuel provision, participating in the whole-body energy homeostasis, growth, development, recovery and immune responses.

As Cruzat et al. point out, the key targets for immunonutrition may include provision of key metabolites for immune cells per se. In other words: Immuno-nutrients feed the immune system and don't suppress but optimize the multi-layered immunte response consisting of

• the inflammatory response and cytokine release, 
• the production of chaperone proteins such as the heat shock proteins (HSPs), 
• changes in the redox balance (including glutathione, GSH metabolism), and 
• the protection of skeletal muscle mass (see Figure 1). 

Thus your reasons to consume immuno-nutrients go well beyond warding off the common cold and encompass (a) performance improvements, (b) the general strengthening of the immune system and (c) the shortening of the exercise recovery period (Nieper. 2005).

Figure 1: Biphasic immuno-inflammatory response to severe exercise and the possible immunonutrition role. Immuno-inflammatory response induced by severe exercise or heavy periods of training and the proposed role of specific nutrients with immune benefits, also called immunonutrition (Cruzat. 2014).

In that, the most widely used supplements are vitamins and minerals. Reliable evidence for their immuno-protective effects, however is scarce and the results are ambigious:

• Vitamin C: South African ultramarathon runners did demonstrate that vitamin C (but not E or beta-carotene) supplementation (about 600 mg day7 1 for 3 weeks) was related to fewer reports of upper respiratory tract infections (URTI) symptoms (Peters 1983, 1990, 1993, 1996; Peters-Futre, 1997).
  
  

  

  Classic ROS-scavengers like vitamin C are not just ineffective, when it comes to countering the increased susceptibility to infection they have also been shown to hamper the adaptational response to exercise | read more.

  These beneficial effects have yet not been replicated by other research teams. Himmelstein, Robergs, Koehler, Lewis and Qualls (1998), for example, reported no alteration in URTI incidence among 44 marathon runners and 48 sedentary individuals randomly assigned to a 2 month regimen of 1000 mg /day of vitamin C or placebo. And in view of the fact that most randomized, placebo-controlled studies have been unable to demonstrate that vitamin C supplements modulate immune responses following heavy exertion (Nieman et al., 1997b, 2002b; Nieman, Peters, Henson, Nevines, & Thompson, 2000b), it should be clear that vitamin C must not be counted among the highly effective immune nutrients. 

Zinc + C, not protetive, but effective? While the evidence supplementing with a combination of vitamin C and zinc would protect you from upper respiratory tract infections (URTIs) is scarce, there are studies like Maggini et al. (2012) which indicate that the provision of a combination of 1000 mg vitamin C plus 10 mg zinc in patients with the common cold will lead to a nonsignificant reductionof rhinorrhoea duration (range 9 – 27%) was seen. Moreover, a pooled analyses of the two studies Maggini et al. conducted shows that "vitamin C plus zinc was significantly more efficient than placebo at reducing rhinorrhoea over 5 days of treatment" (Maggini. 2012). Furthermore, symptom relief was quicker and the product was well tolerated. Despite the fact that the subjects in these experiments were ordinary people, upping your zinc and vitamin C intake, when you've already caught a cold may help you to recover faster and thus get back to the grind earlier.

• Vitamin E: As Niemann et al. point out in their review of the efficacy of various immuno-nutrients, vitamin E functions primarily as a non-specific, chain-breaking antioxidant that prevents the propagation of lipid peroxidation. The vitamin is a peroxyl radical scavenger and protects polyunsaturated fatty acids within membrane phospholipids and in plasma lipoproteins.
  
  The effect of vitamin E supplementation on the inflammatory and immune response to intensive and prolonged exercise is largely unstudied and equivocal. Cannon et al. (1991) found that vitamin E supplementation of 800 IU/day for 48 days attenuated endotoxin-induced IL-6 secretion from mononuclear cells for 12 days after running downhill on an inclined treadmill. Singh et al. (1999) showed no effect of vitamin E supplementation (4 days, 800 IU/day) on the increase in plasma IL-6 following a 98 min treadmill run at 65 – 70% V_ O2max to exhaustion. Petersen et al. (2002) reported no influence of vitamin E and C supplementation (500 mg and 400 mg, respectively, for 14 days before and 7 days after) on the plasma cytokine response to a 5% downhill 90 min treadmill run at 75% VO2max.
  
  

  

  Figure 2: Chronic supplementation with 800 IU of vitamin E (as alpha-tocopherol) has significant negative effects on markers of lipid oxidation and inflammation in triathletes (Nieman. 2004).

  A 2004 study in the course of which triathletes competing in the Kona Triathlon World Championship race event received 800 IU/day of a-tocopherol for two months does even indicate that vitamin E can increase the degree of exercise induced lipid peroxidation and the amount of several cytokines in the blood following a triathlon.Against that background and in view of the previously cited ambiguous results, Niemann et al. (2006) rightly conclude that "vitamin E supplementation to counter immune suppression and oxidative stress in endurance athletes cannot be recommended" (Niemann. 2006).
• Vitamin D: For vitamin D a slightly different image emerges. It appears to be indisputable that athletes with low vitamin D levels are at higher risk of upper-respiratory tract infections - specifically during winter times (He. 2013).
  
  The results of clinical trials investigating the benefits of vitamin D supplementation, however, are less unambiguous. In non-athletes, the monthly administration of 100 000 IU of vitamin D did not reduce the incidence or severity of URTIs; and that despite the fact that the supplement brought the 25OHD levels of the healthy subjects up, significantly (Murdoch. 2012). A meta analysis by Bergman et al. (2013), however indicates that "vitamin D has a protective effect against RTI, and dosing once-daily seems most effective".
  
  

  

  Figure 3: Length of time to viral infection related to initial serum concentration of 25-hydroxyvitamin D.
  Shown are the results of the pharmacodynamic model relating 25-hydroxyvitamin D to length of time before a viral respiratory tract infection (Bergman. 2013)

  Bergamn et al. do yet also point out that "[d]ue to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution" (Bergman. 2013). Against that background it may be a good idea to at least make sure that you are in the "normal range" for vitamin D - irrespective of the fact that low levels may rather be a marker than a trigger of an increased susceptibility to infections that results from uncontrolled inflammation (vitamin D as a negative acute phase reactant | cf. Waldron. 2013).

Next to vitamins, many studies have described the use of proteins, such as whey for supplements or isolated amino acids like glutamine (Kreider. 2008; Cury-Boaventura. 2008).

Simply eating enough: It may sound funny, but in the end it's not surprising that a lack of readily usable energy makes you more susceptible to infections. Firstly, a general calorie restriction is often related to an insufficient intake of important micronutrients (Pendergast. 2002). And even if the intake of all micronutrients is adequate. Important immune factors such as glutamine are (ab-)used as a substrate to produce glucose in the liver and are thus no longer available to "feed" your immune cells. Accordingly it should not surprise you that Niemann and Bishop highlight in their review of "nutritional strategies to counter stress on the immune system in athletes" that the existing data indicates that "physiological stress to some aspects of the immune system is reduced when athletes use carbohydrate during intense exertion lasting 90 min or more" and their own experiments suggest that this means "that athletes using carbohydrate beverages during competitive events will lower their risk of sickness afterwards" (Nieman. 2006).

Figure 4: Mechanisms involving whey proteins as a source of different immunonutrients. (Cruzat. 2014).

In their previously cited review, Cruzat et al. included a nice graphical overview (Figure 4) of the mechanisms by which complete proteins and peptides and their individual amino acids effect the immune system of hard training athletes.

As you can see in Figure 4, Cruzat et al. put a particular emphasis on whey protein - for good reasons.

Firstly, whey contains all the "good" amino acids of which previous studies indicate that they may have direct beneficial effects on the immune system:

• Glutamine: As Cruzat et al. point out, "L-glutamine is probably the most widely recognized immuno-nutrient since it can be used as an oxidizable fuel, a substrate for nucleotide synthesis, a modulator of intermediary metabolism of amino acids, HSP expression and a component of GSH-mediated antioxidant defense" (see Figure 5 | Cruzat. 2014).
  
  Put simply glutamine is the food your immune cells thrive on. Accordingly scientists, athletes and coaches have speculated ever since the early 1990s that supplemental glutamine should be able to prevent the exercise induced immune impairments.
  
  

  

  Figure 6: 5g of glutamine per day led to significant reductions in the occurrance of infections in marathon, ultra-marathon, mid distance runners and rowers (Castell. 1996a).

  Why? Well, exercise depletes the amount of circulating glutamine and will thus "steal" the fodder your immune cells need to survive and function (Wernerman. 2008).
  
  And in fact, there are studies that support the logical conclusion that the repletion of the glutamine that has been burned as alternative fuel during a workout with 0.1 g/kg body weight ameliorates the exercise induced reduction of lymphocytes, and could thus eventually reduce the risk of URTI’s (Castell. 1997).
  
  In that, I deliberately used the conditional, because subsequent studies with fixed (20–30 g/day) or variable (0.3 - 0.5 g/kg body wt) doses of glutamine did not report similar outcomes (Castell. 1996b; Krzywkowski. 2001; Hiscock. 2002). Accordingly, Castell et al. write in their contribution to the BMJ A-Z Supplement review (ed. Newsholme. 2011):
  

  "Overall, there is no consensus or unifying concept to explain the efficacy of exogenous provision of glutamine alone on performance in athletes, although in combination with carbohydrate or other amino acids, significant improvements have been reported." (Newsholme. 2011)

  In other words: Benefits can't be guaranteed, but specifically when glutamine is ingested in amounts of at least 20g/day in addition to carbohydrates and protein supplements it appears as if it could be a useful dietary supplement for hard-training athletes.

Where are all the other supplements gone? As I wrote in the introduction, this list is not supposed to be comprehensive. Furthermore, agents like quercetin, beta-glucan, curcumin or astragalus may be backed by animal studies, their efficacy in human beings does yet warrant further testing - specifically in athletes (Nieman. 2006). Other supplements such as the often-used herb Echinacea purpurea have been shown to fail to stimulate the nonspecific immune response and may be useful only when you are already sick or if the preperations are administered intravenously (Schwarz. 2002).

• Arginine: No, this is not a mistake. L-arginine is in fact the #2 on the list of supplemental immune modulators for hard-training athletes. Needless to say that it's not arginine itself, but rather Nitric Oxide (NO) which acts as a mediator of inflammation and immune system activation in the human body (Krause. 2011 & 2012).
  
  As a SuppVersity reader, you know that arginine has little ergogenic effect. It has beneficial effects in diabetics and may offer benefits for people who want to control their blood pressure. As a immuno-modulator, however it is similarly ineffective as it is as an ergogenic. Benefits can only be expected if the blood levels of arginine are depleted and that is - even with heavy exercise - usually not the case.

Whey protein, however, is more than the sum of its amino acid parts. Yes, whey can contain up to 26% of BCAA, plus L-arginine, L-lysine, L-glutamine.

Figure 7: Effect of maltodextrin (filled square) and maltodextrin plus hydrolyzed whey protein enriched with glutamine dipeptide (filled triangle) supplementation on exercise-induced loss of membrane integrity and depolarized mitochondria in lymphocytes and neutrophils, which are essential for the response against viral infections, such as upper respiratory tract infections (URTI), in athletes after intense training (Cury-Boaventura. 2008).

Whey does yet also contain a range of powerful proteins / peptides, namely betalactoglobulin, alpha-lactalbumin, bovine serum albumin, lactoferrin, immunoglobulins (e.g. IgA), lactoperoxidase enzymes, glycomacropeptides, as well as vitamins such as vitamin D, and minerals such as Ca2+, of these...

• lactoferrin and lactoferricin, demonstrate direct anti-microbial activity and may thus protect you from infections,
• lysosome, lactoperoxidase and diverse globulins and peptides in whey provide a synergistic protective “cocktail” activity against viral and bacterial organisms (Ha. 2003), and
• sulphur-containing amino acids, such cysteine and taurine attenuate the reduction of intracellular GSH concentration induced by intensive exercise (Lands. 1999). 

For all three of them, it is yet not fully established to which extend they contribute to the proven immune-modulating effects of whey (note: the levels of these agents will be higher in concentrates compared to isolates, due to the increased number of processing steps). It is in fact likely that Cruzat et al. (2014) are right, when they say that its the cocktail of amino acids, proteins, peptides and other micro- and macronutrients, vitamins and minerals in whey protein that acts via direct and indirect pathways (e.g. via optimizing the redox status / GSH) on the immune function of athletes.

Bottom line: While there is good evidence for vitamin D supplementation (1,000-2,000IU/day in individuals with low levels and / or hard-working athletes during the winter months) and high doses of glutamine in hard working athletes. There is little doubt that the amino acid + protein + peptide coctail in whey proteins is the "goto supplement" you would choose if you wanted to use only one of the supplements discussed in this article.

Whey Beyond Brawn: 10+ Things You Probably Didn't Know Whey & Peptides That Form During its Digestion Can Do | learn more.

In that, a reasonable dosage suggestion would be similar to that for maximal muscle hypetrophy and range from 20-60g per day - with the higher dosage being consumed in 2-3 servings evenly spread accross the day. Furthermore, studies like the one by Cury-Boaventura et al. (2008) indicate that, during periods of intense training, it may be useful to add glutamine. Either in large amounts of 10-20g per day (5-10g on top of each serving of whey) or, as it was the case in said study, as a dipeptide which has a higher chance of making it past the splachnic bed and not ending up as "fuel" for your organs and or glyconeogenic substrate in the liver.

And yes, if you've already caught a cold, 1 gram (in divided doses) of the the good old vitamin C (if you want to along with 5-15mg of zinc) is useful, as well - along with plenty of rest and sleep, of course ;-) Comment on Facebook!

References:

• Cury-Boaventura, Maria Fernanda, et al. "Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide." European journal of applied physiology 103.3 (2008): 289-294.
• Bergman, Peter, et al. "Vitamin D and respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials." PloS one 8.6 (2013): e65835. 
• Castell, L. M., E. A. Newsholme, and J. R. Poortmans. "Does glutamine have a role in reducing infections in athletes?." European journal of applied physiology and occupational physiology 73.5 (1996a): 488-490.
• Castell, L. M., et al. "Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation." European journal of applied physiology and occupational physiology 75.1 (1996b): 47-53.
• Castell, Linda M., and Eric A. Newsholme. "The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise." Nutrition 13.7 (1997): 738-742. 
• Cruzat, Vinicius F., et al. "Amino acid supplementation and impact on immune function in the context of exercise." Journal of the International Society of Sports Nutrition 201.4 (2014): 11:61.
• Cury-Boaventura, Maria Fernanda, et al. "Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein enriched with glutamine dipeptide." European journal of applied physiology 103.3 (2008): 289-294.
• Ha, Ewan, and Michael B. Zemel. "Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review)." The Journal of nutritional biochemistry 14.5 (2003): 251-258.
• He, Cheng-Shiun, et al. "Influence of vitamin D status on respiratory infection incidence and immune function during 4 months of winter training in endurance sport athletes." Exerc Immunol Rev 19 (2013): 86-101. 
• Hiscock, Natalie, and Bente Klarlund Pedersen. "Exercise-induced immunodepression–plasma glutamine is not the link." Journal of Applied Physiology 93.3 (2002): 813-822. 
• Lands, L. C., V. L. Grey, and A. A. Smountas. "Effect of supplementation with a cysteine donor on muscular performance." Journal of Applied Physiology 87.4 (1999): 1381-1385.
• Krause, Mauricio S., et al. "L-arginine is essential for pancreatic β-cell functional integrity, metabolism and defense from inflammatory challenge." Journal of endocrinology 211.1 (2011): 87-97.
• Krause, Mauricio, et al. "Differential nitric oxide levels in the blood and skeletal muscle of type 2 diabetic subjects may be consequence of adiposity: a preliminary study." Metabolism 61.11 (2012): 1528-1537.
• Kreider, Richard B., et al. "Effects of ingesting protein with various forms of carbohydrate following resistance-exercise on substrate availability and markers of anabolism, catabolism, and immunity." Journal of the International Society of Sports Nutrition 4.1 (2007): 1-11.
• Maggini, S., S. Beveridge, and M. Suter. "A combination of high-dose vitamin C plus zinc for the common cold." Journal of International Medical Research 40.1 (2012): 28-42.
• Murdoch, David R., et al. "Effect of Vitamin D3 Supplementation on Upper Respiratory Tract Infections in Healthy AdultsThe VIDARIS Randomized Controlled TrialVitamin D3 and Upper Respiratory Tract Infections." Jama 308.13 (2012): 1333-1339.
• Newsholme, Philip, et al. "BJSM reviews: A to Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—Part 18." British journal of sports medicine 45.3 (2011): 230-232.
• Nieman, David C., et al. "Vitamin E and immunity after the Kona triathlon world championship." Medicine and science in sports and exercise 36 (2004): 1328-1335.
• Nieman, David C., and Nicolette C. Bishop. "Nutritional strategies to counter stress to the immune system in athletes, with special reference to football." Journal of sports sciences 24.07 (2006): 763-772.
• Nieper, A. "Nutritional supplement practices in UK junior national track and field athletes." British journal of sports medicine 39.9 (2005): 645-649. 
• Pendergast, David R. "Effect of dietary intake on immune function in athletes." Sports medicine 32.5 (2002): 323-337.
• Schwarz, Eveline, et al. "Oral administration of freshly expressed juice of Echinacea purpurea herbs fail to stimulate the nonspecific immune response in healthy young men: results of a double-blind, placebo-controlled crossover study." Journal of Immunotherapy 25.5 (2002): 413-420.
• Waldron, Jenna Louise, et al. "Vitamin D: a negative acute phase reactant." Journal of clinical pathology (2013): jclinpath-2012. 
• Wernerman, Jan. "Clinical use of glutamine supplementation." The Journal of nutrition 138.10 (2008): 2040S-2044S.

Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall

Have you ever felt nauseated after a workout? Or does your protein supplement gives you diarrhea only if you take it right after a workout? Both can be related to the toll  exercise can take on the integrity of your intestinal tract.

To be honest, I was quite surprised that I did not get a hell lot of hatemail in response to the the 'MSG heals the gut study' I posted last Sunday... Be that as it may, I feel sort of awkward to have opened Pandora's box without proving you with some betters tools than mono-sodium glutamate (MSG) to seal the box, or rather your leaky gut, again. Therefore I decided to post this mini-feature on a particular issue all of us will be dealing with: An exercise induced increase in gut permeability. As you are going to see, there are a lot of similarities to the 'classic' leaky gut, which is often implicated in the etiology of chronic inflammatory bowel diseases. In order to understand these similarities, but also the few, yet important differences, we will have to lay some theoretical groundwork.

"What exactly is a leaky gut?"

The easiest way to answer this question would be to say: "That's what everybody and his mama is talking about these days". This definition as concise (and precise) as it may be, is yet about as productive as the talk that's at its heart. So, instead of relying on hearsay, let's rather briefly recap how intestinal wall actually works.

Since the intestines are meant to let nutrients and fluid pass, a certain degree of leakiness is absolutely natural. Problems arise only, when the self-regulatory system is broken and/or the permeability exceeds a normal / healthy threshold (img. by Mariana Ruiz).

The mucosal layer of the intestinal tract is made up of epithelial cells, so-called enterocytes which are connected to one another by specialized proteins. These proteins form the tight junctions (TJ) - a term, you will probably have encountered numerous times before. The main constituents of this kit in between the enterocytes are proteins such as occludin, zona-occludens and claudins. Together, the array of enterocytes and the tight junction form the the intestinal barrier, which allows the absorption of nutrients and water, while preventing the translocation of harmful substances from the gut into the bloodstream.

The integrity of this barrier is influenced by the phosphorylation state of the proteins within the tight junctions.The exact interactions are compilcated and can be looked up elsewhere (Banan. 2005). What's important for you to realize is that during prolonged exercise which is necessarily accompanied by an increase in core temperature, cardiovascular and thermoregulatory responses compromise intestinal blood flow.

With the core temperature usually being lower than the temperature in your intestines, the temperature of your gut can easily approach 41°C during a workout.That's more than your epithelial cells can handle and can lead to structural damage of the 'patches' in the tight junctions + epithelial cell layer (Lambert. 1985).

HIIT veterans or weight lifters are not off the hook

Now, the last paragraph may have sounded as if only long endurance workouts like 10k-runs or marathons could entail damage to the intestinal cells. That's however not the case, since the redirection of the blood away from the splanchnic arteries and to the working muscle that's even more pronounced in high(er) intensity exercise, will initiate an ischaemia reperfusion cycle which can entail oxidative damage not during, but interestingly after the the workout, when the blood rushes back into the intestines (Wijck. 2011).

Take home message: There are two distinct pathways that contribute to the leaky gut during and after a workout (a) heat and (b) ischaemic/reperfusion stress. Both influcne the phosphorylation state of the proteins in the tight junctions and will thus increase the permeability of the gut lining.

It stands to reason that the combination of high intensity and long durations, as you will find it in an ultra-marathon runner, for example, is particularly detrimental to the integrity of the intestinal wall, so that it is not exactly surprising that (ultra-)endurance athletes have the highest prevalence (60-90%) of gastrointestinal distress that which manifests in the form of diarrhoea, nausea, stomach problems, bloating and intestinal cramps (Worobetz.1985; Peters.1999; Jeukendrup.2000)

There is more than one thing you can to to protect, heal and restore your gut integrity

The fact that a "leaky gut" is like an open door not just for exogenous toxins or live bacteria, but also for their 'endotoxic poop' is probably no news for you. In fact, it is also the reason why you want to either prevent the pathological increases in gut permeability, in the first place, and/or (re-)seal the gut as soon as possible after your workouts. In this regards, there are three fundamental and easily implementable strategies that should always be employed before you even think about using specific supplements:

• 

  Figure 1: HSP 70 offers protection against endotoxins (LPS) in vivo (top) and in vitro (bottom; Dokladny. 2010)

  Despite the possible ischaemic / reperfusion stress short high intensity exercise bouts like sprinting are generally less taxing on the integrity of the tight junctions than longer duration medium intensity aerobic workouts. Avoiding these particularly gut-stressing workouts and/or taking special precautions before and after marathons and other endurance events would thus be strategy #1 to keep the epithelial cell layer intact and pathogens and toxins from entering the circulation.
• The natural intracellular expression of heat shock proteins (HSPs) can protect the tight gut junctions during and/or help their restoration after a workout. Just like all our endogenous protection systems the production of HSPs can be trained. Giving your body the time it needs to accommodate by making small, but consistent steps towards longer and/or more intense workouts would therefore be strategy #2.
• That leaves us with strategy #3, of which I hope all of you will be using anyway - even if you have not been aware of its gut protective effect, yet: The provision of adequate fluid supply before, during and after a workout (Lambert. 2008).

As the workout durations become longer and longer and/or the respective intensities higher and higher, solely relying on your bodies self-healing capacity and adequate hydration may seize to work, though. Despite the fact that our bodies accommodate to the ever increasing demand for intracellular protection against heat stress by upregulating the HSP expression (athletes have higher HSP expression to a standardized endurance training protocol than normal individiuals; cf. Fehrenbach. 2000), there is - just as with about every adaptive response - a certain threshold, when hormesis, i.e. the beneficial adaptation to a manageable amount of stress, is no longer an option.

From "A" as in arginine to "Z" as in zinc - a list of things to keep the gut lining intact

While there has been quite a lot of research as of late into which dietary supplements and even regular foodstuff would be able to modulate the heat shock proteins in order to prefer the desired downstream benefits on gut integrity, the number of compounds of which it is reasonable to assume that they can actually make a difference is still very small:

• Colostrum supplementation to cell cultures has been shown to increase the expression of HSP-70 in human epithelial cells; studies with human subjects are rare and ambiguous:  While Marchbank et al., have been able to show that bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes (Marchbank. 2011), Buckley et al. actually observed detrimental effects of 8 weeks of bovine colostrum supplementation on the exercise induced gut permeability in runners (Buckley. 2009).The explanation for these discrepencies is not clear, but may be related to the longer duration / different intensity of the exercise protocols, or differences in the immunoglobolin, peptide or amino acid composition of the supplements.
• Zinc in general and specifically polaprezinc, a zinc based anti-ulcer drug, which has primarily been used in Japan as a means to seal leaky Japanese guts, show some promises, as in the treatment and prevention of increased intestinal permeabilty (Zhang. 2009). It is thought that zinc is critical for tight junction assembly and has been shown to be critical in the protection of the gut lining from the chronic toxic assault of alcohol (Zhong. 2010). That being said, you should keep in mind that alcohol will deplete your bodies zinc stores, so that it cannot be said, if someone with an adequate zinc intake would benefit to the same degree as a zinc deficient alcoholic. Moreover, as "natural" as they may be, even essential minerals like zinc don't come without potential side effects (cf. "After 120 Days Rodents on Diets Containing 2xRDA of Zinc Develop Metabolic Syndrome", read more).
• Glutamine has been used as treatment for patients suffering from irritable bowel syndrome and Crohn’s disease and has been shown to actively increase the expression of HSP70 in critically ill patients (Jonas. 1999; Ziegler. 2005).  
• Berberine could be an ideal addition to glutamine (thx to Maxim Okhrimenko for pointing that out in the comments); berberine does not only modulate the TNF-alpha response in the intestines and increases AKT, but has also been shown to maintain / rescue intestinal glutamine transport and glutaminase activity (Gu. 2009; Amasheh. 2010; Li. 2010; Niu. 2011)
• Probiotics are still an 'under-researched' newcomer and though there is some preliminary evidence pointing to the efficacy of probiotic therapy as a means of improving gut function and enhancing the integrity of the intestinal tight junctions, the ideal supplement regimen, as well as its long-term effects will still have to be elucidated in human studies. Studies by Ewaschuk et al. have yet already shown that the impact factors released from Bifidobacteria infantis can offer a certain degree of protection against experimentally induced colitis in rodents (Ewaschuk. 2008). As far as exercise specific studies are concerned, a recently published paper by Lamprecht et al. is probably the first peer reviewed human study to report allegedly "borderline significant" beneficial effects on gut permeability (measured only indirectly by quantifiying the zonolin conent of the feces) and TNFalpha expression in response to a multi-species probiotics (1010 CFU/day, Ecologic®Performance orOMNi-BiOTiC®POWER) in 23 trained men (Lamprecht. 2012; the study was partially funded with a grant from Winclov, the manufacturer of the respective supplements).
• Butyrate, yet not all short chain fatty acids, have recently been found to decrease gut permeability (Ferreira. 2012). Both data from human studies, as well as exercise specific data is yet still absent.
• Hydroxypropyl methylcellulose (HPMC), which is a non-fermentable fiber, has been shown to protect rodent guts from a high fat diet induced increase in gut permeability (Kim. 2012), as in the case of butyrate its efficacy (and when you think about athletes, tolerability) will yet still have to be confirmed in human trials.
• L-Arginine (and AAKG) as a source of nitric oxide, which is necessary to protect the gut barrier from invaders could have a protective effect, as well (Quirino. 2012); and though this effect is not exercise specific, we know that arginine requirements increase in states of chronic stress, it would therefore be logical that supplementation with l-arginine, or even better AAKG, which comes with a precursor to glutamine will have beneficial effects on the tightness of the guts of intensely training athletes, as well (suggested read: BCAAs, glutamine and ammonia detox) .
• Oats, maybe due to their beta glucan content and their ability to increase the production of short-chain fatty acids in the large intestine, oats offer protection against alcohol induced increases in tight junction permeability (Tang. 2009); exercise specific studies have yet to be conducted, though.Personally I would yet not be surprised if this would turn out to be very effective (note: as long as they are not cross-contaminated, oats are 100% gluten-free)
• Goats milk (powder) has been shown to be equally effective as colostrum in reducing heat and thus most likely exercise induced gut permeability (Prosser. 2004)
• Lactoferrin, a multifunctional protein of the transferrin family that is present in milk may have protective effects against LPS-mediated intestinal mucosal damage and impairments of the barrier function in intestinal epithelial cells (Hirotani. 2008)
• Vitamin A in adequate amounts is necessary to maintain gut integrity; it is likely that this is all the more true if gut integrity and immune function are additionally challenged by strenuous exercise (Quadro. 2000)

I guess, I could find even more supplements (and foods) that may help you protect or restore your gut lining, but let's be honest: As important and beneficial eating and supplementing the right things may be, all your efforts would be foiled if you eat foods and supplements that will have the opposite effect on your gut lining. So here is the complementary and likewise non-exhaustive list of stuff you'd better avoid (at least in high doses) if you want to keep your tight junctions intact and your gut from becoming leaky:

Figure 2: Gliadin peptides induce the release of zonulin which in turn interacts with the tight junctions and increases the diffusion of small molecules (∼350 Da) across the cell membrane. Whether the tight junctions open up wide enough to allow for free diffusion of whole gliadin peptides, whose molecular weight is at least 2000 Da, remains to be determined, though (Heyman. 2011)

• Alcohol will wreak havoc on the permeability of your intestines; probably in consequence of its depleting effect on ileal zinc concentration (Zhong. 2010).
• Gliadin (in wheat/gluten) does actively promote the release of zonolin and the widening of the tight junctions (see figure 2); whether you will notice that or not, depends on the occurrence and extent of an immune response as it is characteristic for Celiac patients. I guess, it's actually not necessary to say that all sorts of other allergens, respectively the ensuing inflammatory response to being exposed to them will have detrimental effects on the integrity of your gut, as well, right?
• ALA, EPA and DHA the dietary omega-3 fatty which may help sooth tight junction permeability in states of chronic inflammation will actually increase it, when the baseline inflammation is already low or they are consumed in excess (Usami. 2001; Roig-Pérez. 2010)
• Copper and iron increase tight junction permeability of caco-2 cells via distinct mechanisms (Ferruzza. 2002)
• Capsaicin, piperine and other hot spices do not only cause a burning sensation in your mouth, it literally burns your intestinal cell lining, as well (Johri. 1992; Tsakura.2007)
• Quercitin by blocking the increase in HSP-70 will increase the suceptibility of your gut to exercise induced increases in permeablity (Kuennen. 2011)
• NSAIDs like aspirin and ibuprofen increase the permeability of the gut ad amplify the potentially detrimental effects of exercise (Lambert. 2007)

Obviously, only few of the last mentioned offenders are exercise specific, but if you start working out with already compromised gut integrity, you can hardly complain if a couple of grams of glutamine, or whatever else you may have picked from the previous list, don't effectively protect your intestinal wall from damage. What's even more important though is that you understand the Janus-faced nature of anti-oxidants and anti-inflammatory compounds. As beneficial as they may be in situations of chronic or acute pathologic inflammation, NSAIDs, quercitin and even your beloved omega-3 can eventually extinguish the 'controlled fire' your body needs to keep all immune and metabolic functions simmering along nicely (suggest reads: "Are you stressed enough for a longer life?" and "Inflammation is a True Fat Burner").

References:

• Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD. TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci. 2010 Dec 1;123(Pt 23):4145-55.
• Banan A,Zhang LJ, Shaikh M,et al. theta Isoform of protein kinase C alters barrier function in intestinal epithelium through modulation of distinct claudin isotypes: a novel mechanism for regulation of permeability. J Pharmacol Exp Ther. 2005; 313:962–82.
• Buckley JD, Butler RN, Southcott E, Brinkworth GD. Bovine colostrum supplementation during running training increases intestinal permeability. Nutrients. 2009 Feb;1(2):224-34.
• Dokladny K, Lobb R, Wharton W, Ma TY, Moseley PL. LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones. 2010 Mar;15(2):153-63. Epub 2009 Jun 24. 
• Ewaschuk JB, Diaz H, Meddings L, Diederichs B, Dmytrash A, Backer J, Looijer-van Langen M, Madsen KL. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol Gastrointest Liver Physiol. 2008 Nov;295(5):G1025-34. 
• Ferruzza S, Scacchi M, Scarino ML, Sambuy Y. Iron and copper alter tight junction permeability in human intestinal Caco-2 cells by distinct mechanisms. Toxicol In Vitro. 2002 Aug;16(4):399-404. 
• Gu L, Li N, Li Q, Zhang Q, Wang C, Zhu W, Li J. The effect of berberine in vitro on tight junctions in human Caco-2 intestinal epithelial cells. Fitoterapia. 2009 Jun;80(4):241-8.
• Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012 Sep;61(9):1355-64.
• Hirotani Y, Ikeda K, Kato R, Myotoku M, Umeda T, Ijiri Y, Tanaka K. Protective effects of lactoferrin against intestinal mucosal damage induced by lipopolysaccharide in human intestinal Caco-2 cells. Yakugaku Zasshi. 2008 Sep;128(9):1363-8.
• Jeukendrup AE,Vet-Joop K, Sturk A,et al. Relationship between gastrointestinal complaints and endotoxaemia, cytokine release and the acute-phase reaction during and after a long-distance triathlon in highly trained men.Clin Sci (Lond). 2000;98:47–55. 
• Jonas CR, Ziegler TR. Potential role of glutamine administration in inflammatory bowel disease. Nestle Nutr Workshop Ser Clin Perform Programme. 1999;2:217-30.
• Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine-mediated changes in the permeability of rat intestinal epithelial cells. The status of gamma-glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharmacol. 1992 Apr 1;43(7):1401-7.
• Kim H, Bartley GE, Young SA, Davis PA, Yokoyama W. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice. Mol Nutr Food Res. 2012 Sep;56(9):1464-76. 
• Kuennen M, Gillum T, Dokladny K, Bedrick E, Schneider S, Moseley P. Thermotolerance and heat acclimation may share a common mechanism in humans. Am J Physiol Regul Integr Comp Physiol. 2011 Aug;301(2):R524-33.
• Lambert GP, Gisolfi CV, Berg DJ, Moseley PL, Oberley LW, Kregel KC. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol. 2002 Apr;92(4):1750-61; discussion 1749. PubMed PMID: 11896046.
• Lambert GP, Boylan M, Laventure JP, Bull A, Lanspa S. Effect of aspirin and ibuprofen on GI permeability during exercise. Int J Sports Med. 2007 Sep;28(9):722-6.
• Lambert GP, Lang J, Bull A, Pfeifer PC, Eckerson J, Moore G, Lanspa S, O'Brien J. Fluid restriction during running increases GI permeability. Int J Sports Med. 2008 Mar;29(3):194-8.
• Lamprecht M, Bogner S, Schippinger G, Steinbauer K, Fankhauser F, Hallstroem S, Schuetz B, Greilberger JF. Probiotic supplementation affects markers of intestinal barrier, oxidation, and inflammation in trained men; a randomized, double-blinded, placebo-controlled trial. J Int Soc Sports Nutr. 2012 Sep 20;9(1):45. 
• Li N, Gu L, Qu L, Gong J, Li Q, Zhu W, Li J. Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells. Eur J Pharm Sci. 2010 Apr 16;40(1):1-8.
• Marchbank T, Davison G, Oakes JR, Ghatei MA, Patterson M, Moyer MP, Playford RJ. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. Am J Physiol Gastrointest Liver Physiol. 2011 Mar;300(3):G477-84.
• Musch MW, Sugi K, Straus D, Chang EB. Heat-shock protein 72 protects against oxidant-induced injury of barrier function of human colonic epithelial Caco2/bbe cells. Gastroenterology. 1999 Jul;117(1):115-22. 
• Niu L, Qiao W, Hu Z, Li N, Huang Q, Gong J, Li Q, Zhu W, Li J. Berberine attenuates lipopolysaccharide-induced impairments of intestinal glutamine transport and glutaminase activity in rat. Fitoterapia. 2011 Apr;82(3):323-30.
• Peters HP, Bos M, Seebregts L,et al. Gastrointestinal symptoms in long-distance runners, cyclists, and triathletes: prevalence, medication, and etiology. Am J Gastroenterol. 1999; 94:1570–81. 
• Prosser C, Stelwagen K, Cummins R, Guerin P, Gill N, Milne C. Reduction in heat-induced gastrointestinal hyperpermeability in rats by bovine colostrum and goat milk powders. J Appl Physiol. 2004 Feb;96(2):650-4.
• Quadro L, Gamble MV, Vogel S, Lima AA, Piantedosi R, Moore SR, Colantuoni V, Gottesman ME, Guerrant RL, Blaner WS. Retinol and retinol-binding protein: gut integrity and circulating immunoglobulins. J Infect Dis. 2000 Sep;182 Suppl 1:S97-S102.
• Roig-Pérez S, Cortadellas N, Moretó M, Ferrer R. Intracellular mechanisms involved in docosahexaenoic acid-induced increases in tight junction permeability in Caco-2 cell monolayers. J Nutr. 2010 Sep;140(9):1557-63.
• Ruiz M. Wikipedia contributors, 'Tight junction', Wikipedia, The Free Encyclopedia, 10 November 2012, 07:58 UTC, <http://en.wikipedia.org/w/index.php?title=Tight_junction&oldid=522300074> accessed 25 November 2012
• Tang Y, Forsyth CB, Banan A, Fields JZ, Keshavarzian A. Oats supplementation prevents alcohol-induced gut leakiness in rats by preventing alcohol-induced oxidative tissue damage. J Pharmacol Exp Ther. 2009 Jun;329(3):952-8.
• Tsukura Y, Mori M, Hirotani Y, Ikeda K, Amano F, Kato R, Ijiri Y, Tanaka K. Effects of capsaicin on cellular damage and monolayer permeability in human intestinal Caco-2 cells. Biol Pharm Bull. 2007 Oct;30(10):1982-6.
• Usami M, Muraki K, Iwamoto M, Ohata A, Matsushita E, Miki A. Effect of eicosapentaenoic acid (EPA) on tight junction permeability in intestinal monolayer cells. Clin Nutr. 2001 Aug;20(4):351-9.
• van Wijck K, Lenaerts K, van Loon LJ,et al. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men.PloS One. 2011; 6.
• Worobetz LJ,Gerrard DF. Gastrointestinal symptoms during exercise in Enduro athletes: prevalence and speculations on the aetiology.N Z Med J 1985; 98:644–6.
• Zhang B, Guo Y. Supplemental zinc reduced intestinal permeability by enhancing occludin and zonula occludens protein-1 (ZO-1) expression in weaning piglets. Br J Nutr. 2009 Sep;102(5):687-93.
• Zhong W, McClain CJ, Cave M, Kang YJ, Zhou Z. The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol. 2010 May;298(5):G625-33. 
• Ziegler TR, Ogden LG, Singleton KD, Luo M, Fernandez-Estivariz C, Griffith DP, Galloway JR, Wischmeyer PE. Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med. 2005 Aug;31(8):1079-86

Ask Dr. Andro: Are Vitamin Supplements Bad For Me (2/2)? 3+1 = 666! The Raw Data Truth about the "Vitamins Kill!" Offspring of the Iowa Women's Health Study

Image 1: "Please Dr. Andro tell me I can keep taking my essential multivitamin! I am just too busy to eat healthy..."

I must admit that I feel kind of awkward as I am about to defend one of those supplements, I consider to be the most dispensable within the dietary regimen of a physical culturist: the so-called multi-vitamin! In essence these small, and lately more often than not large pills do not even fall into the category supplement. With dose-equivalents way beyond what you would actually need, "multivitamins" are not even "replacements", they are madness or, I should say, the mad outgrowth of the prevalent "more is more" mentality that is beginning to harm us on every level of our society... but I am digressing, here. Let's take a look at the actual study which brought about such an upheaval in the supplement-addicted health community on the Internet.

Dietary Supplements and Mortality Rate in Older Women

Image 2: Is this you? No? Maybe she is "The Average American", then? No? Well, but the study says "vitamins are bad for YOU" and she could be one of the subjects (img. medscape.org)

The title alone, actually made me click the study away, back in the day when I first hit upon it, on one of my regular searches for new stories on the medical databases of the World-Wide-Web; and unless you are an old women (I would hope there were some older women reading the SuppVersity, but I guess there are none), you should have disregarded the study, as well. After all, we all know how the game changes after menopause and guess what, of those women, 98.6% were post-menopausal (in case you ever see studies done on ovariectomized rodents, remember that those are "menopausal", too ;-). Ah, and in case you are a post menopausal women with Africa-American or Hispanic background, there is likewise little reason for you to read on, because 99.2% of the women in the study were white (if you question whether or not ethnicity really matters, when it comes to the health effects of vitamins, I suggest you take a look at some reviews like Carmel. 1999).

Now, if you are still with me at this point, I guess that you either are a post-menopausal white woman, or - and I suppose that this will be the case for the majority of you - you have been agitated by the heated debate on the net (and even regular mass-media) in the last couple of days and want someone to tell you that you did not reduce your life-expectancy by -15% by religiously taking your "essential" *rofl* multi-vitamin, everyday. We will see, whether I can be this person (in case it turns out I am not, I have seen more than enough "gurus" you will tell you exactly that, if you promise to buy their "all natural" or "superior source" product in the future).

The Iowa Women's Health Study - Mrs "not so average" American

So, let's see. What we have here is an offshoot of the Iowa Women's Health Study (IWHS), which is one of those highly over-estimate surveys, the media loves, because they boast of ten-thousands of "participants". In the case of the IWHS, "41836 women aged 55 to 69 years"... well, at least that were the women the scientists send their little questionnaires to back in 1986. Interestingly, this is also where the first bias (i.e. a deviation from "objectivity") came into play:

Respondents were slightly younger, had lower body mass index (calculated as weight in kilograms divided by height in meters squared), and were more likely to live in rural areas compared with nonrespondents.

So instead of the average American "older woman", the scientists suddenly had the "slightly younger" not just as obese, better off American older women, as their study object. Moreover, the number of participants dropped to 38772 women or, in other words, the scientists "lost" 7.3% of their study population even before the study actually began. Now, of those, the Mursu et al. selected 29230, who were the "elite" which responded to both the initial 1986 and the 2nd 1997 follow-up questionnaire.

Failure 1: Not representative of "The Average American"

"Ladies, give me as little information about your supplements as possible, please!"

The latter, i.e. the questionnaire, assessed the use of 13 supplements:

• multi-vitamins; 
• vitamins A, beta-carotene, B6, folic acid, B complex, C, D, and E; 
• iron, calcium, copper, magnesium, selenium, and zinc

Now, the scientists show off their wealth of knowledge and state that "[d]ifferent forms of vitamin D, cholecalcif-erol (D3) or ergocalciferol (D2), were not distinguished". While this is obviously important, it would have been even more important to distinguish between different forms of vitamin B6 (pyridoxin vs. P5P), B complex (you can have a complete one, one with equal doses, one particularly high in one B vitamin, etc.), vitamin E (I suppose you read the first installment?), iron (heme, non-heme, chelated, etc.), copper / magnesium, selenium, and zinc (oxide, chelated, etc.), because we know that these different forms of vitamins and minerals are not only differentially absorbed, but also exhibit differential effects on our health and well-being.

Failure 2: Ignorance towards the fact that
not all vitamins / minerals with the same label are created equal

And as if this had not been enough, the scientists did not even care if the ladies popped 1 or 23 of their beta carotene (I hope you do not still believe you can take endless amounts of that orange poison), magnesium, folic acid and B-complex pills.

Failure 3: Careless ignorance towards dosages

Raw foods are dangerous and so is raw data

Hence, the scientists got a set of data that was full of holes from a group of women who are by no means representative of "The Average American" (let alone every human being) - what did they do next? Well, obviously "raw data" is as dangerous as raw meat (or even raw milk), that is why the next step for every good scientists is data processing. In that Mursu et al. were particularly skilful as far as not revealing what they actually did was concerned:

In the minimally adjusted model, we adjusted the association for age and energy intake; in multivariable adjusted model, version 1, we additionally adjusted for educational level, place of residence, diabetes mellitus, high blood pressure, body mass index, waist to hip ratio, hormone replacement therapy, physical activity, and smoking status. For multivariable adjusted model, version 2, we added intake of alcohol, saturated fatty acids, whole grain products, fruits, and vegetables.

Even, or I should say, especially for a physicist, who is a 75% mathematician, the idea that by some sort of mathematical magic you could reliable subtract out all those influence, so that you get the "real picture" of what is going on, with an average human being is so hilarious that I avoid any further comment. Everything that goes beyond the "minimal adjustment" is so full of speculative hypothesis and mainstream paradigms (like "Whole grains are good for you! The more, the better!") that I will simply ignore this data... unfortunately these results of "3+3 = 666" mathematical manipulation were what the scientists (in their press releases) highlighted as their main results and what was accordingly taken up by the laymen (initially I wanted to write idiots, but that would be unfair, because laymen they are) in the editorial offices of the mass media.

Failure 4: Over-"analysis" of the data

Let's get to the raw truth

This would not be the SuppVersity, if I did not have something to offer that goes beyond the angry rants and criticism (see above) you probably have read elsewhere, anyways. So, I went through the pains of compiling and comparing the "real", i.e. the N=X data and not the calculated hazard ratios for you.

Figure 1: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking vitamin A, beta carotene, vitamin C, vitamin D, vitamin E, and finally the multivitamins on overall mortality (data calculated based on Mursu. 2011)

Now, I want you to take a close look at the data for vitamin A, beta carotene, vitamin C, vitamin D, vitamin E, and finally the multivitamins. I don't know what you see, but I see only vitamin A and beta carotene scratching at the increased mortality margin of 1.0 (cf. dotted red line in figure 1). And, just for a better understand, two examples:

• the 1.04 as for vitamin A (minimally adjusted) in 2004-08 indicates a +4% higher risk and 0.80,
• the 0.80 for vitamin E (raw data) in 2004-08 indicates a -20% decrease in mortality risk

So, what would you say, how "dangerous" is taking vitamin pills if you do not process the data to death? Interestingly, things get really nasty, from here. And moreover, they get nasty, where you probably would not have expected it unless you are a very diligent student of the SuppVersity and are thus aware that messing with the methylation cycle via B6 or folic acid supplementation for no reason is not a good idea.

Figure 2: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking vitamin B6, folic acid, B-complex, calcium, and magnesium on overall mortality (data calculated based on Mursu. 2011)

Given the fact that an increasing amount of "old" people are taking magnesium supplementation, I would say that in this case the age-adjustment is probably necessary - if you also consider that back in the 1980s this bias was smaller, since people were not told that taking mg supplements would be necessary for older folks, the respective adjustment will be "too small" and thus I would simply ignore the fact that the 1996 value still signifies a +2% greater risk of dying when you take a magnesium supplement (add to that that the study participants could have taken magnesium in the 10x recommended dosage and the scientists would not know that /see comment on dosage, above). What really surprises me, though is the enormous benefit that is (even in the raw data) associated with calcium supplements - 22% reduced risk according to raw data and 21% reduced risk with age/energy adjustment - impressive!

Figure 2: Raw data and minimally adjusted (age and caloric intake) data on the effect of taking iron, copper, zinc, and selenium on overall mortality (data calculated based on Mursu. 2011)

Last but not least - the worst offenders, the dreaded "heavy metals" ;-) Ok, I guess iron really is a bad guy (at least for post-menopausal women), but even copper, which has gotten such a bad rep, lately turns out to come pretty handy in the female part of the aging American population, ... interestingly only in the early to late 2000s - how come? I'll leave it up to you to make up your mind on this and other questions, but I assume that now, that you know the raw truth, you will not blindly follow Bjelakovic's campaign to "wake up [regulatory authorities] to their responsibility to allow only safe products on the market" (Bjelakovic. 2011), but rather scrutinize his "invited comment" to the Mursu study, which was published in the same issue of the Archives of Internal Medicine and has caused such an upheaval among the increasingly health conscious American and International public.

On Short Notice: PWO EAA Supps for Young & Old, Indoor Pools & Low Testosterone, Life-Savingly Low T3/rT3 Ratios, Copper-Zinc-Manganese, Lifting for Prostate Health +More

Image 1: It's neither just as much, nor just as serious, but I would still venture the guess that it will take you more than 30s to digest today's installment of "On Short Notice" - despite the fact that the new format has no lengthy "short news", anymore ;-)

For this installment of "On Short Notice" I have decided to go a somewhat different route than before: Originally, the first post you would have read after this short introduction would have dealt with the potential negative health effects of homogenized milk. What was intended as a "on short notice" item, did however become lengthier and lengthier, until it finally turned into an "almost full-length post" (a slightly extended version of this article is going to be published on Monday). This "incident" made me revisit the last installments of this series only to realize that the majority of the supposedly "short" On Short News items had become "almost full-length posts" and were thus either somewhat overblown or still to short for what the study / topic had to offer...

To cut a long story short, I decided to stick to the very short items, formerly known as "On Very Short Notice" from now on.  If you have any reasonable objections against this practice, feel free to use the comment area of this post to complain. Do not forget, however, that you can still request a longer article on any particularly interesting topic or simply discuss the blurbs with me and others here or on the SuppVersity Facebook wall... Ready? Let's roll!

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  Figure 1: Ratio of muscle intracellular leucine to blood leucine concentration in response to
  resistance exercise and ingestion of 20 g of essential amino acids in young and older men.

  Older physical culturists can't "eat to grow" benefit from EAA ingestion - at least not to the same extend younger lifters do. And while this alone would hardly qualify as "news", the, or I should say one of the underlying reasons Jared M. Dickinson and his colleagues discuss in a paper that's scheduled to be published in the next issue of the Journal of Clinical Nutrition certainly is (Dickinson. 2012).
  One hour after the 7 young (30 ±2yr) and 6 old (70 ±2yr) male "recreationally active" study participants had performed a standardized leg training program consisting of 8 sets of 10 reps on a Cybex leg extension machine at an intensity of 70%RM (3 min rest between sets) Dickinson et al. supplied them with a 500ml of a fluid that contained 20g of leucine enriched essential amino acids (EAA) (exact composition: histidine 8%, isoleucine 8%, leucine 35%, lysine 12%, methionine 3%, phenylalanine 14%, threonine 10%, and valine 10%). In the hours following the leg training the scientists measured the amino acid flux and took muscle biopsies from the vastus lateralis to quantify the amino acid transporter (the "shuttle" that carries the amino acids from the blood stream into the muscle) expression in the trained leg muscles of their subjects.
  Contrary to what happened in the younger subjects, the expression of the transporter proteins was not further augmented (over exercise alone) in response to the ingestion of the EAA supplement in the older study participants. Consequently, the restoration of the intra- to extracellular amino acid ratio which was complete after 5h in the young subjects took more time and was not completed, when the third biopsy was taken at T=5h in the older subjects (see figure 1). A result, which (re-)emphasizes the paramount importance of physical activity in older people not just to become stronger, but also to ward off sarcopenia (=muscle loss) and subsequent frailty!

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  Figure 2: Unadjusted (top, middle) and adjusted (bottom) testosterone levels in adolescent boys depending on their exposure to chlorinated indoor-pool water before the age of 7y (bottom) and 10y (top, middle) respectively.

  Michael Phelps & Co at high risk of low testosterone - That's at least what we'd have to conclude from a 2011 paper that was published in the International Journal of Andrology by Nickmilder et al. who found that there is a clearcut association with early life exposure to chlorinated indoor-pool water and low testosterone levels in adolescence (and probably later in life, although that was not part of the study; cf. Nickmilder. 2011)
  As the data in figure 2 shows, the association with lower testosterone levels is most pronounced (p < 0.01) when the data was adjusting for inhibin B, FSH, age, time of blood sampling and breastfeeding (figure 2, bottom). With p < 0.05 (=5% chance that this is just coincidence) even the unadjusted values for pool water exposures of >250h before the age of 7 years were however statistically significant and as the scientists point out probably a result of the prolonged exposure of the "highly permeable scrotum" (Nickmilder. 2011)  to chlorinated water.
  

  Intriguingly, Bob Weinhold mentions in his otherwise rather critical comment on the study that Shanna Swan, a professor of preventive medicine at the Mt. Sinai School of Medicine, did not just criticize the "paucity of evidence from other studies", but also her hint at "effects from bath water exposures" as potential confounding factors (Weinhold. 2012). Against that background I suggest you go and take a very close look at the label of whatever cosmetic products you pour into your (male) children's bathwater.

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  Image 2: The dreaded low T3/rT3 ratio appears to be life-saving for critical ill patients. And when you come to think about it, it could well be a "natural mini coma" by which your body diverts all available resources to the one thing that's certainly more important than having a six pack: SURVIVAL!

  Low T3/rT3 ratio protects critical ill from death! While 1000s of visitors of various bulletin boards and discussion groups on the Internet are whining about a too low ratio of the "active" to the "inactive" form of triiodothyronine, the observation Marijke Gielen and her colleagues made, when they studied the chance of critically ill patients to be released early and alive from hospital, would suggest that rT3 is way more than a nasty millstone around the neck of (over-)dieters. After all, Gielen et al. found that the patients with the best blood glucose control and lowest T3/rT3 ratios had a +19% increased chance of being released early and alive (Gielen. 2012). An increase in the T3/rT3 ratio, on the other hand, was independently of glucose management, associated with a -14% lower chance of being released early and alive!
  I guess that this should be reason enough to rethink the generally touted "uselessness of rT3", wouldn't you agree? After all, it could well be that it is the rT3 induced metabolic slowdown that allowed for optimal recovery - much similar to the artificial coma physicians will induce in burn victims or other critically patients to have them recover faster / at all. This would yet also imply that having a very low T3/rT3 ratio is - as I've previously mentioned, by the way - a good indicator of other, non-thyroid related pathologies you should better try to spot and take care of before they will eventually show up and turn you into a subject for a follow up study for Gielen et al. (related: "T4+T3 Combination Therapy Instead of T4 Mono-Therapy")

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  Figure 3 (Zhu. 2012): Vitamin D3 is converted to the active metabolite 1,25(OH)2D3 by sequential 25-hydroxylation and 1a-hydroxylation.

  Slow conversion of D3 to 25-OHD in the obese suggests: Low vitamin D is a result of obesity - not vice-versa! Within the past decade(s) many scientists have observed correlations between higher adiposity and lower vitamin D levels (e.g. Arunabh. 2003). Only within the last 5 years or so, however, those results have been interpreted as "scientific evidence" that low vitamin D levels play a causative role in the current obesity epidemic. First evidence for the opposite, i.e. a causative relationship between obesity and the occurrence of chronically low systemic vitamin D levels in obese individuals (90%+ of the obese women in the study had 25OHD level <50 nmol l⁻¹; Wamberg. 2012), does yet come from a study that has been published in the International Journal of Obesity a couple of weeks ago.
  According to the Wamberge et al. present in their paper, the occurence of low 25(OH)D levels in the sera of obese individuals is a direct consequence of the sluggish bioactivation of vitamin D3 in the subcutaneous adipose tissue of obese patients. The latter is due to the -71% and -49% reduced expression of the two of the enzymes from the cytochrome P450 enzyme cascade (25-hydroxylase and 1α-hydroxylase, to be precise, see figure 3), which are responsible for the conversion of dietary or skin-derived (after sun exposure) vitamin D3 to 25(OH)D, which is the form of "vitamin D" your doctor will usually measure, and the "active" form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)(2)D(3) aka calcitriol.

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  Image 3: That's what active prostate cancer prevention can look like - no vaccine necessary!

  Heavy lifting protects against prostate cancer! This is the result of yet another of a whole host of studies which finally acknowledge the value of weight training with respect to all sorts of health benefits that have previously been ascribed to aerobic training only (Teixeira. 2012). Published ahead of print in the online version of the Scandinavian Journal of Medicine & Science in Sports the paper by Teixeira et al. is the first one to report that strength training can reduce the risk of prostate cancer by (re-)establishing a healthy balance between natural cell death and growth.
  In the course of a 91-day period a group of rodents were exposed to a daily "weight lifting regimen" (=jumping, 4x10 jumps with 50–70% of their body weight strapped to the thorax and 60–s rests between sets). This torture lead to an increase in corticosterone (=cortisol), DHT and testosterone levels, and brought about a healthier ratio of cell growth to apoptosis in the prostates of the animals than it was present in the age-matched sedentary control.

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  Figure 4: Building muscle requires more than just pumping existing fibers full of protein (click on the image to read up on the details)

  Scientists confirm Intermittent Thoughts on Building Muscle: Myostatin allows cells to "blow up", but does not facilitate structural changes. What's funny though, is that Lee et al. obviously feel that this is a great thing; and while it may actually be in the context of sarcopenia (pathological muscle dystrophy), where agents that block myostatin could proof very valuable tools, it just confirms that these agents are of little use, if not counterproductive for athletes and physical culturists who would always have to be on the look-out not to outgrow the necessary (re-)construction process, of which I have argued in the Intermittent Thoughts on IGF-1 an Its Splice Variants, already that it is necessary to keep the ever-growing muscles functional.
  So, in case you have a few vials of a real myostatin inhibitor lying around (not the hilarious egg-derived supplement that was sold a couple of years ago by snake oil vendors), you better talk to your medical practitioner about some growth hormone, as well, if you don't want to end up huge, but so weak that you can't make it up the five stairs in front of your gym ;-)

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  Image 4: While some experts say otherwise it appears illogical that the increase in breast tissue density, that's characteristic of women with a non-android body fat distribution would increase breast cancer risk. The majority of studies still ascribes a much higher increase in cancer risk to abdominal obesity (=android fat).

  Silicon boobs? Not necessary if you stay in shape! While the overall size still is a matter of genetics, the density of the female breast shows such a strong negative association with the android : gynoid ratio in young women (one standard deviation up corresponds to a -20% reduction in dense breast tissue; Dorgan. 2012) that it would seem as if simply staying in shape and thus avoiding the accumulation of body fit in the "unfemale" android areas could would (other factors like breastfeeding etc. aside) save one or another woman from a still very much underestimated and by no means just monetarily costly operation (cf. Bolton. 2012). And let's be honest: What are those silicon balls worth anyway, when the blubber starts shortly beneath? What certainly is bad news for the adolescent obesity generation , though is that childhood obesity is an even stronger predictor of low amounts of dense breast tissue. Even after adjustment for adult obesity each BMI z-score, i.e. one standard deviation upwards, was associated with a -27% decrease in tender breast tissue.
  Against that background it appear dubious, whether or not the often touted association between dense breast tissue and breast cancer risk is by any means a causative one... after all Abu-Abid et al. report in their review on the literature that abdominal obesity, i.e. an android body fat pattern is one of the best predictors of increased risk for all cancers (Abu-Abid. 2002).
• Are manboobs a sign of intelligence? Could be if we put any faith into the relation between the size of your hippocampus and your intellectual capacity, the findings Janine Bayer and her mostly female colleagues (this could be important, who knows maybe this is a feminist conspiracy!?) report in their latest paper on the effects a certain genetic polymorphicism (rs700518) in the aromatase enzyme CYP19A1 will have on both systemic as well as hippocampal estrogen levels and had the volume of the posterior hippocampal gray matter (Bayer. 2012). Unfortunately most manboobs today are a simple result of overaromatization due to obesity and whether this is a hallmark feature of superior intelligence appears at least questionable to me (suggested read: "Chest Fat, Bitch Tits, Chesticles and How to Get Rid Off Them")

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  Image 5: 1x 1g of taurine = 1.5% faster 3k-times in trained middle distance runners - another benefit of the underrated sulfur amino acid, taurine

  Taurine works for 3k-runs as well that's the simple message of a recently published study by Balshaw et al. In the randomized, double-blinded crossover experiment the ingestion of 1,000mg of taurine immediately prior to a 3km run increased the time-trial performance of the eight trained middle-distance runners by statistically significant 1.5%, on average (Balshaw. 2012); this does allegedly not sound like much, but if you take into consideration that this was a single serving effect it is actually quite impressive compared to the the ~1% performance increment in the narrow range of 90-120s activities that has recently reported to come out of weeks of beta alanine supplementation.
  So, if the testosterone boosting, anti-diabetic effects of taurine (see "Up to 180% Increase in Testosterone & More From Taurine") did not already convince you to invest the ~$20 for a 500g batch of this sulfur amino acid, maybe these results and a couple of hours in front of the TV watching track & fields events at the Olympic Games '12 can ;-)

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  Figure 5: Glucose metebalism markers of oxidation and nitric oxide (top) calculated artheorscleortic risk (bottom, left) and body weight gain (bottom right) in the different groups

  Differential and common effects of zinc, copper and manganese supplementation on body weight gain, glucose metabolism and cardiovascular health have recently been reported by scientists from the Usmanu Danfodiyo University in Nigeria. In their paper that has been published in the Journal of Oxidative Medicine and Cellular Longevity Muhammad et al. report that the provision of high copper (4mg/kg), high manganese (10mg/kg) and high zinc (20mg/kg) diets or the addition of all three supplemental minerals to the diets of salt-loaded hypertensive male Wistar rats all offered at least some protection against the oxidative stress, dyslipidemia, and insulin resistance that's associated with hypertension.
  As the data in figure 5 goes to show, the provision of additional copper does yet appear to exert the most benefits. In view of the short duration of the study, it would yet be more than premature to recommend copper only supplementation regimens in the absence of proven and most importantly specific deficiencies. Rather than that those of you who are suffering from the triumvirate of elevated blood pressure, insulin resistance and dislipidemia would probably be better off if they increased their overall intake of these trace minerals.

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  Image 6: Sounds stupid, but if you are concerned about your dopamine receptor count, you better make sure to eat the bun and order an extra large coke (the original with tons of sugar, of course ;-)

  High fat / low carb = reduced striatal dopamine receptor availability this is the quintessence of a short communication that has been published in the International Journal of Obesity three days ago. According to E van de van de Giessen and his co-workers, rats on a high fat high fat diet (this is no typo but the way of the researchers to acknowledge that the "original high fat diet" as it is interpreted by most scientists is almost equally high in carbohydrates (calorie-wise) as it is in fat; not so for the "High Fat High Sugar High Fat" (HFHS hf) diet in the van de Giessen study. Compared to the regular high fat diet, the HFHS-hf diet ameliorated the increase in energy intake, but reduced the availability of D2 & D3 receptors in the nucleus accumbens.
  Overall, the ratio of fat to carbohydrate in the diet and not as it has previously been speculated the degree of adiposity or the total energy intake were the most and only significant correlate of the central dopamine receptor downregulation the researchers observed in their test animals (Giessen. 2012). In view of the fact that Fetissov et al. speculated in 2002, already, that "[l]ow D2 receptor expression may be causal for an exaggerated dopamine release observed in obese rats during food ingestion" (Fettisov. 2002) this is bad news - as it would indicate that the low carb induced reduction of dopamine receptor density could precipitate to reward driven episodes of overeating... an emphasis is on the conditional, here, as the majority of low-carb dieters will probably confirm my gut feeling that during the low carb diet, the exact opposite appears to be the case (at least as long as we are talking about even more fatty foods ;-).

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  Image 8: According to Hwang et al. it does not matter how you cook your broccoli, if you want to keep the glucosinolates intact. The main point is that you do it fast!

  Cooking your veggies without water reduces cholesterol oxidation and improves potassium status that's what a group of Japanese researchers who declare they do not have any affiliation with the producer of multi-ply cookware, Vita Craft Japan Ltd, found in a 2-week intervention study in the course of which both the "just eat your veggies" and the "eat your veggies, but cook them without water in multi-ply cookware(TM)" (the product reference is #5123) increased their beta carotene and vitamin C levels and decreased their LDL and total cholesterol levels, but only the "without water cookers" had significantly reduced oxidized LDL and profoundly improved (=lower) Sodium : Potassium ratios in their urin (Mori. 2012).
  Now, while this sounds as if it would make sense to buy this cooking "gear" things look somewhat different, when you take a look at the absolute differences and outcomes. While the oxidized LDL levels did in fact improve more in the muli-ply group this brought them just back into the exact same range where they were hovering in the other groups, as well. Similarly, the Na:K ratio was better, but it did improve in the "regular cooking" group as well and would thus probably end up in the same range, after another 2-6 weeks of vegetable eating - regardless of whether you cook them with water or not. Things would probably not be much different for the glucosinolate content of broccoli of which Hwang et al. report in the same issue of the International Journal of Food Sciences and Nutrition report that, they decreased significantly and time-dependently during boiling, steaming and microwaving (Hwang. 2012)
• Black tea, lemon and honey: Can you stack it? Yes, you can! Camellia sinensis, Citrus limon and Apis mellifera all have a record of being potent antioxidants, but according to a paper in the August issue of the International Journal of Food Sciences and Nutrition lemon-flavoured black tea becomes an even more potent health drink, when you "spike" it with honey (Pereira. 2012).
  Moreover, Pereira et al. found that the darker species of the different honeys from Lavandula stoechas, Erica sp. pl. and other indigenous floral species from north-east Portugal they tested were more potent than the light amber varieties.

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  Image 9: The powdery Matcha tea is not only already high in catechines, it will also release>130x more of it's EGCG content into the brewing water than most regular green teas! And as if that wasn't enough, it has a 64% higher caffeine concentration (6.4 vs. 3.9mg/g), as well.

  Matcha tea has an uber-potent 137x increased EGCG content! This is one of the "oldie but goldie" studies I hit upon when I did "colleteral research" in response to a Highbrow Paleo member complaining that the over-potent Matcha tea literally blew him away. Actually not very surprising in view of the fact that it contains 137x more EGCG than regular green tea (brand China Green Tips; cf. Weiss. 2003). And while the selection of a specifically catechin rich fraction will figure here, as well, much of the effect is probably simply a result of the increased surface area and thus the greater efflux of the bioactive ingredients into the brew the tea is steeped in.
  In view of the previously reported negative effects very high doses of green tea catechins can have on your testicular health all matcha lovers out there should better limit their daily consumption to one or two cups of the exclusive brew (see "20% Reduction in Testosterone with 5 Cups of Green Tea").
• Oral anti-oxidants restore glutathione in diabetic skin At least in rodents this works pretty damn well. According to Sokmen et al. all it takes to restore the natural antioxidant defense system in the skin of streptozotocin-induced diabetic rats (model of type II diabetes) are 250 mg/kg vitamin C, 250 mg/kg vitamin E and 0.2 mg/kg selenium (Sokmen. 2012). The human equivalent of these orally supplied antioxidants would be 40mg/kg vitamin C, 45 IU/kg vitamin E and 30µg/kg selenium - all much too high to benefit anyone who is not diabetic, by the way.

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  Image 10: Usually I am really enthusiastic about new technologies, but looking at how careful physicists handle nanomaterials, and how food designers and the cosmetic industry unleash them on the costumers, like the US and UDSSR unleashed the a-bomb radiation on their own soldiers, ignorant of the (un?)known dangers.

  Nano-sizing fish oil doubles absorption - This is the result of a recently conducted rodent trial by Tanmoy kumar Dey the results of which are soon going to be published in Food Research International (kumar Dey. 2012). The more than +50% increased absorption the scientists found for their nano emulsified fish oil in the small intestine of the lab rats is - at least in my humble opinion - somewhat frightening. Firstly, I am really not sure we really need the hilarious amounts of fish oil, where the use of respective products would make sense (it should be said, though, that this new formula has been developed for parenteral nutrition, specifically). We have, secondly, not the slightest idea if those nano-sized fish oil molecules behave anywhere similar to their fluffy large brethren - who tells us that they don't have the exact opposite effect on our health?
  And third and lastly, if nano-sized fish oil is absorbed 100% more efficiently, all other nanomaterials - especially those that are nor increasingly popular in the cosmetic industry - will have a similarly increased "bioavailability" and could thus not only reach places in our body they were never intended to reach, but do just that in very significant amounts!

References

• Abu-Abid S, Szold A, Klausner J. Obesity and cancer. J Med. 2002;33(1-4):73-86. Review.
• Arunabh S, Pollack S, Yeh J, Aloia JF. Body fat content and 25-hydroxyvitamin D levels in healthy women. J Clin Endocrinol Metab. 2003 Jan;88(1):157-61.
• Balshaw TG, Bampouras TM, Barry TJ, Sparks SA. The effect of acute taurine ingestion on 3-km running performance in trained middle-distance runners. Amino Acids. 2012 Aug 2.
• Bayer J, Rune G, Kutsche K, Schwarze U, Kalisch R, Büchel C., Sommer T. Estrogen and the male hippocampus: Genetic variation in the aromatase gene predicting serum estrogen is associated with hippocampal gray matter volume in men. Hippocampus. 2012.
• Boulton TN, Malacrida C. Women and cosmetic breast surgery: weighing the medical, social, and lifestyle risks. Qual Health Res. 2012 Apr;22(4):511-23.
• Dickinson JM, Drummond MJ, Coben JR, Volpi E, Rasmussen BB, Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise, Clinical Nutrition. 2012.
• Dorgan JF, Klifa C, Shepherd JA, Egleston BL, Kwiterovich PO Jr, Himes JH, Gabriel KP, Van Horn L, Snetselaar LG, Stevens VJ, Barton BA, Robson AM, Lasser NL, Deshmukh S, Hylton NM. Height, adiposity and body fat distribution and breast density in young women. Breast Cancer Res. 2012 Jul 16;14(4):R107.
• "Caffeine." Encyclopedia of Drugs, Alcohol, and Addictive Behavior. Ed. Rosalyn Carson-DeWitt. Vol. 1. Gale Cengage, 2001. eNotes.com. 11 Aug, 2012 <http://www.enotes.com/caffeine-reference/>
• Fetissov SO, Meguid MM, Sato T, Zhang LH. Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake. Am J Physiol Regul Integr Comp Physiol. 2002 Oct;283(4):R905-10.
• Gielen M, Mesotten D, Wouters PJ, Desmet L, Vlasselaers D, Vanhorebeek I, Langouche L, Van den Berghe G. Effect of Tight Glucose Control with Insulin on the Thyroid Axis of Critically Ill Children and Its Relation with Outcome. J Clin Endocrinol Metab. 2012 Aug 7.
• Hwang ES, Kim GH. Effects of various heating methods on glucosinolate, carotenoid and tocopherol concentrations in broccoli. Int J Food Sci Nutr. 2012 Jul 10.
• kumar Dey T, Ghoshb S, Ghoshb S, Koleyc H, Pubali, D. Comparative study of gastrointestinal absorption of EPA & DHA rich fish oil from nano and conventional emulsion formulation in rats. Food Research International. 04 Aug 2012.
• Lee SJ, Huynh TV, Lee YS, Sebald SM, Wilcox-Adelman SA, Iwamori N, Lepper C, Matzuk MM, Fan CM. Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci U S A. 2012 Aug 6.
• Mori M, Hamada A, Mori H, Yamori Y, Tsuda K. Effects of cooking using multi-ply cookware on absorption of potassium and vitamins: a randomized double-blind placebo control study. Int J Food Sci Nutr. 2012 Aug;63(5):530-6. Epub 2012 Jan 9.
• Muhammad SA, Bilbis SL, Saidu Y, Adamu Y. Effect of Antioxidant Mineral Elements Supplementation in the Treatment of Hypertension in Albino Rats. Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 134723, 8 pages, 2012.
• Nickmilder M, Bernard A. Associations between testicular hormones at adolescence and attendance at chlorinated swimming pools during childhood. Int J Androl. 2011 Oct;34(5 Pt 2):e446-58.
• Oosting A, Kegler D, Wopereis HJ, Teller IC, van de Heijning BJ, Verkade HJ, van der Beek EM. Size and Phospholipid Coating of Lipid Droplets in the Diet of Young Mice Modify Body Fat Accumulation in Adulthood. Pediatr Res. 2012 Jul 31.
• Pereira C, Barros L, Vilas-Boas M, Ferreira IC. Potentiating effects of honey on antioxidant properties of lemon-flavoured black tea. Int J Food Sci Nutr. 2012 Aug 3.
• Sokmen B, Basaraner H, Yanardag R. Combined effects of treatment with vitamin C, vitamin E and selenium on the skin of diabetic rats. Hum Exp Toxicol. 2012 Aug 2.
• Teixeira GR, Fávaro WJ, Pinheiro PF, Chuffa LG, Amorim JP, Mendes LO, Fioruci BA, Oba E, Martins OA, Martinez M, Martinez FE. Physical exercise on the rat ventral prostate: Steroid hormone receptors, apoptosis and cell proliferation. Scand J Med Sci Sports. 2012 Jul 26. 
• van de Giessen E, la Fleur SE, Eggels L, de Bruin K, van den Brink W, Booij J. High fat/carbohydrate ratio but not total energy intake induces lower striatal dopamine D2/3 receptor availability in diet-induced obesity. International Journal of Obesity. 7 August 2012.
• Wamberg L, Christiansen S, Paulsen SK, Fisker S, Rask P, Rejnmark L, Richelsen B, Pedersen SB. Expression of vitamin D-metabolizing enzymes in human adipose tissue—the effect of obesity and diet-induced weight loss. International Journal of Obesity. 17 July 2012.
• Weinhold B. Can indoor swimming alter hormones in boys? Environ Health Perspect. 2012 Jan;120(1):A18.
• Weiss DJ, Anderton CR. Determination of catechins in matcha green tea by micellar electrokinetic chromatography. J Chromatogr A. 2003 Sep 5;1011(1-2):173-80. 
• Zhu J, DeLuca HF. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet? Arch Biochem Biophys. 2012 Jul 1;523(1):30-6.