Archive for the ‘Cause of DD’ Category

Diverticular Disease: The Fibre Story

Thursday, September 14th, 2017

In the early part of the 20th century constipation was not generally related to any individual illness. The idealised achievement of daily defaecation meant constipation was common particularly in the elderly. Treatment was not free until the NHS came along and natural and herbal laxatives were well used medications. Diverticular disease (DD) became recognised more before WW11. The distinguishing symptoms were pain, fever and diarrhoea. A low residue diet was recommended to reduce diarrhoea and give the bowel rest. Serious pain sometimes resulted in surgery. Infection and inflammation (diverticulitis) were not always present but pieces of food and faeces were trapped in diverticula. Avoidance of coarse fruit and vegetables, seeds and pips was recommended.

Hospital diet sheet for diverticulitis 1961………”forbidden foods – all fried foods, pips and skins of fruits, pastry, suet puddings, coarse stalky vegetables, salads, onions and celery, chunky marmalade, jam with pips or skins, wholemeal or brown bread, coarse biscuits-Ryvita, digestive, Allbran, oatmeal, Weetabix, Shredded Wheat, fruitcake or scones, nuts, dried fruit.”

A significant change in diet started about 1970 when treatment for diverticular disease (DD) was suddenly reversed.

Hospital diet sheet for diverticulis 1982………..”you can eat a normal varied diet but include…… (all of the forbidden foods from 1961 except fried food)….SUPPLEMENT meals with 2 teaspoonfuls of unprocessed bran twice daily. EAT LESS white flour in any form and white and other sugars. DIETARY FIBRE ….by helping to restore normal function of the digestive tract, fibre can be useful in the treatment of constipation and diarrhoea”

  • Who persuaded health professionals that wheat bran was good for diarrhoea?
  • What was the evidence for this complete reversal of treatment?
  • Did anyone ask patients if this helped them?
  • Who was behind this change?


The individual who had the greatest influence on the treatment of DD in the last 100 years was surgeon Denis Parsons Birkitt. One biography title calls him ‘The Fibre Man’ another ‘How a Humble Surgeon Changed the World’. These volumes describe a one eyed Northern Irish man whose Christian beliefs were greatly impassioned by a group at university. Religious practice and fervour were the engine and steering wheel of his life and medical practice. After surgical qualification, a position as ships doctor and war time service with the Royal Army Medical Corps followed, then employment by the Colonial Office meant he practiced overseas for about 30 years.

Birkitt became well known in Uganda. Using the network of Christian missions and hospitals and extended safaris, he became interested in what he called ‘geographical medicine’. He found that hydrocelle cases occurred in particular areas and were caused by a microscopic worm carried by mosquitos.The same type of investigation eventually uncovered the cause of a cancer in children which became known as Birkitt’s lymphoma. An insect vector he proposed was not to blame, but the Epstein-Barr virus was discovered. The cancer/virus connection became the platform for intensive research into cancer causes by specialists worldwide. Birkitt’s fame spread, aided by his brilliant, charismatic oratory and invitations to preach and lecture worldwide on cancer.

Ugandan independence affected medical services and Birkitt’s surgical practice finished. He was employed by the Medical Research Council External Scientific Staff in London in 1964. His African travels continued collecting ‘geographical’ data on cancers and diseases. Writing, lecturing and preaching tours continued.


The fibre story only started in 1967 in London. At the age of 56, Birkitt was introduced to a retired naval physician Captain T.L. Cleave. Cleave was one of several doctors who had used wheat bran to treat constipation. Cleave thought that excessive sugar and refined carbohydrates were behind the diseases in Western countries which were not found inAfrica. Birkitt considered meeting Cleave was one of the most important occasions of his professional life. He had been introduced to the concept of ‘Western diseases’ and ‘one cause’ of different diseases and that cause was considered to be diet. In 1969 he used his network to obtain samples of faeces to weigh and with the time taken for them to pass through the body. He used groups of people who had different diets. He had contact with Dr Alec Walker, Dr Hugh Trowell and Dr Ted Dimock in Africa who had previously carried out such studies, and Dr George Campbell who had worked with Cleave. Burkitt thought Providence had brought these contacts into his life in perfect order. He was convinced that the Lord was calling him to a wider, more important commitment in medicine. He was determined to step even more wholeheartedly into popularising not only the neglected field of nutrition but preventative medicine as well. Medical researchers who had previously produced articles and books on this theme had not managed to change traditional medical opinions on dietary fibre. The role of dietary fats was then fashionable. Birkitt had the gift of oratory, the contacts and the clout from his cancer work to become the spokesman for his colleagues and previous investigators.

People who attended Birkitt’s messianic talks write mostly about the slides showing the voluminous heaps of the stools of Ugandan rural villagers. He certainly knew how to get their attention. His biographers describe how he used slides and stories to get his points across. Biblical parables come to mind. He could demonstrate that increased weight of stools was generally associated with quicker passage of food through the body. This was the basis of his opinions and conclusions. His subjects did not include the old or infirm but were predominantly young and healthy with different lifestyles and diets. There was much overlap between diets and individuals, the amount of fibre in the different diets was  perversely assumed according to the size of stools. It was obvious that the stools of the rural villagers were in a class of their own in size. At the sides of paths in the bush a squatting position was inevitable. The location suggests some urgency. Is this the model the western world should achieve by increasing dietary fibre levels to the 150g per day? This figure was calculated from a “personal communication” which said that men eat at least 1Kg of plantain at each main meal. Plantain is 6g fibre per 100g therefore the total dietary fibre intakes are 150g/day. Similar calculations gave fibre levels of 130g/day for the Kikuyu tribe and 100g/day for Venda males in South Africa. These levels are equivalent to about 50 portions/day of porridge oats! Vegetarians in the West have about 40g/day of fibre. The claim that diverticular disease is caused by not using a squatting position on Western toilets is also based on the rural Ugandans habits. This is used to promote sales of devices to modify water closets. Birkitt himself did not comply with this claim. Helping constipation should not be confused with causing disease


There are reports that Ugandans have large, wide bowels and a common surgical emergency is twisting of the colon (volvulus). Widespread use of herbal laxatives to meet African defaecation ideals has been mentioned. We didn’t hear much about the ‘African’ problems. Earlier missionaries and doctors were aware that some diseases becoming common in the Western world were not found in Africa. Birkitt’s information from his networks and travels agreed. Coronary heart disease, gallstones, appendicitis, diverticular disease (DD), diabetes, varicose veins, haemorroids, hiatus hernia, peptic ulcer and colon cancer were the Western diseases. They were only occasionally found in African individuals who had adopted an urban, Western lifestyle, but not necessarily a Western diet as found by other researchers. Also noted was that a Western individual could have more than one of these typical diseases.

Apart from the Inuit, who Birkitt described as one hiatus in his dietary research, there was no mention of any peoples who had little dietary fibre but no Western diseases. The Massai, Chewya and Watus tribes were noted by other African missionaries. Mormons and Seventh Day Adventist had Western diets but low levels of Western diseases; no smoking was offered as a possible explanation. Birkitt knew that coronary heart disease was linked to cigarette smoking but persisted with a low dietary fibre explanation of its cause.


  1. The distribution (epidemiology) of Western diseases found in the 1960s/70s was distinctive, suggesting a lifestyle and possibly single cause.
  2. Wheat bran can help relieve constipation in some people.
  3. Increased dietary fibre will in general pass through the body faster with speedier evacuation and softer stools.


  1. The rural African diet protects against Western diseases
  2. The change in disease patterns when individuals emigrated to Western countries was due to a change in diet.
  3. Increase in prevalence of Western diseases in countries which were previously low was caused by the adoption of a Western diet.
  4. Western diseases are caused by insufficient fibre in the diet. Copious amounts of wheat bran would prevent, treat and cure the ailments of the Western world.

There is no evidence, biological link or possible extrapolation between the facts and conclusions. There are many lifestyle differences to account for individual and regional variations in disease patterns and colon function. Choosing assumed dietary fibre levels and ignoring examples which do not conform is not valid epidemiological evidence. There are many food ingredients which promote bowel movement, not just wheat bran. For example, Birkitt found in Ireland, that plenty of potatoes matched the effects of bran; or was it an effect of the national beverage? It is an essential physiological mechanism that more undigested food residues will give quicker passage and larger stools, just like drinking more fluids results in increase urination. If disease affects these mechanisms, can they be overloaded?


Neil S Painter was a surgeon at the Manor House Hospital in London. He had spent most of the 1960s studying diverticular disease. Unlike Birkitt he had patients to treat. He was responsible for insight into the mechanisms of diverticula formation and researched the effects of drugs on the diseased colon. Segmentation in the sigmoid colon resulted in pockets of high internal pressure which forced hernia through the colon wall to give diverticula on the outside.

Cleave persuaded Painter to use unprocessed wheat bran in his medical practice and for the treatment of constipation in uncomplicated diverticular disease. The trial took place between 1967 and 1971, involved 70 patients, replacing previous laxative use and an assessment of symptoms at 1 and 2 months. Many of the aged, 70 patients had other western diseases whose treatment may not have helped their bowel problems. The results were presented by how many of the 12 symptoms were relieved or abolished, not by how many patients had been helped. It is possible that the 17% of the patients with repeated problems could have produced a majority of the symptoms in this type of presentation. Some patients could not tolerate bran, some still required occasional laxatives. Some symptoms were not relieved by bran, some were reduced and just over half disappeared during the trial period. Stools were softer and passed with less straining thus helping constipation. Painter emphasised that the bran regime did not prevent attacks of painful diverticular disease or acute diverticulitis. 3 patients were admitted to hospital. The amount of bran added to the diet varied to meet the trial end point of daily defaecation and varied between 6 teaspoons/day to several tablespoons daily. 3 patients had frequent passage of small hard stools with diarrhoea episodes attributed to laxatives, these became more regular with bran. This type of constipation appears to be the basis of treating diarrhoea with bran. That diarrhoea might be a symptom of irritation, infection or inflammation was not considered.

Painter asked Trowell to write a letter to the British Medical Journal to support the use of bran for intestinal conditions. A mutually beneficial collaboration with Birkitt published a paper on fibre and diverticular disease in 1971. Although headed ‘for debate’ it transformed treatment of diverticular disease by previously sceptical health professionals. Painter had got on board the bran wagon.


Medical research for decades tried to find evidence to support Birkitt, his colleagues and Painter. Trials did not consider anything but dietary fibre, involved small numbers of subjects and no controls. Effects of bran and high fibre diets were always balanced by a change in proportion of other foodstuffs. This was particularly relevant in animal tests which attempted to produce diverticula by reducing fibre in their natural diets. Publications which did not agree with the fibre theory were counteracted. The letters pages of medical journals were the equivalent of today’s Twitter and Facebook. Opinions were divided but Birkitt welcomed the disagreement as publicity.

How did the fibre gospel achieve such worldwide publicity? Described as a human dynamo obsessed with fibre, Birkitt’s charisma and lecturing prowess were reasons that attracted the media and publishers. Increased sales of breakfast cereals were another. Kellogg sponsorship of lecture tours, worldwide medical symposia on the fibre content of diet and paying for the publication if a bibliography by Trowell, gave medical backing for promotion of cereal products. For patients, bran could be a useful cheap medication in the absence of any other treatment on offer for diverticular disease. There was also an element that patients could be blamed for their problems because of their choice of diet.

The fibre message was far more effective in the USA than in the UK. Particularly controversial was Birkitt’s opinion that colon cancer could be prevented by a high fibre diet. Medical journals were reluctant to publish the idea of many diseases having a common cause. However in 1972 the British Medical Journal agreed to publish a lecture beforehand. This was Birkitt’s breakthrough in getting into print his opinions on diseases which were increasing in Western countries in the 20th century. He theorised the relationship of dietary fibre as the cause of the various diseases.

The voluminous flow of articles by Birkitt and his colleagues in medical journals had slowed down considerably by 1976. Now he felt that he could only write about fibre and not medical conditions he had no involvement in. He had no new personal research to report on and maybe exhausted usable medical journals. He did continue involvement in collaborative books on dietary fibre.

At the age of 65, Birkitt had to retire from the Medical Research Council resulting in reduced income. He believed that the Lord would provide, as he had done in the past, if he wanted the work to continue. His friends found him an appointment as Honorary Senior Research Fellow and a room at St Thomas’s hospital. Kellogg, who had sponsored lecturing tours since 1972, provided an honorarium, secretary and expense account for lectures “on the understanding that their cereal products would not be promoted”. Kellogg sponsorship of symposia and speaking appointments continued.

Other authors had jumped on the fibre bandwagon with popular publications. Birkitt had been unable to find a publisher for a book for the general public. After several rejections, in 1977, a 28 year old Martin Dunitz approached Birkitt about producing a book. A property company registered in 1977 changed its name to Martin Dunitz Ltd in 1978. The book ‘Don’t forget fibre in your diet’ appeared in 1979 to be the first from this publisher. There was emphasis that readers should look for the word “bran” in cereal products.


A means of continually controlling constipation would be preferable to the stop/start regime of laxative use. Daily wheat bran can achieve this in many people but not all. Concerns arose about wheat bran’s ability to reduce absorption of minerals such as iron from food. Bran could provoke urgency which the less mobile and elderly could not cope with. Painter’s trial showed that a standard dosage, taken like a medicine, did not take into account the fibre present in a person’s normal diet. Wheat intolerance and gluten sensitivity were not considered at that time and a requirement for daily defaecation is now outdated.  One patient was satisfied by a sterculia product. Nowadays, regular supplementation with an ispaghula preparation is popular to keep stools soft. So many foods and lifestyles affect bowel function as well as health, age and disease. Exercise and hydration are important. DD can have such variable effects that only an individual can find by trial and error what is best for them.

Dietary fibre can increase comfort and reduce symptoms but it does not follow that reduced levels are the cause of disease. In bowel complaints characterised by pain and diarrhoea such as IBD (Crohn’s and ulcerative colitis) and IBS (irritable bowel syndrome) wheat bran is far from helpful. Bran is not appropriate when there is diarrhoea with diverticular disease (DD).The problem with DD is to distinguish the reason for pain and symptoms. Are there muscle spasms, strictures or narrowing of the colon, chronic inflammation or age-related dysfunction compounded by the structural damage to the colon? Increasing numbers of research publications disprove the dietary fibre theory of the cause and treatment of DD and suggest other relevant factors, yet after half a century there are still some believers to be found. Maybe this is because medicine still has little else to offer patients.


Colon cancer was probably the first of the western diseases to be successfully disputed as a dietary fibre deficiency disease, others have followed over the decades, diverticular disease is hopefully the last. Fibre can have varied sources and bran is less fashionable now, fats and sugar wax and wane in popularity and publicity. Research into the relationship between diet and disease however has not faltered. Surveys and computers programs produce data which often disagrees and confuses. The popular headlines present results as risk levels which may or may not be relevant to actual numbers. There are fashions in recommendation of superfoods, supplements etc. Regional differences in diet are still used to claim reduced risk of western diseases. We have Mediterranian, Japanese, Eskimo etc. diets. Currently emphasis is on fermented foods from Eastern Asia to counteract western diseases through effects on gut microorganisms. Are omnivore humans so sensitive to small changes in diet? Should more emphasis be placed on how food is produced and treated before it is eaten? Diet is not the only way noxious substances can get into the body, we breathe as well as eat.

An overlooked but important work by Birkitt, Painter and their colleagues was the value of their epidemiology research. For DD in particular was the look at its early appearance in the 20th century. The suggestion that there could be one cause of western diseases was not appreciated at the time. Was it a mistake to choose the level of dietary fibre? At that time only lung cancer and heart attacks were considered the effects of smoking. Epidemiology is not static and other cancers and the western diseases including DD, follow a same pattern of prevalence and mortality during the 20th century. That pattern follows the worldwide use of cigarettes. Western diseases appear when and where Western cigarettes are smoked, diet can only modify their effects.

© Mary Griffiths 2017


The Fibre Man by Brian Kellock , 1985, Lion Publishing plc, ISBN 0 85648 583 7

Burkitt, Cancer, Fibre. How a humble surgeon changed the world. By Ethel R. Nelson, 1998, TEACH Services Inc, ISBN 1-57258-093-3

Diverticular disease of the colon, A deficiency disease of western civilisation. By Neil S Painter. 1975, William Heinemann Medical Books Ltd, ISBN 0 433 24660 x

Don’t Forget Fibre In Your Diet. To help avoid many of our commonest diseases. By Dennis Burkitt. 1979, Martin Dunitz Ltd, IBSN 0 906348 07 2 Pbk

Dietary Fibre, Fibre-depleted Foods And Disease, Edited by H. Trowell, D. Birkitt and K. Heaton, 1985, Academic Press, ISBN 0-12-701160-9.

Nutrition and Killer Diseases. Edited by J Rose. 1982, Noyes. Diseases of affluence, DP Birkitt, Pp 1-7. Essential fatty acids and chronic degenerative diseases, HM Sinclair, Pp 69-83.

The Saccharine Disease, Conditions caused by the taking of refined carbohydrates such as sugar and white flour. By T.L. Cleave. 1974, John Wright & Sons Ltd. ISBN 0 7236 0368 5.

Out of Africa. What Drs Price and Burkitt discovered in their studies of Sub-Saharan Tribes. By The Weston A Price Foundation.

Medical Aspects of Dietary Fibre. A report of the Royal College of Physicians of London, 1980, Pitman Medical, ISBN 0-272-79609-3.

Some Diseases Characteristic of Modern Western Civilisation (Crookshank lecture 19.5.72) By DP Burkitt. Br med J. 1973, 1, 274.

Diverticular Disease of the Colon: A Deficiency Disease of Western Civilization. NS Painter & DP Burkitt. Br Med J. 1971, 2, 450.

The Diet Delusion. By Gary Taubes. 2007, Vermilion. ISBN 9780091891411.

Trick and Treat. By Barry Groves. 2008, Hammersmith Press Ltd. ISBN 978-1-905140-22-0.

Diverticular Disease: Genetics and Collagen

Thursday, July 9th, 2015

Compared with other diseases, advancements in science and technology left diverticular disease (DD) behind decades ago. Worldwide occurrence, poor quality of life, level of mortality and healthcare costs should have generated far more research effort. Preoccupation with dietary fibre levels, constipation and ageing has and still is stunting research. Fibre levels have benefits for constipation and symptoms but research into cause, prevention and other treatments has been overtaken by the necessary investigations into the surgical rescue of DD effects. Recently valid trials and surveys have disputed traditional thinking about a dietary cause and revealed a genetic factor. (more…)

Diverticular Disease And Colon Cancer

Thursday, April 3rd, 2014

Does having diverticular disease (DD) increase the risk of colon cancer (CC)?  One expert would say “yes” and another would answer “no”. Much depends on the design of studies, choice of patients, what data is fed into the computer for statistical analysis, interpretation of the results and what opinions and conclusions are made.

Research can be based on the occurrence of the two separate diseases, how many people with DD have CC and how many people with CC have DD (1). Comparison can be made with the levels of CC and DD which would be expected in the general population. Information can be expanded by including different types of cancerous lesions and their position in the colon. The diagnosis of DD is not so stable. Diverticulitis but not diverticulosis was indicated to be in a long-term causal relationship with increased risk of left-sided CC (2). However, these conditions at diagnosis can change. Diverticulitis can revert to diverticulosis with few further problems, or, diverticulosis can later progress to diverticulitis or even further to serious complications. This is a basic problem in DD research. (more…)

Cigarette Smoking: The Cause Of Diverticular Disease?

Wednesday, June 19th, 2013

Two previous articles relate to this theory of the cause of diverticular disease (DD). “Colon wall muscles in diverticular disease” and “Diverticular disease: updated epidemiology” can be found on this website. Because of the length of this article, many details with supporting references have not been included and a summary is provided.


The worldwide epidemiology of diverticular disease (DD) is the same as that of the smoking epidemic used by many organisations and charities to show the relationship between smoking and lung cancer and many Western diseases. The grouping of countries by the timing and extent of DD correspond historically with the introduction of “Western” cigarettes. The types of tobacco and additives in the Western products and their promotion are related to the pattern of disease and they are designed to deliver the maximum amount of nicotine into the body. The changes in the colon wall with DD reflect the pharmacological action of nicotine in the chronic dosing produced by cigarette smoking. Ethnic differences in the metabolism of nicotine and different sensitivity in longitudinal and circular colon wall muscles could explain differences in the sites of disease particularly between Eastern and Western countries. Changes in the colon wall structure with DD are similar to those found in blood vessels caused by smoking. Such changes are found in the lungs of children subjected to passive smoking. Could DD also start this early in life?


There is a plethora of reports of research and opinions on what might be the cause of diverticular disease (DD). Research is often carried out in the hospital situation where the diagnosis of diverticulosis, diverticulitis or the treatment of complications takes place. Patients can then be surveyed to find out why they came to be in that situation. This tends to result in the cause of symptoms being blamed for the disease which is not the same as why or when the disease started in the first place. The formation of diverticula, the basis of diagnosis, is a later stage in its progression.

‘Symptoms’ such as excessive flatus (1), straining on defaecation (2) or constipation (3) have been suggested as the cause of DD. Statistical analyses point to ‘risk factors’ such as red meat or alcohol consumption, low physical activity or ageing. ‘Associations’ are found with obesity, hypothyroidism, industrialisation and Western diseases. ‘Predispositions’ are found with certain genetic diseases and familial environment. Recent research on twins with DD estimated that 40% of  the chance of DD was inheritable with the environmental effects at 60% (4). Another study estimated that 53% of susceptibility to DD resulted from genetic factors (5).

Research has produced some facts about DD which cannot be disputed –

  • The muscles in parts of the colon are in an apparent contracted state which is not reversible
  • Collagen and elastin components of the colon wall have changed to a more rigid form
  • Nerves and cells controlling the muscles have changed
  • Electrical activity and colon movements are disordered
  • There is increased sensitivity to acetylcholine – the normal neurotransmitter in colon function – due to increased numbers of receptors
  • There is damage to nitergenic neurones which affect relaxation of colon wall muscles
  • Pressure inside the colon can be increased during normal function or by drugs, resulting in the blow-out of diverticula

Opinions have varied on the order in which these changes occurred. Pressure and the formation of diverticula came before the other effect (6) or the muscle and nerve changes are a result of inflammation (7). Deterioration in the vagus nerve with age has been hypothesized (8). The greatest influence on opinion has been the dietary fibre theory of the early 1970s (9). Low levels of dietary fibre have been promoted as the cause of all the colon changes. The theory still persists in some research (10), while other reports consider human and animal experiments on diets to be unreliable (11) and that fibre can be detrimental to DD (12).

The idea, that the changes in the colon precede and predispose to the formation of diverticula, rather than as a consequence of the disease, has recently been published (13). Research on the cause of DD needs a rethink without a preconceived or traditional basis. Information available publically can be used to give a plausible explanation of what might cause DD and some of its characteristics.


1 Wynne-Jones G. Lancet 1975, Aug 2, 211.

2 Sikirov BA. Med Hypotheses 1988 26, 17.

3 Jones DJ. BMJ 1992, 304, 1435.

4 Granlund J et al. Aliment Pharmacol Ther 2012, Mar 20. Epub ahead of print.

5 Strate LL et al. Gastroenterology 2013, 144, 736.

6 Floch MH et al. World J Gastroenterol 2006, 12, 3225.

7 Spiller R. J Clin Gastroenterol 2006, 40(3 suppl), S117.

8 Yun AJ et al. Med Hypotheses 2005, 64, 252.

9 Painter NS et al. BMJ 1971, 2, 450.

10 Floch MH. J Clin Gastroenterol 2006, 40(3 suppl), S121.

11 Commane DM et al. World J Gastroenterol 2009, 15, 2479.

12 Peery AF et al. Gastroenterol 2012, 142, 266.

13 Mattii L et al. PLoS One 2013, 8, e57023.

© M Griffiths 2013


A previous article (Diverticular disease: updated epidemiology) on this website used data from barium enema and colonoscopy examinations to update the worldwide pattern of occurrence of DD and illustrated this in graphical form. Countries with insufficient data were not included. The results showed four groups of countries distinguished by the date of appearance of DD and subsequent changes in its levels.

Group 1. Australia, England, USA, Sweden. DD appeared before the 1930s, peaked at about 60% between 1970-1980 then fell slowly.

Group 2. European countries. DD appeared about 1960 and reached 50% around 1980

Group 3. Asian countries and Brazil. DD has been rising since its appearance about 1970.

Group 4. African and Middle East countries, Peru, China. DD first appeared about 1970 but levels have remained low.

People in Group 1 countries have been smoking ‘Western’ cigarettes since the beginning if the 20th century when they were invented. Group 2 reflects the import and flooding of ‘Western’ cigarettes into Europe and the take over of national cigarette companies after WW11. Group 3 is the effect of aggressive trading in the Far East by ‘Western’ tobacco companies around 1970. Group 4 countries have largely resisted the impact of ‘Western’ cigarettes due to trade restrictions, poverty or preference for their own forms of nicotine administration. These groups of countries are in keeping with the model of the cigarette epidemic described by Lopez et al in 1994 (1) which has been cited and used by researchers, charities and organisations since.

The appearance of DD corresponds to the consumption of ‘Western’ cigarettes or those manufactured from ‘Western’ tobaccos and not from previous local or national products. This explains some of the anomalies which have been highlighted. The Japanese were heavy smokers without much DD around 1970 but émigrés to Hawaii had developed DD within a generation. This has been attributed to diet change but the brands of cigarettes available to them certainly changed. In Japan after 1970, cigarette consumption reduced with the ‘Western’ type cigarettes but the levels of DD began to increase. Another paradox is China – the world’s heaviest smoking population. China has resisted international tobacco companies and has low levels of DD. ‘Western’ cigarettes are smoked by ethnic Chinese in Hong Kong or Singapore with significant DD levels. Birkitt (2) noted patches of low DD prevalence in the West, Mormons and Adventists are averse to cigarette smoking and only 10% to 15% of vegetarians smoke (3). The differences in DD levels between Uganda and Britain around 1970, the relationship to urban and industrial societies, wealth and Western diseases, have been used to support the dietary fibre theory but they are all related to smoking of ‘Western’ cigarettes. Most of the old research on colon function with DD ignored the smoking habits of patients, concentrating only on diet.

Some countries were opened up to transnational tobacco companies around 1990 e.g. Taiwan and DD was diagnosed there in 2.5% of ultrasound examinations in 2001 (4). The collapse of the Soviet Union produced newly independent countries. These have been targeted by international tobacco companies with imported cigarettes and privatisation of local tobacco farms and manufacturing. A report in 2011 showed that 16.2% of colonoscopy patients in a Moscow survey had diverticulosis (5). Will there be a Group 5 of countries where the DD epidemic starts around the new millennium? By the 1950s 80% of adults smoked in Britain and even more were subjected to passive smoking. With changing attitudes to smoking, the prevalence of DD may never again be as high as in Group 1 countries, particularly when that generation has passed.


1 Lopez AD et al. Tob Control 1994, 3, 242.

2 Birkitt DP British Medical Bulletin 1984, 40, 387.

3 Crowe FL et al. BMJ 2011, 343, d4131.

4 Chou YH et al. Am J Surg 2001, 181, 122.

5 Prilepskaia SI et al. Eksp Klin Gastroenterol 2011, 2, 22.

© M Griffiths 2013


Western cigarettes have different characteristics compared with locally produced products in emerging countries or other forms of sustaining nicotine addiction using tobacco. Flue-dried, ‘blonde’ tobacco varieties are blended to give a less irritant smoke of lower pH. This makes deep inhalation easier. The addition of menthol in some products and flavourings enhances the sensory and addictive potential (1)

Tests for nicotine and tar levels using standard mechanical ‘puffs’ related to older, cruder types rather than the cigarettes largely redesigned in the 1950s. Filter tips, types of paper and the blending of tobacco enabled reduction in nicotine and tar levels to legal conformity in countries. However, smokers compensated by more and deeper puffs to achieve their nicotine fix (2). The USA had no product standards for cigarettes or other tobacco products until June 2009 so that industry could have made any changes for marketing advantage (3).

Winder (4) describes how the reduction in delivery of nicotine and tar from cigarettes after the 1950s paralleled an increase in nitrate content from 0.5% to 1.5%. This enhanced combustion and increased yields of nitrogen oxides and N-nitrosamines in the smoke. The nitric oxide from the smoke opened up airways then deeper inhalation increased nicotine and tar uptake and promoted cancer at sites deeper in the lungs. Vleeming et al (5) concluded that nitric oxide contributed to nicotine addiction. Wu et al (6) compared levels of tobacco specific nitrosamines (TSNAs) from a global brand of cigarettes with TSNAs from local brands. In 10 out of 14 countries the global brand produced higher levels of TSNAs. An exception was Brazil where local cigarettes were higher. (Brazil was also an oddity in Group 3 countries of the epidemiology results).

The international tobacco companies aim to control their products from start to finish – from the genetic selection of tobacco plants, their growth conditions, use of pesticides, harvesting, drying, blending, additives, cigarette design, production and marketing. There are no lists of ingredients as on food and drugs. Genetically modified tobacco plants have been allowed in Europe since 1994. Companies were also interested in nicotine analogues – biologically active compounds which would not affect nicotine levels in statutory tests (7).

Farm workers harvesting tobacco leaves are susceptible to nicotine exposure producing symptoms of ‘Green Tobacco Sickness’ (8) which requires treatment by anticholinergic drugs. In one study a mutagenic change was found more often when farmers were applying pesticides to the crops. One particular liver metabolic enzyme variant was associated with DNA damage induced by pesticides (9). Pesticides are used to protect the tobacco crop from insect damage. If the insecticides used were of the type that interferes with the enzyme (acetylcholinesterase) which breaks down acetylcholine in the gut nervous system, then there may be another detrimental effect of cigarettes on the human colon which has not so far received much attention. Neonicotinoid insecticides, if used, have activity similar to nicotine and might enhance its effects.


1 Yerger VB. Tob Control 2011, 20, ii29.

2 Hoffmann D et al. J Toxicol Environ Health 1997, 50, 307.

3 Tynan M et al. Morbidity & Mortality Weekly Report 2010, 59, 487 (CDC)

4 Wynder EL et al. Environ Health Perspect 1995, 103 Suppl 8, 143.

5 Vleeming W et al. Nicotine Tob Res 2002, 4, 341.

6 Wu W et al. Nicotine Tob Res 2005, 7, 443.

7 Vagg R et al. Addiction 2005, 100, 701.

8 Satora L et al. Pol Arch Med Wewn 2009, 119, 184.

9 Da Silva FR et al. Environ Mol Mutagen 2012, 53, 525.

© M Griffiths 2013


Messages are transmitted between one nerve ending and the next nerve cell by the chemical acetylcholine. This also bridges the gap between the second nerve fibre and the muscle to relay the message to contract. An enzyme, acetylcholinesterase, is secreted by nerves to inactivate acetylcholine and limit the time and intensity of the contraction. Stimulation of the second (postsynaptic) nerve cell also elevates the production of nitric oxide (NO) which is the neurotransmitter for the relaxation of the colon muscles (1). This all takes place in the networks of nerves in the colon known as the gut brain. The cyclic contraction and relaxation of the longitudinal and circular muscles is the basis of all types of coordinated movements in different parts of the colon.

Nicotine fits and blocks the receptors on the second nerve cell and sends its own signal to produce acetylcholine at the colon muscle. A feedback controlling mechanism may also be affected (2). Nicotine is not inactivated by acetylcholinesterase and continues its activity until the transmission system is blocked. Also blocked is the production of NO to relax the colon muscles. These effects are also the basis of the insecticidal properties of nicotine. Reduced levels of NO would normally increase propulsive activity of the colon (3) but not when the stimulation system is also blocked. The net effect is the locking of muscles in the ‘on’ position and with uncoordinated movements. An increase in the numbers of receptors for acetylcholine is a response to the chronic effects of nicotine, this also alters the response to neurotransmitters and drugs (4).

The effect of nicotine on smooth muscle (the type of muscle fibre) in the colon has had little attention compared with that in the walls of blood vessels. The chronic effects of nicotine from cigarette smoke produce narrowed, stiffened and less responsive artery walls (5). There are the same changes in collagen structure in arteries as there are in colon walls where it is considered a major factor in the onset of structural changes in diverticular disease (6). Changes in muscle elastin content are the same in diverticular disease as in the pulmonary artery (7). Arteries to the colon would also be affected. Are the weak places in the colon where diverticula form, a result of movement between rigid arteries and rigid colon wall?


1 Kodama Y et al. J Smooth Muscle Res 2010, 46, 185.

2 Mandl P et al. Brain Res Bull 2007, 72, 194.

3 Dinning PG et al. Neurogastroenterol Motil 2006, 18, 37.

4 Ke L et al. J Pharmacol Exp Ther 1998, 286,825.

5 Enevoldsen MS et al. J Biomech 2011, 44, 1209.

6 Bode MK et al. Scand J Gastroenterol 2000, 35, 747.

7 Ludeman L et al. Best Practice & Research clinical Gastroenterology 2002, 16, 543.

© M Griffiths 2013


Nicotine is broken down in the liver by an enzyme known as CYP2A6. The main chemical formed is cotinine which is excreted from the body in urine. This provides a convenient marker for smoking and the rate of inactivation of nicotine. Cotinine and other chemicals produced are also known to have activity in the body but have not had much attention (1). Most of the research relates to activity in the brain where variations in CYP2A6 are a genetic contribution to addiction (2).

The enzyme CYP2A6 is not a single entity, some 40 variants have been found which produce differences in the rates and pathways by which nicotine is broken down and other chemicals produced. This has a great effect on smoking behaviour and disease. People who metabolise nicotine rapidly smoke more to sustain the body level of nicotine and at the same time increase the intake of carcinogens (3). There are reports that females process nicotine faster that males and are more likely to become addicted. Current smokers also have increased metabolism (4).

Liver enzymes such as CYP2D6, CYP2C19 or CYP2A6*18 have been shown to vary with ethnicity (5) (6). However a variant of CYP2A6 known as CYP2A6*4 is perhaps the most significant in producing ethnic differences in the effects of cigarette smoking. CYP2A6*4 is not active in the metabolism of nicotine. People with this variant enzyme produce different metabolic chemicals, have far less cotinine excreted in urine and have significantly reduced rates of lung cancer. Nakajina (7) compared the frequency of CYP2A6*4 and other reduced activity variants present in ethnic groups. The results were, Whites 9.1%, Blacks 21.9%, Korean 42.9% and Japanese 50.5%. There are differences between individuals in the ethnic groups but the different metabolic pathway for nicotine in Eastern populations, particularly Japanese, is well documented.


1 Schroff KC et al. Toxicology 2000, 144, 99.

2 Tutka P et al. Pharmacological Reports 2005, 57, 143.

3 Derby KS et al. Cancer Epidemiol Biomarkers Prev 2008, 17, 3526.

4 Bloom J et al. Pharmacogenet Genomics 2011, 21, 403.

5 Benowitz NL et al. J Natl Cancer Inst 2002, 94, 108.

6 Vasconcelos GM et al. Pharmacogenomics J 2005, 5, 42.

7 Nakajima M et al. Clin Pharmacol Ther 2006, 80, 282.

© M Griffiths 2013


The longitudinal and circular muscles in the colon wall contract and relax rhythmically to move along the residues of digestion. Different movements are found in different parts of the colon to enable mixing, drying and evacuating functions. To achieve this, the longitudinal and circular muscles differ in their response to neurotransmitters. Sensitivity can also vary along the colon length. There are examples of different responses to drugs and neurotransmitters including those related to the acetylcholine and NO systems affected by nicotine. The chemicals produced by the metabolism of nicotine differ in Western and Eastern ethnic populations, cotinine is an example. A greater effect on longitudinal muscle, used for example, in mass peristalsis and evacuation of faeces, would give the typical Western pattern of colon changes in the descending and sigmoid colon on the left side of the body. The level of the enzyme CYP2A6*4 in ethnic groups appears to relate to the position of diverticula in the colon.


% of CYP2A6*4 in ethnic group

Ref (1)

% with DD only

in left colon

JAPANESE   50.5 13.3 (2)
KOREAN     42.9 15.5 (3)
BLACKS      21.9 41.7 (4)
WHITES        9.1 80.0 (5)


1 Nakajima M et al Clin Pharmacol Ther 2006, 80, 282.

2 Takano M et al. Dis Colon Rectum 2005, 48, 2111.

3 Lee KM et al. J Korean Med Sci 2010, 25, 1323.

4 Golder M et al. World J Gastroenterol 2011, 17, 1009.

5 Painter NS et al. BMJ 1972, 2, 137.

© M Griffiths 2013


Diverticular disease is diagnosed when diverticula are found in examinations because of symptoms or screening for bowel cancer mainly in the over 50s. It was considered an inevitable consequence of old age, but this has changed. The mean age of people admitted for hospital treatment has dropped, more are under the age of 50 and need emergency surgery (1). The lowest age is often in the 20s when surveys report the age range of people with DD. A study in California found hospital admissions increased most rapidly in patients 20 to 34 years old (2). The relatively recent DD epidemic in Japan resulted in 2.2% of patients below the age of 29 and only 14.3% over 70 years old (3). This suggests that people get DD before they grow old. Diverticulitis in teenagers has been reported without reference to the hereditary diseases which affect collagen and predispose to diverticula formation. It is accepted that passive smoking increases the risk of cardiovascular disease and lung cancer. Passive smoking by children causes changes in elasticity and collagen and gives structure and function disorder in the lungs (4). Such changes are found in the colon before the formation of diverticula, could DD start in children subjected to passive smoking?


1 Jeyarajah S et al. Int J Colorectal Dis 2008, 23, 619.

2 Etzioni DA et al. Am Surg 2009, 75, 981.

3 Kubo A et al. Jpn J Med 1983, 22,185.

4 Bosdure E et al. Rev Mal Respir 2006, 23, 694.

© M Griffiths 2013


The ratio of males to females in surveys of DD varies according to countries. There are ethnic, social and cultural reasons why women may not smoke and this reduces the incidence of DD and the pattern can be retained after immigration. Women, especially the elderly, are reported to have different responses to the drug carbachol (acts like acetylcholine and nicotine) and to NO release (1) which are relevant to the effects of smoking. Passage through the colon was slower in females than males (2) and smoking slows colon transit time in males. There is evidence that females have different activity of liver enzymes including CYP2A6 which metabolises nicotine (3). This explains why females have a greater addiction to nicotine, greater difficulty in giving up smoking and are a target of tobacco companies. Are females more susceptible to DD if they smoke?


1 Maselli MA et al. Dig Dis Sci 2011, 56,352.

2 Sadik R et al. Scand J Gastroenterol 2003, 38, 36.

3 Anderson GD Int Rev Neurobiol 2008, 83, 1.

© M Griffiths 2013


In the past there have been pointers to a relationship between cigarette smoking and DD. It has been estimated that over 90% of lung cancer was caused by cigarette smoking. During the 20th century there was significant correlation between deaths from DD and deaths from lung cancer for both men ( r =0.68 ) and women ( r =0.92 ). Women’s deaths from DD rose steeply with their cigarette consumption ( r =0.87 ). This relationship for men was distorted by the supply of cigarettes to the armed forces during the two world wars and the death toll in the conflicts resulting in two waves of low male population through the rest of the century. In the approach to the 21st century, increasing smuggling and counterfeiting of cigarettes made such studies irrelevant.

Nicotine from cigarettes has considerable effects on colon function of otherwise healthy people but most research on DD ignored the smoking habits of patients. Parameters such as transit time are not only affected by the level of fibre in the diet. Diet has never explained different levels of DD in males and females, or the differences in DD characteristics in different countries. Cigarette smoking, nicotine and its metabolism does offer an explanation. Comparisons between countries should take into consideration changes in the ethnic composition of its residents.

Effects on neurotransmitters and hormones other than acetylcholine have been produced by smoking and changes in these in people with DD are unfolding. Nitric oxide has been implicated as a key molecule in the control of colon movement and pain perception. More research is needed on the effect of nitric oxide supplied externally from smoke on that produced by the body to effect normal colon function.

The epidemiology of DD is dynamic, as is the smoking epidemic and probably the contents of cigarettes. Information is now available on the physiological effects of smoking, neurotransmission and nicotine metabolism which was not available to pioneers of research into DD and other diseases have had much more attention. There are many unanswered questions but this jigsaw of evidence suggests a picture of the cause of DD which merits consideration.

Some researchers did not find that smoking cigarettes had a significant effect on DD but trial design could affect conclusions. Recent research has shown that cigarette smoking increases the risk of complications in patients with DD (1), and Turunen et al. (2) found that the development of complicated disease proceeded more rapidly in smokers. Usai et al. concluded that smoking was a predictive factor for diverticulitis (3). Women who smoked had increased risk of symptoms and perforation/abscess complications than non-smokers (4). Crowe et al (5) found greater risk of admission to hospital or death with heavy smokers compared with light smokers. Cigarette smoking is implicated in many ‘Western’ and ‘affluence’ diseases. There is now evidence that DD should be added to that list


1 Papagrigoriadis S et al. Br J Surg 1999, 86, 923.

2 Turunen P et al. Scandinavian Journal of Surgery 2010, 99, 14.

3 Usai P et al. Dig Liver Dis 2011,43, 98.

4 Hjern F et al Br J Surg 2011, 98, 997.

5 Crowe FL et al. BMJ 2011, 343, d4131.

© Mary Griffiths 2013