Tyna Moore, ND, DC

Tolle Causam

Harnessing, supporting, and increasing a patient’s vitality is always the main goal as a naturopathic physician. Increasing their vitality by honing the Vis Medicatrix Naturae is the most potent medicine. When one thinks of “Anti-Aging Medicine,” thoughts of bioidentical hormone replacement, advanced scientific medical applications, and latest technologies come to mind. This article is an argument for the often overlooked and underappreciated medicine of muscle mass.

After nearly a decade of specializing in regenerative injection therapies (RITs) and documenting thousands of clinical outcomes, I have concluded that these therapies are only as good as the patient’s ability to mount a modulated inflammatory response, induce appropriate cell signaling, and regenerate their tissues. While skill of the practitioner is obviously a critical factor, several other variables, such as diet, hormones, and inflammation, play a role. Through clinical observation, I have found that the most important factor determining whether a patient will consistently improve from RIT is the level of lean muscle mass on the patient’s frame. Skeletal muscle, as an organ system, turns out to have incredible health benefits.

Nourishing, building, and strengthening the skeletal muscle organ system by building lean skeletal muscle mass is a fundamental treatment guideline that is the most potent anti-aging and regenerative medicine available. It is also one of the most basic ways to increase vitality.

Aging and Muscle

The hallmarks of cellular aging are a reduction in pluripotent stem cells, mitochondrial dysfunction, oxidative stress, and cell death. These are most often caused by chronic inflammation and increased adiposity from fatty infiltrate. It’s a vicious cycle that perpetuates itself. Sarcopenia, Greek for “poverty of flesh,” is both a contributor and a direct result of aging.

The process of muscle loss begins for most people in their 30s and 40s, with a loss of up to 8% per decade until the age of 70 years, after which the loss increases to 15% per decade.¹ Many aging adults also suffer from insulin resistance, hormonal imbalance, type 2 diabetes mellitus, dyslipidemia, hypertension, heart disease, and increased adiposity, all of which can be attributed to sarcopenia as a root cause.

Causes of sarcopenia are varied and plentiful, but deconditioning and lack of proper strength training exercise is at the core. In my experience, most people who exercise lean towards aerobic activities like running, biking, and walking, none of which build lean skeletal muscle mass effectively or efficiently. Other factors that influence sarcopenia include poor food choices that are low in quality protein and the physiologic anorexia of aging. Muscle wasting is further perpetuated by declines in hormonal output and increases in inflammation. Social isolation, loneliness and depression can also play a role.

The metabolic effects of sarcopenia include a decrease in resting metabolic rate due to a decrease in lean-muscle mass as well as subsequent decreases in overall physical activity. This leads to frailty syndrome. While this is commonly seen as a geriatric problem, it really is an all-ages problem, particularly in women who are often striving to be thin and have under-eaten for the bulk of their lives. People often believe that, because they still fit into the same size pant from years prior, all is well; however, they could very well be carrying around significant fat stores and low muscle mass. Even in young women, body-mass index (BMI) appears to underestimate obesity. A recent study showed that while BMI classified some young women as normal weight, when body fat percent was measured by DEXA, there was a significant discrepancy: BMI showed only 32.5% as being overweight or obese while DEXA showed 48.6% as being obese. Biomarkers like leptin, high-sensitivity C-reactive protein (hsCRP), and IL-6 were significantly higher in the DEXA-identified obese group, as well.²

Age-related muscle loss is accompanied by other tissue changes. The physiologic processes of sarcopenia and osteoporosis occur nearly simultaneously. Sarcopenia results mainly in a loss of type II muscle fibers. Elderly adults suffer from a bone-muscle unit loss of 50% while the quality of the bones also deteriorate during this process.³ This becomes a self-perpetuating cycle that is further compounded by changes in nutritional and hormonal status. Furthermore, a hallmark of sarcopenia is fatty infiltration, where muscles fibers are replaced by adipose tissue. This fatty intramuscular infiltration significantly decreases muscle strength and is associated with increased risk of future mobility loss.^4,5 Loss of lean muscle mass, strength, and mobility are all critical factors in aging. Falls and fractures in the elderly are attributable to this loss of skeletal muscle mass, with the hip usually fracturing before the fall takes place. Sarcopenia has been shown to increase the risk of falls by up to 3 fold. Regardless of bone mineral density, the degree of fatty infiltration in muscles has been found to increase the risk of hip fractures.¹² The triad of bone, muscle, and adipose tissue impairment has recently been coined osteosarcopenic obesity syndrome.⁶

Inflammation perpetuates these tissue changes. Ectopic fat is known to be pro-inflammatory in nature. Inflammatory cytokines contribute to muscle catabolism,^7,8 an elevated inflammatory state is associated with loss of muscle mass, strength, and function,^9,10 and chronic systemic inflammation is a known contributor to cachexia.¹¹

Muscle as an Anti-Aging Therapy

Muscle comes into play as a major overall treatment of nearly every chronic degenerative condition. Skeletal muscles represent up to 40% of the total body mass and contain 50–75% of all body proteins.¹² Building skeletal muscle reverses causes of aging such as sarcopenia, tissue atrophy and loss of integrity, inflammation, obesity, blood sugar dysregulation, hormonal decline and related decreased libido, mitochondrial dysfunction, brain atrophy, and immune decline, to name a few. The simplest and fastest route to avoid and reverse sarcopenia is by simply lifting heavy things regularly. Strength training through lifting weights will accomplish this.

Skeletal muscle acts as an endocrine organ by secreting insulin-like growth factor (IGF)-1, which regulates insulin metabolism and stimulates protein synthesis. In response to progressive overload resistance exercise, IGF-I levels are substantially elevated, resulting in skeletal muscle hypertrophy.¹³ Skeletal muscles also secrete the myokines IL-6, IL-8, IL-15, brain-derived neurotrophic factor (BDNF), and leukemia inhibitory factor (LIF). BDNF is neuroprotective,¹⁴ and while IL-6 is a pro-inflammatory cytokine when produced in other parts of the body, when it is secreted by contracting skeletal muscle, it is anti-inflammatory.¹⁵ It may also increase glucose uptake into the muscle cells via increased glucose transporter type 4 (GLUT4) translocation, emphasizing the role of skeletal muscle in maintaining glucose homeostasis.¹⁶ The recently discovered myokine irisin is thought to mediate the beneficial effect of exercise by inducing browning in adipose tissue, which could improve metabolic health.¹⁷ The act of resistance training is known to lead to the increased production of testosterone, human growth hormone (HGH), and cortisol.^18,19 Type 2 and 3 iodothyronine deiodinases have been identified in skeletal muscle, indicating that skeletal muscle may also be a major target of thyroid hormone signaling.²⁰

The overall effects of sarcopenia include a decrease in resting metabolic rate and reduction in physical activity, which leads to an increase of fatty infiltrate and fat mass, particularly visceral fat. Visceral obesity is known to directly increase inflammation and insulin resistance, further contributing to the development and progression of sarcopenic obesity,²¹ and promoting atherosclerosis, neurodegeneration, and tumor growth.²²

The Benefits of Strength Training

Strength training has been shown to improve the status of many biomarkers that correlate with inflammation and disease. In one study, early improvements in biomarkers including triglycerides, LDL-cholesterol, HDL-cholesterol, and total cholesterol were noted, but with continued and prolonged strength training, improvements in CRP and glucose also occurred, suggesting that long-term support and training of skeletal muscle mass is the ticket to more pronounced metabolic improvements.²³ When considering that the worldwide rate of nonalcoholic steatohepatitis (NASH) is around 30%, strength training adds a powerful tool in its treatment. One study showed that, while resistance training did not reduce body weight significantly, and indeed overall weight loss was very slight, resistance training was specifically associated with a fall in the amount of liver fat on ultrasound examination.²⁴

Evidence suggests that mitochondrial dysfunction is a major contributor to sarcopenia and therefore aging. Resistance training has been shown to stimulate myofibrillary and muscular mitochondrial synthesis, as well as activation of signaling proteins. Mitochondrial impairment, normally seen with inactivity, is reversed with resistance training. Resistance training also appears to reverse the aging process at the phenotypic gene coding level.²⁵

Perhaps the most notable and immediate response to strength training is pain reduction. Clinical studies in patients with fibromyalgia, neck pain, back pain, and joint pain consistently support strength training as an effective pain reliever.^26-30 Pain reduction is a common and powerful side effect of gaining strength around a joint complex and the spine, as well as in the posterior chain muscle group. In the US, 2–5% of all doctor’s visits are for low back pain, which equates to $86 billion in healthcare costs.³¹ Americans spend at least $50 billion annually on treating low back pain, with indirect annual costs being estimated at over $100 billion.³² Most notably, those disabled by chronic low back pain account for as much as 80% of these annual costs.³³

An exciting application for strength training is the positive alteration of the immune system. One small study looked at 10 female multiple sclerosis patients who participated in an 8-week program of twice-weekly progressive resistance training. Pre- and post-training assessment of serum concentrations of cytokines IL-2, IL-4, IL-6, IL-10, CRP, TNF-α, and IFN-γ were measured. At the end of the study, at-rest levels of IL-4, IL-10, CRP, and IFN-γ were significantly reduced, while levels of TNF-α were non-significantly reduced, and IL-2 and IL-6 remained unchanged. These results suggest that progressive resistance training may have an impact on cytokine concentrations in individuals with MS and should be looked at more closely in larger studies.³⁴ In the elderly, immune function has been shown to be preserved more robustly in those who were physically conditioned. While short physical exercise programs do not appear to result in major reversal of immune senescence, highly conditioned elders have been found to display less evidence of immune senescence.³⁵

The anti-aging benefits of strength training may be partially explained by hormesis. Hormesis is the phenomenon by which exposure to low doses of a toxic or unhealthy substance or condition has a beneficial effect. For example, regular exposures to mild stress improve stress tolerance. A cornerstone of aging is a decrease in the adaptive abilities of an organism due to failure of maintenance and repair mechanisms. Hormetic processes can stimulate the pathways of maintenance and repair, which should lead to an anti-aging and anti-fragility response and improve the functional ability of cells and the organism overall.³⁶ Strength training induces a potent hormetic response. This hormetic stress, plus adequate recovery and re-feeding, is where the magic lies in successful strength training.

As with any sport, the guidance of a properly trained strength and conditioning coach is the ideal way for any patient to safely begin a treatment protocol of strength training. While muscle hypertrophy may be aesthetically pleasing, strength may be more important than muscle size. Fewer repetitions with heavier weights may produce a more robust hormetic response, and compound lifts like squats and deadlifts can give us more bang for our buck while also providing profound hormetic and hormonal benefits.³⁷ But big lifts like the deadlift and squat need to be taught and coached by a professional in order to be performed and programmed properly for the patient’s overall safety and well-being. Sending patients to a book reference or a website to learn the sport of weight lifting is like sending them to learn how to play hockey by themselves: knowing how to ice skate does not a safe and effective hockey player make.

Conclusion

The multitude of benefits derived from nourishing, building, and strengthening the skeletal muscle organ system has been described here with the hope that more clinicians will begin to appreciate muscle’s powerful impact on all disease processes. We are only beginning to understand the potent medicine that this organ system offers, and, as we learn more, we can all encourage our patients to take up the act of strength training as part of a complete naturopathic treatment plan.

References:

1. Grimby G, Saltin B. The ageing muscle. Clin Physiol. 1983;3(3):209–218.
2. Clark MK, Dillon JS. BMI misclassification, leptin, C-reactive protein, and interleukin-6 in young women with differing levels of lean and fat mass. Obes Res Clin Pract. 2011;5(2):e85–e92.
3. Ji HM, Han J, Won YY. Sarcopenia and Osteoporosis. Hip Pelvis. 2015;27(2):72–76.
4. Goodpaster BH, Carlson CL, Visser M, et al. Attenuation of skeletal muscle and strength in the elderly: the health ABC study. J Appl Physiol. 2001;90(2):2157–2165.
5. Visser M, Goodpaster BH, Kritchevsky SB, et al. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol.2005;60(3):324–333.
6. Ilich JZ, Kelly OJ, Inglis JE. Osteosarcopenic Obesity Syndrome: What Is It and How Can It Be Identified and Diagnosed? Curr Gerontol Geriatr Res. 2016;2016:7325973.
7. Garcia-Martinez C, Lopez-Soriano FJ, Argiles JM. Acute treatment with tumour necrosis factor-α induces changes in protein metabolism in rat skeletal muscle. Mol Cell Biochem. 1993;125(1):11–18.
8. Haddad F, Zaldivar F, Cooper DM, Adams GR. IL-6-induced skeletal muscle atrophy. J Appl Physiol. 2005:98(3):911–917.
9. Nicklas BJ, Hsu FC, Brinkley TJ, et al. Exercise training and plasma C-reactive protein and interleukin-6 in elderly people. J Am Geriatr Soc. 2008;56(11):2045–2052.
10. Schaap LA, Pluijm SMF, Deeg DJH et al. Higher inflammatory marker levels in older persons: associations with 5-year change in muscle mass and muscle strength. J Gerontol. 2009;64(11):1183–1189.
11. Seelaender M, Laviano A, Busquets S, et al. Inflammation in cachexia. Mediators Inflamm. 2015;2015:536954.
12. Frontera WR, Ochala J. Skeletal muscle: a brief review of structure and function. Calcif Tissue Int. 2015;96(3):183–195.
13. Singh MA, Ding W, Manfredi TJ, et al. Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders. A J Physiol. 1999;277(1):E135–E143.
14. Numakawa T, Suzuki S, Kumamaru E, et al. BDNF function and intracellular signaling in neurons. Histol and Histopathol. 2010, 25(2):237–258.
15. Pedersen BK. The anti-inflammatory effect of exercise: its role in diabetes and cardiovascular disease control. Essays Biochem. 2006;42:105–117.
16. Carey AL, Stenberg GR, Macaulay SL, et al. IL-6 increases insulin stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMPK.Diabetes. 2006;55:2688–2697.
17. Bostrom PA, Wu J, Jedrychowski MP, et al. A PGC1-a-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–468.
18. Kraemer WJ, Hakkinen K, Newton RU, et al. Effects of heavy-resistance training on hormonal response patterns in younger vs older men. J Appl Physiol. 1999;87(3):982–992.
19. Kraemer WJ, Ratamess NA. Endocrine responses and adaptations to strength and power training. Sports Med. 2005;35(4):339–361.
20. Salvatore D, Simonides WS, Dentice M, et al. Thyroid hormones and skeletal muscle — new insights and potential implications.Nature Rev Endocrinol. 2014;10(4):206–214.
21. Choi KM. Sarcopenia and sarcopenic obesity.Korean J Int Med. 2016;31(6):1054–1060.
22. Handschin C, Spiegelman BM. The role of exercise and PGC1alpha in inflammation and chronic disease.Nature. 2008;454(7203):463–469.
23. Ribeiro, AS, Tomeleri, CM, Souza, MF, et al. Effect of resistance training on C-reactive protein, blood glucose and lipid profile in older women with differing levels of RT experience. AGE. 2015;37:109.
24. Zelber-Sagi S, Buch A, Yeshua H, et al. Effect of resistance training on non-alcoholic fatty-liver disease: a randomized clinical trial. World J Gastroenterol. 2014;20(15):4382–4392.
25. Wilkinson SB, Phillips SM, Atherton PJ, et al. Differential effects of resistance and endurance exercise in the fed state on signalling molecule phosphorylation and protein synthesis in human muscle. J Physiol. 2008;586(15):3701–3717.
26. Collado-Mateo D, Dominguez-Muñoz FJ, Adsuar JC, et al. Effects of exergames on quality of life, pain and disease impact in women with fibromyalgia: A randomized controlled trial. Arch Phys Med Rehabil.2017;March 18. Epub Ahead of Print.
27. Lee BC, McGill SM. The effects of short-term isometrictraining on core/torso stiffness. J Strength Cond Res. 2015;29(6):1515–1526.
28. Sjøgaard G,Christensen JR, Justesen JB, et al. Exercise is more than medicine: The working age population’s well-being and productivity. J Sport Health Sci. 2016;5(2):159–165.
29. Andersen LL, KjÆr M, SØgaard K. Effect of two contrasting types of physical exercise on chronic neck muscle pain. Arthritis Rheum. 2008;59(1):84 –91.
30. Barene S,Holtermann A, Oseland H, et al. Effects on muscle strength, maximal jump height, flexibility and postural sway after soccer and Zumba exercise among female hospital employees: a 9-month randomised controlled trial.  J Sports Sci. 2016;34(19):1849.
31. Fritz JM, Magel JS, McFadden M, et al. Early physical therapy vs usual care in patients with recent-onset low back pain- A randomized clinical trial. 2015;314(14):1459–1467.
32. HoyD, March L, Brooks P, et al. The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014;73:968–974.
33. Chiodo AE, Alvarez D, Graziano G, et al.Acute Low Back Pain. University of Michigan: Guidelines for Clinical Care. http://www.med.umich.edu/1info/FHP/practiceguides/back/back.pdf. Updated 01/2010. Accessed 04/04/2017.
34. White LJ, Castellano V, McCoy SC. Cytokine responses to resistance training in people with multiple sclerosis. J Sports Sci. 2006;24(8):911–914.
35. Bruunsgaard H, Pedersen BK. Effects of exercise on the immune system in the elderly population. Immunology and Cell Biology.2000 Oct;78(5):523–531.
36. Rattan SIS, Eskildsen-Helmond YEG, Beedholm R. Molecular Mechanisms of Anti-Aging Hormetic Effects of Mild Heat Stress on Human Cells. Nonlinearity Biol Toxicol Med. 2004;2(2):105–116.
37. Gradari S, Pallé A, McGreevy KR, et al. Can Exercise Make You Smarter, Happier, and Have More Neurons? A Hormetic Perspective.Front Neurosci. 2016;10:93.

Dr Tyna Moore is the Medical Director of Core Wellness Clinic in Portland, OR. She specializes in the application of natural pain solutions and regenerative injection therapies to treat all varieties of musculoskeletal conditions. As both a Naturopathic and Chiropractic physician, she brings a unique perspective and expertise to the diagnosis and treatment of pain and orthopedic conditions. Dr Moore practices exclusively Regenerative Injection Therapies and non-surgical pain management for orthopedic and musculoskeletal conditions. Dr Moore teaches regenerative medicine around the world and educates physicians as well as the general public online at www.drtyna.com.