"Heme-Induced N-Nitroso Compounds and Fat Oxidation"
In a review attempting to downplay the role of heme in the link between
meat and cancer, funded by the National Cattlemen's Beef Association, they
noted that it's important to remember that all the rat and mouse studies
suggesting harm from heme didn't evaluate exposure conditions
that were representative of any kind of realistic human exposures. Instead
the rats were given heme at levels corresponding to up to 360,000 times
the level of meat recommended in the dietary guidelines. But hey,
at least you know what might happen if you ate 20 tons of meat a day
and were a rodent. What about the human studies?
Heme iron can promote the formation of N-nitroso compounds.
Why should we care about the diet-induced formation of these compounds in our gut?
Because a number of these compounds are known to cause DNA damage.
In fact, one of them, methylnitrosourea, is actually used to induce colon cancer.
And at higher levels of meat consumption, concentrations of apparent, total
Nitroso-compounds were found to be on the same order as the concentration
of N-nitroso compounds in cigarette smoke.
OK, but that was at like 2 to 4 burgers a day worth of meat.
At like half a burger a day, people were pooping out
no more of the nitroso compounds than those eating none.
Going from a half burger's worth to 4 burgers a day gives you a big spike,
but cutting out meat completely just brought you down
to about half-burger levels.
What about just like normal meat consumption, like one burger a day?
It's not just 2 or 4 burgers worth that can do it.
One quarter-pounder can also do it.
That looks to be about where levels start shooting up.
That's one potential way heme iron may play a major role
in colorectal cancer promotion--- the N-nitroso pathway.
The other is fat peroxidation, oxidized fat that may also lead
to mutagenic DNA damage.
Just a few days eating just like a burger a day
significantly increased a biomarker of fat oxidation in people's stool.
How do we know whether it's the heme itself that's responsible
for both these processes? Well, if you give people a heme supplement alone,
you can increase fecal levels,
whereas a nonheme iron supplement appeared to have no effect.
A bump with heme iron, but back down on nonheme iron,
suggesting it's the N-nitroso compounds from the ingestion of heme
that may be accounting for the increased cancer risk.
But that so-called heme supplement wasn't a supplement at all.
They just fed people like 4 ounces of liver pate and blood sausage.
So this should be labelled like this, in which case no big revelation.
And the same thing with fat oxidation. Was it the heme itself
or any number of other things found in a blood sausage diet?
The best evidence we have that heme itself is playing a role
is that if you remove the heme, you can get a significant drop
in N-nitroso compound formation.
But note, it was only about a quarter, so there must be other factors.
And indeed, there was a strong correlation with the amount
of nitrites in their stool, which can be involved directly
in the production, and are found in both processed
and, to a lesser extent, unprocessed meat.
Now the soy appears to have a significant suppressive effect
on fecal N-nitroso concentrations. That piqued my interest,
since the trigger for my whole deep dive into heme
was Impossible Food's attempt to recreate the taste of meat
using a plant-based heme protein in place of the muscle-based heme protein.
The company likes to say how the heme in the Impossible Burger is atom-for-atom
identical to the heme found in meat, and so would be expected to have
similar effects. But if soy can have a mediating effect, since
the Impossible Burger is a soy-based burger, maybe that changes things.
They had people eat a high meat diet with and without soy,
and got about a 40% drop in the concentration of those potentially
carcinogenic compounds eating the same amount of meat when the soy was added.
Now, it turns out they didn't end up making much less;
it's just that they boosted their fecal output by about 40%.
About a 40% bigger stool size because they were eating
about a half a cup of soybeans. But that's good because
bigger poops mean lower carcinogen concentrations
and reduced intestinal transit time, all resulting in less potential
carcinogen contact with the bowel wall.
But this was because they used whole soybeans, which would give them
like six grams of fiber, whereas the Impossible Burger only has
about half that since it's made from more of a soy protein concentrate.
The question of safety then becomes whether or not the N-nitroso compounds
formed in our intestines as a result of the heme are DNA-damaging
or cancer-causing? When you see the term ATNC,
that stands for apparent total N-nitroso compounds,
measuring just a nonspecific broad class of compounds,
some of which are definitely genotoxic and carcinogenic.
But further work is required to establish that the specific ones that pop up
when we eat meat, further work that we'll turn to next.