SuppVersity Science Round Up Seconds: Wheat Gluten Hydrolysates Fail, Exposure to Air Pollutants During Workout Reduces Brain Benefits, Homocysteine, B-Vitamins, Cognitive Impairment and Mortality

Before the profound weight loss (A) you don't see any of the glucose sucking and fad burning brown fat depots (black spots in B) on the neck of the in (B) 'foermerly obese', now only 'overweight' subject (also take a look at how the visceral fat in the abdominal region in (A) is actually pushing the organs upwards; img Vijgen. 2012)

Those of you who have listened to yesterday's show will have noticed that despite its flow the number of things you can discuss in a 1h podcast is simply very limited, to say the least. This is also why these Friday posts are probably never going to be simple summaries of the SuppVersity Science Round Up of the day before. The same is true for today and still I decided not to use the allegedly lame logo I did for the first two installments, but provide you with some 'real science' evidence of the absence of brown adipose tissue on the obese and it's magical reappearance after shedding 100lbs+ subsequent to a gastric bypass operation, instead (see image on the right).

Assuming that you have no idea what this "evidence" is for, I would suspect that you missed the live show yesterday and also did not find the time to download and listen to the podcast, yet -- right? Well, you should either download and listen to the show now and digest the Seconds later, or you read the following paragraphs first and download the podcast later.

What is not an option, however, is to miss one or another - I mean you can hardly want to eat the seconds if you have not had the main dish yet... and after listening to the podcast, I cannot imagine you don't want at least some seconds. Apropos seconds, here are today's seconds...

• Wheat gluten hydrolysate is not the new goto protein supplement - certainly not for female distance runners and probably not for anyone else, either! These are the kinds of studies that really annoy me. Studies that start out with blatant statements like "WGH [Wheat gluten hydrolysate] has been reported to suppress post-exercise rises in serum creatine kinase in male distance runners" (Hirao. 2012).
  
  

  

  Figure 1: CK, AST, ALT response in the "success trial" with men. In women even the miniscule beneficial effect on CK was not there. No reason to even think about buying a gluten hydrolysate as you new go-to protein supplement with only 5.6g of leucine/100g (whey has 50% more) and almost no GSH replenishing cysteine in it (0.9g vs. 3g+ in whey, which is more than +200% more).

  Sentences like that make the null-results of the study they precede look like the exception to the rule and are still nothing but a concession to a bias (let's hope not due to the grant from Nisshin Pharma Inc. which was the manufacturer of the wheat gluten hydrolysate used in this study). A bias, due to which an isolated observation as the slightly blunted increase in CK is blown up as if a slightly lower CK level was what could turn a sedentary pencil pusher into the next Hussein Bolt (Aoki. 2012).
  
  So, even if you are not afraid of the evil in gluten (which I believe not everyone has to), I strongly caution against making the switch from a high EAA protein with ton's of GSH boosting cysteine in it like whey to a mediocre grain protein, which is a potential allergen and contains tons of glutamine your body will readily turn into glucose, once it passes through the portal veign into the liver (I bet a large part won't even make it into systemic circulation).
  
  And as far as the purported "gender difference" goes the study at hand tries to blame the null result on (Hiriao. 2012), I suspect that it is rather the indisputable difference between the long-distance running at a continuous pace the women in the study at hand did, versus the totally different strains the guys in the previous study were exposed to during a soccer training + mini-match, which made the difference.
• Working out next to a street takes away some of the beneficial cognitive effects due to ultrafine particulate matter (UFPM) exposure. "Working out in the fresh air will promote weight loss more than working out inside." You heard me state that in one of the previous installments of the SuppVersity Science Round Up on Super Human Radio. Now this is still correct and based on sientific evidence, but at least as far as the cognitive benefits are concerned, working out outside does also have its downsides - at least for those of you who live in the inner city area.
  
  

  

  You better watch what you breath while you run.

  During a 12-week program the researchers from the Universiteit Brussel, the Hasselt University and the Royal Military Academy measured the improvements in physical performance, changes in serum markers and corresponding ultrafine particulate matter (UFPM) concentrations in the enviromnent in which their 15 previously untrained subjects conducted their aerobic training program thrice a week (Bos. 2012). What Bos et al. found was that the UFPM levels were signfificantly higher in the urban compared to the rural environment and that the higher UFPM exposures correlated with increases in leukocyte counts (p = 0.02), neutrophil counts (p = 0.04), and eNO levels (p = 0.002) that were exclusively observed in the group that trained in the urban environment.
  
  With the latter being markers of inflammation which exert their effects systemically, i.e. not just in the lung or musculature of which you may be thinking now, but also in the brain, it is no wonder that
  

  "reaction times on the Stroop task improved in the rural group (p = 0.001), but not in the urban group" (Bos. 2012). 

  What's comforting, though, is that the physical fitness did increase to a similar extend in both arms of the study.
• Homocysteine levels, mortality, cognitive impairment and which nutrients can offer some protection. I am not sure about what your impression is, but for whatever reason homocystein seems to be 'out of vogue' -- probably no room for it on the research agenda with all the hype surrounding vitamin D. It used to be all the rage in CVD risk research and today's news item is actually ain't about cardiovascular health, either.
  
  What the researchers from China and Taiwan actually were interested in was the correlation of high and low homocysteine levels with cognitive impairment and the corresponding nutrient intakes. In that Xiu et al. paid particular attention to the "B-vitamins" and found the following correlations between the mortality, cognitive status, homocystein levels and nutrient intake of their 1412 study participants (Xiu. 2012):
  

  • 

    Figure 2: Unadjusted mortality in the four quartiles of homocysteine levels (top); mortality according to homocysteine levels in subjects with different degrees of cognitive impairment (based on Xiu. 2012)

    if you go by the unadjusted data in figure 2, it's plain obvious that the all-cause mortality increases linearly from one quartile to the other 
  • this relation between plasma homocysteine levels and all mortality remained statistically significant after adjustments for age, sex, smoking status, BMI, physical function and general health were made
  • of the general foods, the scientists assessed, only regular fish intake had a statistically significant effect on homocysteine levels, with higher intakes being associated with lower homocysteine levels
  • of the b-vitamins choline was the only one with a significant association with plasma homocysteine levels (suggested read "Old School Supplement Choline Could Save Your Live and Liver!") 
  • neither betaine, nor vitamin B1, B2, B3 or B6 intakes did show statistically significant correlations with plasma homocysteine (not even "borderline significant; p > 0.15 for all, most way hither)
  • of the plasma markers, folate showed a highly significant correlation with homocysteine (14.4 nmol/L in the lowest HCY and 8.70 nnmol/L in the highest HCY group)
  • PLP, the active form of vitamin B6, came in close second with 70.3 nmol/l in the lowest HCY quantile and only 44.4 nmol / l in the highest quantile.
  Now, if you consider the fact that higher intakes of B-vitamins are probably not doing much to lower homocysteine levels int he elderly (at least not dose-dependently, when they are already getting enough) oddity #1, another look at the data in figure 2 will reveal oddity #2: The surprisingly high mortality in the lowest homocysteine quartiles in the patients with severe cognitive decline - how come? I mean, with low homocysteine they should not be at risk of having severe cognitive decline, anyway - right?
  
  Actually if you follow this rationale you can almost answer the question yourself. If you have low homocysteine and severe cognitive decline, the severe cognitive decline can hardly be from high homocysteine levels, so it must have another obviously pathological reason, or as the scientists have it
  

  "The joint effects of the 2 variables [homocysteine and cognitive decline] were most pronounced with severe cognitive impairment where mortality HRs ranged from 5- to 18-fold across a wide range of homocysteine concentrations. The findings with hypohomocysteinemia provide some insight into what might be an optimal range for this analyte in peripheral blood and tissues. The low concentrations may be seen with severe illness and malnutrition, and our study population comprises the health-vulnerable aged. For these reasons, we adjusted these associations for BMI (using the World Health Organization chronic energy deficiency category of, 18.5 kg/m 2 ), and we excluded those who died in the first year of follow-up. The findings were unchanged. Because mortality among the very old may have skewed the joint effects, these are presented for those ≤75 years and over, but again with similar findings." (

  A sarcastic person would now probably say: "We all have to go some time!" and just wave his hands at these results. True! And I am the last to advice you to become over-anxious. Yet in the mean time it would appear prudent to make sure to get your homocysteine levels checked from time to time, not to forget that choline is a b-vitamin as well and not to fall for the idea that you cannot overdose on B-vitamins - I don't have to remind you of the negative effects, specifically folic acid supplementation can have on all sorts of cancer (e.g. breast cancer, where a high folic acid intake from foods and supplements is associated with a +30% risk of cancerous growth; cf. Kim. 2006).

In case you are looking for the post on "ammonia accumulation brain-fog, toxicity, liver 'pathologies' and workout performance", yeah it was on the list, but I decided it would be a shame to tackle that within a short two paragraph seconds items. Don't worry I am not going to forget about it, after all its in my humble opinion one of the main reasons the diets and workout regimen of the many ambitious physical culturists fail. If you are still looking for more and have not listened to the podcast, yet, this would be the right moment to download the file from the Super Human Radio Network server (click here to download), otherwise the latest short news on the SuppVersity Facebook Wall may offer some diversion ;-)

References:

• Aoki K, Kohmura Y, Suzuki Y, Koikawa N, Yoshimura M, Aoba Y, Fukushi N, Sakuraba K, Nagaoka I, Sawaki K. Post-training consumption of wheat gluten hydrolysate suppresses the delayed onset of muscle injury in soccer players. Exp Ther Med. 2012 Jun;3(6):969-972. Epub 2012 Apr 3.
• Bos I, De Boever P, Vanparijs J, Pattyn N, Panis LI, Meeusen R. Subclinical Effects of Aerobic Training in Urban Environment. Med Sci Sports Exerc. 2012 Oct 15.
• Cankurtaran M, Yesil Y, Kuyumcu ME, Oztürk ZA, Yavuz BB, Halil M, Ulger Z, Cankurtaran ES, Arıoğul S. Altered Levels of Homocysteine and Serum Natural Antioxidants Links Oxidative Damage to Alzheimer's Disease. J Alzheimers Dis. 2012 Oct 29.
• Guest PC, Urday S, Ma D, Stelzhammer V, Harris LW, Amess B, Pietsch S, Oheim C, Ozanne SE, Bahn S. Proteomic analysis of the maternal protein restriction rat model for schizophrenia: Identification of translational changes in hormonal signalling pathways and glutamate neurotransmission. Proteomics. 2012 Oct 16.
• Hirao T, Koikawa N, Aoki K, Sakuraba K, Shimmura Y, Suzuki Y, Sawaki K. Female distance runners show a different response to post-workout consumption of wheat gluten hydrolysate compared to their male counterparts. Exp Ther Med. 2012 Apr;3(4):641-644.
• Kim YI. Does a high folate intake increase the risk of breast cancer? Nutr Rev. 2006 Oct;64(10 Pt 1):468-75.
• Vijgen GH, Bouvy ND, Teule GJ, Brans B, Hoeks J, Schrauwen P, van Marken Lichtenbelt WD. Increase in brown adipose tissue activity after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2012 Jul;97(7):E1229-33. Epub 2012 Apr 24.
• Xiu LL, Lee MS, Wahlqvist ML, Chia-Yu Chen R, Huang YC, Chen KJ, Li D. Low and high homocysteine are associated with mortality independent of B group vitamins but interactive with cognitive status in a free-living elderly cohort. Nutr Res. 2012. Ahead of print.

Vitamins B1, B2, B5 & B6 & Glucose Management | Part VII of the "There is More To Glucose Control Than Low Carb"- Series. Any Real Benefit From Supplementing With "Bs"

Funny or obscene? A woman w/ low vitamin B and thus fortified cornflakes is among the "top images" Google will show you, when you search for B-vits

There is an often overlooked reason I am addressing thiamin (B1), riboflavin (B2), panthotenic acid (B5) and pyridoxine (B6) in one installment of the "There is More to Glucose Control Than Carbohydrates"-Series (read previous installments): They are all necessary to store glycogen in the liver (Supplee. 1942).

In general, a whole foods diet, as recommended in previous SuppVersity articles will easily cover the B-vitamin needs of the average sedentary and physically active individual - in spite of minimally increased requirements for B2 & B6, in particular (Manore. 2000; Woolf. 2008).

You can learn more about this topic at the SuppVersity

Proteins, Peptides & Blood Glucose

SFA, MUFA, PUFA & Blood Glucose

Vitamin D & Diabetes

Glucose Manager Calcium?

Flush & No-Flush Niacin & Diabesity

Vitamin C & Glucose Control

As a SuppVersity reader you do yet know that "adequate" and optimal intakes can differ significantly and the fact that the provision of additional B-vitamins does not have ergogenic effects does not exclude the possibility that it may have beneficial effects on blood glucose management.

The initially mentioned inability to convert glucose to glycogen and to store the latter in the liver, for example, would already set you up to increases in blood glucose levels. The latter will in turn increase the urinary loos of the water-soluble vitamins, so that a deficiency in one of the initially named B-vitamins could trigger a whole "pro-diabetic" cascade that leaves the by then (pre-)diabetic individual deficient even in those of the B-vitamins of which he or she is actually getting enough from his or her diet (+ supplements).

Annual spending Alzheimer patients >65y in the US from 2010 to 2050 (projection, in billion U.S. dollars;  Alzheimer's Association. 2010)

This article is exclusively about the beneficial effects of b-vitamins on glucose control: The conclusions I draw based on the evidence presented in this article do not affect potential cognitive benefits from "optimal" (=within the RDA) intakes of B-vitamins (in particularly folate, and B-12, which are not part of this overview, anyway) in the young (Herbison. 2012) and old , where they are furthermore "confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline" (Douaud. 2013).

Conclusive evidence for anti-diabetic or insulin-sensitizing effects of B-vitamin supplements is yet still scarce. Even the notion that (pre-)diabetics suffer from low levels of the said B-vitamins is still controversial. This does not mean, though, that there were no promising study results I could report. For thiamine, for example, ...

• 

  Figure 1: Effects of lipophilic thiamine on HbA1c (top) and insulin requirements (bottom) of type I diabetics (Valerio. 1999(

  Valerio et al. report that the provision of a lipophilic form of thiamine (benzoyloxymethyl-thiamin) at 50mg/day lead to improvements in HbA1c and reduced insulin requirements in children with type I diabetes (Valerio. 1999) - the difference between the active and the placebo arm of the study did yet not reach statistical significance
• Obrenovich et al. report in a 2003 that thiamine, or rather benfothiamine bocks the oxidative damage due to the presence of excessive amounts of glucose in the blood of a rodent model of diabetes - their results have been replicated in human studies by Stirban et al. an other researchers several times over the past decade (Stirban. 2006)

Corresponding evidence for riboflavin is hard to find. While there are studies that suggest the presence of reduced levels of this b-vitamin in both type I and type II diabetics, direct beneficial effects of vitamin B2 supplementation on glucose management have not been reported.

A very similar picture, i.e. reduced levels in type II diabetics, but no reports of direct metabolic benefits from the provision of supplemental vitamin B5 from randomized controlled human trials, emerges if you do a database search for panthotenic acid.

Figure 1: 2h glucose and insulin response to oral glucose tolerance test before (white) and after 25 days of B5 depletion (red), as well as during B5 refeed (violet) in a healthy male subjects (Bean. 1995)

The results of a study from the mid 1950s, when scientists still put healthy individuals on nutritionally deficient diets still indicate. After 25 days without significant amounts of panthotenic acid in the diet, the subjects' insulin sensitivity was notably compromised (Figure 1, red) and was not normalized within only 10 days on a diet with 133x the normal amount of panthotenic acid (Figure 1, violet).

Mind the vitamin <> vitamin interactions: Even if there is no reason for high dose pantothenic acid supplementation to inhibit the cellular uptake of glucose directly, it's well possible that it messes with glucose metabolism via interactions with other water solube vitamins like vitamin B6 aka pyridoxin, the excretion of which is increasing, whenever the intake of panthothenic acid exceeds an (in humans undetermined) sane threshold.

In fact, the extreme elevation of the insulin levels in the "reload phase" would rather suggest that extreme amount of vitamin B5 will compromise, not improve your insulin sensitivity - contrary to edema, severe fatigue, joint pains, reduced protein metabolism, reduced phosphorus, raised VLDL triglycerides, calcification (from calcium pantothenate), dehydration, gastrointestinal symptoms, and depression, a decreased insulin sensitivity is yet not on the "official list of side effects"* of high panthotenic acid intakes (*by "official" I refer to the lists everyone copies ad pastes from the major health information outlets on the Internet).

And what about B6? It's in all my supplements, so it must be good!

If I had to write the bottom line to today's installment of the "There is More to Glucose Control Than Carbohydrates" series now, it would probably be very short and certainly very disappointing for the various supplement junkies out there. Luckily (?) there is still one of the B-vitamins missing: Pyridoxine or vitamin B6 - and you should expect the only B-vitamin that can produce severe toxic effects when it is consumed in very high amounts chronically (peripheral nerve damage) should be able to bring about at least minimal increases in insulin sensitivity / cellular glucose uptake, as well, right?

Well, unfortunately, that's not the case. In 1980, already, a group of scientists from the Gandhi Medical College Hospital in India were able to show that the provision of 40mg of pyrodixine per day had "did not bring about any significant alterations in either the oral glucose tolerance or the insulin response to glucose" in thirteen adult maturity-onset diabetics - and that in spite of the fact that 7 of them were actually vitamin B6 deficient!

Mind the "hidden" B-sources: If you are still concerned that you may not be getting your Bs in, you are probably an OTC supplement junkie. In that case I suggest you briefly take a look at the pre-workout, post- workout and whatever other products in your stack... what? Oh, they all contain 10x the RDA and more of these B-vitamins - that's surprising, right?

A major disappointment? Although this article focused exclusively on the benefits of the water-soluble B-vitamins on glucose control, the results are still paradigmatic for the overall "potency" of vitamin-B-supplements. They are all the rage, but the benefits are overblown, in many cases simply non-existent.

If we discard the well established beneficial effects of benfothiamine on the side-effects of elevated blood glucose levels, and the highly disputed benefits of pyridoxine in diabetic peripheral neuropathies (alleviation of sympthoms, no change in nerve damage; Bernstein. 1988 & 1990), there is actually no reason to even consider taking extra amounts of any or all of these vitamins if you are (a) no diabetic and (b) no junk food eater - and let's be honest, if either (a) or (b) applies you have got more important issues to deal with than potentially suboptimal B-vitamin intakes and their effects on glucose tolerance.

Reference:

• Bean, William B., et al. "Pantothenic acid deficiency induced in human subjects." Journal of Clinical Investigation 34.7 Pt 1 (1955): 1073. 
• Bernstein, A. L., and C. S. Lobitz. "A clinical and electrophysiologic study of the treatment of painful diabetic neuropathies with pyridoxine." Current topics in nutrition and disease (USA) (1988).
• Bernstein, Allan L. "Vitamin B6 in clinical neurology." Annals of the New York Academy of Sciences 585.1 (1990): 250-260.
• Herbison, Carly E., et al. "Low intake of B-vitamins is associated with poor adolescent mental health and behaviour." Preventive medicine 55.6 (2012): 634-638.
• Manore, Melinda M. "Effect of physical activity on thiamine, riboflavin, and vitamin B-6 requirements." The American journal of clinical nutrition 72.2 (2000): 598s-606s.
• Supplee, G. C., R. C. Bender, and Z. M. Hanford. "Interrelated vitamin requirements. The influence of thiamin, riboflavin, pantothenic acid and vitamin B6 on liver glycogen reserves." Journal of the American Pharmaceutical Association 31.7 (1942): 194-198.
• Valerio, G., et al. "Lipophilic thiamine treatment in long-standing insulin-dependent diabetes mellitus." Acta diabetologica 36.1-2 (1999): 73-76.