40 vs. 20g PWO Protein Sign. Boost Recovery After Muscle Damage / High Dietary Nitrate = No Supplement Benefits?

High nitrate without beetroot? Not a problem, check out Jonvik's complete list of high nitrate foods in Table 1.

Not every study is worth its own SuppVersity article... that's not because it wasn't well done, or boring, though. Sometimes there's just not that much to discuss beyond the mere results. Today that's the case for two studies by Doering et al. and Jonvik et al. that are supposed to be published in one of the upcoming issues of the International Journal of Sport Nutrition and Exercise Metabolism. A journal from which I also took five additional studies which make a guest appearance in the bottom line of today's installment of the SuppVersity Short News.

Read about rather exercise-related studies at the SuppVersity

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HbA1c, Bone Health, BFR & More | Jan'17

TeaCrine®, ALA, Tribulus, Cordy-ceps, Sesamin...

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• Higher post-workout protein intake may have hitherto overlooked benefits on recovery after exercise-induced muscle (Doering 2016) -- Even though the observation that increasing the post-workout protein intake from ~30 to ~40 grams (consumed in three bolus feedings at two-hour intervals post exercise) "provided moderate to large beneficial effects on recovery that may be meaningful following EIMD [exercise-induced muscle damage]" (Doering 2017). Is unquestionably one of those results that are worth mentioning in the SuppVersity Short News - the "just the gist" version of regular SuppVersity Articles.
  

  

  Figure 1: The high protein dose (0.6g/kg in 6h post-workout) provided a "moderate beneficial" effect on peak isometric force recovery; with only -3.6% the HPI treatment helped to sign. lower reduction in peak isometric force which amounted to -8.6% with the MPI aka medium (3g/kg) protein treatment (Doering 2017).

  And that's in spite of the fact that the post-cycling test showed no inter-group difference between the medium (MPI = 0.3g/kg body weight) and high (HPI = 0.6g/kg) protein group, (HPI=2395±297 s vs. MPI=2369±278 s; d =0.09) and because the HPI consumption provided a moderate beneficial effect (d=0.66) on the loss of afternoon peak isometric contractile force (-3.6%, d=0.09 compared to the MPI -8.6%, d=0.24), as well as a large beneficial effect (d=0.83) on the fatigue over the eight-hour recovery.
  
  For resistance trainees who will always leave the gym with a certain degree of muscle damage, the hastened peak force recovery is obviously important... whether a difference in the 6h post recovery actually matters, on the other hand, may be debatable (it's unlikely that you'd still measure a difference after 24h, but not impossible).
• High dietary nitrate intake - Could it explain why nitrate supplements don't work for highly-trained / professional athletes? (Jonvik 2016) --  While it is difficult to answer this question based on a recent study by Jonvik, Kristin L., et al. their data from 553 athletes (n=226 females: 172±8 cm, 65±9 kg, BMI 22±2 kg/m2; n=327 males: 181±11 cm, 72±14 kg, BMI 22±3 kg/m2) from strength (n=71), team- (n=242) or endurance (n=240) sports indicates that the mean nitrate intake (ca. 70-180 mg/d) of these Dutch athletes is not significantly higher than that of the average European (31–185 mg/d | Gangolli et al. 1994) or US (~40-100mg/day) citizen.
  

  

  Figure 2: If you see that the female (A) and (B) male athletes got the lion's share of nitrate from vegetable sources and take a look at their individual breakdown in (C), you won't be surprised that people on the DASH diet get up to >1200mg+ nitrate/day. In those people, extra nitrate may in fact simply fizzle out.

  Accordingly, I have to go back on my previously voiced hypothesis that a high baseline nitrate intake could explain why most studies in trained athletes such as most recently Nyakayiru et al. (2016), Callahan et al. (2016), and Lowings et al. (2017) did not find significant performance benefits, while studies in exercise noobs tend to find benefits. Rather than a difference in baseline intake, it's thus probably a difference in terms of the significance of the increase in blood flow on the performance of trained vs. untrained muscles.
  

  

  Table 1: Tabular overview of nitrate content according to food-group (left) and of various vegetables (right).

  One thing I should mention, though, is that, without testing the nitrate intake of the individuals in a given study, directly, all the above has to remain educated guesswork.

Salt reduction is for "hard-sweating" athletes not; and another new study actually shows that even athletes who consume a meal after workouts can speed up rehydration if they consume a 50 mmol/L NaCl solution (Evans 2017) - I guess salting your food to taste may yet be enough for most of you | learn more.

Things that don't work: Often-times scientists exaggerate the practical relevance of their results in the conclusions to their studies. This goes so far that, for a layman, sometimes even a null-result appears to support the purchase of a given supplement. One of the reasons this happens is that no one wants to read studies with null results... no one, but SuppVersity readers, I guess, because you understand that it's  just as important to know what doesn't work as it is to know what does work.

To cut a long story short: Here's what soon-to-be-published studies from the International Journal of Sport Nutrition and Exercise Metabolism have to tell you about "things that don't work". One of these things are the nitrate and beetroot supplements in trained or elite athletes on land (Callahan 2016, Nyakayiru 2016) and in the water (Lowings 2017  | see discussion about nitrate intakes above). Likewise on this list of barrel-bursts is coconut water, which does, probably due to its low sodium/potassium ratio, not improve markers of hydration or exercise performance in a recent study by Peart, et al (2016) | Comment on Facebook!

References:

• Evans, Gethin H., et al. "A Sodium Drink Enhances Fluid Retention During 3 Hours of Post-Exercise Recovery When Ingested With a Standard Meal." International Journal of Sport Nutrition and Exercise Metabolism (2017): 1-21.
• Doering, Thomas M., et al. "The Effect of Higher Than Recommended Protein Feedings Post-Exercise on Recovery Following Downhill Running in Masters Triathletes." International journal of sport nutrition and exercise metabolism (2016): 1-17.
• Gangolli, Sharat D., et al. "Nitrate, nitrite and N-nitroso compounds." European Journal of Pharmacology: Environmental Toxicology and Pharmacology 292.1 (1994): 1-38.
• Jonvik, Kristin L., et al. "Habitual Dietary Nitrate Intake in Highly Trained Athletes." International Journal of Sport Nutrition and Exercise Metabolism (2016): 1-25.
• Lowings, Sam, et al. "Effect of Dietary Nitrate Supplementation on Swimming Performance in Trained Swimmers." International Journal of Sport Nutrition and Exercise Metabolism (2017): 1-24.
• Mensinga, Tjeert T., Gerrit JA Speijers, and Jan Meulenbelt. "Health implications of exposure to environmental nitrogenous compounds." Toxicological reviews 22.1 (2003): 41-51.
• Nyakayiru, Jean, et al. "No Effect of Acute and 6-Day Nitrate Supplementation on VO2 and Time-Trial Performance in Highly-Trained Cyclists." International Journal of Sport Nutrition and Exercise Metabolism (2016): 1-25.
• Peart, Daniel J., Andy Hensby, and Matthew P. Shaw. "Coconut water does not improve markers of hydration during sub-maximal exercise and performance in a subsequent time trial compared to water alone." International Journal of Sport Nutrition and Exercise Metabolism (2016): 1-19.

Mercury Toxicity - Is Your Whey Protein Worse than Your Amalgam Fillings? Maybe, but That's not so Bad, Anyway...

Could your whey protein contribute more to your mercury exposure than your 20-year old amalgam fillings?

30 years ago Eggleston, et al. published a paper in "The Journal of Prosthetic Dentistry" which confirmed that there is a statistically significant "positive correlation between the number of occlusal surfaces of dental amalgam and mercury levels in the brain (p < .0025 in white matter)" (Eggleston. 1987). Only recently Bentsson et al highlighted that modern amalgam fillings may leak even more of the toxic substance into your saliva (from where it will take a tour around your body). And earlier this year the European Union banned amalgam fillings - albeit only for kids and without admitting that they are a definite health threat.

High-protein diets are much safer than some 'experts' say, but there are things to consider...

Practical Protein Oxidation 101

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Satiety: Casein > Whey? Wrong!

Protein Timing DOES Matter!

High Protein not a Health Threat

You already knew all that? Well, in that case, you were probably also aware of the fact that the dietary and environmental mercury exposure of the average Westerner will significantly outweigh the contribution of amalgam fillings to your daily mercury load. Furthermore, I would venture the guess that you are soon going to tell me that you're avoiding high-mercury fish, live in a very clean area and don't buy food and other products from China, right? That's all good for you, but have you ever thought about the mercury content of your beloved whey protein?

Table 1: Sources and estimates of daily human exposures to various forms of mercury (Gochfeld 2003).

No!? Well, I have to admit, I haven't done that either... at least not before I hit on Leticia Fraga Matos Campos de Aquino's latest paper in the Journal of Food Composition and Analysis (de Aquino 2017).

Listen to me talk about this and other studies on Super Human Radio: Download "SHR # 2003 :: SuppVersity Science Roundup: Is There Mercury in Whey Protein - Exogenous Insulin Prevents T2DM Cure - Non-Nutritive Sweeteners Increases Appetite for Sweets - Possible SIBO Recovery Without Antibiotics" here.

It's a study in which the authors measured the total mercury (THg) content of nineteen brands of whey protein with different formulations and estimated the potential health risks of mercury exposure to humans through whey protein consumption.

Figure 1: Total (organic + inorganic) mercury content of 19 samples of whey proteins from Brazil (de Aquino 2017)

As you can see in Figure 1 the exact amount of mercury in the nineteen (undisclosed) whey protein products varies significantly, ranging from 0.548 ± 0.029 ng/g 9.41 ± 0.295 ng/g of whey protein. Sounds pretty bad, right? Well, as the authors point out, "[t]hese concentrations [are] below the maximum limit for food products" (de Aquino 2017). Still, the scientists' calculations indicate

"that potential health risks related to exposure to total mercury from whey protein ingestion need more attention from researchers and more studies are needed, especially including specific intake of mercury from other food products that are included in a balanced diet" (de Aquino 2017).

Eventually, only more sophisticated follow-up studies will be able to assess the influence of the other components in whey protein, its solubility, the metal oxidation state, the retention percentage, the intake frequency, and the absorption rate and efficiency of excretion mechanisms and thus to determine if the up to ~300 ng of mercury you could be washing down with every 30g shake is a significant threat to your health, or not. As of now, it appears to be very unlikely, though - if nothing else than because a US study shows that a single serving of fish (228g) bought in New Jersey could contain 50000 ng or 50µg according to a 2005 study by Burger, et al (learn more about mercury in fish).

If you want to worry about whey protein or your protein intake in general - worry about its oxidation | more

Do you have to avoid using whey now? The answer is no. Irrespective of whether your whey protein contains as little as 0.548 ng or as much as 9.41 ng mercury per gram, you're not going to surpass the (albeit generous) upper 710 ng/kg of body weight intake limit of the WHO (US EPA says < 1000ng/kg | Rice 2004). After all, that's 53µg/day and thus not one, not two and not even three, but rather approximately 188 whey protein shakes (each made with 30g of powder) for an individual with a body weight of 75 kg - I guess even the craziest bodybuilding nuts won't be able to achieve those daily intake levels.

Personally, I have to admit that I still find it noteworthy that a whey protein will have - in the worst case - 3-fold more mercury than bread, cereals, various oils and fats, sugar and preserves or nuts and even 13-19-fold more mercury than fruits and vegetables (calculated based on data from the UK | Rose 2010) - but NO, that's not a reason to panic and whether that's more or less than you'd get from amalgam fillings depends on their size, integrity and the source you cite. In fact, studies will say that the daily exposure from amalgam fillings is anything from <1µg to 17µg - and that does not depend on sponsorship. Accordingly, there's no consensus on whether you should (Folwaczny 2002) or shouldn't (Larkin 2002) get them removed at the risk of significant mercury exposure during the removal procedure | Comment on Facebook!

References:

• de Aquino, Leticia Fraga Matos Campos, et al. "Mercury content in whey protein and potential risk for human health." Journal of Food Composition and Analysis (2017).
• Bengtsson, Ulf G., and Lars D. Hylander. "Increased mercury emissions from modern dental amalgams." BioMetals (2017): 1-7.
• Burger, Joanna, and Michael Gochfeld. "Heavy metals in commercial fish in New Jersey." Environmental Research 99.3 (2005): 403-412.
• Egan, S. K., et al. "US Food and Drug Administration's Total Diet Study: intake of nutritional and toxic elements, 1991–96." Food Additives & Contaminants 19.2 (2002): 103-125.
• Eggleston, David W., and Magnus Nylander. "Correlation of dental amalgam with mercury in brain tissue." The Journal of prosthetic dentistry 58.6 (1987): 704-707.
• Folwaczny, Matthias, and Reinhard Hickel. "Should amalgam fillings be removed?." The Lancet 360.9350 (2002): 2081.
• Gochfeld, Michael. "Cases of mercury exposure, bioavailability, and absorption." Ecotoxicology and Environmental Safety 56.1 (2003): 174-179.
• Larkin, Marilynn. "Don't remove amalgam fillings, urges American Dental Association." The Lancet 360.9330 (2002): 393.
• Rice, Deborah C. "The US EPA reference dose for methylmercury: sources of uncertainty." Environmental research 95.3 (2004): 406-413.
• Rose, Martin, et al. "Dietary exposure to metals and other elements in the 2006 UK Total Diet Study and some trends over the last 30 years." Food Additives and Contaminants 27.10 (2010): 1380-1404.

Battling Small Intestinal Bacterial Overgrowth (SIBO) With Probiotics | Some Bugs as Effective (50%) as Antibiotics

Battling bacteria w/ more bacteria. Sounds odd, but works like a charm.

Those who haven't made the mistake not to "like" the SuppVersity on Facebook may already have seen it in the news: SIBO, i.e. the overgrowth of bacteria in the small intestine, may be linked to heart disease. The link, according to a study by Ponziani, et al. (2017), who found a significantly elevated arterial stiffness in SIBO patients, could be a combination of inflammation and a lack of vitamin K.

More common and obvious complaints of SIBO patients include gastrointestinal discomforts and malabsorption. Eventually, the on-going bacterial overgrowth can yet also have systemic inflammatory effects and the translocation of bacteria into the gut stream displays a persistent risk factor for sepsis (Quigley 2006).

Learn more about probiotics and the microbiome a the SuppVersity

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Glutamine your gut + fat loss

'No Sugar' foods mess up 'ur gut

Spore-forming = better probiotics

Sweeteners vs. microbiome?

Unfortunately, the not exactly abundant currently available research indicates, as Zhong et al. write in their latest paper in the Journal of Clinical Gastroenterology that "antibiotics alone may be inadequate for SIBO decontamination" (Zhang 2017). This is bad news because, as previously hinted at, ...

Figure 1: Bacterial flora along the gastrointestinal tract; relative concentrations of bacteria at various points in the adult human intestine. Note these concentrations apply only to species that can and have been cultured (Quigley 2006).

"[...] the delicate balance between host and environment is central to intestinal homeostasis. The intestinal epithelium is exposed on a daily basis to the bacterial antigens of the commensal microflora that in turn induce a state of controlled inflammation. This physiologic response to bacterial antigens is not harmful to the host and generates both the induction of immune tolerance and the secretion of immunoglobulin A (IgA). [...] In disease states, a proinflammatory response to these same luminal antigens leads to the development of such disorders as celiac sprue and inflammatory bowel disease" (Quigley 2017) 

Next to the well-known localized bowel-related consequences, SIBO can also trigger weight loss as well as vitamin and mineral deficiencies due to defective nutrient uptake. In this context the following nutrients are particularly worth mentioning (Dukowicz 2007):

• fat-soluble vitamins A, D, E, K, as well as vitamin B12, and iron
• dietary protein (high risk of hypoalbuminemia)

Folate, on the other hand, may be produced/absorbed in excess (that's because of an increased synthesis of folate by small bowel bacteria | Camilo 1996).

Proton pump inhibitors do not cause SIBO, but they sign. increase your risk of developing it: Even though Ratuapli et al. write in their 2012 study that "[i]n [their] large, adequately powered equivalence study, PPI use was not found to be significantly associated with the presence of SIBO as determined by the GHBT", studies using more accurate measures of SIBO than the glucose hydrogen breath test (e.g. duodenal or jejunal aspirate culture) suggest that it clearly predisposes to the development of SIBO - with PPI users being 7-8-fold more likely to develop SIBO than non-users (Lo 2013) - to which extent this may be thwarted by primary diseases, the type of PPI (older studies show much higher SIBO rates) and the administration frequency is unfortunately not addressed in either Lo's meta-analysis or the individual studies.

In observational studies, SIBO has even been linked to Parkison's disease (Gabrielli 2011; Fasano 2013), cirrhosis (=liver disease | Gupta 2010), fibromyalgia (Pimentel 2001) and other diseases and syndromes. For all of them, however, the links are putative and a causal involvement of SIBO has yet to be demonstrated.

Table 1: If you want to know if you suffer from SIBO, don't do the lactulose breath test. It's intolerably inaccurate. Plus: As Lo et al. point out, all diagnostic breath tests for SIBO may simpler to administer, less invasive, and less costly than duodenal/jejunal aspirate culture, they are yet also comparatively less sensitive and specific (Lo 2013).

I guess that you will still be interested in the usefulness of probiotics in SIBO therapy - in spite of the correlative nature of the previously mentioned links between SIBO and life-threatening diseases, right? Well, this is what Zhong et al. did and found: Using all the usual databases, they identified studies that (1) assessed the efficacy of probiotics for preventing or treating SIBO; (2) enrolled  >10 patients; and (3) displayed the prevention outcomes or treatment outcomes. To exclude studies that do not meet these criteria data, two authors independently screened the initially 393 records. Eventually, Zhang et al. ended up with 18 studies that were pooled into the meta-analysis. Here's what they found:

• Do probiotics prevent the occurrence of SIBO? Six studies investigated the occurrence of SIBO in patients with probiotics use. The pooled analysis of all studies suggested that patients using probiotics exhibited a slight predisposition toward a decreased incidence of SIBO when compared with those not using probiotics, but without statistical significance (RR=0.63; 95% CI, 0.29-1.36; P=0.24) (Fig. 2). Also, high heterogeneity was presented (I2=84.4%, P<0.05).
  

  

  Figure 2: FIGURE 2. Forest plot showing the incidence of SIBO for probiotic users compared with the nonprobiotic users. CI indicates confidence interval; RR, relative risk; SIBO, small intestinal bacterial overgrowth (Zhang 2017).

  However, the evaluation solely including the RCTs displayed an insignificant result (RR=0.54; 95% CI, 0.19-1.52; P=0.24), without a substantial change in the heterogeneity (I2=83.7%, P<0.05).
• Do probiotics help with SIBO eradication? The pooled decontamination rate from studies using either probiotics alone and studies using probiotics + antibiotics was 62.8% (51.5% to 72.8%), with high heterogeneity (I2=71.1%, P<0.05).
  

  

  Figure 3:  Pooled SIBO decontamination rate, grouped by probiotics alone or probiotics plus antibiotics. CI indicates confidence interval; SIBO, small intestinal bacterial overgrowth (Zhang 2017)

  The pooled rate of successful treatment was 53.2% (40.1% to 65.9%) for probiotics alone and 85.8% (69.9% to 94.0%) for probiotics plus antibiotics. Individual studies testing both confirm the superiority of antibiotics vs. probiotics as a stand-alone treatment with the former yielding beneficial effects in 38% vs. 18% (Saad 2014).
  
  A different image emerges when we compare antibiotics, alone, vs. antibiotics + probiotic trials. Here, Zhang's results suggested that patients with SIBO using probiotics have a significantly higher SIBO decontamination rate compared with the nonprobiotic users (RR=1.61; 95% CI, 1.19-2.17; P<0.05), and a lower level of heterogeneity (I2=25.7%, P=0.25).

If you review the results you will have to admit that it remains questionable whether antibiotics are dispensable. What appears to be certain, however, is that their combination with probiotics will yield the greatest chance of successfully battling SIBO.

Furthermore, their chronic use may, as the data in Figure 2 indicates, protect you from developing SIBO - in particular if you belong to one of the SIBO risk groups because of structural/anatomic features such as small intestine diverticula, small intestine strictures, surgically created blind loops, resection of ileocecal valve, etc., motility disorders such as gastroparesis, small bowel dysmotility, celiac disease, etc., IBS or metabolic disorders such as diabetes, or hypochlorhydria, organ system dysfunction, including, cirrhosis, renal failure, pancreatitis, etc., or medications such as antibiotics and drugs that suppress the gastric acid production.

You may remember that VSL#3 has been in the SuppVersity news before... for it's ability to reduce the fat over the course of 4 weeks of overfeeding twenty young men (caloric surplus 1000 kcal/day on a high fat (55%) diet) by impressive >50%. For all these studies, you got to keep potential conflicts of interest in mind | more.

So, if probiotics work, which and how much do I take? I know that many of you don't care about anything of what I've written about. The only thing you want is exact advice which products you should buy. Ok, let's see. The strains that were used are: (1) Bacillus clausii at a dosage of 2 bn CFU twice a day for one month in Scarpellini et al. (2006 | 57% success rate), and the same dosage thrice daily in Gabrielli, Maurizio, et al. (2009 | success rate of 48%); (2) L. casei strain Shirota in Barrett et al. (2008), in form of one bottle of Yakult® (6.5x10^9 + 1 g lactose per dose), consumed daily for 6 weeks this yielded an impressive success rate of 64%; (3) VSL#3 a proprietary mix of Bifidobacteria, Lactobacilli and Streptococcus thermophilus at a dosage of 110bn CFU with improvements of SIBO in 58% of the subjects w/ cirrhosis; (4) Duolac Gold probiotic containing Bifidobacteria, Lactobacilli and Streptococcus thermophilus at a dosage of 5 bn viable cells in a lyophilized powder form with a relatively low improvement rate of 24% - likewise in patients with liver cirrhosis.

In the short run Soifer et al. saw benefits with one of the often-seen mixes of Lactobacillus casei (3.3 x 10^7 UFC), Lactobacillus plantarum (3.3 x 10^7 UFC), Streptococcus faecalis (3.3 x 10^7 UFC) and Bifidobacterium brevis (1.0 x 10^6 UFC). The product (Bioflora) was yet administered for only 7 days and the only outcome measure were subjective intestinal complaints. Similarly semi-useless measured were used by Ockeloen, et al. (2012) who administered a single capsule with 1 × 10^9 Bifidobacterium and Lactobacillus per day,

As you may guess, it is - without head-to-head comparisons - difficult to tell which of the products would be your best choice. Personally, though, I would gravitate to (1)-(3) from the list above as they've been used in the longer run and with inaccurate, but at least direct breath tests for SIBO instead of simple improvements in gastrointestinal complaints. If that's not going to work you can still resort to Rifaximin at a dosage of >800mg/d (here, more helps more | Lauritano 2005) and restore a healthier microbiome w/ post-antibiotic probiotic therapy | Comment or ask questions!

References:

• Barrett, Jacqueline S., et al. "Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome." World J Gastroenterol 14.32 (2008): 5020-5024.
• Camilo, Ermalinda, et al. "Folate synthesized by bacteria in the human upper small intestine is assimilated by the host." Gastroenterology 110.4 (1996): 991-998.
• Dukowicz, Andrew C., Brian E. Lacy, and Gary M. Levine. "Small intestinal bacterial overgrowth: a comprehensive review." Gastroenterol Hepatol (NY) 3.2 (2007): 112-22.
• Fasano, Alfonso, et al. "The role of small intestinal bacterial overgrowth in Parkinson's disease." Movement Disorders 28.9 (2013): 1241-1249.
• Gabrielli, Maurizio, et al. "Bacillus clausii as a treatment of small intestinal bacterial overgrowth." The American journal of gastroenterology 104.5 (2009): 1327.
• Gabrielli, Maurizio, et al. "Prevalence of small intestinal bacterial overgrowth in Parkinson's disease." Movement Disorders 26.5 (2011): 889-892.
• Gupta, Ankur, et al. "Role of small intestinal bacterial overgrowth and delayed gastrointestinal transit time in cirrhotic patients with minimal hepatic encephalopathy." Journal of hepatology 53.5 (2010): 849-855.
• Kwak, Dong Shin, et al. "Short-term probiotic therapy alleviates small intestinal bacterial overgrowth, but does not improve intestinal permeability in chronic liver disease." European journal of gastroenterology & hepatology 26.12 (2014): 1353-1359.
• Lauritano, Ernesto Cristiano, et al. "Rifaximin dose‐finding study for the treatment of small intestinal bacterial overgrowth." Alimentary pharmacology & therapeutics 22.1 (2005): 31-35.
• Lo, Wai–Kit, and Walter W. Chan. "Proton pump inhibitor use and the risk of small intestinal bacterial overgrowth: a meta-analysis." Clinical Gastroenterology and Hepatology 11.5 (2013): 483-490.
• Lunia, Manish Kumar, et al. "Probiotics prevent hepatic encephalopathy in patients with cirrhosis: a randomized controlled trial." Clinical Gastroenterology and Hepatology 12.6 (2014): 1003-1008.
• Ockeloen, L. E., and J. M. Deckers-Kocken. "Short-and long-term effects of a lactose-restricted diet and probiotics in children with chronic abdominal pain: a retrospective study." Complementary therapies in clinical practice 18.2 (2012): 81-84.
• Pimentel, Mark, et al. "Small intestinal bacterial overgrowth: a possible association with fibromyalgia." Journal of Musculoskeletal Pain 9.3 (2001): 105-113.
• Ponziani, et al. "Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms." World J Gastroenterol. 2017 Feb 21;23(7):1241-1249. doi: 10.3748/wjg.v23.i7.1241.
• Quigley, Eamonn MM, and Rodrigo Quera. "Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics, and probiotics." Gastroenterology 130.2 (2006): S78-S90.
• Ratuapli, Shiva K., et al. "Proton pump inhibitor therapy use does not predispose to small intestinal bacterial overgrowth." The American journal of gastroenterology 107.5 (2012): 730-735.
• Scarpellini, E., et al. "Bacillus clausii treatment of small intestinal bacterial overgrowth in patients with irritable bowel syndrome." Digestive and Liver Disease 38 (2006): S32.
• Soifer, L. O., et al. "Comparative clinical efficacy of a probiotic vs. an antibiotic in the treatment of patients with intestinal bacterial overgrowth and chronic abdominal functional distension: a pilot study." Acta gastroenterologica Latinoamericana 40.4 (2010): 323-327.
• Zhang, et al. "Probiotics for Preventing and Treating Small Intestinal Bacterial Overgrowth: A Meta-Analysis and Systematic Review of Current Evidence." Journal of Clinical Gastroenterology: April 2017 - Volume 51 - Issue 4 - p 300–311 doi: 10.1097/MCG.0000000000000814.

Where do Your Strength Gains Come From? Muscle Activity > Hypertrophy > Initial Strength - 3/5 Candidates Matter

Find out what's taking you from PR to PR, is it an increase in muscle size or activation on how important is how strong you already are?

Have you ever asked yourselves why you've been adding 20lbs of weight to your squat and your legs still don't look any bigger? If you're a man you're probably not happy about that. I am not sure if the insights into Balshaw et al.'s recent study provide into the mechanism behind the resistance-training-induced strength gains will help you will make you happy/-ier, but certainly smarter ;-)

The British scientists got to the bottom of your gains by assessing the individual and combined contribution of the adaptations in neural (agonist quadriceps EMG, antagonist hamstring EMG) and morphological (quadriceps muscle volume and θp, the fascicle pennation angle) variables.

Are you looking for muscle builders for your new workout plan? Find inspiration here:

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Based on the data from their 12-week study in twenty-eight healthy young men, who had not completed lower body RT for >18 months and were not involved in systematic physical training, the scientists were able to calculate the individual contribution of the previously named variables and the trainees' baseline strength on the effect of the following workout:

"After a brief warm-up of submaximum contractions of both legs, participants completed four sets of ten unilat eral isometric knee extensor contractions of each leg; with sets alternating between dominant and non-dominant legs. Each set took 60 s with 2 min between successive sets on the same leg" (Balshaw 2017). 

To differentiate potential interference with explosive vs. sustained contractions, the participants were further randomized to two groups:

• the explosive contraction group completed short, explosive contractions with participants instructed to perform each contraction “as fast and hard as possible” up to ≥80% MVT for ~1 s, and then relax for 5 s between repetitions.
• the sustained contraction group completed prolonged contractions at 75% MVT, with 2-s rest between contractions. 

For both groups, the scientists provided a computer monitor that displayed the rate of torque development (10-ms time epoch) and a target torque trace 2 s before every contraction, in the explosive and sustained contraction group, respectively.

Without a follow-up study in trained individuals, we have to speculate to which extent increases in muscle activity, hypertrophy, and the pre-training strength explain the variability of strength gains in trained individuals. The above is my estimate - just an educated guess.

What does the study tell us about better-trained individuals? If we compare the results of the study at hand to related study, it may be possible to make predictions about the driving forces of muscle growth in better-trained individuals, eventually, though, the study would have to be repeated with a different subject group to tell for sure.

As Balshaw et al. point out, their results are in line with other EMG studies assessing the effect of training on the lower extremities. What is interesting, however, is that they conflict with a study by Erskine et al. (2014) who found only a marginal correlation between improved activity patterns and strength gains for the biceps a muscle with an already high level of activation even in untrained individuals.

This result is important for our prediction because it suggests that a higher baseline activation level will reduce the contribution of improvements in agonist neural drive to the strength gains. This, in turn, obviously suggests that, in trained individuals who have already undergone significant improvements in neural drive, muscle activity will contribute significantly less to the strength gains than it does in untrained individuals. An equivalent to Figure 3 for well-trained athletes may thus look as I have sketched it in the figure on the left-hand side: Hypertrophy could make the largest, while improved muscle activation, only a marginal contribution to strength gains - but keep in mind: that's just an educated guess that is based on the assumption that the relative contribution of hypertrophy will increase as the relative contribution of improvements in muscle activation patterns will decrease over time (Note: Whether the three variables will then still explain 60% of the variation appears questionable, though; thus the 10% reduction in total predictive power in the figure above).

Each subject performed the above isometric knee extensor RT thrice a week (3/week). Before and after isometric maximum voluntary torque (MVT) as well as the neural drive to the agonist (QEMGMVT) and antagonist (HEMGANTAG) were assessed simultaneously. In addition, QUADSVOL was determined with MRI and QUADSθp with B-mode ultrasound.

Figure 1: Relationships of percentage change (∆) in knee extension may. voluntary torque (MVT) and ∆ quadriceps muscle volume (QUADSVOL; r = 0.461, P = 0.014), b ∆ quadriceps muscle fascicle pennation angle (QUADSθp; r = −0.207, P = 0.291), after 12 wks of resistance training. Solid and dashed lines indicate the trend of the relationship between variables and 95% confidence intervals, respectively. Black triangles denote sustained-contraction resistance training participants (n = 15); white circles denote explosive-contraction resistance training participants (n = 13 | Balshaw 2017)

I have to say that the way the scientists plotted the data is a bit odd - with the strength gains being the actual outcome variable of interest, I would expect it to be placed on the vertical, not the horizontal axis... but anyway. Figures 1-2 tell you that...

• hypertrophy contributes quasi-linearly to the gains (Figure 1 A) - I would estimate the reciprocal of the slope of the linear regression line to be ~2.5, meaning for each 1 % increase in muscle volume there was a 2.5% increase in maximal voluntary torque;
• agonist activity changes contribute quasi-linearly to the gains (Figure 2 A) - I would estimate the reciprocal of the slope of the linear regression line to be "only" ~0.8, meaning for each 1% increase in muscle activity there was a 0.8% increase in maximal voluntary torque;
• pre-training strength negatively predicts the strength gains (Figure 2 C) - What may sound odd, initially, is actually only logical. The stronger you are at baseline, the lower your strength gains are going to be. For this relationship, I would estimate the slope of the linear regression analysis to be approx. -1.5, which means that for each extra Newton-metre (nM) of pre-training maximal voluntary torque, the increase in response to training will be reduced by 1.5%;
• pennation angle and antagonist activity changes do not contribute clearly to the strength gains (Figure 1 B, Figure 2 B) - you know that because there was no clear correlation between the corresponding variables in the regression analysis the scientists did

So, there's clear evidence that size gains (hypertrophy), muscular activation (EMG) and, of course, the baseline strength determine the strength gains in resistance training rookies.

Figure 2: The relationships between the percentage change (∆) in knee extension maximum voluntary torque (MVT) and: (A) ∆ quadriceps EMG at knee extension MVT (QEMGMVT; r = 0.576, P = 0.001); (B) ∆ antagonist hamstrings EMG during knee extension MVT (HEMGANTAG; r = 0.298, P = 0.123) and (C) pre-training knee extension MVT (r = −0.429, P = 0.023), after 12 weeks of resistance training (Balshaw 2017).

The pennation angle, and antagonist activity (here the hamstring) on the other hand appear to contribute only marginally to the increase in strength gains the previously untrained subjects saw over the course of the 12-week study.

Figure 3: The scientists' multiple regression analysis reveals the strength of the contribution of each variable the scientists assessed in their study (Balshaw 2017).

So, what's the most important contributor? That's difficult to tell. With the individual correlations being relatively weak, one cannot rely on the previously calculated slopes. Those give you an idea of what the real-world contribution would be if there was a perfect correlation between the individual variables.

To answer the above question, we will thus have to turn to the subsequent multiple regression analysis of which the scientists highlight that it "found for the first time that these three variables simultaneously contributed to the total explained variance in strength" (Balshaw 2017).

Even if you take the  size gains (hypertrophy), muscular activation (EMG) and, of course, the baseline strength them into account, these variables explain only 60% of the total variance in strength gains - with the individual contributions (see Figure 3) being agonist neural drive, aka the muscle activation (EMG) explaining 30.6%, the size gains 18.7% and the pre-training strength 10.6% of the strength gains the rookies made over the course of the 12-week study... which leads me to an inevitable question: What about experienced strength trainees? I knew you'd be asking that and have addressed this question in the red box above Figure 1, so read it before you ask about the implications for trained individuals on Facebook!

References:

• Balshaw, Thomas G., et al. "Changes in agonist neural drive, hypertrophy and pre-training strength all contribute to the individual strength gains after resistance training." European Journal of Applied Physiology (2017): 1-10.
• Erskine, Robert M., Gareth Fletcher, and Jonathan P. Folland. "The contribution of muscle hypertrophy to strength changes following resistance training." European journal of applied physiology 114.6 (2014): 1239-1249.

Role of Muscle and CNS in Diet-Induced Decline of Exercise-Induced Energy Expenditure | Caffeine & Nicotine May Help!

While "calories count" when it comes to losing body fat, the notion that you would always burn the same amount of energy with a given workout - irrespective of your energy intake - is completely bogus and only one of the reasons why meticulous calorie counting won't work. 

Let's address it right away: Yes, the paper Tariq I. Almundarij et al. published in the peer-reviewed journal "Physiological Reports" (Almundarij 2017) deals with a rodent experiment, but with the goal of the study being to identify the fundamental mechanisms behind, not the extent of metabolic adaptation to calorically reduced energy intakes, this does not disqualify its results as irrelevant for humans - on the contrary (and trust me, I'd prefer a human or at least a pig study, too).

With that being said, let's take a look at what the scientists did to "investigate the role of MC4R in the modulation of muscle work efficiency, and test the hypothesis that energy restriction alters economy of activity through decreasing the response to central activation of MC4R" (Almudarij 2017).

You can find more diet related wisdom in the True or False articles at the SuppVersity

Pasta "Al Dente" = Anti-Diabetic

Vinegar & Gums for Weight Loss

Teflon Pans Will Kill You!

Yohimbine Burns Stubborn Fat

You Can Wash Pesticides Away

High Volume Diet = Success

For their study, the scientists used male Sprague-Dawley rats (total N = 48) which were selected to measure adaptive thermogenesis in a baseline population - not because Martin et al. (2010) have mad ethe argument that these animals are potentially metabolically morbid, anyway, but rather because they are metabolically morbid. Just as metabolically morbid as human beings for whom the ever-increasing obesity rates indicate that we are similarly susceptible to diet-induced obesity and the associated detrimental health effects.

These rats were subjected to 3 weeks of 50% calorie restriction (CR). Over the course of this - in rodent years - intermediate time period, the scientists assessed their lab animals resting and nonresting energy expenditure (EE) and calculated the total, as well as the activity-associated EE, muscle thermogenesis, and sympathetic outflow.

Figure 1: Three weeks of 50% calorie restriction (CR) significantly suppressed both resting and nonresting EE, including physical activity-related EE, i.e. the energy you spend while working out (Almundarij 2017).

You can see the results of this basic measurement in Figure 1: The prolonged food restriction resulted in a 42% reduction in daily energy expenditure, a 40% decrease in resting energy expenditure, and a 48% decline in nonresting energy expenditure.

Dieting is when you leave only 360kcal not 600kcal in the gym, despite doing the same workout

What is particularly interesting, yet often forgotten when we talk about dieting (especially within the fitness community), is the fact that the energy that you will burn during exercise will also decrease significantly (see Figure 1G). One of the implications of the study at hand we cannot ignore is that the reduced physical activity energy expenditure stems from "the dampening of both the amount and energetic cost of activity" (Almundarij 2017) - and the latter, i.e. the reduced energy expenditure in response to a standardized exercise regimen amounts to a 30-40% decrease in EE that would degrade the 600kcal you believe to be burning on the treadmill to a meager 360-420 kcal/session!

Figure 2: Fat & lean mass and the rel. (%) difference in body comp. w/ ad-libitum vs. restricted diet (Almundarij 2017).

This 180-240kcal difference, alone, could easily explain why you see people complaining all over the internet that "[they] don't lose weight, even though [they're] doing everything right, not missing any of their daily workouts and not cheating on [their] diets" (modeled on the often-heard complaint of dieters worldwide).

Illustration of the allegedly over-simplified example calculation to show the significance of the fasting-induced reduction in AIEE for meal timing and fat loss as observed in Garaulet 2013.

Never forget the importance of reductions in activity-induced energy expenditure: You may remember an older study that has recently resurfaced on Facebook from previous SuppVersity articles about fasting: The study, "Timing of food intake predicts weight loss effectiveness" (Garaulet. 2013), indicates that having your major meals in the AM when dieting favors fat loss even if the total energy intake is identical. Knowing how significant the reduction in activity-induced energy expenditure (AIEE) in man is (%-age wise its contribution to the metabolic downregulation is much higher in man vs. rodent), the results of the study at hand may easily explain why CICO (=the C-alories I-n vs. C-alories O-out hypothesis) failed in Garaulet's study.

Let's illustrate that with a simple example (see Figure to the left). Let's assume the reduction in AIEE is indeed 40%. Let's further assume that you'd "burn" ~1000kcal from working out and walking in your waking phase before the PM meal and only 150kcal after the PM meal when eating an energetically balanced. According to Cooker, that would put your effective AIEE while dieting to 600kcal + 150kcal when you eat in the PM, but 1000kcal + 90kcal if you eat the meal in the AM. Obviously, this oversimplified example assumes that the metabolism would not slow down over the day (which will be the case). Eventually, the difference will thus certainly be smaller (maybe 15% instead of the 31% in my example). That does not mean, though, that it could not still be statistically and practically significant (note: it is unlikely that a relevant reduction would be observed for intermittent fasting in the absence of a significant caloric deficit).

In this context, it is also important to emphasize that these decreases in EE were significant even when the reductions in body weight and lean mass were taken into account. In other words, it is not the often-cited loss of lean mass (alone) which mediates the reduction in basal and exercise-induced energy expenditure. This alone, however, is nothing we didn't observe in previous human studies, already. What's truly new, however, is that the study at provides extended mechanistic insight into the origin of these unwanted reductions in energy expenditure. In fact, the study at hand ...

is the first report of reduced muscle NETO [norepinephrine turnover], indicating lower SNS drive to skeletal muscle after 3 weeks of food restriction (Fig. 2), an effect not seen during short-term energy restriction (Dulloo et al. 1988)" (Almundarij 2017).

With the importance of skeletal muscle to both resting and activity EE, (Zurlo et al. 1990; Gallagher et al. 1998), "this low SNS drive" could, as the authors further point out significantly "contribute to both the resting and nonresting aspects of adaptive thermogenesis" (Almundarij 2017).

Figure 3: The MC4R induced increase in energy expenditure in the study at hand is probably not coincidentally of a similar magnitude as the effects of nicotine (Almundarij 2017).

Nicotine targets the mechanism even more directly than caffeine: Even though the safety of nicotine as a fat loss adjuvant is, as previously discussed in detail, debatable, I think it's worth mentioning that Mineur et al. have shown 6 years ago that nicotine's effect on food intake are mediated by an activation of POMC neurons, neurons that will then activate the very melanocortin 4 receptors of which the study at hand shows that their medical activation can - albeit only partly - restore the reduced energy expenditure in dieting rats (as you can see in Figure 3, the MC4R agonist will, just as it has been shown for nicotine in humans, also increase the energy expenditure in non-dieting rats.

The latter, i.e. the ability of the muscle mass to react to central nervous system stimuli, however, is not lost while you're dieting. It is - and that's a primary result of the study at hand - rather centrally (in the brain) deactivated. Otherwise, the muscles wouldn't have reacted to either the central MC4R agonist nor any form of physical activity with an increase in thermogenesis. This result is of paramount importance, because it does, as the authors point out, ...

"[...] provide potential avenues to counter adaptive thermogenesis and [thus to] promote continued weight loss and weight maintenance through targeting physical activity EE and skeletal muscle thermogenesis (Almundarij 2017).

Now the bad news is that the melanocortin 4 receptor agonists Almundarij et al. used in their study are not (yet?) ready to be used in human beings. Other tools to increase the decreased norepinephrine turnover in skeletal muscle, however, are available and you'll all be familiar with their names: caffeine or ephedrine (and to a lesser extent green tea extract).

Figure 4: Effects of caffeine (CAF) and ephedrine (EPH) alone or in combination (C+E) on epinephrine levels during exercise. 12 recreational runners (10 males and 2 females; 6 regular coffee drinkers and 6 irregular or non-caffeine users) ingested placebo (PL), CAF 4 mg/kg, EPH 0.8 mg/kg or C+E (CAF 4 mg/kg and EPH 0.8 mg/kg). After 90 minutes of rest they performed a 10km run while wearing a helmet and backpack weighing 11kg; the intensity of this effort was >90% of VO2peak; * p < 0.05 vs PL; † p < 0.05 vs EPH; ‡ p < 0.05 vs CAF; § p < 0.05 vs C+E (Magkos 2004)

As Magkos et al. pointed out in their 2004 paper in Sports Medicine, "[b]oth drugs may enhance norepinephrine turnover, but each one alone only modestly". This supposition is supported by both previous human data (Berkowitz 1970), as well as data presented in the researchers own paper which shows that the benefit of combining the two is mostly due to the prolongation and potentiation of caffeine's effect by ephedrine (or vice versa; cf. Dulloo 1992).

Figure 5: There is a link for nicotine and there may even be a link of caffeine to the melanocortin 4 receptor - one that's mediated by the POMC neurons.

Unfortunately, corresponding data on caffeine's muscle-specific norepinephrine turnover is (and I openly admit that) not yet available. That's mostly because research has not really zoned in on the autonomic modulation of muscle compared to adipose tissue; and where it did, this was not about the effect of caffeine and co., but the upstream effects of melanocortin receptor activity (Gavini 2014), which would yet be a downstream target of the caffeine, if Laurent et al. are right and "caffeine ingestion promotes corticotropin-releasing factor release from the hypothalamus [...], which, in turn, increases POMC release" and - guess what - downstream melanocortin 4 receptor activity.

In a different context this relationship has already been established (Bhorkar 2014), whether and to which extent caffeine stimulates the melanocortin 4 receptors (MC4R), however, is - at least as far as I know - not known. Anyway... when all is said and done, there's still no doubt that caffeine, even when it's used alone, will still have a significant enough effect on the sympathetic nervous system (SNS) to promote weight loss and weight maintenance in multiple diet studies (Dulloo 1989; Westerterp‐Plantenga 2005) - and let's be honest: many people won't even care if that involves an increase in MC4R activity or not ;-)

If your diet of choice is a ketogenic diet, caffeine will not just help you to compensate the reduction in exercise-induced energy expenditure and thus "restore the calories" you leave in the gym. A recent study shows that it will also help you to get and stay in ketosis - and that's even when you've been cheating on carbs | learn more.

So what's the implication for human beings? Even though a reduction in thermogenesis at rest contributes less to the reduction in energy expenditure during periods of restricted dietary intake in humans compared to rodents. The effect of on non-resting EE and thus regular activity- and exercise-induced EE is proportionally even higher - and increases the more weight you lose (Leibel  1995).

Now, this effect reflects in a reduced central activation of hypothalamic melanocortin receptors, which could be countered by medical intervention only theoretically. After all, corresponding drugs as they have been used for experimental purposes on the rodents in the study at hand are still in the early experimental phase - that they do work without short-term side-effects has yet been demonstrated in obese individuals by Chen et al. (2015) who observed a 111 kcal/24 h increase in REE.

For the average gymrat, these drugs will yet probably never be available legally. Against that background you can count yourselves lucky that Almundarij et al.'s results also point to another, already available and (if used sensibly) perfectly safe class of drugs. central nervous stimulants like the ubiquitous caffeine. These agents have a proven record of being able to promote diet-induced fat loss by increasing/restoring SNS-induced thermogenesis (Dulloo 1988 & 1989) - especially when used in conjunction with exercise so that they can partly compensate the diet-induced reduction in sympathetic tone and thus restore the significantly reduced energy expenditure during workouts to near-normal levels.

It is often belittled, but even in non-dieting humans, the increase in energy expenditure following the consumption of caffeine is significant (Astrup 1990).

In conjunction with caffeine's ability to shift the fuel oxidation from glucose to fatty acids and its likewise central nervous system-mediated lipolytic (=fat releasing) effect on fat cells, it is thus still the most widely available and best-researched diet aid - an aid that doesn't make dieting obsolete, but one that will partly compensate the negative effect of prolonged energy restriction on basal and exercise-induced thermogenesis. Ah, ... and let's not forget that nicotine is a viable yet, as previously discussed, less harmless OTC alternative of which we know already that it acts via the same downstream signaling cascade as a melanocortin receptor agonist (Mineur 2011) | Comment!

References:

• Almundarij, Tariq I., Chaitanya K. Gavini, and Colleen M. Novak. "Suppressed sympathetic outflow to skeletal muscle, muscle thermogenesis, and activity energy expenditure with calorie restriction." Physiological Reports 5.4 (2017): e13171.
• Astrup, A., et al. "Caffeine: a double-blind, placebo-controlled study of its thermogenic, metabolic, and cardiovascular effects in healthy volunteers." The American journal of clinical nutrition 51.5 (1990): 759-767.
• Berkowitz, Barry A., James H. Tarver, and Sydney Spector. "Release of norepinephrine in the central nervous system by theophylline and caffeine." European journal of pharmacology 10.1 (1970): 64-71.
• Bhorkar, Amita A., et al. "Involvement of the central melanocortin system in the effects of caffeine on anxiety-like behavior in mice." Life sciences 95.2 (2014): 72-80.
• Bracco, David, et al. "Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women." American Journal of Physiology-Endocrinology and Metabolism 269.4 (1995): E671-E678.
• Chen, Kong Y., et al. "RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals." The Journal of Clinical Endocrinology & Metabolism 100.4 (2015): 1639-1645.
• Dulloo, A. G. "Stimulation of thermogenesis in the treatment of obesity: A rational approach." Journal of obesity and weight regulation (USA) (1988).
• Dulloo, A. G., et al. "Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers." The American journal of clinical nutrition 49.1 (1989): 44-50.
• Gavini, Chaitanya K., et al. "Leanness and heightened nonresting energy expenditure: role of skeletal muscle activity thermogenesis." American Journal of Physiology-Endocrinology and Metabolism 306.6 (2014): E635-E647.
• Garaulet, Marta, et al. "Timing of food intake predicts weight loss effectiveness." International journal of obesity 37.4 (2013): 604-611.
• Laurent, Didier, et al. "Effects of caffeine on muscle glycogen utilization and the neuroendocrine axis during exercise 1." The Journal of Clinical Endocrinology & Metabolism 85.6 (2000): 2170-2175.
• Leibel, Rudolph L., Michael Rosenbaum, and Jules Hirsch. "Changes in energy expenditure resulting from altered body weight." New England Journal of Medicine 332.10 (1995): 621-628.
• Magkos, Faidon, and Stavros A. Kavouras. "Caffeine and ephedrine." Sports Medicine 34.13 (2004): 871-889.
• Mineur, Y. S., Abizaid, A., Rao, Y., Salas, R., DiLeone, R. J., Gündisch, D., ... & Picciotto, M. R. (2011). Nicotine decreases food intake through activation of POMC neurons. Science, 332(6035), 1330-1332.
• Mountjoy, Kathleen G. "Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes." Biochemical Journal 428.3 (2010): 305-324.
• Westerterp‐Plantenga, Margriet S., Manuela PGM Lejeune, and Eva MR Kovacs. "Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation." Obesity 13.7 (2005): 1195-1204.