Saturday, August 27, 2016

10g/d BCAA Sign. Affect Gut Tenants & Metabolites - Is This the Reason for Good or Bad Effects of BCAA Supplements?

One major problem with all the "gut microbiome"-research is that we're still having a hard time predicting the health outcomes of specific changes in the total and relative numbers of bacteria.
I have to admit that the last posts about BCAAs, here at SuppVersity.com, were mostly "bad news" for BCAA guzzlers, not because I am biased or like to rant, but simply due to the fact that the studies that have been done lately had negative or no results.

With the publication of the latest study from the Institute of Disease Control and Prevention at the Academy of Military Medical Sciences in Beijing this changed - even if the title, "Metabolic shifts and structural changes in the gut microbiota upon branched‑chain amino acid supplementation in middle‑aged mice" (Yang. 2016) doesn't say anything positive.
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Taurine Modulates the Microbiome, Too!
I guess, I don't have to tell you about the importance of gut microbiota to human health. After all, the 'gut bugs' have gained extensive attention not just in the medical community, but also in the media lately. I myself have written repeatedly about the human microbiome and its contribution to our health.

It's likewise no news for you that the composition of your gut microbiome is heavily influenced by environmental facturs - including and first and foremost your diet - including your supplements like BCAAs. In their latest study, the Chinese researchers wanted to get to the bottom of previously reported beneficial and ill effects of BCAA supplements and planned a study. A study in which male BALB/C mice were housed identically, received identical diets and exercise, but different drinking water. In that, the mice were randomly assigned to two groups: (1) unsupplemented (control, n = 9) and (2) supplemented with BCAAem (in drinking water; 1.5 mg/g body weight per day) beginning at 11 months of age (n = 9).
Figure 1: The BCAAem supplement contained (in %): leucine 31.3; lysine 16.2; isoleucine 15.6; valine 15.6; threonine 8.8; cysteine 3.8; histidine 3.8; phenylalanine 2.5; methionine 1.3; tyrosine 0.7; and tryptophan 0.5 (Yang. 2016).
If you scrutinize the data in Figure 1 you will notice that the supplement was not a simple BCAA supplement, but rather an EAA supplement with a focus on BCAAs - with respect to the potential anti-depressant effects I've written about in previous articles this could  be a practically relevant difference. One you should think of before you start guzzling the human equivalent, i.e. 0.122 g/kg of BCAAs (e.g. if you weigh 80 kg that's ~10g) per day, of the amino acid dosage that was used in the study at hand.
What do I make with the decrease in Enterobacteriaceae - Is that good or bad news? Pitout et al. (2008) have called Enterobacteriaceae an "emerging public-health concern" due to their recently discovered links to bloodstream infections that occur in response to urinary tract infections with one of the nasty multidrug-resistant Enterobacteriaceae (mostly Escherichia coli). The answer to the previously posed question, whether that's a good or bad thing should thus be easy to answer: a good one.
To get to the bottom of effects, the gut microbiomes of the mice were analysed by 16S rDNA sequencing. Quantitative polymerase chain reaction was performed to identify Bifdobacterium spp. in the gut, and gas chromatography–mass spectrometry was conducted for faecal-metabolite detection - all to find out whether a BCAA-rich EAA mix would work any "magic" on the mouse gut - magic that could explain the metabolic effects scientists observed in previous studies.
Figure 2: OUT numbers for specifc bacterial groups (Yang. 2016).
It took ages (that's what 15 months are - in rodent terms, at least) until it became significant, but eventually, the BCAA supplement facilitated a statistically significant increase in the  OUT numbers for the specifc bacterial groups the scientists tested (Figure 2).
Do BCAAs work only for older people? They, for sure, seem to work best in old mice. It is thus obvious to assume that it will be old human beings, where they're the most useful. Also, if you scrutinize the data in the paper you will see that each of the beneficial effects occured only late in the life of the rodents, i.e. from month 11-15.

Bifidobacteria DNA counts improved only in aged mice, too (Yang. 2016)
This doesn't just include the buffered decrease in total bacterial numbers, but also the changes of the gut make-up of which - if we are honest - we'd have to say that they were not exactly positive when the animals were younger. After all, the highest level of the allegedly "good" bifidobacteria was observed in the control, not the BCAA group, and changes in the "bad" (that's relatively certain for once) LPB occured exclusively in the old mice, too.
How's that? Well, it was not completely surprising that the results showed that "the structure of the gut microbiota changed, and BCAAem-supplementation in mice slowed the change speed of gut microbiota which is due to age" (Yang. 2016): a result that is in line with the age-specificity of many of the benefits of BCAAs scientists have observed in both human and rodent studies, where similar high BCAA amino acid products have been shown to help conserve lean mass and/or even extend the life of smaller animals - in a similar way as caloric restriction does. This doesn't mean that the other changes Yang et al. recorded were irrelevant, though: "
"In addition, the abundance of the Akkermansia and Bifdobacterium increased in BCAAem-supplemented mice, while the ratio of Enterobacteriaceae decreased in BCAAem-supplemented mice" (Yang. 2016).
These changes in the bacterial make-up of the lab animals, namely increases in the numbers of bacteria which are generally considered "healthy" and decreases in the numbers "unhealthy" enterobacteriaceae, could just as well (or even more likely) be responsible for the differences in a literal dozen of metabolites, representing sugar and lipid metabolism, the scientists observed when they compared the metabolome in the guts of the supplement to the control group.
Figure 3: Serum LBP concentrations in the two groups at 11 and 15 months (Yang. 2016).
Furthermore, the visibly significant difference in LPB (see Figure 3), the acute phase cousin of the pro-inflammatory LPS, i.e. lipopolysaccharides, that migrate from the gut where they are produced by "bad" bacteria through the gut wall to start their inflammatory and potentially auto-immunity triggering assaults in your body alone could make BCAA supplements interest for the elderly - and only for them! After all, the difference resurfaced only in the last months of the normal life expectancy of the lab animals in the study at hand.
Table 1: Average percentages (not total counts!) of gut microbiota at the genus level in two groups at 11 and 15 month (Yang. 2016).
And what does all that mean? Well, I have addressed part of the question in the blue box explaining the benefits of lowering the number of Enterobacteriaceae. Since the scientists also observed a significant reduction of the animal lipopolysaccharide-binding protein (LPB | see Figure 3) in the serum of the supplemented rats, it is furthermore safe to say that the administration of a BCAA-rich (not pure BCAA) EAA supplement had downstream systemic anti-inflammatory effects. After all, LPS belong to the group of highly pro-inflammatory gut metabolites that are (a) produced by certain bacteria, often the same ones that will also facilitate the entry of LPS into systemic circulation, by (b) increasing the permeability of the gut lining ("leaky gut").

Now, while the previously discussed changes do in fact, as Yang et al. point out indicate "lower antigen loads in the host gut" of the supplemented animals. The lists they provide (e.g. Table 2) are still of questionable explanatory power. After all, we still know way too little to say whether the relative reduction in allegedly "good" lactobacilli in the BCAA group is bad news and whether that's relevant bad news. The same goes for the other changes. You can thus be sure that this is/was not the last SuppVersity article about BCAAs and their effects on the gut microbiome | Comment!
References:

  • Pitout, Johann DD, and Kevin B. Laupland. "Extended-spectrum β-lactamase-producing Enterobacteriaceae: an emerging public-health concern." The Lancet infectious diseases 8.3 (2008): 159-166.
  • Yang, Zhan, et al. "Metabolic shifts and structural changes in the gut microbiota upon branched-chain amino acid supplementation in middle-aged mice." Amino Acids (2016): 1-15.