Supplement Review: Lactulose - Isomerized Lactose With Prebiotic, Anti-Constipation, -Cancer, -Hyperammonia, -Salmonella, -Endotoxin & Pro-Mineral Absorption Effects

Don't worry: There is more than flatulence and diarrhea to lactulose... I mean, why do you think I'd write about it, then?

I am not sure if all of you have already heard of 4-O-β-D-galactopyranosyl-D-fructose aka lactulose, a synthetic nondigestible sugar you can buy either as a white, odorless powder or as a syrup. It tastes, contrary to what you may expect, pretty good, a bit like hilariously sweet honey, if you asked me, and sweet enough to be used as an "artificial" sweetener. A sweetener that has traditionally been sold as a medicinal drug for decades but is not appearing on an ever-increasing number of ingredient lists of so-called "functional" food products. Despite the fact that the market has grown appreciably over the last 10 years (Panesar & Kumari. 2011), lactulose is after all not yet as "popular" as inulin and the rest of its prebiotic brethren.

From drug, to supplement to food additive

The mere fact that the easiest but certainly not cheapest way to acquire lactulose is still the pharmacy obviously doesn't imply that you can use it as any other over-the-counter (it is OTC, even in Germany ;-) supplement. And that's true in spite of the fact that your doctor may actually prescribe it, if you are suffering from hepatic encephalopathy, constipation, or salmonella (Schumann. 2002).

Lactulose content (mg/l) of milk (Marconi. 2004)

There is "natural" lactulose in milk: Due to the fact that lactulose can be produced by the heat-induced isomerization of lactose (see inset in figure to the left for a reaction curve for milk that's heated at 130°C), all varieties of heat treated milk, even the low-temperature pasteurized variety will contain a certain, albeit low amount of lactulose (see figure to the left).

If that was all lactulose was good for, it would yet probably not have made it into the SuppVersity Supplement Review. The latter is rather due to its ever-increasing presence in "functional foods", where it is used as a prebiotic for its impressive beneficial effects on the composition of the colonic microflora.

If lactulose is added to the formula milk, such babies have same composition of the colonic microflora as the breast-fed babies (Knol. 2005).

I see, now you're listening... I would suggest, then, that we take a brief look at other established and suspected benefits lactulose supplements / lactulose-enriched functional foods have to offer:

• Constipation - I already mentioned it in the introduction. If you ask your doctor about lactolose supplements, he will probably raise his eye-brow and say: "Are you constipated?" While the general recommendation is to treat constipation by increasing your water intake, the amount of fibrous foods you eat, etc. lactulose has a long history as an intermediate adjunct to these changes in patients of all ages, including babies.
  
  
  Flatulence Warning: Don't ingest lactulose before your first date with the girl or guy of your dreams ;-)
  Lactulose is an osmotic laxative. This means it will draw more water into the the colon and can thus offer relief of constipation, including chronic constipation within about 24-48h. When it reaches the intestine, the lactulose molecule is still intact. Lactulose is not digested in the small intestine as the specific disaccharidase is lacking.
  
  It transits unchanged to the colon where it serves as an energy source for the carbohydrate-splitting bacteria, predominantly lactobacillus acidophilus and L-bifidus (Saarela et al., 2003; Cardelle-Cobas et al., 2011; Hernandez-Hernandez et al., 2012).

Lactulose "feeds" the good bacteria in your gut: As you can see in the figure to the left, the continous ingestion of 5g of lactulose for 42 days lead to statistically significant increase in the  16 healthy volunteers who were included in Bouhnik et al.'s controlled, randomised, double-blind, parallel group trial (Bouhnik. 2004).

• These bacteria split lactulose into its active components that will then exert the previously mentioned osmotic effect. Unfortunately, the fermentation process, will usually give rise to some gas... especially in people who are not used to the ingestion of fibrous foods this can lead to temporary gaseous social incompatibility (aka flatulence; cf. Blanc. 1992).

• 

  Table 1: Summary of treatment, comparison and results of studies on the effects of lactulose on PSE that were reviewed by Conn et al. (1977) and Heredia et al. (1987); (+) clinical improvement, (=) no significant difference, (±) treatment lead to improvement in psychometric tests

  Portal systemic encephalopathy (PSE) therapy - According to Prasad et al. (2007) lactulose exerts significant beneficial effects on the impaired neuronal function and cognitive performance of PSE patients. In the corresponding study that involved thirty-one patients received lactulose treatment for 3 months (+30 controls who did not) the lactulose group showed significant improvements in their quality of life and emotional behavior.
  
  It must be said, though that not all pertinent studies were able to detect significant beneficial effects of lactulose supplementation on PSE. In fact, more than 50% of the studies Conn et al. (1977) as well as Heredia et al. (1987) have reviewed (see Table 1) were unable to detect a significant difference between the patients in the lactulose and those in the healthy control group.
• Salmonella - While peer-reviewed studies on the effects of lactulose in patients with nontyphoid salmonella (Schumann. 2002), there is plenty of anecdotal evidence that lactulose at dosages of up to 60 g per day (diarrhea alert!) can kill the intruders by inducing a a sharp drop of the colonic pH, which makes the survival of salmonella difficult.
• Endotoxins - As a SuppVersity reader you know that endotoxins are what you could call the "toxic poop" of the bacteria that colonize your gut. In a 2003 study Koutelidakis et al. were able to show that jaundice patients who had been pretreated with lactulose showed a significantly reduced increase in endotoxins after surgery. These observations are supported by animal experiments that have shown that oral lactulose administration reduced the mortality associated with endotoxin in obstructive jaundice. 

• 

  Tired, exhausted, had to cut your workout short today? Is it the flu, or just too much BCAAs? | learn more

  Reduction of blood ammonia levels - This effect of lactulose can actually come very handy for the average protein addicted gymrat as well.
  
  You will probably remember the article about the BCAA induced performance decrements from November 2012 ("Chronic High Dose BCAA Supplementation Reduces Endurance Performance by 43% Plus: How Ammonia, Glutamine, Arginine & Low Carb Could be Involved" | read more).
  
  If said effects are actually a consequence of the ammonia accumulation it may come handy to reduce the baseline ammonia influx from the gut by reducing its production via the acidifying effects of lactulose (Wright. 2011).
• Cancer - Not directly gym-relevant, but certainly as important is the protective effect lactulose may have on colon carcinogenesis. This type of cancer usually develops in the presence of high amounts of secondary bile salts, which could partially explain the reported lower rate of cancer recurrence in colon cancer patients who were treated with lactulose. Rodent studies by Verma & Shulka also suggest that lactulose has a direct protective effect on the DNA of the colon mucosa of rats (Verma. 2013; note: on a per gram basis inulin, which was also tested in this study was a more effective DNA protector).
  
  In addition to its (more or less) direct effects, the lactulose induced increase in bifidobacteria may also have cancer protective effects - not just in the colon, but in the mammary gland and liver, as well (Reddy. 1993)
• Enhancement of mineral absorption - When you surf through the blogosphere you will be confronted with horror-stories about the inhibitory effects all sorts of food products are supposed to have on the absorption of calcium, magnesium iron and co. Against that background it's almost relieving to know that lactulose can significantly augment the absorption of calcium, magnesium, zinc, copper, iron (Seki. 2007).

  

  Figure 1: Effects of 2g and 4g lactulose added to a standardized test meal on the absorption (measured by urinary excretion) of calcium and magnesium in 24 healthy volunteers (Seki. 2007)

  Pometto al. report that the effects are sufficient enough to exert anti-osteoporotic effects in a rodent model (Pometto. 2006). Whether the same goes for human beings hasn't been established, though.

If you review the overall effects, I guess you will be able to trace most of them back to the prebiotic properties of lactulose. The latter is a good thing, but in view of the fact that lactulose is by no means the only prebiotic with promising health effects the question is.

A word of caution to everyone out there with existing intestinal problems: As you may remember from the SuppVerstiy Facebook News Whelan et al. have only recently published a paper that reviews the the evidence that some prebiotics in high doses worsen functional symptoms in IBS and Crohn's patients. (Whelan. 2013 | cf. SvFb Post).

Do we actually need lactulose? As I pointed out in the previous paragraphs, lactulose has plenty of health benefits. It is yet questionable which, if any are "exclusive" to the isomerization product of lactose which has the nasty tendency to produce socially unwanted side effects and highly impractical such as flatulence and diarrhea.

If you don't overdo it (1-2g/day is a good starting dose) you should however be able to avoid loose stools and control the gas production. In this case lactulose can more very handy as one out of many tools you can use to increase the prebiotic content of your diet. Plus: Contrary to most other prebiotics lactulose tastes actually pretty good and can be used as a tasty and healthy sweetening agent in all sorts of products. The latter is also the reason that I expect that you will see it on more and more ingredient labels of commercially available food products in 2014 and beyond.

References:

• Aït-Aissa, A. and Aïder, M. (2013), Lactulose: production and use in functional food, medical and pharmaceutical applications. Practical and critical review. International Journal of Food Science & Technology
• Blanc, P., Daures, J. P., Rouillon, J. M., Peray, P., Pierrugues, R., Larrey, D., ... & Michel, H. (1992). Lactitol or lactulose in the treatment of chronic hepatic encephalopathy: Results of a meta‐analysis. Hepatology, 15(2), 222-228. 
• Knol, J., Scholtens, P., Kafka, C., Steenbakkers, J., Gro, S., Helm, K., ... & Wells, J. (2005). Colon microflora in infants fed formula with galacto-and fructo-oligosaccharides: more like breast-fed infants. Journal of pediatric gastroenterology and nutrition, 40(1), 36-42.
• Koutelidakis, I., Papaziogas, B., Giamarellos-Bourboulis, E. J., Makris, J., Pavlidis, T., Giamarellou, H., & Papaziogas, T. (2003). Systemic endotoxaemia following obstructive jaundice: the role of lactulose. Journal of Surgical Research, 113(2), 243-247.
• Marconi, E., Messia, M. C., Amine, A., Moscone, D., Vernazza, F., Stocchi, F., & Palleschi, G. (2004). Heat-treated milk differentiation by a sensitive lactulose assay. Food Chemistry, 84(3), 447-450. 
• Reddy, B. S., & Rivenson, A. (1993). Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2-amino-3-methylimidazo [4, 5-f] quinoline, a food mutagen. Cancer research, 53(17), 3914-3918. 
• Panesar, P. S., & Kumari, S. (2011). Lactulose: production, purification and potential applications. Biotechnology advances, 29(6), 940-948.
• Pometto, A., Shetty, K., Paliyath, G., & Levin, R. E. (Eds.). (2005). Food biotechnology. CRC Press.
• Seki, N., Hamano, H., Iiyama, Y., Asano, Y., Kokubo, S., Yamauchi, K., ... & Kudou, H. (2007). Effect of lactulose on calcium and magnesium absorption: a study using stable isotopes in adult men. Journal of nutritional science and vitaminology, 53(1), 5-12.
• Schumann, C. (2002). Medical, nutritional and technological properties of lactulose. An update. European Journal of Nutrition, 41(1), i17-i25.
• Van Boekel, M. A. J. S. (1998). Effect of heating on Maillard reactions in milk. Food Chemistry, 62(4), 403-414. 
• Wright, G., Chattree, A., & Jalan, R. (2011). Management of hepatic encephalopathy. International journal of hepatology, 2011.

Dairy - The Good, the Bad or The Ugly? Latest Studies On Heart Disease, Diabetes, Cancer, Obesity and Co. Plus: What Dairy Peptides Do For Your Heart, Gut, Brain, etc.

Do you take Liz Hurley's word and set all warnings about the "non-paleo-ness" of dairy in general and milk in particular at naught? Or do you put faith into the "got milk?" campaign? Personally, I'd suggest not to do one or the other. I'd rather suggest you join me and take a look at a selection of recent studies.

If you've been following the SuppVersity Facebook News and / or have read previous SuppVersity articles on milk and dairy, you will be aware that I am not exactly convinced that the mere existence of allergic reactions and the "fact" that "our ancestors did not drink milk before ..." *put your favorite guesstimate here* allows for the conclusion that we are "not meant" to consume cow's milk. I am nevertheless open to scientific arguments that would convince me that dairy is bad for me - it's just that I don't see this evidence outside of "western diet + dairy makes you fat and that makes you sick" contexts.

What I do see, though, are papers such as the one Sandra Abreu or the recent review by Flávia Galvão Cândido et al. - studies that tell us that the intake of milk is negatively associated with the clustering of cardiometabolic risk factors in adolescents (Abreu. 2013), and reviews which conclude that "the consumption of low-fat dairy products may be an important strategy to prevent and control T2DM [type 2 diabetes]" (Cândido. 2013).

The evidence that dairy is bad for us all is simply not there

But hey, ... let's tackle the evidence one by one. I mean, there is plenty of news-worthy material here and we don't want the fun to be over prematurely, do we? So, let's start with a brief sketch of what Sandra Abreu and her colleagues from the University of Porto base their assessment that the intake of milk, but not total dairy, yogurt, or cheese, is negatively associated with the clustering of cardiometabolic risk factors in Spanish adolescents - shall we?

No! Full-fat dairy is not bad for you: While most of the epidemiological studies with their hilariously unreliable food questionnaires appear to suggest that only low fat dairy was good for your heart, a recent study from the Harvard School of Public Health found a clever way to test the association more objectively. Instead of questioning their subjects, 2837 US adults aged 45 to 84 years, they tested the amount of certain phospholipids in their blood and found that "plasma phospholipid 15:0, a biomarker of dairy fat, was inversely associated with incident CVD [-19%] and CHD [-26%]." (de Oliveira Otto. 2013) The fact that other dairy related phospholipids were not associated (neither positive nor negative) with cardiovascular and coronary heart disease risk does yet, as the scientists rightly point out, warrant further investigation.

"To test th[e] hypothesis [that a higher dairy product intake is associated with lower cardiometabolic risk factor clustering in adolescents], a cross-sectional study was conducted with 494 adolescents aged 15 to 18 years from the Azorean Archipelago, Portugal. We measured fasting glucose, insulin, total cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body fat, and cardiorespiratory fitness. We also calculated homeostatic model assessment and total cholesterol/high-density lipoprotein cholesterol ratio. For each one of these variables, a z score was computed using age and sex. A cardiometabolic risk score (CMRS) was constructed by summing up the z scores of all individual risk factors. High risk was considered to exist when an individual had at least 1 SD from this score. Diet was evaluated using a food frequency questionnaire, and the intake of total dairy (included milk, yogurt, and cheese), milk, yogurt, and cheese was categorized as low (equal to or below the median of the total sample) or “appropriate” (above the median of the total sample). The association between dairy product intake and CMRS was evaluated using separate logistic regression, and the results were adjusted for confounders." (Abreu. 2013)

I know that sounds really sophisticated, but in the end, it's just standard procedure for cross-sectional studies like this - studies with one unfortunate downside: It's impossible to detect causal relationships. 

Figure 1: Dietary intake in the low and "adequate" dairy-, milk-, yogurt-intake groups (Abreu. 2013)

Keep that in mind, when you take a closer look at the data in Figure 2 which indicates that the average adolescent milk connoisseur of whom you can see in Figure 1 that he / she consumes significantly more energy on a daily basis has a significantly reduced cardiometabolic risk (predicted by cardiometabolic risk score; CMRS):

Figure 2: Cardiometabolic risk in "adequate" vs. low dairy, milk, yogurt and cheese consuming adolescents; adjusted for parental education , pubertal stage, low-energy reporter, energy intake, total fat , protein , and dietary fiber intake.

I personally was surprised to see a statistically significant protective effect only with milk - it's not that I had expected to see that for all forms of dairy, but based on previous studies I would have expected the fermented yogurt products to outperform conventional milk.

The negative effects of cheese on the other hand are by no means surprising. Food logs do after all include all types of "cheese" including the fake yellow vegetable oil based cheese analogues the kids shovel down with their pizzas, burgers and the rest of the fast food dirt. A high cheese intake has thus (unfortunately) become an indicator of low diet quality and the results of the study at hand hardly a credible marker that cheese is bad for you.

If 95% of your "dairy intake" comes from pizza, you are unlikely to see...

... any of the following benefits of dairy peptides, Blanca Hernández-Ledesma, María José García-Nebot, Samuel Fernández-Tomé, Lourdes Amigo, and Isidra Recio summarized in a soon-to-be-published review in the peer-reviewed scientific journal International Dairy Science:

• 

  Figure 3: Reduction of systolic blood pressure in mmHg per mg/kg of the said peptide you consume - mind the logarithmic scale(!); data calculated based on rodent studies summarized in Hernández-Ledesma (2014)

  Cardiovascular health effects due to the antihypertensive, anti-inflammatory, general antioxidant and hypocholesterolaemic properties of various dairy peptides
• Intestinal health effects due to the ability of dairy peptides to modulate and regenerate the gut mucosa, increase mineral absorption, exert local anti-inflammatory effects at the gastrointestinal level
• Antidiabesity effects that are related to both direct pro-insulinogenic effects of dairy peptides ant their ability to increase satiety. 
• Central nervous system relaxant and antinociceptive (pain-killing) effects
• Immune health which is promoted by antimicrobial and immunomodulatory peptides that are either already present in dairy or arise during the digestion process
• Anticancer effects that are mediated by the overall anti-inflammatory properties of certain dairy peptides, as well as direct anti-proliferative effects of dairy

Now, it goes without saying that you won't see the same effect from eating some goat kefir as Miguel et al. (2010) observed it, when they administered fraction 58-68 of goat casein to their lab rodents, but the data in Figure 3 can explain the well-established blood pressure lowering effects of dairy in general and the whey and casein induced BP reduction Figueroa et al. observed only recently in a study with obese women (Figueroa. 2013; see SuppVersity Facebook News).

Bottom line: You can't expect dairy to fully protect you against diabesity, cancer and a leaky, you can't expect it to lean you out in days, and you can't expect it to build muscle overnight, but you can expect general health benefits not detriments from incorporating a variety of fermented and unfermented dairy products into your diet - as long as you ain't lactose intolerant.

"Are Camels the Better Cows? Cancer, CVD, Allergies,Infections & More - Camel Milk Prevents or Fixes All These Ailments" | more

One thing you should keep in mind, though, is the unfortunate fact that the amount of "non-dairy" cheese, cream and other products is increasing by the day. Especially the former, the fake yellow vegetable oil based cheese analogues is something you want to avoid. The same goes for many of low fat products. While much of the "magic" is in the peptides, most of the commercially available "diet" products contain tons of sugar and all sorts of questionable additive to make up for the loss of color, taste and texture that's brought about by the removal of the fat. And lastly all products that extend the shelf-life to "eternity" by adding questionable preservatives.

References

• Abreu, S., Moreira, P., Moreira, C., Mota, J., Moreira-Silva, I., Santos, P. C., & Santos, R. (2013). Intake of milk, but not total dairy, yogurt, or cheese, is negatively associated with the clustering of cardiometabolic risk factors in adolescents. Nutrition Research.
• Cândido, F.G., Ton, T. S., & Alfenas, R. D. C. G. (2013). Dairy products consumption versus type 2 diabetes prevention and treatment; a review of recent findings from human studies. Nutr Hosp, 28(5), 1384-1395.
• de Oliveira Otto, M. C., Nettleton, J. A., Lemaitre, R. N., Steffen, L. M., Kromhout, D., Rich, S. S., ... & Mozaffarian, D. (2013). Biomarkers of dairy fatty acids and risk of cardiovascular disease in the multi‐ethnic study of atherosclerosis. Journal of the American Heart Association, 2(4), e000092.
• Figueroa, A., Wong, A., Kinsey, A., Kalfon, R., Eddy, W., & Ormsbee, M. J. (2013). Effects of Milk Proteins and Combined Exercise Training on Aortic Hemodynamics and Arterial Stiffness in Young Obese Women With High Blood Pressure. American Journal of Hypertension, hpt224. 
• Freedman, B. J. (1980). Sulphur dioxide in foods and beverages: its use as a preservative and its effect on asthma. British Journal of Diseases of the Chest, 74, 128-134.
• Hernández-Ledesma, B., García-Nebot, M.J., Fernández-Tomé, S., Amigo, L.,
  Recio, I., Dairy protein hydrolysates: Peptides for health benefits, International Dairy Journal(2014), ahead of print
• Iammarino, M., Di Taranto, A., Palermo, C., & Muscarella, M. (2011). Survey of benzoic acid in cheeses: contribution to the estimation of an admissible maximum limit. Food Additives and Contaminants: Part B, 4(4), 231-237.

Androgen 3-Some: BPA Exposure & Free Testosterone in Men. TRT Good For the Prostate. DHT, Allopecia (Hair Loss) & Monascus Fermentation. Plus: Mycotoxins in GCB Supps

Coffee and green coffee bean extracts are by no means the only way by which you are exposed to mycotoxins. Corn, for example, is likewise a favorite for the toxic mold. The same goes for almost all other grains. Common routes of exposure are, amongst others cereals, breads, wines, and even mils and meats (of swine ad turkey, not chicken; Duarte. 2010)

36%, 32%, 10%, and 16% these are the SuppVersity Figures of the week and the percentages of green coffee bean supplements (remember the chlorogenic acid news in Thursday's installment of the Science Round-Up) that were contaminated with Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid, respectively.

"Mycotoxins occurred in the following concentration ranges: ochratoxin A: 2.7–136.9 µg/kg, ochratoxin B: 3.5–20.2 µg/kg, fumonisin B1: 110.0–415.0 µg/kg, mycophenolic acid: 43.1–395.0 µg/kg." (Vaclavi. 2013)

These poisonous substances are produced by fungi that form during (inproper) storage and are suspected to inhibit protein synthesis, damage macrophage systems, inhibit particle clearance of the lung, and increase sensitivity to bacterial endotoxins... ah, I almost forgot ochratoxins also wreak havoc on your hormones (Frizzell. 2013).

So far for the bad news, now the good one: According to the researchers calculations even with most contaminated of the 50 products they the average consumer who adheres to the suggested dosing protocol will still be well within the tolerable weekly intake (TWI) of 120 ng/kg body weight per week and tolerable daily intake (TDI) of 2000 ng/kg body weight per day for ochratoxin A and fumonisin B₁, respectively (these values were estimated by the EU Scientific Committee on Food (SCF) and the European Food Safety Authority (EFSA) - corresponding values of the "well-meaning" FDA or any other US government agencies are - as usual - not available).

Let's get to our androgen threesome

• 

  SuppVersity readers know: Tea is not only good for your prostate (learn more), it can also help you lose weight (read more)

  Testosterone replacement improves prostate issues (Ko. 2013) -- Contrary to what common "wisdom" will tell you scientists from the Yeungnam University College of Medicine in Korea can tell you that the 17 out of  46 patients who suffered from lower urinary tract symptom before they underwent TRT using intramuscular injection of 3 months bases injection of testosterone 1,000 mg undecanoate over a year achieved significant improvements (decrements) on the International Prostate Symptom Score (IPSS).
  
  Needless to say that "[d]uring the median follow up of 15.1 months, no patients experienced urinary retention, BPH-related surgery, or admission for urinary tract infection".

• BPA and low testosterone, you better know what to look at (Zhou. 2013) -- Talking about testosterone, there is finally some relatively reliable human data on the effects of BPA exposure on the hormone levels in men.

  

  Figure 1: Relative difference in free androgen index (FAI), androstenedione (AD), free testosterone (FT), SHBG, inhibin (INB), prolactin (PRL), follicle stimulating hormone (FSH), estrogen (E2) an total testosterone (T);  comparing the men with to the men without workplace exposure in the Zhou study

  As you can see in figure 1 the effects would go unnoticed, if you do not test for free hormones, but just checked the amount of total testosterone. How you can recognize that from the data? Well, the figures above the bars are the p-values. All that are >0.5 would suggest that this effect is statistically non-significant, so that every study not looking at things like the free androgen index (FAI) or the free testosterone levels (FT) will miss the 15% and 10% reduced levels of the latter and conclude: That it does not make a difference, if your serum contains 3.198 or 0.276mg/L as it was the case in the exposed and non-exposed subjects in this study from the Shanxi Medical University, because BPA won't harm you anyway.

• The fermented solution to all problems androgen?  (Chiu. 2013) Monascus bacteria that is used to ferment red mold rice, a traditional spice that is consumed throughout Asia could prevent androgenetic alopecia, benign prostate hyperplasia and prostate cancer.

  

  Figure 2: Changes in testosterone an DHT mice on TRT (control) w/w-out 0.2 & 0.5% Monascus extract in chow, corresponding images of the stained slices from the prostate and hair loss compared to standard treatment with finasteride (Chiu. 2013)

  The results of a recent study from the Department of Environmental and Occupational Health at the National Cheng Kung University Medical College clearly suggest that the way in which a monascus extract suppressed baldness in male B6CBAF1/j mice 

  

  Learn how to modulate DHT/T naturally.

  • decreased PSA levels  
  • decreased tumor volume and
  • decreased prostate cancer incidence, 
  • decreased dihydrotestosterone (DHT),
  • but left testosterone unchanged
  The effect was dose-dependent and was observed with 0.5-3% of the extract in the rodent diets. While it is not unlikely that the results will translate into human studies, it should be obvious that at least for the >0.5% doses, supplementation will be necessary.
  
  Irrespective of these latest study results, previous research indicates that Monascus-fermented products have many functional secondary metabolites, including monacolin K, citrinin, ankaflavin, and monascin and these have been shown to possess anti-inflammatory, antioxidative, cholesterol-lowering effect, and antitumor activities. Probably all of you will be familiar with at least one of them: Red Yeast Rice, the natural statin. And if you are not into spices or extracts, there are also other foods and even wines that are fermented with Monascus.

---

That's it for today: I know ladies, with today's focus on the male hormones, I owe you (big time?). But don't worry, there are also a couple of Facebook News, you may be interested in

• 

  Suggested read: "Carbohydrate Shortage in Paleo Land" (read more)

  "Oldie but goldie: T3, rt3 and carbohydrate intake in hyper- and eucaloric scenarios - Something worth considering for those constantly battling low T3 an high rT3 levels (read more)
• Omnipresence of "healthy" Subway sandwiches correlates w/ obesity rates - "Countries with the highest density of Subway restaurants such as the USA (7.52 per 100,000) and Canada (7.43 per 100,000) also tend to have a higher prevalence of obesity in both men (31.3% and 23.2%, respectively) and women (33.2% and 22.9%, respectively)." (read more)
• Understanding the neurological side effects of statin drugs - US scientists observed unusual swellings within neurons, which the team has termed the "beads-on-a-string" effect (read more)
• DHEA supplementation at 25gm/day to restore female fertility - A recent study from Turkey would suggest that this could actually work (read more)

If that's still not enough, come back tomorrow for another serving of the latest news from the realms of exercise, nutrition and health sciences, here at the SuppVersity! In the mean time, enjoy your weekend, everone!

References:

• Chiu HW, Chen MH, Fang WH, Hung CM, Chen YL, Wu MD, Yuan GF, Wu MJ, Wang YJ. Preventive effects of monascus on androgen-related diseases: androgenetic alopecia, benign prostatic hyperplasia, and prostate cancer. J Agric Food Chem. 2013 May 8;61(18):4379-86.  
• Duarte SC, Pena A, Lino CM. Ochratoxin a in Portugal: a review to assess human exposure. Toxins (Basel). 2010 Jun;2(6):1225-49. doi: 10.3390/toxins2061225. Epub 2010 Jun 1. Review. 
• Frizzell C, Verhaegen S, Ropstad E, Elliott CT, Connolly L. Endocrine disrupting effects of ochratoxin A at the level of nuclear receptor activation and steroidogenesis. Toxicol Lett. 2013 Mar 13;217(3):243-50.  
• Ko YH, Moon du G, Moon KH. Testosterone replacement alone for testosterone deficiency syndrome improves moderate lower urinary tract symptoms: one year follow-up. World J Mens Health. 2013 Apr;31(1):47-52.
• Vaclavik L, Vaclavikova M, Begley TH, Krynitsky AJ, Rader JI. Determination of Multiple Mycotoxins in Dietary Supplements Containing Green Coffee Bean Extracts Using Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry (UHPLC-MS/MS). Journal of Agricultural and Food Chemistry. May 2013 [ahead of print].
• Zhou Q, Miao M, Ran M, Ding L, Bai L, Wu T, Yuan W, Gao E, Wang J, Li G, Li DK. Serum bisphenol-A concentration and sex hormone levels in men. Fertil Steril. 2013 May 4.

Do You Have the Gut(s) to Lose 8% Belly Fat in 12 Weeks? Lactobacillus gasseri (LG2055) Can Fix Your Gut Problems

As a diligent student of the  SuppVersity, you'll obviously know that beer is not the main cause of the eponymous belly (Bobak. 2003). Although..., when when you come to think about it: For every glass of beer you drink, you're probably drinking a glass of probiotic yogurt less ;-)

You've done everything you could and still feel like a whale? You've been low-carbing, even have made sure you are in ketosis by consuming an only 10% protein diet and still the fat won't disappear? Well, I guess it sounds unfair, if I do now tell you that you YOU JUST DON'T HAVE THE GUTS it takes to get rid of that pouch that blocking the view on your toes, when you are standing.

Now calm down, I am not talking about not being able to curb your insatiable appetite or skipping 90% of your workouts, here. I am talking about your gut(s), literally! Your digestive tract and it's inhabitants. Those critters which are also at the heart of the soon-to-be-published paper by scientists from the Milk Science Research Institute in Fukoaka, Japan (Kadooka. 2013) - a paper, the results of which I am about to present in the next few paragraphs.

Probiotic in fermented milk shred visceral fat

I am not telling you something new, when I say (or write) that scientists have long identified the modulation of the gut microbiome, i.e. the bacterial ecosystem in your intestines, could be the long-sought-for lever to get rid or at least ameliorate the negative effects of the way we live and eat promotes the expansion of the highly inflammatory "stress fat" that fills the room between the organs in your trunk. Most of the hitherto published peer-reviewed research has yet been conducted in rodents. The existing evidence from well-controlled human studies, on the other hand is scarce.

Suggested read: "Probiotics for Athletes: The Supplemental 10 Billion CFS Leaky Gut Solution for the Fermented Food Refusinek?" (read more)

One of these studies has been conducted by Kadooka et al. in 2010 (Kadooka. 2010). In the pertinent paper the researchers from the Milk Science Research Institute in Japan reported that the provision of 200g/day of fermented milk containing 10^8 colony-forming units (cfu)/g of Lactobacillus gasseri strain SBT2055 (LG2055) led to significant reductions in visceral fat in male and female subjects with " higher body mass index" (BMI: 24.2-30.7 kg/m²) who had been randomized to the active arm of the study. Now, roughly three years later, are about to publish a follow-up paper with great practical relevance, as it summarizes the results of what Kadooka et al. say is the first human trial that examines the effect of different doses of probiotics on abdominal adiposity.

"We know that it works, but we don't know how much we need to elicit the desired effects"

The design of the study at hand is essentially identical with the one in the 2010 trial. It is based ona multi-centre, double-blind, parallel-group RCT with 210 healthy Japanese adults with large visceral fat areas (80.2–187.8 cm²), who were now randomly assigned to three instead of two groups who consumed 200g of fermented milk with either 1,000,000 CFU (1m), 10,000,000 CFU (10m) or just the normal yogurt probiotics (control) per gram for 12 weeks.

The intention was to determine whether the effect of LG2055, which is by the way a probiotic lactic acid bacterium that originates from the human intestine, would be observed with lower / more realistic dosage regimen as well and whether possible reductions in the effect size would be dose-dependent.

Figure 1: Reduction in visceral and subcutaneous adipose tissue, as well as waist circumference after 8 and 12 weeks on 1,000,000 CFU/g or 10,000,000 CFU/g yogurt drink; data expressed relative to group baseline (Kadooka. 2013)

If you take a look at the results, the first thing that strikes the eye in figure 1 is that the lactobacilli did their job and that in both the low and high dose group:

• Even in the 10x and 100x lower dosages there was a significant reduction in the amount of visceral fat the  33/36 respectively 36/35 men and women in the in the 1 million and 10 million CFU/day groups, respectively.
• The effect size of both dosages of LG2055 was identical, so that it would not actually matter if you consume just 100g or 1kg of an imaginary commercially available milk drink with 1,000,000 CFU of LG2055 per 100g.

In view of the >8% reduction in visceral fat mass, it should not come as a surprise that the reduction in waist size was likewise statistically significant - both on its own, as well as in comparison to the control group, What is yet not so obvious and probably somewhat disappoint for you is the fact that the reduction in the ugly, but benign subcutaneous fat was statistically and practically non-significant.

"Visceral fat loss, only? But what about my thigh fat?"

Not all probiotics are created equal: As the scientists emphasize in the discussion, the "it is also worth noting that the test FM containing both LG2055 and yogurt cultures reduced abdominal adiposity when compared with the control FM containing yogurt cultures alone, even though the bacterial counts of LG2055 (106 and 107 cfu/g) were lower than those in the yogurt cultures (109 cfu/g)." (Kadooka. 2013) The observed superiority of this particular strain of bacteria stands in line with previous rodent studies and is imho one of the reasons we are seeing so much research in this area. How's that? Well, easy: If you came up with a particularly potent strain and patented that, this would be the literary cash machine.

If you are no newbie to the SuppVersity you will yet be aware that it is by no means extra-ordinary that "healthy fat burners", which work their weight loss magic mostly by modulating local and/or whole body inflammation, have little or no effects on the amount of subcutaneous body fat.

If you discarded any statistical shenanigan and simply went by the height of the small bars in the middle of figure 1, you could yet probably argue that it appears as if there was a trend towards greater subcutaneous fat loss in the high(er) dose LG2055 group. If you went a step further and made the unwarranted assumption that you could simply compare the results from the study at hand to those of the aforementioned 2010 study b Kadooka et al. you could support this argument by stating that there was a clear trend here with 1.2%, 2.6% and 3.3% reductions in subcutaneous fat with LG2055 at concentrations of 1, 10 and 100 million CFU per gram of the fermented milk drink.

In the overall context it is yet important to point out that it is as of yet unknown whether the composition of colonic microbiota has a direct influence on abdominal and/or subcutaneous adipose tissue (Hildebrandt. 2009; Conterno. 2011). Moreover, ...

"[...] environmental factors, including genetics and age, makes it difficult to discuss the causal relationship between adiposity and intestinal microbiota." (Kadooka. 2013)

The latter are particularly difficult to access in a study like this, where the subjects maintain their habitual mode of living, including diet, and no strict dietary control is applied. Kadook et al. are thus right to point out that "the relation ship between adiposity and intestinal microbiota" has to be investigated more closely "under a strict diet, together with the latest methodology" (Kadooka. 2013) to finally make some progress in our understandings of the intricate interaction between the human gut microbiome and our metabolism.

---

Even the nicest subtenants can become a real problem, when they come over without being asked. Unfortunately, all sorts of gut bacteria (even the "good" ones) have a similarly nasty habit of translocating through a leaky gut wall into parts of your body, where you don't wont them (learn more)!

Bottom line: In view of the fact that the subjects shed the superfluous body fat in the absence of a reduced energy intake and/or exercise / increases in physical activity, the results are unquestionably impressive. To speak of "probiotic fat burner" would yet still not be warranted. After all, the subjects were all overweight and had an average body fat content of 32%, the baseline diet does - at least by the available data - not look really optimal (protein intakes of 0.8g/kg; macro-composition of 15/57/28% from protein, carbs and fats) and the non-disclosed insulin and HbA1c levels as well as the markers of inflammation will probably have left more than enough room for the "get healthy lose weight" effect.

Against that background I have my doubts that you can expect anywhere similar effects in lean, let alone athletic individuals. This does yet not negate the general usefulness of probiotics, after all, health is something you take for granted only, when you've never been sick - if you want to avoid that, the incorporation of fermented foods makes sense for everyone from the sedentary slob to the elite level athletes*...

* Note: I am writing the above although it gives me tummy aches (pun intended). Specifically with respect to the use of high dose probiotic supplements, I am asking myself, whether we really know enough about the potential downstream effects of long-term / high dose supplementation. In that, I am particularly concerned about shifting the balance from an "A"-dominant and unhealthy state in which the attributes "good" and "bad" are all of the sudden reversed and the previously dominant "bad" strain X gets totally replaced by the allegedly "good" strain Y that will then turn out to be just as nasty as X, once its natural arch enemy X is no longer present.

References:

• Bobak M, Skodova Z, Marmot M. Beer and obesity: a cross-sectional study. Eur J Clin Nutr. 2003 Oct;57(10):1250-3.
• Conterno L, Fava F, Viola R, et al. Obesity and the gut microbiota: does up-regulating colonic fermentation pro- tect against obesity and metabolic disease? Genes Nutr. 2011; 6:241–260.
• Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology. 2009; 137:1716–1724.
• Kadooka Y, Sato M, Imaizumi K, Ogawa A, Ikuyama K, Akai Y, Okano M, Kagoshima M, Tsuchida T. Regulation of abdominal adiposity by probiotics (Lactobacillus gasseri SBT2055) in adults with obese tendencies in a randomized controlled trial. Eur J Clin Nutr. 2010 Jun;64(6):636-43. 
• Kadooka Y, Sato M, Ogawa A, Miyoshi M, Uenishi H, Ogawa H, Ikuyama K, Kagoshima M, Tsuchida T. Effect of Lactobacillus gasseri SBT2055 in fermented milk on abdominal adiposity in adults in a randomised controlled trial. Br J Nutr. 2013 Apr 25:1-8. [Epub ahead of print]
   

Fat Advantage: 61% Lower Rates of Metabolic Syndrome in High Fat, 101% Higher Rates in Low Fat Dairy Lovers

"Got milk" is not the question health conscious supermen and -women should pose. "Got full fat milk, fermented dairy and cheese" is the line to remember (the original image was part of the "Got Milk Campaign")

While diet fads come and go, the advice the wise (not seldom obese or otherwise sick) experts on the boards and panels of our well-meaning governments is calling "dietary recommendations" is about as resistant to reform as the dreaded MSRA strains are to the antibiotics doctors are throwing at you whenever you sneeze. Against that background the recent trend we are seeing with respect to an increase in the recommended amount of dietary protein does almost amount to a quantum leap; a leap with a significant caveat, however. A fat caveat, so to say:

"A healthy diet includes [...] lean meats, poultry, fish, beans and fat-free or low-fat dairy products" (NIH. 2012).

Luckily, you as a SuppVersity reader do not have to rely on the NHI's thwarted interpretations of the latest research they claim to use, when they are "turning discovery into health" (no joke, this is a literal citation from the footer of the NHI website!), but can compare it to my thwarted interpretations of the latest research and cherry picked data ;-)

Cherry pick of the day: Longitudinal large scale study on dairy intake and metabolic health

 For Today, this means that you get to enjoy the latest results of a large scale observational study from the University of Sydney that's based on datasets from the Blue Mountains Eye Study (BMES) a population-based cohort study of common eye diseases and other health conditions in residents aged 49 years and over in the Blue Mountains area, west of Sydney. A longitudinal study the baseline information was obtained in 1992/1994 from  and complemented by follow-up ten years later.

The data sets included food frequency questionnaires, as well as anthropometric and biochemical assessments all of which were included in the present analysis of the association betweenn dairy consumption with the ten-year incidence of Metabolic syndrome (MetSyn) and type 2 diabetes. What's so special about this dataset, is that the food questionnaires were actually detailed enough to assess the effects of full- and low-fat dairy, separately - a very important advantage, as a cursory glance at the data in figure 1 reveals.

Figure 1: Odds ratios (95% confidence intervals) of incident metabolic syndrome according to quartiles of reduced/low fat,
regular fat and total dairy product intake (data based on Louie. 2012; adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2))

While the standard analysis for total dairy consumption (figure 1, left) yielded neither conclusive, nor statistically significant results (the p-values for the different models can be found in the upper right corner of the respective graphs). The categorization into low- and high fat dairy and the adjustments for age and sex (basic model), smoking status, physical activity (metabolic equivalents), dietary glycemic load, fibre from vegetables, total energy intake and family history of type 2 diabetes (model 1) and calcium (model 2) yields very clear and, after adjustment for calcium intake, pretty unflattering result the formulators of the afore mentioned "dietary recommendations" will probably file in their already bristling "statistical outliers"-folder:

• after adjustment for calcium intake subject in quartiles 2 / 3 / 4 of low-fat dairy are 50% / 145% / 101% more likely to be struck by metabolic syndrome, than those in the lowest quartile of low fat dairy intake (p = 0.043), while
• subjects in the highest quartile of full-fat dairy intake are - depending on the adjustments made -  48% / 59% / 61% less likely (base model / model 1 / model 2) to suffer frommetabolic syndrome, than those in the lowest quartile of high fat dairy intake (p-values:  0.018 / 0.004 / 0.004)

Yet while the scientists are well aware, that these results stand in stark contrast to the initially cited dietary recommendations, is it not this contrast that surprises them, but rather the fact that a similar significant benefit was not observed for type II diabetes, which is, after all, one of the hallmark features of the rather loosely defined triad of obesity, insulin resistance and cardiovascular disease(s), we usually refer to as 'metabaolic syndrome':

"Due to its higher saturated fat content, regular fat/high fat dairy products were previously believed to increase the risk of type 2 diabetes as a high saturated fat intake is associated with insulin resistance . However, cohort studies and a meta-analysis now suggest otherwise, with higher regular fat/high fat dairy consumption being considered mostly neutral or protective for type 2 diabetes. The results of the present study are consistent with these findings that higher regular fat dairy consumption may be protective of MetSyn and type 2 diabetes. The potential harmful effects of higher saturated fat from regular fat dairy products may have been offset by the protective components of regular fat dairy such as trans-palmitoleate, a fatty acid nearly unique to ruminant foods. Circulating level of trans-palmitoleate was shown to be significantly associated with reduced risk of type 2 diabetes (Q5 vs Q1: 62% reduced risk, p-trend < 0.001). Moreover, the protective effect of trans-palmitoleate may be exerted via the suppression of hepatic fat synthesis, where the latter was strongly associated with insulin resistance." (Louie. 2012; my emphases)

In view of these mechanism, it is all the more surprising that the study at hand and many previous studies didn't find any significant correlations between (regular fat) dairy intake and type II diabetes.

Reduction in metabolic risk, but no effect on type diabetes? Hold on...

Wolverine could be the only face of the "Got Milk" campaign who does not have to care about potential negative health effects of homogenized milk.

And upon a cursory read of the latest literature it does in fact seem as if "null findings" like this, were nothing special. Only recently by Sluijs et al. who had analyzed datasets from a nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) includind a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403; cf. Slujis. 2012):

"This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study." (Sluijs. 2012)

If we do yet take a closer look at the actual results the actually not so surprising truth is that there was a statistically significant inverse association with diabetes for cheese (p = 0.01) and fermented dairy (p = 0.02).

An association that suggests a 12% reduction in diabetes risk in those study participants who consumed the most cheese and fermented dairy (cheese, yogurt, and thick fermented milk)

And since you all know your real foods, I guess I don't have to tell you that despite the fact that there are low fat varieties of cheese yogurts and other fermented milk products, 90% of them contain way more than the 1.5% let alone 0.1% fat the allegedly healthy low fat "milk" is boasting of. Mere coincidence? I don't think so. Reason to assume that low-fat milk will make you sick? No, but certainly not an argument to avoid the full-fat variety simply because it contains fat (which is the only argument the average dietitian has to favor low- over full-fat dairy products).

Mutant Milk!? New Research Fuels the Flames on Hushed Up Concerns About Ill Health Effects of Homogenized Milk 

Ask Dr. Andro: Are Colostrum and Milk Products in General Healthy Muscle Builders, a Waste of Money or Toxic Waste?

All about milk: Browse past news and articles at the SuppVersity

^ Suggested reads

Additional recent dairy science: Similar beneficial findings for all-cause mortality and fermented dairy (yet inconclusive results for CVD and diabetes) come from the recently published Whitehall II study (4526 subjects,72 % men, mean age 56 years; Soedamah-Muthu. 2012) and for dairy intake during adolescents and diabetes (-38% risk reduction for 2 servings per day or more) from a reanalysis of somewhat questionable data (who remembers exactly how much dairy he had during his adolescence?) from the Nurses' Health Study II cohort that comprises 37,038 women who completed a food-frequency questionnaire about their diet during high school were followed from the time of return of the questionnaire in 1998-2005 (Malik. 2012).


References:

• Louie JC, Flood VM, Rangan AM, Burlutsky G, Gill TP, Gopinath B, Mitchell P. Higher regular fat dairy consumption is associated with lower incidence of metabolic syndrome but not type 2 diabetes. Nutr Metab Cardiovasc Dis. 2012 Sep 26. pii: S0939-4753(12)00193-7. 
• Malik VS, Sun Q, van Dam RM, Rimm EB, Willett WC, Rosner B, Hu FB. Adolescent dairy product consumption and risk of type 2 diabetes in middle-aged women. Am J Clin Nutr. 2011 Sep;94(3):854-61.
• NIH. Health in the News: Love Your Heart. February 2012. < http://newsinhealth.nih.gov/issue/feb2012/feature1 > retreived Oct 02, 2012.
• Soedamah-Muthu SS, Masset G, Verberne L, Geleijnse JM, Brunner EJ. Consumption of dairy products and associations with incident diabetes, CHD and mortality in the Whitehall II study. Br J Nutr. 2012 Jun 7:1-9.
• Sluijs I, Forouhi NG, Beulens JW, van der Schouw YT, Agnoli C, Arriola L, Balkau B, Barricarte A, Boeing H, Bueno-de-Mesquita HB, Clavel-Chapelon F, Crowe FL, de Lauzon-Guillain B, Drogan D, Franks PW, Gavrila D, Gonzalez C, Halkjaer J, Kaaks R, Moskal A, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Ricceri F, Rinaldi S, Rolandsson O, Sacerdote C, Sánchez MJ, Slimani N, Spijkerman AM, Teucher B, Tjonneland A, Tormo MJ, Tumino R, van der A DL, Sharp SJ, Langenberg C, Feskens EJ, Riboli E, Wareham NJ; InterAct Consortium. The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study. Am J Clin Nutr. 2012 Aug;96(2):382-90.

Digest This! Fermented Soybean Liquid Destroys Proton Pumps and Thus Impairs Nutrient Absorption

Image 1: Natto, a traditional Japanese food made
from soybeans fermented with Bacillus subtilis.
Does not even look healthy, does it?
(image from Wikipedia.de, uploaded by Gleam)

As a studious visitor of the SuppVersity, you have probably banned all conventionally processed soy-containing products from your homes, already (at least I would hope so). Yet, those of you who frequent the various nutrition blogs from the paleo- and similar "healthy-eating" spheres, will probably have come across information about the miraculous benefits that are ascribed to "traditionally fermented" soy products. And, yes indeed, a recent study published in the Journal of Agricultural Food Chemistry (Wang. 2011) was able to reproduce the results of previous studies, which had shown  that fermented soybean liquid alleviates peptic ulcers. Yet, what your soy-friendly nutrition-guru from the XYZ-Blog did not tell you, the fermented soybean liquid does this by destroying your proton pumps.

Edit: Ola just made a comment on some possible flaws in the study design (cf. bottom of the page) which made me re-read the whole study with the interesting result that what I already took for an hypothesis, only (the "destruction of the proton pump"), is re-phrased in the summary of the paper as destruction of "the acidic microenvironment created by PP [proton pumps]". If this is actually the correct version and the formulation "destruction of the proton pumps" rather the result of incompetent translation, this would put into question, whether the fermentation process really created a toxic variety of soy, or not. As studies dating back to the late 1980s show, there is yet a potential issue with "gut irritants" or rather antigenic foods such as soy and damages to the intestinal wall / epithelium. In how far this holds true for the variety of available soy products (and other antigen containing products, including milk!), would warrant individual investigation, though.

Wang and his co-workers tested the effects of fermented soybean liquid (FSL), which - other than some Internet sources would have it - "exhibit[s] higher contents of isoflavonoids (2.5-17.3-fold) and essential amino acids (1.5-4.0-fold) than the nonfermented" soybean liquid, on Helicobacter pylori over a 3 month period in 37 volunteers with gastric peptic ulcers (GPU) and found that "FSL administered at 1 g/20 mL tid [...] eradicated Helicobacter pylori (HP) by 82%".

Image 2: Electron micrograph of H. pylori possessing multiple flagella (negative staining)
(image by Yutaka Tsutsumi, Fujita Health University School of Medicine)

Interestingly, though, further experiments including kinetic analysis and the chyme-shelter testing revealed that "direct infection by bare HP [Heliobacter plyori]  cells is unlikely" in gastric peptic ulcer (GPU) patients. So, if fermented soybean liquid alleviates GPU, the mechanism must be one that is independent of its effects on HP - put simply, fermented soybean liquid "destroys" [I am citing from the study here] the proton pumps!

For those of you, who have not yet read of the nasty effect even over the counter proton pump inhibitors have on nutrient absorption: The proton pumps are those parts of your gut which release H+ ions into the stomach juice, thus acidify it and allow for the first step of digestion to take place. Many of the enzymes involved in this process are released or activated exclusively in an acidic milieu. And optimal PH-control, which is obviously impossible with blocked or even destroyed proton pumps, is a vitally important requisite for optimal nutrient absorption (esp. vitamins, minerals and protein).

So, a potential of permanently impaired digestion and a higher isoflavonoid load than in the "evil" conventional soy-products? Are you still sold on the idea that fermentation has been practiced for centuries and thus must be a valid way of transforming a "poisonous" food into a panacea?