Dr. Sharma's Obesity Notes

Unbeknownst to many readers, the first 10 years of my research career was built largely on studying the effects of salt (or rather sodium chloride) on blood pressure.

In over 40 peer-reviewed publications, we described in excruciating detail the physiological effects of increasing and decreasing sodium intake, in many cases using single-blind randomised trial designs in hundreds of volunteers.

We not only examined the effects of salt on blood pressure but also on a wide range of physiological, metabolic and psychological parameters. We studied the effects on acid-base balance, we conducted genetic studies, we even performed in vitro studies on cells cultured from “salt-sensitive” and “salt-resitant” individuals.

In many respects, these studies left me as confused about the role of sodium on these parameters as I was before. Not that we did not report findings that helped us better understand the complex physiology of sodium homeostasis – it is just that we failed to convincingly demonstrate any major health implications of these findings. In some cases we even reported adverse consequences of sodium restriction resulting both in significant elevations in plasma lipids and insulin resistance (perhaps not surprising given that reducing sodium intake markedly stimulates both the sympathetic and renin-angiotensin systems – the very systems we seek to block to reduce cardiovascular risk).

That was almost 20 years ago – the field does not appear to be much clearer today.

Thus, although surprising to some, I must admit that I was by no means surprised by the report on sodium released last week by the Institute of Medicine, with the rather revealing conclusion that,

“…the evidence from studies on direct health outcomes was insufficient and inconsistent regarding an association between sodium intake below 2,300 mg per day and benefit or risk of CVD outcomes (including stroke and CVD mortality) or all-cause mortality in the general U.S. population.” (or any other population for that matter)

This is not to deny that despite considerable methodological problems (not least in the actual measurement of salt intake), there is evidence to support the idea that higher salt intake may affect blood pressure and possibly cardiovascular risk. However, the data is certainly  far less conclusive than food bloggers and health activists would lead us to be believe.

Not surprisingly, the same activists and organisations are now up in arms stopping just short of criticizing the scientific credibility of the IOM expert committee – no doubt, the same folks would have been applauding the conclusions of this “illustrious panel”, had the findings been more in line with their own activist agendas.

What is perhaps even more infuriating to those who have always considered the issue of sodium recommendations a slam-dunk case is the statement by the IOM that, there is in fact no basis on which to draw recommendations for the general public in recognition of the fact that significant proportions of the population may require higher sodium intakes and may even be likely to suffer harm from overly enthusiatic sodium restriction.

While I have no illusions that this report will in any way put the century old debate to rest (indeed the report calls for further research), I think that there is a much bigger message in this report that should let us tread cautiously when it comes to dietary recommendations in general.

Let us remember that associations (on which so many of our assumptions about healthy diets depend) simply do not prove causality, even when backed by seemingly plausible biological hypotheses derived largely from rodent toxicology. We should also remember that fancy statistical predictions on the vast number of lives lost or saved by altering the population intake of this or the other nutrient, are generally based on sometimes rather heroic assumptions that may well explain whey they are rarely (if ever) borne out by actual interventions.

Thus, whether we are talking about salt, fat, carbs, sugar, fibre, gluten, calcium, Vit D, dairy or red-meat, a degree of humility in advocating for policies and other measures to reduce or increase this or the other is generally in order.

Seldom in the field of nutrition are things as cut and dried as some will have us believe – if only food were as simple as tobacco.

AMS
New Delhi, India

Disclaimer: I was invited to be on the IOM Expert Committee but had to decline due to other obligations.

“Cardiometabolic” is a term that is often used (often synonymous with “metabolic syndrome”) to describe the constellation of cardiovascular risk factors (many of which happen to be metabolic).

A study by Teoh and colleagues from across Canada, published in the Canadian Journal of Cardiology, examined risk assessment and management patterns by primary care physicians, working both in primary care teams (PCT) and in solo practice.

Based on an analysis of almost 2,500 patients (40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least 1 of the following: dyslipidemia, type 2 diabetes mellitus (T2DM), or hypertension.), most (~90%) were abdominally obese and at least 52.2% had metabolic syndrome.

Cardiovascular risk, was often miscalculated and behavioural modification was recommended in fewer than 50% of patients (compared to pharmacotherapy in >70%).

Overall, guideline-recommended control of cardiometabolic risk factors was achieved in only about 10% of patients.

Not surprisingly, the authors are not happy about how obesity and cardiovascular risk is currently being assessed in primary care and call for a paradigm change in assessing and managing obesity and cardiovascular risk with more aggressive lifestyle interventions.

While this is certainly a laudable goal, there is ample evidence that simply telling people to “eat-less-move-more” is not the answer. In fact, even simply putting more allied health into these teams may also not be the answer.

As the authors note,

“We found that evidence for exercise and nutrition counselling aimed at encouraging sustained negative energy balance was disappointingly infrequent. This was surprising because 5 PCTs had a diabetes educator and 7 had a dietitian on staff or as part of the extended care program.”

In fact, it was particularly surprising to note that,

“Management of CMR factors appeared to be no more effective in PCTs compared with the more traditional Solo practices.”

Thus, the paradigm shift is probably not so much in recognising the importance of “lifestyle” interventions but rather in their delivery – so far I have yet to see a successful sustainable delivery model outside of the rather artificial constraints of clinical intervention trials that demonstrate “successful” lifestyle management.

This is not to say that “lifestyle” interventions cannot significantly improve cardiometabolic risk factors. However, the effort to achieve and maintain these changes in clinical practice in enough patients to make a significant impact on outcomes is generally underestimated.

Not to say that such a model may not not exist in some corner of the earth – it is just that most health systems have yet to figure out how to do this.

AMS
Edmonton, AB

Teoh H, Després JP, Dufour R, Fitchett DH, Goldin L, Goodman SG, Harris SB, Langer A, Lau DC, Lonn EM, John Mancini GB, McFarlane PA, Poirier P, Rabasa-Lhoret R, Tan MK, & Leiter LA (2013). Identification and Management of Patients at Elevated Cardiometabolic Risk in Canadian Primary Care: How Well Are We Doing? The Canadian journal of cardiology PMID: 23465284

Few events are likely to command your attention as urgently as a sudden interruption of blood flow to your heart muscle.

Fortunately, thanks to the miracle of modern cardiac revascularization, you may well find yourself amongst the many, who today survive this “heart-wrenching” event – a situation which often precipitates remarkably intense longings for lifestyle change.

Indeed, at no time (other than January 1), would you meet anyone more determined to swear off their cigarettes, convert to the solemn teachings of Canada’s Food Guide and embrace the rejuvenating powers of exercise – an only fitting response to celebrate this new lease on life.

This is why many modern health systems dedicate a significant amount of personnel and resources to the exploitation of this life-changing moment with the laudable goal of “re-habilitating” the fortunate survivor to a life of healthier habits.

But, you may ask, is even such a dramatic event enough to prompt lasting betterment in the victims? And, will those, who have brought this upon themselves through their supposedly unholy practice of gluttony and sloth, really manage to turn things around?

This burning question has now been thoroughly examined by Billie-Jean Martin (a former Obesity Network Bootcamper) and colleagues from the University of Calgary, in a paper published in OBESITY.

Happily enough, almost 4,000 participants, studied one year after their participation in a 12-week rehabilitation program (which invoked the dedicated services of exercise physiologists, nurses, registered dieticians, social workers and clinical psychologists), did indeed experience a small but measurable improvement in aerobic fitness – a parameter known to forecast survival.

Sadly, however, not everyone benefitted equally. Despite enthusiastic participation in the program, obese patients (who also happened to start off on a poorer footing in terms of exercise capacity) showed a lesser sustained improvement in peak estimated metabolic equivalents (a sciency measure of aerobic fitness) than their less corpulent counterparts.

Prejudiced readers should, however, not jump to the conclusion that the obese participants were perhaps less enthusiastic or committed to this enterprise.

Indeed, during the 12 week intervention, the obese group increased their weekly mins at the prescribed exercise heart rate by 40 mins (from 123 to 163), whereas their leaner peers merely managed to add a measly 10 mins to their routine (from 153 to 164). Clearly, the obese participants were not shying away from the extra effort – if anything, they were working substantially harder (relatively speaking) than their leaner colleagues.

Notably, at one year, BOTH groups had regressed in their enthusiasm to slightly BELOW their baseline weekly mins of exercise heart rates; the obese group fell back to 121 mins, while the normal weight group fell back to 150 mins.

Thus, to be fair, NEITHER group managed to sustain the recommended 160+ mins of weekly exercise heart rate at 12 months.

It would seem that neither the “life-changing” occurrence of clogged coronaries nor 12 weeks of the dedicated services of an inter-disciplinary team of healthcare professionals, appears to be all that life-changing after all.

Would a 16 week program, a 24 week program, or perhaps even a 52 week program have lead to better results?

My gut tells me that any “time-limited” behavioural-change program will always produce “time-limited” behavioural change.

Apparently, the situation for cardiac rehab appears no better than the story for weight loss – when “treatment” stops, the lifestyle/weight comes back.

Incidentally, the Albertan actors in this story are no better or worse than the rest of Canada.

According to a recent report from Statistics Canada, three in four smokers with respiratory disease do not quit smoking; most people with diabetes or heart disease will not become more physically active and virtually no one diagnosed with cancer, heart disease, diabetes or stroke will increase their intake of fruit and vegetables.

Nonetheless, I am told, cardiac rehab efforts have demonstrated benefits in a host of modifiable cardiovascular risk factors, at least during and perhaps for a few months following the intervention.

However, the durability of these efforts certainly leave substantial room for improvement across the full spectrum of body shapes and sizes.

AMS
Edmonton, AB

Martin BJ, Aggarwal SG, Stone JA, Hauer T, Austford LD, Knudtson M, & Arena R (2012). Obesity negatively impacts aerobic capacity improvements both acutely and 1-year following cardiac rehabilitation. Obesity (Silver Spring, Md.), 20 (12), 2377-83 PMID: 22627915

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Regular readers will note my past interest in hypertension, especially with regard to managing this condition in people with excess weight.

A paper by Michael Weber and Colleagues, now presents an analysis of the relationship between body size and hypertension treatments on cardiovascular event rates, in a paper published in The Lancet.

The paper consists of a prespecified analysis of the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial, that compared the effect of single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine on hard cardiovascular outcomes.

Based on BMI, the full ACCOMPLISH cohort was stratified into obese (n=5709), overweight (n=4157), or normal weight (n=1616) categories.

In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients.

In contrast, there were no differences in outcomes between the BMI groups in those allocated benazepril and amlodipine(18·2, 16·9, and 16·5, respectively).

From these findings the authors conclude that.

“..thiazide-based treatment may give less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension.”

Given the known differences in physiology, where obesity related hypertension is largely mediated by volume expansion and sodium retention, these findings may not be all that surprising.

Clearly, including a diuretic in the treatment regimen for obesity related hypertension makes a lot of sense – now we have the outcome data suggesting that such a regimen also reduces hard outcomes.

AMS
Calgary, Alberta

Hat tip to Scott Kahan for alerting me to this study.

One of the hypotheses that I developed in the early 2000′s, based on the finding that adipose tissue produces a number of molecules that can directly affect vascular function, was that perivascular fat (found around virtually all blood vessels down to the tiniest arterioles) may play an important role in mediating tissue blood flow.

In a collaboration with Dr. RM Lee at McMaster, in 2006, we published a paper in Cardiovascular Research, in which we reported our finding that perivascular adipose tissue may promote vasoconstriction through the production on superoxide anion.

Using rings of superior mesenteric artery (MA) we fount that rings with intact perivascular adipose tissue (PVAT (+)) showed a greater contractile response to electrical field stimulation (EFS) than rings with PVAT removed (PVAT (-)).

Furthermore, superoxide dismutase (SOD) reduced the contractile response to EFS more in PVAT (+) MA than in PVAT (-) MA.

Inhibitors of NAD(P)H oxidase and cyclooxygenase exerted a greater inhibition on EFS-induced contraction in PVAT (+) MA than in PVAT (-) MA.

We also found that inhibitors of tyrosine kinase (tyrphostin A25) and MAPK/ERK (U 0126) attenuated EFS-induced contraction in PVAT (+) MA in a concentration-related manner, while inactive forms of these inhibitors (tyrphostin A1 and U 0124) did not inhibit the response.

Exogenous superoxide augmented the contractile response to EFS and to phenylephrine in PVAT (-) MA, and this augmentation was blunted by inhibition of tyrosine kinase and MAPK/ERK.

Finally, EFS increased superoxide generation in isolated PVAT and PVAT (+)/(-) MA, which was attenuated by NAD(P)H oxidase inhibition.

We also used RT-PCR to demonstrate the mRNA expression of p(67phox) subunit of NAD(P)H oxidase and immunohistochemical staining confirmed its localization in the adipocytes of PVAT.

Thus, we were able to show that PVAT enhances the arterial contractile response to perivascular nerve stimulation through the production of superoxide mediated by NAD(P)H oxidase, and that this enhancement involves activation of tyrosine kinase and MAPK/ERK pathway.

Since then, many other laboratories have explored the role of perivascular fat in the regulation of vascular function and this has become quite an area of interest for many labs around the world.

According to Google Scholar, this paper has been cited 69 times.

AMS
Gioâna, Brazil