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.
References
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
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