Whole Health Source: Butyric Acid: an Ancient Controller of Metabolism, Inflammation and Stress Resistance?
"Butyrate, and other short-chain fatty acids produced by gut bacteria**, has a remarkable effect on intestinal permeability.... investigators are using oral butyrate supplements and butyrate enemas to treat inflammatory bowel diseases such as Crohn's and ulcerative colitis. Some investigators are also suggesting that inflammatory bowel disorders may be caused or exacerbated by a deficiency of butyrate in the first place ...butyrate is found in the gut [and is] produced by intestinal bacteria from carbohydrate that the host cannot digest, such as cellulose and pectin. Indigestible carbohydrate is the main form of dietary fiber"
An Interesting Finding
Susceptible strains of rodents fed high-fat diets overeat, gain fat and
become profoundly insulin resistant. Dr. Jianping Ye's group recently
published a paper showing that the harmful metabolic effects of a
high-fat diet (lard and soybean oil) on mice can be prevented, and even
reversed, using a short-chain saturated fatty acid called butyric acid
(hereafter, butyrate). Here's a graph of the percent body fat over time
of the two groups:
The butyrate-fed mice remained lean and avoided metabolic problems.
Butyrate increased their energy expenditure by increasing body heat
production and modestly increasing physical activity. It also massively
increased the function of their mitochondria, the tiny power plants of
the cell.
Butyrate lowered their blood cholesterol by approximately 25 percent,
and their triglycerides by nearly 50 percent. It lowered their fasting
insulin by nearly 50 percent, and increased their insulin sensitivity by
nearly 300 percent*. The investigators concluded:
about the butyrate treatment caused their food intake to decline after 3
weeks, dropping roughly 20% by 10 weeks. The investigators cleverly
tried to hide this by normalizing food intake to body weight, making it
look like the food intake of the comparison group was dropping as well
(when actually it was staying the same as this group was gaining
weight). This does cast some doubt on the health-promoting effects of
high-dose butyrate.
I found this study thought-provoking, so I looked into butyrate further.
Butyrate Suppresses Inflammation in the Gut and Other Tissues
In most animals, the highest concentration of butyrate is found in the
gut. That's because it's produced by intestinal bacteria from
carbohydrate that the host cannot digest, such as cellulose and pectin.
Indigestible carbohydrate is the main form of dietary fiber.
It turns out, butyrate has been around in the mammalian gut for so long
that the lining of our large intestine has evolved to use it as its
primary source of energy. It does more than just feed the bowel,
however. It also has potent anti-inflammatory and anti-cancer effects.
So much so, that investigators are using oral butyrate supplements and butyrate enemas
to treat inflammatory bowel diseases such as Crohn's and ulcerative
colitis. Some investigators are also suggesting that inflammatory bowel
disorders may be caused or exacerbated by a deficiency of butyrate in
the first place.
Butyrate, and other short-chain fatty acids produced by gut bacteria**,
has a remarkable effect on intestinal permeability. In tissue culture
and live rats, short-chain fatty acids cause a large and rapid decrease in intestinal permeability. Butyrate, or dietary fiber, prevents the loss
of intestinal permeability in rat models of ulcerative colitis. This
shows that short-chain fatty acids, including butyrate, play an
important role in the maintenance of gut barrier integrity. Impaired
gut barrier integrity is associated with many diseases, including fatty
liver, heart failure and autoimmune diseases (thanks to Pedro Bastos for
this information-- I'll be covering the topic in more detail later).
Butyrate's role doesn't end in the gut. It's absorbed into the
circulation, and may exert effects on the rest of the body as well. In
human blood immune cells, butyrate is potently anti-inflammatory***.
Butyrate Increases Resistance to Metabolic and Physical Stress
Certain types of fiber reduce atherosclerosis in animal models, and this effect may be due to butyrate production produced when the fiber is fermented. Fiber intake was associated with lower blood markers of inflammation in the Women's Health Initiative study, and has been repeatedly associated with lower heart attack risk and reduced progression of atherosclerosis in humans. Butyrate also sharply reduces the harmful effects of type 1 diabetes in rats, as does dietary fiber to a lesser extent.
Butyrate increases the function and survival of mice with certain
neurodegenerative diseases. Polyglutamine diseases, which are the most
common class of genetic neurodegenerative diseases, are delayed in mice
treated with butyrate (1, 2, 3).
Many of you have probably heard of Huntington's disease, which is the
most common of the class. I did my thesis on a polyglutamine disease
called SCA7, and this is the first suggestion I've seen that diet may be
able to modify its course.
Yet another interesting finding in the first paper I discussed: mice
treated with butyrate were more cold-resistant than the comparison
group. When they were both placed in a cold room, body temperature
dropped quite a bit in the comparison group, while it remained
relatively stable in the butyrate group, despite the fact that the
butyrate group was leaner****. This was due to increased heat
production in the butyrate group.
Due to the potent effect butyrate has on a number of bodily processes,
it may be a fundamental controller of metabolism, stress resistance and
the immune system in mammals.
An Ancient Line of Communication Between Symbiotic Organisms
Why does butyrate have so much control over inflammation? Let's think
about where it comes from. Bacteria in the gut produce it. It's a
source of energy, so our bodies take it up readily. It's one of the
main molecules that passes from the symbiotic (helpful) bacteria in the
gut to the rest of the body. Could it be that the body receives
butyrate as a signal that there's a thriving colony of symbiotic
bacteria in the gut, inducing immune tolerance to them? The body may
alter its immune response (inflammation) in order to permit a mutually
beneficial relationship between itself and its symbionts.
Sources of Butyrate
There are two main ways to get butyrate and other short-chain fatty
acids. The first is to eat fiber and let your intestinal bacteria do
the rest. Whole plant foods such as sweet potatoes, properly prepared
whole grains, beans, vegetables, fruit and nuts are good sources of
fiber. Refined foods such as white flour, white rice and sugar are very
low in fiber. Clinical trials have shown that increasing dietary fiber
increases butyrate production, and decreasing fiber decreases it (free full text).
Butyrate also occurs in significant amounts in food. What foods contain
butyrate? Hmm, I wonder where the name BUTYR-ate came from? Butter
perhaps? Butter is 3-4 percent butyrate, the richest known source. But
everyone knows butter is bad for you, right?
After thinking about it, I've decided that butyrate may have been a
principal component of Dr. Weston Price's legendary butter oil. Price
used this oil in conjunction with high-vitamin cod liver oil to heal
tooth decay and a number of other ailments in his patients. The method
he used to produce it would have concentrated fats with a low melting
temperature, including butyrate, in addition to vitamin K2*****. Thus,
the combination of high-vitamin cod liver oil and butter oil would have
provided a potent cocktail of fat-soluble vitamins (A, D3, K2), omega-3
fatty acids and butyrate. It's no wonder it was so effective in his
patients.
* According to insulin tolerance test.
** Acetate (acetic acid, the main acid in vinegar), propionate and
butyrate are the primary three fatty acids produced by intestinal
fermentation.
*** The lowest concentration used in this study, 30 micromolar, is
probably higher than the concentration in peripheral serum under normal
circumstances. Human serum butyrate is in the range of 4 micromolar in
British adults, and 29 micromolar in the hepatic portal vein which
brings fats from the digestive tract to the liver (ref). This would likely be at least two-fold higher in populations eating high-fiber diets.
**** Due to higher mitochondrial density in brown fat and more mitochondrial uncoupling.
***** Slow crystallization, which selectively concentrates triglycerides with a low melting point.
"Butyrate, and other short-chain fatty acids produced by gut bacteria**, has a remarkable effect on intestinal permeability.... investigators are using oral butyrate supplements and butyrate enemas to treat inflammatory bowel diseases such as Crohn's and ulcerative colitis. Some investigators are also suggesting that inflammatory bowel disorders may be caused or exacerbated by a deficiency of butyrate in the first place ...butyrate is found in the gut [and is] produced by intestinal bacteria from carbohydrate that the host cannot digest, such as cellulose and pectin. Indigestible carbohydrate is the main form of dietary fiber"
An Interesting Finding
Susceptible strains of rodents fed high-fat diets overeat, gain fat and
become profoundly insulin resistant. Dr. Jianping Ye's group recently
published a paper showing that the harmful metabolic effects of a
high-fat diet (lard and soybean oil) on mice can be prevented, and even
reversed, using a short-chain saturated fatty acid called butyric acid
(hereafter, butyrate). Here's a graph of the percent body fat over time
of the two groups:
The butyrate-fed mice remained lean and avoided metabolic problems. Butyrate increased their energy expenditure by increasing body heat
production and modestly increasing physical activity. It also massively
increased the function of their mitochondria, the tiny power plants of
the cell.
Butyrate lowered their blood cholesterol by approximately 25 percent,
and their triglycerides by nearly 50 percent. It lowered their fasting
insulin by nearly 50 percent, and increased their insulin sensitivity by
nearly 300 percent*. The investigators concluded:
Butyrate and its derivatives may have potential application in the prevention and treatment of metabolic syndrome in humans.There's one caveat, however: the butyrate group at less food. Something
about the butyrate treatment caused their food intake to decline after 3
weeks, dropping roughly 20% by 10 weeks. The investigators cleverly
tried to hide this by normalizing food intake to body weight, making it
look like the food intake of the comparison group was dropping as well
(when actually it was staying the same as this group was gaining
weight). This does cast some doubt on the health-promoting effects of
high-dose butyrate.
I found this study thought-provoking, so I looked into butyrate further.
Butyrate Suppresses Inflammation in the Gut and Other Tissues
In most animals, the highest concentration of butyrate is found in the
gut. That's because it's produced by intestinal bacteria from
carbohydrate that the host cannot digest, such as cellulose and pectin.
Indigestible carbohydrate is the main form of dietary fiber.
It turns out, butyrate has been around in the mammalian gut for so long
that the lining of our large intestine has evolved to use it as its
primary source of energy. It does more than just feed the bowel,
however. It also has potent anti-inflammatory and anti-cancer effects.
So much so, that investigators are using oral butyrate supplements and butyrate enemas
to treat inflammatory bowel diseases such as Crohn's and ulcerative
colitis. Some investigators are also suggesting that inflammatory bowel
disorders may be caused or exacerbated by a deficiency of butyrate in
the first place.
Butyrate, and other short-chain fatty acids produced by gut bacteria**,
has a remarkable effect on intestinal permeability. In tissue culture
and live rats, short-chain fatty acids cause a large and rapid decrease in intestinal permeability. Butyrate, or dietary fiber, prevents the loss
of intestinal permeability in rat models of ulcerative colitis. This
shows that short-chain fatty acids, including butyrate, play an
important role in the maintenance of gut barrier integrity. Impaired
gut barrier integrity is associated with many diseases, including fatty
liver, heart failure and autoimmune diseases (thanks to Pedro Bastos for
this information-- I'll be covering the topic in more detail later).
Butyrate's role doesn't end in the gut. It's absorbed into the
circulation, and may exert effects on the rest of the body as well. In
human blood immune cells, butyrate is potently anti-inflammatory***.
Butyrate Increases Resistance to Metabolic and Physical Stress
Certain types of fiber reduce atherosclerosis in animal models, and this effect may be due to butyrate production produced when the fiber is fermented. Fiber intake was associated with lower blood markers of inflammation in the Women's Health Initiative study, and has been repeatedly associated with lower heart attack risk and reduced progression of atherosclerosis in humans. Butyrate also sharply reduces the harmful effects of type 1 diabetes in rats, as does dietary fiber to a lesser extent.
Butyrate increases the function and survival of mice with certain
neurodegenerative diseases. Polyglutamine diseases, which are the most
common class of genetic neurodegenerative diseases, are delayed in mice
treated with butyrate (1, 2, 3).
Many of you have probably heard of Huntington's disease, which is the
most common of the class. I did my thesis on a polyglutamine disease
called SCA7, and this is the first suggestion I've seen that diet may be
able to modify its course.
Yet another interesting finding in the first paper I discussed: mice
treated with butyrate were more cold-resistant than the comparison
group. When they were both placed in a cold room, body temperature
dropped quite a bit in the comparison group, while it remained
relatively stable in the butyrate group, despite the fact that the
butyrate group was leaner****. This was due to increased heat
production in the butyrate group.
Due to the potent effect butyrate has on a number of bodily processes,
it may be a fundamental controller of metabolism, stress resistance and
the immune system in mammals.
An Ancient Line of Communication Between Symbiotic Organisms
Why does butyrate have so much control over inflammation? Let's think
about where it comes from. Bacteria in the gut produce it. It's a
source of energy, so our bodies take it up readily. It's one of the
main molecules that passes from the symbiotic (helpful) bacteria in the
gut to the rest of the body. Could it be that the body receives
butyrate as a signal that there's a thriving colony of symbiotic
bacteria in the gut, inducing immune tolerance to them? The body may
alter its immune response (inflammation) in order to permit a mutually
beneficial relationship between itself and its symbionts.
Sources of Butyrate
There are two main ways to get butyrate and other short-chain fatty
acids. The first is to eat fiber and let your intestinal bacteria do
the rest. Whole plant foods such as sweet potatoes, properly prepared
whole grains, beans, vegetables, fruit and nuts are good sources of
fiber. Refined foods such as white flour, white rice and sugar are very
low in fiber. Clinical trials have shown that increasing dietary fiber
increases butyrate production, and decreasing fiber decreases it (free full text).
Butyrate also occurs in significant amounts in food. What foods contain
butyrate? Hmm, I wonder where the name BUTYR-ate came from? Butter
perhaps? Butter is 3-4 percent butyrate, the richest known source. But
everyone knows butter is bad for you, right?
After thinking about it, I've decided that butyrate may have been a
principal component of Dr. Weston Price's legendary butter oil. Price
used this oil in conjunction with high-vitamin cod liver oil to heal
tooth decay and a number of other ailments in his patients. The method
he used to produce it would have concentrated fats with a low melting
temperature, including butyrate, in addition to vitamin K2*****. Thus,
the combination of high-vitamin cod liver oil and butter oil would have
provided a potent cocktail of fat-soluble vitamins (A, D3, K2), omega-3
fatty acids and butyrate. It's no wonder it was so effective in his
patients.
* According to insulin tolerance test.
** Acetate (acetic acid, the main acid in vinegar), propionate and
butyrate are the primary three fatty acids produced by intestinal
fermentation.
*** The lowest concentration used in this study, 30 micromolar, is
probably higher than the concentration in peripheral serum under normal
circumstances. Human serum butyrate is in the range of 4 micromolar in
British adults, and 29 micromolar in the hepatic portal vein which
brings fats from the digestive tract to the liver (ref). This would likely be at least two-fold higher in populations eating high-fiber diets.
**** Due to higher mitochondrial density in brown fat and more mitochondrial uncoupling.
***** Slow crystallization, which selectively concentrates triglycerides with a low melting point.
