Water - Your Cheap, Effective & Safe Nootropic - Up to 31% Increased Cognitive Performance With 25ml of Plain Water

The complex neuronal clockwork in your brain needs water to run smoothly. But how much water does it need?

If you have been reading SuppVersity articles for more than a week, you will know that a lack of water can easily turn an Einstein into a Neanderthal (learn more).

Fully convincing experimental evidence for the efficacy and, more importantly, optimal amount(s) of water as a 'nootropic supplement' in non-dehydrated individuals, as it has just been provided by a recent study from the University of East London and the University of Westminster (Edmonds. 2016), however, has not been available...

Not available, yet?! That is, obviously, before Edmonds and colleagues set out to investigate the dose-response characteristics of the effects of acute water supplementation on cognitive performance and mood.

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And the scientists did not stop with a classic 'proof of concept study' in which they tested the generality of the phenomenon by assessing both adults (Study 1) and children (Study 2), but they also explored this phenomenon systematically in adults and children, using visual attention (letter cancellation) and memory (digit span) tasks that have been employed in previous studies.

Figure 1: Overview of the study design (Edmonds. 2017).

"All participants completed the thirst and mood scale, followed by baseline cognitive tests. They were then offered either 25 ml, 300 ml, or no water and were encouraged to drink the full amount, which all of them did. After water consumption there was an interval of approximately 20 min, which is the interval commonly reported in the literature reviewed above, during which the participants spent time quietly. Following the interval, participants completed the second set of scales and cognitive tests." (Edmonds. 2016).

In all experiments, the subjects (3x32 adults, mean age of participants was 21.0 years in
114 each group (300 ml, SD = 2.5 years; 25 ml, SD = 3.6 years; no water, SD = 2.8 years in Study 1 | 60 children aged 7 to 10 years in Study 2) were offered either no water, 25 ml or 300 ml water to drink. In both studies, performance was assessed at baseline and 20 min after drinking (or no drink); on thirst and mood scales, letter cancellation and a digit span test.

Figure 2: Relative changes in cognitive performance (vs. baseline test) in all three conditions (Edmonds. 2016)

As you would expect, for both children and adults, a large drink (300 ml) was necessary to reduce thirst. What may surprise, you that even a small drink (25 ml) was sufficient to improve the subjects' visual attention (at least in the letter cancellation test).

Figure 3: Rel. change in thirst and mood in adults and kids according to treatment condition (Edmonds. 2016).

The scientists own analyses of their results highlight the following main study outcomes:

• in adults, a large drink improved digit span, but there was no such effect in children, 
• in children, but not adults, a small drink resulted in increased thirst ratings, 
• both children and adults show dose-response effects of drinking on visual attention. 

The most important finding of the study at hand is thus probably that the subject's visual attention is enhanced by small amounts of fluid and appears not to be contingent on thirst reduction.

Don't waste your money on hydrogen-rich (H+) water. Its only scientifically verifiable effect is that it makes those people who sell it rich and those who fall for the scam poor | learn more.

What's the mechanism here? Well, even though the study at hand provides interesting insights into the practical applicability of water consumption on memory performance, but it does not really reveal the underlying mechanism.

In contrast to what the researchers expected, the effect was not consistently related to thirst reductions and most importantly, it appeared to differ for children and adults according to tasks. As the authors point out these "contrasting dose-response characteristics could imply cognitive enhancement by different mechanisms for these two domains" - further research with well-hydrated (and thus smart) scientists is, therefore, necessary.

Changes in the hemodynamic response in the brain would be a worthwhile starting point for such studies, for example. Links to mouth rinsing could be explored and plain water could and should be compared to flavored low-/no-energy drinks and energy-containing drinks like those of which previous studies have shown that they can increase cognitive performance even if they are not ingested, but (mouth-)rinsed (Sanders. 2012; Turner. 2014) | Comment!.

References:

• Edmonds, Caroline J., et al. "Dose-response effects of water supplementation on cognitive performance and mood in children and adults." Appetite 108 (2017): 464-470.
• Sanders, Matthew A., et al. "The gargle effect rinsing the mouth with glucose enhances self-control." Psychological Science 23.12 (2012): 1470-1472.
• Turner, Clare E., et al. "Carbohydrate in the mouth enhances activation of brain circuitry involved in motor performance and sensory perception." Appetite 80 (2014): 212-219.

Hydrogen-Rich (H+) Water Helps Athletes Perform, Improves Our Health & Prolongs Our Lives, Really? - True or False

Is H+ rich water more effective than other 'snake oil versions' of water?

Recently, Raymond asked on the SuppVersity Facebook page whether I could "please do something on the subject of hydrogen supplementation via water or gas" - and that's what I plan to do today.

As Raymond rightly points out, the use of H+ water "seems to be a big deal in longevity circles, and perhaps it holds promise for 'our crowd' as well". The obvious question is: rightly so? Or, more specifically, is there credible evidence that H+ water has ergogenic and health-promoting effects in gymrats, athletes, and Mr. & Mrs. Average Joe.

If you want to make your water "ergogenic", use it to boil a fresh coffee ;-)

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Unfortunately, the best evidence in favor or H+ therapy comes from rodents, where hydrogen gas of less than 4 % was given by inhalation. If we follow Ichihara, et al. and summarize the results of pertinent studies, we would find a broad range of pathologies that includes 31 disease categories and 166 disease models, including human diseases, as well as treatment-associated pathologies with a predominance of oxidative stress-mediated diseases and inflammatory diseases.

Table 1: Overview of Clinical trials published as of June 2015 (from Ichihara, et al. 2015).

So, yes there's evidence that H+ treatments (specifically in gaseous form) can have health benefits - at least in common models of human disease. Evidence that guzzling expensive H+ water will have immediate or chronic performance enhancing effects are yet as scarce as RCTs that would confirm the practical relevance of the results of in vitro and animal studies in healthy or sick human beings.
In humans and with respect to the significantly more popular consumption of H+ water, however, we have almost only pilot studies like the one by Aoki et al. (2012):

• Anti-fatigue effects in soccer players (Aoki, et al. 2012) --  In the study from the University of Tsukuba, each of the 10 soccer players who participated in the study was examined twice in a crossover double-blind manner; they were given either HW or placebo water (PW) for one-week intervals. Subjects were requested to use a cycle ergometer at a 75 % maximal oxygen uptake (VO2) for 30 min, followed by measurement of peak torque and muscle activity throughout 100 repetitions of maximal isokinetic knee extension. Oxidative stress markers and creatine kinase in the peripheral blood were sequentially measured.
  

  

  Figure 1: Unimpressive - Sequential changes of blood lactate levels during exercise. Blood lactate levels in the athletes given PW significantly increased immediately after exercise compared to the levels at pre-exercise (*p < 0.05 vs. time 0. #p < 0.05 vs HW, N = 10 | Aoki. 2012).

  An analysis of the data shows that the oral intake of HW prevented an elevation of blood lactate during heavy exercise. That alone is not enough to impress anyone, but since HW also ameliorated the early peak torque decline during maximal isokinetic knee extension. On the other hand, significant changes in blood oxidative injury markers, such as d-ROMs and BAP, or creatine kinase after exercise were not observed.

Even though the lactate reduction is not half as relevant as the "lactate hypothesis of fatigue" would suggest (Taylor. 2016), it is still interesting to see that H+ has opposite effects to bicarbonate, which has been shown to allow for significant increases in lactate production by buffering the conversion of this alternative brain and muscle fuel to performance impairing lactic acid.

Don't confuse H+ water with deep sea water (DSW): If you want to learn more about the latter, I suggest you read the most recent review from Malaysia (Nani, et al. 2016) | download for free

Whether that's also why H+ has been found to inhibit the growth of colon cancer cells in vitro and if the results of Runtuwene, et al. have any real-world relevance, requires further research.

Figure 2: Schematic summary of molecular mechanisms of hydrogen (Ichihara. 2015).

Potential physiological mechanisms that could explain the anti-cancer effect, as they are illustrated graphically in Figure 2 from Ichihara, et al. (2015), have been identified years ago. The "master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated" (Ichihara. 2015), and as of now, it has not been identified.

Don't waste your money on oxygen-enriched (O-) water either! In the conclusion to his paper in the British Journal of Medicine a researcher from the Duke University rightly points out "oxygenated water fails both quantitative analysis and practical physiological tests of exercise performance and recovery". That's also because "[o]nly miniscule quantities of O2 can be dissolved in drinking water compared with that required for exercise, and significant intestinal absorption of O2 is unsubstantiated." In the absence of counter-evidence it is thus only logical for him to conclude that "[e]rgogenic claims for oxygenated water therefore cannot be taken seriously" (Piantadosi. 2006).

And yet, in view of the fact that a reduction in oxidative stress and inflammation appears to be an essential downstream effect of the effects of H+ on one or several unknown "master regulators", it can hardly surprise us that there are studies to suggest...

• 

  Figure 3: Plasma glucose and insulin concentrations in response to a 75-g OGTT before (○) and after (●) consumption of hydrogen-rich pure water for 8 weeks in 6 patients with IGT (Kajiyama. 2008).

  improvements in glucose management in type II diabetics (Kajiyama. 2008); the test water of which the subjects consumed 900ml/day for 8 weeks was produced by dissolving hydrogen gas directly into the pure water, yielding hydrogen-rich pure water with the following physical properties: pH 6.7 ± 0.1, low electric conductivity (0.9 ± 0.2 μS/cm), high dissolved hydrogen (1.2 ± 0.1 mg/L), low dissolved oxygen (0.8 ± 0.2 mg/L), and an extremely negative redox potential (−600 ± 20 mV)
• increased antioxidant defenses & improved lipids in subjects with metabolic syndrome (Nakao. 2012; Song. 2013); 1.5–2 L/day and 0.8-1 L/day administered for 8 weeks and 10 weeks in Nakao et al. and Song et al., respectively 
• improved oxidative status and quality of life in patients treated with radiotherapy for liver tumors (Kang. 2011); in the study hydrogen-rich water was produced by placing a metallic magnesium stick into drinking water (final hydrogen concentration; 0.55~0.65 mM)

Whether and to which extent this is related to or corollary with the increase in pH Ostojic and Stojanovic (2014) observed in exercised subjects in response to 14 days on 2l of hydrogen-rich water per day. In said study, the subjects', "52 presumably healthy physically active male volunteers" (Ostojic. 2014),

"[...i]ntake of HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 - 0.08; p < 0.001), and postexercise pH by 0.07 (95% confidence interval; 0.01 - 0.10; p = 0.03) after 14 days of intervention. [In addition, f]asting bicarbonates were significantly higher in the HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001)" (Ostojic. 2014).

If that was the mechanism, though, you'd yet be better off with bicarbonate supplementation which will lead to much more significant improvements in pre- and post-exercise pH. And as if the lack of an understanding of the mechanism was not yet enough, the fact that many have been conducted in thoroughbred horses is likewise not exactly adding to the persuasiveness of the few studies that focus on the purported ergogenic effects of H+ (Tsubone. 2013).

As scarce as the evidence of health benefits (Ohta. 2014) of H+ may be, it is much more convincing than the quasi-non-existent evidence for relevant ergogenic effects. 

So what? The evidence for health benefits of H+ water consumption or H+ inhalation, as scarce as it may be, is, almost extensive compared to the number of studies that investigated the often-advertised performance enhancing effects of H+ water - performance enhancing effect of which the only reliable human RCT shows that they are at best statistically, but hardly practically relevant.

Based on the currently available evidence, H+ water consumption / H+ gas inhalation can thus hardly be recommended  as an ergogenic practice in gymrats and/or pro-athletes | Comment on Facebook!

References:

• Aoki, Kosuke, et al. "Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes." Medical gas research 2.1 (2012): 1.
• Ichihara, Masatoshi, et al. "Beneficial biological effects and the underlying mechanisms of molecular hydrogen-comprehensive review of 321 original articles." Medical gas research 5.1 (2015): 1.
• Kajiyama, Sizuo, et al. "Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance." Nutrition Research 28.3 (2008): 137-143.
• Kang, Ki-Mun, et al. "Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors." Medical gas research 1.1 (2011): 1.
• Nani, Samihah Zura Mohd, et al. "Deep Sea Water: Beneficial Resource for Health." Evidence-Based Complementary and Alternative Medicine (2016).
• Ohta, Shigeo. "Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine." Pharmacology & therapeutics 144.1 (2014): 1-11.
• Ostojic, Sergej M., and Marko D. Stojanovic. "Hydrogen-rich water affected blood alkalinity in physically active men." Research in Sports Medicine 22.1 (2014): 49-60.
• Nakao, Atsunori, et al. "Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study." Journal of clinical biochemistry and nutrition 46.2 (2010): 140-149.
• Piantadosi, Claude A. "“Oxygenated” water and athletic performance." British journal of sports medicine 40.9 (2006): 740-741.
• Runtuwene, Joshua, et al. "Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer." PeerJ 3 (2015): e859.
• Song, Guohua, et al. "Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome." Journal of lipid research 54.7 (2013): 1884-1893.
• Taylor, Janet L., et al. "Neural Contributions to Muscle Fatigue: From the Brain to the Muscle and Back Again." Medicine and science in sports and exercise (2016).
• Tsubone, Hirokazu, et al. "Effect of treadmill exercise and hydrogen-rich water intake on serum oxidative and anti-oxidative metabolites in serum of thoroughbred horses." Journal of equine science 24.1 (2013): 1.

Water Before Meals Doubles Weight Loss Success - Study Said to Confirm Diet Myth Gets Falsely Overgeneralized

Could this large glass of water really be the "diet game changer" some mainstream media make it look like? Or, are we - once again - dealing with the abuse of science to attract readers by propagating dubious dieting myths?

The advice to "drink a glass of water before every meal" is about as old as human efforts to lose weight. Yet despite the fact that an increase in daily water consumption is widely advocated as a useful tool to aid weight loss and even included in popular weight loss programs like Weight Watchers, there is, according to the latest systematic review of the association between water consumption and body weight,  little evidence to support this practice outside of energetically restricted interventions (Muckelbauer. 2013).

In other words: While we do have evidence that replacing caloric beverages with water/diet beverages works (Tate. 2012), we have little evidence that simply drinking more will accelerate weight loss and almost no evidence of the potential benefits water preloading before meals, in particular.

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Quite surprising, isn't it. I mean, it should be obvious that drinking a glass or two of water before a meal would be a highly promising strategy to reduce meal energy intake by modifying an individuals’ perception of fullness prior to eating by, as Parretti et al. (2015) put it, "consuming a 'preload' of water". Nevertheless, Daniels' 2010 systematic review identified only two small laboratory studies that specifically investigated whether water preloading reduced energy intake. As Parretti et al. point out in the introduction to their own study,

"[b]oth studies compared participants given a water preload of 500 ml for 30 min before an ad libitum meal with those not given a preload and found that energy intake at the meal was lower for the preload group compared with the no-preload group" (Parretti. 2015). 

Thus, evidence to suggest that water preloading may improve the effectiveness of weight loss programs is there. Experimental evidence to confirm that is yet ultra-scarce. In fact, the only RCT (Dennis. 2015) to directly examine the effects of water preloading before meals on weight loss was published five years ago. In said study, 48 adults with overweight or obesity were allocated to a hypocaloric diet plus 500 ml of water before meals every day (water preload group) or a hypocaloric diet alone intervention (nonwater group) over 12 weeks.

Figure 1: Dennis et al. were the first to show that drinking 500 ml of water before meals everyday can boost the weight loss success of overweight and obese individuals participating a 12-week diet intervention (Dennis. 2010).

As you can see in Figure 1, the subjects in the water group lost ~2kg more weight than their peers and showed a 44% greater decline in weight over the 12 weeks than the nonwater group. That's interesting because the energy intake during test meals was suppressed by the additional water load only at baseline, yet not after 12 weeks on the preloading protocol (see Figure 2).

Figure 1: In a previous study the beneficial effect of the water preload on food energy intake wore off. The subjects in Dennis' study still lost more weight with the preload, but with respect to the long-term efficacy of drinking 500ml of water before every main meal this is an important result we should not forget (Dennis. 2010).

One of the things we will have to look for when analyzing Paretti's more recent study is thus whether she made sure to check if the appetite reducing effects persist. After all, their study was very similar to the one by Dennis, with an important difference in the study population which was not predominantly middle aged or older white men and women in Paretti's study. Otherwise there are only very few surprises with regard to the study design. Here's what we're talking about:

• a two-group randomized controlled trial with eighty-four adults with obesity 
• all participants were given a face-to-face weight management consultation at baseline (30 min) and a follow-up telephone consultation at 2 weeks (10 min)
• participants were randomized to either drinking 500 ml of water 30 min before their main meals or an attention control group where participants were asked to imagine their stomach was full before meals (*)
• primary outcome was weight change at 12-week follow-up

In that, the "(*)" denotes something you might consider weird... and what should I say? It is weird to imagine that your stomach is full before a meal, but that's Parretti's way of turning a regular RCT into an attention controlled RCT, where the dummy procedure disguised the true intent of the study and provided a nonspecific intervention that in some ways matched preloading.

Table 1: Self-reported adherence for both groups - (I) intervention group, (C) control group (Parretti. 2015).

It is thus not really surprising that the subjects in the control group (C) hardly managed to follow the scientists advise once a week, while the majority of the subjects in the intervention group (I) consumed their water preload on at least two of three meals per day. The data in Table 1 does yet still leave no doubt that the adherence declined significantly over the 12-week period. Whether the Parretti study is able to answer the previously raised question, if the chronic use of water preloads may reduce their efficacy, is thus highly questionable. I mean, after 12 weeks, almost half of the subjects didn't use the preload anymore.

Table 2: Self-reported fullness and satiety scores for both groups - (I) intervention group, (C) control group; fullness and satiety scores can range from 1 to 10 (Paretti. 2015)

Against that background, I would not interpret the stable satiety and fullness levels from week 2-9 as evidence that there is no such habituation effect. And in view of the lack of data on the actual food intake, the satiety and fullness data is pretty much irrelevant, anyways (just as there's a disconnect between mTOR and actual muscle gains, there are also disconnects between appetite, fullness and food / energy intake - if you don't measure the relevant outcome you're groping in the dark).

Figure 2: Weight loss (in kg) over the 12-week study period (unadjusted values | Parretti. 2015)

What is relevant and hard to reject, though ,is the fact that the water preloading group lost 1.3 kg more than the subjects in the control group (see Figure 2) - with a statistically significant difference of 1.2 kg still remaining when the data was adjusted for ethnicity, deprivation, age, and gender, the lack of which had been an issue in the previously referenced study by Dennis et al. (2010).

The reason I am still not thrilled is simple: Parretti's study was celebrated in the laypress as the breakthrough research that demonstrates that you can easily lose weight by simply drinking 500ml of water before each and every of your meals. Unfortunately, this is not just a broad overgeneralization of the results it is simply a completely false interpretation of the study. What Parretti's study does suggest (not prove) is that drinking 500ml will accelerate the weight loss on energy reduced diet.

"Chewing gums will help you lose weight" - That's another commonly heard dieting myth. One that may actually be true, though... albeit only if the gum is a nicotine gum, which could in fact promote fat loss | more

Trigger vs. support - That's an important difference! The most significant result of the initially referenced meta-analysis by Muckelbauer et al. was after all the disparity between studies of individuals dieting for weight loss and those who were on ad libitum diets. A disparity which suggest a weight-reducing effect of increased water consumption occurs only if you are on an energetically reduced diet (just like the subjects in the study at hand). In studies in general mixed-weight populations like you and me, however, such an effect has - as of yet - not been observed. It is thus more than questionable, whether pre-diluting each and every of your meals with 500ml water is going to help you stay lean. What it may do - and that's in fact something the Peretti study suggests - is to help you stick to a calorically restricted diet and thus lose weight faster and more effectively | Comment on Facebook!

References:

• Daniels, Melissa C., and Barry M. Popkin. "Impact of water intake on energy intake and weight status: a systematic review." Nutrition reviews 68.9 (2010): 505-521.
• Dennis, Elizabeth A., et al. "Water Consumption Increases Weight Loss During a Hypocaloric Diet Intervention in Middle‐aged and Older Adults." Obesity 18.2 (2010): 300-307.
• Muckelbauer, Rebecca, et al. "Association between water consumption and body weight outcomes in children and adolescents: A systematic review." Obesity 22.12 (2014): 2462-2475.
• Parretti, Helen M., et al. "Efficacy of water preloading before main meals as a strategy for weight loss in primary care patients with obesity: RCT." Obesity (2015).
• Tate, Deborah F., et al. "Replacing caloric beverages with water or diet beverages for weight loss in adults: main results of the Choose Healthy Options Consciously Everyday (CHOICE) randomized clinical trial." The American journal of clinical nutrition 95.3 (2012): 555-563.

Every Sip of Plain Water Reduces Your T2DM Risk, Oxidized Proteins are Better Indicators of Metabolic Health Than Oxi-Lipids and Melatonin Can Rein Expanding Fat Cells in

The "apple a day" is the epitome of nutritional factors influencing your health.

Alright, it's Thursday and about time for a brief update on the latest nutrition research studies including a re.appreciation of the role of melatonin in obesity protection, the importance of drinking enough water (not tea or coffee) for anyone who's looking to keep insulin sensitive and the overlooked importance of so-called "Advanced Oxidation Protein Products (AOPPs)" of which a recent study in the peer-reviewed scientific journal Nutrition Research says that they "are more related to metabolic syndrome components than biomarkers of lipid peroxidation" (Venturini. 2015).

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Speaking of AOPPs, what if we simply start with this #2 on the list of parameters for the determination of oxidative stress in metabolic syndrome (MetS) patients? Alright, then.

• Advanced Oxidation Protein Products (AOPPs) are more Related to Metabolic Syndrome Components than Biomarkers of Lipid Peroxidation (Venturini. 2015) - As previously hinted at, AOPPs are not exactly the #1 marker of how severe one's metabolic syndrome is. Rather than advanced oxidation protein products (AOPPs), most researchers use markers of lipid peroxidation to determine the level of oxidative stress in metabolic syndrome (MetS) patients - because they are more reliable? No, but rather because that's what they've done for decades in spite of the fact that a direct comparison between protein and  has not been performed yet.
  
  The aim of a recent study from the University of Londrina was thus to compare protein peroxidation with lipid peroxidation measured by two different methodologies [tert-butyl hydroperoxide initiate chemiluminescence (CL-LOOH) and ferrous oxidation-xylenol orange (FOX) assay]. The hypothesis the scientists wanted to prove was that AOPPs would be more related to MetS than oxidative markers of lipid peroxidation. To validate it, they conducted a cross-sectional study with 76 patients with MetS and 20 healthy subjects serving as controls.
  
  The results of the study unsurprisingly confirmed that that the prooxidant-antioxidant index (PAI) assessed as AOPPs/TRAP ratio progressively increased (p<0.05) according to the number of MetS components. For the AOPPs and total radical-trapping antioxidant parameter (TRAP) it took five components, e.g. obesity, insulin resistance, etc. for them to increase (p<0.05) when five components were compared to three components.
  

  

  Table 1: Here's the problem: Neither the hydroperoxide count nor FOX which are often measured to assess the oxidative assault in order to classify the severity of MetS show sign (bold) correlations with the quantity, i.e. MetS severity they're supposed to quantify (Venturini. 2015).

  More importantly, though, the spearman`s test the scientists conducted to evaluate the predictive value of AOPPs confirmed high correlations of the quantity of damaged proteins, the  waist circumference (WC) (r= 0.318, p<0.01), fasting glucose (r= 0.250, p<0.05), HOMA-IR (r= 0.043, p<0.01), triacylglycerol (r= 0.713, p<0.0001), hsCRP (r= 0.275, p<0.05) and uric acid (r= 0.356, p<0.01) levels, whereas there was inverse correlation with HDLc (r= −0.399, p<0.001).
  
  That's not better than the prooxidant-anioxidant index, though, but significantly more reliable than a simple measure of lipid peroxidation. As the authors point out, "[i]n a broader context, the impact of this original work lays in the importance of determining AOPP in the study of metabolic syndrome patients; understanding the mechanisms by which an early event in MetS pathophysiology, such as oxidative stress act on chronic diseases will enable us to comprehend the rationale which underlies intervention in such conditions" (Venturini. 2015). As always, though, more studies are warranted to confirm the present data.
• Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice (Favero. 2015) - Before I discuss the results of the study at hand, let me briefly deal with the rumor that taking melatonin supplements would make you insulin resistant that's all over Facebook, recently.
  
  While there's no doubt that the study people cite to substantiate their claims shows a sign. reduction in the clearance of glucose during an oral glucose tolerance test, the whole regimen Rubio-Sastre et al. used is BOGUS, ... unless obviously you take your melatonin pill and start pigging out on a glass of liquid sugar there-after instead of going to bed. In other words, with the timing being "take a melatonin pill, wait for the melatonin to hit your blood stream, do the glucose tolerance test", the protocol has nothing to do with the way you're supposed to take melatonin, i.e. 1-2 hours after your last meal and ~1h before you go to bed without bedtime candy. When it's released at the right time and away from the immediate post-prandial phase, melatonin is after all a negative predictor of your T2DM risk (McMullan. 2013).
  

  

  Figure 1: Melatonin acts it anti-metabolic-syndrome magic right at the level of the fat cell (Favero. 2015)

  Against that background it's not really surprising that a team of scientists from the University of Verona recently observed that "[m]elatonin supplementation by regulating inflammatory infiltration ameliorates obesity-induced adipokine alteration" (Favero. 2015). That's a result that stands in line with those of previous studies showing that
  • melatonin will increase the expression of leptin in fat cells and thus tell your body there was more fat around (Alonso-Vale. 2005) - something that may be interesting particularly for reduced obese people who cannot lose weight / regain weight easily;
  • melatonin will also inhibit the formation of new fat cells and storage of extra-energy in (Alonso‐Vale. 2009; Zhang. 2010) - an effect of which most people ignore that it could be partly responsible for the acute reduction in insulin sensitivity, especially in under-muscled post-menopausal women as they were used as subjects in the Rubio-Sastre study, because any reduction in lipid storage in the fat cells obviously means that the extra energy would have to be stored elsewhere;
  • melatonin promotes the browning of white and activity of brown fat cells and thus the positive metabolic activity of your body fat (Heldmaier. 1974; Tan. 2011)
  That's in contrast to lean mice, where the adipokines were unaffected and the effects on body weight may - as previous studies show depend on keeping the levels youthful (Wolden-Hanson. 2000; Zanuto. 2013).
• Higher plain water intake is associated with lower type 2 diabetes risk: A cross-sectional study in humans (Carroll. 2015) - As a SuppVersity reader you know about the importance of optimal hydration, right (if not click here)?
  
  If so, you will probably not be extremely surprised that researchers from the University of Bristol found that not British tea, but rather a high plain water intake is associated with lower type 2 diabetes risk in 138 adults from Southwest and Southeast England who answered a cross-sectional online survey assessing T2D risk (using the Diabetes UK risk assessment), physical activity (using the short International Physical Activity Questionnaire), and consumption of fruits, vegetables and beverages (using an adapted version of the Cambridge European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire).
  

  

  Figure 2: Fully adj. associations between intake of beverages (mL/d) and diabetes risk score (Carroll. 2015)

  More specifically, the scientists found (a) a significant negative association between plain water intake and type II diabete (T2D) risk scores and (b) an impressive 0.72 pt reduction in T2D risk score for every 240mL cup of water consumed per day
  
  That's in contrast to the significant positive correlation the scientists observed for full-fat milk and the non-significant correlation for caffeinated beverages. Likewise worth mentioning is probably that (a) the effects were most pronounced in older individuals aged 60–69 years and people with a high, but not extreme waist circumference of 100-109 cm. Why's that important? Both the age group and the waist size indicate being at a decisive point at which the next months or centimeters can make the difference between staying slightly insulin resistance and developing full-blown diabetes.

What else? Well, since this is a "nutrition research update", I guess it may be worth mentioning the recent scientific debate about the role of exercise in losing and maintaining weight. In several comments in scientific papers scientists have argued that the role of exercise in weight loss had been exaggerated and they are - you as an active individual know that - right; despite the fact that we all know that diet and exercise are only two sides of the 'healthy lifestyle coin' (Brady. 2015).

Whether you're young or old, nutrition counts, but it's not the only determinant of your psychological and physiological health | Learn more about the role of nutrition in aging.

What they forget is that exercise has proven beneficial effects on your psyche and congnition (Hughes. 1984; Stephens. 1988; Wankel. 1993; Laurin. 2001, etc.). What they forget is that exercise will keep you mobile and your bones and muscles from withering away (Rogers. 1993; Daley. 2000; Williams. 2002). What they forget is that exercise is one of the main determinants of whether it's fat or other tissue weight you're losing when you're dieting and what they forget is that physical fitness is a much better determinant of one's metabolic health than the ratio of height²/weight scientists call the "body mass index" (BMI). Make sure you don't forget that when you read one of these infectious articles on Internet | Comment on Facebook!

References:

• Alonso-Vale, Maria Isabel Cardoso, et al. "Melatonin enhances leptin expression by rat adipocytes in the presence of insulin." American Journal of Physiology-Endocrinology and Metabolism 288.4 (2005): E805-E812.
• Alonso‐Vale, Maria Isabel Cardoso, et al. "Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPβ transcriptional activity." Journal of pineal research 47.3 (2009): 221-227.
• Brady, Anne O., et al. "Physical Activity and Exercise: Important Complements to Nutrition in Older Adults." Handbook of Clinical Nutrition and Aging. Springer New York, 2015. 355-374.
• Carroll, Harriet A., Mark G. Davis, and Angeliki Papadaki. "Higher plain water intake is associated with lower type 2 diabetes risk: A cross-sectional study in humans." Nutrition Research (2015).
• Daley, Monica J., and Warwick L. Spinks. "Exercise, mobility and aging." Sports Medicine 29.1 (2000): 1-12.
• Favero et al. "Melatonin reduces obesity and restores adipokine patterns and metabolism in obese (ob/ob) mice." Nutrition Research (2015): in press.
• Heldmaier, Gerhard, and Klaus Hoffmann. "Melatonin stimulates growth of brown adipose tissue." (1974): 224-225.
• Hughes, John R. "Psychological effects of habitual aerobic exercise: A critical review." Preventive medicine 13.1 (1984): 66-78.
• Laurin, Danielle, et al. "Physical activity and risk of cognitive impairment and dementia in elderly persons." Archives of neurology 58.3 (2001): 498-504.
• McMullan, Ciaran J., et al. "Melatonin secretion and the incidence of type 2 diabetes." Jama 309.13 (2013): 1388-1396.
• Rubio-Sastre, Patricia, et al. "Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening." Sleep 37.10 (2014): 1715.
• Venturini, Danielle, Andréa Name Colado Simão, and Isaias Dichi. "Advanced Oxidation Protein Products (AOPPs) are more Related to Metabolic Syndrome Components than Biomarkers of Lipid Peroxidation." Nutrition Research (2015).
• Rogers, Marc A., and William J. Evans. "Changes in skeletal muscle with aging: effects of exercise training." Exercise and sport sciences reviews 21.1 (1993): 65-102.
• Stephens, Thomas. "Physical activity and mental health in the United States and Canada: evidence from four population surveys." Preventive medicine 17.1 (1988): 35-47.
• Tan, D‐X., et al. "Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity." Obesity Reviews 12.3 (2011): 167-188.
• Wankel, Leonard M. "The importance of enjoyment to adherence and psychological benefits from physical activity." International Journal of Sport Psychology (1993).
• Williams, Glenn N., Michael J. Higgins, and Michael D. Lewek. "Aging skeletal muscle: physiologic changes and the effects of training." Physical Therapy 82.1 (2002): 62-68.
• Wolden-Hanson, T., et al. "Daily Melatonin Administration to Middle-Aged Male Rats Suppresses Body Weight, Intraabdominal Adiposity, and Plasma Leptin and Insulin Independent of Food Intake and Total Body Fat 1." Endocrinology 141.2 (2000): 487-497.
• Zanuto, Ricardo, et al. "Melatonin improves insulin sensitivity independently of weight loss in old obese rats." Journal of pineal research 55.2 (2013): 156-165.
• Zhang, Liangming, et al. "Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγ expression and enhancing Runx2 expression." Journal of pineal research 49.4 (2010): 364-372.

The Latest Gut Microbiome Modulators: Beneficial Effects of Cacao, Negative Effects of Acidic Water and Preliminary Evidence of the Negative Impact of Gluten & Whole Grains

Pancakes al cacao & your gut: Bad grains and good cacao?

There is an increasing amount of interesting scientific publications on the role of the gut microbiome in health and disease. Unfortunately, the evidence on what exactly influences the number and types of bacteria in our gut in a beneficial way and even what exactly a "beneficial way" actually is, is yet largely unknown.

In today's installment of the SuppVersity Short News, I am going to take a closer look at a selection of recent studies that may shed at least some light at the previously mentioned questions.

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• Cacao as a gut microbiome modulator - The first study we're going to look at deals with cacao. Cacao and its effect on the gut microbiome. In said study, 3-week-old Wistar and Brown Norway rats were fed, for 4 weeks, either a standard diet or the following three isoenergetic diets containing increasing proportions of cocoa flavonoids from different sources: one with 0·2 % polyphenols (from conventional defatted cocoa), and two others with 0·4 and 0·8 % polyphenols (from non-fermented cocoa, very rich in polyphenols).
  
  

  

  Only the regular theobromine containing cacao did also reduce the weight gain in the three-week study (Massot-Cladera. 2014).

  What the scientist found, when they analyzed the serum Ig concentrations, faecal IgA levels, microbiota composition and IgA-coating bacterial proportion at the end of the study and compared them to those at the beginning was a significant beneficial effect on the mucosal IgA levels and microbiota composition from all supplements. The 0.2 % cacao diet which contained a higher proportion of theobromine and fibre, however, had a more profound impact on the aforementioned parameters - in spite of the fact that there was less cacao in the diet. Obviously, the caffeine-like bitter alkaloid from cacao is contributes to the beneficial effects of cacao in a similar way as the polyphenols.
  
  As the body weight data in Figure 1 shows, the theobromine containing conventional cacao was also the only one that was able to reduce the diet induced weight gain in the rats. This could, but does not necessarily have to be related to the higher levels of Bacteroides, Bifidobacterium and Lactobacillus bacteria in the gut of the rodents that received the "cheap" conventional cacao.
• Acidic water triggers type I diabetes - probably by modulating the gut microbiome - No, I am not trying to advertise bicarbonate, here. I am just reporting the results of a recent study from the Medical University of South Carolina which found that a stain of mice that's particularly susceptible to type I diabetes developed insulitis and hyperglycemia rapidly, only when the mice were maintained on acidic pH water (AW).
  
  

  

  Suggested Article: "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals! Causative or Corollary? Plus: Are Grains, not Meats the Main Offenders in Our Diet?" | read more.

  The scientists also observed that this effect could be countered by fecal transplants and was obviously triggered by changes in the diversity of the gut flora that occurred, when the pH of drinking water was in the acidic range and were probably related to the proinflammatory cytokine response in the intestinal mucosa.
  
  As you as a SuppVersity reader know previous studies in humans have already shown that a "High Dietary Acid Load Doubles Risk of Type II Diabetes in Lean Individuals!" (read more) - Who knows, this could also be related to the effect on the gut microbiome!?
• Gluten and whole grains as modulators of the gut microbome - In two recent randomized cross-over trials, researchers from the University of Copenhagen determined the impact of dietary gluten or whole grains on the gut microbiome and host metabolic health.
  
  What the researchers found was what the recent backlash against gluten and "healthy" whole grains on the internet would suggest the already overweight "[p]articipants had slightly elevated fasting glucose levels and increased waist circumference" (Ibrügger. 2014).
  

  

  Table 1: Overview of the products used in the randomized controlled cross-over trials (Ibrügger. 2014)

  Whether that's related to the effects on the gut microbome is unfortunately something I can't tell you, yet. Why? Well, the currently available paper refers to a future publication that would outline the detailed results. All I can tell you now is that the study used the products listed in Table 1 and, more importantly, that it is its high statistical power, which, due to the large sample size and the crossover design, "allows detecting even small diffrences in the outcome variables" (Ibrügger. 2014).

Suppversity Suggested: "Stevia Kills Good Gut Bacteria - One Study Enough to Stop Using the Natural Sweetener? Probably Not in View of its Anti-Diabetes, Anti-LDL, Anti-Viral & Anti-Cancer Effects" | more

Bottom line: It's a pity that we still can't tell for sure what the "optimal" gut microbiome looks like. Moreover, the currently available scientific evidence suggests that what is considered "optimal" may well depend on your type of diet and / or your metabolic health.

Against that background the previously presented results offer nothing but a brief glimpse at what may become one of the hottest topics in obesity and diabetes prevention in the future. At the moment, though, all the results and any recommendations that are based on these results have to be considered preliminary. And this is also true for the gluten + whole grain study of which you will certainly read again, here at the SuppVersity | Comment on Facebook!

References:

• Ibrügger, S., et al. "Two Randomized Cross-Over Trials Assessing the Impact of Dietary Gluten or Wholegrain on the Gut Microbiome and Host Metabolic Health." J Clin Trials 4.178 (2014): 2167-0870.
• Massot-Cladera, Malen, et al. "Impact of cocoa polyphenol extracts on the immune system and microbiota in two strains of young rats." British Journal of Nutrition 112.12 (2014): 1944-1954.
• Sofi, M. Hanief, et al. "pH of drinking water influences the composition of gut microbiome and type 1 diabetes incidence." Diabetes 63.2 (2014): 632-644.