Who is at most Risk of Adverse Health Effects from Overexposure to Nitrates and Nitrites?
Infants less than 4 months of age are most at risk of adverse health effects from over exposure to nitrates and nitrites through ingestion of formula diluted with nitrate contaminated water.
Although there is no nutritional indication to add complementary foods to the diet of a healthy term infant before 4 to 6 months of age, the American Academy of Pediatrics suggests that home-prepared infant foods from vegetables (i.e. spinach, beets, green beans, squash, carrots) should be avoided until infants are 3 months or older.
Gastroenteritis with vomiting and diarrhea can exacerbate nitrite formation in infants and has been reported to be a major contributor to methemoglobinemia risk in infants independent of nitrate / nitrite ingestion.
In addition, the pregnant woman and her fetus might be more sensitive to toxicity from nitrites or nitrates at or near the 30th week of pregnancy.
Individuals with glucose-6-phsphate dehydrogenase (G6PD) deficiency may have greater susceptibility to the oxidizing effects of methemoglobinemia inducers.
Sleep is a normal and indeed essential part of our lives. But if you think about it, it is such an odd thing to do. At the end of each day we become unconscious and paralysed. Sleep made our ancestors vulnerable to attack from wild animals. So the potential risks of this process, which is universal among mammals and many other groups, must offer some sort of evolutionary advantage. Research in this area was slow to take off. But recently there has been a series of intriguing results that are giving researchers a new insight into why we sleep and what happens when we do it.
Why do I sleep?
Scientists simply don’t know for sure. In broad terms researchers believe it is to enable our bodies and especially our brains to recover. Recently researchers have been able to find out some of the detailed processes involved. During the day brain cells build connections with other parts of the brain as a result of new experiences. During sleep it seems that important connections are strengthened and unimportant ones are pruned. Experiments with sleep-deprived rats have shown that this process of strengthening and pruning happens mostly while they sleep. And sleep is also an opportunity for the brain to be cleared of waste. A group led by Prof Maiken Nedergaard at the University of Rochester Medical Centre in New York discovered a network of microscopic fluid-filled channels in rats that clears waste chemicals from the brain. Prof Nedergaard told us when her research was first published in 2013 that this process occurs mostly when the brain is shut off. “You can think of it like having a house party. You can either entertain the guests or clean up the house, but you can’t really do both at the same time.”
What happens when I don’t get enough sleep?
It seems that a lack of sleep alters the way in which the genes in the body’s cells behave. Researchers at Surrey University in Guildford have found that genes involved in inflammation seem to increase their activity. Dr Malcolm von Schantz, who is involved with the Surrey research, believes that the genes are responding to lack of sleep as if the body is under stress. He speculates that in the distant past in times of stress our ancestors’ bodies would prepare themselves for injury by activating these inflammation genes which would cushion the effects of attacks by wild animals or human enemies. “It puts the body on alert for a wound but no wound happens,” he told Sleep Advice. “This could easily help explain the links between sleep deprivation and negative health outcomes such as heart disease and stroke.” In modern times though preparing for an injury that never happens has no beneficial effect – in fact the consequent activation of the immune system might increase the risk of heart disease and stroke.
Why is it hard to think when I am tired?
The expression “half asleep” might be an accurate description of what is going on in the brain when you are feeling slow-witted. Research suggests that parts of the human brain may well be asleep when it is sleep-deprived. Studies on whales and dolphins show that when asleep they continue to use half of their brain to swim and come up to the surface for air. A study on human patients showed that something similar goes on in our brains. As they became more sleep-deprived, parts of their brain became inactive while they were still awake. What’s more the local sleep areas move around the brain. So although when we go to bed we think one moment we are awake and then there is an abrupt change to sleep – it may well be more of a continuous process.
What is the role of dreaming?
That’s a question that psychiatrists, notably Carl Jung and Sigmund Freud, have tried to answer but with limited success. More recently a team at the ATR Computational Neuroscience Laboratories in Kyoto in Japan has begun trying to answer some of these questions by building the beginnings of a dream-reading machine. They asked volunteers to doze off in an MRI scanner and recorded their brain patterns. The volunteers were then woken up and asked to tell researchers what they were dreaming about. The team then listed 20 separate categories of dream content from these accounts such as dwelling, street, male, female, building or computer screen. The researchers then compared the accounts with the pattern of activity in the area of the brain responsible for processing visual information – and to their amazement they found that there was a correlation. So much so that they could predict which of the 20 different categories they had listed the patient had dreamt of with 80% accuracy. The device is a very rough tool but it may well be a first step to something that can see in more detail what happens in our dreams and so help researchers learn more about why we dream.
How is modern life affecting our sleep patterns?
Several studies show that the light bulb has led people shifting their day and getting less sleep. On average we go to bed and wake up two hours later than a generation ago. The US Centres for Disease Control reported in 2008 that around a third of working adults in the US get less than six hours sleep a night, which is 10 times more than it was 50 years ago. In a later study it was also reported that nearly half of all the country’s shift workers were getting less than six hours sleep. And a study led by Prof Charles Czeisler of Harvard Medical School found that those who read electronic books before they went to bed took longer to get to sleep, had reduced levels of melatonin (the hormone that regulates the body’s internal body clock) and were less alert in the morning. At the time of publication he said: “In the past 50 years, there has been a decline in average sleep duration and quality. “Since more people are choosing electronic devices for reading, communication and entertainment, particularly children and adolescents who already experience significant sleep loss, epidemiological research evaluating the long-term consequences of these devices on health and safety is urgently needed.”
What’s stopping you sleeping?
– One in eight of us keep our mobile phones switched on in our bedroom at night, increasing the risk our sleep will be disturbed.
– Foods such as bacon, cheese, nuts and red wine, can also keep us awake at night.
Many studies report that there is evidence that sleep loss is associated with obesity, diabetes, depression and lower life expectancy – while others, such as Prof James Horne, a sleep researcher at Loughborough University believes that such talk amounts to “scaremongering”. “Despite being ‘statistically significant’, the actual changes are probably too small to be of real clinical interest,” he told Sleep Advice. “Most healthy adults sleep fewer than that notional ‘eight hours’ and the same went for our grandparents. “Our average sleep has fallen by less than 10 minutes over the last 50 years. Any obesity and its health consequences attributable to short sleep are only seen in those few people sleeping around five hours, where weight gain is small – around 1.5kg per year – which is more easily rectified by a better diet and 15 minutes of daily brisk walking, rather than by an hour or so of extra daily sleep.” A team from the universities of Surrey and Sao Paulo in Brazil have spent the past 10 years tracking the health of the inhabitants of Bapendi, a small town in Brazil where modern day lifestyles haven’t yet taken hold. Many of the inhabitants of this town get up and go to bed early. The investigators hope to find out soon whether the old adage “early to bed and early to rise” really does make us, if not “wealthy and wise”, at least “healthy and wise”.
What are U.S. Standards and Regulations for Nitrates and Nitrites Exposure?
EPA has set an enforceable standard called a maximum contaminant level (MCL) in water for nitrates at 10 parts per million (ppm) (10 mg/L) and for nitrites at 1 ppm (1 mg/L).
EPA believes that exposure below this level is not expected to cause significant health problems.
All public water supplies must abide by these regulations.
Given present technology and resources, this MCL is also a level to which water systems can reasonably be required to remove this contaminant should it occur in drinking water.
Once a water source is contaminated, the costs of protecting consumers from nitrate exposure can be significant. This is because:
Nitrate is not removed by conventional drinking water treatment processes.
Its removal requires additional, relatively expensive treatment units.
Intake Nitrate Limits
The Joint Expert Committee on Food Additives (JECFA) of the Food and Agriculture Organization of the United Nations / World Health Organization and the European Commission’s Scientific Committee on Food have set an acceptable daily intake (ADI) for nitrate of 0–3.7 milligrams (mg) nitrate ion / kilogram (kg) body weight. This intake appears to be safe for healthy neonates, children, and adults. The same is also true of the EPA reference dose (RfD) for nitrate of 1.6 mg nitrate nitrogen / kg body weight per day (equivalent to about 7.0 mg nitrate ion / kg body weight per day).
JECFA has proposed an ADI for nitrite of 0–0.07 mg nitrite ion/kg body weight. EPA has set an RfD of 0.l mg nitrite nitrogen/kg body weight per day (equivalent to 0.33 mg nitrite ion/kg body weight per day).
Bottled Water and Food Additives Nitrate Limits
The FDA regulates allowable levels of inorganic nitrate and nitrite in bottled water [FDA 2005] as well as levels allowable in foodstuffs.
The FDA’s bottled water standard is based on the EPA standards for tap water. The bottled water industry must also follow FDA’s Current Good Manufacturing Practices (CGMPs) for processing and bottling drinking water. If these standards are met, water is considered safe for most healthy individuals. However, although not often reported, bottled water outbreaks do occur.
Allowable nitrite levels in bottled water:
Nitrate 10 mg/L (as nitrogen)
Nitrite 1 mg/L (as nitrogen)
Total nitrates, nitrites 10 mg/L (as nitrogen)
Allowable nitrite levels as an additive to foods:
As a preservative and color fixative, with or without sodium nitrite, in Smoked, cured sablefish; Smoked, cured salmon; Smoked, cured shad, so that the level of sodium nitrate does not exceed 500 parts per million (ppm) and the level of sodium nitrite does not exceed 200 ppm in the finished product.
As a preservative and color fixative, with or without sodium nitrite, in meat-curing preparations for the home curing of meat and meat products (including poultry and wild game), with directions for use which limit the amount of sodium nitrate to not more than 500 ppm in the finished meat product and the amount of sodium nitrite to not more than 200 ppm in the finished meat product.
The food additive potassium nitrate may be safely used as a curing agent in the processing of cod roe, in an amount not to exceed 200 ppm of the finished roe.
The U.S. Department of Agriculture’s (USDA’s) Food Safety and Inspection Service (FSIS) regulates food ingredients approved for use in the production of meat and poultry products. This includes inspection for required labeling of meat products when substances such as sodium nitrate are used in meat packaging.
Environmental Nitrate and Nitrite Standards
The current water standard for nitrate is based on levels considered low enough to protect infants from methemoglobinemia.
Some published results suggest a possible association between nitrate exposure during pregnancy and human malformations.
However, a review of the toxicology in relation to possible adverse effects on reproduction and development offers no evidence for teratogenic effects attributable to nitrate or nitrite ingestion.
The present maximum contaminant level appears to adequately protect even sensitive populations from nitrate-induced toxicity.
EPA concludes that the evidence in the literature showing an association between exposures to nitrate or nitrites and cancer in adults and children is conflicting.
Key Points of Nitrate and Nitrite Standards
The current water standard for nitrate is based on protection of infants from methemoglobinemia.
In vivo conversion of nitrates to nitrites significantly enhances nitrates’ toxic potency.
We might feel drowsy as we start to fall asleep, but our brain is still active, and noises or discomfort can disturb us. As we drift into light sleep, an area of the brain called the hypothalamus starts to block the flow of information from our senses to the rest of the brain. But it will still let through noises, which need to be able to wake us up. After about half an hour of light sleep, most of us enter a type of deep sleep called slow-wave sleep. Our brains become less responsive and it becomes much harder to be woken up. But some things will always get through – such as our names being called out loudly. Missing out on parts of our usual sleep cycle reduces the quality and quantity of sleep.
We all have a built-in body clock which tells us when we are tired. It helps synchronise thousands of cells in our body to a 24-hour cycle called the circadian rhythm. The main synchroniser for our body clock is light. Our eyes react to light and dark, even when our eyelids are closed. Daylight prompts our brains to reduce the production of the sleep hormone melatonin. This makes us feel more alert. If we get less sleep during the night, because of going to bed late or waking up early, we’re unlikely to get as much deep sleep as we need.
The wrong temperature
Our core body temperature should drop by half a degree when we are asleep. So as sleep approaches, our body clock makes blood vessels in our hands, face and feet open up, in order to lose heat. But if we get too cold, we get restless and find it hard to sleep. Or if our bedrooms or duvets are too warm, our bodies can’t lose heat, which can also cause restlessness.
Stimulating food and drink
We can have trouble sleeping after we consume food and drink that act as stimulants.
Drinks high in caffeine make it harder to fall asleep and can interfere with our deep sleep. Caffeine can stay in our system for many hours, so our sleep quality can be affected by the caffeinated drinks we consume earlier in the day.
In the course of a night we usually have six to seven cycles of REM (rapid eye movement) sleep, during which our brains process the information we’ve absorbed during the day. This leaves us feeling refreshed. But a night of drinking means we’ll typically have only one to two cycles and wake up feeling tired.
Foods containing a chemical called tyramine, such as bacon, cheese, nuts and red wine, can keep us awake at night. This is because tyramine triggers the release of noradrenaline, a brain stimulant.
A busy mind
Stress is the enemy of sleep. In bed, our mind is left free to wander and anxiety concerning sleep will only make it worse. It’s difficult to keep track of time when you’re lying down in the dark waiting for sleep. People often nod off and wake up again but it feel as if they’re getting no sleep at all. This delivers fragmented sleep with much less time spent in the important deep sleep stages.
Sleep experts recommend that people with this problem get up and do an activity which distracts the mind from worry – such as a puzzle – before trying to sleep again.
Nitrates and nitrites can be categorized into inorganic and organic forms based on their chemical structure. There are similarities and differences between these two chemical forms that affect their pharmacokinetic and pharmacodynamic properties and their subsequent biologic effects in humans. This artical will focus on inorganic nitrates.
Inorganic Nitrates and Nitrites
Inorganic nitrate (NO3–) and nitrite (NO2–) are water soluble (as a result of their interaction with the positively charged portions of polar water molecules)
and commonly exist as salts of nitric acid and nitrous acid, respectively. They are often bound to a metal cation such as Na+ or K+ and occur naturally through the fixation of atmospheric nitrogen and oxygen as part of the environmental nitrogen cycle (the cyclic movement of nitrogen in different chemical forms from the environment, to organisms, and then back to the environment as illustrated).
Inorganic nitrites are also produced endogenously through oxidation of nitrous oxide (NO) formed from the enzymatic degradation of L-arginine and through the reduction of nitrate with xanthine oxidoreductase.
Organic Nitrates and Nitrites
The organic forms of nitrates and nitrites are more complex and most are synthesized medicinal products (except ethyl nitrite). Organic nitrates are small non-polar hydrocarbon chains attached to a nitrooxy-radical (-ONO2; -ONO for amyl and ethyl nitrite). The addition of aliphatic or aromatic groups of variable length and volume affect the lipophilic properties of these molecules. It has been suggested that for some molecules, the greater the number of –ONO2 groups, the greater its potency; (the potency being dependent on the molecule’s lipophilicity).
Nitrates and Nitrites exist in organic and inorganic forms.
The chemical form affects the pharmacokinetic and pharmacodynamic properties of nitrates and nitrates.
Inorganic nitrates and nitrites are generally more water soluble than organic nitrates and nitrates.
Inorganic nitrates and nitrites are produced endogenously and exogenously.
Organic nitrates and nitrites are mostly synthesized medicinal products.
Organic nitrates and nitrites are generally more complex and lipophilic than inorganic nitrates and nitrites.