Sirs, Peckham et al's selective reporting of the findings of the SCHER report (2011) risks giving readers of your journal a highly misleading interpretation of data on the fluoride intake of children in areas supplied with water containing 1 mg/l of fluoride.

Careful analysis of the full detail of the SCHER report (2011) shows that 6 to 12 year olds will not exceed the recommended upper limit (UL) of 2.5 mg per day even if they are routinely taking fluoride supplements (as tablets, drops or lozenges), swallowing 10% of their toothpaste, and consuming around two or three times as much water per day as the European Food Safety Authority (EFSA) estimates to be likely. It also shows that 1 to 6 year olds are very unlikely to exceed the recommended UL of 1.5 mg of fluoride per day unless they are routinely taking fluoride supplements, swallowing around 40% of their toothpaste and possibly also putting more than the recommended amount of paste on their brush.

SCHER's estimates were based on figures provided by EFSA which, in its earlier 2005 report, states: "Children aged 1-8 years have fluoride intakes from food and water well below the UL provided the fluoride content of their drinking water is not higher than 1.0 mg/l." It also states: "For children older than eight years and adults the probability of exceeding the UL on a normal diet is estimated to be low. However, consumption of water with a high fluoride content, e.g., more than 2-3 mg/l, predisposes to exceeding the UL." The target level in fluoridation schemes in England is 1 mg/l.

The above suggests that Peckham et al have not correctly represented what SCHER was saying in the body of its report. Further, it should be borne in mind that medical and dental practitioners in England do not prescribe fluoride supplements to children in fluoridated areas and that parents are advised to supervise their children's toothbrushing up to about the age of seven - in both fluoridated and non-fluoridated areas - to ensure that they put only a pea-sized amount of toothpaste on the brush and they do not swallow any after they have finished brushing.

Finally, in the specific context of the Peckham et al hypothesis on hypothyroidism, it is worth noting SCHER's conclusion that "a systematic evaluation of human studies does not suggest a potential thyroid effect at realistic human exposures to fluoride."

Yours sincerely,

Michael A Lennon OBE Professor Emeritus University of Sheffield

Dr John F Beal MBE Hon Senior Lecturer in Dental Public Health University of Leeds

Conflict of Interest:

Dr John Beal - Vice Chair, British Fluoridation Prof Michael Lennon - Scientific Advisor, British Fluoridation Society

The World Health Organisation's setting of global viral hepatitis elimination targets, focused on hepatitis B & C, is most welcome¹. In their commentary article, Hellard, Sacks-Davis & Doyle describe strategies by which hepatitis C elimination by 2030 can be achieved by a combination of direct acting antiviral drugs against hepatitis C, opioid substitution therapy and needle and syringe programmes ².

The authors are optimistic of achieving this World Health Organisation hepatitis C virus elimination target. They describe in detail how hepatitis C could be eliminated in persons who inject drugs in Australia with the aforementioned strategies.

Hellard et al focus on persons who inject drugs as the subgroup with the highest prevalence of hepatitis C disease. This is true in other developed countries. However, what is striking about their reflections on hepatitis C elimination in the Australian context is the absence of reference to hepatitis C in men who have sex with men and the potential impact of immigration.

Hepatitis C virus infection in Human Immunodeficiency Virus -infected men who have sex with men has been increasingly recognised in Europe and North America for over a decade. The epidemiology of sexual transmission of hepatitis C has recently been reviewed by Chan et al³.

International migration of persons from high prevalence developing countries to developed countries risks the introduction/ re-introduction of hepatitis C. The complex interplay between immigration and viral hepatitis has recently been reviewed by Sharma et al⁴.

Countries which aim to achieve the World Health Organisation target of hepatitis C elimination by 2030 need to monitor the evolving epidemiology of hepatitis C in all at-risk groups be they persons who inject drugs, men who have sex with men or immigrants as part of their hepatitis C elimination strategies.

Hellard et al acknowledge the high cost of direct acting antivirals as a barrier to elimination, but point out that prices are likely to fall in future. Despite this, many developing countries will not be able to afford hepatitis C direct acting antivirals on any significant scale. The state of public health in some of the poorest developing countries is unfortunate. I note that according to the World Health Organisation "..1.1 billion people has no access to any type of improved drinking source of water" (sic)⁵. For resource-poor countries, the chances of achieving hepatitis C elimination by 2030 appear slim.

In conclusion, the goal of hepatitis C elimination by 2030 is possible in developed nations with robust strategies targeting all at-risk groups. Regrettably, there is less room for optimism in the most resource-poor developing countries where simple aspirations like supplying safe drinking water take priority.

Conflict of Interest:

None declared

The analysis of data on the prevalence of hypothyroidism in areas with different concentrations of fluoride in the public drinking water supplies, by workers at the University of Kent,[1] is interesting but by no means conclusive. The authors rightly emphasise that their findings do not prove that fluoridation causes people to develop the condition,but only that there is a clear correlation. In fact this study raises more questions that it actually answers.

Public Health England's Water Fluoridation Health Monitoring Report for England 2014 [2], so widely cited by supporters of the practice, is in fact riddled with statistical improprieties. It has become the norm for the dental public health sector to dismiss all complaints that fluoridation is harmful to thyroid function, and the 2014 PHE report fails to mention it at all. This study appears to challenge that position.

In this new study the authors report that there is an at least 30% greater prevalence of hypothyroidism in areas with more than 0.3mg/l of fluoride in the public water supplies. However, this limit is not a threshold; it is merely the dividing point between two out of the three arbitrarily chosen ranges of fluoride concentration in drinking water. The apparent 'boundary' between a safe and an unsafe concentration of fluoride is an experimental artifact, not a representation of what happens in real life.

So it is only permissible to draw a generalised conclusion from this study. This is disappointing. Fluoride overdose is now endemic - half of all children growing up in fluoridated water areas develop at least some detectable form of dental fluorosis, the only visible biomarker for incipient fluoride toxicosis. In non-fluoridated areas the prevalence of this condition is around one quarter.

Clearly, other sources of bioavailable fluoride are already contributing to this undesirable body-burden. If there is a causative link between fluoride absorption and thyroid function, then it is reasonable to propose that all bioavailable fluoride sources may contribute to the problem. This would imply that that many people may be prone to hypothyroidism due to the increasing background contamination of our foods and dental products with fluoride. If so, this might suggest that the extra fluoride in some water supplies may be pushing more people over the threshold at which GPs start to notice that more of their patients have this condition.

Another missed opportunity?

There is one intriguing feature of this study that illustrates what could be done to clarify our understanding of the medical consequences of water fluoridation, if only the government would stop prevaricating and put some real effort into sorting out the whole mess.

This new study compares hypothyroidism prevalence across the country with data on the average annual fluoride level maintained in drinking water supplies during 2012. Those of us in the Lake District will be aware that, although the authors show (correctly) that West Cumbria was not fluoridated in 2012, in fact the region has been fluoridated since around 1970.

The local water supplier, United Utilities, shut down its fluoridation activities in 2007 to carry out maintenance, resuming fluoridation in September 2013. So for six years those people who had been drinking fully fluoridated water for up to almost forty years had their access to the 'benefits' of this product interrupted.

Both accidents and anomalies can provide unique opportunities to examine novel questions that that may never be considered when looking at generalised data, and this six year halt to fluoridation in West Cumbria provided just such an opportunity. So it is unfortunatle that the new study does not reveal whether the risk of hypothyroidism in West Combria is elevated.

It would have been enormously interesting to learn how prevalent hypothyroidism was in this area before and during, and is now after, that fluoride-free interlude. Was the prevalence of the condition elevated before fluoridation stopped? If so, did it fall, during the hiatus in supply? And has it increased again since?

Presumably raw data are available to answer these questions, but have not yet been analysed. It would be fascinating to see whether or not the prevalence of hypothyroidism changed. The results of such an analysis might yet provide support for proposing that correlation may reasonably imply causation and, if so, whether stopping the practice in other fluoridated areas might bring similar relief to the afflicted.

Douglas Cross, CSci, CBiol. FSB.

References

1. Peckham S, Lowery D, Spencer S.(2015) Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water. J Epidemiol Community Health 2015;0:1-6. doi:10.1136/jech-2014-204971

2. Public Health England. Water Fluoridation. Health monitoring report for England 2014. PHE publications gateway number: 2013547, 2014.

Conflict of Interest:

None declared

We commend the authors for taking the hypothesis that cancer may have its roots in early life social conditions seriously [1]. Social inequalities exist for many cancer types and are usually attributed to differences in lifestyles and behaviours. Thus, attempts at primary prevention are often confined to relatively proximal disease risk factors at the individual level.

Cancer development has mainly been considered as a consequence of DNA mutations and consequently tends to be viewed through the lens of molecular biology. However, cancer may be a disease model particularly relevant to investigate how the social becomes biological, via a lifecourse approach. Many socially stratified biological mechanisms have been identified as being part of the causal chain of risk for cancers: material exposures (including inert ones such as asbestos, or living ones such as the Helicobacter pylori virus) and behavioural mechanisms (including tobacco consumption and fatty food intake). Furthermore, the lifecourse approach is of particular interest when studying cancer because of the long latent time period during which exposures occur, before the onset of disease. There is increasing evidence for the role of chronic stress from early life in cancer development and progression.

Upstream, cancer aetiologies differ, some being exogenous in origin (viruses, smoking) and others endogenous (hormonal cancers). However all cancers are at some point rooted in the immune and inflammatory system, and thereby their initiation is susceptible to factors affecting biological mechanisms at some point along this aetiological pathway. If the immune system is impaired from killing-off damaged cells, the risk of developing tumour cells is heightened [2]. A damaged immune system is also an important accelerator of cancer progression [3]. This root in the immune system is currently the source of the most promising immune-therapy treatment for many cancers [4]. In fact, there is increasing evidence that chronic stress may influence immune and inflammatory systems, implicating socially driven epigenetic mechanisms, which may represent an overall set of early life social determinants of cancer development over the lifecourse [5]

Evidence on the link between early life stress and cancer in epidemiology remains sparse and inconclusive, and presents difficult methodological issues. Measuring early life physiological stress remains a challenge, but one worth investing in since acute versus chronic stress, and the timing of stress in early life may be important for subsequent stress responses. Stressful events are likely to be experienced differently depending on an individual's hierarchical position on the social gradient. Individuals lower on the social gradient may be more vulnerable to the physiological or behavioural effects of stressful environmental exposures with fewer resources and buffering strategies at their disposal compared to individuals with a higher social position [6]. Social gradients may also confer stress to individuals via status anxiety, which has also been shown in non-human primates [7]. Intra-familial conditions occurring from conception into adolescence may program physiological responses during sensitive periods of development, altering an individual's biology, rendering them susceptible when faced with exposures later in life [8]. We hypothesize that taking into account socially driven early life exposures to chronic stress is important to understanding the aetiology of cancers, which have a common root in the immune and inflammatory systems. These systems form part of the overall physiological stress response.

We have inadequately attempted to examine this hypothesis, showing that early life adversity and social position is associated with adult cancers before the age of 50 [9]. However, due to a gaping hole in the available lifecourse data combined with good quality cancer incidence data in adulthood, the hypothesis remains to be fully investigated. As well as having mortality data, cancer incidence data provided by registries would allow for a better understanding of cancer aetiological pathways from early life social conditions onwards, and potentially highlight new areas for the primary prevention of cancers. We agree with the authors' point about investing resources into data, and we would emphasise the need for quality data on cancer incidence specifically. To truly get to grips with the aetiology of cancers, concerted investment in the birth cohort studies, and their linkage with registries is paramount.

1 Vohra J, Marmot MG, Bauld L, et al. Socioeconomic position in childhood and cancer in adulthood: a rapid-review. J Epidemiol Community Health 2016;70:629-34. 2 Stewart TJ, Abrams SI. How tumours escape mass destruction. Oncogene 2008;27:5894-903. 3 Kim R, Emi M, Tanabe K. Cancer immunoediting from immune surveillance to immune escape. Immunology 2007;121:1-14. 4 Dustin ML. Cancer immunotherapy: Killers on sterols. Nature 2016;531:583 -4. 5 Kelly-Irving M, Mabile L, Grosclaude P, et al. The embodiment of adverse childhood experiences and cancer development: potential biological mechanisms and pathways across the life course. International Journal of Public Health 2013;58:3-11. 6 Baum A, Garofalo JP, Yali AM. Socioeconomic Status and Chronic Stress: Does Stress Account for SES Effects on Health? Ann N Y Acad Sci 1999;896:131-44. 7 Sapolsky RM. The Influence of Social Hierarchy on Primate Health. Science 2005;308:648-52. 8 Bailey DBJ, Bruer JT, Symons FJ, et al., eds. Critical thinling about critical periods. Baltimore: Paul H. Brookes publishing co. 2001. 9 Kelly-Irving M, Lepage B, Dedieu D, et al. Childhood adversity as a risk for cancer: findings from the 1958 British birth cohort study. BMC Public Health 2013;13:767.

Conflict of Interest:

None declared