Bicarbonate + Beta-Alanine Supplementation, HIT Exercise Performance and Energy Substrates in 71 Trained Cyclists

If there's one take-home message from the study at hand, it is: While both SB& BA work, it depends on the sport/exercise test if the effects will be significant.

If you've been following my articles at the SuppVersity for some time, you will know that I have covered beta-alanine and sodium bicarbonate, two of the few ergogenic supplements for which we have enough evidence to assume that they actually work, extensively in the past.

You will yet also remember that the synergistic effects you'd expect to see when you combine intra- (beta alanine) and extra-cellular (sodium bicarbonate) H+ buffers didn't show in every pertinent study in the SuppVersity archive.

Danaher, et al. (2014), for example, found no effect of combining both during performance test with fixed intensity and volume, while Tobias et al. (2013), whose study tested upper body performance and didn't limit either intensity or volume, did - it almost doubled the total work the subjects performed. Why's that important? Well, if you look at the study design of the latest bicarb + beta-alanine (BB) study by scientists from the University of Sao Paulo (da Silva 2018) you will find that both the training intensity and the total volume were capped. Therefore, it is not totally surprising that the performance benefits didn't reach statistical significance (there were benefits, though).

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

This doesn't mean, however, that the study wasn't worth looking at. After all, the scientists had their reasons to standardize the workload - without this standardization da Silva et al. wouldn't have been able to achieve their aim to conduct the first study that would investigate the energy metabolism during high-intensity exercise and cycling time-trial performance objectively - and that's only possible if you use work-matched tests that guarantee that one group won't exercise 10 minutes longer or at 10% higher work rates than the other. But let's (re-)address that later and take a closer look at the other key parameters of what I feel is a well-designed, interesting and eventually highly educative study - despite and/or because of the lack of significant performance differences:

• 

  If you develop digestive issues like "the runs" whenever you try to use sodium bicarbonate aka baking soda (NaHCO3), try to "serial load" it | learn here how that works.

  The subjects in da Silva 2018 were 72 trained cyclists (5 ± 4 years of experience in cycling, 9 ± 3 h of training/week, consisting of 235 ± 92 km/week) with a VO2max of 59-60 ml/kg/min that shows that they were real athletes (What's a high VO2max?). 
• Beta-alanine was preloaded for a month at a comparatively high dose (28 days at 6.4g/d; two capsules were ingested four times daily vs. maltodextrin (error in abstract) placebo).
• The 0.3g/kg body weight of sodium bicarbonate (or calcium carbonate placebo) was supplemented within max. 5 minutes 60 minutes before the performance test in 1-g gelatin capsules under supervision to ensure full compliance. Gastrointestinal discomfort was reported prior to and 60 min using a 10-point scale - serial loading protocol as I've described it in previous articles about the bicarb was not used.
• The food intake during the supplementation period was 'monitored' via 3-day food diaries the subjects had to fill on 2 non-consecutive weekdays and 1 weekend day. The analyses of these food logs showed that the subjects consumed ~2200kcal/d with approximately 52%, 18.5%, and 26.5% of the energy coming from carbs, protein, and fats, respectively - without inter-group differences.

The actual testing sessions that were conducted after pre-test and familiarization sessions consisted of a high-intensity intermittent cycling protocol (4x 60s at 110% of the subjects' individual maximal power-output with 60s rests between bouts) that was followed by a 30-kJ time-trial performance test. Both tests performed twice - once before and once after the 28 days of beta-alanine or placebo supplementation (compare the illustration of the study design and main trials in Figure 1).

Figure 1: Experimental design (upper panel) and overview of the main trials (lower panel). BA β-alanine, SB sodium bicarbonate, PL placebo, CaCO3 placebo for sodium bicarbonate, lac plasma lactate analysis, gas blood gas analysis, HICT-110% high-intensity cycling test performed at 110% of Wmax (da Silva 2018)

As it is necessary for any double-blind, parallel-group, placebo-controlled trial, the participants were randomly allocated to the BA (β-alanine + placebo; n = 20, 3 drop-outs), SB (placebo + sodium bicarbonate; n = 20, 3 drop-outs), BASB (β-alanine + sodium bicarbonate; n = 20, 1 drop-out), or PLA (placebo + placebo; n = 20, 2 drop-outs) groups and asked to identify their group allocation (i.e., BA or maltodextrin and SB or calcium carbonate) to verify the blinding process.

How can you effectively blind beta-alanine and sodium bicarbonate, when one gives you the tingles and the other one the runs? That's a valid question and you could argue that the fact that three volunteers reported paresthesia with BA (BASB group) and nine participants (SB: 5; BASB: 4) reported gastrointestinal discomfort after ingesting sodium bicarbonate confirms that blinding is not possible for the two agents. Even though seven volunteers in the BA, five individuals in SB, six in BASB, and five in the PLA group rightly identified the arm (BA/PLA) they had been randomized to, the Fischer’s exact test showed a p-value of p = 0.85 for BA and p = 0.82 for SB, respectively - hence suggesting efficient blinding in spite tingling and tummy aches ;-)

Maltodextrin (the abstract falsely claims it was dextrose, which would be a very bad placebo due to its characteristic taste) and calcium carbonate were the placebos for BA and SB. Moreover, the randomisation was performed in blocks of 4 with groups being matched for time to complete a 30-kJ test to avoid significant baseline performance differences between the groups. And finally, blood was sampled before and in-between exercise bouts and the time trial, respectively, and the VO2 consumption measured continuously before and during the HICT110% test.

Figure 2: Effects of β-alanine (BA) and sodium bicarbonate (SB) on the time to complete 30-kJ time-trial performance. The grey bar on c represents the 95% confidence interval of the coefficient of variation of the test. Positive and negative confidence intervals crossing zero on d were deemed nonsignificant (da Silva 2018).

Now, as previously announced, da Silva et al. did not find a significant effect of any of the three supplementation protocols on the subjects exercise performance. Both, Figure 2 (c) & (d) do yet suggest non-significant performance improvements - with the largest effect size being and a borderline significant effect being observed in the BA + SB group.

Measurable effects, but no significant performance increases - so what?

As previously hinted at, these results are not completely surprising, because the ergogenic effects of H+ buffers, in general, and bicarbonate in particular, critically depends on the build-up of sufficient amounts of H+ to be buffered. Within the very short (~60s) bouts of exercise that was aborted when the subjects hit the 30-kJ mark this requirement probably wasn't met - or, in view of the non-significant benefits, it was at least not met to a sufficient degree.

Figure 3: The amelioration of the decline in blood pH and bicarbonate shows that the SB treatment did what it was supposed to do - work as a buffer. However, as Figure 2 shows, the differences in pH and blood HCO3 were obviously too small to make a significant difference during the very short 30kJ performance test (da Silva 2018).

As Figure 3 shows, this doesn't mean that the buffers didn't work (SB successfully buffered the decrease in blood pH and we can assume that a muscle biopsy would have shown slightly reduced intra-cellular H+ levels due to BA). It just means that the biochemical differences to the control trial were too small and the inter-group variance too large to detect significant performance benefits.

My plot of the effect sizes for the impact of beta-alanine (BA), sodium bicarbonate (SB), the combination of both (BASB), and placebo on the glycolytic energy contribution illustrates quite nicely that it's bicarbonate, not beta-alanine that will keep you going towards the end of a team sport event or in the sprint before the finish line.

Why does SB increase the important glycolytic energy contribution during short bursts of high-intensity exercise, while BA fails? This is a relevant question because it's said increased ability to tap into your glycogen stores that will provide the 'second wind' you need to win the decisive sprints in team sports and track and field. If we assume that the SB-advantage is not a result of bicarbonate messing with the indirect measurement of the glycolytic energy contribution (remember no biopsies were performed), da Silva et al. suggest that absence of this benefit in BA may be due "to the total amount of H+ that can be neutralised by the working muscles" by sodium bicarbonate v. beta-alanine, respectively.

The scientists argue as follows: "Assuming the typical 6 mmol/l increase in blood bicarbonate following SB ingestion and 5 l of total blood volume, then SB ingestion would allow the neutralisation of ~ 30 mmoles of H+ above baseline (based on the 1:1 stoichiometry of HCO3− and H+ reaction). This is approximately two times more than the ~ 15 mmoles of H+ that a typical 80% increase in muscle carnosine (from 20 to 35 mmol/kg dry muscle after BA supplementation) can neutralise in both legs (assuming that legs correspond to 30% of BM, that 40% of leg mass is skeletal muscle, and that 70% of wet muscle is water—therefore, 3 kg of dry muscle times ~ 5 mmoles of H+ per kg of dry muscle that can be neutralised by a 15 mmol kg−1 dry muscle increase in muscle carnosine). Therefore, the effects of SB on the glycolytic activation could be more easily detectable than those of BA due [to] a possibly greater ability of SB to neutralise H+" (da Silva 2018).

With that being said, we could have been able to be more specific if it were not for two important limitations of the study the scientists willingly admit in the discussion of the results: The first limitation is the lack of direct muscle analyses that could have (a) told us if and to which degree the muscle carnosine actually changed in response to the BA supplementation and (b) confirmed that the indirect measurement of the effects on energy metabolism was indeed accurate. The second limitation, which is not related to the study design, is a temporary malfunctioning of laboratory equipment which made it impossible for da Silva et al. "to undertake the estimation of the energy systems in all participants" (da Silva 2018) - maybe, the analysis of a complete dataset would have shown measurable and significant increases in glycolytic energy contribution for BA, as well.

The same must be assumed of the lactate buffering effects of SB. In the scientists' multiple comparison analysis of the post-HICT-110% plasma lactate levels in the SB group, the latter approached significance (t = − 1.82, p = 0.074), and were significantly higher after the 30-kJ TT in both, the SB only (t = − 2.67, p = 0.01) and the BASB group (t = − 2.61, p = 0.011).

Figure 4: Effects of β-alanine (BA) and sodium bicarbonate (SB) supplementation on the absolute contribution of the energy systems during the HCT-110% test (da Silva 2018). The increase glycolytic flux and improved ability to tap into the readily available glucose sources can be ascribed to the pH buffering effect of SB (Sutton 1981).

Unfortunately, lactate still has an unwarrantedly bad rep (Cairns 2006). It is thus important to note that increased lactate levels are a necessary consequence of an increased use of glucose and by no means a reason to expect performance decrements. In fact, almost all SB studies which tested the level of lactate in the subjects' blood found it to be significantly increased in the presence of significant performance benefits! That's something people tend to forget in a day and age where even the superiority of glucose as the #1 substrate for high-intensity exercise is questioned (sorry keto fans, but that's simply what the contemporary evidence says - keto-adapted or not ;-).

"So, beta-alanine and sodium bicarbonate don't work, neither taken alone or in combination?" No, that's not what the study says. While significant effects on the performance markers measured in the study at hand were not observed, da Silva et al. found non-significant increases in exercise performance in both tests, especially, when the two H+ buffers were combined, and a potentially highly relevant 20% increase in the subjects ability to tap into their glycogen stores in the SB and BASB groups - in the "right" sport, this difference may well make the difference between winning an Olympic medal and ending up with a disappointing fourth rank (check out the infobox for more info why only sodium bicarbonate, but not beta-alanine, had this beneficial effect).

Bodybuilders have a sign. elevated muscle carnosine levels, it is yet not clear if that's an adaptational response to prolonged repetitive exposure to low muscle pH, the consumption of high carnosine foods like chicken, supplement use, or the use of anabolic steroids (Tallon 2005). Other studies show that men store more carnosine than women (Mannion 1992), omnivores more than vegetarians (Harris 2007), and that genetic factors which have hitherto only been confirmed in our omnivore 'cousins', the pigs (D'Astous-Pagé 2017), may figure as well. It is thus hardly surprising that the BA research as such yielded highly variable results which are, just as it's the case for the study at hand, difficult to interpret if the changes in muscle carnosine aren't measured.

Moreover, in view of the previously mentioned non-significant performance increases my provocative statement from the question at the beginning of this conclusion, i.e. that BA and SB "don't work" should rather read "exert mea-surable, yet highly variable performance benefits", which simply may not have reached statistical significance, because (1) the effiacy of both agents has a high inter-individual varia-bility, with BA potentially failing in subjects with diet- or training-related naturally high carnosine levels (cf. Figure 5) and SB countering its own ergogenic effects via gastrointestinal distress (which was reported by nine participants in the study at hand), or because (2) H+ buffers excel in exercise capacity tests, i.e. tests in which you exert yourselves to the point of volitional exhaustion, as opposed to performance tests with a fixed point like the 30 kJ test in the study at hand, or because (3) the results of the study at hand despite being one of the better-powered investigations, may still "lack of statistical significance [...] due to insufficient statistical power to detect small effects" (my emphasis in da Silva 2018) - it's also possible that all three contributed synergistically to the lack of statistical significance of the results.

Instead of trying to make a general statement about the two ergogenics, which have also made the ISSN's TOP5 list of OTC ergogenic supplements, only recently (Kerksick 2018), we should use the publication of the study at hand to remind ourselves that the benefits of any supplement are sports-, exercise- and as the pronounced benefits in Tobias et al. (2013) suggest (see data in and caption of Figure 6) potentially even muscle-specific (e.g. upper vs. lower body).

Figure 6: With an upper-body Wingate test, the study by Tobias et al. (2013) I covered 5 years ago used didn't just use an exercise capacity test that didn't limit the total work done, but also tested the effects on a different muscle group - et voila: Tobias et al. found significant increases in total work and mean power with the combination of BA +SB.

So, what should you do? Well, one thing should be obvious: you should not throw away your 5kg bag of sodium bicarbonate and your 1kg tub of beta-alanine. Even though the performance benefits in the study at hand were at best borderline significant, there's a reason that both agents have been around for years (beta-alanine) and decades (bicarbonate) in the absence of sufficient research to tell for sure who will and who won't benefit from using them | Comment!

References:

• Cairns, Simeon P. "Lactic acid and exercise performance." Sports Medicine 36.4 (2006): 279-291.
• Carr, Benjamin M., et al. "Sodium bicarbonate supplementation improves hypertrophy-type resistance exercise performance." European journal of applied physiology 113.3 (2013): 743-752.
• da Silva, Rafael Pires, et al. "Effects of β-alanine and sodium bicarbonate supplementation on the estimated energy system contribution during high-intensity intermittent exercise." Amino Acids (2018): 1-14.
• Danaher, Jessica et al. "The effect of β-alanine and NaHCO3co-ingestion on buffering capacity and exercise performance with high-intensity exercise in healthy males." Eur J Appl Physiol (2014) 114:1715–1724.
• Harris, Roger C., et al. "The carnosine content of V Lateralis in vegetarians and omnivores." (2007): A944-A944.
• Kerksick, Chad M., et al. "ISSN exercise & sports nutrition review update: research & recommendations." Journal of the International Society of Sports Nutrition 15.1 (2018): 38.
• Mannion, A. F., et al. "Carnosine and anserine concentrations in the quadriceps femoris muscle of healthy humans." European journal of applied physiology and occupational physiology 64.1 (1992): 47-50.
• D'Astous-Pagé, Joël, et al. "Identification of single nucleotide polymorphisms in carnosine-related genes and effects of genotypes on pork meat quality attributes." Meat science 134 (2017): 54-60.
• Sutton, J. R., N. L. Jones, and C. J. Toews. "Effect of pH on muscle glycolysis during exercise." Clinical science 61.3 (1981): 331-338.
• Tallon, Mark J., et al. "The carnosine content of vastus lateralis is elevated in resistance-trained bodybuilders." Journal of Strength and Conditioning Research 19.4 (2005): 725.
• Tobias, Gabriel, et al. "Additive effects of beta-alanine and sodium bicarbonate on upper-body intermittent performance." Amino acids 45.2 (2013): 309-317.

Cutting Carbs After PM HIIT Workouts Will Make You Cross the Finish Line Before Anyone Else: 3% Faster Time Trial, 9% More Power and Twice as Much Fat Mass Lost in 7 Days

Don't be a fool. Simply eating no carbs in the PM is not going to yield the same results. It's all about timing it correctly with your workouts... workouts? Yes, bad  news: you got to get off the couch, bro; workout daily: one light, one HIIT day.

I've written about the adaptational response to "training low", i.e. doing endurance training on a low carbohydrate diet previously. In January, this year, for example, I have reported the results of a study from the French National Institute of Sport that showed that strategically cutting carbs in the PM and thus "sleeping low" will trigger game-changing Performance gains in only 3 weeks (read the article).

Now, the scientists go one better: In their latest study, Laurie-Anne Marquet and colleagues investigated the effect on an even shorter timescale - a timescale that is short enough to consider "sleeping low" as a possible  pre-competition strategy... well, assuming that it would work its performance-enhancing magic within as little as the 7 days, during which the subjects' in Marquet's study followed the "no carbs after your workout" (="sleep low" | SL) prescription the researchers copied from their own previously discussed study.

Are you looking for more information about fasted cardio? Find inspiration in these articles:

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Health Benefits of Fasted Cardio

Overall, 21 endurance-trained male cyclists (mind the typo about the # in the abstract of the original study, in case you read it; the summary says 11, not 21, which is the correct number) volunteered to participate in the study. All were healthy, aged between 18 and 40 years, and training at least 12 h/week, having at least 3 years of prior training. Their mean (±SD) age was 31.2 ± 7.1 years, their mean body mass was 71.1 ± 5.6 kg, their mean maximal oxygen consumption (VO2max) was 64.2 ± 6.0 mL/min/kg, and their mean maximal aerobic power (MAP, W) was 342 ± 38.3 W.

To isolate the effects of the dietary / carbohydrate modulating intervention, the subjects who trained
according to their habitual training program, initially (1st week) ate according to their usual dietary habits, documenting their food intake via a daily food diary. These diaries were then compared to the prescribed carbohydrate pattern in the 2nd week, which set their CHO intake at 6 g/kg per day.

Figure 1: Graphical overview of the study design; CHO: carbohydrates; HIT: high‐intensity training session; LIT: light intensity training session; SL: Sleep‐Low; CON: Control; MAP: Maximal aerobic power (Marquet. 2016).

After the dietary standardization and the pre-test at the end of this period, the subjects were randomly assigned to two different groups undertaking the same one-week training program.

The study used pre-bed protein shakes, a strategy to build muscle.

Nightly protein shakes, glycogen depletion and lean muscle mass: In contrast to what some people may expect, the no-carbs before bed strategy did not lead to measurable decreases in lean mass. Whether and to which extent that was a result of the protein shake both groups consumed before bed cannot be answered without doing another study. What I can tell you based on previous research, however, is that this, i.e. having a protein shake "before" (not necessarily right before) bed, is a very promising strategy to maximize net protein retention (see "12-Week Study: 25g Bed-Time Protein Almost Doubles Size & Increases Strength Gains" | more).

The built-in and significant difference between the group can be found in the nutritional guidelines according to which all subjects consumed the same amount of 6g/kg CHO, in total, but periodized their carbohydrate intake differently over the day. Specifically,...

• the control group trained with a high CHO availability (control group, CON group, n = 9) with an even spread of CHO intake over the day and between training sessions,
• the "sleep low" (SL) group (n = 12 | mind the typo in the scientist' abstract) trained with a CHO intake that was periodized within the various days in a way that no CHO was consumed between the high-intensity interval training sessions (HIIT) held

Practically speaking: The subjects in the "sleep low" group were thus doing truly fasted or, rather, glycogen depleted low-intensity cardio in the morning of each of three of the six otherwise identical workout days.

Figure 2: 20km cylcling times and mean power output in pre- and post-test (Marquet. 2016).

Against that background, it is all-the-more surprising that the subjects saw both: significant reductions in their time-trial times (-3.32%) and improvements in their average power production during the workouts (+9.17%). What is not surprising is that the data in Figure 1 indicates that these power improvements occurred specifically in the latter part of the workout, i.e. when the glycogen stores are running out and the training effect from training low in the AM shows.

Table 1: Rating perception of effort (RPE) during the 20 km cycling time-trial every 5 km (Marquet. 2016).

In contrast to what you would expect, the scientists did not detect a significant difference between group and pre and post tests for the substrate oxidation, markers of lipid oxidation and stress markers - or, more specifically there was ...

• no decrease in CHO oxidation in the SL group and 
• no increase in FAT oxidation in the SL group
• no increased cellular damage in form of lipid oxidation, and
• no significant difference in the subjects' stress response (plasma catecholamines),

... in the high-performing "sleep low" aka "SL" group. Now, there's a (small) catch, though, that should be mentioned in spite of the lack of statistical significance: the scientists observed a small increase in the subjects' rate of perceived exertion during the light AM sessions (+13%), as well as the post-intervention time trial (+10%) in the "sleep low" group. Moreover, the last-mentioned increase is more or less identical to the increase in average power production during the post-test on day 7. Accordingly, it is questionable if one should call this already non-significant effect a "catch", at all.

Brad Schoenfeld's 2014 "Fasted Cardio"-study falsifies the myth of superior long-term (4 week) fat loss in non-glycogen-depleted non-athletes on a moderate energy deficit (more). It does not exclude, however, that the glycogen-depleted subjects of the study at hand could see increased fat loss in the short or long term.

"And the subjects got ripped, right?" Not exactly. While the statement from the headline is 100% accurate, the total fat loss was (and this is not surprising in view of the study duration) marginal: statistically significant −395 ± 491 g in the SL and statistically non-significant −151 ± 363 g in the control group.

The reason that it is still worth mentioning is that previous studies suggested that doing AM cardio on empty would not increase fat loss (even over longer periods of time). So, how can we consolidate these conflicting results? Well, while further research appears necessary, I could imagine that both, the advanced training status of the subjects' in the study at hand and the fact that they were actually glycogen-depleted and not, as the subjects' in Schoenfeld's seminal paper (Schoenfeld. 2014), "only fasted", so that, if anything, their liver glycogen may have been lowered | Comment!

References:

• Marquet, Laurie-Anne, et al. "Periodization of Carbohydrate Intake: Short-Term Effect on Performance." Nutrients 8.12 (2016): 755.
• Schoenfeld, Brad, et al. "Body composition changes associated with fasted versus non-fasted aerobic exercise." Journal of the International Society of Sports Nutrition 11.54 (2014). Previously discussed, here!

Blood Flow Restriction in Athletes: Did We Get it All Wrong? Must BFR-Cuffs be Worn After, not During Each Set?

If that's you. It's well possible that you've done it all wrong. Wearing the cuffs after the set may be the way to go!

You may have followed up on my recent suggested read in the SuppVersity Facebook News and read up on the recent scientific debate on the (non-)usefulness of training with cuffs (BFR-style). Well, after reading the full text of a recent study by Conor W. Taylor et al. (2015), I have to say: Maybe we have only done it wrong.

In their study, the researchers from the Loughborough University in Leicestershire had their subjects, 28 healthy trained males who were cycling 120 ± 66 km per week, all cuffed up after each set of a standardized sprint training. That's very dufferent from trying to sprint with cuffs on your legs (and usually reduced intensity) and appears to be - that's at least what the study results suggest - a potential game-changer.

You can learn more about BFR and Hypoxia Training at the SuppVersity

BFR, Cortisol & GH Responses

BFR - Where are we now?

Hypoxia + HIIT = Win?

BFR for Injured Athletes

Strength ⇧ | Size ⇩ w/ BFR

Training & Living in Hypoxia

Now, the good news is: The study involved both an acute and chronic exercise + BFR study of the effects of post-spring-training blood flow restriction.

• In Study 1, a between groups design determined whether 4 weeks (2 d/wk) of SIT (repeated 30 s maximal sprint cycling) combined with post-exercise blood flow restriction (BFR) enhanced maximal oxygen uptake (VO2max) and 15km cycling time trial performance (15km-TT) compared to SIT alone (CON) in trained individuals.
• In Study 2, using a repeated measures design, participants performed an acute bout of either BFR or CON. Muscle biopsies were taken before and after exercise to examine the activation of signalling pathways regulating angiogenesis and mitochondrial biogenesis.

As a science expert you'll know that study 2 probably wouldn't have been done if the results of Study 1 had not been encouraging.

Figure 1: Pre- to post-changes in VO2max (absolute, top-right), relative (top-left), MAP (bottom-left), 15k time trial (bottom-right) | I marked the individuals who saw positive and negative effects for you, the # on the buttons indicate the number of subjects who benefited (green) or saw no / detrimental effects (orange | original data from Taylor. 2015).

"Encouraging", in this case, means that the scientists observed a highly significant VO2max with post-workout BFR by 4.5% (P = 0.01) but was unchanged after CON.

So, does the increase in VO2 have anything to do with my gainz? Directly? No. But if there's an effect on hypertrophy it would - just as the effect on VO2 found in the study at hand - depend on increases in the stress response. Now, the more recent studies have shown that the necessary reduction in weight lifted when you do it with cuffs makes it practically useless for athletes. So, in conjunction with the study at hand, it's only logical to ASSUME that using the hypoxic stress after a set COULD provide an ADDITIVE stimulus (normal BFR training takes away from the regular stimulus, because it will.force athletes to refuce the weights and cannot fully compensate for that | see the results of this study.

The small advantage in the 15k time trial, on the other hand, did not reach statistical significance. That's "bad news", but the trend indicates that this might change with long(er) term studies.

Figure 2: Changes (%) in physiological and performance variables before and after CON and BFR training interventions (Taylor. 2015).

Whether that may change with a longer-term study will still have to be elucidated. What appears to be certain, though, is that the existing difference is not mediated by changes in PGC-1α, VEGF and VEGFR-2 mRNA expression between protocols. In fact, of all parameters the scientists tested to identify the underlying mechanism only the  mRNA levels of HIF-1α, the hypoxia-inducible factor 1-alpha, of which a recent paper by Lindholm and Rundquist (2015) highlights that it would be otherwise attenuated with long-term endurance exercise and thus lead to a blunted response to long-term exercise training (that's why rookies see fast results and pros only marginal results), differed significantly between groups (P = 0.04) 3 h after the cuffs were applied to the subject's legs.

Bottom line: While it is possible that the differences the scientists observed were triggered by BFR induced extra-stress (namely hypoxia, thus increases in Hypoxia-inducible factor 1-alpha), we will need additional (longer-term) studies to prove practically relevant improvements in time-trial performance and identify a definitive mechanism.

The benefits of blood flow restriction in healthy athletes may be less pronounced than the advocates would have it. If reversing the order of exercise and applying the cuff can solve that, this would be awesome!

With that being said, the results - although not fully convincing, yet - are quite exciting. After all, they really suggest that instead of training with cuffs, athletes who want to benefit from the additional low oxygen stress would have to copy the protocol of the study at hand and thus apply lower limb blood flow restriction within 15s of each sprint... or after each set of leg curls or squats? Well, that's a question we cannot answer based on the study at hand, but it would certainly be interesting to test what would happen if you applied the cuffs right after a set of biceps curls. Well, as you can see, there's still a lot of research to be done and as you know, the SuppVersity is going to be where you can learn about the results first ;-) | Comment on Facebook!

References:

• Lindholm & Rundqist, et al. "Skeletal muscle HIF-1 and exercise." Experimental Physiology (2015): Accepted Article.
• Taylor, et al. "Acute and chronic effect of sprint interval training combined with post-exercise blood flow restriction in trained individuals." Experimental Physiology (2015): Accepted Article.