Resveratrol Consumption During Endurance Training Significantly Improves Physical Performance and Cardiac Function in the Rat Model

Improvement in physical performance is an ever-present ongoing goal for both clinical and nonclinical purposes.  It is well known that endurance training can improve physical performance by increasing energy metabolism in skeletal muscles, as well as improved cardiac function, particularly when undergoing more intense exercise sessions.  It is also well known that resveratrol, a polyphenolic compound found in many edibles including grapes and red wine; possess a wide range of cardiovascular benefits in humans. 

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In mice, resveratrol has been found to increase skeletal muscle mitochondrial biogenesis, fatty acid oxidation, and also improved exercise performance in a way that is similar to exercising alone without supplementation of the compound.  Specifically, one study found that resveratrol supplementation in the diet of aged mice (fed a “Western diet”) increased physical performance, suggesting that resveratrol may stimulate the same physiological pathways as exercise alone.  What is unknown, however, is whether the health beneficial effects of resveratrol can improve exercise performance greater than the act of exercising alone. Does supplementation with resveratrol further improve the benefits of exercise?

In addition to physiological improvements based on exercise-related activity, resveratrol is very well known for cardiovascular benefits in humans.  However, to date, nearly all of the studies focusing on resveratrol and cardiovascular health in humans have been related to the prevention of pathological conditions of the heart, and very little on the effect of resveratrol on skeletal muscle and cardiac function in those undergoing some form of exercise.  The study presented today, which I first discovered a few days ago from a new internet news sources, focused on these very questions.

Methods

For this study, 50 male Wistar rats were obtained at age 8 weeks of age.  Throughout the study, rats had free access to drinking water and were fed ad libitum.  Rats were either fed a standard chow diet, or a standard chow diet plus 4g of resveratrol per kg bodyweight (dosage equivalent to 146mg resveratrol per kg bodyweight per day).

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Rats were exercised on a calibrated motor driven rodent treadmill with an electrical simulation for foot shock.  When rats were 9 weeks of age, they were acclimated to the treadmill.  The exercise treatment began when the rats were 10 weeks of age and was performed by having the rats run daily progressions for a total of 60 minutes that started off at 10m/min with a 0% incline, and eventually increased to 20m/min at a 0% incline.

Endurance training occurred 5 days per week for 12 weeks.  To encourage the rats to run on the treadmill, a combination of electrical stimulation and puffs of air were used.  After the 12 weeks of endurance training, exercise performance was assessed in the then-22 week old rats.  Exercise performance was evaluated by a graded exercise test to exhaustion (at a 0% incline).  The test began with 10m/min for 1 minute, 11m/min for 1 minute, 12m/min for 1 minute, 13m/min for 2 minutes, 15m/min for 5 minutes, 17m/min for 5 minutes, and 20m/min until exhaustion. A rat was determined to be exhausted when the animal could no longer run on the treadmill as determined by the rat spending less than half the time or more than 30 seconds on the electrical stimulus and resistant to the puffs of air.  Control rats were sedentary (did not undergo endurance training), were acclimated to the treadmill and handled 5 days per week.

Exercise treatments were as follows: 1) sedentary rats fed a standard diet; 2) sedentary rats fed a standard diet plus resveratrol (see dosage above); 3) rats undergoing endurance training while on a standard diet; and 4) rats undergoing endurance training while on a standard diet plus resveratrol (see dosage above).

Muscle force measurements were taken on the soleus muscles (back part of the calf).  Also in this muscle, maximum twitch and tetanic forces were sequentially recorded in both left and right sides.  Also measured was fatigue index, which is calculated to be the ratio of initial to final force, measured during stimulation. 

In regards to cardiovascular and other physiological measurements, the following were taken: transthoracic echocardiography, non-invasive blood pressure, glucose and palmitate oxidation rates, glucose tolerance (after a 5 hour fast), and insulin tolerance.

After 10 weeks of diets and/or exercise treatments, food intake and whole body energy metabolism were measured in the rats.  Oxygen consumption, CO2 production, heat production, respiratory exchange ratio, lipid and glucose oxidation, and physical activity were also measured. Finally, lipids (triacylglycerol and free fatty acids) and gene expression were measured.

Results

  • Endurance training significantly reduced the weight of rats fed either the standard diet or the diet with resveratrol added compared with sedentary rats.
  • Supplementing diets of sedentary rats with resveratrol significantly improved exercise performance (25% improvement).
  • 12 weeks of endurance training alone increased the endurance of rats compared to sedentary rats.

o   Comparing endurance training alone with endurance training plus resveratrol supplementation further increased exercise performance by 20%.

  • Endurance training plus resveratrol significantly increased the twitch force in the tibialis anterior muscle (front portion of shin) by 18% when compared to endurance training alone.
  • There did not appear to be any differences between endurance training alone and endurance training plus resveratrol in regards to the tetanic muscle force in the tibialis anterior muscle.

o   In the soleus muscle, twitch and tetanic forces were both significantly increased (58% and 22%, respectively) in endurance training plus resveratrol rats compared to endurance training alone.

o   These results suggest that resveratrol supplementation in the diet during endurance training increases the isometric force production by skeletal muscles.

  • Fatigue index was not different between endurance training rats and endurance training plus resveratrol rats.

o   Resveratrol does not increase endurance capacity of isolated skeletal muscles.

o   The increased endurance seen in rats with a resveratrol-supplemented diet is not directly attributed to resistance to muscle fatigue, which is consistent with human findings that running performance is more closely correlated with cardiovascular performance than muscle-fiber type distribution.

  • Increased exercise performance in rats undergoing endurance training and resveratrol-enriched diets was associated with significantly improved LV ejection fraction and fractional shortening (i.e. improved cardiac function).

o   There were significant improvements in LV diastolic function in exercise + resveratrol rats compared to exercise rats alone.

  • Resveratrol in the diets of rats during endurance training improved both glucose and insulin performance more than rats undergoing endurance training alone.
  • The respiratory exchange ratio in exercise + resveratrol rats was significantly lower compared to exercise-alone rats.
  • Fatty acid oxidation was significantly higher in exercise + resveratrol rats than in exercise-alone rats.

o   Results indicate resveratrol in the diet enhances cardiac muscle fatty acid oxidative capacity which contributes to increased cardiac function in the rat.

  • For both exercise-alone rats and exercise + resveratrol rats, high levels of activity increased both heart rate and peak systolic pressure (therefore overall cardiac function), though in exercise + resveratrol rats, LV developed pressure, coronary flow, and cardiac work were even more increased then in exercise-alone rats.

o   Results suggest resveratrol in the diet of rats increases the hearts’ ability to adapt to increased workloads that are induced by exercise.

  • Resveratrol reduced the expression of several pro-inflammatory genes.
  • Resveratrol reduced inflammatory mediators and increased expression of cardiac adiponectin.

o   Results suggest resveratrol supplementation during endurance training exercise alters cardiac energy metabolism and reduces cardiac inflammation.

  • Exercise + resveratrol elevated AMP-activated protein kinase phosphorylation when compared with exercise-alone.
  • Exercise + resveratrol increased the expression of PGC1-α (a transcriptional regulator of mitochondrial biogenesis and function).

o   Results suggest resveratrol supplementation during endurance training exercise enhances performance through increased cardiac fatty acid metabolism.

Conclusions

According to the results of this study, rats that consumed resveratrol as part of their daily diets during 12 weeks of endurance training were able to run longer and further than rats that underwent endurance training alone.  Resveratrol supplementation was associated with improved strength in soleus and tibialis anterior leg muscles which likely played a big role in the improved exercise performance.

This study showed that resveratrol supplementation significantly improves physical performance and cardiac function in rats.  What about humans?  Would we see the same results? Or is this just a special occurrence for rodents?  Recent studies have shown that resveratrol supplementation improved mitochondrial efficiency in overweight middle aged men, which indicates that the results we’ve seen here in rats may not be limited to that particular species.

The results of this study also found that resveratrol supplementation in the diets of rats undergoing endurance training increased whole body oxygen consumption, as well as whole body fat oxidation and ultimately improved aerobic exercise capacity.  Based on these results, resveratrol and exercise (specifically, endurance training) act together to improve skeletal muscle oxidative capacity and metabolism, which overall aids in the significantly improved endurance capacity of the skeletal muscles.

The authors also claimed that the increased oxidation of fat seen in rats consuming resveratrol and undergoing exercise training are not only improving exercise performance, but also helping to prevent insulin resistance in pre-diabetic persons undergoing moderate exercise.  Also, since humans are notorious for not being able to maintain vigorous exercise programs (for the most part), resveratrol supplementation in the diet coupled with more moderate exercise may be equally as beneficial as just performing a very vigorous exercise regime alone.

These results suggest that resveratrol supplemented in the diet contributes to improved endurance capacity in rats undergoing endurance training significantly improves exercise performance greater than exercise alone, which could potentially have significant clinical and nonclinical applications where improved physical performance needs to be “helped along” due to a persons’ inability to perform vigorous exercise (due to injury, illness, laziness…).  We can’t be certain these results will carry over into humans from the rat model, however, the few studies within humans that are in existence gives hope that we may see similar mechanisms at work.

As an aside, I’m really curious about these results.  As a distance runner myself (I’ll be training for marathon #4 shortly), I’m interested in trying a little self-experimenting and perhaps supplementing my marathon training with some form of resveratrol.  Anyone want to sponsor me?  ;-)  Also, I’m wondering how one should pace oneself at “water stops” of the Marathon du Medoc to effectively increase their endurance without becoming unpleasantly sloshed (what is Marathon du Medoc? Read about it here.).  This last wonderment is said jokingly, as I’m sure the alcohol involved would negate any benefits of the resveratrol at the rate most people consume it during the race.

What do you all think about this topic?  Would you try supplementing your diet with resveratrol to help increase exercise/endurance performance?  Are you waiting until more research with humans comes out to even try?  Please feel free to leave your comments below (reminder: any unapproved/unsolicited HTML tags will be promptly removed).

Source: Dolinsky, V.W., Jones, K.E., Sidhu, R.S., Haykowsky, M., Czubryt, M.P., Gordon, T., and Dyck, J.R.B. 2012. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats. Journal of Physiology 590(11): 2783-2799.

DOI: 10.1113/jphysiol.2012.230490
I am not a health professional, nor do I pretend to be. Please consult your doctor before altering your alcohol consumption habits. Do not consume alcohol if you are under the age of 21. Do not drink and drive. Enjoy responsibly!

4 comments for “Resveratrol Consumption During Endurance Training Significantly Improves Physical Performance and Cardiac Function in the Rat Model

  1. jim peck
    June 22, 2012 at 5:25 pm

    A little confusion: were they fed 4 g/kg/d or 146 mg/kg/d? Even in the lower dose, I would have to consume about 13 g/day for my 200 lb body weight. That's a very high dose of any kind of supplement.

  2. June 22, 2012 at 8:14 pm

    I apologize for the confusion. The dosage was 4g of resveratrol per kg of food. That is equivalent to 146mg of resveratrol per kg body weight per day.

    A next step for this study would be to examine a variety of doses to see how low of a dose one can administer and still see similar beneficial effects.

    Thanks for your question/comments!

  3. Wineknurd
    June 24, 2012 at 1:24 pm

    Becca I think you just gave Lance Armstrong his defense against the latest doping allegations :)

    That 13 g / day for a 200 lb person can be spread out to ~3 g a meal over 4 meals, maybe even less per meal if you consider adding it to a training regimen of 5 – 6 meals / snack / supplements. This isn't an unusual amount when you look at supplements like creatine, which many bodybuilders take in at 10 g / day.

    I think you hit the nail on the head Becca with your dosing / efficacy comment. Need to figure out how low a dose is both bio-available and how much your body can process in one dose. No sense in taking 3 g if your body can only handle 2 g every 4 hours!

  4. June 25, 2012 at 1:33 pm

    I know, right! I'm so tempted to start taking a resveratrol supplement during my marathon training to see how that goes. Certainly couldn't hurt, since my training has been less than stellar lately :)

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