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Don't fall victim to frailty: evidenced-based strategies for lifelong power in aging individuals.


Loss of muscle mass with aging is a common process that begins in our 40s and accelerates as the years pass. Decreased muscle mass with aging can lead to "sarcopenia," a state of decreased muscle mass and strength that reduces metabolic rate, contributes to insulin resistance and increased risk of type 2 diabetes, promotes unhealthy blood lipid profiles, and promotes hypertension. (22)


However, age-related loss of muscle mass need not be the dramatic, inevitable decline expected by most people. Targeted interventions can reverse this muscle loss and improve performance as a result. Strength training by itself can help restore muscle mass and reverse the unhealthy consequences of sarcopenia. (23) However, results could potentially be enhanced by combining strength training with the supplements creatine and branched-chain amino acids. (24), (25)


Since its introduction in the early 1990s, creatine use has exploded among bodybuilders and athletes interested in gaining muscle mass and strength.

Even if you're not interested in building big muscles like a bodybuilder, there are health benefits to increasing muscle mass. By increasing muscle mass, you can support bone density, improve balance, and reduce injuries, along with preventing debilitating muscle wasting. (26), (27)

Creatine is not just for weight lifters. A study of creatine supplementation in men (average age 70 years) demonstrated that strength training plus creatine increased muscle mass by 7.26 lbs. In contrast, men who performed the same strength training program and consumed placebo gained only 2.86 lbs of muscle mass. Creatine and strength training also improved leg strength and endurance. (28) Strength, endurance, and lean tissue are maintained 12 weeks after stopping creatine supplementation and engaging in a reduced-intensity training program. (29)

Similar results were observed in another study that included women (age 65 and older), with outcomes in females comparable to males. (30) Increased strength and muscle mass led to 3.2% increase in bone mineral content over 12 weeks of strength training supplemented with creatine, compared to 1% decrease without training or creatine. (31)

The most popular form of creatine is creatine monohydrate, generally taken as a "loading" phase of 15-20 grams per day (generally split into 3-4 doses of 5 grams) for 5-7 days, followed by weeks to months of 2-5 grams per day. (32) An alternative form, poly-ethylene glycosylated (PEG) creatine, provides similar effects at one-fourth to one-half the dose of creatine, i.e., 1.25-2.5 grams per day. (33) Athletes taking creatine for up to 21 months have shown no adverse effects on kidney function, lipid values, or other basic health measures. (34) People with kidney diseases (such as glomerulonephritis, glomerulosclerosis, or interstitial nephritis) should not take creatine supplements unless so directed by their physician.


The so-called branched-chain amino acids (valine, isoleucine, and leucine) are amino acids that are essential to muscle maintenance and growth. BCAA are widely used by athletes and weight lifters to accelerate recovery after exercise. (35)

When combined with strength training, BCAA protein powder supplements reduce muscle soreness and accelerate recovery. Doses of BCAA used successfully have varied widely in studies, generally from 5 g up to 20 g per day. (36)

Leucine has been shown to increase muscle protein synthesis. (36) A metabolite of leucine called hydroxy-methylbutyrate (HMB) is useful to help non-athletes gain muscle mass and increase physical performance. A study of 31 men and women, average age 70 years, showed enhanced muscle growth and fat loss with supplementation of HMB, 3 g per day, combined with strength exercises performed 5 times per week. (37)

While HMB and creatine each possess unique muscle mass-increasing effects, additive benefits develop when the two are combined with resistance exercise. In one study, over a 3-week training period, those who supplemented with both creatine and hydroxymethylbutyrate (HMB) gained more lean mass than those who only utilized one of the supplements. (38) By increasing strength and muscle mass, we can expect bone density to increase, balance to improve, metabolic rate to accelerate, and insulin responses to normalize.


Energy boosters are supplements that increase energy, but not through replacement of low hormone levels or correcting nutrient deficiency. These agents boost energy and performance through a variety of unique mechanisms.


The adaptogen rhodiola (Rhodiola rosea) is a relatively recent discovery to the US, but has been used for centuries to enhance strength and resilience by people in the mountainous regions of northern Europe and central Asia.

Recent randomized, double-blind research confirms the observations made in real-world experiences. Individuals with stress-related fatigue experienced increased stamina and mental focus upon supplementing with 576 mg of rhodiola extract per day. (39) In this study, a reduction in cortisol response to awakening stress appeared to be part of the explanation behind the observed effects. No side effects were observed in the treatment group.

In another study, increased exercise endurance was observed in young healthy volunteers who supplemented with rhodiola, 200 mg per day. (40)

Interestingly, a double-blind study involving a competitive rowing team showed that rhodiola supplementation increased total antioxidant levels in the plasma of those taking the supplement vs. those taking placebo. (41)


L-Tyrosine (tyrosine) is the amino acid source that provides the starting material for the synthesis of several neurotransmitters, including dopamine, epinephrine (adrenaline), and norepinephrine, and is also involved in the function of organs responsible for making hormones, including the thyroid gland.

Tyrosine supplementation has been studied and applied successfully by the US military as a means of maintaining performance and mood in the face of prolonged, stressful situations such as battle or sleep deprivation. (42), (43) Tyrosine appears to reduce the perceived effects of stress, though relatively high doses may be required for these effects (up to 100 mg/kg, or 7,000 mg for an averaged-sized adult). (44)

Tyrosine supplementation has been observed to decrease rather than increase blood pressure. (45)

Theoretically, the combination of tyrosine with tryptophan (a precursor of serotonin) could have potential for even more marked energy and mood-elevating effects. (46) The long-term safety of L-tyrosine in excess of 1,000 mg per day, however, is not known.


Vitamin D      5,000-6,000 IU per day
Iodine         500-1,000 mcg per day
DHEA           10-25 mg per day (women) / 25-50 mg per day (men)

Pregnenolone   100-300 mg per day
BCAA           5-20 grams per day
HMB            3 grams per day
Creatine       15-20 grams per day (loading phase) / 2-5 grams per day

Rhodiola       200 mg per day
Tyrosine       1,500-7,000 mg per da
Phenylalanine  50-100 mg per day
Taurine        1,500 mg-6,000 mg per day
Melatonin      1-3 mg per night, 1-2 hours before sleep
L-Tryptophan   250-2,500 mg at bedtime
Valerian       300-600 mg, one hour before bedtime


phenylalanine, provides the backbone for the body to synthesize the hormones that modulate the stress response, epinephrine and norepinephrine. Low phenylalanine means low adrenaline and low energy. Adequate availability of phenylalanine means access to epinephrine and norepinephrine when you need it. Because depression may, at least in part, be related to lower levels of these hormones, phenylalanine in the amount of 150-200 mg per day has been used successfully for treatment of depression, with effects similar to prescription drug imipramine. (47)

Please use judgment in your use of phenylalanine. If used properly, it can suit your needs: boost energy, and smooth the inevitable fluctuations in mood and stamina. If used unwisely, trouble can result, including high blood pressure and anxiety. (48)

Low doses and occasional use are the keys with phenylalanine, e.g., 25-50 mg, 2 times per day. Evening doses should be avoided, since insomnia can result.

People with the genetic disorder called phenyl-ketonuria (PKU) need to avoid phenylalanine-containing foods and supplements and therefore should not take phenylalanine. Also, anyone with hypertension should use phenylalanine carefully under the supervision of a health provider. (48) People with tardive dyskinesia may not be able to correctly process phenylalanine, and should therefore avoid phenylalanine supplementation. L-phenylalanine competes with several other amino acids for uptake into the body and the brain. For best results, phenylalanine should therefore be taken between meals, or away from protein-containing foods.


Taurine is an amino acid found particularly in protein-rich foods like eggs, meat, and fish. Among its many effects in the human body, taurine is an important constituent of bile and participates in the absorption of fats and fat-soluble vitamins. (49) Some studies have suggested that, along with omega-3 fatty acids, taurine is the component of fish that confers its substantial cardiovascular benefits. (50)

Several studies have suggested that taurine supplementation at a dose of 2,000 mg enhances endurance exercise performance (cycling, running, rowing), possibly by reducing lactate production; its effects may be enhanced when taken in combination with caffeine. (51), (52) Studies of mental performance and information processing have also suggested positive effects of taurine, also in combination with caffeine and glucuronolactone. (53), (54) Taurine supplementation is safe in adults at doses of 1,500-6,000 mg daily. (49)


In the modern world, people are forever searching for ways to abbreviate the need for sleep. Sleep is commonly sacrificed for the sake of enjoying more waking hours. The National Sleep Foundation recommends that adults sleep at least 7 hours nightly, but 29% of US adults fail to get even this much sleep. (55) Chronic sleep deprivation can lead to overreliance on stimulants to boost energy and to compensate for the performance-reducing effects of sleep deprivation.

In truth, there is simply no healthy means to reduce your need for sleep. The fact is, we need our sleep. Any effort to reduce our need for sleep forces us to pay the price with reduced physical, mental, and emotional performance--even increased mortality. (56) If we accept this fact, then let's ask the question: can we enhance sleep quality to derive greater daytime physical performance?

First, a brief sleep primer. Sleep is a mind-active, body-inactive state. Like the seasons of the year, the brain proceeds through a predictable series of phases distinguishable by intensity, frequency, depth, duration, and content. The effects of disrupting sleep phases, even with a full night of sleep, are serious, as evidenced by sleep disorders like sleep apnea, a condition involving pauses in breathing that occurs during sleep. They include snoring, disturbed sleep, reduced concentration and memory, mood disorders, excessive sleepiness and, if left untreated, cardiovascular disease, decreased health-related quality of life, and increased incidence of motor vehicle accidents. (57)

In general, non-restorative sleep has been associated with excessive daytime sleepiness, high blood pressure, higher levels of inflammation. (58), (59), (60)

One useful strategy to derive maximum benefit from sleep is to ensure, even enhance, the duration and quality of deepest phases of sleep. (59) Unfortunately, some prescription sleep agents, especially the benzodiazepine class, introduce some undesirable effects on sleep, including abbreviated rapid-eye movement (REM) sleep and next-day sleepiness. (60)

Diminished pineal gland secretion of the natural human sleep hormone, melatonin, (61) accounts for a gradual decline in sleep duration and quality as we age. (62)

Melatonin is available as a dietary supplement and is a useful agent to encourage the body's physiologic acceptance of sleep: body temperature is lowered, blood pressure reduced, and REM sleep prolonged. (63), (64) Dose needs vary from 1-3 mg per night to generate these effects. Melatonin is best taken at least 1-2 hours before sleep is desired, unlike the 30 or so minutes of a sleeping pill. The key is to start with a low dose, even as low as 0.5 mg, and build gradually to determine the ideal dose for you. High-dose melatonin is typically reserved for other uses, such as the treatment of cancer or sarcoidosis.

L-tryptophan, an amino acid that converts to the sleep-regulating hormone, serotonin, can also be useful to encourage sleep, though the effects on sleep architecture are complex. (65) Interestingly, tryptophan depletion is a tool used in research to explore the effects of both tryptophan and serotonin on sleep; tryptophan depletion (e.g., low-protein diet) has been found to adversely affect sleep patterns. (66) Tryptophan, usually in the dose range of 250-2,500 mg, shortens the amount of time to achieve sleep (shortened "sleep latency") and increases deep sleep and REM. (67)

Valerian (Valeriana officinalis)is the leading medicinal herb for the treatment of insomnia. It has, in multiple double-blind studies, been shown to improve sleep quality even in people with restless leg syndrome, in which abnormal discomfort and movement of the legs disrupts sleep, using a dose of 800 mg before bed. (68), (69), (70) Faster sleep onset and increase in slow-wave phase sleep also develops with valerian supplementation. (71) The optimal dose of valerian as the extract remains uncertain, though most clinical studies have used doses in the range of 300 to 600 mg taken one hour before bedtime; side-effects have compared favorably to placebo. (72), (73)


Frailty--age-related deterioration in physical strength and performance--is a critical concern for aging individuals. A growing body of literature demonstrates that nutrients, hormones, and herbal extracts can be used to ward off age-related weakness and enhance human performance throughout life span. Optimizing human performance relies on five pillars: ensuring basic nutritional status, restoring performance-enhancing hormones, preventing muscle weakness and enhancing strength, boosting energy, and restoring healthy sleep. This multifaceted program can help you ensure supercharged performance--for life.

If you have any questions on the scientific content of this article, please call a Life Extension[R] Health Advisor at 1-866-864-3027.


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By William Davis, MD
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Title Annotation:REPORT
Author:Davis, William
Publication:Life Extension
Article Type:Report
Date:Mar 1, 2010
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