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Friday, May 7, 2021

Birth cohorts and obesity: What do they tell us


Every so many years, national data are gathered on dietary habits and such surveys also provide data on many non-dietary variables, including BMI.  The data thus gathered on weight and height refer only to the date of measurement. It cannot tell us when an individual might have become overweight or obese, given that the sample will be comprised of individuals ranging in age from tens to the nineties. Thus, if a sample is taken in 1960, the extent to which subjects watched TV would vary very considerably. However, if a birth cohort born in 1960 is followed thereafter, then they all experience the same opportunity for TV viewing. 

A recent paper in the Proceedings of the National Academy of Sciences, provides data on birth cohorts and obesity in the US(1). They used data from NIH longitudinal studies: The National Longitudinal Study of Adolescent to Adult Health (Add Health) (2); The Americans' Changing Lives (ACL) survey (3); Mid Life in the United States (4); Health and Retirement Study (5). The main aim of the study was to determine for different birth cohorts, the age at which the mean body mass index (BMI) reached 30, indicative of obesity.  The data are presented in the table below:


Birth cohort                             Age in years at
                                             which mean cohort BMI
                                        is equal or greater than 30 kg/m2
1980-1984                              30-39
1965-1969                              40-49
1955-1959                              50-59
1950-1954                              60-69

These data clearly indicate younger cohorts will endure the adverse effects of obesity for decades longer than their older or siblings or their parents. Cohorts born between 1905 and 1945 never reached a mean BMI indicative of obesity throughout their lives. However, all readily hit the overweight range (BMI 25.0-29.9 kg/m2) from their thirties onwards and some of the cohorts were knocking on the door of obesity. For example, the cohort born between 1940-1945 reached a mean BMI of 29.4 in their seventies. 

The data we obtain from birth cohorts are critically important in understanding the epidemiology of obesity. However, many take the uncomplicated but incorrect view that both overweight and obesity are entirely a recent phenomenon. In my book “Ever seen a fat fox – the biology of human obesity” I cover several earlier birth cohort studies and BMI (6) .



Researchers at the US National Bureau of Economic Research examined the birth cohort changes in BMI using data collected by the National Center for Health Statistics covering subjects born between 1882 and 1986 (7). Their results show that in 1880, average BMI was within the normal weight range (20-25 kg/m2) at about 22. Mean BMI of black females reached 25 by 1900, while for white males, black males and white females the dates that a mean BMI of 25 was achieved was respectively, 1905, 1915 and 1920. Again, black females led the way in achieving a BMI in excess of 30 by the year 1940 with all others achieving this about 1960. Another set of research from the same US Bureau provides data on the BMI of US military recruits from 1864 to 1991(8). These are more robust data because they are based not on models but on measured weight and height. If we take men aged 45 years, the average BMI increased from 23.3 to 26.5 over this time period but the greatest part of this increase (60%) was in the period 1894 to 1961. Only 20% of the rise in BMI was explained post 1961. 

We can also look at more modern data gathered in Denmark and which looks at the rate of change in body weight in two groups (9). The first are 19-year-old military recruits studied since 1945. The second is a set of children aged 7,8,9,10 and 11, all born in 1930. In both cases, the prevalence of obesity was low at the outset of the studies at about 3 obese persons per thousand of the population. That trebled by 1960 but remarkably, it did not change at all between 1960 and 1990. However thereafter obesity again trebled to a level of about 30-40 obese persons per 1000 of the population. This wave-like growth in obesity, which I call the tsunami of lard, has also been recorded by the researchers at the US Bureau of Economic Research in their 1882-1991 modeling of the growth of obesity in the US. The concept that the rise in obesity has not been linear but wave-like is important in evaluating the present crisis of obesity. As ever in science, progress in our knowledge grows from embracing anomalies and exceptions and not from burying awkward data. 


(1) Yang YC, Walsh CE, Johnson MP, Belsky DW, Reason M, Curran P, Aiello AE, Chanti-Ketterl M, Harris KM. Life-course trajectories of body mass index from adolescence to old age: Racial and educational disparities. Proc Natl Acad Sci U S A. 2021 Apr 27;118(17): e2020167118. doi: 10.1073/pnas.2020167118. PMID: 33875595.
(2) https://addhealth.cpc.unc.edu/ 
(3) https://www.icpsr.umich.edu/web/NACDA/studies/4690 
(4) http://midus.wisc.edu/puboverview.php 
(5) https://hrs.isr.umich.edu/about
(6) https://www.amazon.com/Ever-Seen-Fat-Fox-Explored/dp/1910820083 
(7) Komlos J, Brabec M (2010) The trend of mean BMI values of US adults, birth cohorts 1882-1986 indicates that the obesity epidemi
began earlier than hitherto thought. National Bureau of Economic Research. Available from:  http://www.nber.org/papers/w15862 .
(8) Costa D, Steckel RH. Long term trends in health. Welfare and economic growth in the United States.  In RH Steckle and R,Floud eds Health and Welfare during Industrialization, Chicago: university of Chicago Press, 1997.
(9) Olsen LW, Baker JL. Holst C, Sørensen TI. Birth cohort effect on the obesity epidemic in Denmark Epid 2006;17:292-295.



Tuesday, April 6, 2021

Obesity goes viral - but not with Covid


 

It is a given that as soon as a child starts to attend a pre-school creche, they will come home with sniffles and occasionally a sore eye from conjunctivitis. The root cause is an adenovirus which will be readily spread as droplets in expired air and, because the adenovirus is not easily disinfected, it is readily spread by shared surfaces. Sound familiar? There is one particular adenovirus that attracts the attention of those in the obesity field that are capable of thinking outside the box, a rare breed, let it be said. Back in 1982, veterinary researchers in Mumbai noted that when chickens were injected with canine distemper virus, they became very fat. Shortly afterwards, other viruses were shown to be drivers of obesity such as the virus that causes scrapie in sheep or an avian adenovirus known as SMAM-1 . Studies then turned to humans to explore if there might be  link between excess body weight and some virus and the candidate virus that has emerged is the adenovirus 36 or Adv 36. The first study (n= 502) to show this was in 2002, with an infection prevalence of 11% in those of normal weight and 30% among the obese population . Since then, an additional 36 studies have examined the role of  Adv 36 in human obesity and a recent systematic review of the literature in this field  has concluded that: ”Strong evidence suggested a possible association between viral infection and obesity” . In general, this blogger dislikes association studies but in this instance, it is the best we can do since it would be unethical to experimentally infect a human with Adv 36. There are, however,  data other than association data to help us understand the role of Adv 36 in obesity. That very first study of Adv 36 in human obesity also included 26 pairs of twins (20 identical and 6 non-identical). What was important in this study was that infection was discordant among the twins, that is, one twin was positive and one was negative for infectivity. The infected twins had a higher body mass index (26.1 v.24.5 kg/m2) and a higher overall % body fat (29.6 v. 27.5 as measured using hydrondensitometry or dual  emission X-ray absorptiometry).

 

The experimental data from animals consistently shows among chickens, rats and monkeys that experimental infection with Adv 36 causes obesity. All show a significant rise in adiposity and all show no change whatsoever in energy intake. Perhaps the most interesting study was at the Wisconsin Primate Research Centre where blood samples were taken from Rhesus monkeys every 6 months for 90 months. The samples were stored frozen and accessed to test for Adv 36 infection . This study therefore relied on natural infection rather than experimental infection. Only those monkeys that remained  seronegative for Adv 36 over an initial 18 moths were included in the study. During this Adv 36-free period, bodyweight changed very little (0.3% or 0.04 kg). However, once they became naturally infected, body weight increased by 15% or 1.7 kg. 


Both the discordant twin study and the longitudinal monkey study of natural infection provide compelling evidence for a possible role of Adv 36 in human obesity. The stand-out discovery is that neither in experimentally infected or naturally infected animals did energy intake change. So how does Adv 36 cause increased fat mass if it has zero effect on energy intake? It does this by stimulating stem cells in adipose tissue to differentiate into adipocytes thus creating more fat cells (hyperplasia)  . The virus also causes a shift in biochemical regulation of fat and glucose metabolism such that the fat cells get fatter (hypertrophy). All of this centres around a protein enzyme, AMP kinase, which is a central regulator in intracellular levels of energy stores. 


So where does this leave us? The answer is, unchanged. Genes load the gun but the environment pulls the trigger so while obesity is highly heritable (multiple twin studies,) it is the obesogenic environment that matters: cheap, palatable and energy dense foods and a totally sedentary environment. Nobody would suggest that viral infection is the cause of obesity but it deserves more than its current orphaned role. 


Wednesday, March 31, 2021



Nutrients, immunity and Covid.


Food manufacturers, food celebs and wannabe diet experts often discuss the immune boosting properties of some food or nutrient. Our immune system is a highly complex and  orchestrated network of mechanisms that help us fend off infections and the entry of unwanted foreign matter into our bodies. So, when the issue of “boosting” the immune system is raised, it is not unreasonable to ask what part of the immune system you expect to be boosted. Do you want those antibodies (A type) that line the exterior of the body such as the gut and lungs to be smarter at keeping foreign bodies out? Do you want to boost the ability of the body to produce circulating antibodies (G type) to foreign matter that have gained entry into the body? Do you want to boost the so-called cytokine storm that wreaks havoc in Covid? Do you want to boost those antibodies (E type) that are involved in allergic reactions?


Many nutrients are involved in different parts of the immune system  and a deficiency can cause a significant impairment of that system . But how do you define deficiency? Firstly, measuring dietary patterns to ascertain micronutrient status is a waste of time. At the level of the individual, such measures are totally unreliable. They may give a broad sweep but they lack the definition needed to allow us make any prediction of biochemical deficiency. Secondly, when micronutrient deficiency is measured in dietary terms, it is against particular dietary reference values, the ones you might see on a packet of breakfast cereal.  With these, we can have cut-off points, below which population intakes of a nutrient would be a cause for concern. Many with intakes below that minimum threshold of dietary intake may show biochemical deficiencies but, such is the variation in human nutrient requirements, that many with intakes below that value will be perfectly healthy. 


Cut-off levels, based on blood biochemical values, can sharpen our expectation that an individual is prone to some nutritional disorder and in such instances, nutritional supplements and dietetic advice will help restore these blood value to normal. As normality is restored, the many biochemical pathways that depend on the nutrient in question will be fully operational. But here lies the hub of the problem. Once normality is reached, further intake of the nutrient will have no effect. The petrol tank of a Jaguar has 50% greater capacity than that of a Fiat Punto. Fitting an additional petrol tank will not make the Punto overtake the Jag. When a biochemical need is met, that’s it. 


So should we routinely use nutritional supplements? If someone is restricting their food intake to manage their weight, it might be wise to use them. Equally, as we get older, our appetite falls as does our ability to absorb vitamin B12, and again, their use may be a good insurance. And there are specific clinical needs for certain vitamin supplements such as folic acid in pregnancy, multi-micronutrients in cystic fibrosis or calcium for low bone density. Routine use of nutritional supplements is perfectly acceptable but with the current pandemic, there has been a plethora of recommendations for supplementary intakes of individual minerals and vitamins.


In the present pandemic,  many immune related nutrients have come to prominence, none more so than vitamin D. Recommending vitamin D supplements to boost the immune system begs the question: Is it possible that the immune system of your target population is actually limited by another immune related micronutrient. If you don’t know that, focusing on one vitamin is pretty foolish. Besides vitamin D, many other micronutrients are involved in protecting us from unwanted visitors. Vitamins A and C are centrally involved in maintain the integrity of outward facing barriers such as the lung, the gut and the skin. Vitamin E, zinc, iron, selenium and copper all play a role in the systemic immune system. Fish oil type fatty acids can play a significant anti-inflammatory role, the opposite to immune boosting. So, focusing on one nutrient doesn’t seem to make sense. 


The case has been made that Vitamin D plays a particularly significant role in Covid. A first point to note is that vitamin D is a fat soluble vitamin which is preferentially stored in fatty tissue. As people become overweight and obese, blood vitamin D levels fall as it is shunted into fatty tissue. Body fat is among the highest drivers of Covid complications. A study published by the UK Biobank showed that whereas those with Covid had lower levels of blood vitamin D than those who were healthy, these differences disappeared when the data were adjusted to take account of confounding factors, of which obesity was the most important. 


A recent randomized clinical trial published in the Journal of the American Medical Association examined the effect of boosting Vitamin D status in Covid patients. One group received a single high oral dose of vitamin D which led to a doubling of their blood vitamin D levels. The control group received a placebo which had not effect on their blood vitamin D levels.  The treatment with vitamin D had no statistically significant effect on in-hospital mortality, admission to intensive care  or requirement for mechanical ventilation. Three recent UK reports from government advisory agencies (the National Institute for Clinical Excellence, the Scientific advisory Committee on Nutrition and Public Health England) concluded that there is presently no evidence to support a specific role for vitamin D in the prevention and treatment of vitamin D .  


Eating a healthy diet with lots of variety of food type and food colour, maintaining a healthy weight and keeping fit don’t make headlines. But they save lives.





Nutrients, immunity and Covid.

Food manufacturers, food celebs and wannabe diet experts often discuss the immune boosting properties of some food or nutrient. Our immune system is a highly complex and  orchestrated network of mechanisms that help us fend off infections and the entry of unwanted foreign matter into our bodies. So, when the issue of “boosting” the immune system is raised, it is not unreasonable to ask what part of the immune system you expect to be boosted. Do you want those antibodies (A type) that line the exterior of the body such as the gut and lungs to be smarter at keeping foreign bodies out? Do you want to boost the ability of the body to produce circulating antibodies (G type) to foreign matter that have gained entry into the body? Do you want to boost the so-called cytokine storm that wreaks havoc in Covid? Do you want to boost those antibodies (E type) that are involved in allergic reactions?

Many nutrients are involved in different parts of the immune system  and a deficiency can cause a significant impairment of that system . But how do you define deficiency? Firstly, measuring dietary patterns to ascertain micronutrient status is a waste of time. At the level of the individual, such measures are totally unreliable. They may give a broad sweep but they lack the definition needed to allow us make any prediction of biochemical deficiency. Secondly, when micronutrient deficiency is measured in dietary terms, it is against particular dietary reference values, the ones you might see on a packet of breakfast cereal.  With these, we can have cut-off points, below which population intakes of a nutrient would be a cause for concern. Many with intakes below that minimum threshold of dietary intake may show biochemical deficiencies but, such is the variation in human nutrient requirements, that many with intakes below that value will be perfectly healthy. 

Cut-off levels, based on blood biochemical values, can sharpen our expectation that an individual is prone to some nutritional disorder and in such instances, nutritional supplements and dietetic advice will help restore these blood value to normal. As normality is restored, the many biochemical pathways that depend on the nutrient in question will be fully operational. But here lies the hub of the problem. Once normality is reached, further intake of the nutrient will have no effect. The petrol tank of a Jaguar has 50% greater capacity than that of a Fiat Punto. Fitting an additional petrol tank will not make the Punto overtake the Jag. When a biochemical need is met, that’s it. 

So should we routinely use nutritional supplements? If someone is restricting their food intake to manage their weight, it might be wise to use them. Equally, as we get older, our appetite falls as does our ability to absorb vitamin B12, and again, their use may be a good insurance. And there are specific clinical needs for certain vitamin supplements such as folic acid in pregnancy, multi-micronutrients in cystic fibrosis or calcium for low bone density. Routine use of nutritional supplements is perfectly acceptable but with the current pandemic, there has been a plethora of recommendations for supplementary intakes of individual minerals and vitamins.

In the present pandemic,  many immune related nutrients have come to prominence, none more so than vitamin D. Recommending vitamin D supplements to boost the immune system begs the question: Is it possible that the immune system of your target population is actually limited by another immune related micronutrient. If you don’t know that, focusing on one vitamin is pretty foolish. Besides vitamin D, many other micronutrients are involved in protecting us from unwanted visitors. Vitamins A and C are centrally involved in maintain the integrity of outward facing barriers such as the lung, the gut and the skin. Vitamin E, zinc, iron, selenium and copper all play a role in the systemic immune system. Fish oil type fatty acids can play a significant anti-inflammatory role, the opposite to immune boosting. So, focusing on one nutrient doesn’t seem to make sense. 

The case has been made that Vitamin D plays a particularly significant role in Covid. A first point to note is that vitamin D is a fat soluble vitamin which is preferentially stored in fatty tissue. As people become overweight and obese, blood vitamin D levels fall as it is shunted into fatty tissue. Body fat is among the highest drivers of Covid complications. A study published by the UK Biobank showed that whereas those with Covid had lower levels of blood vitamin D than those who were healthy, these differences disappeared when the data were adjusted to take account of confounding factors, of which obesity was the most important. 

A recent randomized clinical trial published in the Journal of the American Medical Association examined the effect of boosting Vitamin D status in Covid patients. One group received a single high oral dose of vitamin D which led to a doubling of their blood vitamin D levels. The control group received a placebo which had not effect on their blood vitamin D levels.  The treatment with vitamin D had no statistically significant effect on in-hospital mortality, admission to intensive care  or requirement for mechanical ventilation. Three recent UK reports from government advisory agencies (the National Institute for Clinical Excellence, the Scientific advisory Committee on Nutrition and Public Health England) concluded that there is presently no evidence to support a specific role for vitamin D in the prevention and treatment of vitamin D .  

Eating a healthy diet with lots of variety of food type and food colour, maintaining a healthy weight and keeping fit don’t make headlines. But they save lives.





Wednesday, December 2, 2020

Popes, priests and persecution: Catholicism and chocolate



 

This blog is an extract from a chapter of a book I am now completing:"A history of food and dining" which will be published to 2021

 

Popes, priests and persecution: Catholicism and chocolate

When the Spanish conquistadors arrived in Mexico, they encountered many new foods that would transform the dietary habits of Western Europe. They brought back potatoes, tomatoes, chillies, vanilla, squash, French and Lima beans, peanuts, pineapples and  avocados. But there were one food that would be regarded as a gastronomic luxury: chocolate. 

Chocolate was consumed as a hot drink by the Aztecs and was quickly adapted by the Creole community that mixed Aztec and Spanish traditions. Creole women found it hard to stay focused during lengthy high masses and never ending sermons delivered by the Dominican friars in the city of Chiapa Real, on the Mexican-Guatemalan border. Their maids would arrive during mass bearing chocolate drinks and biscuits to sustain the concentration of these devout women. However, the Bishop noted that there was a competitive element among the Creole women to ascertain who could have their chocolate drink and biscuits served up in the most luxurious style. He decided to excommunicate anyone partaking of chocolate during mass and despite the pleas of the English Friar, John Gage who recorded these events, his order was implemented. The women abandoned the Basilica and moved to the non-Dominican community who were more than happy with their financial contributions and where they could continue enjoying chocolate drinks during mass. Alas, the bishop died from a poisoned chocolate drink  and Gage records that the finger of blame lay with his female Creole flock. 

The Dominicans and the Jesuits didn’t see eye to eye on chocolate. The two orders detested one another with the Dominican Friar Gage writing: “But above all, is this envy and hatred found between Dominicans and the Jesuits” and that “of the two, the Jesuits are more bold and obstinate in malice and hatred”. The more austere Dominicans were of the view that the Lenten fast was broken by drinking chocolate while the Jesuits, who as we will see had a vested interest in chocolate, opposed this view. And so, the Vatican was faced with two powerful forces arguing over chocolate and religious fasts. Eventually, a Jesuit-leaning Pope Alexander VII, came down in favour of the Jesuits with the famous law “Liquidum non frangit jejunum”, (“Liquids do not break the fast”). But the argument rumbled on and in time required the opinions of no less than 6 successive Popes before the issue waned.

The Jesuits did have a significant vested interest in chocolate. Firstly, they enticed Amazonian indigenous peoples out of their normal habitat and settled them in villages where they worked and worshipped in the Catholic faith. “Besides regular indoctrination, the natives were constrained to work for the settlers, the Crown and the fathers themselves, although preserving their free status. This was the basis of a system of free Indian labour that was adopted a century later in the Amazon region”. Another account of these settlements describes how the priests micro-managed the lives of these slaves: “So regimented were the natives that it is said that the Jesuit fathers rang a bell every night to tell the men it was time to perform their marital duties with their wives.”

With this labour, the Jesuits became one of the biggest exporters of Brazilian cocoa beans for chocolate processing. On one occasion a ship from South America arrived in Cadiz with several large boxes addressed to the Procurator-General of the Jesuits. The contents were said to be chocolate, but the dockers found them too heavy to lift and, when the customs officers inspected further, they found gold bars coated with chocolate. Between 1743 and 1745, the Jesuits accounted for 80% of all cocoa beans exported from the Amazonian region.

The Dominicans return to the story of chocolate through their very significant role in the Spanish Inquisition. Heresy was a major crime for the Inquisitors, but witchcraft was also very much on their agenda. Chocolate was strongly associated with magic and is mentioned in a report of the Inquisition: “Chocolate was frequently implicated in cases that came before the Spanish inquisition. The several chocolate-associated Inquisition documents presented here, appear as relics from a past era, where distrust, fear and suspicion influenced human behaviours and practice. Prying eyes and ever-vigilant Dominicans characterized the era and one never knew when there might be a knock on the door with an order to appear before the tribunal”.  Magic and chocolate are synonomous.

Joan Harris in her novel “Chocolat”, now a much acclaimed film, tells the story of Vianne and her daughter Armande, who set up a chocolate shop in a sleepy town in rural France and who was made utterly unwelcome by the Mayor and the local catholic priest.  Looking out at the church she muses: “Before Christ – before Adonis was born in Bethlehem or Osiris sacrificed at Easter – the cocoa bean was revered. Magical properties were attributed to it. Its brew was sipped on the steps of sacrificial temples; its ecstasies were fierce and terrible. Is this what he fears? Corruption by pleasure, the subtle transubstantiation of the flesh into a vessel for debauch? Not for him the orgies of the Aztec priesthood”.

The mystical nature of chocolate id also described by Nina Haratischvilli, in her novel “The Eighth life”, which documents the history of Georgia and narrates the story of her great, great grandfather, a chocolatier trained in Budapest and Vienna, who ran a chocolate factory in Tbilisi.  She writes of  her great, great grandfathers chocolate and its “magic secret formula that would revolutionise the taste of hot chocolate… The taste was incomparable: savouring it was like a spiritual ecstasy, a supernatural experience. You melted into the sweet mass, you became one with this delicious discovery, you forgot the world around you, and felt a unique sense of bliss”. 

It is somewhat ironic that the great Christian feast of Easter heralds the highest annual  sales of chocolate in the from of eggs and bunnies, each a symbol of fertility. The next highest period is the day of romance and love Valentine’s day. Sex and magic have helped sell chocolate: “The lady loves Milk Tray “ and “Black Magic”. Despite the naysayers who would peddle the myth of chocoholics, the silken mouthfeel of chocolate and its alluring and seductive  aroma will always be with us.


Sunday, March 29, 2020

A Rant on Risk.

Apologies for a long delay in posting. I'm busy researching a book: "The story of food and dining"



Risk is an abstract concept and the perception that a risk exists, or the degree of that risk, is determined by an individual’s worldview. Pail Slovik at the University of Oregon has written many research papers on the topic. For the general public, risk is determined by three factors. First a high level risk is associated with dread. Everyone knows an obese person and would have seen overweight friends lead long, happy and healthy lives into old age. Thus, obesity and overweight is not dreaded. However, motor neuron disease is dreaded, seen as a fatal disease with a slow decline in wellbeing and with a growing dependence on others. A second factor is familiarity. These days, most of us know someone who was diagnosed with cancers. Decades ago cancer was, in effect,  a death sentence. However, many cancers are now manageable and allow those who contract cancer to enjoy a long and happy life. So, cancer is seen as a risk which is familiar and something not to be feared as it once was. The third factor is control. Those who smoke know the risk but they retain the belief that at any point, they can quit smoking. But, during the height of the BSE crisis, Variant Creutzfeldt–Jakob disease (vCJD), was a condition which was outside our personal control. We might be a vegetarian but who’s to say that your vegetable curry wasn’t contaminated with gelatin. You might avoid a T-bone steak but could you be sure that the minced beef you just bought is BSE free. In fact, vCJD hits all the buttons: it is dreaded, it is unfamiliar and it is totally outside your control.
One would imagine that toxicologists, whose speciality involves all manners of risk analysis would have a clear and objective understanding of risk, independent of their worldview. Thus it shouldn’t matter if you are Christian, Jew, or Muslim when, as a toxicologist you consider the scientific data on the hazards to human health of some chemical or biological risk. But Slovik’s study challenges that. When presented with several scenarios, toxicologists were asked to rate the risk. In the US, male toxicologists had a higher risk tolerance than their female counterpart. The same was true in Europe except that European toxicologists had a much lower tolerance of any given  of risk compared to their US counterparts. Right now, in the midst of this Covid 19 pandemic, we can see geographic or cultural variation of risk perception and thus differing strategies of risk management. In some countries, economic issues hold a higher ranking than societal issues leading to quite different messaging to the general population (Obrador, Trump, Bolsonaro).

Risk assessment is purely scientific while risk management is tainted with the politics of the problem. It follows the seat belt rule. When research showed that seat belts would save lives, car manufacturers were asked to install them in new cars. Then the were obliged to do so by law and drivers were asked to use them. In turn, drivers were legally required to wear them. In the realm of risk managements there are vested interest which either promote or downplay the risk according to their interests. And there are rogue scientists who exploit the scare to self-promote themselves[1],[2],[3], [4]  There are also very eminent scientists, experts in the field of epidemiology,  who query and challenge scientific opinion[5]. Where true debate can be held, we should remember that dissent is the oxygen of science.
In an environment where all hazards to human health are properly managed, there is no reason for people to go beyond that system and take a risk. But around half the global population don’t enjoy such sanitized existence and they have to take risks. Hunger, they say, is the best sauce and the those who suffer hunger will take risks to meet their nutritional needs. They have no choice. And it a world which favours the privileged societies, social distancing in the current Covid 19 pandemic is easy to comply with, albeit annoying to endure. But in the slums of the great cities of the world, the townships of Johannesburg, the Favelas of Sao Paulo or among the 18 million US citizens who live in trailer parks, social distancing is challenging and the risks that it seeks to mitigate can’t easily be avoided. But its not just among the world’s disadvantage that risk is tolerated.
Opioids and obesity, each account for 40,000 deaths annually in the US[6]. When populations find risk acceptable, politicians are slow to act. Herein the rant ends and I feel better-cheaper than therapy!!

Monday, August 5, 2019

Pooh poohing the obesity microbiome theory



Nutrition has fashions and the most attractive fashions are those that promise the most in terms of beneficial effects. An important determinant of durability of a nutrition fashion is the challenges it poses to experimental challenge. At present, the best example of a long living nutrition fashion is the human gut microbiome which represents all of the bacteria we house in our lower gut. Their main evolutionary basis was the extraction of energy from food carbohydrates that are not amenable to digestion by our digestive enzymes. However, in recent times these bacteria have been associated with many diseases. If you get the wrong bacteria in your gut you increase the risk of many diseases such as (non-exhaustive list: depression, anxiety, autism, cancer of the lung and colorectum, pancreatitis, liver disease and many gut disorders such as irritable bowel syndrome, Crohn’s disease and ulcerative colitis. Of particular importance is infection of the gut with Clostridium difficile which can be fatal in up to 30% of cases. Considerable success has been achieved using faecal transplants of such patients with encapsulated bacteria  from a healthy donor.

Another condition which receives considerable attention in relation to the gut microbiome is obesity The gut microflora of obese persons differ from those with a normal weight and when obese persons lose weight their gut microbe population moves in the direction of normal. But the big question is cause and effect. Does an adverse microbiome population cause obesity or does obesity cause an adverse microbiome population? In an attempt to answer that question, a recent study examined the impact of faecal transplantation of people with severe obesity (but who were metabolically healthy, with no sign of type 2 diabetes, fatty liver or the metabolic syndrome) with a capsule containing filtered faecal extract from a healthy normal weight female[1]. Twenty severely obese subjects (BMI 35+,Kg/M2) were randomly assigned to either the treatment arm (encapsulated faecal transplant) or a placebo arm (similar capsules with glycerol and colouring matter). The treatment arm began with a booster level of transplantation which was then followed by a reduced maintenance dose. They were told to eat normally and were closely monitored throughout the 12 week treatment period. Probiotics were not permitted for the study duration and for 4 weeks prior to treatment. Antibiotic treatment was not permitted for 8 weeks prior to the treatment and then throughout the treatment.

The obese patients did not lose weight. So, if the microbiome theory of obesity is correct, why not? The first question : “did the faecal transplant alter the gut microbiome composition’? And the answer is ‘yes, it did’. Faecal samples were taken at several instances during the intervention and the gut microbiome quickly resembled that of the healthy lean donor and that was sustained throughout the study. The gut-microbiome theory also states that the underlying effect is a change in the type of bile acids secreted with less taurocholic acid type bile in faeces. So did the faecal transplant cause a reduction of faecal taurocholic acid? Again, yes it did. And finally, central to the obesity-gut microbiome theory is that the obese type is that the obesity type microbiota alters the production of a gut hormone which plays a role in weight regulation, the hormone glucagon-like peptide (GLP). Did the change with treatment? No it didn’t.

Now, just as one swallow never made a summer, one experiment never copper fastened a scientific theory. But it opens the debate. It challenges the theory and that is what drives scientific enquiry. Flaws can be found in this study and the authors list a few. Maybe it wasn’t long enough for weight loss to occur. Maybe, but I doubt it since weight loss can rapidly respond to treatment. Maybe the faecal transplant dose wasn’t strong enough. Maybe, but I doubt this also, since the dose in use in the study changed the composition of the microbiota.

So I’m left with the view that more studies like this need to be completed to properly address this question. But let me leave you with my final thought. Obesity is a consequence of overeating and the caloric balance theory of obesity is to the microbiome theory what the Mona Lisa is to graffiti. To paraphrase Bill Clinton: It’s the calories, stupid.  






[1] Allegretti J et al (2019) Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients. Clinical Gastroenterology and Hepatology (In press, available online)