Friday, September 14, 2012

Fire in the Whole by Jerry Brainum

             Control Inflammation to Get Bigger, Stronger and Healther

The body responds to injuries, infections and irritations with inflammation. In an acute stage, inflammatory processes aid healing. Uncontrolled, or chronic inflammation, however, is the cornerstone of every major disease.
    Research shows that uncontrolled inflammation is the underlying cause of cardiovascular disease, cancer and asthma. Some diseases, such as arthritis, are obviously driven by inflammation. In others the effects of inflammation are more subtle but just as damaging. In Alzheimer’s disease inflammation leads to the gradual destruction of the brain.
     While cholesterol and saturated fat are often implicated as the main players in cardiovascular disease, the true villain is underlying inflammation. Some studies show that C-reactive protein, a general indicator of inflammation in the body, is a more reliable indicator of incipient cardiovascular disease than is blood cholesterol.
     Inflammatory responses involve several body systems, among them hormones and immune cells. The positive side of inflammation is that it sets the stage for the healing process, along with the eradication of invading pathologens like bacteria and viruses. Special proteins called cytokines signal immune cells like neutrophils and macrophages to migrate to sites of injury or damage, where they enable the body to keep the invasion localized and marshal a more focused defense.
Inflammation and Training

Inflammation has both good and bad effects on exercise. The muscle-growth process is initiated by exercise-induced injury. The body compensates for the injury by stepping up processes such as muscle protein synthesis, which leads to increases in muscle size and strength. As with any injury, the body’s initial response to exercise-induced muscle damage is localized inflammation. It’s a positive effect, as the arrival of neutrophils and other immune cells results in the clearance of debris and preparation of the damaged muscle for repair.
    Neutrophils are produced in bone marrow and circulate in the blood, where they represent 50 to 60 percent of circulating leukocytes—a.k.a. white blood cells. They constitute the first line of defense against infection. Neutrophils produce free radicals, which are used to kill invading bacteria. Unfortunately, it’s a shotgun approach in that free-radical release also damages the cell membranes of healthy tissue.
Neutrophils begin to appear at the site of muscle damage within an hour after the damage occurs. They can remain there for up to five days. They can gobble up excess debris in the damaged area—a process known as phagocytosis—and they produce proteases, or protein-digesting enzymes, that further degrade cellular debris produced by muscle damage.1 Meanwhile, the other immune cells that react to muscle inflammation, such as macrophages, release cytokines and help mop up the excess debris damage that would otherwise impair efficient muscle repair and regeneration.
     The effects of the initial immune responses are tempered and controlled by nitric oxide. Without nitric oxide, the free radicals that immune cells produce could damage healthy tissue, delaying the healing process.
The muscle damage exercise inflicts also breaks down the fatlike outer layer of muscle cells, which leads to the release of arachidonic acid, an omega-6 fatty acid found in meat and eggs. Arachidonic acid is the precursor of a number of inflammatory chemicals, such as prostaglandins. Cyclooxygenases, or COX enzymes, are required to convert the arachidonic acid into active prostaglandins—the substances responsible for most of the pain caused by inflammation.
     One prostaglandin, PGF2A, is involved in several aspects of postexercise muscle repair, including nitric oxide release and protein synthesis. The more damaging the exercise, the greater the release of PGF2A. So eccentric muscle contractions, which usually involve lowering weights, release more PGF2A because they damage the muscle more. Using over-the-counter painkillers, including aspirin and ibuprofen, appears to inhibit postexercise muscle repair because they inhibit the COX enzymes your body needs to convert arachidonic acid into PGF2A. Research supporting that conclusion, however, used doses of 2,400 milligrams of ibuprofen or higher, far more than what’s used routinely to treat pain. Most studies show that a 400-milligram dose—the amount typically used to treat acute pain—doesn’t interfere with PGF2A synthesis.

                           Who’s Inflamed?

     While a controlled amount of postexercise muscle inflammation fosters muscle repair and regeneration, too much slows muscle repair. Many older people are in a chronic state of inflammation, which leads to the release of substances, such as cytokines and cortisol, that are linked to muscle breakdown. If the process continues unabated, sarcopenia, or severe muscle loss, can result in frailty and weakness.
      A recent study, however, demonstrated that older people who took ibuprofen and similar drugs had a dramatic increase in muscle mass, almost as if they used anabolic steroids. How can that happen if the same painkillers interfere with muscle growth? Out-of-control inflammation has a catabolic effect on older people’s muscle because of excess cytokines and other inflammatory chemicals. Block the inflammation with drugs, and the muscles perk up rapidly.
     The obese are also affected by excess inflammation. While in the past fat tissue was thought to be inert—or merely a storage depot for excess energy—recent research shows that fat cells release more than 100 mostly inflammatory substances, collectively known as adipokines. In other words, people who are carrying excess bodyfat are in a chronic state of inflammation and are in a position to develop cancer, cardiovascular disease and diabetes.
      The worst is the deep-lying abdominal bodyfat. Known as visceral fat, it’s far more dangerous than fat found on the thighs or hips because it’s constantly being broken down and released. That means adipokines are constantly being released into the blood.
     Research shows that it’s harder for those who have excess bodyfat to build muscle. One reason is that they are releasing more free fatty acids into their blood. Excess blood fat stimulates a protein called nuclear factor beta, which in turn activates proinflammatory genes—a kind of double whammy of inflammation. Among the substances it activates, tissue necrosis factor alpha, or TNF-a, is particularly catabolic in muscle, which may partially explain why it’s so much harder for those who have too much bodyfat to build muscle.
      Exercise blunts the release of many inflammatory compounds, making exercise itself anti-inflammatory. On the other hand, moderate-to-low-intensity exercise (50 percent of maximum oxygen intake or less), such as mild walking, is inflammation-neutral.2 Exercise must therefore be of sufficient intensity to impart any anti-inflammatory benefits.
Inflammatory Compounds and Muscle

   Recent studies show that contracting muscle produces cytokines that act on muscle in ways different from what happens with other parts of the body. For example, a cytokine called interleukin-6 exerts inflammatory effects in most tissues of the body. In fact, it also works in concert with cortisol to break down muscle, an effect most often seen in older people. One study indicates that having an abundance of inflammatory markers, including interleukin-6, limits the body’s capacity for processing oxygen.3
Active people have less interleukin-6 and other inflammatory mediators. Older people, who have more interleukin-6 in their bodies, are more likely to have chronic inflammation as well.4
     One hypothesis is that overtraining sets in due to an excess release of interleukin-6.5 That appears to be more likely with extended endurance exercise rather than shorter bouts of high-intensity work, like bodybuilding training. In any case, interleukin-6 can penetrate the protective blood-brain barrier, and once in the brain, it triggers ACTH release, which in turn triggers the release of cortisol. Interleukin-6 in the brain also aids the synthesis of serotonin, leading to feelings of fatigue. Other triggers for excess interleukin-6 release are hypoglycemia, or low blood sugar, and dehydration.
    By and large, interleukin-6 is beneficial. It’s released directly within muscle as a result of muscular contraction. As with PGF2A, the extent of interleukin-6 release in muscle depends on the duration, intensity and mass involved in exercise.

6 The primary stimuli to interleukin-6 release in muscle are the following:

• Low muscle glycogen
• Intake of niacin, a B-complex vitamin
• Heat
In contrast, here are the factors that blunt interleukin-6 release:
 • Carbohydrate intake
• Antioxidant use
• Anti-inflammatory drugs, such as ibuprofen
• Moderate endurance exercise
     The same interleukin-6 that produces inflammatory effects in nonmuscle tissue has anti-inflammatory effects in muscle. For example, it blocks the release of inflammatory mediators such as TNF-a. TNF-a is also suspected of being an agent of insulin resistance, a precursor of diabetes. Exercise may protect against insulin resistance when a muscle contraction signals the release of interleukin-6. That may also help explain the 60 percent reduction in diabetes produced by weight training.
     Although the genes that produce interleukin-6 in muscle are silent at rest, activated only through intense muscle contraction, interleukin-6 also acts as an energy sensor. If you’re low on muscle glycogen, interleukin-6 released from muscle aids in the breakdown of bodyfat for energy.7 It works by activating a protein that helps your body use fat for energy and another protein that boosts glucose uptake into muscle. That helps account for why contracting muscle protects against insulin resistance—and diabetes—by releasing interleukin-6.
     A recent mouse study illustrates perhaps the most interesting effect related to bodybuilding and interleukin-6.8 It found that mice lacking the substance cannot develop larger muscles, even when they overload their muscles during exercise as weight-training humans do. Mice that produced interleukin-6 in their muscles, however, did increase muscle mass. The effect was traced to a stimulation of satellite cells, the major muscle repair cells, by interleukin-6.
     Still another muscle-produced cytokine or myokine is interleukin-15. Researchers observed a gradual rise in that substance after subjects lifted weights, with it peaking in 24 hours. In muscle, it produces potent anabolic effects and blocks muscle breakdown. It also appears to encourage bodyfat loss. No doubt interleukin-15 will emerge in the future as an “ergogenic aid” to building muscle and losing fat.
Controlling Bad Inflammation

   While controlled inflammation in muscle is helpful if you’re looking for mass gain and bodyfat loss, chronic overall inflammation is a harbinger of disability and mortality. There are several ways to temper the flames, the most important by far being to reduce excess bodyfat.9
    Eating a lot of trans fats is associated with higher concentrations of inflammatory chemicals in the body.10 Taking dietary antioxidants can neutralize much inflammation damage.11 One of the most efficient dietary supplements for reducing inflammation is fish oil. It increases a natural anti-inflammatory agent in the body called resolvin E1 and interferes with arachidonic acid’s production of inflammatory prostaglandins. Taking in too much omega-6 fatty acids, which are abundant in most vegetable oils, leads to excessive amounts of inflammatory prostaglandins and pain. Since omega-6 sources are already abundant in most people’s diets, stick with fish oil supplements and avoid the ones that contain omega-6s. For purposes of reducing out-of-control inflammation in the body, take 10 to 15 grams a day of fish oil in divided doses. Use liquid versions; trying to get that amount from capsules would mean swallowing 10 to 15 pills a day.
1 Tidball, J.G. (2005). Inflammatory processes in muscle injury and repair. Am J Physiol Regul Integr Comp Physiol. 288:R345-R353.
2 Markovitch, D., et al. (2008). Acute moderate intensity exercise in middle-aged men has neither an anti nor pro-inflammatory effect. J Appl Physiol. In press.
3 Kallo, I.J., et al. (2007). Markers of inflammation are inversely associated with VO2 max in asymptomatic men. J App Physiol. 102:1374-1379.
4 Maggio, M., et al. (2006). Interleukin-6 in aging and chronic disase: A magnificent pathway.

©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.

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