Lift Lighter to Get Bigger

There are generally a few main objectives that individuals have when they start working out.  Some want to get strong, some improve their endurance and conditioning, some want to focus on improving their athletic performance and others want to lose weight or tone up.  Then there are those who are focused on gaining muscle.  Downing protein shakes and searching for that perfect combination of exercises and intensity techniques to squeeze every bit of muscle growth out that they can.  Traditionally we have believed that higher loads (heavier weights) stimulate more muscle fiber and the related biochemical factors that do the best job of coaxing out precious muscle growth.  Certainly if you follow the bodybuilding literature and half of what is written on the internet the notion of harder and heavier is pushed over and over, but what if it is wrong?  What if the path to developing more muscle growth is actually…lighter weights?

Over the past few years a body of research literature has been growing showing that training at lighter loads may be an equal if not more effective way to stimulate hypertrophy (muscle growth).

Ogasawara et al. (2013) compared the effect of high-load bench presses at 75% of 1 repetition maximum (1RM) to low-load presses performed with 30% 1RM.  When performing the high-load exercises the subjects did 3 sets of 10 reps, 3 times a week for 6 weeks.  The low-load protocol was 4 sets to failure also performed 3 times per week for 6 weeks.  MRI images of the triceps and pectoralis major (chest) showed similar increases for both groups.  Additionally both groups showed increases in strength though the high-load group did see a larger increase.  One of the interesting aspects of this study was that it used a within-subject design.  The subjects trained for 6 weeks using 75% of 1RM, took twelve months off from training then performed the 30% 1RM program.  This addresses some of the biological issues involved with using different subjects though the authors theorized that some of smaller strength level improvements seen in the low-load portion of the study could be the result of residual strength improvements from the high-load training done the previous year.

Measureable growth in muscle mass is challenging to quantify and takes a long time. In the research setting various measures of muscle protein synthesis are used to determine if muscle growth is being stimulated and to what extent.  Increased muscle protein synthesis (MPS) does not magically mean that someone will be walking around looking like Arnold Schwarzenegger circa 1980 but a consistent program that is followed for an extended period of time coupled with proper supportive nutrition and recovery should result in someone increasing their muscle mass within their natural genetic capacity.

Burd et al. (2010) examined the effect of different loads and volumes by utilizing three different training conditions.  The first group utilized a resistance that was 90% of 1RM and performed 4 sets to failure.  The second group used 30% of 1RM and preformed 4 sets to a volume that was work matched with the 90% group so they stopped before failure.  The third group also used 30% of 1RM but performed their 4 four sets to failure.  Myofibrillar muscle protein synthesis, sarcoplasmic protein synthesis and a mixture of the two were measured at 4 hours and 24 hours after exercise.

In the mixed protein synthesis at 4 hours all 3 groups were elevated but the 90% and 30% failure groups were significantly more so then the work matched group.  At 24 hours all three conditions continued to be elevated with the 30% failure group clearly showing the highest values.  With myofibrillar protein synthesis we again see increases in all 3 conditions while the two failure groups show significantly higher rates of synthesis.  At 24 hours only the 30% to failure group still shows significant increases.  Similar changes were seen in sarcoplasmic protein synthesis where there failure groups showed increases at 4 hours though the work matched group did not.  Again at 24 hours only the 30% failure group showed elevated levels.

This study shows low-load high volume training (30% failure) to be more effective at increasing muscle protein synthesis then high-load low volume training.  How high-load high volume training would measure as compared to low-load high volume and high-load low volume training would be an interesting follow up study.

Regarding myofibrillar protein synthesis, when the impact of the 90% failure group and 30% work match group are considered, it appears that contraction intensity has a greater impact on synthesis rates at 4 hours while volume of exercise which is more related to the degree of muscle fiber activation affects the duration of muscle protein synthesis.  The real question that is then raised is what the impact of 24 hour as opposed to 4 hour myofibrillar protein synthesis values are when it comes to actual hypertrophy. Regarding sarcoplasmic and mixed protein synthesis, the similar results also support the notion of the benefit of low-load high volume to failure training.  We’ll save the discussion of what the meaning of different types of muscle protein synthesis mean for another day.

It is generally believed that early strength gains which occur in new lifters are the result of neural adaptations that occur in the first few weeks of training and are not related to muscle hypertrophy.  Jenkins et al. (2016) set out to examine the impact of resistance training on untrained men.  Both strength and muscle growth were measured at 2 and 4 weeks.  The subjects trained 3 times per week using either 80% of their 1RM or 30% of 1RM, performing 3 sets to failure.  Despite the previously untrained status of the subjects, similar increases in muscle thickness were seen in both groups.  Ultrasound imaging was used for this measure.  While total training volume was the same for both groups the 30% subjects experienced significantly more time under tension (181%) then the 80% group.  The authors theorized that the increased time under tension was possibly the factor responsible for the stimulus of muscle growth in the 30% group.  The 80% group also demonstrated significant increases in strength that were not seen in the 30% group, further supporting the both the use of heaver resistance for strength gains and the separation of strength and hypertrophy training objectives.

Kumar et al. (2009) had one of the most interesting findings.  They had subjects perform at 20%, 40%, 60%, 75% and 90% of 1RM.  Volume was adjusted so that it was work matched.  The 20% group did 3 sets of 27 reps.  The 40% group did 3 sets of 14 reps.  The 60% group did 3 sets of 9 reps.  The 75% group did 3 sets of 8 reps and the 90% group did 6 sets of 3 reps.   When myofibrillar protein synthesis was measured there was minimal change between 20% and 40% but a significant rise at 60%.  What stands out is that there was no appreciable change between 60%, 75% and 90% suggesting that to maximize protein synthesis it might not be necessary to use heavier and heavier levels of resistance.  Again differentiating maximal strength development from hypertrophy, the evidence suggests higher loads aren’t always the optimal path towards muscle growth.  The replication of this study with subjects training to failure at the higher loads would further delineate if there is a difference between 60%, 75% and 90% or if individuals can achieve optimal results with more moderate loads.  This study clearly shows 60% 1RM is preferable to the lower percentages seen in other studies but you have to take note that the loads are work matched where the studies that show more significant hypertrophy or muscle protein synthesis at lower loads use training protocols that have subjects going to failure.  That one aspect seems to be the key element.

It appears time and again that the studies using training to failure show different results than those that work match.  The issue of time under tension being a major factor for this has been theorized by multiple researchers.  Burd et at. (2012) looked at this specific question, measuring the effect of time under tension with low load training on muscle protein synthesis.  They compared a slow movement with a 6 second lifting and 6 second lowering phase on one leg to a rapid movement using a 1 second up and 1 second down pace on the other.  Both trials used 30% of 1 RM.  The slow leg performed the exercise to failure and the fast side performed an equivalent number of repetitions, not going to failure.  This created a large difference in time under tension for the slow leg as compared to the fast.

Myofibrillar protein synthesis was higher in slow training at the 24-30 hour recovery window.  In the first 6 hours of recovery only the slower group saw elevated mitochondrial and sarcoplasmic protein synthesis (114% and 77%).  These findings along with previous research by the authors lead to the speculation that “maximal fibre activation, and not percentage of maximal muscle strength, is fundamental to induce maximal rates of muscle protein synthesis and we would hypothesize other purportedly important variables that are thought to dictate hypertrophy are largely redundant in their ability to elicit an anabolic response to exercise so long as high levels of muscle fibre recruitment are attained”.

While this is just a sampling of the research on this topic it does begin to present a strong argument for altering some of our closely held beliefs about building muscle.  This doesn’t mean we should stop heavy training.  The research did not say heavy lifting does not produce quality muscle growth.  It does.  And the research clearly shows that heavier loads do a better job of building more strength which is certainly an important objective.  Even if hypertrophy is the primary goal, if more strength is developed in the heavy cycles, when lighter loads are used, they will be heavier when you consider what percentage of 1 repetition max is being used and in theory that should stimulate even more muscle fiber recruitment.

So how should you proceed and put this knowledge to use?  If your main objective is muscle growth, or even if you are just doing a hypertrophy cycle in your training you may want to consider occasionally mixing in a 4-8 week block of lighter loads to failure, then proceeding to a heavier hypertrophy block or a heavier strength block.

If you are the average person who doesn’t want to lift really heavy, an older adult or working with one of those groups and trying to help them add some muscle mass but keep injury risk low then this approach may be beneficial.  Working with more moderate loads can give you some much desired muscle growth in a safer and far more comfortable approach.

If you are a strength or performance athlete you already know you cannot train at your maximum loads year round.  Your joints and muscles need a break from that constant intense stress but you don’t want to just stop training and improving.  Taking a few weeks to train at lighter loads will allow you to stay in the gym and making valuable progress.  If you can increase your muscle mass you increase your potential to develop more strength and power when you return to heavier lifting.  And if your joints are feeling a bit refreshed from facing lower loads and getting to fully recover then all the better for your upcoming training.

Now that you are armed with the knowledge don’t be afraid to get out there and put less weight on the bar.  Just remember to take your sets to failure and slow the repetition pace down.

Burd, N., Andrews, R., West, D., Little, J., Cochran, A., Hector, A., Cashaback, J., Gibala, M., Potvin, J., Baker, S., and Phillips, S. (2012) Muscle Time Under Tension During Resistance Exercise Stimulates Differential Muscle Protein Sub-Fractional Synthetic Responses in Men, J Physiology, Jan 15; 590 (Pt 2): 351-362.

Burd, N., West, D., Staples, A., Atherton, P., Baker, J., Moore, D., Holwerda, A., Parise, G., Rennie, M., Baker, S., and Phillips, S. (2010) Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men, PLoS One, Aug 9;5(8):e12033.

Jenkins, N., Housh, T., Buckner, S., Bergstrom, H., Cochrane, K., Hill, E., Smith, C., Schmidt, R., Johnson, G. and Cramer, J. (2016) Neuromuscular Adaptations After 2 and 4 Weeks of 80% Versus 30% 1 Repetition Maximum Resistance Training to Failure. Journal of Strength & Conditioning Research, Aug: 30(8):2174-85.

Kumar, V., Selby, A., Rankin, D., Patel, R., Atherton, P., Hildebrandt, W., Williams, J., Smith, K., Seynnes, O., Hiscock, N. and Rennie, MJ. (2009) Age-Related Differences in the Dose-Response relationship of Muscle Protein Synthesis to Resistance Exercise in You and Old Men.  The Journal of Physiology Jan 1; 587(Pt 1): 211-217.

Ogasawara, R., Loenneke, J., Thiebaud, R. and Abe, T. (2013) Low-Load Bench Press Training to Fatigue Results in Muscle Hypertrophy Similar to High-Load Bench Press Training. International Journal of Clinical Medicine 4: 114-121.

Burn Fat and Improve Endurance by 70%. Now in Pill Form.

What if I told you there was a way to increase your endurance by 70%?  People would be lining up and asking if we have it in pill form, and we almost do.  Most people are familiar with the idea of “hitting the wall”.  That moment when you are doing some sort of endurFance based activity and you just reach a point where you can’t go on.  Maybe your thinking gets cloudy.  Your muscles don’t seem to work anymore.  Your coordination has suddenly evaporated.  That image of the Ironman triathlete, just yards away from the finish line stumbling around.  So close to the end but unable to even coordinate those last few steps to get across the finish line.

Generally this is the effect of not having enough glucose in the blood stream to supply the brain with sufficient amounts to meet its energy demands.  No matter how badly you want to go, when blood glucose drops too low the brain just says no.  Like an automobile engine running out of gas.  So the longer you can maintain a higher blood glucose level, the longer you can go before hitting that proverbial wall.

Normally regular endurance exercise has three primary affects that spare blood glucose.  1) The transformation of muscle fibers to types with more oxidative capacity, which equals more energy production out of every gram of glucose used as fuel.  2) An increase in the number and activity of mitochondria, the powerhouses of cells where aerobic metabolism occurs. 3) The improved utilization of fatty acid as a fuel source, sparing the use of blood glucose and our stored carbohydrates in the form of liver and muscle glycogen.  Who doesn’t want to use more fat as fuel source.

Of course these changes take a great deal of hard work over a prolonged period of time.  As any new runner or average person struggling to lose body fat will tell you, change is difficult, comes slowly and is often hard to notice at all.

Well thanks to a nifty little molecule called peroxisome proliferator-activated receptor delta (PPARδ) we may be able to hack into our normal metabolic processes and accelerate our fat burning capabilities.  For the performance athlete this means sparing precious blood glucose and carbohydrate stores which will push the proverbial wall out further, enabling significantly longer, and greater achievements.  For the rest of the population the implications are just as significant.  Individuals dealing with obesity and other metabolic diseases may have a tool that helps them manage their conditions and make major improvements in their health.

PPARδ is what is known as a nuclear receptor and under normal circumstances it helps kick off the process of the transformation of muscle fibers to more oxidative types along with increasing the use of fatty acids as a fuel source in skeletal muscle.  It increases this switch to using fat as fuel through its interaction with two mitochondrial proteins, Cpt1b and Pdk4.  Carnitine palmitoyl-transferase 1b (Cpt1b) is an enzyme that limits the rate at which fatty acids are transported into mitochondria.  If you enable more fatty acid to enter, you are able to use more of it as fuel.  Pyruvate dehydrogenase kinase isozyme 4 (Pdk4) is involved in regulating the use of pyruvate.  Pyruvate is a byproduct of the metabolism of carbohydrates and it is then used in another metabolic pathway known as the citric acid cycle (also known as the TCA cycle or Krebs cycle) to produce even more energy.  You don’t need to be a molecular biologist to realize that impacting these two gatekeeper molecules can have a major effect on metabolism.  And now we know that PPARδ seems to be the key to impacting these two key proteins.

In experiments in which mice are manipulated to have more PPARδ, the mice are able to run twice as long as control subjects (Wang et at., 2004).  When the mice are manipulated to not have PPARδ they have problems with the generation of mitochondria and the determination of muscle fiber type (Schuler et al., 2006).  If a drug is introduced that activates PPARδ a cascade of positive metabolic and performance benefits are seen.

PPARδ stimulation increases fatty acid metabolism and improves performance

A recent study by Fan et al. (2017) took a closer look at the role of PPARδ and how its manipulation can impact metabolism and performance.  This study was conducted in mice but keep in mind we use mice for early experiments because their physiology is very close to humans and the results we see serve as successful stepping stones to studies and interventions in humans.  And yes, PPARδ is found and active in humans.

When the authors compared normal mice to ones without PPARδ they found the normal mice showed changes in fuel use from glucose to fatty acid after 4 weeks of running while the mice without PPARδ did not show these same metabolic shifts.  Metabolic activity related to the genes impacted by the two gatekeeper proteins, Cpt1b and Pdk4, which are affected by PPARδ were either reduced by 50% or completely absent.  Performance wise, the mice missing PPARδ were only able to run half as long as the normal mice.  While the shift to fat burning occurred, the mice without PPARδ who ran still saw a change in muscle fiber type and an increase in mitochondria.  Clearly it was the fuel source metabolic change that accounted for the increase in performance.

When the authors treated the mice with a drug that activates PPARδ for 8 weeks they found metabolic changes that indicate a significant shift towards increased fatty acid metabolism.  There was a strong increase in the expression of the two mitochondrial gatekeeper genes Cpt1b and Pdk4 and a decrease in anaerobic glycolysis (carbohydrate fueled metabolism).  When the drug was given to the mine manipulated to not have PPARδ none of the changes that are normally expected occurred indicating that all the metabolic and physiological changes we are concerned with are dependent on muscle PPARδ.  Performance wise, the mice given the PPARδ stimulating drug were able to run for 1.5 hours longer then the mice without it.

Increased endurance via blood glucose sparing

The authors theorized that the reason for the increased performance in the drug treated mice was that the increased fatty acid metabolism stimulated via PPARδ spared blood glucose levels.  Both drug treated and non-drug treated mice stop running and often pass out once they hit a blood glucose level below 70 mg/dL.  In control mice blood glucose levels begin to drop between 90-120 min.  In the drug treated mice, blood glucose levels were able to be maintained for extended periods of time and often did not even begin to drop until after 180 minutes.  These types of glucose sparing improvements are the same that are seen with exercise training.  This switch from glucose to fat fueled metabolism maintains blood glucose levels high enough to continue supporting the needs of the brain and other tissues allowing for the significant increases in performance.

In addition to all of this there was also an up-regulation of 492 genes and a down-regulation of 483 genes within the quadriceps of the tested mice.  These included genes that have roles in carbohydrate and fat metabolisms and insulin activity.

So there you have it.  PPARδ turns out to be the main regulator of changes in energy substrate use in muscles.  Increase its activation and you stimulate muscle cells to use more fat based energy sources, sparing blood glucose and extending performance.  The first question you should be asking now is can we take the drug that was used in this study and achieve the same results in humans.  The version used in mice is unfortunately not safe for humans however a company has already been set up and is in the process of developing a version that is safe for human consumption.  While how to address drugs like this in competitive sport performance is an entirely different problem there is no question it could have significant impacts on a range of metabolically related diseases.  So while you are waiting for your PPARδ stimulator in pill form, get out and do some endurance work and stimulate some fat burning/glucose sparing metabolic changes along with enhancing oxidative capacity of muscle fibers and stimulating the growth of additional mitochondria the old fashioned way, by breaking a sweat and doing some work.

Works Cited:

Fan, W., Waizenegger, W., Lin, C.S., Sorrentino, V., He, M., Wall, C., Li, H., Liddle, C., Yu, R., Atkins, A., Auwerx, J., Downes, M., and Evans, R. (2017) PPARδ Promotes Running Endurance by Preserving Glucose. Cell Metabolism 25, 1186-1192

 Schuler, M., Ali, F., Chambon, C., Duteil, D., Bornet, J.M., Tardivel, A., Desvergne, B., Wahli, W., Chambon, P., and Metzger, D. (2006). PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switch, obesity, and type 2 diabetes. Cell Betab. 4, 407-414.

Wang, Y.X., Zhang, C.L., Yu, R.T., Cho, H.K., Nelson, M.C., Bayuga-Ocampo, C.R., Ham, J., Kang, H., and Evans, R.M. (2004) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol. 2, e294.