Nitrate: A Confusing Controversy That Might Harm You More Than It Helps.

 

Is nitrate carcinogenic or cardioprotective? Let’s dive into a controversy that pits health organisations against themselves.

A few days ago, I came across an alarmist blog post with this headline:

“Colon Cancer On Tap. Nitrate In Drinking Water.”

The post claimed that nitrate in our public drinking water supplies is a major cancer risk. It urged health organisations to reduce the maximum permissible limit of nitrate in our water.

Unfortunately, there are too many of these purveyors of panic around.

 And the health organizations are not helpful in containing them. To the contrary.

 

National health organizations in the US and EU set the nitrate limit for public drinking water at 50 mg/litre. They consider everything above that as a cancer risk.

And here comes the about-face: 

The same health organizations endorse the regular consumption of beet root juice FOR ITS HIGH NITRATE CONTENT (on average 5 times the 50 mg threshold per serving) which is supposed to be protective against cancer (particularly those of the digestive tract from throat to intestine), and cardiovascular disease.

 

If they want to confuse the consumer, they are doing a great job.

After all nitrate is nitrate. Or is it?

 

What Is Nitrate, And How Does It Work? 

Nitrate is a simple molecule that consists of one nitrogen atom and 3 oxygen atoms (NO3).

To get to its health promoting effect the body needs to strip it of 2 of its oxygen atoms, one at a time: First from nitrate (NO3-) to nitrite (NO2-), and then, finally, to nitric oxide (NO).

Now there are three things you should know to realize what this entire controversy is all about.

And I promise, I won’t give you a lecture in chemistry.

First, the body produces its own NO. Far more than it ever could convert from dietary nitrate (about 10 times as much [1]).

The body achieves this feat with an enzyme that rips NO from some amino acid (L-arginine, if you need to know).

The cells that contain this enzyme then use NO to modulate their direct surroundings in a health promoting way. No nitrate required.

 

For example, the layer of cells that line your arteries, (called the endothelium), produce NO to keep the arteries wider and more flexible (the correct term is compliant, but use whatever word you need to imagine elastic, not stiff, arteries).

This is where the cardiovascular benefits of NO come into play. The more flexible the arteries (particularly the large ones that carry the blood from the heart to the body’s limbs), the lower the blood pressure. The wider the small arteries that supply the heart, the better the blood supply to the heart.

 The second thing you need to know is that the human body does not have the ability to turn nitrate into nitrite.

Remember what I said about the step-by-step reduction from nitrate to nitrite to NO?

So if our body is unable to do step 1, how do we get to the health promoting NO?

Via a large detour.

This detour relies on someone else to reduce nitrate to nitrite: a population of specific bacteria which resides on the top of our tongue (and in other parts of our gut).

Ever heard of the microbiome? These guys are part of it.

 When you drink nitrate-loaded beet root juice, you swallow it, and it disappears too fast for these bacteria to act on it.

But once the nitrate enters your blood stream it is delivered and concentrated in your salivary glands.

They excrete the nitrate into the oral cavity via their saliva production. The bacteria have now ample time to reduce it to nitrite.

Ultimately you swallow the nitrite and (part of) it will appear as such in the blood stream.

This whole detour is called the entero-salivary circulation.

You don’t need to remember this tongue twister.

What you should remember is that you can easily monkeywrench that system:

By regularly killing these helpful microbes. Any antiseptic mouthwash (particularly those containing chlorhexidine) will do that. No kidding.

 The third thing you need to know is that NO is a highly volatile molecule with a half life measured in milliseconds [2]. That is, it will disappear VERY quickly.

How far can you travel in, say, 2 milliseconds to do your job?

Not very far. Not even in the realm of cells whose size is measured in micrometers (1 micrometer is one thousandth of a millimeter).

Considering that the acidity of the stomach is an ideal environment to turn nitrite into NO, its ultra-short half-life makes it impossible for NO to show up in the blood stream and relax the arteries.

But that’s exactly what a nitrate pill (containing nitroglycerine) does to an angina patient’s heart. It dilates his heart’s blood vessels and thereby relieves the anginal pain.  

How do we reconcile these two contradictory observations?

Here is what we know today:

Nitrite circulates in the blood as a kind of emergency resource. Once the emergency occurs, it sheds one of its oxygen atoms, turns into NO and comes to the rescue. 

In the cardiovascular system, the emergency alarm sounds when two conditions come together: too little oxygen, and to much acidity.

If enough nitrite is around, NO production will come to the rescue.

That’s exactly what happens in a heart that does not get enough oxygen. And that’s why the oral delivery, or, faster still, the injection of nitrite works so well to relieve the anginal pain that tells the heart’s owner, in a very unpleasant way, that something is wrong.

These three factors – the presence of circulating nitrite, hypoxia (too little oxygen), and acidity – are at work wherever nitrate has a beneficial effect:

• Decreasing the risk of blood clots
• Dilating arteries
• Relieving anginal pain
• Improving exercise performance in athletes
• Improving exercise tolerance in heart failure

All these effects have been well established [3]. The same goes for the health promoting effects of eating foods that are high in nitrate content.

So, why are we afraid of nitrate in the drinking water? Why don’t we actually fortify water with nitrate? Like we fortify salt with iodine, or milk with calcium? 

Because, as everything else in biology or medicine, nothing is as simple as we often think it is.

Now, first to the biology, and then to the evidence.

NO is not the only “fate” of nitrite. There are other more complex molecules that the body can produce from nitrite. Some of those are the so-called N-nitroso compounds (NOC).

The whole process is called nitrosation.

These NOC molecules are known to increase the risk for certain cancers.

What is also known is what inhibits nitrate and nitrite to go down the path to NOC:

the concurrent delivery of Vitamin C and/or many of the flavonoids that are components of these nitrate-rich vegetables.   

Now to the “supporting” evidence of the alarmist bloggers.

The post that I mentioned in the beginning cites a large observational study that investigated how the exposure to public drinking water with high vs. low nitrate “contamination” affects cancer risk [4].

The number of participants sounds impressive: 1.7 million people were followed for their colorectal cancer events for 15 years.

And lo-and-behold those with an exposure to water in the highest quintile of nitrate content had a 16% increased risk of cancer compared to those people in the lowest exposure quintile.

There are so many things wrong with this study, that I would need a separate post to dissect it.

One of it being the fact that it is an observational study that observed the association between an exposure (that couldn’t even be measured reliably) and an outcome (cancer).

When will those writers who draw causal conclusions from observational study finally get it that association can NEVER prove causation.

It is a statistical fact that you learn in university statistics course 101.

But let’s be generous, and NOT question the questionable.

Let’s just look at the figures: 16% sounds impressive.

Spoiler alert, it isn’t impressive at all when you look at the absolute figures.

Of the 1.7 million people, almost 6000 developed cancer.

That is 0.3%, or 3 of every thousand people.

At this rate, the 16% difference translates into a difference of 5 people for every 10.000 people.

 So, if you take 10.000 people, 30 might get cancer if they drink “highly nitrate-contaminated” water, as opposed to “only” 25 of 10.000 people who drink the least-contaminated water.

I don’t know how you feel about this, but to me the nitrate in drinking water isn’t a clear and present danger.

A recent review of the evidence comes to the conclusion that …

“…most adverse health effects related to drinking-water nitrate are likely due to a combination of high nitrate ingestion and factors that increase endogenous nitrosation.” [5]

Would I recommend any nitrate supplement if there was any?

 No, because drinking beet root juice, is a clean and safe alternative. It delivers the nitrate, and it delivers what prevents the body from turning nitrate into something potentially cancerous.

That’s why we use beet-root juice as an intervention option in our “science kit” for biohacking lifelong health and functional longevity. You can read more about it on our website.

To monitor the effects on vascular function, aging and blood pressure we use the WIFI-capable devices of @Withings.

As Hippocrates said:

"Let food be thy medicine and medicine be thy food."

And let beet juice be thy drink.

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PS:

This post contains referral links for the Withings devices on Amazon. If you purchase the device from there, I will receive a small commission at no additional charge to you.

 

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References

 [1]     Ghasemi A. Quantitative Aspects Of Nitric Oxide Production From Nitrate And Nitrite. EXCLI J 2022;21:470–86. doi:10.17179/excli2022-4727.

[2]     Thomas DD. The biological lifetime of nitric oxide: Implications for the perivascular dynamics of NO and O2. Proc Natl Acad Sci 2001;98:355–60. doi:10.1073/pnas.011379598.

[3]     Mills CE, Khatri J, Maskell P, Odongerel C, Webb AJ. It is rocket science - why dietary nitrate is hard to Beet! part II: further mechanisms and therapeutic potential of the nitrate-nitrite-NO pathway. Br J Clin Pharmacol 2016. doi:10.1111/bcp.12918.

[4]     Schullehner J, Hansen B, Thygesen M, Pedersen CB, Sigsgaard T. Nitrate in drinking water and colorectal cancer risk: A nationwide population-based cohort study. Int J Cancer 2018;143:73–9. doi:10.1002/ijc.31306.

[5]     Ward MH, Id RRJ, Brender JD, Kok TM De, Weyer PJ, Nolan BT, et al. Drinking Water Nitrate and Human Health : An Updated Review 2018:1–31. doi:10.3390/ijerph15071557.