Friday, June 22, 2012

Aging: what can we control? By Jerry Brainum

     In 2006 scientists from the School of Ocean Sciences at the University of Wales, Bangor, found an unusual specimen growing on the seabed in the icy waters off the north coast of Iceland. It was an ocean quahog, a clam also known as Arctica islandica. What made that particular mollusk unique was its age: It was between 405 and 410 years old and still very much alive and thriving. It’s now the oldest living creature on earth, eclipsing the old record of 220 years held by another clam found in 1982. The longevity of the newly discovered marine Methuselah makes the human longevity record of 122 seem paltry.
    I’d wager that most people would be happy to live to 100 or more, provided that life span also included a high quality of life. (Living a long time in poor health is hardly ideal.) Most bodybuilders would opt to follow the example of Jack LaLanne, who died in January, 2011 at age 96. Jack exercised up to the end, and I can verify that his grip was as strong as that of a man a half his age. When asked the secret of his high level of health and fitness, the fitness legend cited his lifelong workouts and focus on good nutrition. The fact that he was a slight man who hadn’t been overweight for most of his life also figured into his longevity.
We cannot entirely halt the aging process, but we can slow it down and maintain our quality of life through the passing years. Contrary to popular opinion, many degenerative diseases associated with aging are not inevitable. Absent genetic anomalies, the two main causes of death, cardiovascular disease and cancer, are largely preventable through exercise and diet.
     A recent study involving 2,401 twins proved that exercise slows the aging process at the molecular level. Those who engaged in regular exercise had lower rates of cardiovascular disease, type 2 diabetes, high blood pressure, obesity and osteoporosis. The authors noted that a sedentary lifestyle “increases the propensity to aging-related disease and premature death.” One portion of the study measured the length of telomeres in participants’ white blood cells. Telomeres are the ends of chromosomes, and their length determines how much more a cell can replicate and repair itself. Shorter telomeres mean faster aging. While all of the subjects in the study had shorter telomeres with age, those who were inactive had considerably shorter telomeres than those who remained active. In fact, the most physically active subjects had telomere lengths that would indicate that they were biologically 10 years younger than their physically inactive counterparts.
     Many scientists who study aging differentiate chronological from biological aging. Chronological aging refers to your age in years. Biological aging refers to it from a functional point of view. A 30-year-old can be biologically 50 and a 60-year-old biologically 30. The factors that affect biological age are known as biological markers. In 1991 two scientists from Tufts University published Biomarkers: The 10 Determinants of Aging That You Can Control, whichoffered the then-revolutionary premise that by eating correctly and keeping the body strong through lifting weights, people could extend the quality of life almost indefinitely.
     The salient question these days is whether ongoing research on aging confirms the tenets offered 21 years ago in Biomarkers. Let’s take a look at those biomarkers:
1) Muscle mass. As most people age, lean muscle is gradually replaced by bodyfat. The loss of muscle may result in a loss of mobility, the primary reason older persons wind up in nursing homes. For a bodybuilder the importance of maintaining muscle increases when you get past age 40. While you may not be able to retain the same mass that you had at 20, the muscle you do retain will improve your quality of life. So the key is to continue training long after your competition days are over. That’s precisely what most bodybuilding champions do.
2) Strength. A lack of exercise leads not only to muscle loss that accelerates past age 40 but also to a loss of strength. What happens is that the fast-twitch-muscle fibers, which are responsible for both muscle mass and strength, atrophy, or shrink, while the slow-twitch fibers, which are smaller and weaker, become dominant. Studies show that most people who don’t exercise lose 20 percent of the fast-twitch fibers in their thighs between 30 and 70. Fast-twitch fibers also dictate speed of movement, and their atrophy accounts for the slowness associated with age. Connective-tissue aging and degenerative diseases, such as arthritis, also play a role.
     A major myth—debunked by research—is that you cannot build muscle or strength past a certain age. True, muscular strength and size do peak around age 35, but muscle exhibits a remarkable plasticity and responds to exercise at almost any age. Tufts University researchers found that even those in their 90s who relied on canes or walkers were able to discard them following a weight-training program. Okay, you won’t see any of them challenging Phil Heath at the Mr. Olympia, but their increased mobility was a victory as fulfilling as winning any title.
3) Basal metabolic rate. The BMR refers to how many calories you burn at rest. That measure in turn largely determines how much bodyfat you carry. Those with a higher BMR can take in more calories without gaining fat. Conversely, those with a low BMR can get fat rapidly if their calorie intake is ahead of their physical activity. The BMR naturally declines with age, chiefly because of muscle loss. Muscle determines BMR, since muscle burns the most calories at rest. Studies with master athletes—over age 40—show that some decline is inevitable. On the other hand, the decline is less in those who continue to lift weights. Just doing aerobics will do little or nothing to prevent the age-related decline in BMR.
4) Bodyfat percentage. Many older people weigh no more than they did during their earlier years but look much different, usually because of bodyfat. As people age, they become less active yet may still eat the same number of daily calories, resulting in more bodyfat. The change in body composition is often so gradual that the term “creeping obesity” has been applied. In years past, bodyfat was considered more of an aesthetic problem than anything else. Ongoing research, however, has linked excess fat to overall inflammation.
Fat is far more than the inert energy storage site it was long considered. Bodyfat is an active endocrine organ, releasing more than 100 chemicals collectively known as adipokines. Most of them are inflammatory mediators, playing active roles in most diseases. Having excess fat in the midsection is particularly dangerous. Visceral fat is linked to insulin resistance, cardiovascular disease, diabetes and the onset of the metabolic syndrome. The good news is that it’s also the most labile, or easily manipulated, kind of bodyfat, the first to go when you take up a sensible diet and exercise.
A low level of bodyfat is good for a number of health benefits over the years: low blood insulin, low blood lipids, lower overall inflammation and lower blood pressure. Consider how rare it is to see an obese person living past age 90.
5) Aerobic capacity. Many bodybuilders ignore this one. For example, I know a former top bodybuilding champion, now in his 60s, who doesn’t do any formal aerobic exercise. He believes that cardiovascular benefit can be derived entirely from weight training. He also suffers from heart disease; aerobics would significantly improve his condition.
    While weight training can duplicate many of the cardiovascular effects of aerobics, the specificity-of-exercise principle, as the physiological literature calls it, comes into play. Various forms of exercise specifically focus on certain body systems. For building strength and muscle, nothing tops weights. For flexibility, stretching reigns supreme. For working the heart and lungs, aerobics is best.
    From a longevity point of view, there are many good reasons to incorporate aerobics into your weight-training program. Long-term heavy lifting imposes structural changes in the heart that predispose you to congestive heart failure. You can avoid that if you continue to exercise or if you modify those structural changes by also doing aerobics. Aerobics is also the most effective way to control bodyfat, since fat can be oxidized, or burned, only in the presence of oxygen.
     Still another reason it’s prudent to maintain aerobic fitness has to do with organelles in the cell called the mitochondria, where the cell’s energy comes from and where fat is burned. The more mitochondria in your cells, the more fat you can burn and the more oxygen you can process to produce ATP, the elemental cellular energy source. Nothing beats aerobics for triggering mitochondrial synthesis, which appears to boost natural antioxidant functions that add a further level of protection to the cells. One theory of aging is that the loss of mitochondria leads to cellular death. If that theory holds true, aerobics may be a kind of fountain of youth.
 6) Glucose tolerance. Many people become insulin insensitive with age, which sets them up for diabetes and accelerated aging. When there’s too much glucose in the blood, the excess sugar combines with protein, leading to a loss of tissue strength, a process that’s thought to be responsible for the stiffness linked to aging.
More recent studies show that high blood glucose and insulin counts are associated with Alzheimer’s disease. What’s called insulin-degrading enzyme breaks down insulin, as well as a protein called beta-amyloid, in the brain. If the brain has too much glucose and insulin, the insulin-degrading enzyme doesn’t effectively clear out the beta-amyloid. Many researchers consider its buildup in the brain the primary underlying cause of Alzheimer’s disease.
     Blood glucose can be controlled by keeping your bodyfat low, working out and maintaining as much muscle as possible. Lifting weights promotes the activity of GLUT-4, a protein that transports glucose from the blood into the muscle. In fact, that process may be the reason lifting weights helps lower the risk of diabetes by more than 60 percent. Eating excess saturated fat is also linked to insulin resistance, especially in those who are sedentary. In those who lift weights, a certain amount of saturated fat acts as a substrate for testosterone synthesis. Testosterone, in turn, provides numerous antiaging benefits, especially to muscles.
Unfortunately, most medical professionals still subscribe to the long-standing myth that testosterone is linked to prostate cancer. A new study published in the January 29, 2008, issue of the Journal of the National Cancer Institute analyzed the results of 18 prior studies that included 3,886 men with prostate cancer and 6,438 men who were cancer-free. The researchers found no asociation between cancer risk and the blood amounts of any sex hormones, including testosterone, estrogen, DHEA and DHT.
7) Cholesterol-to-HDL ratio. Having excess cholesterol in the blood has long been considered a risk for cardiovascular disease, the leading cause of mortality, but recent studies show that the older you get, the less role blood cholesterol plays in cardiovascular disease. Some recent research even shows that a sudden drop in plasma cholesterol may be a harbinger of dementia. Other studies show that cholesterol intake from food provides an anabolic effect in older persons who lift weights. Among its other functions, cholesterol acts as the direct precursor of testosterone synthesis, and testosterone is associated with gains in muscular size and strength.
    High-density lipoprotein is considered the beneficial form of cholesterol. Composed mostly of protein, HDL helps ferry excess cholesterol in the blood back to the liver, where it is degraded into bile, then excreted. That’s the only way the body can rid itself of superfluous cholesterol, since, unlike fat, cholesterol cannot be oxidized. HDL also helps prevent the oxidation of low-density lipoprotein, which is also produced in the liver and is the major cholesterol transporter in the blood. LDL becomes dangerous when oxidized, and paroxanase, the built-in antioxidant found in HDL, prevents that. HDL increases when you exercise, stop smoking and lose bodyfat. The levels are also increased when you drink a small amount of alcohol.
8) Blood pressure. Preventing obesity, doing aerobics and controlling sodium intake will help prevent hypertension, a.k.a. high blood pressure. High blood pressure eventually causes congestive heart failure and is the primary risk factor for strokes. While drinking small amounts of alcohol helps prevent cardiovascular disease, excess amounts are closely linked to stroke. Chronic hypertension also gradually destroys the neurons in your brain, resulting in vascular dementia, which is nearly indistinguishable from Alzheimer’s. Taking plenty of potassium (at least 5,000 milligrams daily) and magnesium (at least 600 milligrams daily) will also block hypertension by blunting sodium mechanisms and other pathways.
 9) Bone density. The mineral content that provides bone density begins to leak from bones when you turn 30. Small-boned women who don’t do any weight-bearing exercise and are calcium- and estrogen-deficient are at high risk for osteoporosis. A lack of testosterone is associated with the onset of osteoporosis in men. Older men who walk around hunched over are likely exhibiting spinal degeneration resulting from a long-term testosterone deficiency.
Exercise, especially weight-bearing exercise such as weight training, maintains bone density over the years. That’s particularly true if certain bone-building elements, such as calcium, magnesium and vitamin D, are included in the diet. You also want to optimize the acid-to-alkaline balance to prevent the leaching of vital structural minerals from bone—the best way is to eat fruits and vegetables to balance the acidity that results from a high protein intake.
10) Regulating internal temperature. The most important thing to do here is to make sure you drink enough fluid. The sensation of thirst is impaired in many older people. That, in turn, can result in dehydration. Lack of sufficient fluids imposes stress on the kidneys, eventually leading to loss of kidney function. A low blood volume from dehydration interferes with oxygen delivery to muscles and other tissues, impairing energy levels and producing fatigue. In hot weather dehydration may result in cardiovascular collapse and death in older people. From a bodybuilding perspective, dehydration promotes catabolic reactions in cells, leading to muscle loss. On the other hand, keeping cells hydrated has anabolic effects.
    Maintaining these 10 biomarkers of age will improve your quality of life as you age. You’ll look and feel better. You may never achieve the life span of an Arctic clam, but look on the bright side: You won’t ever have to worry about ending up as chowder, either.
Guralnik, J.M. (2008). Successful aging: Is it in our future? Arch Int Med. 168:131-32.

 ©,2012, Jerry Brainum.Any reprinting in any type of media, including electronic and foreign is expressly prohibited.


Thursday, June 14, 2012

A Cancer Answer? by Jerry Brainum

A Cancer Answer?

Jerry Brainum

DIM-ing the danger with diet
    Prostate cancer is the most common form of cancer, accounting for 29 percent of newly diagnosed cases. It’s also the second leading cause of death in men. Prostate cancer has particular relevance to bodybuilders because of its association with several hormones, including testosterone, estrogen and insulinlike growth factor 1 (IGF-1).
     Androgens are known to speed the initial growth of prostate tumors, although recent evidence shows that the androgen involved isn’t testosterone but rather a metabolite called dihydrotestosterone (DHT). DHT is also associated with male pattern baldness and acne, two common side effects of anabolic steroid use. Many anabolic steroids are built on a DHT structure and are favored because they can’t be converted into estrogen. DHT, however, also causes prostate gland enlargement. On the other hand, more recent evidence shows that, similarly to testosterone, the prostate gland only accepts a finite amount of DHT, which would indicate that larger amounts of DHT circulating in the blood have no relationship to the onset of prostate cancer, although it's still implicated in benign prostate enlargement.
    Estrogen may be a more potent promoter of prostate cancer than testosterone or DHT. Most of the estrogen synthesized in men is a result of conversion of free testosterone by way of the enzyme aromatase, found in muscle, fat and brain tissue and at numerous other sites. Estrogen is the bane of bodybuilders’ existence, since it’s associated with increased subcutaneous fat, water retention and gynecomastia, or excess male breast tissue.
     Increased levels of IGF-1 often appear in conjunction with both breast and prostate cancers. While most bodybuilders are familiar with the anabolic properties of IGF-1, few realize that it’s also a potent stimulus to cell division; any type of cancer is essentially rampant cell division. Adding IGF-1 would be tantamount to adding oil to a fire. The ongoing debate in medicine is whether IGF-1 is a marker or stimulus of tumor formation. IGF-1 may be produced locally by tumors as a means of increasing metastasis, or spreading throughout the body. That makes sense, as IGF-1 is known to be produced in local tissues, such as muscle.IGF-1 also seems to block a process called apoptosis, which involves cell self-destruction. In the case of preserving heart and brain cells, the blocking of apoptosis by IGF-1 is a good thing; not so good with tumor cells!
     Prostate cancer has been linked to race (black men have higher rates), age (older men have increased rates) and family history (if you have an immediate male relative who had the disease, you likely inherited an increased tendency to get it). The good news is that research points to several potent nutritional preventives.
Many of those nutrients are found in fruits and vegetables. That’s ironic since many bodybuilders avoid eating fruits and vegetables because of the perception that they’re high in carbohydrates, particularly fructose But even staunch low-carb advocates, such as the late Dr. Robert Atkins, have wisely revised their former guidelines to allow limited portions of the more protective fruits and veggies.
     Cruciferous vegetables, which include brussels sprouts, broccoli, cabbage, kale and cauliflower, are particularly protective against cancer. They contain a host of chemicals known to induce enzymes that detoxify and destroy carcinogens, including glucobrassicin, which is converted upon being cooked or crushed into another substance, indole-3-carbinol (I3C). Once you ingest it, I3C is exposed to the acid environment of the gut and transformed into several products, among the most active being 3,3’–diindolylmethane (DIM).
      I3C and DIM may be familiar to some bodybuilders. Both substances have appeared in commercial food supplements touted to help break down excess estrogen. Of the two, DIM is far more stable and potent. It’s known to convert active estrogens into relatively inactive forms, which offers benefits for the prevention of estrogen-related cancers.
     Recent studies show that DIM may be even more potent against prostate cancer than was initially realized. In one recent study in which three types of prostate-cancer cell lines were exposed to DIM, all three committed immediate suicide, or apoptosis.1 The same study showed that when normal skin cells were exposed to DIM, no harm or damage ensued, thereby indicating that DIM attacks only cancerous cells. The effect also occurred in a previous study when breast cancer cells were similarly exposed to DIM.
      Another study found another mechanism whereby DIM destroyed prostate cancer cells.2 In that case DIM blocked the effects of DHT. Most prostate cancers are initially sensitive to the presence of DHT, and when its activity is blocked, the tumor shrinks and disappears.
     This second study also raises the question of whether DIM may help rid the body of both excess estrogen and DHT, each of which bodybuilders consider troublesome. DIM doesn’t inhibit the formation of DHT, as does the drug finesteride (Proscar), but rather blocks it at the cell-receptor level, making its activity more akin to the way the drug Nolvadex blocks estrogen cell receptors without actually inhibiting estrogen synthesis. Whether DIM works systemically or only at the level of the prostate gland is a question that awaits an answer.
1 Nachshon-Kedmi, M., et al. (2003). Indole-3-carbinol and 3,3’–diindolylmethane induce apoptosis in human prostate cancer cells. Food Chem Toxicol. 41:745-52.
2 Hien, T., et al. (2003). Plant-derived 3,3’–diindolylmethane is a strong androgen antagonist in human prostate cancer cells. J Biol Chem. 278:21136-21145.

Thursday, June 7, 2012

Glutamine and the brain by Jerry Brainum

A few years ago, glutamine went from being an obscure, conditionally essential amino acid to the latest nutrient "star." This elevated status was based on findings that glutamine seemed to help preserve muscle under highly stressful conditions that featured a major loss of body protein. Such conditions included severe burns, after major surgical procedures, and any catabolic illness characterized by major protein loss. This isn't a trifling issue, either, since it's the loss of protein that spells impending death for patients suffering from such catabolic illness as AIDS and cancer. Glutamine was used in parenteral nutrition formulas to help stabilize hospitalized  catabolic patients. One physician who was involved in providing nutrition for such patients, Scott Connelly, realized that glutamine could be of value to athletes and bodybuilders, and glutamine became the "secret" ingredient in his Met-rx food supplement.
     It made sense that glutamine supplementation would be of value to athletes, since glutamine is the most abundant amino acid in muscle and blood, comprising 60% of the amino acid content of muscle. Glutamine plays a role in the body's synthesis of urea, the major nitrogen waste product of protein metabolism. It's also vital for helping the body to degrade ammonia. Glutamine also acts as a nutrient precursor for glutathione, one of the most important built-in antioxidants in the body.Glutamine is called a "conditionally essential" amino acid because normally the body can produce glutamine from other amino acids, such as glutamic acid. But under high stress conditions, the body is unable to keep up with the metabolic demand demand for glutamine, and it then becomes essential for health. Among other functions, glutamine is required for activation of certain immune cells, as well as use as an energy source for producing new cells in the intestinal tract.Glutamine protects cells against stress effects by activating special cellular protection proteins called heat shock proteins.These heat shock proteins temper the activity of inflammatory factors produced under stress. Out of control inflammation has a catabolic effect in muscle. Indeed, some studies show that glutamine is capable of blunting the effects of cortisol, the major catabolic hormone in the body, as well as myostatin, a protein that blocks muscle growth.
   The most controversial aspect of glutamine is its role in protein synthesis and muscle growth. While the putative mechanisms of glutamine, such as interference with both cortisol and myostatin, should favor an anabolic milieu in muscle, studies where supplemental glutamine have been provided to bodybuilders have shown little or no effect on muscle protein synthesis and muscle growth. On the other hand, a key cellular anabolic signaling factor in muscle cells is their state of hydration. A hydrated cell is anabolic, while a dehydrated cell is catabolic. Glutamine provides potent effects in promoting cellular hydration. In the cell, glutamine promotes a potent osmotic effect, pulling water into the cell, which boosts cell hydration.Glutamine may also help increase muscle and liver glycogen stores depleted after exercise. Studies show that those who follow the popular low-carb diet plans have 25% lower stores of glutamine.Some studies suggest that glutamine may promote the release of growth hormone, as well as gonadotropin-releasing hormone, which would have the effect of boosting testosterone release in the body. With its favorable effects on anabolic hormones, coupled with its blunting of catabolic factors, such as cortisol and myostatin, it's hard to understand how glutamine would not be of use to bodybuilders. Indeed, studies show that glutamine can offset the blunting of immune response that is common after intense exercise.
    A recent study illustrated an interesting role of glutamine in the body.The study noted that the brain contains high levels of glutamine synthetase, the enzyme that produces glutamine in the body.Apparently, this high level of the glutamine-producing enzyme offers potent brain protection through various means.GS is particularly active in the frontal lobe of the brain, the site of memory and intelligence, and the site most prone to neurodegenerative disease. In diseases of the brain, GS activity is blunted, which means there is less glutamine produced in the brain.A major cause of the damage induced by such diseases as Alzheimer's disease is excess inflammation. Much of this inflammation results from the activity of oxidants. Glutamine acts as an antioxidant in the brain, and also blocks the activity of inflammatory substances that kill brain cells.Not only that, but glutamine can help repair DNA damage in the brain, preventing excess brain damage.In the body, 800 DNA lesions occur per hour in cells, about 19,200 hits a day.DNA repair normally takes care of this, but the DNA repair mechanisms tend to downgrade with age. In some people, however, DNA repair is maintained, and those are the folks who live to 100 or more. A process called autophagy allows the body to degrade and remove old cells that aren't working or are damaged. This process is necessary for the body to replace those cells with new cells. When glutamine levels are reduced in the brain, autophagy slows, allowing the build-up of damaged cells that can result in brain degeneration. So it seems that glutamine is required for protecting the brain against stress, and in this manner, can also protect against the onset of diseases such as Alzheimer's.
    But what about those studies showing that glutamine seems to be useless for building muscle? For one, glutamine works best under catabolic conditions, and unless you are training extremely intensely, to the point of overtraining, the normal stores of glutamine in the body will indeed be enough to cover your needs, and taking supplemental glutamine won't add much. But the situation changes dramatically when you either overtrain, or train especially hard. In that case, the body will be unable meet the increased demand for glutamine, and some supplemental glutamine would likely be of some benefit.
    The main problem with glutamine supplementation is that since it's used as a primary fuel by intestinal cells, most of the oral glutamine ingested is taken up by these cells, rather then delivered to the blood. One way around this is to consume small doses of glutamine, no more than 5 grams at a time, several times a day. A recent study found that a supplemental form of glutamine called Sustamine, which consists of a dipeptide form of glutamine (two bonded amino acids, in this case, glutamine and alanine) increased blood glutamine levels 224% above that of free form L-glutamine. This bonded form is the same type provided to catabolic hospital patients, since it's more stable in liquid solutions compared to free glutamine.

Chen, J, et al. Glutamine acts as a neuroprotectant against DNA damage, beta-amyloid, and H202-induced stress.Plus one 2012;7;e33177.

©,2012, Jerry Brainum.Any reprinting in any type of media, including electronic and foreign is expressly prohibited.