Nitrites are great again

Nitrites are now safe again

Here's what a major textbook on cancer once wrote about nitrites:

N-nitrosamines and other N-nitrosocompounds are potential human carcinogens. Research has focused on stomach, esophagus, liver, and urinary bladder cancers from dietary exposures and lung cancer from tobacco smoke exposure. . . . The greatest exposure in the United States is from processed meats and until recently, beer. Endogenous formation occurs in the stomach from nitrosatable amines and nitrate used as a preservative, which is converted to nitrites by bacteria. The host capacity to form N-nitrosamines is associated with risk of stomach and esophageal cancer. ^[1]

This is what doctors and patients were taught for decades. Nitrites were carcinogenic because they reacted to form nitrosamines when in contact with stomach acid. ^[2][3]. The WHO recommended a limit of nitrite to be 0.06–0.07 mg/kg. Don't eat bacon, we were told. And so we started seeing uncured bacon in our stores labeled “Nitrite Free!”

Nitrate, which can be converted to nitrite, can have cardiovascular effects, but as always everything depends on the dose. Although ingestion of large doses of nitrite can produce methemoglobinemia, earlier research associating nitrite with cancer is increasingly being discounted by some researchers who view nitrate-nitrite-nitric oxide as an equilibrium. ^[4]

Bacon, nature's perfect health food, now with more nitrite!

The current view is that nitrite (NO−2) is formed naturally in the body from nitrate (NO−3). Only 4.8% of our dietary intake of nitrites comes from cured meats. Nitrite in blood is rapidly converted to nitrate with a half life of 110 seconds,^[5] which means it could never reach a toxic level (normal levels are 50–100 nanomoles per liter). It is non-enzymatically converted to nitric oxide (NO), which is an important messenger molecule. In other words, not only is it not harmful, it's essential for health. And everything the textbook said about it is wrong.

Humans get about 60% of their nitrate from leafy vegetables, notably spinach. Nitrite is added to food to inhibit the growth of the anaerobic bacterium Clostridium botulinum, which causes botulism poisoning. Mice fed on a nitrate- and nitrite-deficient diet die within 22 months.^[6] That might sound scary until you remember that mice only live for 12 to 18 months.

So, with the resurrection of cholesterol and animal fats, does this mean bacon, like eggs, is now the perfect food? Should Whole Foods stock it and get rid of all that deadly ‘uncured’ stuff? No, they won't. Many of those claims on package labeling are not really believed by the manufacturer. They're no more meaningful than the claim that gluten-free shampoo is safer for you or that Cheerios is healthier because it will (maybe) lower your cholesterol.

Nitrites are the cure for global warming?

Methane is formed from methanogenic archaea in the rumen of cattle, sheep, and goats by the enzyme methyl-coenzyme M reductase (MCR). It's claimed that methane from ruminants contributes about 20% of global methane emissions, which some researchers now claim may contribute to global warming, although so far the connection is still hypothetical.

It wasn't me, I swear

An oxidant called 3-nitrooxypropanol (3-NOP, aka Bovaer) binds to the active site of MCR and oxidizes an essential SH group, inhibiting production of methane in bacteria. The effect only lasts for 5 hours at a concentration of 1 μM,^[7] after which the bacteria reactivate the enzyme. 3-NOP is rapidly absorbed by the intestine and makes its way through the animal's bloodstream, and is then denitrated in the liver. This probably explains why 100× more 3-NOP is needed to produce the effect in the animal than in cultured bacteria. 3-NOP is metab­ol­ized to nitrate, nitrite, and 1,3-propanediol. A by-product is hydrogen (H₂) gas.

All the papers on the subject present 3-NOP as a cure for global warming. But if nitrite is now safe again, why not just give nitrite to the cows? Nitrite is an equally potent inhibitor, and unlike 3-NOP it remains in the gut instead of being absorbed, so it will stay out of the milk and meat. The authors claim that 3-NOP is better because it crosses the bacterial cell membrane, while nitrite doesn't. The reasoning is that nitrite acts outside the bacterial cell and 3-NOP acts inside the cell.^[8] This sounds like an ad hoc excuse and it needs to be substantiated.

The US FDA has approved 3-NOP in cattle feed. The researchers claim, without evidence, that it increases yield. That means farmers will almost certainly use it. But its safety depends almost entirely on the new claims that nitrite is non-carcinogenic. It also depends on the assumption that 3-NOP won't be found to do anything unexpected, such as produce a highly carcinogenic nitrosamine derivative.

Glyphosate and Bovaer structure

Can science be trusted to evaluate the toxicity of 3-NOP? If you were a scientist, would you risk saying anything against the global warming hypothesis? You'd lose your funding if you did. Just as when the tobacco industry started publishing claims that smoking tobacco was harmless, people have a right to be skeptical when someone discovers that all this time nitrites were safe now that they suddenly prevent global warming.

Does air pollution cause autism?

Autism spectrum disorder (ASD) is a collection of disorders that are primarily genetic and developmental in origin. So it sounds highly implausible that air pollution could be a factor. But air pollution, specifically nitric oxide (NO), has been postulated as a cause of ASD.^[9] Their argument is as follows:

Nitric oxide is an important signaling molecule in the brain that's involved in formation of dendritic spines. (True). The authors found elevated levels of nitric oxide in an ASD mouse model. (Possibly relevant if the mouse model is adequate, which is doubtful). A nitric oxide donor molecule called S-nitroso-N-acetyl penicillamine (SNAP) given at very high doses (20 mg/kg) for ten days reduced synaptogenesis in normal mice. (They have convincing data.) Therefore, air pollution, which contains nitric oxide, causes autism. (A non-sequitur . . . sigh . . . .)

The authors produce a giant pathway diagram ^[10] invoking every possible type of pathogenic mechanism, which is a roundabout way of saying they have no idea how it would work. And there are several big pieces of the proof still missing. Can nitric oxide in air pollution ever produce anywhere near this high a concentration? Does air pollution exposure correlate with the time of appearance of the disorder? Do babies in rural areas have less ASD? Without those pieces, all we have is a hypothesis that something they want to get rid of does something bad.

Does glyphosate cause Alzheimer's disease?

Then there's the new claim that glyphosate causes Alzheimer's disease. ^[11] The news media are running with it, but the abstract alone tells you that they gave an enormous dose: 50 or 500 mg/kg daily for 13 weeks, which was lethal to at least 10% of the mice. The animal model was 3xTg-AD transgenic mice and the results in their Figure 3 were barely significant.

My conclusion is that they've found the one thing that doesn't cause Alzheimers, the only mitigating factor being the fact that there is no mouse model for AD that is anywhere close to adequate, so we can't be sure.

The chemical industry has learned that it doesn't pay to dispute these findings. They might even welcome them. Soon enough, we'll see products labeled “New and Improved!, Glyphosate free!” much as we're now seeing “BPA-free” plastics which contain a slightly different monomer, such as BPS or BPF. It's not dishonesty. They already know BPA, or glyphosate, or whatever are just the latest media punching bags, but they also know few will believe them if they say so. So they put the claim in their advertising.

Conclusion

There's a tendency for environmental researchers to pick a pre-defined problem, preferably one the government is interested in, and find a link to the bad molecule du jour. They know they'll get funding if they find a correlation and risk being ostracized if they don't. Findings like the one above exonerating nitrite are more convincing at first glance because they seem to challenge this principle. But a cynic might think it's quite a coincidence that nitrite is declared safe just as Bovaer, which produces it, comes along.

The challenge is not just that toxicology is an inexact science. A great many people also remain unconvinced that methane, which remains resident in the atmosphere for only a decade, could do anything to the climate. We've seen how things that are thought safe—saccharin, red dye no. 2, tobacco, and hundreds of others—are suddenly found to be harmful. What if they're wrong about 3-NOP, too?

That is the risk of basing policy on scientific research. A scientific paper is merely a hypothesis; it can never be the definitive word on any topic. And so even respectable textbooks get things completely wrong, and government bureaucrats get to choose which finding supports the policy they want.

dec 14 2024, 5:09 am