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Health Protocols

Exercise Enhancement

Integrative Interventions

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

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 treatments 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. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.

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