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09/01/2004

Nitrates and Chocolate

I just had lunch and finished with a few chocolate covered
raisins. I was heartened to read an AP news item in the Star
Ledger (8/30/2004) stating that dark chocolate may be good for
the heart, if not for the waistline. In these times of changing food
pyramids and conflicting claims about all sorts of diets, it’s
always comforting to find that some foods that taste good may
have some redeeming features. It’s been known for some time
that chocolate contains flavonoids, antioxidants that battle all
those free radicals and such.

But now comes a chocolate study from the host city of the
Olympics. Cardiologists at Athens Medical School wanted to
know the effect of chocolate on endothelial cells in the walls of
blood vessels. The flexibility of blood vessel walls is considered
an indication of the health of the cardiovascular system. The
Greek study involved finding healthy young volunteers who
consented to eat a bar of dark chocolate and then subject
themselves to ultrasound examination. I doubt they had any
trouble finding volunteers and, sure enough, the blood vessels
did appear more flexible for those eating the chocolate.

According to the article, the flexibility lasts at least three hours.
I guess that, for optimum heart benefit, I should carry my dark
chocolate covered raisins with me and pop a few every three
hours or so. Unfortunately, the article warns that the possible
weight gain cancels out any beneficial effects of the chocolate.
I’ll continue eating my raisins in moderation.

I also like an occasional hot dog and felt better after reading
another article, “Bad Rap for Nitrate?” by JR Minkel in the
September issue of Scientific American. The hot dog is
composed of – well, maybe it’s better we not know. At any rate,
a lot of us find it to be a tasty item to place in a bun and smother
with all sorts of condiments. Aside from its fat content, a rap
against the hot dog has been the use of nitrates as a preservative.
Nitrates have been thought to be linked to stomach cancer.
Where did this idea originate? In the 1950s, there were studies
showing that substances called N-nitrosamines, derivatives of
nitrates, not only damaged DNA but also caused cancer in rats
and other animals.

Since then, however, many studies have failed to find any
connection between nitrate consumption and stomach cancer in
humans. In fact, there is work in progress to see whether nitrates
can be used in therapies to treat certain infections and prevent the
formation of ulcers. Nitric oxide, NO, plays an important role in
these studies. Over five years ago, in my first Bortrum column
(5/12/1999), I discussed NO and the part it plays in the action of
Viagra. At the time, researchers were beginning to appreciate
the major roles that NO plays in the body and I predicted that NO
would undoubtedly pop up in future columns. This is one of
them.

In 1994, Jon Lundberg in Sweden and Nigel Benjamin in
England led independent studies that found there was a lot of NO
gas in human stomachs. Both thought that the NO might be
playing a role in killing germs in the stomach, based on the
knowledge that when white blood cells carried NO to microbes,
the microbes were weakened.

In researching this column, I found on the Web two articles from
the January 1 issue of the Journal of Clinical Investigation, one
by Lundberg and his colleagues, the other by Mark Gladwin of
the National Institutes of Health in Bethesda, Maryland. I
learned some interesting things about spit. Excuse me, I mean
saliva. Did you know that our tongues are bathed in about a liter
and a half of saliva every day? This saliva contains both nitrates
and nitrites (NaNO3 is sodium nitrate; NaNO2 is sodium nitrite).
We chemists say that the nitrate is “reduced” to nitrite when we
take away the one oxygen atom. Kick off the sodium (Na) and
take away another oxygen and we have reduced the nitrite to NO.

The nitrate that we swallow with our hot dog takes a circuitous
path. It gets absorbed in the upper small intestine and most of it
gets excreted through our kidneys. However, 25 percent of the
nitrate gets concentrated in saliva and ends up back in our mouth.
This time, the nitrate in the saliva gets reduced to nitrite by
bacteria living in clefts in our tongue. Now we swallow the
nitrite and it gets to the stomach, which is quite acidic. In the
acid environment of the stomach, the nitrite forms various
compounds but a large portion of it ends up as NO gas. NO is
known to affect blood flow. The drug Viagra promotes the
formation of NO, which in turn promotes the dilation of blood
vessels, allowing blood to flow more readily into an organ
peculiar to the male anatomy.

Let’s see what else the nitrate-nitrite-NO trio does for us.
Benjamin’s group wanted to see whether nitrites have any effects
on harmful bacteria such as E. coli or Salmonella. They put
these and other harmful bacteria in stomach acid and in stomach
acid to which nitrite had been added. The bacteria seemed to
enjoy the stomach acid, spending hours in it without any damage.
The situation was different in the stomach acid with nitrite
added. In an hour all the bacteria were dead. It’s clear that
nitrites are on our side.

How does the protective action of nitrites work? Remember that
the nitrite comes from the nitrate that we ingest. People who fast
will have much less nitrite in their saliva than people who eat
significant amounts of nitrate. Lundberg’s group collected saliva
from people who had no nitrates and those who had taken nitrate
tablets. They then placed saliva samples from these subjects in
the stomachs of rats. The rodents receiving the saliva from the
nitrate eaters showed thickening of the mucous membranes
lining the stomach and increased blood flow. Both the increased
blood flow and mucous production are known factors in the
prevention of infection and ulcers. The rats receiving the saliva
from those who did not take nitrate tablets showed no change in
blood flow or mucous thickening.

Bottom line – the tables have turned and it now appears that the
nitrate-nitrite-nitric trio helps us fend off those microbes that
would do us harm. It seems that spinach and lettuce also contain
nitrates so one does not have to eat hot dogs to get the benefit of
nitrate consumption. Meanwhile, researchers are trying to figure
out how to apply NO chemistry to the treatment of skin
infections (an NO cream has been made which is targeted to the
treatment of skin infections in developing countries).

One of the problems in applying NO therapies internally is the
complication that one effect of NO is to lower blood pressure. In
fact, there were some early problems with Viagra for men taking
medications that had nitrates in them. As I recall, the nitrates
and the Viagra taken together led to significant lowering of blood
pressure, which in extreme cases could be fatal. We’ve seen how
this can happen since nitrates get converted to nitrites, which in
turn get converted in part to NO. The double dose of NO from
the nitrates and the Viagra apparently dilates those blood vessels
more than is healthy in some individuals. Balancing the
lowering of blood pressure with the infection-fighting properties
of NO is a challenge for researchers.

An article titled “Say Yes to NO” in an American Chemical
Society publication prompted my first column, in 1999. If all
goes well, we may have a future article titled “Bravo to NO!”.

Allen F. Bortrum



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Dr. Bortrum

09/01/2004

Nitrates and Chocolate

I just had lunch and finished with a few chocolate covered
raisins. I was heartened to read an AP news item in the Star
Ledger (8/30/2004) stating that dark chocolate may be good for
the heart, if not for the waistline. In these times of changing food
pyramids and conflicting claims about all sorts of diets, it’s
always comforting to find that some foods that taste good may
have some redeeming features. It’s been known for some time
that chocolate contains flavonoids, antioxidants that battle all
those free radicals and such.

But now comes a chocolate study from the host city of the
Olympics. Cardiologists at Athens Medical School wanted to
know the effect of chocolate on endothelial cells in the walls of
blood vessels. The flexibility of blood vessel walls is considered
an indication of the health of the cardiovascular system. The
Greek study involved finding healthy young volunteers who
consented to eat a bar of dark chocolate and then subject
themselves to ultrasound examination. I doubt they had any
trouble finding volunteers and, sure enough, the blood vessels
did appear more flexible for those eating the chocolate.

According to the article, the flexibility lasts at least three hours.
I guess that, for optimum heart benefit, I should carry my dark
chocolate covered raisins with me and pop a few every three
hours or so. Unfortunately, the article warns that the possible
weight gain cancels out any beneficial effects of the chocolate.
I’ll continue eating my raisins in moderation.

I also like an occasional hot dog and felt better after reading
another article, “Bad Rap for Nitrate?” by JR Minkel in the
September issue of Scientific American. The hot dog is
composed of – well, maybe it’s better we not know. At any rate,
a lot of us find it to be a tasty item to place in a bun and smother
with all sorts of condiments. Aside from its fat content, a rap
against the hot dog has been the use of nitrates as a preservative.
Nitrates have been thought to be linked to stomach cancer.
Where did this idea originate? In the 1950s, there were studies
showing that substances called N-nitrosamines, derivatives of
nitrates, not only damaged DNA but also caused cancer in rats
and other animals.

Since then, however, many studies have failed to find any
connection between nitrate consumption and stomach cancer in
humans. In fact, there is work in progress to see whether nitrates
can be used in therapies to treat certain infections and prevent the
formation of ulcers. Nitric oxide, NO, plays an important role in
these studies. Over five years ago, in my first Bortrum column
(5/12/1999), I discussed NO and the part it plays in the action of
Viagra. At the time, researchers were beginning to appreciate
the major roles that NO plays in the body and I predicted that NO
would undoubtedly pop up in future columns. This is one of
them.

In 1994, Jon Lundberg in Sweden and Nigel Benjamin in
England led independent studies that found there was a lot of NO
gas in human stomachs. Both thought that the NO might be
playing a role in killing germs in the stomach, based on the
knowledge that when white blood cells carried NO to microbes,
the microbes were weakened.

In researching this column, I found on the Web two articles from
the January 1 issue of the Journal of Clinical Investigation, one
by Lundberg and his colleagues, the other by Mark Gladwin of
the National Institutes of Health in Bethesda, Maryland. I
learned some interesting things about spit. Excuse me, I mean
saliva. Did you know that our tongues are bathed in about a liter
and a half of saliva every day? This saliva contains both nitrates
and nitrites (NaNO3 is sodium nitrate; NaNO2 is sodium nitrite).
We chemists say that the nitrate is “reduced” to nitrite when we
take away the one oxygen atom. Kick off the sodium (Na) and
take away another oxygen and we have reduced the nitrite to NO.

The nitrate that we swallow with our hot dog takes a circuitous
path. It gets absorbed in the upper small intestine and most of it
gets excreted through our kidneys. However, 25 percent of the
nitrate gets concentrated in saliva and ends up back in our mouth.
This time, the nitrate in the saliva gets reduced to nitrite by
bacteria living in clefts in our tongue. Now we swallow the
nitrite and it gets to the stomach, which is quite acidic. In the
acid environment of the stomach, the nitrite forms various
compounds but a large portion of it ends up as NO gas. NO is
known to affect blood flow. The drug Viagra promotes the
formation of NO, which in turn promotes the dilation of blood
vessels, allowing blood to flow more readily into an organ
peculiar to the male anatomy.

Let’s see what else the nitrate-nitrite-NO trio does for us.
Benjamin’s group wanted to see whether nitrites have any effects
on harmful bacteria such as E. coli or Salmonella. They put
these and other harmful bacteria in stomach acid and in stomach
acid to which nitrite had been added. The bacteria seemed to
enjoy the stomach acid, spending hours in it without any damage.
The situation was different in the stomach acid with nitrite
added. In an hour all the bacteria were dead. It’s clear that
nitrites are on our side.

How does the protective action of nitrites work? Remember that
the nitrite comes from the nitrate that we ingest. People who fast
will have much less nitrite in their saliva than people who eat
significant amounts of nitrate. Lundberg’s group collected saliva
from people who had no nitrates and those who had taken nitrate
tablets. They then placed saliva samples from these subjects in
the stomachs of rats. The rodents receiving the saliva from the
nitrate eaters showed thickening of the mucous membranes
lining the stomach and increased blood flow. Both the increased
blood flow and mucous production are known factors in the
prevention of infection and ulcers. The rats receiving the saliva
from those who did not take nitrate tablets showed no change in
blood flow or mucous thickening.

Bottom line – the tables have turned and it now appears that the
nitrate-nitrite-nitric trio helps us fend off those microbes that
would do us harm. It seems that spinach and lettuce also contain
nitrates so one does not have to eat hot dogs to get the benefit of
nitrate consumption. Meanwhile, researchers are trying to figure
out how to apply NO chemistry to the treatment of skin
infections (an NO cream has been made which is targeted to the
treatment of skin infections in developing countries).

One of the problems in applying NO therapies internally is the
complication that one effect of NO is to lower blood pressure. In
fact, there were some early problems with Viagra for men taking
medications that had nitrates in them. As I recall, the nitrates
and the Viagra taken together led to significant lowering of blood
pressure, which in extreme cases could be fatal. We’ve seen how
this can happen since nitrates get converted to nitrites, which in
turn get converted in part to NO. The double dose of NO from
the nitrates and the Viagra apparently dilates those blood vessels
more than is healthy in some individuals. Balancing the
lowering of blood pressure with the infection-fighting properties
of NO is a challenge for researchers.

An article titled “Say Yes to NO” in an American Chemical
Society publication prompted my first column, in 1999. If all
goes well, we may have a future article titled “Bravo to NO!”.

Allen F. Bortrum