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marylin monroe
Showing posts with label folic acid. Show all posts
Showing posts with label folic acid. Show all posts

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.

      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.

      Aspartame's Anti-Insulinogenic Effects During a Workout; Optimal Protein Intake on a Diet is Relative. Plus: Folate Fortification, Spirulia, Succinate, Sucrose, Pork Brain & the Low Cholesterol-Suicide Connection Reviewed!

      Unbelievable: The results of the latest study from the University of Western Sidney appear to suggest that you could keep your insulin levels at bay, if you mixed your sugary intra-workout supplement with aspartame-laden diet coke instead of water! The mechanism that's behind this phenomenon does yet still have to be elucidated.
      You may be surprised to see a long headline, a long post and a couple of bullet points: "Looks like On Short Notice, reads like On Short Notice, but is not published on Saturday? What's that?" The answer to this question is easy. Lot's of interesting stuff I have come across as of late! And while some of them, like the study on the marginal utility of higher protein intakes on a diet would actually deserve their own post, I decided to give you the "long(er) version of a short notice" in order not to miss any of them... and yes, this means there is going to be more than today's news on the unexpected anti-insulinogenic effects of aspartame, the only partly expected outcomes of the US folic acid fortification program, the aforementioned protein study, the usefulness of spirulina, succinate and sucrose supplements for athletes and physical culturists and some brainy insights into a possible connection between low cholesterol, depression and suicide risk in men and women... ah, ok I see, you are already reading the aspartame item - well, go for it!
      • The astonishing anti-insulin effects of intra-workout aspartame consumption Meanwhile even bodybuilders who are injecting and "supplementing" with all sorts of unquestionably unhealthy stuff are so afraid of the hitherto still rather vaguely established pro-carcinogenic effects of aspartame that supplement companies place huge stickers on the boxes of their products saying "ASPARTAME FREE!" Now, I am pretty sure that a recently published study that was conducted by scientists from the School of Science and Health at the University of Western Sydney in Campbelltown, Australia (Siegler. 2012), won't do much about that, but you will probably have to agree that it is still remarkable, to say the least, that the co-administration of an artificial sweetener which has not produced any glucose, insulin or whatever response in previous trials (cf. "Sweeter than your tongue allows") would do that!?
        Figure 1: While the mechanism is still unknown and the results need to be repeated in a second experiment, there is no question that the drop in insulin during the workout (see arrow(s)) which occurred during the carbohydrate + aspartame trial in the presence of identical glucose ingestion and blood glucose levels warrants further investigations (based on Siegler. 2012)
        During the four trials, which were separated by 7-10 days of rest, the 9 healthy, recreationally active males (age: 22±2 years; height: 180±9 cm; weight: 78.6±8.5 kg; participating in regular physical exercise at least twice per week) who had volunteered for this (in the eyes of some aspartame extremists, probably unethical undertaking ;-) cycled fasted for 60 minutes in a climate controlled laboratory. The only difference between the four sessions was the "intra-workout nutrition" the participants were fed, with...
        1. carbohydrate - 2% maltodextrin and 5% sucrose (figure 1, C),
        2. carbs + aspartame - 0.04% aspartame with 2% maltodextrin and 5% sucrose (figure 1, CA),
        3. water - plain water, only (figure 1, W), and
        4. aspartame + malto - 0.04% aspartame with 2% maltodextrin (figure 1, A)
        As it is common practice in studies like this, "all participants were instructed to follow the same diet and training schedule for the three days prior to each experimental trial." (Siegler. 2012, my emphasis)
        The respective intra-workout beverages were to be consumed in boluses of 4ml/kg body weight before and at 15-minute intervals throughout the trial. For the CHO groups this summed up to a total carbohydrate intake of 104.4±11.3g per participant and did - probably not to your surprise - cause a corresponding increase in insulin levels... with one exception, however: the intraworkout period in the CHO + Aspartame group (figure 1, red), when the insulin level dropped, during the exercise sessions and bumped back up to the same level as in the carbs only control afterwards (see figure 1).
        As the researchers point out, we do not yet have a mechanistic explanation for this phenomenon... nor can we even be sure that this was not some sort of strange artifact, so that
        "the disparity between insulin levels [does not only] warrant further investigation with a larger cohort of clinically relevant subject populations (e.g. metabolic syndrome, diabetes, etc.) [, but must also] be considered when designing nutrition-based, exercise intervention studies [in the future]" (Siegler. 2012
        That this observation could actually have very practical implications, both, in view of its potentially compromising effects on blood glucose levels in diabetics, where any insulin blocking effect of aspartame would probably reduce the already compromised glucose uptake even more, as well as in view of the anti-lipolytic (=blocks the release of fat from the cells) of insulin during a workout, which could actually be blocked with a minuscule amount of aspartame ... but alas, until the results have been confirmed and the mechanism behind this effect has been elucidated, what we are doing here is more or less intellectual masturbation - nothing to feel bad about, but still not the real deal ;-)
      • Figure 2: This is what the USDA expected to happen - more folic acid in food = higher intake (here in the elderly) = lower homocysteine levels; the reality looked pretty different, though, at least in adolescents the folic acid intake went up, but the homocysteine levels did not go down; moreover the B12 levels have declined as well... how much of this is related to confounding factors still has to be elucidated, but as of now it does not seem as if the fortification program was the success the USDA wanted it to be (Mc Bride. 2007).
        US adolescents and their "healthy grains" are now folic acid fortified, but are they also healthier? According to a study that has just been published in the Journal of Public Health, the great idea to put another artificial vitamin into our the food chain and fortify "healthy" cereal-grain products with folic acid, was so "successful" that the average US teen (14y at the time the fortification program began, 18y now) does now have 16% higher folate and 14% higher B6 concentrations.
        Instead of the expected decrease in homocysteine levels, of which scientists still believe that it plays in imminently important role in the development of heart disease, its serum levels did likewise increase by 17%, while the serum concentrations of vitamin B12 decreased by 11 % post-fortification. The additional ~118 μg folate/d the subjects ingested from the fortified food products, appeared to be particularly useless (or even detrimental?) for boys / young men whose total homocysteine (tHcy) levels increased by 24%  to a much greater extent than in the girls / young women.
        Honestly, I don't really know what to make of these results at the moment, ... at least nothing better than to shake my head over the hilariousness of trying to turn junk(-food) into (good) food by simply enriching it with artificial vitamins. On the other hand, I am happy that even Daniel A. Enquobahrie and his colleagues feel that it is "warranted to investigate the significance of these improvements in folate status on clinical outcomes, in the post-fortification era." (Enquobahrie. 2012) - and that not just because the fortification program did not produce the desired results, but also because the folic acid intake already started to exceed the RDA in many of the subjects. This, and the alarming decrease in B12 levels of which Katherine L. Tucker had cautioned in the 2007 interview with Judy Mc Bride, already, that "better diagnosis for B12 deficiency should be given high priority"(Mc Bride. 2007) do not "warrant", imho, they rather make it imperative to follow the effect of this "nationwide health program" very closely.
      • Figure 3: The principle of relativity for protein based body recompositioning diets - When it comes to weight los, the word "high" in high protein diets must always be seen in the context of habitual protein intake and to whom we are comparing our dieters; or put simply: The average SAD dieter benefits from every gram, the average bodybuilder will hardly benefit from the 7th whey shake.
        Effectiveness of high(er) protein diets for weight loss depends on spread / change vs. baseline not on total protein intake That's basically how you could summarize the conclusion of the latest review of the existing data on the influnece of (high) protein intakes on changes in body composition by John D. Bosse and his colleagues from the University of Utah. To find out whether either the protein change (=high protein diets are only effective when the change in protein intake from baseline to intervention is large enough) or the protein spread theory (=those dieters within a cohort with the highest protein intake will see the most beneficial changes in body comosition) could explain the different outcomes of previous studies best, the researches collected an impressive dataset comprising 51 peer-review studies the analysis of which yielded the following two main results (Bosse. 2012):
          1. The 35 successful dietary interventions had on average 58.4% higher average protein intakes than those trials in which the authors had not been able to observe an additional beneficial of going high protein over the standard calorical restriction approach
          2. The 17 successful (=greater anthropomorphic changes than with calorie restriction alone) of the 25 studies, where the baseline protein intake of the subjects was available, the increase in protein intake was 28.6% (if you ate 100g protein per day before, that would mean you would eat 128.6g while you are dieting), minimal increases in 4.7% range, on the other hand, did not provide any additional benefit over energy reduction, alone.
          Overall, the review does therefore support the original hypothesis of the researchers that there are certain thresholds which have to be surpassed before dieters will see any benefits from an increase in protein intake. This does yet also mean, that for someone who is already eating 200g of protein on a daily basis, the addition of a protein shake with 20g of protein is probably not going to make so much of a difference as it would be way below the 28.6% change in protein intake, the protein change theory would prescribe (see [2] in the list above). As a matter of fact going higher and higher (e.g. like eating 300g of protein per day), will, if anything stall, not propel your progress, after all, there will be too little room for other nutrients, when you are already getting the lions share of your daily energy intake from protein... and NO you cannot lose weight without being in a caloric deficit, even if that is not readily calculable by the idiotic "calories-in-vs-calories-out" equation.
        • The BMJ Supplement Review says: Thumbs up for sucrose, thumbs down for succinate and undecided  for spirulina In installment #36 of the A-Z of Nutritional Supplement Supplements, a series dedicated to review the pros and cons of purported ergogenic aids, the authors conclude that ...
          Figure 4: In view of the fact that the TCA or citric acid cycle is one of the #1 aerobic source of cellular energy (APT) and succinate is one of its intermediates it makes sense that supplementation could improve exercise performance, but hitherto this has not been confirmed.
          • ...the studies on spirulina fail to "study well-trained individuals", to use appropriate standardization regimen with relevance for physical culturists and athletes, identify the active ingredients and their effect on the antioxidant status, of which the respective scientists speculate that it would be the underlying mechanism of the observed ergogenic effects on chronic low-intensity exercise regimen
          • ...the research on succinate (only) supplementation is basically non-existent and claims with respect to its permanence enhancing effects is mostly based on theoretical considerations about its role in the TCA cycle 
          • ...despite the general trend within our society, where the overconsumption of sucrose (table sugar) is one of the major offenders to public health, "there may be value in, or at least room for, its inclusion in sports products targeting the provision of carbohydrate fuel during exercise"
          Nothing exciting, but a realistic and educative analysis, which has all the classic elements you should keep in mind, whenever you try to find out whether a product is worth its money: What research is there? What are the results? Are the positive results significant for me as a person? And... in the case of succrose: Could the use of this ergogenic aid be an obstacle for another goal of mine? I mean, you can benefit from guzzling tons of sugary drinks during your workouts, but if "looking good naked" is your primary goal and your performance only a means to an end - it is probably not wise to do so ;-)
        • Figure 5: Suicide risk in psychiatric patients /w (SA) or w/out (PS) prev. suicide attempt and surgical control (SC) in lowest, 2nd and 3rd cmp. to highest quartiles (Olié. 2011)
          Can pork brain in milk tell us something about suicide? Those of you who are on the SuppVersity Facebook news RSS channel will already know the image on the right. I only saw it today, but as Mark mentioned on my Facebook wall, he has used it (the image not the brain) in lectures before... be that as it may, that reminded me of an older study on the highly significant correlation between cholesterol levels and suicide attempts Emilie Olié and her colleagues observed in a 2010 study on the reliability of serum cholesterol levels as a predictor of the suicide risk in 3207 subjects [510 patients with a history of suicidal attempts (SA), 275 patients with no history of suicidal attempts (PC), and 2422 surgical controls (SC); Olié. 2011].
          The exact mechanism for the highly significant increase in suicide risk, esp. among women with previous suicide attempts in the lowest (1st quartile) is still not fully elucidated, Olié et al reference previous studies which suggest that low serum cholesterol levels, a "potentialmarker of central nervous systemcholesterol", impair the serotoninergic activity and" increase impulsivity" and thus precipitate to severe depression and the tendency and ability to pot a premature end to your life.
          In view of the fact that this and similar results were derived exclusively from analysis of psychiatric patients and considering that the cholesterol levels in the SA group were already significantly lower that in the PC and SC control (178±36 mg/dL vs. 217±43 mg/dL and 219±52 mg/dL, respectively) we should be very wary of transferring these results 1:1 to the "normal" people. 
        I guess this is enough for today. After all, news are not so different than protein, it's the relative intake that makes all the difference - in other words: If I keep flooding you with those awesome posts, you won't appreciate each and every of them the same way you do now... and we don't want that to happen, do we? 
          References:
          • Bosse JD, Dixon BM. Dietary protein in weight management: a review proposing protein spread and change theories. Nutr Metab (Lond). 2012 Sep 12;9(1):81.
          • Enquobahrie DA, Feldman HA, Hoelscher DH, Steffen LM, Webber LS, Zive MM, Rimm EB, Stampfer MJ, Osganian SK. Serum homocysteine and folate concentrations among a US cohort of adolescents before and after folic acid fortification. Public Health Nutrition. 2012; 15: 1818-1826.
          • Mc Bride. Foods To Be Fortified With Folic Acid. USDA ARS. News. February 7, 2007. < http://www.ars.usda.gov/is/ar/archive/jun97/folate0697.htm > retrieved on September 14, 2012.
          • Olié E, Picot MC, Guillaume S, Abbar M, Courtet P. Measurement of total serum cholesterol in the evaluation of suicidal risk. J Affect Disord. 2011 Sep;133(1-2):234-8.
          • Siegler J, Howell K, Vince R, Bray J, Towlson C, Peart D, Mellor D, Atkin S. Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise. J Int Soc Sports Nutr. 2012 Aug 1;9(1):36.
          • Zemski AJ, Quinlivan RM, Gibala M, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance: Part 36. Br J Sports Med. 2012 Sep;46(12):893-4. 

          Ask Dr. Andro: Are There NO Changes in the New N.O.-Xplode 2.0 Advanced Strength Formula?

          The official SuppVersity Supplement Shoot-Out!
          The longstanding veteran, NOXplode AVPT,
          is challenged by a clone of its own, 
          NOXplode 2.0 Advanced Strength -
          which will be the last pre-workout standing?
          Question Dr. Andro: What the... is BSN trying to scam costumers? At first sight the labels of the old and the new Advanced Strength version of N.O.-Xplode seem to be absolutely identical.

          Answer Dr. Andro: I am usually not soliloquizing, but in this case I thought that many of you may have had the same thought, when they spotted the new(?) BSN N.O-Xplode 2.0 - Advanced Strength in the "new products" column of their favorite supplement vendor: a lot of boastful claims in the product description, but no eye-catching changes in the actual formula.... Reason enough to devote a few hours of my precious time to scrutinize the labels of the old N.O.-Xplode AVPT and the purportedly "new" N.O.-Xplode 2.0 Advanced Strength.


          N.O.-Xplode AVPT vs N.O.-Xplode 2.0 - Fight!

          Well, let's start with the most obvious. The packaging got redesigned! I would not mind, but actually I find the new "darker" design looks a little cooler... well, I guess the ugly blue "now 25% more" sticker was bordering unfair competition, anyway. After all, BSN has been selling this "value" *lol* edition of the AVPT version of NOXplode for years now. So, if you are looking for a nice-looking addition to your supplement stash and red is your favorite color, the new BSN NOXplode 2.0 container could be just what you've always been waiting for  :-)

          If, on the other hand, you are more interested in the content of the fancy new container, I suggest you follow my lead, click at the image above and have a look at the labels... let's see, what have we got here?

          The basics - Calories, Carbs, Vitamins and Co.

          The FDA approved nutritional information is the part of the label that - the information on the carb content aside - will interest people the least, I guess. Nevertheless, I had hoped to see improvements in the types of vitamins the guys from BSN used. An adequate dose of methylcobalamine (B12), some pyridoxal-5-phosphate instead of the inactive pyridoxine HCL, we are bombarded with in all protein containing supplements, anyways, and some active methyl-tetrahydrofolate instead of the folic acid that the FDA is forcing upon you in each in every foodstuff you eat, would have been nice, yet obviously too expensive improvements (cf. table 1)

          AVPTNOXplode2.0Dr. Andro's thoughts
          Total calories25kcal25kcalidentical
          Total carbs6g6gidentical
          Total sugars0g0gwtf! As if a glucose polymer was no sugar
          Vitamin B6 from pyridoxine HCL25mg20mginstead of reducing the amount BSN had better invested in some P5P, the bioactive version of pyridoxine
          Folate from folic acid400mcg300mcgobviously someone @BSN got wind of the studies which show that the cheap folic acid (in excess) does more harm than good... I guess you know why they did not replace it with a reasonable dose of the active methyl-tetrahydrofolate
          Vitamin B12 from cyanocobalamine120µg120µgidentical, but still not absorbable (cf. "Want B12? Drink Milk")
          Calcium from Calcium Phosphate75mg75mgidentical & insignificant
          Phosphor from various phosphates535mg200mgsomeone got wind that the average Western diet already contains way too much phosphate and that the phospates in the original formula were the reason for diarrhea in some people
          Magnesium from various phosphates360mg60mgin view of the lack of magnesium in typical Western diets, the higher dose in the old formula was better - as long as your stomach could tolerate it ;-)
          Sodium from various phosphates 235mg300mgwell, isn't that great? Cut down magnesium, ramp up sodium... I guess its more stomach friendly, but is it also healthier?
          Potassium from various phosphates75mg75mgit is unfortunate and ridiculous that the FDA does not allow more than this amount per serving
          Table 1: Comparison of the fundamental nutrients, vitamins and minerals in the formula
          (based on nutritional information from BSN and a major online vendor)

          The Problem... ahh, I mean "Proprietary" Blend ;-)

          Now, things are getting a little complicated. How do you evaluate a supplement where you know that something is in there, but have no clue in which amount? Well, I guess this would not matter if we were talking about the FDA-invented difference between sugar and glucose polymers (isn't it interesting that the FDA let's the supplement companies make a difference, here?), it is however of tremendous importance to know whether the undisclosed overall amount of the AVPT or ASPM (Advanced Strength & Performance Matrix) part of the 18.0g and 19.6g proprietary blend in NOXplode AVPT and NOXplode 2.0 Advanced Strength contain 90% or 30% glucose polymers. With the latter being the first ingredient on the label, we can only be sure that it is the major ingredient in this part of the formula and since we know that we get 6g of non-sugar carbs, there probably is little room for the additional working ingredients in this part of the formula, anyway.

          I hope you understand the problem we are facing here. The one (and only) thing, we can do, is to compare the order in which the ingredients are listed (the latter complies to the relative amount of the individual ingredient, with those ingredients with the highest amounts being listed first) and evaluate whether the changes BSN has made in terms of the specific ingredients and their ratios do make sense.


          AVPT NOXplode2.0Dr. Andro's thoughts
          Total weight of proprietary blend18.0g19.6gthis means that BSN has generously rounded up the +1.6g diffrence in what they advertise as "2 more grams of active ingredients" (cf. BSNOnline)
          N.O. Meta-FusionL-Arginine AKG, L-Citrulline Malate, RC-NOS™ (Rutacarpine 95%), L-Citrulline AKG, L-Histidine AKG, NAD (Nicotinamide Adenine Dinucleotide), Gynostemma Pentaphyllum (Leaves & Stem) (Gypenosides 95%)L-Arginine-Alpha Ketoglutaric Acid, L-Citrulline-Malic Acid Interfusion, L-Citrulline-Alpha Ketoglutaric Acid, L-Histidine-Alpha Ketoglutaric Acid, NAD (Nicotinamide Adenine Dinucleotide), Gynostemma (90% Gypenosides) (Leaves & Stem)BSN has removed the rutacaropine, which induces vasodilation via CGRP (Duan. 2007) and added a lower amount of l-histidine AKG which does of course figure in the generation of NO, but has of yet not been shown to independently induce vasolidation; maybe the BSN-guys thought it would fit well with the (probably) extended amount of beta alanine, since β-alanyl-L-histidine, i.e. carnosine is what we actually want
          AVPT / ASPMModified Glucose Polymers (Maltodextrin), Di-Creatine Malate, Trimethylglycine, Creatine Ethyl Ester -Beta-Alanine Dual Action Composite (CarnoSyn®), Sodium Bicarbonate, Sodium Creatine Phosphate Matrix, Creatinol-O-Phosphate-Malic Acid Interfusion, Glycocyamine, Guanidino Proplonic Acid, Cinnulin PF® (Aqueous Cinnamon Extract) (Bark), Ketoisocaproate Potassium, Creatine AAB (Creatine Alpha-Amino-N-Butyrate)Modified Glucose Polymers (Maltodextrin), Beta-Alanine (CarnoSyn®), Di-Creatine-Malic Acid Interfusion, Betaine HCL, Sodium Bicarbonate, Creatine-Sodium Phosphate Matrix, Creatinol-O-Phosphate-Malic Acid Interfusion, Glycocyamine, Creatine Ethyl Ester HCL, Guanidino Propionic Acid, Cinnamon Extract (Bark) (Cinnulin PF®), Ketoisocaproate Potassium, Creatine-Alpha-Aminobutyric Acid Matrix (Creatine AAB™)the same fancy creatines without any substantial research supporting their superiority over creatine monohydrate as in AVPT (personally I see no reason to boast with the slogan "no creatine monohydrate", after all CM is the only form of creatine that has proven in scientific studies time and again that its working!); it seems, though, as if the beta alanine content increased - while this would be a good thing, its mere speculation based on its position within the list of ingredients in the proprietary blend; why BSN replaced the 'real' betaine (trimethylglycine) with the 'digestive aid' betaine HCL eludes me
          Ener-Tropic Xplosion™L-Tyrosine, Taurine, Glucuronolactone, Methylxanthine (Caffeine), L-Tyrosine AKG, MCT's (Medium Chain Triglycerides)[Coconut], Common Periwinkle Vinpocetine 99%, Vincamine 99%, Vinburnine 99% (Whole Plant)L-Tyrosine, Taurine, Glucuronolactone, Methylxanthine (Caffeine), L-Tyrosine-Alpha Ketoglutaric Acid, MCT's (Medium Chain Triglycerides), Lesser Periwinkle (95% Vinpocetine, 98% Vincamine, 98% Vinburnine [Whole Plant])BSN is trying to trick you on this one by just using a different name for the same ingredient - the common and the lesser periwinkle denote the same plant, the only difference is that the purportedly improved NOXplode 2.0 contains an inferior extract
          Phospho-Electrolyte Replacements / CompositeDi-Calcium Phosphate, Di-Potassium Phosphate, Di-Sodium PhosphateDi-Calcium Phosphate, Di-Potassium Phosphate, Di-Sodium Phosphateits telling that the "replacement" in the AVPT became a "composite" in NOXplode 2.0 - I already alluded to the inferior mineral composition of the "new" version in table 1
          Glycerol Hydrating Polymers™ / Glycerol Polymer ComplexPotassium Glycerophosphate, Magnesium Glycerophosphate, Glycerol StearatePotassium Glycerophosphate, Magnesium Glycerophosphate, Glycerol StearateI suppose BSN changed the name to "polymer complex", because it sounds way more sophisticated; in fact, its the same stuff as in the AVPT version
          Table 2: Detailed analysis and comparison of the ingredient profile of the proprietary blends of NOXplode AVPT and NOXplode 2.0 Advanced Strength (based on nutritional information from BSN and a major online vendor)
          As you can see from the juxtaposition of the ingredient profiles in table 2, the changes are mediocre at best and the potential increase in the beta alanine content is the only improvement I can find... what about you?

          Conclusion - Love It or Hate It!

          I guess, some of you are expecting me to rip BSN's marketing coup apart. Well, I guess I could, but let's be honest, obviously there was and still is a huge amount of trainees out there who loved the old formula and kept buying it even when everybody told them that arginine was not working, the new XY was all the rave and their first generation pre-workout would not be worth the cost of its container. In case you are one of those patrons who made the old NOXplode the best-selling preworkout supplement of all times, chances are you will like its almost identical twin, as well. If, on the other hand you, you hated the old version and/or are satisfied with your current pre.workout regimen, I see no reason to invest the 35.99$ into a professionally redesigned redesigned red plastic container.

          Biotin, Folic Acid & B12 & Glucose Management | Part IX of the "There is More To Glucose Control Than Low Carb" - Series: Are Extra "B"s Good for Non-Diabetics as Well?

          There is evidence for beneficial effects of B7 and B12 in Alzheimer's. Yet although the this disease is often called "diabetes of the brain" the evidence that B7 and B12 would do anything but ameliorate the damage due to increased blood glucose levels and decreases insulin sensitivity is non-existent.
          I guess, you will remember that my analysis of the role of thiamin (B1), riboflavin (B2), pantothenic acid (B5) and pyridoxin (B6) revealed... well, what did it reveal? Not much, aside from the fact that the importance of these B-vitamins in glucose management is probably overrated. For niacin, the fifth B-vitamin I have covered in this series, thing looked much different: At high doses niacin (as nicotinic acid) will have profound effects on your glucose metablism and whether those are beneficial or bad for you may eventually depend on the timing of your niacin supplements.

          In today's installment of the "There is More to Glucose Control Than Low Carb"-Series, we will tackle the rest of the B-vitamin pack to find out whether we have to add biotin (B7), folic acid (B9) and cobalamin (B12) to our list of "non-carbohydrate nutrients" with profound effects on blood glucose management.
          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
          In view of the fact that B12 is one of the shining stars on the supplement firmament and its role in mitochondrial health, it appears to be logical to assume that a couple of additional cobolamine pills (or even injections) will also help you maintain / improve your insulin sensitivity. If we take a look at one of the standard lists of symptoms that occur with low B12 levels, we will yet find
          "Pernicious anemia (numbness and tingling in hands and feet / nerve damage), shortness of breath, severe fatigue, birth defects, dementia, confusion, poor memory, depression, reduced WBCs and platelet formation, loss of appetite, weight loss, sore tongue, headaches, and nausea,"
          but not a single hint that low vitamin B12 levels could compromise your blood glucose management. And still, even if there is no direct link between vitamin B12 and diabetes, there is more than one good reason for diabetics to take cobalamine supplements:
          • Glucose management is not among the standard functions of B7 and B12.
            improvements in diabetic neuropathy (Yaqub. 1992; Sun. 2005)
          • increased risk of gestational diabetes with low B12 levels (Krishnaveni. 2009)
          • epigenetic programing that increases type II diabetes risk in the offspring of B12 deficient mouse and man (Yajnik. 2008; Deshmukh. 2013) 
          • diabetes induced cobalamine depletion (Solomon. 2011)
          • the central role of B12 in the methylaction cycle and its role in glucose management (Finer. 2013)
          On the other hand, many of the results of previous studies are of questionable value in view of the fact that serum vitamin B12 do not adequately reflecting vitamin B12 status in patients with type 2 diabetes (Obeid. 2013). It is thus no wonder that peer-reviewed evidence that would confirm any beneficial effects of B12 supplementation on glucose management is absent.
          B12 injections & L-5-MTHF supplements? For both, folic acid and methylcobalamine the provision of adequate intake levels is essential for overall health. And with both you will find people who have a hard time meeting their biological requirement due to digestive (B12; esp. elderly individuals) and genetic defects (no conversion of folic acid to fale). For these people, but not for Mr. and Mrs. Average Joe it may thus be worth spending the extra bucks on hydroxcobalamine injections and L-5-Methyltetrahydrofolate (L-5-MTHF) supplements, even if they won't have immediate beneficial effects on their blood glucose management.
          The same lack of conclusive evidence for it's direct contribution to / beneficial effects on glucose control can be found for folic acid, as well. Just like B12 it appears to help to buffer the neurological side effects of insulin resistance and reduce increased homocysteine levels of which some, but not all scientists believe that they would increase your risk of heart disease.
           
          If it were not for biotin which has a whole host of peer-reviewed studies to support its ability to improve the insulin sensitivity of diabetic and pre-diabetic animals (Reddi. 1988) and human beings (McCarty, 1999).
          Figure 1: Both blood lipids and glucose management of the diabetic subjects improved w/ chromium picolinate (600µg Cr) +biotin (2 mg) in study by Cesar Albarracin et al. (2008)
          As it was the case in the study by Albarracin et al. Figure 1 is based on, biotin is often co-administered with chromium picolinate. As you can see with quite some success and the same increase in insulin release that will also occur in healthy individuals on high dose chromium supplements (learn more).

          Beware: High dose biotin supplements are not necessarily good for healthy individuals!

          And even though there is evidence that biotin will also have beneficial effects on glucose management, when it is administered (again in high doses of 1-2g) without chromium to patients with diet-induced insulin resistance & diabetes (Koutsikos. 1996; Zhang. 1996) and patients with type I diabetes (Hemmati. 2013), I have to warn you: If you don't have blood glucose issues to begin with, taking several grams of biotin per day could do more harm than good.
          Figure 2: Changes in glucose (fasting glucose and insulin levels) and lipid management triglyceride and total cholesterol) after 4 weeks on 3x5mg/day biotine in healthy and diabetic individuals (Báez-Saldaña. 2004)
          In the study that generated the data in Figure 2 (Báez-Saldaña. 2004), biotin failed to produce any (not even insignificant) improvements in glucose management in the diabetic subjects and led to allegedly non-significant increases in blood glucose and insulin levels in the healthy study participants (see Figure 2). With 3x5mg/day the dosage was yet exorbitantly high. It's thus not surprising that the effects were similarly detrimental as those of the high dose chromium regimen by the means of which Masharani et al. messed with the insulin sensitivity of their likewise healthy subjects a previously discussed study from 2012 (read more).
          Biotin, rather for blood lipid than blood glucose management: Rather than for blood glucose, you may want to use biotin supplements for blood lipid management. As Asdrúbal Aguilera-Méndez and Cristina Fernández-Mejía argue in a 2012 paper in the scientific journal BioFactors, biotin works by increasing c-AMP and AMPK - both well, known mechanism that are triggered by lipid-lowering herbs and meds, as well. Larrieta et al. even argue that pharmacological doses of biotin will reduce the expression of lipogenic genes - genes which control, among other things, the conversion of glucose to triglycerides and the storage of the latter in the adipose organ. In a way, this mechanism could also be responsible for the increase in serum glucose Báez-Saldaña et al. observed in their high dose biotin supplementation study.
          Well, the beneficial effects on blood lipids have been observed by  Marshall et al., as well (Marshall. 1979) - at only 0.9mg/day. In their study of the "effects of biotin on lipids and other constituents of plasma of healthy men and women", they observed (a) a significant negative correlation between plasma and biotin levels and (b) a reduction in plasma lipids in response to biotin supplementation that depended not on the dosing, but on the baseline levels, meaning that volunteers who initially had elevated levels of lipids showed greater lipid reductions than those who had normal levels of lipids.

          Similar benefits occur at 1x5mg as they were administered by Revilla-Monsalve et al. to 18 diabetic and 15 normo-glycemic individuals. In contrast to the 3x5mg overdose in the previously cited study, though, the "[b]iotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects." (Revilla-Monsalve. 2006).
          So how much do you take? If you are asking me, the answer would be none, and that despite the fact that over here in Germany "food" is not as intoxicated... ah, I mean "fortified" with additional folic acid.
          If you insist on supplementing stick to 400mcg (600mcg, when pregnant) of folic acid and max 500mg of methylcobolamine (highly orally bioavailable form of B12) per day. That's plenty.
          And biotin? Well <500mcg per day probably won't hurt you.
          So what? All useless? In the end, "useless" is probably a bit too strong of a word. There is no doubt that folic acid and B12 supplements won't be able to reverse diabetes, but they can ameliorate the side effects and are essential for women who want to make sure they don't pass your own pre-diabetes on to your offspring.

          Biotin on the other hand, appears to have a place in the treatment of acute diabetes. For the average insulin sensitive SuppVersity reader who does not have elevated triglyceride levels or other blood lipid issue, high amounts of supplemental biotin (anything beyond 1mg per day chronically and 5mg per day in the short run) could even have similarly detrimental health effects as their comrades in crime, the highly popular chromium picolinate supplements.
          References:
          • Albarracin, Cesar A., et al. "Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes." Diabetes/metabolism research and reviews 24.1 (2008): 41-51.
          • Báez-Saldaña, Armida, et al. "Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects." The American journal of clinical nutrition 79.2 (2004): 238-243.
          • Deshmukh, Urmila, Prachi Katre, and Chittaranjan S. Yajnik. "Influence of maternal vitamin B12 and folate on growth and insulin resistance in the offspring." (2013): 145-156.
          • Finer, S., et al. "The role of the one‐carbon cycle in the developmental origins of Type 2 diabetes and obesity." Diabetic Medicine (2013).
          • Hemmati, Mitra, Homa Babaei, and Mohammadreza Abdolsalehei. "Survey of the Effect of Biotin on Glycemic Control and Plasma Lipid Concentrations in Type 1 Diabetic Patients in Kermanshah in Iran (2008-2009)." Oman medical journal 28.3 (2013): 195.
          • Koutsikos, Dimitris, et al. "Oral glucose tolerance test after high-dose iv biotin administration in normoglucemic hemodialysis patients." Renal failure 18.1 (1996): 131-137.
          • Krishnaveni, G. V., et al. "Low plasma vitamin B12 in pregnancy is associated with gestational ‘diabesity’and later diabetes." Diabetologia 52.11 (2009): 2350-2358. 
          • Larrieta, Elena, et al. "Pharmacological concentrations of biotin reduce serum triglycerides and the expression of lipogenic genes." European journal of pharmacology 644.1 (2010): 263-268.
          • Marshall, M. W., et al. "Effects of biotin on lipids and other constituents of plasma of healthy men and women." Artery 7.4 (1979): 330-351.
          • Masharani U, Gjerde C, McCoy S, Maddux BA, Hessler D, Goldfine ID, Youngren JF. Chromium supplementation in non-obese non-diabetic subjects is associated with a decline in insulin sensitivity. BMC Endocr Disord. 2012 Nov 30;12(1):31. 
          • McCarty, M. F. "High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes." Medical hypotheses 52.5 (1999): 401-406.
          • Obeid, Rima, et al. "Serum vitamin B12 not reflecting vitamin B12 status in patients with type 2 diabetes." Biochimie 95.5 (2013): 1056-1061.
          • Reddi, Alluru, et al. "Biotin supplementation improves glucose and insulin tolerances in genetically diabetic KK mice." Life sciences 42.13 (1988): 1323-1330.
          • Revilla-Monsalve, Cristina, et al. "Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia." Biomedicine & pharmacotherapy 60.4 (2006): 182-185.
          • Solomon, Lawrence R. "Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment." Blood reviews 21.3 (2007): 113-130.
          • Sun et al. "Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials."ACTA NEUROLOGICA TAIWANICA 14.2  (2005): 48-54.
          • Yajnik, C. S., et al. "Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study." Diabetologia 51.1 (2008): 29-38.
          • Yaqub, Basim A., Abdulaziz Siddique, and Riad Sulimani. "Effects of methylcobalamin on diabetic neuropathy." Clinical neurology and neurosurgery 94.2 (1992): 105-111. 
          • Zhang, Hong, et al. "A high biotin diet improves the impaired glucose tolerance of long-term spontaneously hyperglycemic rats with non-insulin-dependent diabetes mellitus." Journal of nutritional science and vitaminology 42.6 (1996): 517-526.