Areca, the Not So Healthy Nut

The thought of a diet rich in nuts conjures up healthy images, but for the areca nut this could not be further from the truth. Areca catechu, often erroneously referred to as the betel nut as it often consumed with the totally unrelated leaf of the betel piper vine (see Figure 1), is a major public health concern across South and East Asia. Data suggests that the areca nut is consumed by a quarter of the world’s population and is the third most common substance of abuse after tobacco and alcohol. The habit of chewing areca products is steeped and ingrained so deeply in many of the South and East Asian cultures that it has gained immense popularity in these communities. The habit of areca nut chewing has moved with migratory communities and it is not uncommon to see the tell-tale signs of red spittle (produced as a by-product of chewing areca products) in the streets of London, Birmingham, Leicester and Leeds. Unlike tobacco and alcohol, which are forbidden in some Asian cultures, areca nut is well accepted and even encouraged as an aid to promote digestion after a meal. For children it may be given as a sweet after meals, and as a child growing up in London it was not uncommon to go to the local areca nut (paan) shop on a Friday night after dinner for a round of sweet paan (areca nut with coconut and spices, wrapped up in a betel leaf). The adults would have a different variety of paan, consisting of areca nut mixed with raw tobacco, slaked lime and a mixture of spices. Today this is still a common tradition in many households, even though these practices date back thousands of years to the early Vedic scriptures in ancient India.[1] Further, many religious ceremonies will have the areca nut as its centre and it is often used to mark auspicious events and even as dowry in some cultures. So deep is the cultural and societal acceptance of this humble little nut that the deleterious affects from chewing have been grossly understated.

Areca nuts on betel leaves
Figure 1: Areca nuts on betel leaves. (Image by Ananthy94)

The areca nut habit has taken a nasty turn since the development of a commercial product known as pan masala. This consists of plastic-packed powdered areca and tobacco and, despite attempts at legislation, is sold on street corners across Asia for a few Rupees – significantly cheaper than cigarettes.[2] It has caused a massive surge in the popularity of areca products and, as there is poor labelling, the tobacco content.

A report appearing in the Economist found that areca products represented an industry worth 10 billion dollars in India alone in 2012.[3] The global production of areca was estimated to be nearly 0.8 million tonnes in 2009 with over 55% of this production from India, and 25% from China. Furthermore the industry provides employment to many millions, including over 30 million people in India. Despite its harmful effects, the growth in consumption and production are mirrored at a growth rate of about 4% annually, suggesting that the habit is far from being in decline.[4]

So what is it about areca that makes it so popular? Studies have shown that areca is as addictive as heroin and have demonstrated an areca dependency syndrome in chronic chewers.[5] Its stimulant properties make it popular with those who need to stay awake – drivers, labourers and factory workers all use areca in societies where a double espresso or a Red Bull would be an unaffordable luxury. However, the heroin-like dependency is just one of its many dangers. Reports also show that in India there are over 5 million children under the age of eight who are addicted to areca-related products.

The main threat is that areca nut is an independent risk factor for head and neck cancer (see Figure 2).[6] [7] [8]

Oral cancer
Figure 2: Patient with oral cancer. (Image by Welleschik)

Head and neck cancer has been described as an epidemic across South and East Asia (see Figure 3), with approximately 70,000 new cases in India every year. The prognosis is poor, due to late detection, and head and neck cancer is responsible for ~48,000 deaths across India.[6] Rates of oral squamous cell carcinoma in countries such as India are the highest in the world. Oral submucous fibrosis (OSF) is an areca-related pre-cancerous condition that results in patients only being able to open their mouth by a few millimetres. Eight percent of patients undergo malignant transformation.[9] There is still no cure for this condition since its discovery in South Africa in 1952. The author’s discovery over a decade ago that high levels of copper in the nut causes an up-regulation of the enzyme lysyl oxidase is a still a front runner in the race to explain this enigmatic disorder.[10] [11]

Age-standardised death rates from Mouth and oropharynx cancers by country (per 100,000 inhabitants)
Figure 3: Age-standardised death rates from Mouth and oropharynx cancers by country (per 100,000 inhabitants). (Image by Lokal_Profil, CC-BY-SA-2.5)

So what is the future for this not so healthy nut? In many countries in South and East Asia, areca consumption remains a scourge of society and despite attempts to legislate and even ban it, sales continue to surge. Compared to smoking and alcohol, areca has received a fraction of the attention attributed to other public health issues in developing countries and has largely remained under the radar for public health researchers in the West, making this a tough nut to crack!

— Dr Chet Trivedy, NIHR Academic Clinical Lecturer in Emergency Medicine, W-CAHRD


  1. Strickland SS. Anthropological perspectives on use of the areca nut. Addict Biol. 2002;7(1):85-97.
  2. Gupta PC, Warnakulasuriya S. Global epidemiology of area nut usage. Addict Biol. 2002; 7(1): 77-83.
  3. The Economist. Chewed out. Oral cancer in India. 2012.
  4. Prakash Kammardi TN, Raganath L, Ranjith Kumar PS. A report on the areca nut in the national economy. University of Agricultural Science, Bangalore.
  5. Winstock AR, Trivedy CR, Warnakulasuriya S, Peters TJ. A dependency syndrome related to areca nut use: some medical and psychological aspects among areca nut users in the Gujarat community in the UK. Addict Biol. 2000;5(2):173-9.
  6. Gupta B, Ariyawardana A. Johnson NW. Oral cancer in India continues in epidemic proportions evidence base and policy initiatives. Int Dent J.2013;63(1): 12-25.
  7. Trivedy C , Warnakulasuriya S, Peters TJ. Areca nuts can have deleterious effects. BMJ.1999;318:1287.
  8. Warnakulasuriya S , Trivedy C , Peters TJ. Areca nut use: An independent risk factor for oral cancer. BMJ. 2002; 324:799-800.
  9. Trivedy C , Craig G, Warnakulasuriya S. The oral health consequences of chewing area nut. Addict Biol. 2002; 7(1):115-25.
  10. Trivedy C, Baldwin D, Warnakulasuria S, Johnson N, Peters TJ. Copper content in Areca catechu (betel nut) products and oral submucous fibrosis. Lancet.1997;340: 1447.
  11. Trivedy C, Meghil S, Warnakulasuriya S, Johnson NW. Harris M. Copper stimulates human oral fibroblasts in vitro: a role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med. 2001; 30(8):465-70.

Care that is Not Just Unskilled but Abusive

Maternal care is disrespectful to the point of abuse in many of the countries of the world.[1] How can it be that members of the caring professions can so abuse their position of trust? This short editorial argues that a culture of poor care can develop among perfectly ordinary people – indeed, we know this from the iconic experiments of Zimbardo [2] and Milgram.[3] As the Good Samaritan experiment shows,[4] people are exquisitely sensitive to their environment, especially their social environment.[5] So, here is my model for how an abusive culture develops:

— Richard Lilford, CLAHRC WM Director


  1. The Lancet. Achieving respectful care for women and babies. Lancet. 2015. 385:1366.
  2. Haney C, Banks C, Zimbardo P. A Study of Prisoners and Guards in a Simulated Prison. Washington, D.C.: Office of Naval Research. 1973.
  3. Milgram S. Behavioral Study of Obedience. J Abnorm Psychol. 1963; 67(4):371-8.
  4. Darley JM, Batson D. “From Jerusalem to Jericho”: A Study of Situational and Dispositional Variables in Helping Behavior. J Pers Soc Psychol. 1973; 27(1): 100-8.
  5. Bandura A, Ross D, Ross SA. Transmission of aggression through imitation of aggressive modelsJ Abnorm Soc Psychol. 1961; 63: 575-82.

…And While Talking about Culture and Misbehaviour

A recent Lancet editorial addresses the retraction by BioMed Central of 42 articles published by medical researchers in China.[1] The fraudulent articles emanate from prestigious centres in many parts of the country. This information furnishes a possible explanation for the finding that effectiveness studies that provide null results in North America often provide positive results in China.[2]

— Richard Lilford, CLAHRC WM Director


  1. The Lancet. China’s medical research integrity questioned. Lancet. 2015; 385:1365.
  2. Hartley LC, Girling AJ, Bowater RJ, Lilford RJ. A multi-study analysis investigating systematic differences in cardiovascular trial results between Europe and Asia. J Epidemiol Comm H. [ePub].

Demographic Dividend Divided

Readers of the CLAHRC WM News Blog will be familiar with the concept of the demographic dividend – the opportunity for economic growth when the dependency ratio improves as a result of falling birth rates and before it declines due to an increasing proportion of elderly people. Asian prosperity has been fueled, at least in part, by favourable dependency ratios. However, distorted sex ratios at birth from the usual 105:100 to about 116:100 (males to females) is now resulting in a mismatch in early adulthood and consequent declining marriage rates. This mismatch accumulates over decades and will lead to a 30% imbalance within a few decades – the mathematics were explicated in more detail in a recent article of the Economist.[1] The situation is further aggravated by the “flight from marriage” as more well-educated women delay or eschew the idea of committing themselves to one man. The social effects of all this are hard to foresee, but it is well known that single men are a restless lot, prone to violence and available for army conscription.

— Richard Lilford, CLAHRC WM Director


  1. The Economist. Bare branches, redundant males. The Economist. 18th April 2015.

Further Evidence from Informal Settlements

At last slum health, featured in previous blogs, is starting to receive the attention it deserves. A recent report on the Mathare settlement in Nairobi, Kenya [1] correlates how far a person lives from a public toilet and risk of disease. The further a person lives from the facility, the more likely they are to be chronically unwell, especially with diarrhoeal diseases and childhood stunting. As readers know, poor nutrition and sanitation create a vicious circle. Also, the risk of violence against women rises with distance from a public facility. Clean water and sanitation remain huge challenges for slum dwellers. Improved sanitation would also produce an educational and economic dividend. Meanwhile toilet design has improved, for example, with the invention of the composting toilet, so cost-effective, logistically feasible improvements are possible and likely to be highly cost-effective. The CLAHRC WM Director liked this paper because it integrated disease surveillance, geospatial mapping, and the personal accounts of slum dwellers, to create a rich account of pathways to poor health.

— Richard Lilford, CLAHRC WM Director


  1. Corburn J & Hildebrand C. Slum sanitation and the social determinants of women’s health in Nairobi, Kenya. J Env Public Health. 2015. [ePub]

Measuring the Quality of Life: Holy Grail

The standard method to measure quality of life (QoL) is to convert a generic quality of life score to a utility value, thus:

Score on a generic quality of life questionnaire X Conversion factor (tariff) = Utility

The QoL score must be generic because it has to cover all ailments, from deafness to paraplegia to depression.

The conversion factor converts this score to a utility that provides a common 1-0 (best health to death) scale, but also allows for negative values (worse than death). The most commonly used QoL questionnaire is the EQ-5D, which has only five dimensions (mobility, ability to care for oneself, ability to perform usual activities, pain/discomfort, and anxiety/depression). There is reason to question whether this is sufficiently broad for health (narrowly defined) use. For instance, it might not fully capture the utility loss from blindness. If it does not fully capture health narrowly defined, then it may be assumed that it falls shorter still for health more broadly defined to include effects of social care, economic independence, and overall happiness. Scales such as the WALY (Wellbeing-Adjusted Life Years) scale try to capture these outcomes. However, it is cumbersome to have two separate scales; ideally we need one, covering the same dimensions, but without introducing distortions by double counting some of them, but not others. Work is ongoing to sort this all out by collating information on many dimensions and eliminating those that largely duplicate information that others capture more specifically.

Enter Amartya Sen, an economist who won the Economics Nobel Prize in 1998 (alright, technically the Svergies Riksbank Prize in Economic Sciences). He emphasised human capabilities and argued that happiness was not enough – it was more important to have the capacity to understand and appreciate what the world has to offer and to be involved politically, than to simply have a hedonic life. Professor Jo Coast, collaborator of CLAHRC WM, has produced a score called ICECAP-A (ICEpop CAPability measure for Adults) for the purpose of measuring capabilities.[1]

Capability-based measures and patient perceived quality of daily life are fundamentally different constructs and pin-point the fundamental philosophical distinctions that lie at the heart of the quality of care debate. Like Candide in Voltaire’s play, I would gladly sacrifice happiness for an intellectual appreciation of the world and what lies beyond.

— Richard Lilford, CLAHRC WM Director


  1. Al-Janabi H, Flynn T, Coast J. Development of a self-report measure of capability wellbeing for adults: the ICECAP-A. Qual Life Res. 2012; 21(1): 167-76.

Use of Language: Race is to Ethnicity as Sex is to Gender

The CLAHRC WM Director has often puzzled over the use of “gender” vs. “sex”, and “ethnic group” vs. “race” in scientific writing. They are not synonyms; gender and ethnicity are social constructs, while and sex and race are biological. The former are not “polite” terms for the latter. Philip Steer, Emeritus Editor of an exceptionally lively speciality journal BJOG: An International Journal of Obstetrics and Gynaecology, has written a sure-footed article on this topic.[1] Agreeing that race is the appropriate term to describe groups with a similar place of origin, irrespective of culture, he recommends the National Library of Medicine MeSH groupings. Five continental groupings (African, American, Asian, European, and Oceanic) are broken down by sub-region – for example, European into ‘White European’ and ‘Mediterranean’. Gone is the term Caucasian, which was used to describe broader origins than just the Caucasus area and which, the CLAHRC WM Director learned, has eugenic overtones.

The article makes some other interesting points. Africa has the greatest human genetic diversity among the continents, accounting for as much as 80% of all human genetic variation. This is because of the bottleneck created by the exodus from Africa of a relatively small group of Homo sapiens about 70,000 years ago. These migrants mated with Neanderthals and spread out to colonise the rest of the globe. All of this is of interest to CLAHRC Africa, which has an interest in preventing hypertension and stroke. Salt is the prime causal suspect and there is evidence that some African people may be especially prone to salt-induced hypertension as a result of a widespread allele. Since intake of salt has increased rapidly over the past century we are developing protocols to identify the main source of salt in the diet. In due course we will design an intervention to tackle this. We are working closely with colleagues in the African Population Health Research Center (APHRC) and Malawi on this project.

However, the whole question of race will become progressively less important in science and medicine in the future for two reasons. First, gene sequencing will increasingly enable scientists and doctors to hypothecate genetic variation at the individual level, rather than the level of the group/race.[2] [3] The arrival of personalised medicine will reduce the importance of race and it has always been the case that there is far more variation within, than between races. Second, mating across racial boundaries will increasingly dilute correlation between race and genetic configuration and vitiate the effects of Homo sapiens great migration out of Africa.

— Richard Lilford, CLAHRC WM Director


  1. Steer P. Race and Ethnicity in Biomedical Publications. BJOG. 2015: 122(4): 464-7.
  2. Burchard EG, Ziv E, Coyle N, et al. The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice. New Engl J Med. 2003; 348: 1170-5.
  3. Jeffers C. The Cultural Theory of Race: Yet Another Look at Du Bois’s “The Conservation of Races”. Ethics. 2013; 123(3): 403-26.

Risk adjusted outcomes – again!

This interesting paper [1] shows that risk-adjusted Patient Reported Outcome Measures (PROMs) produce more outliers by surgeon than Standardised Mortality Ratios (SMRs). Presumably the distribution of PROMs was more skewed than the distribution of SMRs. However, surgeons accounted for only a small proportion of all unexplained variance in the distribution of PROMs, so little could be achieved by weeding out a few individual surgeons. In addition, risk adjustment can under-adjust so that a true positive becomes a false negative. For example, controlling for hospital type could obscure poor performance in types of hospital that attract poorly performing surgeons. A better way to scrutinise surgical performance might be to analyse surgical skill by observing recordings of operations and analysing them by experts or automated systems.[2] These results could be correlated with PROMs to identify truly excellent surgeons who could give proctorship to those whose processes and outcomes were less good. We think the future of quality monitoring lies in triangulating ‘performance data’ and using it in local improvement programmes.[3] [4] — Richard Lilford, CLAHRC WM Director References:

  1. Varagunam, M; Hutchings, A, Black, N. Do patient-reported outcomes offer a more sensitive method for comparing the outcomes of consultants than mortality? A multilevel analysis of routine data. BMJ Qual Saf. 2015; 24(3): 195-202.
  2. Hampton T. Efforts seek to develop systematic ways to objectively assess surgeons’ skills. JAMA. 2015; 313(8): 782-4.
  3. Department of Health. Guidance on the routine collection of Patient Reported Outcome Measures (PROMs). London: Department of Health. 2009. [Online].
  4. Lilford R, & Rosser D. What’s Up Doc? Health Serv J. 2013; 123:19-21.

Very Fresh Blood for Transmission: Probably Not Worth the Effort

This is the largest trial (over 1,200 patients per group) to compare extremely fresh (less than a week old on average) with standard (about three weeks old) blood transfusion in sick adult patients.[1] ‘Old’ blood has lower oxygen carrying capacity than fresh blood, and accumulates potentially harmful metabolites. However, there are costs associated with trying to give everyone fresh blood. In the end this study showed a null result with the point estimate favouring old blood. The death rate was high (over one third) so the trial ‘excluded’ the rather large adverse effect of a 16% increased death rate found in observational studies.

— Richard Lilford, CLAHRC WM Director


  1. Lacroix J, Hébert PC, Fergusson DA, et al. Age of Transfused Blood in Critically Ill Adults. New Engl J Med. 2015;372:1410-8.

An Apple a Day…

The old adage, “an apple a day keeps the doctor away” has been put to the test by Davis et al. in a recently published cross-sectional study.[1] The authors studied over 8,000 US adults, comparing those who ate “an apple a day” (based on a dietary recall questionnaire), with those who did not, on the primary outcome of “keeping the doctor away” – no more than one self-reported visit to a physician in the previous year.

The study identified 753 adults who ate at least one apple a day, and, compared to non-apple eaters, they had higher levels of education, were less likely to smoke, and were more likely to be from a racial or ethnic minority (P<0.001). However, after adjusting for socio-demographic and health-related characteristics, there was no statistically significant difference in physician visits (OR 1.19, 0.93-1.53, P=0.15); though they did appear to use fewer prescription medicines (OR 1.27, 1.00-1.63). So maybe we should start using “an apple a day keeps the pharmacist away”?

— Peter Chilton, Research Fellow


  1. Davis MA, Bynum JPW, Sirovich BE. Association Between Apple Consumption and Physician Visits Appealing the Conventional Wisdom That an Apple a Day Keeps the Doctor Away. JAMA Intern Med. 2015. [ePub].