Beta-Alanine, Widely Used, but Rarely Tested for Safety!? Individual Studies Find Serum / Muscle Taurine is Reduced by >20%, However the Totality of Evidence Suggests...

Reductions in muscle and especially serum taurine have indeed also been observed in humans, but the fact that they do not occur in lower dose studies and cannot be observed consistently in studies using higher dosages (6g) suggests that they shouldn't be a problem for the average BA user.

Regular SuppVersity readers will be familiar with the way(s) in which taurine (#TAU) and beta-alanine seem to both complement and antagonize each other. Beta-alanine, in particular, has been found to deplete muscular (and other tissue) taurine stores - a problem, generations of scientists have used to study the ill health effects of taurine-deficiency.

While studies have never reported clinical taurine depletion in response to beta-alanine supplements, we have to consider the possibility that ...

If it works (no runs + high intensity+volume exercise) bicarbonate is the king of H+buffers:

Caffeine + Bicarb Make Champions

Bicarb + Asp = Muscle Magic!?

NaCHO3 & Leg Days're a Breeze

+100% Anaerobic Endurance

Bicarb Buffers Creatine

Instant 14% HIIT Boost

... the corresponding studies (a) were not long enough in duration, didn't use (b) the same crazy amounts of beta-alanine (#BA) of which I am sure that some bros out there are taking it and (c) - most importantly - won't manifest before literally the last taurine molecules have been bumped by BA.

Note: A possible lack of histidine to recombine w/ BA is probably not a problem given the high protein intakes of the average beta-alanine supplementing athlete/gymrat.

Now, a recent study from the University of Sao Paulo (Dolan 2019) cannot fully address all of issues a-c, but the systematic risk assessment and meta-analysis can provide us with an overview of what human and animal studies that investigated an isolated, oral, β-alanine supplementation strategy can tell us so far about the following 5 safety primary outcomes

• side effects reported during longitudinal trials, 
• side effects reported during acute trials, 
• effect of supplementation on circulating health-related biomarkers, 
• effect of supplementation on skeletal muscle taurine and histidine concentration, and 
• safety-related outcomes from animal trials. 

For the analysis, the quality of evidence for outcomes was ascertained using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework, and all quantitative data were meta-analyzed using multilevel models grounded in Bayesian principles.
The first at least somewhat surprising result in Dolan et al.'s recently published paper  (2019) is the mere number of studies they came up with:

101 human and 50 animal studies were included in the study. Tingling was the only persistently reported "side effect".

Much less to anyone's surprise who has ever felt "the tingles", paraesthesia was the most commonly reported side effect of oral BA supplementation. With an 8.9-fold increase in odds of "tingling" and a crazy variability [95% credible interval (CrI): 2.2, 32.6] this odd feeling was - and that's good news - also the only reported side effect.

Taurine deficiency: If you're asking yourself why you should care about taurine deficiency, the following list of possible consequence may come handy: impaired vision, central nervous system and cardiac function; reduced bile flow, hence impaired fat digestion, and high blood lipids, impaired metabolism and elimination of toxins; reduced antioxidant defenses; impaired passage of sodium, potassium and possibly calcium and magnesium ions into and out of cells, immune imbalances; reduced muscular performance, etc.

This observation is in line with the lack of differences in terms of the participants' dropout rates when the scientists compared the active (#BA) to the placebo (#PLA) treatment; the tingles are, after all, not that bad and have been avoided in many trials by supplementation timing BA with foods and/or splitting larger into multiple smaller dosages to avoid that they would be messing with blinding the study participants to the treatment (BA or PLA).

As far as common "safety markers" are concerned, β-Alanine supplementation caused a small increase in circulating alanine aminotransferase concentration (#ALT | effect size, ES: 0.274, CrI: 0.04, 0.527), although mean data remained well within clinical reference ranges. 

The small increase in ALT is not a problem - exercise alone will increase it much more as you've learned here. 

Now, while this sounds problematic, ALT is eventually just an enzyme that metabolizes alanine, and - as I explained in "Three Reasons Why Your Doctor May Falsely Believe Your Kidney, Liver or Heart Were Damaged" (Moussa 2015), in detail - not a valuable tool for diagnosing liver damage, in particular in athletes.

Hence, the more important, unquestionably health-relevant and, at least on my part, long-awaited result of the meta-analysis of human data is this:

The scientists found no evidence of a main effect of β-alanine supplementation on skeletal muscle taurine (ES: 0.156; 95% CrI: −0.38, 0.72) or histidine (ES: −0.15; 95% CrI: −0.64, 0.33) concentration. 

You can see a forest plot displaying the effect of β-alanine supplementation on skeletal muscle taurine concentration in humans in Figure 1. As usual, the study-specific intervals represent individual effect size estimates and sampling error, while the diamond represents the pooled estimate generated with Bayesian inference along with the 95% credible interval (95% CrI). This analysis included 83 observations (63 β-alanine/18 placebo) - in short: There's no measurable effect according to the meta-analysis at hand.

Figure 1: Even if you didn't read the rest of this article an effect size of 0.156 with confidence levels ranging from -0.38 to +0.72 should qualm your worries over the taurine depleting effects of appropriately dosed (max. 3-6g/d) beta-alanine supplements - even if individual studies such as Blancquaert et al. report >25% reductions in plasma taurine.

What about the outliers, i.e. Blancquaert et al. (2017) and Harris et al. (2010)? Well, even though both studies found potentially relevant effect sizes, the confidence intervals tell you that the effects were at least so heterogeneous that it would be stupid to argue that they provide limited but relevant evidence that there could be an issue, after all - and that's despite the fact that the statistically at best borderline significant relative reduction in plasma and muscle taurine (p = 0.063 and p = 0.156, respectively) Blanquaert et al. observed was quite large, i.e. -25% in plasma and -13% in skeletal muscle after 23 days on a rather high dose of beta-alanine of 6g/day (see data in Figure 2).

Figure 2: If the Blancquaert human study, the data of which I've used to calculate the relative change in plasma (blue) and muscle (orange) levels of beta-alanine, histidine, and taurine in response to 6g/d of beta-alanine, was the only study we had, it may provide reason for concern... not just for taurine, but even more so for histidine of which the subjects in the BA group consumed a relatively normal amount of 2.1g/d.

So there is reason to worry - at least for people who can't live without worries? Well, as previously hinted at, rodent studies clearly demonstrate that overdoing it on beta-alanine can deplete your taurine levels. However, to achieve a significant reduction of taurine the minimal "daily dose was ≥3% β-alanine in drinking water" (Dolan 2019). The human equivalent of this dosage may mirror the practice of some bros who still believe in the "more helps more"-principle, but the totality of the evidence seems to suggest that within the recommended dosing scheme of 3-6g/d issues w/ local or systemic taurine deficiency shouldn't be an issue... in the short run: long-term studies (years vs. days and months) are imho still warranted.

Looking for what in theory should be the optimal H+-buffer stack? Look no further! Simply (re)view my 2018 article on #BA + #bicarbonate | more

So, what's the verdict then? Within commonly applied (performance enhancing) dosing schemes of 1.5-6-5g/d beta-alanine (#BA) is likely to cause the tingles (if administered as a bolus). Moreover, BA could trigger small and physiologically irrelevant increases in the alanine-metabolizing (liver-) enzyme ALT (learn more about those and how the enzyme is by no means liver-specific, here). The depletion of your cellular taurine stores, on the other hand, doesn't seem to be an issue if you don't dose your supplements based on bro-logic, i.e. "if some's good more is going to get me even more jacked!".

In other words, potentially serious side effects due to the depletion of taurine (and/or histidine, which is even more unlikely given the overall high protein intakes of the average BA consumer) must be feared only by those morons among you whose daily beta-alanine intake is more than 10 times the regular human dose of ~3-6g/d | Comment on Facebook!

References:

• Blancquaert, Laura, et al. "Effects of histidine and β-alanine supplementation on human muscle carnosine storage." Med Sci Sports Exerc 49.3 (2017): 602-609.
• Dolan, Eimear, et al. "A Systematic Risk Assessment and Meta-Analysis on the Use of Oral β-Alanine Supplementation." Advances in Nutrition (2019).
• Harris, Roger C., et al. "Simultaneous Changes In Muscle Carnosine and Taurine During and Following Supplementation with b-alanine." Medicine & Science in Sports & Exercise 42.5 (2010): 107.
• Saunders, Bryan, et al. "24-Week β-alanine ingestion does not affect muscle taurine or clinical blood parameters in healthy males." European journal of nutrition (2018): 1-9.