Maximizing Training-Induced Cellular Adaptation: Training Low, Carb Cycling, Altitude & Hypoxia Training for Athletes

The mitochondria are the cell-constituents where the most relevant aspects of (endurance-)exercise-induced adaptations take place, and hence the main, but not the only target of the strategies highlighted in these assorted "cliff notes".

Usually, I am not a fan of writing about review papers (without attached meta-analysis) but in view of popular demand, I am going to give it a try and provide you with the "cliff notes" on the latest review of the theoretical background and practical implications of training with a goal the authors of the paper call "Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle (Hawley 2018).

Cliff notes, if you will on surpassing "barriers to [human] performance" - including the 2h mark for a marathon.

High-protein diets are for endurance athletes too... if they're higher in carbs than in protein ;-)

Practical Protein Oxidation 101

5x More Than the FDA Allows!

More Protein ≠ More Satiety

Protein Oxidation = Health Threat

Protein Timing DOES Matter!

More Protein = More Liver Fat?

In order to keep it both comprehensive and clear, I will draw on a modified version of the original paper's structure with what I consider the main implications as headlines. In that I will start with something people tend to forget or rather to push far back in their heads:

World class athletes are both born and raised

I know, it sounds unfair, but even the "American Dream" in its original formulation by Truslow Adams doesn't guarantee equal chances for everyone, but rather a "better and richer and fuller [life] for everyone, with opportunity for each according to ability or achievement" (Adams, republished in 2017) - never forget that: more often than not, it is after all not a lack of achievement, motivation, or the amount of work you have been investing that's to blame for your inability to become an NFL-quarterback, a world-cup winning soccer player, or a box champion - It's your damn genes PLUS the ways you cultivated them from your earliest days on.

Note: We don't have the "endurance athlete"-geneset, yet! While many companies offer services that will allegedly tell you what kind of sport you would excel in, the guys running the companies must have constructed a time machine if they can indeed provide you with reliable information, because as of 2018, we haven't discovered this geneset, yet!

Figure 1: VO2 curve of "fittest" athlete in a scientific study, an Olympic gold medalist cross-country skier (Burtscher 2011)

Keywords in this context are: Extreme VO2max values (the current record amounts to the 90.6 mL/kg/min scientists measured on an Olympic gold medalist cross-country skier Burtscher et al. observed in 2011, see Figure 1) maximal metabolic flexibility, optimal ATP management, highly efficient handling of oxidative stress, and a resilience to fatigue that goes way beyond "being able to tough it out".

Accordingly, the most important and, in fact, the only practical implication, here, is: Accept that not everyone is meant to be a world-class athlete in whatever sport it is you want to excel in.

Train low, compete high - Carbohydrate cycling

This is one of the many strategies I've written about. The corresponding articles discuss papers showing that:

• Cutting carbs after your HIIT training for 7 days before competition may significantly up your time-trial performance (in a carb-replete state) - Read article
• "Sleeping Low" (not recharging glycogen stores after PM workouts) may lead to game-changing performance gains within only 3 weeks of training | read article

The exact underlying mechanisms are too complicated to be elaborated within these cliff notes, let's just say they are part of an interaction of training-induced responses and nutrient availability that is behind many of the practical implications discussed today.

Figure 2: Skeletal muscle signaling responses after a single bout of endurance exercise are amplified in the face of low glycogen availability (Hawley 2018); AMPK and PGC-1 are the best-known motors of this process.

If you go low-carb for one, two or three weeks, or rather cut out carbs after or before training seems to matter relatively little; in fact, the (at best almost full) depletion of glycogen seems to be the main modulator of the desired adaptational response, as it signals your muscles that they have to improve their ability to burn fat (without compromising the ability to burn glucose, as high-fat diets would).

Post-workout carb fasting and glycogen depleted cardio in the morning | more.

Train low, compete high - How is it done?  Lower your carb intake temporary to train with low(ish) glycogen levels to trigger increases in the mitochondrial building protein PGC1-alpha and build a bigger metabolic engine. "Temporary" can be a continuous low-carb diet for 1-2 weeks in the offseason (don't expect to see great performance benefits before you return to training with well-stocked glycogen stores, though), or by the means of intermittent carbohydrate fasting (e.g. after working out in the PM). As with the previously suggested method, you cannot expect performance improvements while you're still "training low" - to see the full benefits of your efforts, you will have to up your carb intake again.

Train high, compete low - Altitude training (LLTH & LHTL)

It's almost an old hat and, above all, one whose beauty in terms of its efficacy has long been overestimated... and still, there is as Hawley et al. point out, effective for both, professional athletes, as well as anyone else who seeks to maximize his training response.

Figure 3: Effects of altitude/hypoxic training vs. sea-level training on RBC (10^5 cell/μl) - with average levels of 4-6 million cells the increases range from < 5% to >50% with some researchers claiming only athletes with initially low(ish) RBC counts will see significant benefits - a hypothesis others see very skeptical, though (Park 2016).

Most researchers still believe that the increase red blood cell count in altitude/hypoxic training vs. sea-level training is the most relevant factor contributing to the beneficial effects of training high, competing low (and/or sleeping high and training low).

The masks are no alternative for altitude training; they will - at best train your inspiratory muscle which is yet not a bottleneck to performance.

As early as in the 1970s, scientists from the GDR (yes, those who also beat everyone else when it came to doping) found that the effects occur after only a few weeks of training and become observable only after returning to sea levels (hence "train high, compete low"). Even for this strategy, though, it is still too early to make definitive recommendations as to the intricate details of the "ideal" protocol. It's not even clear if athletes should prefer LLTH or LHTL, i.e. live low and train high or live high and train low protocols.

What is 100% clear, however, is that masks like the one on the right are a waste of money (unless you want to train your inspiratory muscle).

Training in hypoxia - What to expect from altitude training? If you want to learn more about altitude training and take a look at the performance increases in a bunch of studies, I suggest you take a look at the free FT of Baker's and Hopkins' paper "Altitude training for sea-level competition" in Sportscience Training & Technology here!.

Train hot, compete cool - Heat acclimatization training

While the adaptation-augmenting effects of training in the heat are partly mediated by the same fundamental mitochondrial building protein as both previously discussed training strategies (PGC-alpha), the triggers belong (supposedly) to a series of aptly named "heat shock proteins". While it has become clear that they're not expressed exclusively in response to heat stress, their elevation seems to be responsible at least for the chronic adaptational effects.

Figure 4: Thermoregulation is an important part of exercise performance (Wikipedia).

Heat acclimatization does yet have both, chronic and acute effects endurance athletes can benefit from. Especially, if they know that their next competition will take place in the heat, heat acclimatization in the classic sense of getting accustomed to working out in the heat is both important and, as studies like James et al. (2018) have shown only recently.

Time to fatigue during a cycling bout at 85% Vo2max. Before the time trial, subjects exercised for 30 minutes at 45%Vo2max and performed 15 × 3 to 8-minute intervals at 75%Vo2max interjected with 15 × 3 to 8-minute active recovery periods at 45% Vo2max. Following this 180-minute sequence, subjects cycled to fatigue at 85% Vo2max. Equal boluses of each supplement were provided at 10-minute intervals over the 180-minute period before the fatigue test (as published in Kerksick & Roberts 2010).

Which supplements do really work? I know it's not popular, these days, but there's simply absolutely no doubt that carbohydrates (2:1 glucose:fructose) are the #1 performance enhancing supplement for endurance athletes... and that does not refute the previous claim that intermittent carbohydrate reductions can augment the adaptational response to exercise.

The only supplement that comes at least close to carbs in terms of the amount and quality of research is caffeine at doses of 3-6 mg/kg.

The effects of additional protein (see Figure on the left) has been investigated thoroughly recently; preliminary evidence clearly supports that adding protein to cho supplements will improve endurance performance.

That's in contrast to one of the new hype-supplements, i.e. dietary nitrates or supplemental nitrate salts, which appear to yield measurable benefits only in untrained individuals, yet not athletes. In a similar vein, the often-recommended antioxidants have almost no scientific back-up when it comes chronic performance improvements in athletes. In fact, it seems as if there were short-term benefits and long-term reductions in the adaptational response (keyword: hormesis).

Beta-alanine and, even more so, sodium bicarbonate have their value as intra- and extracellular pH buffers (Carr 2011; Christensen 2017). Another buffer, but one that buffers your PCr reserves does also have some, but not ample evidence of its benefits on endurance performance: creatine (Indranil 2016)! Only very conflicting results are yet available for ketone supplements with some studies, such as Cox et al. (2016) showing beneficial, while others, such as O’Malley et al (2017) demonstrating significant performance decrements - more studies and comparisons of different types of ketone supplements (salts vs. esters) are necessary to say who will benefit and who won't. 

Figure 5: Mean (±SD) kilometer split times during the 5-km time trial James et al. used as their subjects in a recent study investigating the effect of heat acclimatization (HA) and pre-cooling (PC) individually and in conjunction  (James 2018).

In their study, the scientists from the University of Brighton used both, a heat acclimatization (HA) and/or precooling (PC) in nine amateur trained runners who completed 5-km treadmill time trials (TTs) in the heat (32° C, 60% relative humidity) under 4 conditions; no intervention (CON), PC, short-term HA (5 days—HA) and STHA with PC (HA + PC). Mean (±SD) performance times were - you can see the results in Figure 5 - and what do you see? Yes, HA works, PC does not and won't add significantly to the benefits of heat acclimatization significantly, either.

Keep muscle and recover faster - Higher protein intakes

While it is a matter of fact that carbs are the #1 performance enhance for endurance athletes, their protein requirements have long been underestimated significantly. And that's not necessarily just because of potential muscle loss beyond what's considered optimal for marathon running and co.

Figure 6: Overview of the potential effects of protein ingestion on supporting the recovery from endurance-based exercise as means to enhance endurance capacity and performance (Moore 2014).

In fact for the skinny endurance runner, the addition of protein usually won't lead to significant increase in muscle mass, anyway. What the recently emerging pro-protein research does show, though, is that it can accelerate post-workout recovery by (a) speeding up the replacement of lost muscle glycogen, as well as (b) preventing/reducing muscle damage. As Moore et al. point out in their 2014 paper, these benefits seem to be determined (or at least confounded) by protein type, protein amount, and protein timing. In their review, the also summarize the potential mechanisms:

"Potential metchanisms include (i) oxidation of amino acids to be used for hepatic gluconeogenesis and (or) deaminiation, or as a fuel source by skeletal muscle mitochondria; (ii) increases in mitochondrial protein synthesis to enhance substrate metabolism and utilization; (iii) promotion of myofibrillar remodelling to maintain muscle protein quality and function by removing old or damaged proteins; (iv) stimulation of net myofibrillar protein synthesis to enable greater muscle force/power output; and (v) promotion of glycogen resynthesis when co-ingested with carbohydrate (CHO)."

Avid SuppVersity readers will have heard about all of these and way more (high) protein benefits in previous articles, ... they've also heard about the at least 30g of quality protein per meal rule which is valid for everyone: strength-, figure-, endurance- and non-athletes - especially when you're cutting  (Hector 2018) or competing at a level (e.g. Tour de France) where you simply cannot eat enough food, gels, bars and what-not to avoid losing weight.

Latest Study Shows that a 3.3 g/kg High-Protein Diet is Safe -- And Yes, This Means it Doesn't Hurt Your Kidney or Liver | more

You run? Eat more protein - Ok, but how much more? If that's the question you've been asking you for years, you'll be happy to hear that studies like Kato et al. are (2016) contributing to our understanding of how much protein endurance athletes actually need. Based on the metabolism of marker amino acids, the researchers calculated that intakes of minimally 1.65 g/kg body weight and an IMHO very conservative recommendation of only 1.83 g/kg body weight for endurance athletes (using the same technique, researchers found the protein requirements of bodybuilders to be even higher ~20% or 2.2 g/kg, to be a bit more precise) | Bandegan 2017) | Comment on Facebook!

References:

• Adams, James Truslow. The epic of America. Routledge, 2017.
• Baker, A., and W. G. Hopkins. "Altitude training for sea-level competition." Sportscience Training & Technology. Internet Society for Sport Science: sportsci. org/traintech/altitude/wgh. html (1998).
• Bandegan, Arash, et al. "Indicator Amino Acid–Derived Estimate of Dietary Protein Requirement for Male Bodybuilders on a Nontraining Day Is Several-Fold Greater than the Current Recommended Dietary Allowance, 2." The Journal of nutrition 147.5 (2017): 850-857.
• Carr, Amelia J., Will G. Hopkins, and Christopher J. Gore. "Effects of acute alkalosis and acidosis on performance." Sports medicine 41.10 (2011): 801-814.
• Christensen, Peter M., et al. "Caffeine and bicarbonate for speed. A meta-analysis of legal supplements potential for improving intense endurance exercise performance." Frontiers in physiology 8 (2017): 240.
• Cox, Pete J., et al. "Nutritional ketosis alters fuel preference and thereby endurance performance in athletes." Cell metabolism 24.2 (2016): 256-268.
• Hawley, John A., et al. "Maximizing Cellular Adaptation to Endurance Exercise in Skeletal Muscle." Cell metabolism 27.5 (2018): 962-976.
• Hector, Amy J., and Stuart M. Phillips. "Protein recommendations for weight loss in elite athletes: A focus on body composition and performance." International journal of sport nutrition and exercise metabolism 28.2 (2018): 170-177.
• Indranil, M., and G. L. Khanna. "Supplementary Effect of Creatine on Cardiovascular Adaptation and Endurance Performance in Athletes." Sports Nutr Ther 1.106 (2016): 2.
• James, Carl A., et al. "Short-Term Heat Acclimation and Precooling, Independently and Combined, Improve 5-km Time Trial Performance in the Heat." The Journal of Strength & Conditioning Research 32.5 (2018): 1366-1375.
• Kato, Hiroyuki, et al. "Protein requirements are elevated in endurance athletes after exercise as determined by the indicator amino acid oxidation method." PloS one 11.6 (2016): e0157406.
• Lundby, Carsten, et al. "Does ‘altitude training’increase exercise performance in elite athletes?." Br J Sports Med (2012): bjsports-2012.
• Moore, Daniel R., et al. "Beyond muscle hypertrophy: why dietary protein is important for endurance athletes." Applied Physiology, Nutrition, and Metabolism 39.9 (2014): 987-997.
• O’Malley, Trevor, et al. "Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males." Applied Physiology, Nutrition, and Metabolism 42.10 (2017): 1031-1035.
• Park, Hun-young, et al. "The effects of altitude/hypoxic training on oxygen delivery capacity of the blood and aerobic exercise capacity in elite athletes–a meta-analysis." Journal of exercise nutrition & biochemistry 20.1 (2016): 15.