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Fecal Transplants Need The Right Support

The fact that the gut microbiota plays an important role in digestion and metabolism should by now be common knowledge. There is now also abundant evidence that obesity is associated with a rarefied microbiome, the causes for which are not entirely clear. 

One of the more adventurous approaches to rectifying this issue has been the idea of using fecal transplants from lean people in an attempt to ‘repoopulate’ (pardon the pun) the gut of people living with obesity.

In one such study by Valentin Mocanu and colleagues from the University of Alberta, in which I happened to be peripherally involved, now published in Nature Medicine, suggests that it may not be enough to just transplant the bugs, but that you also need to support them.

The double-blind study involved 70 volunteers with severe obesity and metabolic syndrome, who were randomised into two groups, one receiving fecal transplants from lean donors (in the form of capsules) vs. placebo capsules. Each of these groups were then further randomised to receive daily supplements of either high-fermentable (HF) or low-fermentable (LF) fiber over 6 weeks. 

This treatment resulted in a significant improvement in HOMA as a measure of insulin resistance in the Fecal-Microbial-Transplant-Low-Fermentable fibre group (FMT-LF), with no changes in any of the other groups. In addition, there was also restoration of the physiologic patterns of GLP-1 secretion in the FMT-LF group. 

As for the microbiome itself, the FMT-LF intervention was associated with increases in bacterial richness (Chao1 index) from baseline to week 6 with the FMT-LF intervention resulting in changes in seven genera and 12 amplicon sequence variants (ASVs), several of which were detectable at week 6, including increases in the relative amounts of Phascolarcobacterium, Christensenellaceae, Bacteroides and Akkermansia muciniphila and decreases in Dialister and Ruminococcus torques.

Most of these changes were no longer apparent after 12 weeks. 

As for why these changes were only seen in the FMT-LF group, the authors have the following speculation to offer,

Possible explanations include the ability of cellulose to act as a bulking and binding agent, which could alter metabolite luminal concentrations, influence gastrointestinal transit and modulate the donor microbe–host mucus layer interface. Cellulose supplementation may also directly alter the function of specific taxa, including cellulose-degrading H2-producing methanogens, leading to changes in gut microbial fermentation efficiency and by-products. Together these factors might constitute mechanisms through which the FMT-LF intervention increases microbial diversity and richness while also potentially inducing functional changes in taxa associated with host HOMA2-IR/IS improvements.

Irrespective of the actual mechanisms, the study does suggest that daily low-fermentable fiber supplementation may be needed to support an FMT intervention to  improve insulin sensitivity, and may perhaps act by differentially modulating engraftment of select bacterial taxa and the enteroendocrine axis. 

Whether or not this approach will ever translate into a viable treatment for patients with metabolic syndrome remains to be seen. 

@DrSharma
Berlin, D

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What Does Exercise Do To Appetite?

Although there is now a solid body of evidence showing that exercise alone has a rather minimal effect on body weight, I have met countless people who swear by how exercise helped them lose weight. Indeed, ‘not enough exercise’ is one of the most common ‘excuses’ I’ve heard from my patients and ‘I need to exercise more’ is probably the most common solution that patients consider for losing weight. 

And clearly, there are those patients, who have lost significant amounts of weight with exercise, which simply cannot be explained by the number of calories burnt (which is generally far less than most people think). 

This led me, several years ago, to postulate the hypothesis that some people lose weight when they begin an exercise program because it reduces their appetite, thus resulting in lower caloric intake. 

However, as much as I love this hypothesis, it seems that the overall effect of exercise on appetite and energy intake is pretty neutral, at least according to a meta-analysis by Kristine Beaulieu and colleagues published in Obesity Reviews.

The researchers reviewed 48 articles that reported the relationship between an exercise intervention and changes in caloric intake, appetite, hunger, satiety, and other features of ingestive behaviour. 

Despite noting that the vast majority of these studies were sadly of rather poor quality, there did not appear to be any significant impact of exercise on caloric intake – in either direction!

While this finding is consistent with the fact that exercise very seldom leads to any significant change in body weight, it does pose the questions of a) why some people claim that exercise helped them lose vast amounts of weight, and perhaps b) why regular exercise is associated with a greater likelihood of keeping weight off. 

As the authors discuss, there are several influences of exercise on ingestive behaviour that may need to be considered (and for which there is some evidence). These include an improvement in satiety quotient as well as potential reduction in overconsumption due to alterations in impulsivity, dietary restraint, food reward/preferences, as well as the notion that the increased energy flux induced by exercise could generate better control of eating behaviour.

However, these mechanisms appear to be, on average, rather minimal in that they may support individuals attempting to reduce their caloric intake but on their own are unlikely to do so.

Obviously, irrespective of any effects on appetite or body weight, the health benefits of regular exercise are indeed profound and manifold. This applies to people of all shapes and sizes. So please don’t get discouraged when your exercise routine does not move those numbers on the scale. 

DrSharma
Berlin, D

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What German General Practitioners Believe About Obesity

Like most doctors, German docs are not particularly knowledgeable about the rather complex biology and psycho-sociology of obesity. However, they do appreciate that obesity is an important health problem, very much relevant to their practice. 

So how do they feel about it and, perhaps more importantly, what are they doing to address it?

This question was examined in a recent qualitative study by Julian Wangler and  Michael Jansky from the University of Mainz, published in the European Journal of Clinical Practice.

For their study, the researchers conducted interviews with 36 German general practitioners about their attitudes, behaviours and strategies towards patients with obesity.

Based on their analysis of the interviews, four types of physicians were identified.

Type 1 were those they described as “The Resigned” – these were doctors who had essentially given up and placed the blame squarely on the shoulders of their patients.  Interviewees in this group went as far as to emphasise that obesity was ‘not a disease like any other’, but rather due to character predisposition involving living to excess or the ‘urge to let themselves go’. They viewed interventions as largely futile, mainly because patients were unwilling to take responsibility. Years of frustration with these patients has led them to doubt whether general practitioners can manage this type of patient effectively. Instead, they see a role for specialists using drugs, psychotherapy or possibly surgery as the final option.

Type 2, called “The Instructors” were doctors who attributed obesity largely to a combination of life circumstances and predisposition, and viewed structured exercise and diet programmes for their patients as delivering the best results. These doctors were often connected to a network of exercise and dietary practitioners resources in the community to which they could refer their patients. However, rather than providing continuous patient consultation at close intervals, they encouraged a ‘focussed and concentrated jump-start’ to ‘set the scenes for consistent and gradual weight loss’ in an individually matched motivational exercise programme. This group of doctors appreciated the use of health apps but was vehemently opposed to the use of medications or surgery, due to the risk of ‘yo-yo effects’.

Type 3, called “The Motivators”, were likewise opposed to the use of medication or surgery, but did have a far more favourable view of people living with obesity than “The Resigned”.  Not only did they recognise the importance of sensitive communication and a collaborative approach to the doctor–patient relationship, but also felt that it is essential to provide enough time for consultation and remain accessible, even with treatment setbacks. Interviewees in this group had sometimes undergone additional training in psychotherapy and psychoanalysis and believed that this knowledge played a valuable role in successful long-term obesity management. 

Type 4, “The Educators” were a mix between Type 2 and Type 3, but placed their bets on the importance of prevention rather than treatment. Although they provide support and care, this group was far more sceptical as to the success of treating obesity once it was established. Rather, they saw it as best to intervene early and to take regular health check-ups as an early warning system very seriously. Some in this group had undergone further training in nutritional medicine. For this group, the issue of medication or surgery did even not come up. 

Irrespective of their “Type”, there was a general sense that ‘successful obesity patient management was often time-consuming, requiring a high level of medical commitment with new attempts at treatment after previous attempts had failed.’  Furthermore, all interviewees decried the severe lack of supporting structures and care services for preventing obesity and managing treatment in primary care.

While this categorisation of primary care practitioners with regards to attitudes and approaches toward obesity management is very informative (if not unexpected), it should concern us that none of these groups appear convinced of the need for or the effectiveness of medications or surgery. Rather, they appear stuck in a world where behavioural or “lifestyle” approaches (with varying levels of motivational, educational, psychological,and community support) are still viewed as the most effective treatments for this chronic disease. 

This not only reflects their individual professional and perhaps personal biases toward obesity and people living with obesity, but also highlights the fact that we still have a long way to go before medical treatments including medications and surgery become the accepted mainstay of obesity management, similar to other chronic diseases for which such treatments exist.

@DrSharma,
Berlin, D

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How Many Years Can Bariatric Surgery Add To Your LIfe?

Yesterday, I discussed the impact of bariatric surgery on life expectancy in Ontario, Canada, which showed a clear positive impact on reducing overall mortality, particularly from cardiovascular disease and cancer. 

But this study is by far not the only data we have on this issue. In fact, a recent meta-analysis by Nicholas Syn and colleagues, published in The Lancet, should dispel any remaining doubts as to the overall impact of having bariatric surgery.

The authors looked at data from over 170,000 participants across 16 matched cohort studies and one prospective controlled trial (the one from Ontario not included!), representing over 1,2 Million patient years. 

Overall bariatric surgery was associated with a reduction in hazard rate of death of 49·2% with median life expectancy being 6·1 years longer than with usual care. In fact, for patients with diabetes, life expectancy was 9.3 years longer (compared to 5.1 years longer in participants without diabetes).

Based on these observations, the numbers needed to treat to prevent one additional death over a 10-year time frame was  slightly greater than 8 for those with diabetes vs. 30 for those without diabetes. This, by any measure, puts bariatric surgery squarely in place as one of the most effective treatments for any serious condition in all of medicine!

In an interesting extrapolation of these results to the global pool of potential surgery candidates, the authors project that even just a 1% increase in rates of bariatric surgery, could translate into 5.1 to 6.6 millions potential life-years saved. 

To anyone who would still prefer to pooh-pooh this vast body of evidence, because they only “believe” in randomised controlled trials, the authors point out that,

Randomised clinical trials with sufficient power to assess a rare outcome such as mortality are unlikely to ever be done because such studies require large sample numbers, long-term follow-up spanning decades, and are prohibitively expensive.

So, this may well be the best evidence we may ever have on this issue – take it or leave it.

Either way, finding a justification to deny or discourage patients with severe obesity from seriously considering surgery as a treatment for their chronic disease is becoming increasingly untenable. 

@DrSharma
Berlin, D

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Saving Lives With Bariatric Surgery ?

In all of my years of working with patients who have undergone bariatric surgery, the most common regret I got to hear was, “I regret waiting so long before deciding to have it”.

While people who have had surgery often look back on the years of good life lost due to their obesity, the good news is that we now have an increasing body of evidence showing that having bariatric surgery does likely increase your life expectancy, thereby increasing your overall lifespan. 

Case in point is the recent paper by Aristithes Doumouras and colleagues from McMaster University, Hamilton, Ontario, published in the Annals of Internal Medicine, showing that undergoing bariatric surgery is associated with a significant reduction in overall mortality.

In this observational study, the researchers compared outcomes in over 13,000 patients who underwent bariatric surgery in Ontario, Canada (which has a public healthcare system), to over 13,000 non-surgical patients matched for index date, age, sex, BMI, diabetes status, and diabetes duration. 

As is typical for most bariatric patients, more than 80% were female, with a mean age of around 45 years and a baseline BMI of 47. Gastric bypass was the most common procedure (87%) with the rest receiving sleeve gastrectomies.

After a median follow-up of just 4.9 years, the overall mortality rate was 1.4% (n = 197) in the surgery group and 2.5% (n = 340) in the non-surgery group, with a lower adjusted hazard ratio (HR) of overall all-cause mortality (HR, 0.68 [95% CI, 0.57 to 0.81]). 

The risk reduction was even greater in patients aged 55 or older with a lower HR of mortality in the surgery group (HR, 0.53 [CI, 0.41 to 0.69]). 

Much of this reduced mortality risk was attributable to lower cardiovascular mortality (HR, 0.53 [CI, 0.34 to 0.84]) and lower cancer mortality (HR, 0.54 [CI, 0.36 to 0.80]).

Although the nature of observational studies is such that one should be cautious in jumping to conclusions regarding causality, the data do strongly support the notion that bariatric surgery may indeed save lives. 

This is not to say that bariatric surgery is entirely without risk – after all, it is still major surgery, where things can always go wrong. On the other hand, for people living with sever obesity, having bariatric surgery appears to be the less risky option, at least as far as mortality is concerned. 

While these data are both impressive and reassuring, one must keep in mind that bariatric surgery is not a cure for obesity. Rather, it is just one step in the management of a life-long chronic disease. 

Unfortunately, despite being offered in a public healthcare system, like virtually everywhere else, post-surgical follow-up and care in Ontario is haphazard and suboptimal, leaving considerable room for improvement. One could well imagine that improving follow-up care may further increase the long-term benefits of undergoing bariatric surgery. 

Nevertheless, it appears that failure to counsel patients with obesity regarding the potential benefits of undergoing bariatric surgery (with reduced mortality being just one of the benefits), can no longer be considered evidence-based practice.

@DrSharma
Berlin, D

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What A Lottery Winner Registry Can Teach You About Winning A Lottery

Clearly the vast majority of people who buy lottery tickets never win – however some do. In fact, there are tens of thousands of people out there who have defied the odds and have indeed held the winning ticket – there are even people who have had a winning streak and won the lottery several times over.

How can we emulate this success? Well, as a first step, we could create a National Lottery Winner Registry, where anyone with a significant lottery win can sign up and answer a bunch of questions regarding their demographics and winning strategy. 

From this vast database of real-life lottery winners, we can surely deduct commonalities that should guide us in our own lottery endeavours. 

As it turns out, there are indeed important features that all lottery winners share – for one, they all held at least one ticket! Most had played the lottery several times before winning (although there were some lucky exceptions). Many bought more than one ticket. Many (especially those with lower winnings) played lotteries with better odds. A substantial number of winners participated in lottery pools. 

On the other hand, there is also a long list of strategies that seem to have worked particularly well for some people. For e.g. some have always played the same numbers, while others have taken pains to chose different numbers every time. Some chose to bet on birthdays whilst others preferred anniversaries. Some bought their tickets early, others waited to the last minute. Some always bought their tickets at the same gas station others chose a random location. Some had more complex game plans and strategies others just trusted their guts or happened to feel lucky that day.

Nevertheless from these interesting data derived from proven “winners” we can certainly create a list of sure-fire strategies that should allow us to follow in their footsteps:

  1. Buy at least one ticket
  2. Buy more tickets if you can
  3. Play low-odd stakes
  4. Be persistent, if your ticket does not win, buy another one
  5. Do whatever works for you.

With this important information gleaned from my Lottery Winner Registry I should surely now be in a much better position to win the next lottery.

If the above seems rather absurd to you, then you’re not wrong. 

On the other hand, some of you may be wishing you had your own Lottery Winner Registry – after all the approach sounds pretty sensible (not to mention scientific!). 

Sadly, while we may not have a National Lottery Winner Registry, what we do luckily have is a National Weight Control Registry, which works pretty much along the same lines. 

You find the few lucky people who have apparently won the long-term weight-loss lottery and ask them how they did it. 

From this we have indeed learned a few things that should be helpful to anyone trying to beat the odds of long-term weight loss.

  1. Eat less – somewhere around 1400 KCals a day
  2. Move more – somewhere around 350-400 KCals a day
  3. Weigh yourself regularly (though how often is pretty much up to you)
  4. Find a strategy that works for you and stick with it (this one is really important!)

Now, with these important insights in hand, anyone should be able to emulate the remarkable success of our long-term weight-loss lottery winners.

But most importantly of all, don’t let anyone ever tell you that long-term weight loss with behaviour change is not possible – after all, these folks have all done it using the above fool-proof strategy, so please, no excuses!

I’m off to buy a lottery ticket.

@DrSharma
Berlin, D

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