Thursday, March 14, 2013

Optimal Carnosine Loading: Taking Beta Alanine With Food Renders the Cheap Bulk Stuff more Potent Than Fancy Time-Released Preparations. Preview: Science Round-Up: Daylight Saving, Stevia Toxicity, Protein Excess & More

Since it's Thursday my voice is back and I am already looking forward to today's SuppVersity Science Round-Up in which Carl Lenore an I are going to "attack" the following topics (tune in live at 1PM EST),
    That pills can rarely compete with whole foods is something you've heard on SHR and read on the SuppVersity often, but that pills - in this case beta alanine pills - are better, when the content is mixed into the food instead of being prepared in form of time-released or whatever else caps may be news to some of you.
  • Summer time and the jet-lag is there... the effects and idiocy of daylight saving.
  • Stevia an anti-fertility sweetener, carcinogen and yet another welcome root of all evil?
  • Dairy & weight loss revisited, when even the abstract contradicts the conclusion.
  • Does too much protein make you fat? Yes it does - at least that's what the latest epidemiological data says.
  • Fish oil makes women hungry, exercise satisfies their cravings and improves gut hormone signalling.
  • High dietary restraint makes women lose their nocturnal progesterone surge
I decided to pick a fast, put practically relevant topic as the SuppVersity news of the day: Beta Alanine Supplementation; or, to be even more precise: "Optimal" beta alanine supplementation.

The less tingles the better!?

What type of food did the subjects eat? In the acute test the data in figure 1 (left + right) is based on, the subjects consumed a standardized breakfast consisting of 4 slices of white bread with chocolate-hazelnut paste, 200ml semi-skimmed milk, 1 banana and 125gr fruit yogurt, and a second meal with 150gr baguette topped w/ 40gr young cheese, 30gr mayonaise and vegetables with a 33cl orange juice (data not shown in figure 1). In the chronic ingestion study (figure 1, middle) participants in the w/ meal groups had 1x800mg cap with their three regular main meals and the fourth with a snack.
As a diligent student of the SuppVersity you will know that a major problem with beta alanine  in scientific studies is that even the "time-released" tabs, the scientists usually use can produce this tingling sensation in all sorts of the body (I can tell you about that, from my more is more days back in the day; you really won't believe in which places you can "tingle" ;-) After my initial excitement and putting some thought into the hitherto still not 100% understood origin of the tingles, I did yet realize that they are not just unnecessary for the BA to work but could in fact be a negative (also physiologically negative) side effect of too much of the potentially toxic substance floating around in your blood stream (cf. Beta Alanine Suffocates Cardiomyocytes; other previous posts on BA).

Don't worry, it is totally unlikely that you will ever achieve serum concentrations that could do any harm, but one thing you should remember is that what you are striving for is not a high amount of beta alanine (BA) in your body. Your goal is to ramp up the intramuscular carnosine stores and that works only if the BA does recombine with the essential amino acid histidine and is subsequently stored within the skeletal muscle.

Food as an "advanced delivery formula"

The recombination / incorporation process is likely to be rate limited, so that it is only logical that any "overshoot" of beta alanine (again nothing your body likes to  have floating around in the system) is going to be cleared before it can do its carnosine loading job. A job that is therefore facilitated by "packaging" the BA molecules with fillers & co in tabs, or - much cheaper and obviously way more natural - by simply ingesting it with food.
Figure 1: Selected time-frame of 8h blood profile of plasma insulin and beta-alanine (BA) after ingestion of 800mg of BA after meal in between meals or with meal (left and right). Effect of chronic ingestion of 4x800mg/day BA for five weeks with or w/out food in regular and sustained released form  ( Stegen. 2013)
As the data in figure 1 that's based on the results of a soon-to-be-published study by Stegen et al. goes to show you, the "food advantage" is (as usual ;-) the 34 male and female subjects (age 19.4y; weight 66kg, daily BA intake at baseline ~230mg/day) derived from ingesting the BA with meals may not be earth shattering.

Still, the subjects who took the BA with a meal did not just have higher muscular carnosine levels than those who took the pure powder, at least in the slow-twitch fibers of the soleus, which are actually not that beta alanine affine as their counterparts in the gastrocnemius, the cheap and ingeniously simple "take it with food" solution to BA supplementation also outperformed the obviously pricier pre-prepared slow-release formula.

Where does the beta alanine go to, if not into the carnosine stores? 

The scientists did yet also make another interesting observation, while only 1.6% of the beta alanine was excreted in the urine (slow release formula) the muscular uptake and the incorporation efficiency of exogenous BA into carnosine is actually so low that "the vast majority (~160g or 95-96%) of the ingested BA is neither going into muscle carnosine nor into the urine" (Stegen. 2013).

While respective scientific studies would still have to be conducted, the most likely hypothesis to explain the "disappearance" of beta alanine are:
  • Oxidation and use for energy production: While the contribution of alpha-amino acids to energy delivery in muscle and other tissues is usually quite low, as compared to carbohydrates and fat, their usage increases (up to 10% of total energy usage) with increasing amounts of the AA in the bloodstream. Evidence suggests that this is also the case for beta-amino acids, where and "excess" would obviously be achieved with dosages as they were used in most of the previous research on beta alanine supplementation (Harris. 2006, Hill. 2007; Baguet. 2009).

    This hypothesis is also supported by the recent revelation that GABA transaminase activity, the enzyme that's required to initiate the oxidation of beta alanine increases upon  BA supplementation (Everaert.2012)
  • Alternative pathways including uptake and incorporation into carnosine in other tissues: While it is not impossible that other organs (e.g. the kidney, liver or brain) avail themselves of small quantities of BA to up their own carnosine levels it is, as the scientists point out " unlikely that the conversion of BA into carnosine in other (non-muscle) tissues is of any quantitative significance, because presence of carnosine and carnosine synthase in non-muscle tissues is several orders of magnitude lower than in muscle" (Stegen. 2013)
Now that we have gotten that straight, the one question that remains is actually pretty simple, unlike the answer unfortuntately....

How does the meal improve the the bioavailability of BA

Personally I still feel that the main effect is the prolonged elevation of beta alanine, the scientists themselves however propose another (at least confounding) factor, which would also explain why simply taking the slow release formula won't work even if it is released just as slow as regular BA with food:

While BA still is often named in the same breath with creatine, the effect size and the likelihood that athletes will see any benefits at all is much smaller than in the case of the supplemental top dog (learn more in  "Beta-Alanine Does not Make it From Bench to Pool Side: Are the Effects Too Short-Lived? Is Swimming the Wrong Sport? Or Was the Dosage of 3.2g/day Simply Too Low?")
"Clausen et al.showed that Na+/K+ pumps in skeletal muscle are stimulated by insulin over a range of concentrations down to low physiological levels (Clausen. 2003). Therefore, it is possible that meal-induced elevations in serum insulin are capable of triggering the sodium-dependent transporter TauT. In our study, a meal-induced effect could only be confirmed in soleus muscle. Considering the fact that this is a more insulin-sensitive muscle, it is not unlikely that the soleus responds better on insulin induced BA uptake. In addition Lavoie et al. demonstrated that insulin-induced translocation of Na+/K+ ATPase subunits to the plasma membrane (Lavoie. 1996), one of the two possibilities to increase Na+/K+ ATPase activity, is restricted to oxidative fiber-type skeletal muscles which are predominantly present in soleus."
Sounds more than logical and can also explain the differential effect on the oxidative = slow twitch fibers of the soleus (cf. figure 1, middle). With the insulin enhanced "pump activity" you have a mechanistic increase in BA uptake, no wonder that this improves the bioavailability, right?



Bottom line: From now on you buy your beta alanine in bulk and spoon-feed yourself with your 4x800mg of BA (the dosage used in the study at hand) after your preferably carb-containing meals and snacks. Don't worry BA is one of the few amino acid supplements that don't have a disgusting taste to them. You can actually add it directly to the food, but I would refrain from doing that before you prepare your meal. As simple as the BA molecule may be, we still don't know what kind of chemical reaction it may be exposed to if you actually cook it or do whatever other "nasty" things to it ;-)

References:
  • Baguet A, Reyngoudt H, Pottier A, Everaert I, Callens S, Achten E, and Derave W. Carnosine loading and washout in human skeletal muscles. J.Appl.Physiol. 2009; 106:837-42.
  • Clausen T. Na+-K+ pump regulation and skeletal muscle contractility. Physiol Rev. 2003; 83:1269-324.
  • Everaert I, De Naeyer H, Taes Y, Derave W. Gene expression of carnosine-related enzymes and transporters in skeletal muscle. Eur J Appl Physiol. 2012 Nov 4.
  • Harris RC, Tallon MJ, Dunnett M, Boobis L, Coakley J, Kim HJ, Fallowfield JL, Hill CA, Sale C, and Wise JA. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino.Acids. 2006; 30:279-89.
  • Hill CA, Harris RC, Kim HJ, Harris BD, Sale C, Boobis LH, Kim CK, and Wise JA. Influence of beta-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity. Amino.Acids. 2007; 32:225-33. 
  • Lavoie L, Roy D, Ramlal T, Dombrowski L, Martin-Vasallo P, Marette A, Carpentier JL, and Klip A. Insulin-induced translocation of Na+-K+-ATPase subunits to the plasma membrane is muscle fiber type specific. Am.J.Physiol. 1996; 270:C1421-C1429.
  • Stegen S, Blancquaert L, Everaert I, Bex T, Taes Y, Calders P, Achten E, Derave W. Meal and Beta-Alanine Coingestion Enhances Muscle Carnosine Loading. Med Sci Sports Exerc. 2013 Mar 5.