Exercise Enhancement
Exercise Enhancement
Last Section Update: 05/2022
Contributor(s): Shayna Sandhaus, PhD; Maureen Williams, ND; Stephen Tapanes, PhD
1 Overview
Summary and Quick Facts for Exercise Enhancement
- Evidence linking better cardiorespiratory fitness to improved health and longevity is overwhelming. In fact, maintaining cardiorespiratory fitness reduces risk of chronic diseases and death more than any drug.
- In this protocol, you will discover innovative ways to maximize the benefits of regular physical activity using an integrative approach. You will also learn about the performance-enhancing effects of various natural agents, including creatine, carnitine, whey protein, omega-3 fatty acids and vitamin D.
- In most people, cardiorespiratory fitness can be improved by performing moderate to intense physical activity on a consistent basis. Balance exercises may also help prevent falls in older adults.
Why is it Important to Exercise Regularly?
Physical inactivity is the fourth leading risk factor for premature death worldwide. Being physically active is one of the most important things you can do for your health. Everyone, regardless of age, gender, and ability, can benefit from regular exercise.
Accordingly, the evidence linking better cardiorespiratory fitness to improved health and longevity is overwhelming. In fact, maintaining cardiorespiratory fitness reduces risk of chronic diseases and death more than any pharmaceutical drug. Regular exercise slows down how quickly the body ages, and reduces the risk of cancer, dementia, osteoporosis, heart disease, stroke, depression, obesity, type 2 diabetes, and high blood pressure.
Exercise, including aerobics, strength or resistance training, stretching, and high-intensity interval training (HIIT), is one of the most powerful anti-aging strategies there is. Exercise powerfully activates a major longevity factor called AMPK (AMP-activated protein kinase)—a key regulator of energy metabolism that is linked to longevity. In addition, regular physical activity has been shown to support healthy immune function, enhance cognitive functioning, improve cardiovascular risk factors, improve age-related loss of muscle mass, and more.
Emerging research now shows that targeted natural interventions, such as creatine, carnitine, branched chain amino acids, glutamine, and vitamin D, can help maximize the health and longevity benefits of exercise.
How Much Exercise Do I Need?
The most recent report of the United States Department of Health and Human Services, updated in 2018, recommends that healthy adults engage in:
- 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous aerobic activity per week, or an equivalent combination; and
- Strength or resistance training at least twice per week.
The 2018 update also noted the following:
- Additional benefits can be obtained by engaging in more than 300 minutes of moderate-intensity activity or 150 minutes of vigorous-intensity activity per week.
- Older adults should target 150 minutes of moderate-intensity physical activity per week, or as much as their health and abilities allow.
- Additional activities that develop flexibility, agility, balance, and coordination (eg, yoga) are encouraged for all age groups.
What are Integrative Strategies to Enhance Exercise Performance?
- Hormone restoration for men and women. Studies in healthy older men have shown that hormone replacement therapy (HRT) increases exercise capacity and muscle strength. Post-menopausal women using conventional HRT had significantly greater improvements in exercise-induced insulin sensitivity than post-menopausal women not using HRT.
- More information is available in the Female Hormone Restoration and Male Hormone Restoration protocols.
- Dietary considerations. Consuming a carbohydrate-containing meal four to six hours before exercise ensures adequate reserves of glycogen (stored carbohydrate energy) in the muscle and liver. The International Society for Sports Nutrition recommends protein and carbohydrate consumption within three hours after exercise.
- Caffeine. Studies suggest caffeine ingested before or during exercise enhances endurance exercise performance. For example, competitively trained males who ingested 5 mg/kg body weight, equivalent to two to four cups of coffee for a 170-pound individual, lifted more total weight on the chest press and generated greater anaerobic power.
- Creatine. In older adults, creatine supplementation, with or without resistance exercise, enhanced muscle strength and mass, increased bone strength, and slowed the rate of sarcopenia. Creatine doses used in studies typically ranged from 5–21 grams per day for a 150-pound individual.
- L-carnitine. Studies demonstrated that supplementation with 2 grams of L-carnitine can improve exercise performance and recovery.
- Branched chain amino acids (leucine, isoleucine, and valine). In a double-blind placebo-controlled study, branched chain amino acid supplementation for three days increased resistance to fatigue and enhanced fat burning for fuel during exhaustive endurance exercise.
- Vitamin D. Sufficient blood levels of vitamin D are important for musculoskeletal injury prevention and recovery, and are associated with reduced inflammation and pain, stronger muscles, and better athletic performance.
- Glutamine. In a controlled two-week trial in male college-aged martial arts athletes, supplementation with 3 grams of glutamine daily for two weeks reduced muscle damage and prevented immune function declines, including during a strenuous training period.
2 Introduction
Physical inactivity is the fourth leading risk factor for premature death worldwide.1 Throughout human history, survival necessitated physical activity. Daily physical work defined and shaped the way the human body functions.
Today, a general lack of physical activity directly contributes to many chronic diseases and reduces life expectancy by about as much as smoking or obesity. Physical inactivity may account for nearly 10% of all premature deaths.2,3
Evidence linking better cardiorespiratory fitness to improved health and longevity is overwhelming.4-7 In fact, maintaining cardiorespiratory fitness reduces risk of chronic diseases and death more than any drug.8-11
Experts have called for a measurement of cardiorespiratory fitness, such as sub-maximal VO2 max estimates, to be added to routine cardiovascular health screening alongside more typical markers, such as cholesterol, blood pressure, and hemoglobin A1C.4,6,7
Physical activity can include a variety of enjoyable activities such as dancing, gardening, sightseeing, and other simple alternatives to sedentary behavior. Even 75 minutes of brisk walking per week has been linked to longevity and substantial health benefits.12
At the cellular level, exercise protects DNA against oxidative damage and rejuvenates energy-producing mitochondria.13-15 Exercise also activates AMPK (AMP-activated protein kinase)—a crucial regulator of energy metabolism.16
In this protocol, you will discover innovative ways to maximize the longevity benefits of regular physical activity using an integrative approach. For instance, hormone restoration, including impressive exercise-potentiating effects of the adrenal hormone DHEA, will be reviewed. You will also learn about the performance-enhancing effects of various natural agents, including creatine, carnitine, whey protein, omega-3 fatty acids, and vitamin D.
3 Types of Exercise
A comprehensive exercise program includes aerobic, muscle strengthening, flexibility, and balance exercises.17,18
Aerobic Exercise
Aerobic exercise is rhythmic and prolonged physical activity that elevates the heart and breathing rates. Examples of aerobic activity include fast walking, running, bicycling, and swimming. Aerobic training increases cardiorespiratory fitness, improves cerebral blood flow, and reduces the risk of death due to heart disease and all causes.17,19-21
"Aerobic exercise" refers to aerobic metabolism, in which oxygen is used to regenerate the energy-storing molecule ATP (adenosine triphosphate) in the mitochondria. Glucose in the blood, glycogen (stored carbohydrate) in muscle cells, and free fatty acids in blood and muscle cells provide fuel for ATP production.22
Muscle-Strengthening Exercise
Muscle-strengthening or resistance exercise involves forceful muscle contraction against external resistance.17 This type of exercise increases muscle strength, size, and endurance, and prevents sarcopenia, or age-related loss of muscle mass and strength. Strength training, when undertaken at an adequate pace, also improves cardiovascular endurance. Examples of muscle-strengthening exercise include weight training using free or machine weights, resistance bands, or body weight.17,18,23
Flexibility Exercise
Flexibility or stretching exercises entail slow and steady stretching of muscle groups. Stretches should be held for 10 to 60 seconds without jerking or bouncing, and repeated two or three times, progressively increasing the stretch. While mild discomfort is expected, flexibility exercises should not be painful, as pain may indicate minor muscle tearing. Flexibility exercise combined with muscle-strengthening exercises improve range of motion and relax muscles. Stretching before exercise may increase mental preparedness, but there is conflicting evidence as to whether it prevents injury. Stretching after exercise, when muscles are warm, may be more effective.17,24-26
Balance Exercise
Balance exercises, such as holding positions on one leg or using balance boards, may help individuals with awareness of motion and relative position problems and may also help prevent falls.17,27 The American Heart Association and American College of Sports Medicine recommend balance exercises for individuals who fall often or have mobility problems. The guidelines include recommendations for the following types of activities18:
- Increasing the difficulty of postures and decreasing the base of support, such as progressing from two-legged postures to one-legged postures
- Movements that disturb the center of gravity, such as heel-to-toe walking and turning in place
- Postures that stress certain muscle groups, such as standing on toes or heels
- Reducing sensory input, such as standing with eyes closed
Muscle strengthening exercise also improves balance by strengthening the muscles and tendons that support joints.17
Recent research has examined how different methods of exercise training affect various aspects of cellular biology, including telomerase activity and telomere length. Telomeres are structural components at the end of chromosomes that play a role in cellular aging and regeneration. During each cell division cycle, telomeres shorten. When they reach a critical length, the cell enters senescence. Shorter telomeres are associated with cardiovascular disease, obesity, and diabetes, as well as a reduced life expectancy. A healthy diet, non-sedentary lifestyle, and regular exercise may be associated with longer telomeres.28
Telomerases are enzymes that add nucleotides to telomeres, thus regulating telomere length. Research indicates telomeres may shorten in a progressive, age-related manner, but telomerase activity decreases steadily from age 4 to 39. After age 40, approximately 65% of people have low but stable telomerase activity levels, while approximately 35% have no detectable activity levels. Studies indicate active adults have an upregulation of telomeric binding factors, which protect telomeres from shortening, as compared to those that do not regularly exercise.29
Other observational studies suggest higher levels of physical activity are associated with longer telomeres, particularly in older individuals. This may be because exercise combats oxidative stress and inflammation, alters telomerase activity, and increases the number of skeletal muscle satellite cells (skeletal muscle precursor cells that help regenerate muscles after an injury).29
In one study, 124 healthy, previously inactive men were randomized into an aerobic endurance exercise group, a high-intensity interval group, a resistance training group, or a control group that did not exercise. Each intervention involved three 45-minute training sessions per week for six months.
VO2max was increased by all three training methods. Telomerase activity was up-regulated two- to three-fold in the endurance and interval training groups, but not the resistance group. White blood cell levels increased in the endurance and interval groups as well. A single bout of endurance training, but not resistance training, increased telomerase activity in certain leucocytes. Thus, aerobic activity may promote cellular health and healthy aging.30
More interventional studies are required to confirm the specific effects of exercise intensity and frequency on telomere length and telomerase activity.
What are the Best Exercises for Heart Health?
4 Benefits of Exercise
Anti-Aging Effects
Abundant evidence supports the anti-aging benefits of exercise. Even a modest amount of leisure time physical activity—just 75 minutes of brisk walking per week—has been associated with longer life expectancy.12 Also, regular exercise correlated with independence in a study of Japanese centenarians.41
Exercise influences several hallmarks of aging, including DNA repair, cellular senescence, and mitochondrial function.13 Resistance exercise decreases oxidative DNA damage in aging individuals14 and increases mitochondrial biogenesis—the creation of new mitochondria—in muscle and brain tissue.15
Exercise can help prevent cardiovascular disease during aging, and helps stave off sarcopenia, or age-related loss of muscle mass and strength.42,43 Improvements in muscle strength resulting from resistance exercise can increase functional capacity and reduce risk of disease and disability in old age.44 Physical activity, especially resistance strength training, also helps maintain healthy bone density during aging.45
Exercise also powerfully activates AMPK—a key regulator of energy metabolism and another major longevity factor.16 AMPK is an enzyme that promotes the burning of glucose and fats to generate cellular energy. AMPK also inhibits aberrant cell growth (ie, cancer), promotes the creation of new mitochondria, and increases insulin sensitivity.16,46,47
AMPK activation may be responsible for many of the health benefits of exercise; conversely, lack of AMPK activation may contribute to the detrimental health effects of a sedentary lifestyle.16,46
The antidiabetic agent metformin also activates AMPK and may mitigate other chronic diseases linked to inactivity, such as heart disease and cancer.46,48,49
Preclinical evidence suggests the magnitude of AMPK activation in response to exercise diminishes with age.50 Therefore, AMPK-activating agents, such as metformin and the plant extract Gynostemma pentaphyllum, may complement exercise in aging adults.
Protecting Against Immune Senescence
The progressive deterioration of the immune system that occurs with aging is termed immune senescence. Immune senescence is associated with poor response to vaccinations and increased risk of infection, cancer, cardiovascular disease, diabetes, and other age-related chronic diseases.51-53
Emerging evidence indicates regular exercise protects against immune senescence and may rejuvenate the aging immune system.51,54,55 In a study in healthy male subjects, those with better cardiorespiratory fitness had lower age-related accumulation of senescent and nonfunctional T cells—a signature feature of immune senescence.56
Human and animal studies have shown that regular exercise favorably affects other markers of immune senescence as well. These include an enhanced vaccination response, lower blood levels of inflammatory cytokines, greater natural killer (NK) cell activity, and better outcomes in viral infections and some cancers.57
Moderate-to-high intensity exercise (ie, 50% to 70% of maximal oxygen consumption) performed on a regular basis (eg, 30 minutes, five days per week) enhances immune function and lowers the incidence of chronic disease.51,55,58
Cardiovascular Protection
Exercise improves several cardiovascular risk parameters, including blood pressure, inflammation, glucose and insulin metabolism, endothelial function, cerebral blood flow, and blood lipids.59,60
A recent meta-analysis of nearly 400 randomized controlled trials with approximately 40,000 participants assessed the effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions and antihypertensive medications (angiotensin-converting enzyme inhibitors, angiotensin-2 receptor blockers, β-blockers, calcium channel blockers, and diuretics) on systolic blood pressure levels in normal and hypertensive individuals.
Endurance and resistance exercise and all classes of antihypertensives lowered systolic blood pressure, as compared with controls. This effect was greater with anti-hypertensive medications across all populations. Among those with hypertension, there was no difference between medication use and endurance or resistance exercise in lowering blood pressure levels. Further research is needed to understand more fully how exercise lowers systolic blood pressure.61
Exercise is also beneficial in the treatment of existing cardiovascular diseases.60,62 According to a review of 63 randomized controlled trials that enrolled nearly 15,000 patients with established coronary heart disease, exercise-based cardiac rehabilitation programs reduced mortality and hospitalizations due to heart disease. In the majority of these studies, exercise also improved patient quality of life.63
Note: Individuals with pre-existing cardiovascular disease should consult a qualified healthcare provider before embarking on an exercise program.
Cancer Protection
Being physically active reduces the risk of developing cancer and improves cancer outcomes. In 2018, the American College of Sports Medicine concluded that there is “…consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors….”285
For example, the DO-HEALTH trial enrolled over 2,100 participants aged 70 years or older and examined the effect of algae-derived omega-3 fatty acids (1,000 mg per day [approx. 333 mg EPA and 667 mg DHA]), vitamin D (50 mcg/day [2,000 IU]), and/or a simple home exercise program (SHEP) on invasive cancer incidence.286 Subjects were randomly divided into one of eight treatment groups, allowing the researchers to test the effects of different combinations of algae-derived omega-3s, vitamin D, and the strength-based home exercise program. These three active interventions, alone or in combination, were compared with placebo treatments and control flexibility exercises. Participants adhered to these treatment allocations for three years.
By the end of the three-year DO-HEALTH trial, each intervention—exercise, omega-3s, and vitamin D—significantly reduced the risk of cancer. However, the combination of all three interventions reduced cancer risk more so than any intervention alone or any combination of two interventions, as shown in Table 1 below:
Table 1. The DO-HEALTH Trial, Interventions and Outcomes | |
---|---|
Intervention |
Cancer Risk Reduction |
Home strength exercises (SHEP) alone |
26% |
Algae-derived omega-3 fatty acids alone |
30% |
Vitamin D alone |
24% |
Algae-derived omega-3 fatty acids and vitamin D |
47% |
Algae-derived omega-3 fatty acids and exercise |
48% |
Vitamin D and exercise |
44% |
All three interventions combined |
61% |
Physical activity is linked to reduced recurrence and mortality in multiple cancers, including breast and colon cancer.291,292 Being physically active can reduce cancer-related fatigue during and after cancer treatment, as well as improve quality of life and reduce treatment side effects.293-295 Exercise has also been shown in various clinical studies to improve body image and mental wellbeing, including reducing anxiety and depression associated with a cancer diagnosis.296
The mechanism(s) by which exercise protects against cancer and improves cancer outcomes are complex and multifactorial. Exercise consumes a lot of energy and causes intracellular metabolic changes, presumably leading to changes in the tumor cells as well. For instance, exercise may attenuate certain metabolic aberrations that underlie cancer cells’ propensity for rapid growth and proliferation.297 Physical activity also has immune-modulating effects, mobilizing cytotoxic immune cells like NK cells that are essential for mounting an immune response against cancer.298,299 Regular moderate-to-vigorous exercise may also decrease the risk of cancer by ameliorating insulin resistance and reducing levels of insulin-like growth factor-1 (IGF-1).300
Cognitive Health
Physical activity can prevent cognitive decline in older adults and reduce the risk of neurological diseases, such as Alzheimer disease and Parkinson disease. Aerobic exercise reduces the loss of brain tissue that occurs with aging.64-68
Abundant evidence indicates physical activity and exercise enhance cognitive functioning and wellbeing across the human lifespan.64,69,70 In a study in 2,747 young adults aged 18‒30 years, greater aerobic fitness was associated with better verbal memory and faster psychomotor speed in middle age.70 Similarly, another study found middle-aged participants who engaged in the most leisure time physical activity were less likely to develop dementia 28 years later as compared with less-active participants.69
Exercise improves cognitive health by enhancing the transmission of information between nerve cells. Brain-derived neurotrophic factor, a signaling protein, appears to play a critical role in this process. Exercise increases the production of brain-derived neurotrophic factor in an area of the brain called the hippocampus, which is vital to learning and memory. Intriguingly, exercise may even increase the size of the hippocampus.64,65
Weight Management
According to recommendations from the American Heart Association and American College of Cardiology, long-term weight loss is best attained with lifestyle change that includes both a low-calorie diet and increased physical activity.71,72
Protection Against Diabetes
Exercise increases insulin sensitivity, helps control blood glucose levels, and improves cardiovascular risk factors, such as high blood pressure and elevated blood fats. Even a single exercise session induces many of these beneficial effects.73-75
Randomized trials have shown that combining physical activity with modest weight loss lowers type 2 diabetes risk by up to 58% in high-risk populations.73,74 In a four-year randomized controlled lifestyle-intervention trial, increased physical activity along with reduced caloric intake resulted in partial or complete remission of diabetes in 11.5% of participants during the first year; 7.3% of participants remained in partial or complete remission after four years.76
Chronic Pain Management
A detailed analysis of 264 published studies, which included nearly 20,000 participants, found that exercise and physical activity is associated with modest improvements in pain, functional capacity, and quality of life. Another review of published studies found that high-intensity strength exercises performed in the workplace three times weekly for 20 minutes markedly reduced pain in the shoulders and spine.77 In a separate analysis, supervised and home-based progressive shoulder strengthening and stretching exercises relieved shoulder pain. For low-grade shoulder pain, exercise provided short-term benefits similar in magnitude to a single steroid injection.78
Preventing Functional Decline with Age: Sarcopenia and Osteoporosis
Sarcopenia refers to progressive loss of muscle mass and strength with age. Osteoporosis is a condition marked by low bone mass, increased bone fragility, and greater fracture risk. Sarcopenia and osteoporosis are both common in older adults; increase risk of falls and fractures; and are linked to frailty, decreased mobility, and a higher risk of death.42,79-85
Physical activity and exercise training, including aerobic activity and strength training, increase bone mass, muscular strength, balance, and mobility.86-88 A review of the scientific literature found regular physical activity is the only intervention that consistently improves frailty and sarcopenia as well as functional performance in older adults.43
Improvements in physical function resulting from exercise have been demonstrated even in the frail elderly, including those living in institutional settings.89,90 A regular program of both aerobic and strength exercise is recommended for adults as well as frail older persons.43
Gut Microbiome Modulation
Microbes in the gastrointestinal tract play a critical role in human health. Increased microbial diversity has been associated with improved metabolism, immune function, and overall health. Disturbances to the balance of these microbes, including reduced diversity of the gut microbiome, have been linked to a wide range of diseases, including obesity, metabolic syndrome, and inflammatory bowel disease.91-94
While a range of factors, such as diet and antibiotic usage, influence the gut microbiome, early evidence suggests exercise may have a positive influence on the gut flora.91 In one study, professional athletes had a significantly higher diversity of gut microorganisms than control groups. Dietary differences between the athletes and control groups may have accounted for some of these effects.93,95
A study in mice found exercise altered gut microbial composition, improved intestinal structural integrity, and reduced gastrointestinal inflammation.96 In another study in mice, exercise increased abundance and diversity of the gut microbiome and protected against a toxin-induced reduction in microbial abundance.97
5 How Much Exercise Do I Need?
Any level of physical activity is preferable to no activity. People who engage in even low levels of physical activity appear to have a 20% reduced risk of death compared with those who are sedentary.18,24,98-100
Every 10 years, the United States Department of Health and Human Services publishes updated Physical Activity Guidelines for Americans.101 Their most recent report recommends adults get 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous aerobic activity per week, or an equivalent combination. In addition, strength or resistance training should be performed at least twice per week.
The report also indicates that more substantial health benefits can be obtained with 300 minutes of moderate-intensity activity or 150 minutes of vigorous-intensity activity each week.
Older adults should target 150 minutes of moderate-intensity physical activity per week, or as much as their health will allow. Balance exercises may also help prevent falls in older adults.
Activities, such as yoga, that develop flexibility, agility, balance, and coordination are also encouraged for all age groups.18,24,98-100
Assessing Cardiorespiratory FitnessDespite its vital importance, cardiorespiratory fitness is not included in ordinary clinical assessment. An urgent need exists to incorporate aerobic exercise testing alongside traditional measurements of blood pressure, glucose, and cholesterol in individual cardiovascular risk assessments.4,7 Cardiorespiratory fitness can be assessed by measuring maximal oxygen uptake, also known as VO2max—the maximum ability of the body to utilize oxygen during exercise. However, direct measurement of VO2max requires maximal physical effort, which is often difficult and may be unsafe for some aging individuals.102,103 Submaximal exercise testing is a popular and more practical alternative to assess aerobic fitness. This approach estimates VO2max by determining the heart rate response to submaximal intensity exercise, such as stair stepping, cycling, or running (or walking) on a treadmill.102-104 These types of tests are accessible through fitness centers or sports medicine facilities. If you are interested in having a submaximal exercise test, check with your healthcare provider. In most people, cardiorespiratory fitness can be improved by performing moderate-to-intense physical activity on a consistent basis.3,7 |
6 Strategies for Enhancing Exercise
Hormone Restoration (Men and Woman)
Age-related decline in levels of testosterone and growth hormone are associated with loss of muscle mass and strength, exercise capacity, and mobility in elderly men. In addition, aging is associated with accumulation of body fat and insulin resistance.105 Diminished muscle mass and strength in the elderly are also accompanied by the rapid age-related decline in the hormone DHEA (dehydroepiandrosterone).106
Testosterone and growth hormone are potent anabolic (tissue-building) agents that increase muscle mass, but they act through different mechanisms. The combination of testosterone and growth hormone has a greater anabolic effect than either hormone alone. In fact, studies in healthy older men have shown that hormone replacement therapy (HRT) with a combined regimen of testosterone and growth hormone, but not either one alone, increased exercise capacity and muscle strength.
Collectively, these studies indicate treatment with moderate doses of testosterone and growth hormone is safe over a six-month period.105 However, long-term use of growth hormone therapy may increase the risk of some cancers.107 People at risk for cancer should consult a healthcare provider before initiating growth hormone therapy, and long-term use may be unwise.
For more information about HRT, see Life Extension's Male Hormone Restoration protocol.
In women, HRT using estrogen and progesterone may also enhance the effects of exercise. In one study, post-menopausal women using conventional HRT had significantly greater improvements in exercise-induced insulin sensitivity than post-menopausal women not using HRT.108
Bioidentical hormone replacement therapy (BHT)—including progesterone, estradiol, and estriol—has become a popular alternative to traditional HRT for the treatment of menopausal symptoms. Bioidentical hormones are structurally identical to human hormones.109-111
Data from a review of studies found the use of bioidentical hormones carries a lower risk of breast cancer and cardiovascular disease, and treatment with BHT has been as effective as conventional HRT for the treatment of menopausal symptoms.112,113 For more information on BHT, see the Life Extension's Female Hormone Restoration protocol.
Dietary Considerations
Proper timing of meals can enhance exercise capacity and aid recovery and tissue repair following exercise.114-116
Consuming a carbohydrate-containing meal four to six hours before exercise ensures adequate reserves of glycogen (stored carbohydrate energy) in muscle and liver. An additional carbohydrate plus protein snack, consumed 30 to 60 minutes prior to exercise, may protect against energy depletion towards the end of an intense exercise session, as well as help prevent breakdown of protein in muscle tissue.115
During prolonged intense exercise (ie, greater than 60 minutes), beverages (10‒15 fl. oz.) containing carbohydrate and electrolytes should be ingested every 15–20 minutes to prevent low blood sugar levels.115
Post-exercise nutrition is important to help replenish glycogen stores and repair muscle tissue damaged during exercise. The International Society for Sports Nutrition recommends protein and carbohydrate consumption within three hours after exercise.115,117
Elderly individuals may require greater post-exercise protein intake to maximize recovery.117 One study showed 20 grams of post-exercise supplemental protein maximally stimulated muscle protein synthesis in young men118; another study found that in elderly men, 40 grams of post-exercise whey protein enhanced muscle protein synthesis more than 20 grams of whey protein.119
Caffeine
Studies suggest caffeine ingested before or during exercise enhances endurance exercise performance. Emerging research also suggests caffeine aids in short-term, high-intensity burst activity performance. For example, competitively trained males who ingested 5 mg/kg body weight of caffeine lifted more total weight on the chest press and generated greater anaerobic power.120 This dose of caffeine corresponds to about 2‒4 cups of coffee for a 170-pound individual.121,122 Approximately 150 to 300 mg of caffeine, or about one to three cups of coffee, has been shown to improve concentration and decision making during and after exhausting exercise.121
Possible mechanisms for the ergogenic effects of caffeine include increased fat burning, reduced fatigue, central nervous system stimulation, and reduced perception of pain.121,123,124 The stimulant effect of caffeine is primarily due to its ability to block adenosine receptors in the brain.125,126
Possible side effects of caffeine consumption include increased heart rate, disturbed sleep, and nervousness; these are generally less pronounced with lower doses.121 The response to caffeine varies considerably from person-to-person.127-129 A recent review suggested older adults may be more susceptible to the sleep-disrupting effects of caffeine than younger individuals, so awareness of sleep quality and modifying caffeine use appropriately is important.130
7 Nutrients
Primary Support
Creatine. Creatine is a compound naturally produced in the body that can also be obtained through the diet, predominantly meats and fish. Not only is supplemental creatine one of the most popular and well-researched ergogenic (performance-enhancing) aids used by athletes,131,132 it is also an effective agent for preventing or slowing age-related muscle loss—known as sarcopenia—and has improved cognitive performance in the elderly.133-135 Mouse studies indicate creatine may hold potential anti-aging effects.136
Numerous studies have shown that creatine supplements can increase muscle mass and enhance athletic performance.132,135 Creatine is most effective as an aid to high-intensity, short-duration activities (eg, sprinting or weight lifting), which derive energy from creatine phosphate.22,131,137
In older adults, creatine supplementation, with or without resistance exercise, has enhanced muscle strength and mass, increased bone strength, and slowed the rate of sarcopenia.134,138 Furthermore, according to one analysis, combining creatine supplementation with muscle strengthening exercise is more effective than exercise alone in increasing muscle mass, strength, and functional performance in older men and women.133
Creatine doses used in studies that enrolled aging subjects typically ranged from 5–21 grams per day, for a 150-pound individual, for limited periods of time.138 Taking creatine supplements with carbohydrate, or protein and carbohydrate, may increase creatine muscle retention.132
L-carnitine. L-carnitine is a compound obtained from food and synthesized in the body from the essential amino acids lysine and methionine. It is required for burning fat for energy production within the mitochondria, and can act as a free radical scavenger.139
Studies have demonstrated that L-carnitine supplementation can improve exercise performance and recovery.139,140 In a randomized, double-blind, placebo-controlled trial, healthy male volunteers who ingested 2 grams of L-carnitine along with 80 grams of carbohydrate twice daily for 24 weeks exhibited 21% increased muscle carnitine content, compared with no change in the control group. This was associated with reduced perception of effort and improvement in exercise performance.140
By reducing free radical generation and muscle soreness, L-carnitine supplementation supports muscle recovery after strenuous exercise.141,142 In a placebo-controlled trial in healthy young men, oral supplementation with 2 grams of L-carnitine for two weeks resulted in significantly reduced markers of oxidative stress and muscle damage following an acute bout of exercise.139
Branched chain amino acids. The essential branched chain amino acids (BCAAs) leucine, isoleucine, and valine are important for the synthesis of muscle protein and are burned by muscle cells for energy.143-147
Human and animal studies have shown that supplemental intake of BCAAs increases exercise endurance.148-150 In a double-blind placebo-controlled study, BCAA supplementation for three days increased fatigue resistance and enhanced fat burning for fuel during an exhaustive bout of endurance exercise that caused glycogen (stored carbohydrate) depletion.151
Like other essential amino acids, BCAAs function as precursors (building blocks) for muscle protein synthesis.152 Importantly, BCAAs, especially leucine, also exert anabolic effects by directly stimulating muscle growth and inhibiting muscle protein degradation.143,153,154
By reducing breakdown of muscle proteins and promoting protein synthesis, BCAAs improve exercise recovery.143,154 In a study in long-distance runners undergoing intense training, BCAA supplementation reduced soreness and fatigue, as well as markers of inflammation and muscle damage.155
Vitamin D. Vitamin D plays an essential role in bone metabolism, muscle function, and immune health. Sufficient blood levels of vitamin D are important for musculoskeletal injury prevention and recovery, and are associated with reduced inflammation and pain, stronger muscles, and better athletic performance.156,157
Apart from its role in preventing fractures and muscle injuries, research also suggests vitamin D may have performance-enhancing effects. Unfortunately, many athletes are vitamin D deficient.156,158 Trials of supplemental vitamin D at dosages of 3,300 to 5,000 IU daily have found improvements in sprinting and jumping performance as well as increased circulating testosterone.156,158,159
One team of scientists suggested supplementing with 4,000 to 5,000 IU per day of vitamin D3, along with 50 to 1,000 mcg per day of a mixture of vitamins K1 and K2 to complement vitamin D’s role in bone and calcium metabolism, could support athletic performance by improving recovery time and muscle function.158
Glutamine. Glutamine, because it is synthesized in the body, is a non-essential amino acid. However, glutamine becomes "conditionally essential" when blood levels are reduced in times of illness and stress.160-163
Glutamine plays a role in immune response to muscle damage.162,164,165 In a controlled two-week trial in male college-aged martial arts athletes, supplementation with 3 grams of glutamine daily for two weeks reduced muscle damage and prevented immune function decline, including during a strenuous training period.166 A controlled clinical trial that used 10 grams of glutamine daily for three weeks in athletes undergoing intensive training found an improvement in immunity as evidenced by white blood cell profiles, including an increase in NK cell activity.167 Another controlled clinical trial found athletes given 5 grams of glutamine immediately after and two hours after intense, prolonged exercise reported roughly 40% fewer upper respiratory infections than those given placebo.168
DHEA. Produced by the adrenal glands, dehydroepiandrosterone (DHEA), along with its sulfated form, DHEA-S, is the most abundant steroid hormone in circulation.169,170 DHEA is a precursor of sex hormones, such as estrogens and androgens. DHEA levels peak around age 25 and decline by roughly 80% by age 75.106,171
Studies show DHEA supplementation has exercise-enhancing effects.106,172 In a study in elderly men and women, DHEA supplementation significantly enhanced muscle growth and strength in response to resistance exercise.106
In a randomized controlled trial, a single dose of 50 mg DHEA increased free testosterone levels above baseline in middle-aged men. This dosing was followed by a bout of HIIT, after which free testosterone remained elevated in the DHEA-supplemented middle-aged individuals.172
Whey protein. Whey protein, a group of milk-derived proteins with a high concentration of essential amino acids and BCAAs, activates muscle protein synthesis and recovery in response to resistance exercise.173 Whey protein supplementation significantly decreases body weight and body fat and increases lean body mass when combined with resistance training.173-176
Whey protein is rapidly digested and absorbed. Leucine, one of the BCAAs in which whey protein is especially rich, plays an important role in muscle protein metabolism, healthy glucose metabolism, and body weight maintenance.147,173,177
In one study, whey protein given to healthy subjects during recovery from maximal-effort exercise significantly increased the amount of muscle satellite cells. These satellite cells, or stem cells, are essential for muscle regeneration.176,178 In another study, high-leucine whey protein hydrolysate was more effective than placebo at increasing muscle and tendon growth after 12 weeks of leg resistance exercise (knee extensor training).179
HMB (β-hydroxy β-methylbutyrate). HMB is a metabolite of the amino acid leucine that helps maintain muscle function and support muscle growth and strength.240 HMB preserves the structure of muscles and supports resistance and endurance training performance.241,242 One potential mechanism of action is the regulation of cell signaling pathways involved in protein synthesis.243
In a randomized, placebo-controlled, double-blind study, 19 healthy older adults were confined to bed rest for 10 days and then underwent eight weeks of a resistance training program. Subjects took either placebo or 1.5 grams CaHMB (calcium β-hydroxy β-methylbutyrate) twice daily from five days before bed rest throughout the rehab program. Those who took the placebo experienced a significant decrease in lean body mass after being on bed rest, while nearly all of those in the treatment group had preserved muscle mass.244 In another randomized placebo-controlled study, 13 subjects accustomed to intense endurance exercise received either placebo or 3 grams HMB per day. After six weeks of daily training and supplementation, all subjects went on a 20 kilometer (12.4 mile) run and then were assessed for muscle damage. The post-run increase in levels of creatine phosphokinase and lactate dehydrogenase, two markers of muscle damage, was reduced in those taking HMB compared with placebo.245
In another double-blind, randomized, placebo controlled trial, approximately 80 people over age 65 were divided into one of four groups: two non-exercise groups, one of which took a placebo and one that took 3 grams CaHMB twice daily, and two resistance exercise groups, one of which took a placebo and another that took 3 grams CaHMB twice daily. Resistance exercise improved lean body mass and performance measures, such as hand grip strength, while supplementation with CaHMB without exercise improved strength and muscle quality. The CaHMB and exercise group showed improvements in weight loss and fat loss, and the authors concluded that “strength, muscle quality, body composition, and functionality in healthy older men and women can be improved through CaHMB supplementation, with and without resistance training.”246
In another trial, 20 men experienced in resistance training were randomly assigned to take 3 grams HMB-FA (the free acid form of HMB) or a placebo before undergoing a resistance training session. Measurements of muscle damage, muscle protein breakdown, and subjective exercise recovery were then taken. The results suggest HMB-FA, when given to trained athletes before exercise, can reduce muscle damage and subjective recovery time.247 A meta-analysis that examined nine studies determined that HMB supplementation during resistance training supports overall and leg strength gains in previously untrained men.248
Carnosine and beta [β]-alanine. Carnosine is a substance naturally produced in the body from the precursors beta [β]-alanine and histidine. It is highly concentrated in brain tissue and muscle. Although well-known for its anti-glycation effects, accumulating evidence suggests carnosine plays important roles in exercise performance and skeletal muscle health. The carnosine component β-alanine also displays ergogenic properties. As it is a precursor to carnosine, multiple studies have used β-alanine supplementation to increase carnosine levels and enhance exercise performance.267-269
Carnosine protects muscles from exercise-related oxidative stress, and buffers lactic acid buildup to reduce muscle fatigue.270 A clinical study in 14 male athletes found that supplementation with 4 grams carnosine daily for 14 days led to a significant attenuation in exercise-induced glutathione loss while also reducing markers of oxidative stress.271
A meta-analysis of 40 individual studies comprising 1,461 participants identified a significant positive overall effect of β-alanine supplementation (ranging from 2 to 6.4 grams daily for 4‒12 weeks), supporting the efficacy of increased muscle carnosine on improved exercise performance and capacity.272 A randomized placebo-controlled trial examining 23 highly trained judo athletes found participants who consumed 6.4 grams β-alanine daily showed a significant improvement in exercise endurance at four weeks.273 In another controlled trial, 30 healthy strength-trained individuals were assigned to placebo or 6.4 grams β-alanine daily for five weeks, after which the β-alanine group showed significant improvements in maximal strength and power output.274 A study that enrolled 12 healthy participants found supplementation with 2 grams carnosine plus 2 grams β-alanine four hours before exercise tests improved some measures of muscle performance and endurance.275
In two double-blind, placebo-controlled, crossover studies, supplementation with 20 mg/kg bodyweight of carnosine plus anserine, a methylated version of carnosine with improved half-life, led to significantly higher power on a standardized fitness test following 6 minutes of high-intensity cycling.276 In another randomized controlled trial of 50 patients with stable chronic heart failure and severe left-ventricular systolic dysfunction, already on optimal medical therapy, 500 mg of carnosine daily in lozenge form for six months led to improved walking distance in the 6-minute walking test and increased aerobic capacity during exercise.277
Overall, many studies have shown positive effects of supplementation with carnosine and/or β-alanine for exercise and sports performance.272,278 However, the literature is not completely consistent. Several studies have reported little or no effect of β-alanine supplementation on measures of exercise performance.279-282 Some authors have suggested the variability of observed effects may be due to variable physiological demands of different sports activities or baseline characteristics of study participants, such as overall nutrition, degree of fitness, and sleep habits.283,284 More studies with large sample sizes and rigorous methodologies are needed to clarify the efficacy of carnosine and/or β-alanine supplementation on exercise performance.
Additional Support
D-ribose. D-ribose is the biologically active form of the naturally occurring sugar, ribose, and is produced in the body from glucose. Ribose is involved in the synthesis of ATP, which provides energy to muscle cells during exercise. Supplementation with ribose has accelerated ATP synthesis following its depletion during intense exercise.180-182
A controlled trial in 12 male recreational body builders found that supplementation with 10 grams of ribose per day for four weeks resulted in greater gains in muscle strength and endurance than placebo.183 D-ribose may also help combat fatigue and improve mood and vitality in aging adults,184 which may allow for increased exercise frequency. A dosing study found taking D-ribose on an empty stomach leads to more efficient absorption than taking it with food.185
Periodically, concerns arise regarding the potential of D-ribose to promote damaging glycation reactions. While ribose can contribute to glycation reactions when present in high concentrations, the amount of D-ribose attained through supplementation is not worrisome. These concerns have been addressed thoroughly in an article titled Restoring Cellular Energy Metabolism in the October 2012 issue of Life Extension Magazine.
Omega-3 fatty acids. A growing body of evidence supports the use of omega-3 fats to improve recovery from strenuous exercise.186,187 Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA), can be beneficial in the prevention and treatment of sarcopenia.188,189 In a controlled study in older adults, daily supplementation with omega-3 fatty acids containing over 1.8 grams of EPA and 1.5 grams of docosahexaenoic acid (DHA) increased the rate of muscle protein synthesis compared with a corn oil, which provided no benefit.189
Coenzyme Q10. Coenzyme Q10 (CoQ10) is an essential component of the series of biochemical reactions that generate energy in the cell’s mitochondria. CoQ10 also functions as a free radical scavenger, protecting cells against oxidative damage.190-192 Clinical studies have demonstrated an exercise-enhancing effect of CoQ10 supplementation.193,194 In a study in trained and untrained individuals, supplementation with 100 mg of CoQ10 for 14 days increased the length of time participants could exercise before reaching exhaustion.194
A randomized controlled study in male runners found that 14 days of CoQ10 supplementation reduced the spike in blood levels of lactate, interleukin-6, tumor necrosis factor-alpha, and C-reactive protein induced by a bout of middle-distance competitive running.195 The dose of CoQ10 used in the study was 5 mg/kg/day, or about 350 mg per day for a 155-pound person.
In an animal study, rats were supplemented with CoQ10 for six weeks during exercise training. This produced beneficial changes in levels of key regulatory proteins, including nuclear factor-kappaB and Nrf2, both of which defend against inflammation and oxidative stress.191
Arginine. Arginine is a conditionally essential amino acid that participates in a variety of metabolic pathways, including protein synthesis. Importantly, arginine is a precursor of nitric oxide (NO), a potent vasodilator. Arginine supplementation may increase blood flow to muscles.196-198
In a controlled clinical trial in competitive male cyclists, supplementation with 6 grams of L-arginine daily for three days increased 20 kilometer time trial performance, reduced oxygen consumption, and reduced systolic and diastolic blood pressure.199 In another controlled clinical trial in untrained college-aged men, supplementation with a product containing 1.5 grams or 3 grams of arginine (along with grape seed extract) for four weeks reduced the time to onset of cycling-induced fatigue as compared with placebo.196
Animal studies indicate arginine supplementation may be beneficial for exercise recovery.200,201 In one study, L-arginine supplementation before a single bout of exercise reduced muscle fiber damage and maintained exercise performance capacity in rats. These effects were attributed to increased muscle nitric oxide content.200
Resveratrol. Resveratrol is a polyphenol compound found in plants and plant foods such as grapes, red wine, peanuts, and Japanese knotweed.202,203 Resveratrol has been shown to favorably influence several factors involved in chronic degenerative diseases, including inflammation, insulin sensitivity, oxidative stress, and endothelial dysfunction.204-208
There is clinical and preclinical evidence that resveratrol can augment the effects of exercise on muscle mitochondrial capacity, increasing energy production and utilization.204,209 In a double-blind placebo-controlled trial in healthy young adults, daily supplementation with 500 mg of resveratrol, plus 10 mg of piperine, a black pepper extract, combined with low-intensity endurance exercise for four weeks significantly increased muscle mitochondrial capacity.204
Two animal studies found resveratrol supplementation improved exercise performance compared with exercise alone.210,211 In one study, rats fed a diet supplemented with resveratrol during 12 weeks of exercise training were able to run longer and further than rats trained without resveratrol. Improved muscle strength was also noted in resveratrol-treated rats.211
Gynostemma pentaphyllum. Gynostemma pentaphyllum is an herb with a long history of use in Chinese medicine as a health tonic. Components of Gynostemma have been shown in preclinical research to activate AMPK—a major regulator of glucose, fat, and energy metabolism in the body.212,213
Animal studies have demonstrated the anti-fatigue effects of Gynostemma.212,214 In one of these studies, polysaccharides derived from Gynostemma extended the exhaustive swimming time of rats. The Gynostemma polysaccharide extracts also lowered blood lactic acid levels and increased liver and muscle glycogen concentrations.212
A study in mice found that the prolonged time to exhaustion from exercise after administration of Gynostemma polysaccharides was linked to reduced oxidative stress and enhanced muscle glycogen levels.214
Cordyceps sinensis. Cordyceps sinensis is a medicinal mushroom used for centuries in China and India to promote vigor, endurance, and longevity.215-217 Scientific studies have found that Cordyceps mycelia boosts exercise performance.216,218
In a double-blind placebo-controlled trial in adults aged 50 to 75 years, 12 weeks of supplementation with an extract of Cordyceps sinensis fermented mycelium delayed fatigue and resulted in improved aerobic performance on an exercise test.215
Another animal study found Cordyceps sinensis mycelia may mimic some of the metabolic benefits of exercise. Supplementation with Cordyceps sinensis in rats increased exercise endurance, despite a lack of training. Significant AMPK activation was thought to be partly responsible for this effect.218 Potential mechanisms for the exercise-enhancing effects of Cordyceps include improved blood sugar regulation, increased insulin sensitivity, and greater production of ATP—the cell’s energy source.215,218
Panax ginseng. Panax ginseng (also called Chinese or Korean ginseng) is a popular herbal medicine used worldwide to increase physical strength and reduce fatigue.219-221 Potential mechanisms for the performance-enhancing effects of ginseng root include improved fat utilization for energy (while sparing glycogen), increased levels of the vasodilating molecule nitric oxide, and mild central nervous system stimulation.219,220,222-226 Multiple clinical trials and animal studies have shown ginseng improves exercise performance and prevents fatigue. It may have stronger effects in older and recreational athletes.220,222,224,226-228
Ginseng appears to delay exercise-induced fatigue.220,221,225,229 In a controlled study in healthy male subjects, eight weeks of supplemental Panax ginseng root extract prior to exercise on a treadmill decreased formation of malondialdehyde—a marker of oxidative stress. Exercise time to exhaustion was significantly prolonged.226
Two types of compounds in ginseng—polysaccharides and ginsenosides—are thought to contribute to its fatigue-fighting properties.219,223,224
Ginsenosides are converted to bioactive compounds, such as compound K, by intestinal bacteria.230 Compound K possesses anticancer, anti-inflammatory, and anti-allergic properties, and contributes to the health-enhancing effects of ginseng.230,231 Fermented ginseng contains compound K, making fermentation one method of enhancing bioavailability.232,233
Rhodiola rosea. Found in mountainous areas of Europe, Asia, and North America, Rhodiola rosea is an herb with a long history of use in traditional medicine as an anti-fatigue, anti-stress, and mood-enhancing agent. Studies have also shown that Rhodiola has positive effects on exercise performance and endurance in humans and animals.234-237 Rhodiola is an adaptogen, increasing the body’s ability to adapt to the stress of physical exercise.238,239 Rhodiola also increases utilization of fat for energy, improves mitochondrial function, and suppresses free radicals.216,238,239
In one controlled trial in active young women, rhodiola improved endurance exercise performance by reducing perceived effort. Subjects given a single oral dose (3 mg/kg body weight, or about 200 mg for a 150-pound person) of rhodiola completed a six-mile time trial on a stationary bicycle significantly faster that subjects given placebo. Rhodiola also lowered the heart rate response to submaximal exercise in this study.234
Another placebo-controlled trial measured the effect of a rhodiola extract standardized to contain 3% rosavins and 1% salidroside in 24 participants. Researchers noted endurance exercise capacity improved one hour after an acute dose of 200 mg of rhodiola extract.237
Rhodiola may lessen exercise-induced muscle damage. In a study in male athletes, four weeks of rhodiola supplementation prior to exhaustive endurance exercise significantly decreased markers of muscle damage. Notably, serum levels of creatine kinase, which rise after vigorous exercise, substantially decreased after rhodiola ingestion.238
Disclaimer and Safety Information
This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.
The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.
- WHO. World Health Organization. 10 facts on physical activity. http://www.who.int/features/factfiles/physical_activity/en/. Last updated 2/2014. Accessed 12/28/2016.
- Lee IM, Shiroma EJ, Lobelo F, Puska P, Blair SN, Katzmarzyk PT. Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. Jul 21 2012;380(9838):219-229.
- Bouchard C, Blair SN, Katzmarzyk PT. Less Sitting, More Physical Activity, or Higher Fitness? Mayo Clinic proceedings. Nov 2015;90(11):1533-1540.
- Despres JP. Physical Activity, Sedentary Behaviours, and Cardiovascular Health: When Will Cardiorespiratory Fitness Become a Vital Sign? The Canadian journal of cardiology. Apr 2016;32(4):505-513.
- Lakoski SG, Willis BL, Barlow CE, Leonard D, Gao A, Radford NB, . . . Jones LW. Midlife Cardiorespiratory Fitness, Incident Cancer, and Survival After Cancer in Men: The Cooper Center Longitudinal Study. JAMA Oncol. May 2015;1(2):231-237.
- Kaminsky LA, Arena R, Beckie TM, Brubaker PH, Church TS, Forman DE, . . . Williams MA. The importance of cardiorespiratory fitness in the United States: the need for a national registry: a policy statement from the American Heart Association. Circulation. Feb 5 2013;127(5):652-662.
- Lee DC, Artero EG, Sui X, Blair SN. Mortality trends in the general population: the importance of cardiorespiratory fitness. Journal of psychopharmacology (Oxford, England). Nov 2010;24(4 Suppl):27-35.
- Bishop-Bailey D. Mechanisms governing the health and performance benefits of exercise. British journal of pharmacology. Nov 2013;170(6):1153-1166.
- EIM. American College of Sports Medicine. Exercise is Medicine: A Global Health Initiative. http://www.exerciseismedicine.org/. Copyright 2017. Accessed 4/6/2017.
- Mossberg KA, Amonette WE, Masel BE. Endurance Training and Cardiorespiratory Conditioning after Traumatic Brain Injury. J Head Trauma Rehabil. 2010;25(3):173-183.
- Reents S. Measuring Fitness: Aerobic Capacity. http://www.athleteinme.com/ArticleView.aspx?id=242. Last updated 2/28/2016. Accessed 12/28/2016.
- Moore SC, Patel AV, Matthews CE, Berrington de Gonzalez A, Park Y, Katki HA, . . . Lee IM. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med. 2012;9(11):e1001335.
- Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Moran M, . . . Lucia A. Exercise attenuates the major hallmarks of aging. Rejuvenation Res. Feb 2015;18(1):57-89.
- Parise G, Brose AN, Tarnopolsky MA. Resistance exercise training decreases oxidative damage to DNA and increases cytochrome oxidase activity in older adults. Exp Gerontol. Mar 2005;40(3):173-180.
- Steiner JL, Murphy EA, McClellan JL, Carmichael MD, Davis JM. Exercise training increases mitochondrial biogenesis in the brain. Journal of applied physiology (Bethesda, Md. : 1985). Oct 2011;111(4):1066-1071.
- O'Neill HM. AMPK and Exercise: Glucose Uptake and Insulin Sensitivity. Diabetes Metab J. Feb 2013;37(1):1-21.
- Johnston BD. Merck Manual. Professional Version. Overview of Exercise. https://www.merckmanuals.com/professional/special-subjects/exercise/overview-of-exercise. Last updated 10/2016. Accessed 4/6/2017.
- Chodzko-Zajko WJ, Proctor DN, Fiatarone Singh MA, Minson CT, Nigg CR, Salem GJ, Skinner JS. American College of Sports Medicine position stand. Exercise and physical activity for older adults. Medicine and science in sports and exercise. Jul 2009;41(7):1510-1530.
- Wang Y, Li M, Dong F, Zhang J, Zhang F. Physical exercise-induced protection on ischemic cardiovascular and cerebrovascular diseases. International Journal of Clinical and Experimental Medicine. 2015a;8(11):19859-19866.
- Burton DA, Stokes K, Hall GM. Physiological effects of exercise. Continuing Education in Anaesthesia, Critical Care & Pain. December 1, 2004 2004;4(6):185-188.
- Ainslie PN, Cotter JD, George KP, Lucas S, Murrell C, Shave R, . . . Atkinson G. Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing. The Journal of physiology. 2008;586(16):4005-4010.
- Baker JS, McCormick MC, Robergs RA. Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise. Journal of nutrition and metabolism. 2010;2010:905612.
- ACSM. American College of Sports Medicine. Resistance Training for Health and Fitness. https://www.acsm.org/docs/brochures/resistance-training.pdf. Copyright 2013. Accessed 1/3/2017.
- Garber CE, Blissmer B, Deschenes MR, Franklin BA, Lamonte MJ, Lee IM, . . . Swain DP. American College of Sports Medicine position stand. Quantity and quality of exercise for developing and maintaining cardiorespiratory, musculoskeletal, and neuromotor fitness in apparently healthy adults: guidance for prescribing exercise. Medicine and science in sports and exercise. Jul 2011;43(7):1334-1359.
- Witvrouw E, Mahieu N, Danneels L, McNair P. Stretching and injury prevention: an obscure relationship. Sports medicine (Auckland, N.Z.). 2004;34(7):443-449.
- Mayo Clinic. Patient Care & Health Info page. Stretching: Focus on flexibility. http://www.mayoclinic.org/healthy-lifestyle/fitness/in-depth/stretching/art-20047931. Last updated 2/21/2017. Accessed 4/6/2017.
- Johnson EO, Soucacos PN. International Encyclopedia of Rehabilitation: Proprioception. Copyright 2017 by the Center for International Rehabilitation Research Information and Exchange (CIRRIE). http://cirrie.buffalo.edu/encyclopedia/en/article/337/. Accessed 1/3/2017
- Shammas M. Telomeres, lifestyle, cancer, and aging. Curr Opin Clin Nutr Metab Care. 2011 Jan;14(1):28–34.
- Arsenis N, You T, Ogawa E, et al. Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget. 2017;8(27):45008–45019.
- Werner C, Hecksteden A, Morsch A, Zundler J, et al. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study. European Heart Journal. Ehy585. 2018.
- Smith-Ryan AE, Melvin MN, Wingfield HL. High-intensity interval training: Modulating interval duration in overweight/obese men. The Physician and sportsmedicine. May 2015;43(2):107-113.
- ACSM. American College of Sports Medicine. High-Intensity Interval Training. https://www.acsm.org/docs/brochures/high-intensity-interval-training.pdf. Copyright 2014. Accessed 4/6/2017.
- Shiraev T, Barclay G. Evidence based exercise - clinical benefits of high intensity interval training. Australian family physician. Dec 2012;41(12):960-962.
- Boutcher SH. High-intensity intermittent exercise and fat loss. Journal of obesity. 2011;2011:868305.
- Gillen JB, Martin BJ, MacInnis MJ, Skelly LE, Tarnopolsky MA, Gibala MJ. Twelve Weeks of Sprint Interval Training Improves Indices of Cardiometabolic Health Similar to Traditional Endurance Training despite a Five-Fold Lower Exercise Volume and Time Commitment. PloS one. 2016;11(4):e0154075.
- Ciolac EG. High-intensity interval training and hypertension: maximizing the benefits of exercise? American journal of cardiovascular disease. 2012;2(2):102-110.
- Jelleyman C, Yates T, O'Donovan G, Gray LJ, King JA, Khunti K, Davies MJ. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis. Obes Rev. Nov 2015;16(11):942-961.
- Weston KS, Wisloff U, Coombes JS. High-intensity interval training in patients with lifestyle-induced cardiometabolic disease: a systematic review and meta-analysis. British journal of sports medicine. Aug 2014;48(16):1227-1234.
- Jung ME, Bourne JE, Beauchamp MR, Robinson E, Little JP. High-intensity interval training as an efficacious alternative to moderate-intensity continuous training for adults with prediabetes. J Diabetes Res. 2015;2015:191595.
- Gibala MJ, Little JP, Macdonald MJ, Hawley JA. Physiological adaptations to low-volume, high-intensity interval training in health and disease. The Journal of physiology. Mar 1 2012;590(5):1077-1084.
- Ozaki A, Uchiyama M, Tagaya H, Ohida T, Ogihara R. The Japanese Centenarian Study: autonomy was associated with health practices as well as physical status. J Am Geriatr Soc. Jan 2007;55(1):95-101.
- Avin KG, Coen PM, Huang W, Stolz DB, Sowa GA, Dube JJ, . . . Ambrosio F. Skeletal muscle as a regulator of the longevity protein, Klotho. Front Physiol. 2014;5:189.
- Landi F, Marzetti E, Martone AM, Bernabei R, Onder G. Exercise as a remedy for sarcopenia. Current opinion in clinical nutrition and metabolic care. Jan 2014;17(1):25-31.
- Manini TM, Pahor M. Physical activity and maintaining physical function in older adults. British journal of sports medicine. Jan 2009;43(1):28-31.
- Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, . . . Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. The Cochrane database of systematic reviews. Jul 06 2011(7):Cd000333.
- Richter EA, Ruderman NB. AMPK and the biochemistry of exercise: implications for human health and disease. The Biochemical journal. Mar 1 2009;418(2):261-275.
- Vincent EE, Coelho PP, Blagih J, Griss T, Viollet B, Jones RG. Differential effects of AMPK agonists on cell growth and metabolism. Oncogene. Jul 2015;34(28):3627-3639.
- Barzilai N, Crandall JP, Kritchevsky SB, Espeland MA. Metformin as a Tool to Target Aging. Cell metabolism. Jun 14 2016;23(6):1060-1065.
- Anisimov VN. Metformin: do we finally have an anti-aging drug? Cell cycle (Georgetown, Tex.). Nov 15 2013;12(22):3483-3489.
- Reznick RM, Zong H, Li J, Morino K, Moore IK, Yu HJ, . . . Shulman GI. Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis. Cell metabolism. Feb 2007;5(2):151-156.
- Turner JE. Is immunosenescence influenced by our lifetime "dose" of exercise? Biogerontology. Mar 29 2016.
- Goronzy JJ, Weyand CM. Understanding immunosenescence to improve responses to vaccines. Nat Immunol. 2013;14(5):428-436.
- Maijo M, Clements SJ, Ivory K, Nicoletti C, Carding SR. Nutrition, diet and immunosenescence. Mech Ageing Dev. Mar-Apr 2014;136-137:116-128.
- Simpson RJ, Kunz H, Agha N, Graff R. Exercise and the Regulation of Immune Functions. Progress in molecular biology and translational science. 2015;135:355-380.
- Simpson RJ, Bosch JA. Special issue on exercise immunology: current perspectives on aging, health and extreme performance. Brain Behav Immun. Jul 2014;39:1-7.
- Spielmann G, McFarlin BK, O'Connor DP, Smith PJ, Pircher H, Simpson RJ. Aerobic fitness is associated with lower proportions of senescent blood T-cells in man. Brain Behav Immun. Nov 2011;25(8):1521-1529.
- Simpson RJ, Lowder TW, Spielmann G, Bigley AB, LaVoy EC, Kunz H. Exercise and the aging immune system. Ageing Res Rev. Jul 2012;11(3):404-420.
- Brown WM, Davison GW, McClean CM, Murphy MH. A Systematic Review of the Acute Effects of Exercise on Immune and Inflammatory Indices in Untrained Adults. Sports medicine - open. 2015;1(1):35.
- Eijsvogels TM, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the Extremes: The Amount of Exercise to Reduce Cardiovascular Events. Journal of the American College of Cardiology. Jan 26 2016;67(3):316-329.
- Wang Y, Li M, Dong F, Zhang J, Zhang F. Physical exercise-induced protection on ischemic cardiovascular and cerebrovascular diseases. International journal of clinical and experimental medicine. 2015b;8(11):19859-19866.
- Naci H, Salcher-Konrad M, Dias S, et al. How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 randomised controlled trials assessing exercise and medication effects on systolic blood pressure. Brit J of Sports Med. 2018. doi: 10.1136/bjsports-2018-099921
- Hegde SM, Solomon SD. Influence of Physical Activity on Hypertension and Cardiac Structure and Function. Curr Hypertens Rep. Oct 2015;17(10):77.
- Anderson L, Oldridge N, Thompson DR, Zwisler AD, Rees K, Martin N, Taylor RS. Exercise-Based Cardiac Rehabilitation for Coronary Heart Disease: Cochrane Systematic Review and Meta-Analysis. Journal of the American College of Cardiology. Jan 5 2016;67(1):1-12.
- Gomez-Pinilla F, Hillman C. The influence of exercise on cognitive abilities. Compr Physiol. Jan 2013;3(1):403-428.
- Bherer L, Erickson KI, Liu-Ambrose T. A review of the effects of physical activity and exercise on cognitive and brain functions in older adults. Journal of aging research. 2013;2013:657508.
- Kelly ME, Loughrey D, Lawlor BA, Robertson IH, Walsh C, Brennan S. The impact of exercise on the cognitive functioning of healthy older adults: a systematic review and meta-analysis. Ageing Res Rev. Jul 2014;16:12-31.
- Tse AC, Wong TW, Lee PH. Effect of Low-intensity Exercise on Physical and Cognitive Health in Older Adults: a Systematic Review. Sports medicine - open. 2015;1(1):37.
- Colcombe SJ, Erickson KI, Raz N, Webb AG, Cohen NJ, McAuley E, Kramer AF. Aerobic fitness reduces brain tissue loss in aging humans. J Gerontol A Biol Sci Med Sci. Feb 2003;58(2):176-180.
- Tolppanen AM, Solomon A, Kulmala J, Kareholt I, Ngandu T, Rusanen M, . . . Kivipelto M. Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia. Alzheimer's & dementia: the journal of the Alzheimer's Association. Apr 2015;11(4):434-443.e436.
- Zhu N, Jacobs DR, Jr., Schreiner PJ, Yaffe K, Bryan N, Launer LJ, . . . Sternfeld B. Cardiorespiratory fitness and cognitive function in middle age: the CARDIA study. Neurology. Apr 15 2014;82(15):1339-1346.
- Higgins JP, Higgins CL. Prescribing exercise to help your patients lose weight. Cleveland Clinic journal of medicine. Feb 2016;83(2):141-150.
- Bray GA, Fruhbeck G, Ryan DH, Wilding JP. Management of obesity. Lancet. Feb 8 2016.
- Stanford KI, Goodyear LJ. Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle. Advances in physiology education. Dec 2014;38(4):308-314.
- Colberg SR, Albright AL, Blissmer BJ, Braun B, Chasan-Taber L, Fernhall B, . . . Sigal RJ. Exercise and type 2 diabetes: American College of Sports Medicine and the American Diabetes Association: joint position statement. Exercise and type 2 diabetes. Medicine and science in sports and exercise. Dec 2010;42(12):2282-2303.
- Asano RY, Sales MM, Browne RA, Moraes JF, Coelho Junior HJ, Moraes MR, Simoes HG. Acute effects of physical exercise in type 2 diabetes: A review. World J Diabetes. Oct 15 2014;5(5):659-665.
- Gregg EW, Chen H, Wagenknecht LE, Clark JM, Delahanty LM, Bantle J, . . . Bertoni AG. Association of an intensive lifestyle intervention with remission of type 2 diabetes. Jama. Dec 19 2012;308(23):2489-2496.
- Rodrigues EV, Gomes AR, Tanhoffer AI, Leite N. Effects of exercise on pain of musculoskeletal disorders: a systematic review. Acta ortopedica brasileira. 2014;22(6):334-338.
- Abdulla SY, Southerst D, Cote P, Shearer HM, Sutton D, Randhawa K, . . . Taylor-Vaisey A. Is exercise effective for the management of subacromial impingement syndrome and other soft tissue injuries of the shoulder? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Manual therapy. Oct 2015;20(5):646-656.
- Edwards MH, Dennison EM, Aihie Sayer A, Fielding R, Cooper C. Osteoporosis and sarcopenia in older age. Bone. Nov 2015;80:126-130.
- Blain H, Rolland Y, Beauchet O, Annweiler C, Benhamou CL, Benetos A, . . . Thomas T. Usefulness of bone density measurement in fallers. Joint, bone, spine : revue du rhumatisme. Oct 2014;81(5):403-408.
- Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, . . . Zamboni M. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. Jul 2010;39(4):412-423.
- He H, Liu Y, Tian Q, Papasian CJ, Hu T, Deng HW. Relationship of sarcopenia and body composition with osteoporosis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. Feb 2016;27(2):473-482.
- Go SW, Cha YH, Lee JA, Park HS. Association between Sarcopenia, Bone Density, and Health-Related Quality of Life in Korean Men. Korean journal of family medicine. Jul 2013;34(4):281-288.
- Kim S, Won CW, Kim BS, Choi HR, Moon MY. The association between the low muscle mass and osteoporosis in elderly Korean people. J Korean Med Sci. Jul 2014;29(7):995-1000.
- Reginster JY, Beaudart C, Buckinx F, Bruyere O. Osteoporosis and sarcopenia: two diseases or one? Current opinion in clinical nutrition and metabolic care. Jan 2016;19(1):31-36.
- Shanb AA, Youssef EF. The impact of adding weight-bearing exercise versus nonweight bearing programs to the medical treatment of elderly patients with osteoporosis. Journal of family & community medicine. Sep 2014;21(3):176-181.
- Beck BR, Daly RM, Singh MA, Taaffe DR. Exercise and Sports Science Australia (ESSA) position statement on exercise prescription for the prevention and management of osteoporosis. Journal of science and medicine in sport / Sports Medicine Australia. Oct 31 2016.
- Castrogiovanni P, Trovato FM, Szychlinska MA, Nsir H, Imbesi R, Musumeci G. The importance of physical activity in osteoporosis. From the molecular pathways to the clinical evidence. Histology and histopathology. Nov 2016;31(11):1183-1194.
- Weening-Dijksterhuis E, de Greef MH, Scherder EJ, Slaets JP, van der Schans CP. Frail institutionalized older persons: A comprehensive review on physical exercise, physical fitness, activities of daily living, and quality-of-life. American journal of physical medicine & rehabilitation / Association of Academic Physiatrists. Feb 2011;90(2):156-168.
- Chin APMJ, van Uffelen JG, Riphagen I, van Mechelen W. The functional effects of physical exercise training in frail older people: a systematic review. Sports medicine (Auckland, N.Z.). 2008;38(9):781-793.
- Cerda B, Perez M, Perez-Santiago JD, Tornero-Aguilera JF, Gonzalez-Soltero R, Larrosa M. Gut Microbiota Modification: Another Piece in the Puzzle of the Benefits of Physical Exercise in Health? Front Physiol. 2016;7:51.
- Robles Alonso V, Guarner F. Linking the gut microbiota to human health. The British journal of nutrition. Jan 2013;109 Suppl 2:S21-26.
- Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, . . . Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. Dec 2014;63(12):1913-1920.
- Bermon S, Petriz B, Kajeniene A, Prestes J, Castell L, Franco OL. The microbiota: an exercise immunology perspective. Exercise immunology review. 2015;21:70-79.
- O'Sullivan O, Cronin O, Clarke SF, Murphy EF, Molloy MG, Shanahan F, Cotter PD. Exercise and the microbiota. Gut Microbes. 2015;6(2):131-136.
- Campbell SC, Wisniewski PJ, Noji M, McGuinness LR, Haggblom MM, Lightfoot SA, . . . Kerkhof LJ. The Effect of Diet and Exercise on Intestinal Integrity and Microbial Diversity in Mice. PloS one. 2016;11(3):e0150502.
- Choi JJ, Eum SY, Rampersaud E, Daunert S, Abreu MT, Toborek M. Exercise attenuates PCB-induced changes in the mouse gut microbiome. Environ Health Perspect. Jun 2013;121(6):725-730.
- Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of Moderate to Vigorous Physical Activity on All-Cause Mortality in Middle-aged and Older Australians. JAMA Intern Med. Jun 2015;175(6):970-977.
- Arem H, Moore SC, Patel A, Hartge P, Berrington de Gonzalez A, Visvanathan K, . . . Matthews CE. Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA Intern Med. Jun 2015;175(6):959-967.
- NIH. National Institutes of Health. National Heart, Lung, and Blood Institute. Recommendations for Physical Activity. http://www.nhlbi.nih.gov/health/health-topics/topics/phys/recommend. Last updated 6/22/2016. Accessed 11/8/2016.
- DHHS. Department of Health and Human Services. Physical Activity Guidelines for Americans: 2nd edition. https://health.gov/paguidelines/second-edition/pdf/Physical_Activity_Guidelines_2nd_edition.pdf. Copyright 2018. Accessed 11/12/2018.
- Gahche J, Fakhouri T, Carroll DD, Burt VL, Wang CY, Fulton JE. Cardiorespiratory fitness levels among U.S. youth aged 12-15 years: United States, 1999-2004 and 2012. NCHS Data Brief. May 2014(153):1-8.
- Sartor F, Vernillo G, de Morree HM, Bonomi AG, La Torre A, Kubis HP, Veicsteinas A. Estimation of maximal oxygen uptake via submaximal exercise testing in sports, clinical, and home settings. Sports medicine (Auckland, N.Z.). Sep 2013;43(9):865-873.
- Percia M, Davis S, Dwyer G. American College of Sports Medicine. Getting a Professional Fitness Assessment https://www.acsm.org/public-information/articles/2012/01/10/getting-a-professional-fitness-assessment. 10/7/2016. Accessed 4/6/2017.
- Giannoulis MG, Martin FC, Nair KS, Umpleby AM, Sonksen P. Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr Rev. Jun 2012;33(3):314-377.
- Villareal DT, Holloszy JO. DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. American journal of physiology. Endocrinology and metabolism. Nov 2006;291(5):E1003-1008.
- Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer? Clinical endocrinology. Feb 2006;64(2):115-121.
- Huffman KM, Slentz CA, Johnson JL, Samsa GP, Duscha BD, Tanner CJ, . . . Kraus WE. Impact of hormone replacement therapy on exercise training-induced improvements in insulin action in sedentary overweight adults. Metabolism: clinical and experimental. Jul 2008;57(7):888-895.
- Borg WP. Point/Counterpoint: The Case Against Bioidentical Hormones. Journal of American Physicians and Surgeons. 2008;13(2):47.
- Moskowitz D. A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Alternative medicine review : a journal of clinical therapeutic. Sep 2006;11(3):208-223.
- Whelan AM, Jurgens TM, Trinacty M. Defining bioidentical hormones for menopause-related symptoms. Pharm Pract (Granada). Jan 2011;9(1):16-22.
- Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. Jan 2009;121(1):73-85.
- Conaway E. Bioidentical hormones: an evidence-based review for primary care providers. J Am Osteopath Assoc. Mar 2011;111(3):153-164.
- Rodriguez NR, Di Marco NM, Langley S. American College of Sports Medicine position stand. Nutrition and athletic performance. Medicine and science in sports and exercise. Mar 2009;41(3):709-731.
- Kreider RB, Wilborn CD, Taylor L, Campbell B, Almada AL, Collins R, . . . Antonio J. ISSN exercise & sport nutrition review: research & recommendations. Journal of the International Society of Sports Nutrition. Feb 02 2010;7:7.
- Kerksick C, Harvey T, Stout J, Campbell B, Wilborn C, Kreider R, . . . Antonio J. International Society of Sports Nutrition position stand: nutrient timing. Journal of the International Society of Sports Nutrition. Oct 03 2008;5:17.
- Aragon AA, Schoenfeld BJ. Nutrient timing revisited: is there a post-exercise anabolic window? Journal of the International Society of Sports Nutrition. 2013;10(1):5.
- Moore DR, Robinson MJ, Fry JL, Tang JE, Glover EI, Wilkinson SB, . . . Phillips SM. Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. The American journal of clinical nutrition. Jan 2009;89(1):161-168.
- Yang Y, Breen L, Burd NA, Hector AJ, Churchward-Venne TA, Josse AR, . . . Phillips SM. Resistance exercise enhances myofibrillar protein synthesis with graded intakes of whey protein in older men. The British journal of nutrition. Nov 28 2012;108(10):1780-1788.
- Woolf K, Bidwell WK, Carlson AG. The effect of caffeine as an ergogenic aid in anaerobic exercise. International journal of sport nutrition and exercise metabolism. Aug 2008;18(4):412-429.
- Spriet LL. Exercise and sport performance with low doses of caffeine. Sports medicine (Auckland, N.Z.). Nov 2014;44 Suppl 2:S175-184.
- Astorino TA, Roberson DW. Efficacy of acute caffeine ingestion for short-term high-intensity exercise performance: a systematic review. Journal of strength and conditioning research / National Strength & Conditioning Association. Jan 2010;24(1):257-265.
- Beedie CJ. All in the mind? Pain, placebo effect, and ergogenic effect of caffeine in sports performance. Open Access J Sports Med. 2010;1:87-94.
- Doherty M, Smith PM. Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis. Scandinavian journal of medicine & science in sports. Apr 2005;15(2):69-78.
- Ribeiro JA, Sebastiao AM. Caffeine and adenosine. Journal of Alzheimer's disease : JAD. 2010;20 Suppl 1:S3-15.
- Urry E, Landolt HP. Adenosine, caffeine, and performance: from cognitive neuroscience of sleep to sleep pharmacogenetics. Current topics in behavioral neurosciences. 2015;25:331-366.
- Yang A, Palmer AA, de Wit H. Genetics of caffeine consumption and responses to caffeine. Psychopharmacology. Aug 2010;211(3):245-257.
- Chen Y, Parrish TB. Caffeine dose effect on activation-induced BOLD and CBF responses. NeuroImage. Jul 1 2009;46(3):577-583.
- Pirastu N, Kooyman M, Robino A, van der Spek A, Navarini L, Amin N, . . . Gasparini P. Non-additive genome-wide association scan reveals a new gene associated with habitual coffee consumption. Scientific Reports. 2016;6:31590.
- Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep medicine reviews. Feb 2017;31:70-78.
- UMMC. University of Maryland Medical Center. Complementary and Alternative Medicine Guide. Supplement. Creatine. http://umm.edu/health/medical/altmed/supplement/creatine. 6/26/2014a. Accessed 4/6/2017.
- Cooper R, Naclerio F, Allgrove J, Jimenez A. Creatine supplementation with specific view to exercise/sports performance: an update. Journal of the International Society of Sports Nutrition. 2012;9(1):33.
- Devries MC, Phillips SM. Creatine supplementation during resistance training in older adults-a meta-analysis. Medicine and science in sports and exercise. Jun 2014;46(6):1194-1203.
- Moon A, Heywood L, Rutherford S, Cobbold C. Creatine supplementation: can it improve quality of life in the elderly without associated resistance training? Current aging science. Dec 2013;6(3):251-257.
- Wallimann T, Tokarska-Schlattner M, Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino acids. May 2011;40(5):1271-1296.
- Klopstock T, Elstner M, Bender A. Creatine in mouse models of neurodegeneration and aging. Amino acids. May 2011;40(5):1297-1303.
- Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS. The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels. Journal of the International Society of Sports Nutrition. 2009;6:6.
- Dalbo VJ, Roberts MD, Lockwood CM, Tucker PS, Kreider RB, Kerksick CM. The effects of age on skeletal muscle and the phosphocreatine energy system: can creatine supplementation help older adults. Dynamic medicine: DM. 2009;8:6.
- Parandak K, Arazi H, Khoshkhahesh F, Nakhostin-Roohi B. The effect of two-week L-carnitine supplementation on exercise -induced oxidative stress and muscle damage. Asian journal of sports medicine. Jun 2014;5(2):123-128.
- Wall BT, Stephens FB, Constantin-Teodosiu D, Marimuthu K, Macdonald IA, Greenhaff PL. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. The Journal of physiology. Feb 15 2011;589(Pt 4):963-973.
- Pandareesh MD, Anand T. Ergogenic effect of dietary L-carnitine and fat supplementation against exercise induced physical fatigue in Wistar rats. J Physiol Biochem. Dec 2013;69(4):799-809.
- Huang A, Owen K. Role of supplementary L-carnitine in exercise and exercise recovery. Medicine and sport science. 2012;59:135-142.
- Shimomura Y, Yamamoto Y, Bajotto G, Sato J, Murakami T, Shimomura N, . . . Mawatari K. Nutraceutical effects of branched-chain amino acids on skeletal muscle. The Journal of nutrition. Feb 2006;136(2):529s-532s.
- Gibala MJ. Protein metabolism and endurance exercise. Sports medicine (Auckland, N.Z.). 2007;37(4-5):337-340.
- Benardot D. Advanced Sports Nutrition. Champaign, Il.: Human Kinetics; 2006.
- MSU. Montana State University. What Fuels Are Used For Exercise? https://btc.montana.edu/olympics/nutrition/fuel05.html. Copyright 1998. Accessed 4/7/2017.
- Kanda A, Nakayama K, Fukasawa T, Koga J, Kanegae M, Kawanaka K, Higuchi M. Post-exercise whey protein hydrolysate supplementation induces a greater increase in muscle protein synthesis than its constituent amino acid content. The British journal of nutrition. Sep 28 2013;110(6):981-987.
- Falavigna G, Alves de Araujo J, Jr., Rogero MM, Pires IS, Pedrosa RG, Martins E, Jr., . . . Tirapegui J. Effects of diets supplemented with branched-chain amino acids on the performance and fatigue mechanisms of rats submitted to prolonged physical exercise. Nutrients. Nov 2012;4(11):1767-1780.
- Crowe MJ, Weatherson JN, Bowden BF. Effects of dietary leucine supplementation on exercise performance. European journal of applied physiology. Aug 2006;97(6):664-672.
- Mittleman KD, Ricci MR, Bailey SP. Branched-chain amino acids prolong exercise during heat stress in men and women. Medicine and science in sports and exercise. Jan 1998;30(1):83-91.
- Gualano AB, Bozza T, Lopes De Campos P, Roschel H, Dos Santos Costa A, Luiz Marquezi M, . . . Herbert Lancha Junior A. Branched-chain amino acids supplementation enhances exercise capacity and lipid oxidation during endurance exercise after muscle glycogen depletion. The Journal of sports medicine and physical fitness. Mar 2011;51(1):82-88.
- Fujita S, Volpi E. Amino acids and muscle loss with aging. The Journal of nutrition. Jan 2006;136(1 Suppl):277s-280s.
- Karlsson HK, Nilsson PA, Nilsson J, Chibalin AV, Zierath JR, Blomstrand E. Branched-chain amino acids increase p70S6k phosphorylation in human skeletal muscle after resistance exercise. American journal of physiology. Endocrinology and metabolism. Jul 2004;287(1):E1-7.
- HCHS. Huntington College of Health Sciences. Smart Supplementation. A Primer on Branched Chain Amino Acids. http://www.hchs.edu/literature/BCAA.pdf. Copyright 2009. Accessed 4/7/2017.
- Matsumoto K, Koba T, Hamada K, Sakurai M, Higuchi T, Miyata H. Branched-chain amino acid supplementation attenuates muscle soreness, muscle damage and inflammation during an intensive training program. The Journal of sports medicine and physical fitness. Dec 2009;49(4):424-431.
- Shuler FD, Wingate MK, Moore GH, Giangarra C. Sports health benefits of vitamin d. Sports Health. Nov 2012;4(6):496-501.
- Ogan D, Pritchett K. Vitamin D and the athlete: risks, recommendations, and benefits. Nutrients. Jun 2013;5(6):1856-1868.
- Dahlquist DT, Dieter BP, Koehle MS. Plausible ergogenic effects of vitamin D on athletic performance and recovery. Journal of the International Society of Sports Nutrition. 2015;12:33.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, . . . Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. The Journal of clinical endocrinology and metabolism. Jul 2011;96(7):1911-1930.
- Alt Med Rev. Monograph: L-Glutamine. Vol. 6; No. 4, pp. 406-410. Copyright 2001 by Thorne Research. http://www.altmedrev.com/publications/6/4/406.pdf. Accessed 4/7/2017.
- UMHS. University of Michigan Health System. Glutamine. http://www.uofmhealth.org/health-library/hn-2856003#hn-2856003-uses. 3/24/2015. Accessed 4/7/2017.
- Legault Z, Bagnall N, Kimmerly DS. The Influence of Oral L-Glutamine Supplementation on Muscle Strength Recovery and Soreness Following Unilateral Knee Extension Eccentric Exercise. International journal of sport nutrition and exercise metabolism. Oct 2015;25(5):417-426.
- Tao KM, Li XQ, Yang LQ, Yu WF, Lu ZJ, Sun YM, Wu FX. Glutamine supplementation for critically ill adults. The Cochrane database of systematic reviews. 2014;9:Cd010050.
- Stehle P, Kuhn KS. Glutamine: an obligatory parenteral nutrition substrate in critical care therapy. Biomed Res Int. 2015;2015:545467.
- Mondello S, Italiano D, Giacobbe MS, Mondello P, Trimarchi G, Aloisi C, . . . Spina E. Glutamine-supplemented total parenteral nutrition improves immunological status in anorectic patients. Nutrition (Burbank, Los Angeles County, Calif.). Jun 2010;26(6):677-681.
- Sasaki E, Umeda T, Takahashi I, Arata K, Yamamoto Y, Tanabe M, . . . Nakaji S. Effect of glutamine supplementation on neutrophil function in male judoists. Luminescence: the journal of biological and chemical luminescence. Jul-Aug 2013;28(4):442-449.
- Song QH, Xu RM, Zhang QH, Shen GQ, Ma M, Zhao XP, . . . Wang Y. Glutamine supplementation and immune function during heavy load training. International journal of clinical pharmacology and therapeutics. May 2015;53(5):372-376.
- Castell LM, Poortmans JR, Newsholme EA. Does glutamine have a role in reducing infections in athletes? European journal of applied physiology and occupational physiology. 1996;73(5):488-490.
- Perrini S, Laviola L, Natalicchio A, Giorgino F. Associated hormonal declines in aging: DHEAS. Journal of endocrinological investigation. 2005;28(3 Suppl):85-93.
- Barrou Z, Charru P, Lidy C. Dehydroepiandrosterone (DHEA) and aging. Arch Gerontol Geriatr. May-Jun 1997;24(3):233-241.
- UMMC. University of Maryland Medical Center. Complementary and Alternative Medicine Guide. Supplement. Dehydroepiandrosterone. http://umm.edu/health/medical/altmed/supplement/dehydroepiandrosterone. 6/26/2014b. Accessed 4/6/2017.
- Liu TC, Lin CH, Huang CY, Ivy JL, Kuo CH. Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training. European journal of applied physiology. Jul 2013;113(7):1783-1792.
- Hayes A, Cribb PJ. Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training. Current opinion in clinical nutrition and metabolic care. Jan 2008;11(1):40-44.
- Miller PE, Alexander DD, Perez V. Effects of whey protein and resistance exercise on body composition: a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2014;33(2):163-175.
- Buckley JD, Thomson RL, Coates AM, Howe PR, DeNichilo MO, Rowney MK. Supplementation with a whey protein hydrolysate enhances recovery of muscle force-generating capacity following eccentric exercise. Journal of science and medicine in sport / Sports Medicine Australia. Jan 2010;13(1):178-181.
- Farup J, Rahbek SK, Knudsen IS, de Paoli F, Mackey AL, Vissing K. Whey protein supplementation accelerates satellite cell proliferation during recovery from eccentric exercise. Amino acids. Nov 2014;46(11):2503-2516.
- Pennings B, Boirie Y, Senden JM, Gijsen AP, Kuipers H, van Loon LJ. Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men. The American journal of clinical nutrition. May 2011;93(5):997-1005.
- Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiological reviews. Jan 2013;93(1):23-67.
- Farup J, Rahbek SK, Vendelbo MH, Matzon A, Hindhede J, Bejder A, . . . Vissing K. Whey protein hydrolysate augments tendon and muscle hypertrophy independent of resistance exercise contraction mode. Scandinavian journal of medicine & science in sports. Oct 2014;24(5):788-798
- Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. American journal of physiology. Regulatory, integrative and comparative physiology. Jan 2004;286(1):R182-188.
- Peveler WW, Bishop PA, Whitehorn EJ. Effects of ribose as an ergogenic aid. Journal of strength and conditioning research / National Strength & Conditioning Association. Aug 2006;20(3):519-522.
- Dhanoa TS, Housner JA. Ribose: more than a simple sugar? Current sports medicine reports. Jul 2007;6(4):254-257.
- Van Gammeren D FD, Antonio J. . The effects of four weeks of ribose supplementation on body composition and exercise performance in healthy, young, male recreational body builders: a double-blind, placebo controlled trial. Current Therapeutic Rsearch. 2002;63(8):486-495.
- Flanigan R, MacCarter D, Shecterle LM, St Cyr JA. D-ribose aids fatigue in aging adults. Journal of alternative and complementary medicine (New York, N.Y.). May 2010;16(5):529-530.
- Thompson J, Neutel J, Homer K, Tempero K, Shah A, Khankari R. Evaluation of D-ribose pharmacokinetics, dose proportionality, food effect, and pharmacodynamics after oral solution administration in healthy male and female subjects. J Clin Pharmacol. May 2014;54(5):546-554.
- Corder KE, Newsham KR, McDaniel JL, Ezekiel UR, Weiss EP. Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women. J Sports Sci Med. Mar 2016;15(1):176-183.
- Jouris KB, McDaniel JL, Weiss EP. The Effect of Omega-3 Fatty Acid Supplementation on the Inflammatory Response to eccentric strength exercise. J Sports Sci Med. 2011;10(3):432-438.
- Jeromson S, Gallagher IJ, Galloway SD, Hamilton DL. Omega-3 Fatty Acids and Skeletal Muscle Health. Mar Drugs. Nov 2015;13(11):6977-7004.
- Smith GI, Atherton P, Reeds DN, Mohammed BS, Rankin D, Rennie MJ, Mittendorfer B. Dietary omega-3 fatty acid supplementation increases the rate of muscle protein synthesis in older adults: a randomized controlled trial. The American journal of clinical nutrition. Feb 2011;93(2):402-412.
- Sarmiento A, Diaz-Castro J, Pulido-Moran M, Kajarabille N, Guisado R, Ochoa JJ. Coenzyme Q10 Supplementation and Exercise in Healthy Humans: A Systematic Review. Current drug metabolism. 2016;17(4):345-358.
- Pala R, Orhan C, Tuzcu M, Sahin N, Ali S, Cinar V, . . . Sahin K. Coenzyme Q10 Supplementation Modulates NFkappaB and Nrf2 Pathways in Exercise Training. J Sports Sci Med. Mar 2016;15(1):196-203.
- Kumar A, Kaur H, Devi P, Mohan V. Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome. Pharmacology & therapeutics. Dec 2009;124(3):259-268.
- Gokbel H, Gul I, Belviranl M, Okudan N. The effects of coenzyme Q10 supplementation on performance during repeated bouts of supramaximal exercise in sedentary men. Journal of strength and conditioning research / National Strength & Conditioning Association. Jan 2010;24(1):97-102.
- Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, . . . Kreider R. Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained and untrained individuals. Journal of the International Society of Sports Nutrition. 2008;5:8.
- Armanfar M, Jafari A, Dehghan GR, Abdizadeh L. Effect of coenzyme Q10 supplementation on exercise-induced response of inflammatory indicators and blood lactate in male runners. Medical journal of the Islamic Republic of Iran. 2015;29:202.
- Camic CL, Housh TJ, Zuniga JM, Hendrix RC, Mielke M, Johnson GO, Schmidt RJ. Effects of arginine-based supplements on the physical working capacity at the fatigue threshold. Journal of strength and conditioning research / National Strength & Conditioning Association. May 2010;24(5):1306-1312.
- Campbell BI, La Bounty PM, Roberts M. The ergogenic potential of arginine. Journal of the International Society of Sports Nutrition. 2004;1(2):35-38.
- McConell GK. Effects of L-arginine supplementation on exercise metabolism. Current opinion in clinical nutrition and metabolic care. Jan 2007;10(1):46-51.
- Ranchordas MK WT. Effect of acute L-arginine supplementation on 20 km time trial performance in competitive male cyclists. British journal of sports medicine. 2011;45:A11.
- Lomonosova YN, Shenkman BS, Kalamkarov GR, Kostrominova TY, Nemirovskaya TL. L-arginine supplementation protects exercise performance and structural integrity of muscle fibers after a single bout of eccentric exercise in rats. PloS one. 2014;9(4):e94448.
- Huang CC, Tsai SC, Lin WT. Potential ergogenic effects of L-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats. Exp Gerontol. Jun 2008;43(6):571-577.
- Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity. Mar 2001;25(3):316-324.
- Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. Plant foods and herbal sources of resveratrol. Journal of agricultural and food chemistry. May 22 2002;50(11):3337-3340.
- Polley KR, Jenkins N, O'Connor P, McCully K. Influence of exercise training with resveratrol supplementation on skeletal muscle mitochondrial capacity. Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. Jan 2016;41(1):26-32.
- Mohammadi Sartang M, Mazloom Z, Sohrabi Z, Sherafatmanesh S, Boldaji RB. Resveratrol supplementation and plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials. Pharmacological research: the official journal of the Italian Pharmacological Society. Jan 13 2017.
- Diaz M, Degens H, Vanhees L, Austin C, Azzawi M. The effects of resveratrol on aging vessels. Exp Gerontol. Dec 01 2016;85:41-47.
- Oyenihi OR, Oyenihi AB, Adeyanju AA, Oguntibeju OO. Antidiabetic Effects of Resveratrol: The Way Forward in Its Clinical Utility. Journal of Diabetes Research. 2016;2016:9737483.
- Chen S, Zhao X, Ran L, Wan J, Wang X, Qin Y, . . . Mi M. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Dig Liver Dis. Mar 2015;47(3):226-232.
- Menzies KJ, Singh K, Saleem A, Hood DA. Sirtuin 1-mediated effects of exercise and resveratrol on mitochondrial biogenesis. The Journal of biological chemistry. Mar 8 2013;288(10):6968-6979.
- Wu RE, Huang WC, Liao CC, Chang YK, Kan NW, Huang CC. Resveratrol protects against physical fatigue and improves exercise performance in mice. Molecules. 2013;18(4):4689-4702.
- Dolinsky VW, Jones KE, Sidhu RS, Haykowsky M, Czubryt MP, Gordon T, Dyck JR. Improvements in skeletal muscle strength and cardiac function induced by resveratrol during exercise training contribute to enhanced exercise performance in rats. The Journal of physiology. Jun 1 2012;590(11):2783-2799.
- Lin-Na S, Yong-Xiu S. Effects of polysaccharides from Gynostemma pentaphyllum (Thunb.), Makino on physical fatigue. African journal of traditional, complementary, and alternative medicines: AJTCAM / African Networks on Ethnomedicines. 2014;11(3):112-117.
- Nguyen PH, Gauhar R, Hwang SL, Dao TT, Park DC, Kim JE, . . . Oh WK. New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum. Bioorganic & medicinal chemistry. Nov 1 2011;19(21):6254-6260.
- Chi A, Tang L, Zhang J, Zhang K. Chemical composition of three polysaccharides from Gynostemma pentaphyllum and their antioxidant activity in skeletal muscle of exercised mice. International journal of sport nutrition and exercise metabolism. Dec 2012;22(6):479-485.
- Chen S, Li Z, Krochmal R, Abrazado M, Kim W, Cooper CB. Effect of Cs-4 (Cordyceps sinensis) on exercise performance in healthy older subjects: a double-blind, placebo-controlled trial. Journal of alternative and complementary medicine (New York, N.Y.). May 2010;16(5):585-590.
- Chen CY, Hou CW, Bernard JR, Chen CC, Hung TC, Cheng LL, . . . Kuo CH. Rhodiola crenulata- and Cordyceps sinensis-based supplement boosts aerobic exercise performance after short-term high altitude training. High altitude medicine & biology. Sep 2014;15(3):371-379.
- Panda AK, Swain KC. Traditional uses and medicinal potential of Cordyceps sinensis of Sikkim. Journal of Ayurveda and integrative medicine. Jan 2011;2(1):9-13.
- Kumar R, Negi PS, Singh B, Ilavazhagan G, Bhargava K, Sethy NK. Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal muscle metabolic regulators. Journal of ethnopharmacology. Jun 14 2011;136(1):260-266.
- Wang J, Li S, Fan Y, Chen Y, Liu D, Cheng H, . . . Zhou Y. Anti-fatigue activity of the water-soluble polysaccharides isolated from Panax ginseng C. A. Meyer. Journal of ethnopharmacology. Jul 20 2010;130(2):421-423.
- Oliynyk S, Oh S. Actoprotective effect of ginseng: improving mental and physical performance. Journal of ginseng research. Apr 2013;37(2):144-166.
- Chen CK, Muhamad AS, Ooi FK. Herbs in exercise and sports. Journal of physiological anthropology. 2012;31:4.
- Bucci LR. Selected herbals and human exercise performance. The American journal of clinical nutrition. Aug 2000;72(2 Suppl):624s-636s.
- Wang LC, Lee TF. Effect of ginseng saponins on exercise performance in non-trained rats. Planta medica. Mar 1998;64(2):130-133.
- Zhao W, Zhang X, Wang W, Zhang L. [Experimental study for the anti-fatigue effect of ginseng general ginsenosides P.E. in vivo]. Wei sheng yan jiu = Journal of hygiene research. Mar 2009;38(2):184-187.
- Nocerino E, Amato M, Izzo AA. The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia. Aug 2000;71 Suppl 1:S1-5.
- Kim SH, Park KS, Chang MJ, Sung JH. Effects of Panax ginseng extract on exercise-induced oxidative stress. The Journal of sports medicine and physical fitness. Jun 2005;45(2):178-182.
- Liang MT, Podolka TD, Chuang WJ. Panax notoginseng supplementation enhances physical performance during endurance exercise. Journal of strength and conditioning research / National Strength & Conditioning Association. Feb 2005;19(1):108-114.
- Jung K, Kim IH, Han D. Effect of medicinal plant extracts on forced swimming capacity in mice. Journal of ethnopharmacology. Jul 2004;93(1):75-81.
- Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicine- ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Current medicinal chemistry. 2009;16(22):2924-2942.
- Kim KA, Yoo HH, Gu W, Yu DH, Jin MJ, Choi HL, . . . Kim DH. A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats. Journal of ginseng research. Apr 2015;39(2):183-187.
- Bae EA, Choo MK, Park EK, Park SY, Shin HY, Kim DH. Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity. Biological & pharmaceutical bulletin. Jun 2002;25(6):743-747.
- Jin H, Seo JH, Uhm YK, Jung CY, Lee SK, Yim SV. Pharmacokinetic comparison of ginsenoside metabolite IH-901 from fermented and non-fermented ginseng in healthy Korean volunteers. Journal of ethnopharmacology. Jan 31 2012;139(2):664-667.
- Hasegawa H. Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. Journal of pharmacological sciences. Jun 2004;95(2):153-157.
- Noreen EE, Buckley JG, Lewis SL, Brandauer J, Stuempfle KJ. The effects of an acute dose of Rhodiola rosea on endurance exercise performance. Journal of strength and conditioning research / National Strength & Conditioning Association. Mar 2013;27(3):839-847.
- Duncan MJ, Clarke ND. The Effect of Acute Rhodiola rosea Ingestion on Exercise Heart Rate, Substrate Utilisation, Mood State, and Perceptions of Exertion, Arousal, and Pleasure/Displeasure in Active Men. Journal of sports medicine (Hindawi Publishing Corporation). 2014;2014:563043.
- Lee FT, Kuo TY, Liou SY, Chien CT. Chronic Rhodiola rosea extract supplementation enforces exhaustive swimming tolerance. The American journal of Chinese medicine. 2009;37(3):557-572.
- De Bock K, Eijnde BO, Ramaekers M, Hespel P. Acute Rhodiola rosea intake can improve endurance exercise performance. International journal of sport nutrition and exercise metabolism. Jun 2004;14(3):298-307.
- Parisi A, Tranchita E, Duranti G, Ciminelli E, Quaranta F, Ceci R, . . . Sabatini S. Effects of chronic Rhodiola Rosea supplementation on sport performance and antioxidant capacity in trained male: preliminary results. The Journal of sports medicine and physical fitness. Mar 2010;50(1):57-63.
- Walker TB, Robergs RA. Does Rhodiola rosea possess ergogenic properties? International journal of sport nutrition and exercise metabolism. Jun 2006;16(3):305-315.
- Slater GJ, Jenkins D. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength. Sports medicine (Auckland, NZ). 2000;30(2):105-116.
- Rittig N, Bach E, Thomsen HH, et al. Anabolic effects of leucine-rich whey protein, carbohydrate, and soy protein with and without beta-hydroxy-beta-methylbutyrate (HMB) during fasting-induced catabolism: A human randomized crossover trial. Clin Nutr. 2017;36(3):697-705.
- Asadi A, Arazi H, Suzuki K. Effects of beta-Hydroxy-beta-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training. Nutrients. 2017;9(12).
- Zanchi NE, Gerlinger-Romero F, Guimaraes-Ferreira L, et al. HMB supplementation: clinical and athletic performance-related effects and mechanisms of action. Amino Acids. 2011;40(4):1015-1025.
- Deutz NE, Pereira SL, Hays NP, et al. Effect of beta-hydroxy-beta-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults. Clin Nutr. 2013;32(5):704-712.
- Knitter AE, Panton L, Rathmacher JA, Petersen A, Sharp R. Effects of β-hydroxy-β-methylbutyrate on muscle damage after a prolonged run. Journal of Applied Physiology. 2000;89(4):1340-1344.
- Stout JR, Smith-Ryan AE, Fukuda DH, et al. Effect of calcium β-hydroxy-β-methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: A randomized, double-blind pilot trial. Experimental Gerontology. 2013;48(11):1303-1310.
- Wilson JM, Lowery RP, Joy JM, et al. β-Hydroxy-β-methylbutyrate free acid reduces markers of exercise-induced muscle damage and improves recovery in resistance-trained men. British Journal of Nutrition. 2013;110(3):538-544.
- Rowlands DS, Thomson JS. Effects of β-Hydroxy-β-Methylbutyrate Supplementation During Resistance Training on Strength, Body Composition, and Muscle Damage in Trained and Untrained Young Men: A Meta-Analysis. The Journal of Strength & Conditioning Research. 2009;23(3):836-846.
- Horowitz AM, Fan X, Bieri G, et al. Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain. Science (New York, NY). 2020;369(6500):167-173.
- Panfoli I, Puddu A, Bertola N, Ravera S, Maggi D. The Hormetic Effect of Metformin: "Less Is More"? International journal of molecular sciences. Jun 11 2021;22(12)doi:10.3390/ijms22126297.
- Malin SK, Stewart NR. Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise. Frontiers in endocrinology. 2020;11:519. doi:10.3389/fendo.2020.00519.
- Kaneto H, Kimura T, Obata A, Shimoda M, Kaku K. Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History. International journal of molecular sciences. Mar 5 2021;22(5)doi:10.3390/ijms22052596.
- Ortega JF, Hamouti N, Fernández-Elías VE, de Prada MV, Martínez-Vizcaíno V, Mora-Rodríguez R. Metformin does not attenuate the acute insulin-sensitizing effect of a single bout of exercise in individuals with insulin resistance. Acta Diabetol. Oct 2014;51(5):749-55. doi:10.1007/s00592-014-0580-4.
- Huang T, Lu C, Schumann M, et al. Timing of Exercise Affects Glycemic Control in Type 2 Diabetes Patients Treated with Metformin. J Diabetes Res. 2018;2018:2483273. doi:10.1155/2018/2483273.
- Erickson ML, Little JP, Gay JL, McCully KK, Jenkins NT. Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy. J Appl Physiol (1985). Aug 1 2017;123(2):444-450. doi:10.1152/japplphysiol.00213.2017.
- Boulé NG, Robert C, Bell GJ, et al. Metformin and exercise in type 2 diabetes: examining treatment modality interactions. Diabetes Care. Jul 2011;34(7):1469-74. doi:10.2337/dc10-2207.
- Myette-Côté É, Terada T, Boulé NG. The Effect of Exercise with or Without Metformin on Glucose Profiles in Type 2 Diabetes: A Pilot Study. Canadian journal of diabetes. Apr 2016;40(2):173-7. doi:10.1016/j.jcjd.2015.08.015.
- Boulé NG, Kenny GP, Larose J, Khandwala F, Kuzik N, Sigal RJ. Does metformin modify the effect on glycaemic control of aerobic exercise, resistance exercise or both? Diabetologia. Nov 2013;56(11):2378-82. doi:10.1007/s00125-013-3026-6.
- Terada T, Boulé NG. Does metformin therapy influence the effects of intensive lifestyle intervention? Exploring the interaction between first line therapies in the Look AHEAD trial. Metabolism: clinical and experimental. May 2019;94:39-46. doi:10.1016/j.metabol.2019.01.004
- Konopka AR, Laurin JL, Schoenberg HM, et al. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. Feb 2019;18(1):e12880. doi:10.1111/acel.12880.
- Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. Jan 2012;35(1):131-6. doi:10.2337/dc11-0925.
- Malin SK, Nightingale J, Choi SE, Chipkin SR, Braun B. Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). Jan 2013;21(1):93-100. doi:10.1002/oby.20235.
- Walton RG, Dungan CM, Long DE, et al. Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial. Aging Cell. Dec 2019;18(6):e13039. doi:10.1111/acel.13039.
- Kristensen JM, Lillelund C, Kjøbsted R, et al. Metformin does not compromise energy status in human skeletal muscle at rest or during acute exercise: A randomised, crossover trial. Physiological reports. Dec 2019;7(23):e14307. doi:10.14814/phy2.14307.
- Pilmark NS, Petersen-Bønding C, Holm NFR, et al. The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial. Frontiers in endocrinology. 2021;12:599164. doi:10.3389/fendo.2021.599164.
- Radak Z, Ishihara K, Tekus E, et al. Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve. Redox biology. Aug 2017;12:285-290. doi:10.1016/j.redox.2017.02.015.
- Perim P, Marticorena FM, Ribeiro F, et al. Can the Skeletal Muscle Carnosine Response to Beta-Alanine Supplementation Be Optimized? Frontiers in nutrition. 2019;6:135. doi:10.3389/fnut.2019.00135
- Budzen S, Rymaszewska J. The biological role of carnosine and its possible applications in medicine. Adv Clin Exp Med. Sep-Oct 2013;22(5):739-44.
- Matthews JJ, Artioli GG, Turner MD, Sale C. The Physiological Roles of Carnosine and beta-Alanine in Exercising Human Skeletal Muscle. Medicine and science in sports and exercise. Oct 2019;51(10):2098-2108. doi:10.1249/MSS.0000000000002033
- Hobson RM, Saunders B, Ball G, Harris RC, Sale C. Effects of beta-alanine supplementation on exercise performance: a meta-analysis. Amino Acids. Jul 2012;43(1):25-37. doi:10.1007/s00726-011-1200-z
- Slowinska-Lisowska M, Zembron-Lacny A, Rynkiewicz M, Rynkiewicz T, Kopec W. Influence of l-carnosine on pro-antioxidant status in elite kayakers and canoeists. Acta physiologica Hungarica. Dec 2014;101(4):461-70. doi:10.1556/APhysiol.101.2014.008
- Saunders B, Elliott-Sale K, Artioli GG, et al. beta-alanine supplementation to improve exercise capacity and performance: a systematic review and meta-analysis. British journal of sports medicine. Apr 2017;51(8):658-669. doi:10.1136/bjsports-2016-096396
- de Andrade Kratz C, de Salles Painelli V, de Andrade Nemezio KM, et al. Beta-alanine supplementation enhances judo-related performance in highly-trained athletes. Journal of science and medicine in sport / Sports Medicine Australia. Apr 2017;20(4):403-408. doi:10.1016/j.jsams.2016.08.014
- Mate-Munoz JL, Lougedo JH, Garnacho-Castano MV, et al. Effects of beta-alanine supplementation during a 5-week strength training program: a randomized, controlled study. Journal of the International Society of Sports Nutrition. 2018;15:19. doi:10.1186/s12970-018-0224-0
- Invernizzi PL, Limonta E, Riboli A, Bosio A, Scurati R, Esposito F. Effects of Acute Carnosine and β-Alanine on Isometric Force and Jumping Performance. Int J Sports Physiol Perform. Apr 2016;11(3):344-9. doi:10.1123/ijspp.2014-0507
- Blancquaert L, Everaert I, Baguet A, et al. Acute preexercise supplementation of combined carnosine and anserine enhances initial maximal power of Wingate tests in humans. J Appl Physiol (1985). Jun 1 2021;130(6):1868-1878. doi:10.1152/japplphysiol.00602.2020
- Lombardi C, Carubelli V, Lazzarini V, et al. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition (Burbank, Los Angeles County, Calif). Jan 2015;31(1):72-8. doi:10.1016/j.nut.2014.04.021
- Berti Zanella P, Donner Alves F, Guerini de Souza C. Effects of beta-alanine supplementation on performance and muscle fatigue in athletes and non-athletes of different sports: a systematic review. The Journal of sports medicine and physical fitness. Sep 2017;57(9):1132-1141. doi:10.23736/s0022-4707.16.06582-8
- Patel KA, Farias de Oliveira L, Sale C, James RM. The effect of β-alanine supplementation on high intensity cycling capacity in normoxia and hypoxia. Journal of sports sciences. Jun 2021;39(11):1295-1301. doi:10.1080/02640414.2020.1867416
- Norberto MS, Barbieri RA, Bertucci DR, et al. Beta alanine supplementation effects on metabolic contribution and swimming performance. Journal of the International Society of Sports Nutrition. Jul 25 2020;17(1):40. doi:10.1186/s12970-020-00365-6
- Sas-Nowosielski K, Wyciślik J, Kaczka P. Beta-Alanine Supplementation and Sport Climbing Performance. Int J Environ Res Public Health. May 18 2021;18(10)doi:10.3390/ijerph18105370
- Brisola GMP, Redkva PE, Pessôa Filho DM, Papoti M, Zagatto AM. Effects of 4 weeks of β-alanine supplementation on aerobic fitness in water polo players. PLoS One. 2018;13(10):e0205129. doi:10.1371/journal.pone.0205129
- Esteves GP, Swinton P, Sale C, et al. Individual Participant Data Meta-Analysis Provides No Evidence of Intervention Response Variation in Individuals Supplementing With Beta-Alanine. International journal of sport nutrition and exercise metabolism. 01 Jul. 2021 2021;31(4):305-313. doi:10.1123/ijsnem.2021-0038
- Brisola GMP, Zagatto AM. Ergogenic Effects of β-Alanine Supplementation on Different Sports Modalities: Strong Evidence or Only Incipient Findings? Journal of strength and conditioning research / National Strength & Conditioning Association. Jan 2019;33(1):253-282. doi:10.1519/jsc.0000000000002925
- Patel AV, Friedenreich CM, Moore SC, et al. American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control. Med Sci Sports Exerc. Nov 2019;51(11):2391-2402. doi:10.1249/MSS.0000000000002117.
- Bischoff-Ferrari HA, Willett WC, Manson JE, et al. Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial. Original Research. Frontiers in Aging. 2022-April-25 2022;3doi:10.3389/fragi.2022.852643.
- Bischoff-Ferrari HA, de Godoi Rezende Costa Molino C, Rival S, et al. DO-HEALTH: Vitamin D3 - Omega-3 - Home exercise - Healthy aging and longevity trial - Design of a multinational clinical trial on healthy aging among European seniors. Contemporary clinical trials. Jan 2021;100:106124.
- DO-HEALTH Trial Collaborators, Bischoff-Ferrari HA. DO-HEALTH Trial home page. Accessed May 13, 2022, http://do-health.eu/wordpress/
- Bischoff-Ferrari HA, Vellas B, Rizzoli R, et al. Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial. JAMA. 2020;324(18):1855-1868. doi:10.1001/jama.2020.16909.
- Bischoff-Ferrari HA, Dawson-Hughes B, Platz A, et al. Effect of High-Dosage Cholecalciferol and Extended Physiotherapy on Complications After Hip Fracture: A Randomized Controlled Trial. Archives of Internal Medicine. 2010;170(9):813-820. doi:10.1001/archinternmed.2010.67
- Irwin ML, McTiernan A, Manson JE, et al. Physical activity and survival in postmenopausal women with breast cancer: results from the women's health initiative. Cancer Prev Res (Phila). Apr 2011;4(4):522-9. doi:10.1158/1940-6207.CAPR-10-0295.
- Meyerhardt JA, Heseltine D, Niedzwiecki D, et al. Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol. Aug 1 2006;24(22):3535-41. doi:10.1200/JCO.2006.06.0863.
- Hilfiker R, Meichtry A, Eicher M, et al. Exercise and other non-pharmaceutical interventions for cancer-related fatigue in patients during or after cancer treatment: a systematic review incorporating an indirect-comparisons meta-analysis. British journal of sports medicine. May 2018;52(10):651-658. doi:10.1136/bjsports-2016-096422.
- Schwartz AL, de Heer HD, Bea JW. Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors. Oncology (Williston Park, NY). Oct 15 2017;31(10):711-7.
- Stout NL, Baima J, Swisher AK, Winters-Stone KM, Welsh J. A Systematic Review of Exercise Systematic Reviews in the Cancer Literature (2005-2017). PM R. Sep 2017;9(9S2):S347-S384. doi:10.1016/j.pmrj.2017.07.074.
- Ramirez-Velez R, Zambom-Ferraresi F, Garcia-Hermoso A, Kievisiene J, Rauckiene-Michealsson A, Agostinis-Sobrinho C. Evidence-Based Exercise Recommendations to Improve Mental Wellbeing in Women with Breast Cancer During Active Treatment: A Systematic Review and Meta-Analysis. Cancers (Basel). Jan 12 2021;13(2)doi:10.3390/cancers13020264.
- Li J, Eu JQ, Kong LR, et al. Targeting Metabolism in Cancer Cells and the Tumour Microenvironment for Cancer Therapy. Molecules. Oct 20 2020;25(20)doi:10.3390/molecules25204831.
- Hojman P, Gehl J, Christensen JF, Pedersen BK. Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment. Cell Metab. Jan 9 2018;27(1):10-21. doi:10.1016/j.cmet.2017.09.015.
- Wang Q, Zhou W. Roles and molecular mechanisms of physical exercise in cancer prevention and treatment. J Sport Health Sci. Mar 2021;10(2):201-210. doi:10.1016/j.jshs.2020.07.008.
- Jurdana M. Physical activity and cancer risk. Actual knowledge and possible biological mechanisms. Radiology and oncology. Jan 12 2021;55(1):7-17. doi:10.2478/raon-2020-0063.