Testing the rule: exercise benefits can only come from exercise

Can Vitamin C Replace Exercise?
The exception that proves (tests) the rule
By Will Block


Linus Pauling—the only winner of two unshared Nobel Prizes—revolutionized the field of chemistry, helped found the field of molecular biology, and made important progress in medical research. Furthermore, Pauling's nutritional supplementation work with antioxidants such as vitamin C remains valid showing that they have substantial health benefits. Also, his ideas about orthomolecular balance and wellbeing are increasingly appreciated by a growing number of health professionals, not to mention the health-conscious public.
Scientists are well aware that exceptions found from testing a generally accepted rule often lead to abolishing the old rule and creating a new one. In a new study, presented in a poster session at the American Physiological Society’s annual meeting in Savannah this past September, researchers investigated whether vitamin C supplementation would be as effective as aerobic exercise for reducing blood vessel constriction.1 And it was just as effective! If this and other findings continue to appear and withstand challenge, not only for vitamin C but for other nutrients as well, the rule that only exercise (but not supplements) can replace the benefits of exercise may be discarded.


The rule that only exercise (but not
supplements) can replace the benefits
of exercise may be discarded.


Poor Vascularity May Lead to a Downward Spiral

In the study, blood vessel constriction was measured by protein endothelin-1 (ET-1) system activity. ET-1 has a constricting action on small blood vessels and this activity is increased in overweight and obese individuals, making small blood vessels more prone to constrict and less able to handle blood flow demand, increasing the risk of vascular disease. Poor vascular tone can lead to a downward health spiral, starting with inflammation and changes in the blood which can cause stroke.


Poor vascular tone can lead to a
downward health spiral, starting with
inflammation and changes in the
blood which can cause stroke.


Vitamin C and Exercise

Lead author Caitlin Dow and her colleagues at the University of Colorado in Boulder followed 35 sedentary, overweight or obese adults for three months. At the start of the study, all of the participants had impaired vascular tone with increased risk of developing high blood pressure and suffering heart attacks and strokes. Twenty participants took 500 mg of vitamin C per day during that time but did not increase their activity, while 15 subjects took a brisk walk 5 to 7 times a week. The trial period lasted three months.


Twenty participants took 500 mg of
vitamin C per day during that time
but did not increase their activity,
while 15 subjects took a brisk walk 5
to 7 times a week. The trial period
lasted three months.


Surprisingly, it was found that ET-1 was reduced to a similar extent in both the vitamin C and exercise groups. While the researchers did not look at the benefits of exercise beyond lowering blood pressure—and there are many— they did find that the participants in the exercise group had increased fitness and stamina. Their conclusion is that Vitamin C may mimic some of the effects of exercise in overweight and obese individuals.


Their conclusion is that Vitamin C
may mimic some of the effects of
exercise in overweight and obese
individuals.


More than 50% Do Not Exercise

While overweight and obese adults are advised to exercise to improve their health, more than 50 percent do not do so. It would seem that incorporating an exercise regimen into a daily routine is challenging. Therefore, the new research suggesting that taking vitamin C supplements daily can have similar cardiovascular benefits as regular exercise in these adults is a good thing.

Reference

  1. The American Physiological Society Press Release. Vitamin C: The Exercise Replacement? September 4, 2015. http://www.the-aps.org/mm/hp/Audiences/Public-Press/2015/44.html Accessed: October 13, 2015.

Can Other Supplements Enhance the Effects of Exercise?

According to the Mayo Clinic, there are seven main benefits to be gained through exercise:1

No. 1: Exercise helps control weight

Exercise can help prevent excess weight gain or help maintain weight loss. According to a recent meta-analysis, in studies lasting 2 years or longer, diet-plus-exercise interventions provided significantly greater weight loss than diet-only interventions.2 However, both diet-only and diet-plus-exercise programs are associated with partial weight regain.


In studies lasting 2 years or longer,
diet-plus-exercise interventions
provided significantly greater weight
loss than diet-only interventions.


No. 2: Exercise fights health conditions and diseases

Regular physical activity can help prevent or manage a wide range of health problems and concerns, including stroke, metabolic syndrome, type 2 diabetes, depression, certain types of cancer, arthritis, and falls.3 Conclusive evidence exists that physical inactivity is an important cause of most chronic diseases.


Regular physical activity can help
prevent or manage a wide range of
health problems and concerns.


No. 3: Exercise enhances mood

For an emotional lift or just to blow off some steam after a stressful day, a workout at the gym or a brisk 30-minute walk can be of value. Physical activity stimulates various brain chemicals that may leave you feeling happier and more relaxed. Also, exercise has been linked to adult neurogenesis in two brain regions—the hippocampus and the olfactory bulb—and has been related to the pathophysiology of mood disorders and mechanism of antidepressant treatments.4


Exercise has been linked to adult
neurogenesis in two brain regions—
the hippocampus and the olfactory
bulb—and has been related to the
pathophysiology of mood disorders
and mechanism of
antidepressant treatments.


No. 4: Exercise increases energy

Regular physical activity can improve your muscle strength and boost your endurance. Exercise and physical activity deliver oxygen and nutrients to your tissues, and help your cardiovascular system work more efficiently. When your heart and lungs work more efficiently, you have more energy to go about your daily chores.


High levels of physical activity,
exercise training, and overall
cardiorespiratory fitness are
valuable to help prevent and treat
cardiovascular diseases.


According to a recent review,5 high levels of physical activity, exercise training, and overall cardiorespiratory fitness are valuable to help prevent and treat cardiovascular diseases. Also, in an 18-month high-impact exercise intervention in premenopausal women, the exercise benefits on physical performance continued to be maintained 3.5 years after intervention.6

No. 5: Exercise promotes better sleep

Do you struggle to fall asleep or to stay asleep? Regular physical activity can help you fall asleep faster and deepen your sleep. Perhaps no daytime behavior has been more closely associated with better sleep than exercise.7 Sleep may serve to conserve energy function (see No. 4). In fact, exercise offers a potentially attractive alternative for insomnia. Sleeping pills have a number of adverse side effects, including increased mortality.


Perhaps no daytime behavior has
been more closely associated with
better sleep than exercise.


No. 6: Exercise puts the spark back into your sex life

Do you feel too tired or too out of shape to enjoy physical intimacy? Regular physical activity can leave you feeling energized and looking better, which may have a positive effect on your sex life. In a study with more than 31,000 men, aged 53 to 90, physical exercise was associated with good erectile function.8


In one study, resveratrol-
supplemented mice ran twice as far
as those not receiving it.


No. 7: Exercise can be fun

There is increasing evidence that regular mental and physical exercise can enhance overall health and functional abilities in older adults. However, enjoyment and fun can convert what is difficult into what is easy. A study describes how a vigorous program of playing polo can provide important mental and physical benefits-even for older adults.9

The bottom line on exercise

Exercise and physical activity are a great way to feel better, gain health benefits, and have fun. According to the Mayo Clinic, as a general goal, you ought to aim for at least 30 minutes of physical activity every day. For weight loss or to meet specific fitness goals, you may need to exercise more.

However, the real bottom line is a combination of exercise and nutrients skewing toward more nutrients and less exercise. In other words, leading to more efficient exercise.


Resveratrol also causes
adaptations in the oxygen transport
system that are similar to
exercise training.


Resveratrol as Exercise Enhancer

In a study published in 2011, senior editor Johan Auwerx and colleagues found that tweaking a specific gene makes muscles twice as strong, opening a new passage for treating muscle degeneration in people who can’t exercise, or perhaps for those who would like the benefits of exercise without spending time in the gym.10 Such a conclusion opens the door to the exercise pill, which has been hinted by resveratrol research, including an earlier study, also presided over by Dr. Auwerx, finding that the herbal extract boosts strength and endurance in mice.10 In this study, resveratrol-supplemented mice ran twice as far as those not receiving it.

Consider also that while studies have shown that resveratrol acts as a caloric restriction mimetic, resveratrol also causes adaptations in the oxygen transport system that are similar to exercise training, the benefits of which are enhanced further when combined with the nutrient.11 In fact, other studies show that resveratrol activates molecular pathways that are analogous to the effects of exercise training.

Vitamins E and C Increase Fat-Free Mass and Muscle Mass Index

A study conducted in 2008 found that in elderly subjects an antioxidant combination, consisting of vitamins E and C was able to increase the amount of fat-free mass resulting from resistance training.12 Sixty-one older men (n=27) and women (n=34) (aged 65.8 ± 3.7, range 60–75) were recruited to participate in a double-blind controlled study, and were randomly assigned to one of four groups: placebo, placebo + resistance training, antioxidant, and antioxidants + resistance training. Subjects had to be physically healthy and not use supplements or medication. The trial lasted for 6 months.


As such, there was an increase of
0.5 ± 1.4 kg in the resistance
training group, whereas the
antioxidants + resistance training
group had an increase of
1.3 ± 1.2 kg, a 160% increase.


The antioxidants mixture consisted of 600 mg per day of vitamin E (dl-α-tocopherol) and 1,000 mg per day of vitamin C. A significant treatment effect was found for fat-free mass and muscle mass index. As such, there was an increase of 0.5 ± 1.4 kg in the resistance training group, whereas the antioxidants + resistance training group had an increase of 1.3 ± 1.2 kg.

To the researchers’ knowledge, this is the first study to examine the effect on fat-free mass and muscle mass index in older adults when antioxidant supplements are combined with 6 months of resistance training.

Amino Acids Improve Exercise Capacity

The same year, researchers investigated whether 30 days of oral supplementation with a special mixture of amino acids (AAs), together with conventional therapy, could improve exercise capacity in elderly outpatients with chronic heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD).13 A group of 95 outpatients (12 women and 83 men; aged 65-74 years) were studied in a randomized, double-blind, placebo-controlled study. The patients performed a basal exercise test and were then randomly assigned to a special oral nutritional mixture of AAs 4 g twice daily (n = 43) or placebo (n = 42).


Supplemented EAAs can
improve the physical autonomy in
subjects with coronary heart disease
and chronic obstrucive
pulmonary disease.


Recent studies show that supplemented essential amino acids (EAAs) may exert beneficial effects on CHF/COPD physical capacity. These studies consistently showed that elderly CHF and COPD improved exercise intolerance after 1-3 months of EAA supplementation (8 g/d).

CHF exercise capacity increased 18.7% to 23% (watts; bicycle test), and 12% to 22% (meters) in 6 min walking test. Moreover, patients reduced their resting plasma lactate levels (by 25%) and improved tissue insulin sensitivity by 16%. COPD subjects received similar benefits as CHF subjects. They increased physical autonomy by 78.6% steps/day and decreased resting plasma lactate concentrations by 23%. EAA mechanisms explaining improved exercise intolerance could be increases in muscle aerobic metabolism, mass and function, and improvement of tissue insulin sensitivity (the latter only for the CHF population). These mechanisms could be accounted for by EAA’s intrinsic physiological activity, which increases myofibrils and mitochondria genesis in skeletal muscle and myocardium, and enhances glucose control. Supplemented EAAs can improve the physical autonomy in subjects with CHF/COPD.


Vitamin D supplementation
increases upper and lower
limb strength.


Vitamin D Bolsters Muscle Strength

A meta-analysis reviewed controlled and randomized controlled trials that measured muscle strength and serum vitamin D concentration in 18-40 year old participant.14 Muscle strength and vitamin D levels were analyzed on upper and lower limb strength with differences calculated to analyze the effects.

Six randomized controlled trials and one controlled trial were identified and quality assessment showed all seven trials were of “good quality.” Data was extracted from 310 adults, 67% female, with mean ages ranging from 21.5 to 31.5 years. Trials lasted from 4 weeks to 6 months and dosages differed from 4000 IU per day to 60,000 IU per week.


These discoveries bring us
ever closer to pharmacological
control of enhancing genetic
expression otherwise requiring
exercise as a trigger.


Upper and lower limb muscle strength had a standardized mean difference of 0.32 (95% CI=0.10, 0.54) and 0.32 (95% CI=0.01, 0.63) respectively, suggesting vitamin D supplementation significantly increased muscle strength in the experimental group for upper and lower limbs. Vitamin D supplementation increases upper and lower limb strength.

Protein, Creatine, Vitamin D and Calcium

Combined exercise with nutritional supplementation reinforces the effects each can have on improving strength, balance and speed.15 The improvement of the musculoskeletal system enhances mobility, contributing to the prevention of sarcopenia and prolongation of the independence and autonomy of older people. The use of supplements should be subject to an analysis of daily nutritional intake, individual energy demands and the choice of a physical endurance exercise practiced and extended in time, to preserve the benefits.

Durk Pearson & Sandy Shaw’s Take on the “Exercise Pill”

Durk & Sandy project that an “exercise pill” is on the horizon. In an article appearing in the September 2013 issue of this publication they develop the case for the pill’s arrival (see “Closing in on Exercise in a Pill? Maybe, Decreased Methylation in Muscle Genome Turns On Exercise-Induced Gene Expression” The Durk Pearson & Sandy Shaw® Life Extension News,™ Vol. 16, No 8) .

First they point out that researchers have identified many of the skeletal muscle genes that are triggered by exercise and contribute importantly to the benefits of exercise. Citing a paper16 that identifies a vital role played by DNA methylation in exercise-induced gene expression, they write that, “DNA methylation is an important process for determining when genes are expressed (turned on) or silenced (turned off) and much has been learned about natural products that are able to trigger increased DNA methylation (which generally decreases gene expression) or decreased DNA methylation (which generally increases gene expression).” In their considered opinion, these discoveries bring us ever closer to pharmacological control of enhancing genetic expression otherwise requiring exercise as a trigger.

As they point out, DNA methylation was found to be decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after they performed acute exercise.

The authors wrote,16 “Exercise induced a dose-dependent expression of PGC-1alpha [an important regulator of mitochondrial biogenesis], PDK4, and PPAR-delta, together with a marked hypomethylation on each respective promoter. Similarly promoter methylation of PGC-1alpha, PDK4, and PPAR-delta was markedly decreased in mouse soleus muscles 45 minutes after ex-vivo contraction,” as were other gene changes.


This leads to the hypothesis
that mild exercise might
be able to provide the benefits that
would otherwise require more
energetic exercise.


“Conversely, reactive oxygen species (ROS) production (induced by H2O2 [hydrogen peroxide]) elicitated hypermethylation.” The authors suggest,17 therefore that, “DNA hypomethylation is an early event in [muscle] contraction-induced gene expression.”

EGCG and Curcumin are Hypomethylating Agents

In other recent research, EGCG17 and curcumin18 have been identified as natural substances that act as hypomethylating agents, e.g., they decrease DNA methylation. According to Durk & Sandy, this suggests that taking proper doses of EGCG and/or curcumin shortly before exercise might enhance the hypomethylation induced by muscle contraction, increasing the beneficial effects of exercise.

This leads to the hypothesis that mild exercise might be able to provide the benefits that would otherwise require more energetic exercise.

However, DNA methylation does not exclusively control exercise-induced gene expression. Thus, the authors16 propose that DNA methylation, “may serve as a selective mechanism to orchestrate the activation of a subset of genes, but clearly, other mechanisms, such as transcription factor activation and recruitment to the chromatin, are likely to be involved.”

Exercise Alters Epigenetic Parameters in Rat Hippocampus

In another paper on exercise and DNA methylation (an epigenetic process),19 researchers found that exercise can alter DNA methylation in the hippocampus of 3-month and 20-month old Wistar rats. As it is known that exercise can improve cognitive processes, DNA methylation is an interesting link that suggests a possible mechanism for the effect of exercise on cognition.

Exercise Epigenetic Modulation of Memory and Cognition

The authors19 first point out that epigenetic mechanisms have been shown to affect cognition in earlier studies where histone deacetylase (HDAC) inhibitors improved memory in aged rodents. Moreover, exercise has also been shown to ameliorate age-related cognitive decline in rodents. Other studies have reported that exercise modulation of HDAC status in the brain enhanced transcription of genes in the brain related to cognitive function.

The researchers therefore studied the effects of exercise on epigenetic changes as a consequence of aging. They followed the effects of two exercise regimens, a single session of treadmill exercise or chronic treadmill exercise, on changes in DNA methylation in the hippocampus.

The findings showed that methylation changes as a result of exercise differed in 3-month old (young) and 20-month old (aged) male Wistar rat hippocampi. They found decreased DNA methyltransferase 1 (DNMT1) activity in senescent human fibroblasts, and suggest that this is correlated with a genome-wide tendency to DNA hypomethylation in multiple vertebrate organs during the aging process.19 Aged hippocampi were found to have lower levels of H3-K9 methylation levels. Explained by the researchers: histone methylation can cause either gene activation or gene repression.

The single exercise experiment in young adult rats resulted in significant decrease in both DNMT1 and DNMT3b, two methyltransferases, which could reduce DNA methylation and, consequently, affect gene expression. In contrast, the single exercise test did not have an effect on the methyltransferases levels in the hippocampi of the 20 month-old (aged) rats. Other details reveal considerable complexity to the pattern of epigenetic changes in the hippocampus in conjunction with exercise in young and old rats. It is interesting to note that EGCG inhibits methyltransferases.

Finally, as per Durk & Sandy, “It appears quite plausible (but not proven) that DNA methylation changes in the hippocampus as a consequence of exercise may play a role in the improved cognition resulting from exercise, but that these effects are different in young vs. old rats. Exercise in a pill? We aren’t there yet, but come back in five years or so.”

References

  1. Mayo Clinic Staff. Healthy Lifestyle Fitness. http://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/exercise/art-20048389. Feb. 05, 2014. Accessed: October 24, 2015.
  2. Wu T, Gao X, Chen M, van Dam RM. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009 May;10(3):313-23. doi: 10.1111/j.1467-789X.2008.00547.x. Epub 2009 Jan 19. Review. PubMed PMID: 19175510.
  3. Booth FW, Roberts CK, Laye MJ. Lack of exercise is a major cause of chronic diseases. Compr Physiol. 2012 Apr;2(2):1143-211. doi: 10.1002/cphy.c110025. Review. PubMed PMID: 23798298; PubMed Central PMCID: PMC4241367.
  4. Yau SY, Lau BW, So KF. Adult hippocampal neurogenesis: a possible way how physical exercise counteracts stress. Cell Transplant. 2011;20(1):99-111.
  5. Lavie CJ, Arena R, Swift DL, Johannsen NM, Sui X, Lee DC, Earnest CP, Church TS, O'Keefe JH, Milani RV, Blair SN. Exercise and the cardiovascular system: clinical science and cardiovascular outcomes. Circ Res. 2015 Jul 3;117(2):207-19.
  6. Heinonen A, Mäntynen J, Kannus P, Uusi-Rasi K, Nikander R, Kontulainen S, Sievänen H. Effects of high-impact training and detraining on femoral neck structure in premenopausal women: a hip structural analysis of an 18-month randomized controlled exercise intervention with 3.5-year follow-up. Physiother Can. 2012 Winter;64(1):98-105.
  7. Youngstedt SD. Effects of exercise on sleep. Clin Sports Med. 2005 Apr;24(2):355-65, xi.
  8. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, Rimm EB. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med. 2003 Aug 5;139(3):161-8.
  9. Vail JD. Polo for all ages: exercise should be functional...and fun! J Psychosoc Nurs Ment Health Serv. 2009 May;47(5):24-7.
  10. Yamamoto H, Williams EG, Mouchiroud L, Cantó C, Fan W, Downes M, Héligon C, Barish GD, Desvergne B, Evans RM, Schoonjans K, Auwerx J. NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function. Cell. 2011 Nov 11;147(4):827-39.
  11. Labonté M, Dionne IJ, Bouchard DR, et al. Effects of antioxidant supplements combined with resistance exercise on gains in fat-free mass in healthy elderly subjects: a pilot study. J Am Geriatr Soc. 2008 Sep;56(9):1766-8.
  12. Dolinsky VW, Dyck JR. Experimental studies of the molecular pathways regulated by exercise and resveratrol in heart, skeletal muscle and the vasculature. Molecules. 2014 Sep 18;19(9):14919-47.
  13. Aquilani R, D'Antona G, Baiardi P, Gambino A, Iadarola P, Viglio S, Pasini E, Verri M, Barbieri A, Boschi F. Essential amino acids and exercise tolerance in elderly muscle-depleted subjects with chronic diseases: a rehabilitation without rehabilitation? Biomed Res Int. 2014;2014:341603. doi: 10.1155/2014/341603. Epub 2014 Jun 9.
  14. Tomlinson PB, Joseph C, Angioi M. Effects of vitamin D supplementation on upper and lower body muscle strength levels in healthy individuals. A systematic review with meta-analysis. J Sci Med Sport. 2015 Sep;18(5):575-80. doi: 10.1016/j.jsams.2014.07.022. Epub 2014 Aug 11.
  15. Vásquez-Morales A, Wanden-Berghe C, Sanz-Valero J. [Exercise and nutritional supplements; effects of combined use in people over 65 years; a systematic review]. Nutr Hosp. 2013 Jul-Aug;28(4):1077-84.
  16. Barrès R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O'Gorman DJ, Zierath JR. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012 Mar 7;15(3):405-11.
  17. Yang CS, Fang M, Lambert JD, Yan P, Huang TH. Reversal of hypermethylation and reactivation of genes by dietary polyphenolic compounds. Nutr Rev. 2008 Aug;66 Suppl 1:S18-20.
  18. Liu Z, Xie Z, Jones W, Pavlovicz RE, Liu S, Yu J, Li PK, Lin J, Fuchs JR, Marcucci G, Li C, Chan KK. Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett. 2009 Feb 1;19(3):706-9.
  19. lsner VR, Lovatel GA, Moysés F, Bertoldi K, Spindler C, Cechinel LR, Muotri AR, Siqueira IR. Exercise induces age-dependent changes on epigenetic parameters in rat hippocampus: a preliminary study. Exp Gerontol. 2013 Feb;48(2):136-9.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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