Withstand Fatigue with Beta-Alanine

Beta-Alanine Fights Fatigue
Along with its role as anti-glycation and fold-right agent
By Will Block

Fatigue makes cowards of us all.
— George S. Patton


The average age of the men and women in the study was 73 years, with an age range from 62–84. The volunteers receiving beta-alanine had nearly 30% improvement in their physical working capacity!
hese are the times that try men’s souls,” wrote Thomas Paine in late 1776 in his opening essay of The Crisis, prefacing the American Revolution. Indeed, in our own era of market melt-down, recession, and financial crisis, we are likewise tried . . . mentally, physically, financially, and spiritually. And when our energy is insufficient to the mounting tasks at hand, we become tired and fatigue sets in.

Did you know that of all the complaints for which people seek medical care, ongoing fatigue is far and away the most common? This is no small complaint. In fact, for most people, sleep or rest does not solve the problem. The cold truth is that fatigue is not easily reversed.

“Unexplained” Fatigue

Generally speaking, fatigue is a weariness caused by exertion, either mental or physical, and usually a combination of both. However, fatigue is also a symptom of many diseases, so if you are experiencing fatigue, it is always advisable to consult with your doctor to rule these out as possibilities.* When diseases are ruled out, fatigue is said to be unexplained or idiopathic. Yet there are explanations—they are just harder to identify with as much precision. Of the possible causes, neurological, psychological, metabolic, muscular, and inflammatory factors should be considered. Some of these are fully in the domain of mental fatigue, a subject that has been addressed in this publication before. (See “Feed Your Head—Exclusive Interview with Life Extension Scientists Durk Pearson & Sandy Shaw®” in the January 1999 issue. This article is available as a pamphlet from Life Enhancement.) Other causes are more indicative of physical fatigue, the inability to continue functioning at the level of one’s normal abilities, given one’s individual physical fitness. Physical fatigue will be our principal focus in this article.


*Do not dismiss the possibilities that fatigue may be caused by many specific diseases or syndromes, including autoimmune diseases, anxiety or panic disorder, blood disorders, cancer, chemical dependency, chronic fatigue syndrome, depression and other mental disorders that feature depressed mood, diabetes, eating disorders, fibromyalgia, heart disease, hypothyroidism, infectious diseases, Lyme disease, lead poisoning, leukemia or lymphoma, muscular dystrophy, physical trauma and other pain-causing conditions, such as arthritis, neurological disorders such as Parkinson’s disease and post-concussion syndrome, pregnancy, sleep deprivation or sleep disorders, superior canal dehiscence syndrome and Wilson’s disease. Please rule these out by seeing your physician.


Age, Activity, and Stress

Aside from the challenges of a perplexing and changing world, there are several aspects to physical fatigue. First, physical fatigue is age-related—the elderly are far more prone to complaints about exhaustion than the young. With age, for example, our neurological system is apt to be in decline. It is also likely that energy metabolism becomes less efficient, with the biochemical reactions necessary to maintain life pummeled, for example, by wear and tear and lower nutrient bioavailability. As we age we are also more prone to muscle mass loss and muscle inefficiency. Within our cells, mitochondria lose their ability to produce enough energy molecules for cellular functions. Oxidative damage to mitochondria may produce a cascade of havoc to other intracellular elements, also affecting protein and lipids, not to mention DNA.

Next, physical fatigue is activity-related—those who engage in higher levels of activity are likely to run out of energy more quickly. Just as fatigue usually becomes particularly noticeable during heavy exercise, when muscle weakness results, it is also true during intensive activity that is not muscle dependent, such as sustained mind work. Whether fatigue is caused by physical or mental activity, one impacts the other. If you’re physically exhausted, it is not the best time to study, to learn something new, or to use your mind. On the other hand, when you’re mentally worn out, it’s the wrong time to exercise.


Did you know that of all the
complaints for which people seek
medical care, ongoing fatigue is far
and away the most common?


Third, physical fatigue is stress related—those who take on greater responsibilities in their work tend to find that exhaustion becomes more common. Of course, stress affects the mind as well as the body. Thus there is usually an element of mental fatigue that accompanies physical fatigue. But even if that is not the case and your spirits are high, stress-related physical fatigue may still be a problem. Certain professions, by the way, are more stressful than others. Think surgeons, stockbrokers, and information technologists (yes, that was voted the single most stressful job, according to a recent online survey).


“A recent study has found that
beta-alanine can decrease the rate of
fatigue in elderly subjects during
exercise by increasing levels of
carnosine in skeletal muscle.


Finally, age-, activity-, or stress-related fatigue are additive and confluent. Recently, for example, a small study concluded that stress has a stronger effect on the elderly than young adults, and that it is activity-dependent.1 The researchers noted that stress hormones affect brain regions involved in decision making, regions that decline in volume with aging, thereby reducing the effectiveness of dopamine transmission. The consequence is fatigue, brought on by age, activity and stress.

Limited Fatigue Relief

While certain dietary supplements may help to alleviate physical fatigue, to date the benefits have varied. Among those that have been shown to be strongly positive are neurological and psychological nutrients such as phenylalanine; choline, omega-3 fish oil, and galantamine; tryptophan and 5-HTP; and acetyl L-carnitine. [For more information, see “Feed Your Head—Exclusive Interview with Life Extension Scientists Durk Pearson & Sandy Shaw” (Jan. 1999), “Maintain Your Brain the Durk Pearson & Sandy Shaw Way,” (May 2004, and on page 17 in this issue), “The Durk & Sandy Way to a Quiet Mind for Sleep or Daytime Calmness” (Sept. 2007), “Refresh Your Brain with ALC” (Sept. 2006), and “Acetyl L-Carnitine May Help with Chronic Fatigue” (Aug. 2004).] These are unquestionably important nutrients for mental stress and some aspects of physical stress. On the metabolism front, it is clear that many nutrients—too numerous to mention—can be of benefit for reducing wear and tear on metabolic systems. Sadly however, these benefits are rarely apparent for reducing fatigue in the short run.

Inflammation is another area that can be addressed by nutrients. Briefly, inflammation is part of the natural healing process. It occurs when body tissue is damaged, or when pathogens or irritants are present. It can be either acute or chronic; the first is acceptable, while the second is usually not, and represents a failure of early defense mechanisms. It may also result from an overwhelming assault on those mechanisms. Prolonged inflammation can lead to chronic inflammation and a progressive shift in the type of cells at the site of inflammation. This may be characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Nutrients that have been shown to be some value are boswellia, bromelain, curcumin, omega-3 fish oil, quercetin, and galantamine (for brain inflammation). There are others. But as valuable as these can be, it is rare that they can produce enough of a benefit to make a perceivable impact against fatigue.

Muscular Support

Lastly we have the muscular realm, and it is here, that nutrients show their . . . er . . . muscle. First in order of importance are the amino acids arginine and citrulline. [See “Putting More Power into Your Life,” (Apr. 2006); also see the sidebar, “Another Way to Increase Exercise Capacity.”] These have been shown to play an important role in muscle enhancement, and that means increased strength, increased endurance, and improved wound healing, by the way. When properly cofactored with other nutrients, arginine and citrulline are among the most important nutrients you can take. Bigger and stronger muscles are definitely helpful for combating fatigue.

Another Way to Increase Exercise Capacity

A few years ago, researchers in Poland investigated whether oral administration of arginine would improve exercise capacity in 17 patients with mild to moderate congestive heart failure (CHF).1 The patients received 3 g of arginine or placebo 3 times daily (9 g/day total) for 7 days. Testing was done on a treadmill according to a standard protocol, and the patients were asked to exercise until fatigue or dyspnea (difficulty in breathing) forced them to stop. After a 7-day washout period, the arginine and placebo regimens were reversed, and the tests were repeated—thus all the patients served as their own controls.

Whereas the controls had an average “Maximal Exercise Test” (MET) duration of 70 seconds on the treadmill, the arginine treatment yielded an average MET of 99 seconds—a 41% improvement. The researchers attributed this effect primarily to improved peripheral vasodilation caused by increased NO production.

Arginine Uptake Is Reduced in CHF

An Australian research team became interested in a more fundamental question, namely, what role does arginine play in the pathophysiology of congestive heart failure?2 They were intrigued by a scientific paradox: although nitric oxide synthase levels are sometimes elevated in the heart muscle of patients with CHF, nitric oxide levels are apparently reduced, contrary to what one would expect. (It is well known that NO levels are deficient in the vascular endothelium in CHF patients, leading to endothelial dysfunction, a consistently observed feature of this debilitating disease—but the role of NO in the heart muscle is a different matter, and a controversial one.)

The researchers studied the effects of infusing radioactively labeled arginine into the circulation of seven patients with moderate to severe CHF. By measuring the subsequent distribution of this “hot” arginine in the blood, the coronary vascular endothelium, and the heart muscle, they inferred that the rate of uptake of arginine by the patients’ heart-muscle cells was substantially reduced, and the rate of clearance of arginine from the patients’ blood was also reduced. In other words, arginine was not entering the cells at the normal rate, presumably because of a CHF-related breakdown in the molecular transport mechanism.

Our Need for Arginine Increases with Age

Endothelial dysfunction promotes not just hypertension, but also the formation of blood clots and of atherosclerotic plaque deposits, which further restrict blood flow and can lead to a heart attack. Nitric oxide is considered to be antiatherogenic, i.e., it helps prevent atherosclerosis. And since it has long been known that endothelial dysfunction increases with age, the importance of having adequate compensatory supplies of arginine, the precursor of NO, also increases with age, even when there are no symptoms of cardiovascular disease.

References

  1. Bednarz B, Jaxa-Chamiec T, Gebalska J, Herbaczynska-Cedro K, Ceremuzynski L. L-Arginine supplementation prolongs exercise capacity in congestive heart failure. Kardiol Pol 2004;60(4):348-53.
  2. Kaye DM, Parnell MM, Ahlers BA. Reduced myocardial and systemic L-arginine uptake in heart failure. Circ Res 2002;91:1198-1203.

Beta-Alanine Lessens Exercise Fatigue

In what must be considered a major breakthrough for muscular development, a recent study has found that beta-alanine can decrease the rate of fatigue in elderly subjects during exercise by increasing levels of carnosine in skeletal muscle.2 Beta-alanine, the rate-limiting precursor of carnosine, has previously been shown to elevate the carnosine content of muscle, something that has not been found clearly for carnosine alone. Carnosine is a dipeptide (beta-alanyl-L-histidine) that is highly concentrated in muscle tissue where its presence is necessary to maintain cellular pH, which is vital for proper muscle function during exercise.

Muscle carnosine content is inversely related to age, according to human and animal studies; the older you get, the less you have.3,4 After the age of fifty, sarcopenia, the loss of muscle mass with age, has been found to affect most people.5-7 That is unfortunate because this diminution is associated with significant loss in strength, power, and the ability to resist fatigue in elderly men and women. Furthermore, when these losses occur there is a deterioration of motor coordination, the result of which leads to an increase in the frequency of falls, consequential injury and even deaths among the elderly.

Unexpected Results—30% More Intensity

Dr. Jeffrey R. Stout of the University of Oklahoma in Norman, who led the beta-alanine placebo-controlled study was surprised, “We weren’t sure that this would impact [our subject’s] physical capacity like it did.”8

When elderly men and women were given 2.4 g of beta-alanine (800 mg, 3 times daily) for 90 days they were able to exercise nearly 30 percent more intensely before becoming fatigued. That’s really remarkable. Just three months of beta-alanine supplementation served to increase physical working capacity by delaying the onset of neuromuscular fatigue in elderly men and women (9 men and 17 women, with an average age of about 73).

Previously, beta-alanine has been found to be beneficial for young men and women (18–30 years of age) by increasing the amount of carnosine in their muscles.9,10 However, the dose was nearly three times greater (6.4 g/day) than in the study with elderly subjects. Adequate levels of carnosine are crucial to helping maintain neutral pH in muscle tissue. In the course of exercising to the point of fatigue—the only way to insure optimum benefit from exercise—the muscles affected become increasing acidic, in part due to lactic acid buildup. Yet, higher levels of carnosine can prevent this buildup and help buffer against this acidity, and higher output can be achieved without “feeling the burn,” the result of lactic acid accumulation.

Beta-Alanine—A Multi-Functional Amino Acid

In addition to its effect as an anti-fatigue agent, beta-alanine also exhibits neurotransmitter activity, by activating glycine and GABA receptors, and promotes anti-glycation effects because it increases carnosine levels in the body.


When chaperones fail to do their work and proteins are misfolded, the result can be manifested at cellular and systemic levels.

Moreover, according to a 2005 study, beta- alanine has additional properties which may be of physiological significance.1 Biological stress increases levels of beta-alanine, which regulates excitotoxic responses and prevents neuronal cell death. From this knowledge, the researchers hypothesized that beta- alanine’s protective role might involve preservation of enzyme structure and function. They monitored heat-induced changes in lactate dehydrogenase (LDH)—an enzyme that catalyses the interconversion of pyruvate and lactate as well as the concomitant interconversion of NADH and NAD+—in the presence and absence of beta-alanine, and observed that beta-alanine suppressed heat-induced LDH inactivation, prevented LDH aggregation, and reactivated thermally denatured LDH. From these observations, they concluded that beta- alanine has chaperone-like activity and may play a cellular role in the preservation of enzyme function. Thus beta-alanine acts like an osmolyte, and may be able to help with proper protein folding.

Reference

  1. Mehta AD, Seidler NW. Beta-alanine suppresses heat inactivation of lactate dehydrogenase. J Enzyme Inhib Med Chem 2005 Apr;20(2):199-203.

Breaking Through the Fatigue Barrier

In the study, participants had their exercise capacity tested on a special exercise bike called an ergometer. Electrodes were attached to their thigh muscles, to measure electrical activity which signals acid build-up. While placebo takers showed no increased ability to withstand fatigue, those taking beta-alanine were able to exercise 28.5% more intensely. Of interest, these results were comparable with an earlier study in which elderly people received similar improvement in exercise capacity after undergoing 12 weeks of endurance training. But the subjects in the current study, it should be noted, were untrained, and the 28.5% increase in the physical working capacity at the fatigue threshold occurred without any type of additional training during the ninety days of supplementation.

Recommended for Everyone Over 60

The elderly have been found to eat less meat, and consequently there is less carnosine available for muscles. And carnosine supplements are not directly bioavailable—they are broken down immediately, and only a small amount is regenerated from the break-down components. On the other hand, beta-alanine triggers the production of carnosine in muscle tissue.

Enthused about the outcome, Dr. Stout recommends beta-alanine to everyone he knows who’s over 60. He even has his own parents on it. “It can’t hurt and it can only help, but elderly folks must be patient,” the researcher said, cautioning that it takes a while for the carnosine to increase in the muscle, perhaps 4 weeks before any benefit is seen. As a final measure of success, participants were able to notice a difference in their ability to move through their daily activities. And they noticed correctly before the researchers were aware who was in the placebo or supplement group.


Enthused about the outcome,
Dr. Stout recommends beta-alanine to
everyone he knows who’s over 60.
He even has his own parents on it.


Several of the subjects said about the supplement, “I don’t care what it is . . . I want more of it.” Perhaps you will too when you see what beta-alanine can do for your personal war against fatigue.

References

  1. Mather, M., Gorlick, M., & Kryla-Lighthall, N. (in press). To brake or accelerate when the light turns yellow? Stress reduces older adults’ risk taking in a driving game. Psychol Sci 2008; http://www.usc.edu/projects/matherlab/pdfs/Matheretalinpress.pdf
  2. Stout JR, Graves BS, Smith AE, Hartman MJ, Cramer JT, Beck TW, Harris RC. The effect of beta-alanine supplementation on neuromuscular fatigue in elderly (55-92 Years): a double-blind randomized study. J Int Soc Sports Nutr 2008 Nov 7;5(1):21.
  3. Stuerenburg HJ, Kunze K. Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. Arch Gerontol Geriatr 1999;29(2):107-13.
  4. Tallon MJ, Harris RC, Maffulli N, Tarnopolsky MA. Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects. Biogerontology 2007;8(2):129-37.
  5. Brooks SV, Faulkner JA. Skeletal muscle weakness in old age: underlying mechanisms. Med Sci Sports Exerc 1994;26(4):432-9.
  6. Chandler JM, Hadley EC. Exercise to improve physiologic and functional performance in old age. Clin Geriatr Med 1996;12(4):761-84.
  7. Doherty TJ, Vandervoort AA, Taylor AW, Brown WF. Effects of motor unit losses on strength in older men and women. J Appl Physiol 1993;74(2):868-74.
  8. Harding A. Beta-alanine helps seniors stave off fatigue. Reuters Health, Nov. 12, 2008.
  9. Stout JR, Cramer JT, Mielke M, O’Kroy J, Torok DJ, Zoeller RF. Effects of twenty-eight days of beta-alanine and creatine monohydrate supplementation on the physical working capacity at neuromuscular fatigue threshold. J Strength Cond Res 2006;20(4):928-31.
  10. Stout JR, Cramer JT, Zoeller RF, Torok D, Costa P, Hoffman JR, Harris RC, O’Kroy J. Effects of beta-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women. Amino Acids 2007;32(3):381-6.


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

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