Beta-alanine: The Harris Study (this is what grad students are actually used for)

I was going to write a review of the Harris study on beta-alanine, but after reading it in detail, I realized it wasn’t a randomized controlled trial at all, but rather a physiological study, with biochemical outcomes, but no “functional” ones. And despite the fact that one of their experiments was a “quasi” randomized controlled trial, I haven’t got a lot to say about it because this was not a study to look at the effectiveness of BA, but rather to profile its effects. On the up side, there was a rather nice recipe for chicken broth–which is where they got their beta-alanine for one of the experimental groups:

“Fresh chicken breast (skinned and boned) was finely chopped and boiled for 15 min with water (1 litre for every 1.5kg of chicken). Residual chicken meat was removed for course filtration. The filtrate was flavoured by the addition of carrot, onion, celery, salt, pepper, basil, parsley and tomato pure, and re-boiled for a further 15 min and then cooled before final filtration through fine muslin at 4 C. The yield from 1.5kg chicken + 1 litre of water was 870ml of stock. A portion of the stock was assayed for total beta-alanyl-dipeptides (carnosine and anserine) and beta-alanine. Typical analyses were: total beta-alanyl-dipeptides, 74.4 mmol per litre; free beta-alanaine, 5.7 mml per litre. From this a dose estimated to yield 40 mg per kg body weight of beta-alanine was calculated and was provided hot to each subject.”

All this and more, in: Harris RC, Tallon MJ, Dunnet M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, Wise JA. The absorption of orally supplied beta-alanine and its effects on muscle carnosine synthesis in human vastis lateralis. Amino Acids, 30: 279-289, 2006.

In brief, they did three experiments.

Experiment 1:

The original purpose of the first experiment was to look at the pharmacokinetics of taking 40mg beta-alanine per kg of body weight in the form of a beta-alanine drink (called Carnosyn) vs. the same dose in chicken broth vs. a drink with no beta-alanine. However, the first few subjects experienced really bad side-effects with the drink (not the broth)–symptoms of flushing, skin irritation and a prickly sensation, which began within 20 minutes of ingestion and lasted for up to an hour. Flushing was reported to occur on the ears, forehead, scalp, upper trunk, arms and back of hands, lower back and buttocks. These symptoms were unpleasant enough that 2 of the 6 subjects refused to take the 40mg/kg dose. So, the investigators decided to study beta-alanine at 20 and 10mg/kg instead. Subjects still had effects on 20mg/kg, but the symptoms were less intense. Only 2 of the 4 subjects who took the 10mg/kg dose had flushing symptoms. None of the subjects had flushing symptoms with the chicken broth, even though the dose of beta-alanine was 40mg/kg in the broth.

In the end, the researchers found that consuming beta-alanine increased the concentration of beta-alanine in the blood. The difference between the drink and the broth seemed to be that beta-alanine levels in the blood were about half for the broth compared to the drink, and took longer to peak with the broth than with the drink, but the total amount of beta-alanine detected was about the same.

There also appeared to be a non-linear relationship between the increase in peak concentration of beta-alanine in the blood, when compared with the dose given in the drink. The peak concentration of beta-alanine (BA) in the blood was 6-8 times higher when subjects drank 20mg/kg of BA than when they drink 10mg/kg of BA. But the peak concentration of BA in the blood was only 2.2 times higher when the subjects drank 40mg/kg of BA compared to when they drink 20mg/kg of BA. So there seems to be a trend of dimishing returns (i.e. every time you double the dose, the peak concentration of BA in the blood doesn’t double, but progressively higher by smaller amounts).

Experiment 2:

The second study was done to see what would happen if the subjects took 10mg/kg of BA every three hours (for instance, did the body develop some sort of “tolerance” to the BA and clear it faster with repeated dosing?)

The peak concentration of BA did not change with each dose. And 3 hours was sufficient time for the subjects to return to baseline concentrations of BA before their next dose. Repeated dosing also did not produce significant side effects, other than occasional mild flushing.

Experiment 3:

The third study was done to see if 4 weeks of taking BA had any adverse effects on blood chemistry.

This study had 16 male subjects in it (the other two had only 6). The subjects were divided into 2 groups. Half the subjects took 800mg of BA, four times a day. Nothing bad happened to them. The other half got a placebo. Nothing bad happened to them either.

Experiment 3.5:

This study was lumped in with the description of experiment 3, but was a separate experiment. The purpose of this study was to look at the effects of BA on muscle. Twenty-one males were recruited. They were physically active and regularly ate meat. These subjects were divided into four groups:

Group 1 (n=5): 800mg of BA, four times a day.
Group 2 (n=5): More frequent dosing. Week one was every hour at doses of 800, 400, 400, 400, 800, 400, 400, and 400mg at 9, 10, 11, 12am and then at 3, 4, 5, 6pm. Week 2, saw an increase to 800mg for the 11 and 5 o’clock doses. Week 3, the 10 and 4 o’clock doses went up to 800mg, and in week 4, all the doses were 800mg.
Group 3 (n=5): L-carnosine in the same dosing regimen as Group 2, but 2000mg and 1000mg carnosine instead of 800mg and 400mg BA
Group 4 (n=6): Maltodextrin in the same dosing as Group 2.

A single muscle biopsy was taken from the vastus lateralis at the beginning and after 4 weeks of supplementation. Extracts were tested for BA, histidine, carnosine and taurine.

Flushing occured in week 2 for four of the five subjects in Group 2; and for 3 of the 5 subjects in Group 3 in week 4; and 1 subject in group 4 (yes, even placebos have side effects!)

BA was below the limit of detection in most muscle extracts both before and after supplementation. The mean carnosine content did increase in all groups, but only statistically significantly in Groups 1-3. No difference was detected between Groups 1-3 with respect to carnosine content.

No change was observed in body mass in any of the four groups.

Conclusions:

The authors concluded in this series of experiments that the maximum practical dose of BA should not exceed 10mg/kg per dose to avoid the unpleasant side effects. They also noted that none of the subjects had side effects when they took the BA through chicken broth and that the peak blood concentrations mimicked those of subjects who took 20mg/kg of the BA drink, despite there being 40mg/kg of BA in the broth. At 20mg/kg, many subjects still had undesired side-effects, so the recommendation from this study is to keep dosing at the 10mg/kg level, which is about 800mg for a guy.

They also concluded that there was a significant enough increase in muscular carnosine with BA supplementation to go to the next step–which would be to see if the increase in muscular carnosine would have effects on intracellular acid-base regulation, “…as a limiting factor to performance with different exercise modalities.”

The Bottom Line:

The thing to take home from this study, is that if you’re going to take BA, then make sure your dose doesn’t exceed 10mg/kg to avoid flushing side-effects. BA is one of the precursors to carnosine, which is actually the molecule of interest in reducing fatigue. You might ask why we’re not supplementing with carnosine instead of BA, and I’m afraid I don’t have a good answer to that question–it may have to do with the pharmacokinetics of carnosine–definitely over the head of this humble methodologist. I know that Biotest makes a time-release version of BA, but how they are ensuring adequate dosing, I’m not entirely sure–because time-release formulations in general can be quite unpredictable. But again, not my field of expertise, so I can’t reallly comment on it either way. Either way, it’s not entirely clear why one would want a steady of level of BA in the blood throughout the day, if activity is restricted to only part of the day. I assuming that carnosine is possibly broken down if it’s in “excess” so you’re interested in keeping the “excess” constant–but why throughout the day, I’m not sure.

There’s nothing in this study to support the use of BA in terms of improving the outcomes we’re interested in (less fatigue, more intense workouts, bigger muscles, or less body fat). It’s all fine to say that there’s more carnosine in the muscle, but does that increase in carnosine translate to anything observable that might indicate that it’s a worthwhile supplement to take? This is where the utility of the physiological study ends, and where clinical research picks up; and the authors of this study acknowledge that and state that there are sufficient physiological results to warrant looking at performance outcomes.

So, I’m going to end this series on beta-alanine here for now. My conclusion from the clinical trials is that there is insufficient evidence, and of the available evidence, there is insufficient quality of evidence to support the use of beta-alanine to produce performance benefits. This doesn’t mean that beta-alanine doesn’t work, but that we are lacking proof of benefit.

It’s funny. We all violently denounce the spam on new “vitamins” or gels, or the use of raw, unpasturized milk as an anabolic agent (I swear, I found this thread on the JPFitness forum), but for some reason a hook gets created by someone somewhere that causes all-out blind acceptance hype for a pill that we should consider just as skeptically as the newest penile enlargement supplement.

I will go back to one my previous points in that my own philosophy is that every decision we make about fitness is a health decision, whether that’s how we train, how we eat, what supplements we take, how we take care of injuries or how we recover from injuries. And that just because physicians don’t take part in the vast majority of this aspect of health, it doesn’t mean that we should hold these decisions to any less of a standard than the ones that physicians are involved in. If you’re going to make the decision to take beta-alanine, then at least make an informed decision about the step that you’re about to take. You should be aware that uncomfortable flushing of your ass is a possible side effect if you don’t take the correct dose. You should also be aware that there is about as much evidence to support the use of beta-alanine in weight lifting as there is evidence to support the use of gel-caps filled with baby powder. Now, this evidence could change in the future–as more studies are done (if any), we will hopefully get a clearer and clearer picture of what role (if any) beta-alanine has in weight training (and other activities); but today, it’s no different than baby powder.