Analysis of the Influence of Nitrite for Public Health

Kang Qiao

Qingdao NO.2 Middle School, Qingdao, 266100, China

Keywords: Nitrite, Public Health, Cardiovascular Disease, Nitrite Pollution.

Abstract: Nowadays, it is necessary to study whether nitrite should be limited strictly or used normally, since nitrite has

both benefits and probable harms. Researchers hold different opinions of nitrite, including if nitrite should be

ingested by people, making people confused on who to believe and which instruction to follow. Thus, the

author conducts this study to have an overview on the previous literature and analyzes the related information

in order to give suggestions to people. Through the analysis, it is concluded that nitrite has advantages of

curing cardiovascular disease, and defensing bacteria. Additionally, it has controversial harms of causing

cancer and deformity, as well as the doubtless harm of nitrite poisoning. To deal with the benefits and harms

of nitrite, people should ingest nitrite properly and the government need to take actions to reduce nitrite

pollution.

1 INTRODUCTION

Nitrite commonly forms in daily food, especially

vegetables, barbecue, and pickled food. With the

development of technology and the improvement of

living standard, people have progressively paid more

attention to food safety, so nitrite in food becomes one

of the hot spots. Nowadays, it is controversial that if

nitrite should be limited strictly or used normally

since nitrite is both beneficial in some aspects, and

has some uncertain harms, such as causing cancer and

deformity. To be specific, news and some articles

provided by social media tell people to focus on the

carcinogenicity and teratogenicity of nitrite, and

provide advice, such as warning people not to drink

water that has been boiled for several times, which

contains more nitrite than normal water. What is

more, there are lots of studies and experiments to

prove that nitrite does not cause cancer and deformity,

but has plenty of benefits. Under this circumstance,

people hesitate about which opinion to believe so that

they may not have the proper strategy to control

nitrite. Therefore, it is necessary to review the

positive and negative influences of nitrite, and give

some suggestions on how to deal with nitrite when we

have not solved this controversy. This paper would

elaborate these points to help people understand

nitrite more clearly, and tell individuals as well as

departments of government to control nitrite to

maximize the benefit and minimize the probable

harms.

Figure 1: Schematic presentation of nitric oxide (NO) generation and metabolism in the body (Machha, Schechter 2011).

200

Qiao, K.

Analysis of the Inﬂuence of Nitrite for Public Health.

DOI: 10.5220/0011243100003438

In Proceedings of the 1st International Conference on Health Big Data and Intelligent Healthcare (ICHIH 2022), pages 200-205

ISBN: 978-989-758-596-8

2 ANALYSIS OF THE BENEFITS

AND HARMS OF NITRITE

2.1 Benefits of Nitrite

2.1.1 Management of Cardiovascular

Disease

As can be seen in figure 1, nitrite can be reduced

to be NO in human body. Up till now, scientists have

found many ways to reduce nitrite to be NO. For

example, nitrite can be reduced by

deoxyhemoglobin, deoxymyoglobin, xanthine

oxidoreductase, cytochrome P450 enzymes,

mitochondrial respiratory chain enzymes, aldehyde

oxidase, carbonic anhydrase, acidic

disproportionation, and reducing agents (e.g.

ascorbate, polyphenols), which only have high

activity in the low-PH and low-oxygen condition

(Machha, Schechter 2011). Additionally, arterial

venous gradient of nitrite in human forearm

circulation shows that nitrite is metabolized to NO

across physiological pH and oxygen level (Cosby,

Partovi, et al. 2003). Thus, NO, reduced from nitrite

and can be formed in low-oxygen condition, is the

substitution of endothelium-derived NO, which is

synthesized from the amino acid L-arginine by the

eNOS enzyme with oxygen. Thus, there would be

more NO in cardiovascular system if people ingest

nitrite.

Figure 2: Schematic presentation of potential mechanisms by which dietary nitrite and nitrate could modulate cardiovascular

health (Machha, Schechter 2011).

NO plays a significant role in improving the

endothelial function since NO can help to maintain

the vascular homeostasis. To be specific, as can be

seen in figure 2, NO can control smooth muscle cells

and circulating blood cells to manage the

proliferation of smooth muscle cell, activity of

platelet, and vasodilation of blood vessels (Naseem

2005). Hence, the lack of NO would cause endothelial

dysfunction, leading to the disruption of vascular

homeostasis, and then result in many cardiovascular

problems. On the contrary, sufficient amount of nitrite

would make cardiovascular diseases below to be

cured.

As for thrombus, abnormal aggression of platelet

would lead to thrombus, which would contribute to

the cerebral thrombosis, myocardial infarction, or

ASO. Fortunately, the intake of nitrite can inhibit the

aggregation of platelet (Johnson et al. 1990). As for

Myocardial ischemia, reperfusion therapy is one of

the most effective treatment to decrease the size of

myocardial infarction area by making blood go back

to the heart. However, reperfusion therapy would

cause myocardial damage, which is a very serious

problem, leading to heart failure, cardiac fibrosis, and

even sudden death. Recent research display that

nitrite would reduce the damage to heart. For

example, Webb et al. found that the retrograde

perfusion with nitrite can decrease the myocardial

infarction area by 60% during the treatment of

retrograde perfusion (Webb et al. 2004).

Hypertension has been one of the commonest disease

in cardiovascular diseases. Nowadays, plenty of

people, especially the middle-aged and the elderly,

are suffered or even die because of hypertension. As

an important way to cure hypertension, the treatment

of nitrite works out pretty well. Scientists found that

18.8 mg of nitrate per kilogram body weight per day,

which would be transformed to nitrite inside body

(Feng 1983), would decrease diastolic blood pressure

by 4.5 mm (Hg Sobko et al. 2010).

2.1.2 Defense against Bacteria

Nitrite can inhibit the growth of anaerobic bacteria,

such as Achromobacter, Aerobacter, Escherichia,

Flavobacterium, Micrococcus, and Pseudomonas.

The function of nitrite of defensing against bacteria,

in my opinion, can be divided into three parts—oral

cavity, gastrointestinal tract, and skin. As for oral

cavity, 25% of the intake of nitrate into human body

Analysis of the Inﬂuence of Nitrite for Public Health

201

would be secrete to oral cavity, and then be reduced

to nitrite by symbiotic bacteria in mouth. Because of

the antibacterial function of nitrite, many bacteria in

mouth can be inhibited. As for gastrointestinal tract,

acidic environment provided by gastric acid would

acidify nitrite, helping to kill bacteria. To illustrate,

Dykhuizen et al. conducted experiment that make

Yersinia enterocolitica, Salmonella Enteritidis,

Shigella sonnei, and Escherichia coli O157 to be

exposed different concentration of nitrite and

different PH. As a result, they found that the acidic

condition and nitrite would cooperate to kill pathogen

(Dykhuizen et al. 1996). Skin is also a weak acidic

environment because nitrite would be released to the

surface of skin with sweat, and nitrite can play a role

in defensing bacteria on skin.

2.2 Harms of Nitrite

2.2.1 Carcinogenicity of Nitrite

The carcinogenicity of nitrite is still sort of

controversial. Some scientists are big supporters of

the opinion that nitrite would lead to cancer. First, the

mechanism of nitrite is very clear. Nitrite does not

cause cancer directly, and most of the intake of nitrite

would be excreted out of body along with urine.

Nevertheless, under acidic condition (PH 1-4) some

of nitrite would decompose into nitrous acid, which

would then decompose into nitroso due to the

instability. After this, nitroso would combine with

secondary amine, a kind of metabolites of protein, to

synthesize nitrosamine, which is a sort of very strong

carcinogen. Nitrosamine would methylate guanine of

RNA and DNA to make mutation occur in cells

(Zhang et al. 2015). Second, some experiments, such

as the experiment conducted by U.S. National

Toxicology Program, showed that although there was

no evidence showing that the sodium nitrite had

carcinogenic activity in the group of female F344/N

rats and male B6C3F1 mice, they found that maybe

the carcinogenic activity displayed in the group of

female B6C3F1 mice according to the positive trend

in the incidences of squamous cell papilloma or

carcinoma (combined) in the forestomach (Program

2008).

Other scientists believe that nitrite does not have

the property of carcinogenicity, so they contradicts

the opinion above respectively. First, the formation of

great amount of nitrosamine is not convincing.

Specifically, nitrite requires nitrite reductase from

certain bacteria to catalyze the reaction of synthesis

of nitrosamine, but healthy people have very little this

sort of bacteria in their stomach. What is more, 500

mg vitamin C can reduce the formation of

nitrosamine in stomach reduce by 99%, so the

everyday diet would almost prevent the formation of

it. What is more, attributing to the acidic environment

in stomach, nitrite would be quickly reduced into NO,

and then released out of body (Griesenbeck et al.

2009). Therefore, it is no need to worry about the

nitrosamine transformed from nitrite. Second, the

experiment of rats and mice is not convincing either.

This research only offer the evidence of

carcinogenicity in forestomach of female B6C3F1

mice, but not offer evidence of carcinogenicity in

other organs or tissues in both female and male mice

and rats (Bryan et al. 2012). Third, as evidenced by

information in figure 3 shown below (Bryan et al.

2012), scientist indicates that the a majority of

research proving that nitrite is carcinogenicity was

conducted several decades ago, and most of more

recent, and better-designed studies showed that nitrite

was not related to cancer.

However, some other scientists raises new point

that nitrite does not cause cancer, but induce cancer

(Huang et al. 2009). Specifically, before the

formation of tumour, cancer cells has already attain

denitrification gene from some symbiotic bacteria

with anaerobic metabolism in human body, and then

survive as cancer stem cells. In certain condition,

these cancer stem cells would move to tumour, and

the gene with the function of denitrification would be

activated. These cells would choose nitrite respiration

to adapt to the microenvironment surrounding the

tumour. Hence, as the source of nutrient of cancer

cells, nitrite may promote the growth of them, but not

cause cancer. However, this idea does not have

enough data, or material supporting it so that the truth

of this theory is doubted.

2.2.2 Teratogenicity of Nitrite

Like the carcinogenicity, the teratogenicity of nitrite

is also controversial. Many materials show the

teratogenicity of nitrite. For example, NaNO2 would

damage the DNA of supporting cell of testis when the

dose of NaNO2 is larger than 150 μg /ml (Ren 2007).

Some other information disproves the teratogenicity

of nitrite. For instance, 0-100 mol/L sodium nitrite

under neutral condition would not hurt DNA of

epithelial cells in stomach. Only when PH falls to 4.2

and the dose of sodium nitrite is more than 50

mmol/L, the DNA might be damaged (Smith et al.

2006). Thus, people cannot reach that strict standard

of environment in their daily life, so the harm

stemming from the teratogenicity would not occur.

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Figure 3: Animal Toxicological Studies of Nitrite Carcinogenicity with Serious Methodological Limitations (Bryan et al.

2012).

2.2.3 Nitrite Poisoning

Nitrate poisoning, also called enterogenous cyanosis,

resulted from too much intake of nitrite or nitrate (a

great part of nitrate would be reduced into nitrite in

human body). 0.3-0.5g nitrite would cause nitrite

poisoning, and more than 3g nitrite would cause death

(Ye 2007). After nitrate gets into human’s body, it

would react with ferrous ion in hemoglobin to oxidize

normal hemoglobin into hemoglobin, which does not

have the ability of carrying oxygen (Ye 2007). In this

regard, all the tissues and organs in human body

would confront oxygen deficit, leading to the

symptoms mentioned above.

3 MEASURES OF

CONTROLLING NITRITE

According to the benefits and harms of nitrite above,

it is difficult to completely prohibit the use of nitrite

because of its benefits in treatment and prevention of

cardiovascular diseases, and the function of defensing

bacterial. Moreover, we cannot intake nitrite as much

as we want since scientists are not sure if nitrite has

car and tera properties, and too much nitrite would

lead to poisoning. Thus, some instructions or

measures are needed to avoid the possible harms and

attain benefits.

3.1 Distinguishing Susceptible

Population

Given the probable harms of nitrite because of the

doubted carcinogenicity and teratogenicity, it is

necessary to find susceptible population, and develop

special diet standard for them to avoid these harms

(Huang et al. 2009). Susceptible population here

might include ones who have medical history of

cancer, especially gastric cancer, in family, ones who

have serious stomach problems, and so on. As for

these susceptible population, they should follow their

own diet standards, such as avoiding consuming

barbecue and pickled food, which contain relatively

high amount of nitrite. If possible, they should also

remember to blanch some vegetables high in nitrite

before cooking, like spinage, to reduce nitrite.

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203

3.2 Avoiding Excessive Intake of Nitrite

Too much intake of nitrite would lead to nitrite

poisoning, so all of people should pay attention to the

amount of nitrite they ingest. For instance, people

should not purchase pickled food without having

labels of expiration rate, and ingredient list, in

informal stalls. According to the analysis of test result

of nitrite content in cooked meat product in Zhoukou

in 2014-2015, products with nitrite beyond the

standard have a proportion of 34.87% among all the

products, and the maximum nitrite content is

1370mg/kg (Zhang, Lu, Sun 2017). If people

consume plenty of packaged food like these, they

might be suffered from nitrite poisoning.

3.3 Control of Nitrate Pollution in

Vegetables

In most of areas in China, nitrates (which would be

reduced into nitrite) in several kinds of leafy and root

vegetables with relatively high consumption are

much higher than normal, and the one with highest

content is 9 times as standard (Ye 2007). Under this

circumstance, it is necessary for the governments and

organizations to control nitrate pollution in

vegetables. Here are some advice: Governments can

request farmers to select vegetables species which

cannot accelerate much nitrate; the Bureau of

Agriculture can come up with new way to use

fertilizers, such as coordinating nitrogen fertilizers

with organic fertilizers.

3.4 Dietary Intervention of Nitrite

Nitrite has the ability of curing cardiovascular

diseases, so doctors can design special daily diet plans

for patients who suffer from cardiovascular diseases,

especially hypertension. According to different

conditions, doctors can adjust the intake of nitrite for

patients in everyday meals.

4 DISCUSSION

This paper analyzes both the benefits and the

probable harms of nitrite comprehensively, and

provide some measures to control the use of nitrite to

not only prevent people from harms, but also take

advantage of nitrite. According to the evidence

provided by past papers, the opinion that nitrite does

not have carcinogenicity and teratogenicity is more

convincing because of the clear, logical arguments,

and plenty of accurate date from experiments.

Nevertheless, the evidence supporting the

carcinogenicity or teratogenicity of nitrite is sort of

insufficient, and has some holes. Although perhaps

nitrite may not cause cancer and deformity, people

should still pay attention to their intake of nitrite since

no one has offered the perfect experiment and

research result to make sure that nitrite would not lead

to cancer, deformity, or maybe some other illness that

scientists have not found. Therefore, scientists should

continue to devote great efforts to the controversy or

carcinogenicity and teratogenicity of nitrite in the

future in order to understand the property of nitrite in

depth so that people can ingest nitrite properly, and

then achieve healthier life.

The influence of nitrite is only one part of food

safety. Food safety nowadays is a serious problem in

many countries. Thus, governments should introduce

new policies to control food products, and supervise

food hygiene; organizations and social medias should

popularize knowledge of food safety; individuals

should follow the instructions and pay more attention

to their everyday food. The more everyone devote to

food safety, the healthier people should be.

5 CONCLUSIONS

Nitrite has benefits of curing cardiovascular disease,

and defensing bacteria. What is more, it has

controversial harms of causing cancer and deformity,

and the doubtless harm of nitrite poisoning. To deal

with the benefits and harms of nitrite, people should

follow instructions to ingest nitrite properly, and

government need to take actions to reduce nitrite

pollution. Additionally, scientists should continue to

explore the carcinogenicity and teratogenicity of

nitrite, in order to make measures of controlling

nitrite more impeccable.

ACKNOWLEDGMENTS

I appreciate my teachers, Jane and Alice, and my

parents, who supported me helped me a lot. Without

their help and encouragement, I cannot complete this

paper.

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