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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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.

Nitrate from Beets Improves Glucose Response to 75g CHO - Antibacterial Mouthwash Blocks This + Other Benefits

Honestly, for me it's not the improved glucose management, but rather the proof that you must not use antibacterial mouthwash that's the takeaway, here.

What? Yes, the use of mouthwash can ruin all beneficial effects of nitrate containing foods - those on your blood pressure, those on your pump and - as a recent study from the Colorado State University indicates - even the beneficial effects the co-ingestion of beetroot juice with carbohydrates will have on obese individuals' glucose tolerance.

Oh, you're not obese? Well, in that case, the effect is not going to reach statistical significance, but since it's not going to be zero and you can learn something about the incompatibility of your nitrate-based pre-workout performance enhancing pump supplement and antibacterial mouthwash, it's still worth reading the rest of today's SuppVersity article.

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At first, it may be odd that a "pump supplement" or "blood pressure regulator" is able to improve one's glucose handling. If we take into consideration that insulin resistance and obesity are characterized by low nitric oxide (NO) bioavailability, however, and know that nitrate the consumption of dietary nitrate (NO3−) increases NO formation, via NO3− reduction to nitrite (NO2−) by oral bacteria, the observations Joseph W. Beals and colleagues made in their latest study do no longer seem that odd.

Figure 1: Schematic of experimental visits. Two modifed oral glucose tolerance tests were administered, on two separate occasions, in a random order. At the start of one visit, participants completed 3 × 1 min mouthwash regimen. Without delay, they then ingested beet juice supplemented with glucose within 5 minutes. Venous blood was sampled repeatedly over 120 minutes and analyzed for concentrations of glucose and insulin. See text for more details (Beals. 2017).

And that's the case for both, (a) the observation that the co-ingestion of dietary nitrate (beet juice) with 25g of glucose (with the CHOs in the juice that's 75 g of total carbohydrates), significantly improved the glucose tolerance of the study's 10 obese adult subjects (34.0 ± 0.8 kg/m²).

Only recently Vasconcellos et al. observed a sign. 10% reduction in blood glucose w/ a beetroot gel.

No, this is no outlier study: Only recently Vasconcellos et al. (2017) were able to prove that the administration of 100g of a nitrate-rich beetroot gel did not significantly improve their young, trained subjects' running performance, but reduced their blood glucose levels by a statistically significant 10% - and don't worry that's not going to give you hypoglycemia, after all that's the glucose level at the anaerobic threshold and thus when stress, gluconeogenesis and the digestion of the CHO-containing gels will increase your glucose levels (see Figure on the left). In other words: It's "just" further evidence of the beneficial effects of nitrate on glucose management.

And it also led to small but visible improvements in the 12 non-obese study participants (body mass index: 26.3 ± 0.8 kg/m²), and (b) the revelation that inhibiting the nitrate NO3- to nitrite NO2- reduction in the mouth by the prior use of antibacterial mouthwash blunted the effects.

Figure 2: Blood glucose concentration afer beet juice plus glucose consumption was greater in the obese compared with the nonobese adults at 60 and 90 minutes (p = 0.004 and denoted by ∗ | Beals. 2017)

While the co-administration of 500 mL of beet juice (BJ | Biotta, Carmel, Indiana, USA), estimated to contain approximately 17 mmol of nitrate, has only marginal effects in lean individuals (who usually don't suffer from reduced NO2-availability), it has practical relevant effects on the glycemia of obese adults, potentially NO2-deficient adults at risk of developing insulin resistance of whom Beals et al. highlight that they may see significant benefits from ingestion of healthy nitrate-rich foods during meals... as long as they stay away from anti-bacterial mouthwash (MW) in form of one 60s rinse with 10 mL of 1.5% H2O2 (Peroxyl; Colgate Oral Pharmaceuticals, Inc., New York, NY) followed by two 60s rinses with 10 mL of antibacterial mouthwash (chlorhexidine digluconate; Corsodyl, BCM Ltd., Nottingham, UK), that is.

Nitrate Supplementation Study Supports "Increased Blood Flow ➲ Increased Performance" Claim From NO-Write-Ups | more

So, what do you have to remember? Firstly: If you're obese or working with overweight / obese clients you can use nitrate-rich foods such as beetroot juice to improve your or your clients' glucose management.

What I would not suggest is to guzzle 500ml beetroot juice with every meal. After all, that's going to add 50g of carbs and thus 200kcal to every meal. The small but significant increase in glucose handling clearly isn't worth that. Choosing meals with a high(er) nitrate content (e.g. meals rich in leafy greens, rhubarb, lettuce, beans, bulb vegetables like garlic and onions, fruiting vegetables like eggplant and squash etc.), on the other hand, should yield similar benefits without extra-kcals.

Secondly: Even if you're lean you can, albeit to a sign. smaller extent, benefit from including high nitrate foods in your meals. After all, another glimpse at Figure 1 reveals that the ridged line with circles that illustrates the postprandial glucose levels after co-ingestion of beetroot juice without the prior use of mouthwash (and thus allowing for the nitrate benefits to unfold) is constantly below the corresponding solid line for the beetroot + mouthwash trial.

Thirdly: We must not forget that the study at hand also signifies that anyone who consumes nitrate supplements to increase his pump, lower his blood pressure or increase his performance, should avoid antibacterial mouthwash (or toothpaste) at least in the vicinity of nitrate consumption to ensure that the important reduction of NO3- to NO2- can even take place | Comment!

References:

• Beals, Joseph W., et al. "Concurrent Beet Juice and Carbohydrate Ingestion: Influence on Glucose Tolerance in Obese and Nonobese Adults." Journal of Nutrition and Metabolism 2017 (2017).
• Vasconcellos, Julia, et al. "A Single Dose of Beetroot Gel Rich in Nitrate Does Not Improve Performance but Lowers Blood Glucose in Physically Active Individuals." Journal of Nutrition and Metabolism 2017 (2017).

Many Probiotics Contain Antibiotic Resistant Bacteria. Plus: Number of Live Bacteria is up to 95% Below Label Claims

Probiotics under urgently needed scrutiny - This is the first study to test for antibiotic resistances and to highlight the discrepan- cy between label claims and the actual number of live bacteria in supplements.

There have been plenty of good news about probiotic supplements in the news (including the SuppVersity News), lately. One thing that is often forgotten, though, is that the effect of the supplements depends on (a) the exact type of bacteria that are in the pills, (b) the ratio of the different strains and (c) the number of bacteria that are still alive.

Unfortunately, this important truth is rarely mentioned in the edutainment articles on probiotics in the laypress and sales pitches you will find all over the Internet.

Another thing, even you may not have thought about yet is however the potential occurrence of antibiotic resistances among the bazillions of bacteria in your allegedly healthy probiotic supplements.

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A group of people who thought of this hitherto overlooked problem are researchers from the  King Abdullah University of Science and Technology in Saudi Arabia and the UCSI University in Malaysia (Wong. 2015). In their recent paper in the scientific journal Nutrition Journal, the international group of researchers are the first to highlight a previously ignored problem i.e. the possibility that certain genes that make bacteria resistant to antibiotics "could transfer to pathogens sharing the same intestinal habitat" - an event that is, as the scientists rightly point out, "conceivable considering the fact that dietary supplements contain high amounts of often heterogeneous populations of probiotics" and could thus "confer pathogens protection against commonly-used drugs" (Wong. 2015).

MRSA in your probiotic supplements? 

Against that background and in view of the numerous reports of antibiotic resistant probiotics in food and biological sources, the antibiogram of probiotics from dietary supplements remains elusive.

Figure 1: Petri dishes from the antibiotic test (top). If the antibiotics still worked on the bacteria in the probiotics, they all should be dead. As you can see (in the graph, as well), that's by no means the case (Wong. 2015).

In fact, Wong et al. are apparently the first researchers to screen five commercially available dietary supplements (the full names were not disclosed) for resistance towards antibiotics of different classes - with somewhat disconcerting results, namely:

• 

  Even probiotics that help weight loss, could transfer antibiotic resistances.

  Probiotics of all batches of products were resistant towards vancomycin.
• Several batches of probiotics from four different brands were also resistant towards streptomycin, aztreonam, gentamycin and / or ciprofloxacin antibiotics (this includes the US and Austrian products, i.e. Cn and Bn, respectively)
• The fifth brand showed a unique resistance towards gentamycin, strepto- mycin and ciprofloxacin antibiotics. 

Now, as previously pointed out, this does not mean that "bad" bacteria which will always be present in your gut, will automatically acquire the same resistances, but the mere fact that it is possible should tell you that the current hype over probiotics as the "go-to supplement" everyone should take is unwarranted, or at least premature.

You're not getting what you're paying for!

The problem with antibiotic resistances is yet not the only intriguing result of Wang's study. The researchers analyses also revealed that you're not just getting more (albeit unwanted) ingredients that you're paying for, they also found a significant discrepancy between the enumerated viable bacteria amounts and the claims of the manufacturers.

Figure 2: Non-strain specific essay that evaluated the number of live bacteria in the products. The products from producers Bi, Bg, and L didn't just contain significantly less living bacteria than the manufacturers claim, the number is even so low that it is absolutely certain that they are 100% useless. The good news may be that the low dose supplements from the Austria(BN) and USA (CN) contained either more or at least roughly the amount of bacteria on the label (Wong. 2015).

In other words, while the scientists claim that you would get more than enough viable bacteria from their product to have a significant impact on your intestinal microbiome, the reality is that many of the good bacteria are dead before you even open the package.

The "live bacteria"-problem can be solved by eating probiotic foods like yogurt. The problem with potential antibiotic resistances, on the other hand, is rampant with foods, too. Even meat (especially chicken) and allegedly extra-healthy products like veggies from the farmers market may be tainted (the latter due to natural fertilizers of animal origin aka slurry).

Bottom line: The transfer of genes that could make bad gut bugs resistant to antibiotic is only a possibility, but it's one with literally fatal consequences. If bacterial strains in your gut have become resistant to antibiotics and you end up - for whatever reason - with an infection, i.e. a rapid multiplication of these bacteria, you could probably find yourself in the emergency room ... or worse.

In conjunction with the proven lack of viable bacteria in the five products from the US, Malaysia and Austria this study casts a shadow on a class of supplements with rapidly increasing sales - a shadow that becomes even darker if you remember my previous warning that we know literally nothing about the far-reaching interactions between the billion of different bacteria in our gut to even know the "good" from the "bad" guys | Comment on Facebook!

References:

• Wong, Aloysius, et al. "Detection of antibiotic resistance in probiotics of dietary supplements." Nutrition journal 14.1 (2015): 1-6.

Get Lean & Stay Lean with Emedin, Galangin & Antibiotics. Plus: Breakfast & Morning Glucose Metabolism. Diet Once, Never Eat to Satiety Again? Adipocyte Size & NAFLD

Instead of making excuses for posting yet another "short news" collection instead of the next installment of the Athlete's Triad series, I will honestly tell you that I simply wasn't in the mood. Moreover, I have the feeling that I have already outlined what is going to work, i.e. train less, eat more and don't get all psyched up about being lean and looking good. Live your life! Against that background my gut tells me that any further details would just get you off track and back into the viscous cycle of overtraining, overdieting and overthinking why things don't work out for you by evoking the impression that as long as you take supplement X you could get away with doing a little bit 'less less' and eat a little bit 'less more'.

This would be about as counter-productive as the eternal quest for the ultimate body fat blocker or fat burner of which today's Get lean and Stay Lean Quickie does actually feature three. While the temporary use of all of them as a crutch or 'afterburner' to a reasonably planned diet and workout regimen certainly makes sense, it's not like anyone of us got fat, because he or she was "fat burner deficient". A fat burner is not an essential nutrient and only an adjunct to diet and exercise! Keep that in mind not just when you read the following short news items, but also whenever you enter a supplement store (real or on the Internet) and find a new "revolutionary fat burner" on sale -- regardless of whether it has Dr. Oz or Mr. O on the packaging it won't actively, i.e. on its own and in the absence of a dialed in nutritional regimen, make you lose body fat.

• Cassia tora (Leguminosae) seed, yet another "next big thing" to get rid of the blubber?  (Tzeng. 2012 --) The results the scientists from the Department of Internal Medicine, at the Pao Chien Hospital in  Ping Tung City will be publishing in the January 2013 issue of Food Chemistry do at at least look intriguing.  Although - and this goes to show you that SuppVersity readers always (well "almost always" ;-) are the first know first - at least one of the active ingredients in Cassia tora, which is also known as Senna tora and is, besides its use in Ayurveda medicine, also used in Sri Lankan cousin, is an old friend: Emodin! The stuff that gives rhubarb the fat burning prowess you read about in not  too long ago, here at the Suppversity.
  
  

  

  CSEE  had dose dependent ameliorative effects on body weight gain and visceral body fat levels that were - ad the highest dose - identical to those of the thiazolidinedione (TZD) drug pioglitazone (Tzeng. 2012)

  After fattening them for 2 weeks with the notorious high fat diet, the Koreans assigned their now obese lab rats to groups who received either
  
  • Cassia seed ethanol extract (CSEE) by oral gavage, once per day for 8 week with CSEE doses of 100, 200, and 300 mg/kg in a volume of 2 ml/kg distilled water,
  • the diabetes drug pioglitazone dosed at 20mg/kg/day, or
  • a placebo, containing just the distilled water.
  Without any effects on the amount of food the animals consumed, the Cassia seed ethanol extract totally blunted the HFD induced weight gain (weight gain was identical to control group on normal chow, see figure to the right).
  
  In that. the highest dosage had the greatest effect on both body weight gain, as well as plasma lipid levels and epididymal WAT sizes in HFD-fed rats. These effects were probably mediated by CSEE's beneficial effect on the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase. In addition, the researchers found that the cassia seed extract directly increased genes that are responsible for fatty acid oxidation and down-regulated their fat synthesizing counterparts in the visceral white adipose tissue of the animals.
  
  Whether CSEE is going to be a go-to supplement of the future cannot be said, now. What is certain, however, is that it constitutes yet another example of a potentially highly effective natural alternative to the established pharmacological 'treatment' (or rather management) of the diabesity epidemic.
  
• Obese, once and forever, unless you diet for the rest of your life? (Kirchner. 2012) -- A paper that's been published in the latest issue of the Journal of the American Diabetes Association, clearly suggests that the ravenous appetite of "reduced-obese" individuals, i.e. people who have been dieting for weeks and months to shed they weight they have accumulated over years is not (solely) psychologically induced gluttony.
  
  

  

  Suggested read: "Longterm 5% Calorie Restriction & Longterm Dieting Make You Fat and Insulin Resistant." (read full article)

  When Kirchner et al. put their diet-induced obese mice were on a  food restricted for 5 weeks, they did in fact reach the same body fat levels as age-matched rodents who had never received anything but the standard chow. Their  blood glucose levels normalized and their insulin sensitivity increased, but the "reduced-obese" mice also showed markedly increased fasting-induced hyperphagia. In fact, when they given ad libitum access to their beloved high fat diet, they ate like there was no tomorrow and ended up gaining weight at a much faster pace than their never-obese peers, who were likewise allowed free access to the HFD.
  
  And it gets even worse, as the conclusion the scientists draw based on their results says that despite the fact that "caloric restriction on a HFD provides metabolic benefits", it may actually require a previously obese dieter to continue on the path of caloric restriction (i.e. never eat to 'satiety') for the rest of his/her life!
  
• Morning to evening decline in insulin response to carbs suggests breakfast is the time where your body reacts most sensitive to carbs (Saad. 2012) -- Likewise published in the latest issue of Diabetes is a study by Ahmed Saad and colleagues from the Mayo College of Medicine in Rochester and the the University of Padova in Italy, which does at first not really sound like it was revolutionary new. Two definitive advantages of the study at hand were yet that the scientists used healthy individuals as subject and gave them regular mixed meals instead of a glucose solution in order to confirm the existence and identify the characteristic features of the diurnal pattern of glucose tolerance most people take for granted.
  
  

  

  The implications of this study for intermittent fasting are not as clear as you may think and certainly don't imply that you must break your fast in the morning (read more about breaking the fast, here)

  Overall 20 healthy volunteers with normal fasting glucose (4.8 ± 0.1 mmol/L) and HbA_1c (5.2 ± 0.0%) participated in the study. They were provided with identical mixed meals during breakfast, lunch, or dinner at 0700, 1300, and 1900 h in a random order on 3 consecutive days. Physical activity was held constant so that e.g. muscle glycogen depletion and subsequent increases in AMPK induced GLUT-4 expression  would not skew the results.
  
  What Saad et al. fonud was that the postprandial glucose excursion was significantly lower (P < 0.01) at breakfast than lunch and dinner. At the same time the β-Cell responsivity to glucose was higher. This means there was more insulin released per unit of glucose, than during lunch or dinner.
  
  The time the hepatic insulin extraction was also lower at breakfast; although the difference reached statistical significance only in comparison to the dinner condition. Since the overall meal glucose appearance did not differ between meals and that the suppression of endogenous glucose production "tended to be lower (P < 0.01) and insulin sensitivity tended to be higher (P < 0.01) at breakfast than at lunch or dinner" (Saad. 2012), it is no wonder that the spike in blood glucose was largely augmented, when the subjects consumed the standardized meal for breakfast.
  
• Adipocyte size is a determinant of non-alcoholic fatty liver disease (NAFLD) risk (Petäjä. 2012) -- One thing scientists still have not really understood is how some obese people seem to be way better off than others, although their BMIs, fat and lean mass appears to be identical. In view of the latest paper by a group of researchers from Finland and Sweden on the association between the average fat cell size and the occurrence of NAFLD, it could well be that ratio of the total adipose volume to the total fat cell number, which obviously is the adipocyte size, may be providing at least another piece to the puzzle that holds the answer to this question.
  
  

  

  In a previos post on the yoyo effect, I already discussed some aspects of adipocyte morphology - read more

  The scientists have studied 119 non-diabetic subjects in a cross-sectional study. The participants had a median age of 39 (26-53) years, and a mean BMI of 30.0±5.7kg/m². Subcutaneous abdominal fat cell size, as well as the total amount of liver fat were measured by proton magnetic resonance spectroscopy, intra-abdominal (IA) and abdominal subcutaneous adipose tissue (SC) volumes by magnetic resonance imaging (MRI) and an additional gene analysis yielded information about the genotype (susceptible or not susceptble to metabolic syndrome) of the individuals.
  
  Simply based on a multiple linear regression analysis, age, gender, BMI, the intra-abdominal to subcutaneous fat ratio and the subject's PNPLA3 genotype, the results were only able to explain 42% of the variation of the liver fat. The inclusion of the adipocyte sizes increased the predictive value by 11%, so that "21% of the known variation in liver fat could be explained by adipocyte size alone" (Petäjä. 2012) This does yet also mean that once we are up to a 90% explanation  (which is unrealistic, by the way) the adipocyte size will only be able to explain "of the known variations".
  
• Antibiotic that's commonly used in animal fattening kills body fat (Szkudlarek-Mikho, 2012) -- Reserachers from the College of Medicine at the University of Toledo in Ohio have found that polyether ionophoric antibiotics including monensin, salinomycin, and narasin, which are widely used in veterinary medicine and as food additives and growth promoters in animal husbandry including poultry farming have toxic effects on adipose cells.
  
  

  

  Whether eating the chicken that ate antibiotics is going to make  you lean does still have to be established. Based on the results of the study at hand, it does however appear likely that eating antibiotics could - I do however doubt that they will achieve that without potentially serious side effects.

  Although previous studies suggest that salinomycin has anti-carcinogenic effects (Huczyński. 2012), the sharp increase in poultry consumption over the last decade(s) and the increased use of these "growth promoting" antibiotics by veterinaries and poultry farmers has often been suspected to be involved in the increase in metabolic and autoimmune diseases.
  
  At least in view of the former, i.e. metabolic diseases in general and obesity, in particular, it may therefore be surprising that the scientists from the University of Toledo discovered that the tested ionophoric antibiotics did not just inhibit the differentiation of cancer, but also that of preadipocytes into adipocytes:
  

  "The block of differentiation is not due to the induction of apoptosis nor the inhibition of cell proliferation. In addition, salinomycin also suppresses the transcriptional activity of the CCAAT/enhancer binding proteins and the peroxisome proliferator-activated receptor γ." (Szkudlarek-Mikho. 2012)

  Now, I would fully subscribe to the scientists suggestion that these "ionophoric antibiotics can be exploited as novel anti-obesity therapeutics", but until that has been done and we know which other cells' differentiation they may inhibit, as well, I'd strongly discourage anyone from 'supplementing' with the antibiotics from his or her poultry farmer next door. After all, you may well end up not just with less body fat, but with less brain tissue, as well... what? You don't care? Oh I see. The doctor must have inserted the cannula into your ears instead of your belly on your last liposuction, right?
  
• Alpinia officinarum, a plant in the ginger family, stops fat gains in its tracks (Jung. 2012) -- Jung, Jang, Ahn and the rest of the researchers from the Korea Food Research Institute in Seongnam, report in their latest paper that an ethanol extract from Alpinia officinarum, a plant in the ginger family that's cultivated in Southeast Asia and is also known as lesser galangal, is yet another mainstay of traditional medicine with significant anti-obesity effects.
  
  

  

  It looks almost like ginger and works almost like ginger, but A. officinarum contains galangin, not gingerol and works via the PPAR-gamma pathway, as well. That's something gingerol doesn't do (Huang. 2012)

  Originally used throughout Asia in curries and perfumes, A. officinarum contains a dietary flavenol called galangin, which has already been shown to exert profound anti-cancer effects (Kapoor. 2012), whether it is solely responsible for the in vitro and in vivo inhibitory effects on lipid accumulation during the differentation of 3T3-L1 adipocytes is not certain, but appears to be likely.
  
  Via its effects on the fat synthesis and breakdown and PPAR-gamma activity the A. officinarum extract (AOE) lead to dose-dependent decreases in body weight gains of mice who were fed a high fat diet. It also reduced the visceral and liver fat deposition and partially restored the abnormally elevated insulin and leptin levels of the rodents.
  

  "Collectively, these results suggest that AOE prevents obesity by suppressing adipogenic and lipogenic genes. AOE has potential for use as an antiobesity therapeutic agent that can function by regulating lipid metabolism." (Jung. 2012)

  Certainly another nice find, but let's be honest, what's the real value of all this herbs? I mean yeah they work almost as effectively (in some cases even better) than pharmacological drugs, but both share a detrimental downside, that's not mentioned under "side effects" on the package insert or supplement bottle: They will only manage a problem the root course of which is the net result of a totally messed up diet.

That's it and since you've gotten the bottom line in advance and another time, just to make sure nobody can over-read it, in the last paragraph of the last news item, I just want to remind everyone that there are a couple of other interesting science news and links, for example about ...

• the pro-carcinogenic effects of shift work and to a lesser degree constantly working at night (read),
• the connection between high GI carbs and prostate cancer (read), or
• the idiocy of battling the high GI carb induced decline in cognitive performance with even more sugar (read)

waiting for you on Facebook. Have a nice day and get lean and stay lean ;-)

References

• Huang TH, Teoh AW, Lin BL, Lin DS, Roufogalis B. The role of herbal PPAR modulators in the treatment of cardiometabolic syndrome. Pharmacol Res. 2009 Sep;60(3):195-206. Epub 2009 Apr 7.
• Huczyński A, Janczak J, Antoszczak M, Wietrzyk J, Maj E, Brzezinski B. Antiproliferative activity of salinomycin and its derivatives. Bioorg Med Chem Lett. 2012 Dec 1;22(23):7146-50.
• Jung CH, Jang SJ, Ahn J, Gwon SY, Jeon TI, Kim TW, Ha TY. Alpinia officinarum Inhibits Adipocyte Differentiation and High-Fat Diet-Induced Obesity in Mice Through Regulation of Adipogenesis and Lipogenesis. J Med Food. 2012 Nov;15(11):959-67.
• Kapoor S. Galangin and its emerging anti-neoplastic effects. Cytotechnology. 2012 Oct 25.
• Kirchner H, Hofmann SM, Fischer-Rosinsky A, Hembree J, Abplanalp W, Ottaway N, Donelan E, Krishna R, Woods SC, Müller TD, Spranger J, Perez-Tilve D, Pfluger PT, Tschöp MH, Habegger KM. Caloric restriction chronically impairs metabolic programming in mice. Diabetes. 2012 Nov;61(11):2734-42. doi: 10.2337/db11-1621.
• Petäjä EM, Sevastianova K, Hakkarainen A, Orho-Melander M, Lundbom N, Yki-Järvinen H. Adipocyte size is associated with NAFLD independent of obesity, fat distribution and PNPLA3 genotype. Obesity. 2012. Ahead of Print.
• Saad A, Dalla Man C, Nandy DK, Levine JA, Bharucha AE, Rizza RA, Basu R, Carter RE, Cobelli C, Kudva YC, Basu A. Diurnal pattern to insulin secretion and insulin action in healthy individuals. Diabetes. 2012 Nov;61(11):2691-700.
• Szkudlarek-Mikho M, Saunders RA, Yap SF, Ngeow YF, Chin KV. Salinomycin, A Polyether Ionophoric Antibiotic, Inhibits Adipogenesis. Biochem Biophys Res Commun. 2012 Oct 31.
• Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM. Reduction of lipid accumulation in white adipose tissues by Cassia tora (Leguminosae) seed extract is associated with AMPK activation. Food Chem. 2013 Jan 15;136(2):1086-94. doi: 10.1016/j.foodchem.2012.09.017.

Forget the Blood Type Diet, Embrace the Gut Type Diet: Eating According to the Likes or Dislikes of Your Bacterial Subtenants Could Keep You Healthy, Lean & Sane.

Image 1: You better feed them right, or your gut bacteria could will disbehave just like the Alien in Ellen Ripley (Sigourney Weaver) in Alien 3 (20th Century Fox).

Eating right for your type, probably is not what it takes to have dietary success. Scientists from the US and Brazil have now found that eating according to the likes an dislikes of your bacterial subtenants seems to could eventually have a much greater potential (Wu. 2011) in keeping you healthy and, as the results of the joint research efforts of Canadian and Irish scientists shows, psychologically sane (Bravo. 2011).

Scientists estimate that the genome of the sum of our gut microbia is about 100x more complex than our own gene-sequence and the type and ratio of the 300-1000 different species within your intestinal tract have a major impact not only on how you digest your food, but also on how you look, feel and perform. It is therefore particularly interesting that Gary D. Wu and his colleagues established (for the first time) the existence of a stable microbiome composition that appears to be specialize to strive on a specific diet.

Note: Currently, the data is still too scarce and the variety of gut microbia, as well as their interactions too complex, for any reliable conclusions on whether it is "optimal" to eat according to your current gut biome or whether and in which way it would benefit your health, performance or body composition to modify / tweak the composition of the latter by dietary strategies and/or supplements or even medications. Even the idea of "optimizing" the microbial composition of our guts for "optimal" macro-nutrient usage is illusive, as it could well be that the specialization of our gut bacteria, i.e. their efficiency in using only little of the dietary energy for themselves and redirecting the rest to us, could theoretically be among the reasons for the obesity epidemic, as well.

In a preliminary analysis Wu et al. had established that in 98 healthy volunteers, whose stool they had analyzed for its individual microbiome composition there was a high correlation between habitual diets (measured by dietary questionnaires; data cf. figure 1, below) and the predominant type of bacteria.

Bacteroide enterotype was highly associated with animal protein, a variety of amino acids, and saturated fats, suggesting that meat consumption as in a Western diet characterized this enterotype. [...] The Prevotella enterotype, [...] was associated with [...] high values for carbohydrates and simple sugars, indicating association with a carbohydrate-based diet more typical of agrarian societies.

As one would expect, "self-reported vegetarians (n = 11) showed enrichment in the Prevotella
enterotype (27% Prevotella enterotype vs. 10% Bacteriodes enterotype; p = 0.13)" and the one self-reported vegan was in the Prevotella enterotype group, as well.

Image 2: Prevotella histicola is a major driving force of tooth decay (King's College). Its relatives in the gut, on the other hand, have been found to be implicated in insulin resistance and infertility due to endotoxin-related inflammation.

Now, if you are a dentist or did some research in the area of "caries" for whatever reason, the name "Prevotella" will probably sound remotely familiar. After all, the Prevotella species has been found to be associated with severe early childhood caries (e.g. Tanner. 2011). These are also the guys, whose poisonous lipolysaccharide dung increases the synthesis of the inflammatory cytokine TNF-alpha (Kim. 2007), which, in turn, has long been known to induce insulin resistance (Hotamisligil. 1999) - quite smart from the bacteria, isn't it? After all, if your body does not suck up the glucose the Prevotella will have more sugar to feed on. What may be less smart, though ,is that the endotoxin (lipolysaccharides are considered endotoxins) induced inflammation will also compromise testicular function on multiple levels, which in turn would deprive future generations of bacteria of their hosts.

Figure 1: Associations (Spearman correlation; -1: max neg. / +1 max pos.) between habitual dietary intake of sugars, vitamins & minerals, fats, amino acids, proteins and micronutrients and bacterial composition, where enterotype 1 is bacteriode dominant, and enterotype 2 is prevotella dominant (data adapted from Wu. 2011)

The polysaccharide A (PSA) produced by Bacteroides, an even larger class of bacteria which obviously strives on a high fat, high protein diet (or rather what mainstream dietitians call "high protein"), on the other hand, has recently been implicated in beneficial modulations of the immune system (Troy. 2010) and apparently even protects the nerves from he central nervous system from demyelation (Ochoa-Repáraz. 2010), i.e. the destruction of the insulating myelin layer. There is however a broad variety among the Bacteroides and as Wexler in his aptly titled paper "Bacteroides: the good, the bad, and the nitty-gritty." points out (Wexler. 2010):

The bacteria maintain a complex and generally beneficial relationship with the host when retained in the gut, but when they escape this environment they can cause significant pathology, including bacteremia and abscess formation in multiple body sites.

Based on the results of Wu's study, which also showed that a short-term dietary intevention (10 days) could not change the Bacteriode dominance of the 10 subjects who had been randomly assigned to high fat/low or a low fat/high fiber diets, we can thus only say that we probably are "optimized" for a certain macronutrient composition. Whether this is a beneficial or detrimental adaptation has still to be determined. What has however been established (in a rat model) is that chronic treatment with the probiotic bacteria Lactobacillus rhamnosus

[...] induced region-dependent alterations in GABAB1b mRNA in the brain [, ...] reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus [and] reduced stress-induced corticosterone and anxiety- and depression-related behavior.

Bravo et al. ascribe these beneficial psycho-physiological effects to the "modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain". And highlight the "bidirectional communication of the gut–brain axis" as a possible target to treat stress-related disorders.

Image 3: The antibiotic vancomycin could potentially induce obesity month after treatment.

Did you know that Thuny et al. clearly showed that (Thuny. 2010) combined treatment with vancomycin-plus-gentamycin in patients with infective endocarditis was associated with a significant gain in BMI of +2.3kg/m² in the first year after discharge from hospital. For a man of 180cm this would be ~7.5kg. Vancomycin, by the way happens to be the cousin of Avoparcin an antimicribial growth promoter that has been used in the EU for fattening animals for about a year before it was prohibited in 1997.

In defense of "antibiotics" and as a word of caution against exuberant enthusiasm for all bacteria it should yet be mentioned that alternative antibiotics did not exhibit the same profound effects in the Thuny study. Moreover, observations in germ-free mice suggest that (Bäckhed. 2006)

[germ-free] animals are protected from diet-induced obesity by two complementary but independent mechanisms that result in increased fatty acid metabolism: (i) elevated levels of Fiaf, which induces Pgc-1α; and (ii) increased AMPK activity.

In view of the ever increasing resistance towards antibiotics, it is however unrealistic to assume that we will see similar effects in humans after the administration of individual or even combined high-dose antibiotics.

Moreover, more and more scientists argue that, based on the growth-promoting effects of antibiotics in food animals (Linn. 2011), it is more than likely that the long thought of relation between gut microbiota and the human obesity epidemic is real and that research into the detailed working principles of antimicrobial growth promoters (AGP) in animals may reveal hitherto overlooked underpinnings of obesity an respective treatment strategies.

We will see what future research will bring. Yet, while you are waiting for me to keep you on par with the results, I suggest you better stay away from growth or non-growth promoting antibiotics if you want to stay healthy, sane and slim.