Is nitrogen that drains from paddocks into aquifers and waterways contributing to New Zealand's high rate of colorectal cancer?
Michael Baker is hard to reach. He had to bump his interview with the Listener to be vaccinated on live television. He apologised: "This is a really important topic."
Covid-19 has shone a light on public health expertise, and Baker is a respected source of advice. He's professor of public health at the University of Otago, Wellington, and part of the Ministry of Health's Covid-19 Technical Advisory Group. He was this year made a member of the New Zealand Order of Merit for services to public health science.
It seems an opportune time to ask him about other issues that concern him — such as the apparent association between colorectal cancer and elevated nitrate in drinking water.
In New Zealand, he notes, the risk of colorectal cancer is much higher than in many other countries, which makes him wonder whether something in the environment is to blame. "The causes are probably multi-factorial, but it's suggestive from a number of studies that there is an association with elevated nitrate in drinking water," he says. "It might only account for a small percentage of cases, but that's still important when applied to our second-biggest cause of cancer deaths."
The backbone of the nitrate compound is nitrogen, an abundant element in air needed by all plants and animals. But more isn't necessarily better. Carbon is vital for life, yet the effects of plumping up the atmosphere with it are becoming obvious. We also plump up soil with nitrogen, much of it extracted from air and turned into synthetic nitrogen fertiliser. This boosts crop yields and is recognised as a primary factor in the past century's population explosion. It helps produce half the world's food.
But there's a downside. Some of that nitrogen dissipates as greenhouse gas or washes into aquifers and waterways. It has contaminated streams and lakes around the world, fuelled algal growth that suffocates aquatic species, and caused coastal "dead zones". Its effects on human health are less clear.
Babies and bowels
Historically, waterways and aquifers contained little nitrate, and its presence is generally attributed to agricultural intensification. It's rare, though, to drink water that exceeds the safety levels in this country of 11.3 milligrams of nitrogen per litre, based on World Health Organisation (WHO) guidelines. That was set to avoid "blue baby syndrome" in babies fed infant formula mixed with tap water).
Baker says the "blue baby" maximum doesn't consider chronic exposure to lower levels. Dr Tim Chambers, a senior research fellow who works with Baker, agrees: "The perception is that if it's under 11.3mg, there's only a risk for infants under six months. So, for adults, there's essentially considered to be no risk, no matter how high the concentration. But if you read the studies on chronic exposure, especially the high-quality ones, that's not what's indicated."
In a 2018 study comparing drinking water and cancer records in Denmark, water nitrate levels above only 0.87mg/l were linked with a higher incidence of colorectal cancer. The incidence jumped again at 2.1mg/l – about a fifth of the maximum acceptable level.
Chambers knows of 11 studies showing an association between elevated nitrate in drinking water and colorectal cancer. But for him, the Danish study was "a wake-up call". Denmark has robust measurements of nitrate in drinking water going back decades, he notes. "Trying to collate a national data set here is a huge challenge."
Queenstown-based water engineer Jayne Richards couldn't agree more. Richards examined drinking water records for her master's thesis, which Chambers and Baker co-supervised. Because there is no central database in this country, she had to request data from 67 district councils and 119 private drinking water suppliers. She also measured nitrate in a sample of Southland homes with unregistered supplies.
A co-authored paper based on her thesis will soon be published in the journal Environmental Research. Although only a preliminary study, it suggests that nitrate in drinking water could be contributing to 0.8-5.6% of colorectal cancers here.
Richards and her co-authors believe that about 7-10% of the population drink water that could increase their risk of colorectal cancer. They found notably high nitrate levels in Canterbury and Southland, and in rural water supplies that serve small numbers of people. City supplies, which are generally well treated, did not have high levels.
At this stage, however, there is no cause for alarm, says public health physician Brian Cox, an associate professor and director of the Hugh Adam Cancer Epidemiology Unit at the University of Otago. Even for those drinking nitrate-rich water, the risk is small compared with eating a diet high in processed meat.
It can also be hard to deduce what else might be going on, Cox says. "The development of cancer typically requires regular exposure for at least a decade, so it's preferably the lifetime accumulation of exposure that needs to be measured, not current exposure. In this case, the relationships that have been found are weak enough that they may be explained by other things. We can't yet be confident that something else isn't at play."
Baker agrees. "We need a reasonable sense of proportion. The evidence is on the weaker end of the spectrum and association does not necessarily mean causation. In rural areas, there are likely to be different dietary patterns, exercise patterns or other differences. They may be driving the association."
The Danish study attempted to account for known risk factors, such as eating meat, drinking alcohol and smoking, by including people's highest education level as a rough proxy for these habits. Other studies report that Danes with more education tend to have healthier, vegetable-rich diets and be non-smokers. More education dented the cancer's incidence, but the nitrate link persisted.
Nitrate's carcinogenic potential has long been contemplated. In 2010, the WHO's specialised cancer agency, the International Agency for Research on Cancer (IARC), considered multiple studies into many types of cancer and nitrate. Its verdict? No evidence from epidemiological studies of an increased risk from food, and inadequate evidence in humans that nitrate in drinking water is carcinogenic. But, it noted in its final conclusion, "ingested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans".
Endogenous nitrosation, which is a chemical reaction inside the body, is the core of the suspicion cast on nitrate. Nobody suspects nitrate itself of causing cancer – our bodies need some of its nitrogen, and much of it exits swiftly in urine. Instead, concern lies with nitrate's transformation, with the aid of mouth bacteria and stomach acid, into nitrite and eventually nitrosamines. Many nitrosamines mutate DNA in a tumour-promoting fashion.
That's less alarming than it sounds, says Peter Cressey, a chemical risk assessor at the Institute of Environmental Science and Research (ESR) and a member of the United Nations' expert committee that looks at the safety of chemicals in food. That is because the IARC examines theoretical – rather than real-life – risk, says Cressey.
The European Food Safety Authority, which does take real-life factors into account, has stated that the acceptable daily intake might be exceeded for people with medium to high exposure if all sources, including environmental contamination, are taken into account.
That accounting has been done for New Zealanders. Commissioned by the New Zealand Food Safety Science & Research Centre, Cressey and ESR toxicologist Dr Belinda Cridge recently assessed dietary and drinking water exposure to nitrate. Fonterra and the Ministry of Business, Innovation & Employment requested and co-funded the study, which has been reviewed by a toxicologist at the Ministry for Primary Industries and submitted to the journal Food Additives & Contaminants.
Cressey says their findings are reassuring. By combining food and drinking water nitrate data with national surveys of food consumption, they show that nitrate intakes from all sources are well below the internationally agreed acceptable daily intake. Averaged across water supplies, water contributed less than 10% of nitrate intake.
Most water is drunk near mealtimes or in beverages, they report. This matters because vitamin C and polyphenols from fruit and vegetables, and possibly tea and coffee, inhibit nitrosamines being formed.
Children, the study found, mostly drink water between meals as fruit-based drinks containing vitamin C. But do they really? "That's one area where trends have probably changed," Cressey admits. "Unfortunately, the most recent national nutrition survey is from 2008-09.
"Most of the nitrate we eat is from lettuce and potatoes," he says. It's plentiful in watercress, celery, spinach and kūmara – as are compounds that protect against nitrosamine formation. Water contains no such compounds, but if it reaches the gut near mealtimes, Cressey says that food's protective compounds should be sufficient.
Chambers and other epidemiologists have questioned that and other assumptions in the study. But Cressey rejects the criticisms and says he is satisfied that Kiwis aren't at higher risk of colorectal cancer from their drinking water. He also points out that no other country has reduced its nitrate limit.
Jörg Schullehner, who led the Danish study, says any change would be a political decision. "Denmark and the EU align their water standards with WHO guideline values. It would be easier for countries to lower the nitrate standard if the WHO re-evaluated its guideline first."
The Ministry of Health asked the WHO if it had plans to review the guideline, or to commission further research. The response noted that although it is plausible that ingested nitrate could potentially cause colorectal cancer, other epidemiological studies have shown mixed associations and the Danish study did not establish a causal relationship.
Others remain curious. "The IARC says it's a probable carcinogen in certain conditions, and the more robust epidemiological evidence supports that," says Chambers. "You cannot conclusively rule it out without sufficient evidence to do so. The precautionary principle should apply to protect public health."
Doubt has also been cast on how the cancer could form at the end of the digestive tract, given that nitrosamines mostly form in the stomach and are absorbed in the small intestine. But Chambers believes there may be an explanation. "Nitrosamines can travel to the colon attached to meat compounds. There's also some suggestion that nitrate-reducing bacteria in the large intestine contribute to nitrosamine formation," he says.
Baker points out that fitting together all the pieces of a cancer puzzle is often a protracted process. "It took years to confirm even the dramatic association between asbestos exposure and mesothelioma."
Meanwhile, several meta-analyses of studies have shown a statistically significant link between nitrate in water and colorectal cancer. One study, published last year, originally showed no association, but Chambers and his colleagues found errors and wrote to the journal that published it. "The lead author agreed, made the changes we suggested, and says it completely changed the results."
The Otago scientists plan to delve further. "We hope to accumulate a data set that will nail it for New Zealand," says Cox. He has data on colorectal cancer; Chambers is trawling councils for longer-term drinking water data. "We're in the early phase of figuring out if a study is viable."