Managing Your Risk: The Obesity Paradox – Can Genetics Provide a Clue?

Managing Your Risk: The Obesity Paradox – Can Genetics Provide a Clue?


Paradox, when thinner means sicker and
heavier means healthier. Now, wait a minute.
That’s just – that sounds like this is the opposite of what you hear from everybody
all the time including most of my videos on this channel. Well, now think about it. There are places where this occurs. In
fact, I’ve got a video from a New England Journal article titled “Heavier but
Healthier.” In that video, they did the research showing that yes, people that
stop smoking gain weight. Even though they gain weight, they’re clearly
healthier than they were prior to stopping smoking. So what’s going on
there is you’re obviously weighing the risk of obesity versus a much heavier
risk of smoking on your metabolism. Now, is this a collection of examples like
that? I would say yeah there’s a lot of that component to it, but it’s also still
a significant debate when – within the medical community, preventive medicine
community. I will tell you this. It’s actually as I’ve seen it and I’ve been
through this some of the science behind these discussions. I really feel like
it’s more often used as – as a justification for keeping weight for
having weight but we’ll talk about that a little bit later as we get to the end
and we start bottom lining it. Now, this is a book by Dr. Carl J. Lavie. Dr. Carl J. Lavie is
not a – he’s not an – an untrained doc. He’s not a non expert who’s just written some
inflammatory stuff. He’s a well-respected endocrinologist that covers some data. In
fact, if you look at nature magazine, a very very well-respected
magazine, he – he’s co-authored a significant review article on this topic,
“Healthy versus Unhealthy Lean: The Obesity
Paradox in Nature Reviews Endocrinology.” If you look at the – just
the title and abstract, again you see Carl J. Lavie there. The title 2015 and again
not a lightweight Journal at all. The nature magazines are one of the most
well-respected magazines in science in the world. Now, I’m going to skip over
some of the text on here. It basically is just saying, look, overweight and obesity
of reach epidemic proportions in the US and most of the rest of the world; and
here’s where the paradox comes in. “Some individuals with obesity can be
considered healthy with regards to their metabolic and cardiorespiratory fitness
which has been termed the obesity paradox.” Now, those of you who are
beginning to think of the Schwarzenegger adjustment to BMI are thinking exactly
along the right terms. Before the Schwarzenegger adjustment came up, people
said, you know what everybody with BMI in the high 20s 30s and above has a health
problem. Other people began to say, wait a minute what if you’re built like Arnold
Schwarzenegger? You don’t have fat or Schwarzenegger during his prime. You
don’t have fat, I don’t think he has much fat right now either. Is it the fat or is
it the mass? Originally, there was some question about maybe that muscle creates
burden on the heart as well. No, it’s the fat mass and that’s part of what’s
going on here. Now, they’re going on to say look there are people that have
significant fat mask – mass that are still healthier than people that are
light weight. We just covered one of those situations. We’ve covered a couple
of articles for example in in a population in China where there was
some similarities, but again, what are the – what are some details around this? This
is the crux of the debate. So his article goes on to discuss the suggestion that
greater emphasis should be placed on improving fitness rather than weight
loss per se in the primary and secondary prevention of cardiovascular disease. At
least in patients with overweight in class 1 obesity. In other words, for
people that are just a little bit overweight, should we focus more on
exercise or should we focus on weight loss? And will again get to the bottom
line on that a little bit later. This is another article that has contributed to
this debate and it brings up a very interesting technique. This is a session –
it’s in JAMA, the Jama Network, and again JAMA is no lightweight either. This is
association between obesity and cardiovascular outcomes. It’s a
systematic review and meta-analysis using of articles that use Mendelian
randomization studies. Now, what is that? Well here’s – here’s going to be a
significant component of this video. We’re going to talk about Mendelian
randomization studies. Now, if we were going to – this is a comparison between
Mendelian randomization and randomized clinical trials. If we were going to say,
“look, we want to find out whether obesity causes heart disease or if it’s just
related to it.” Then you would have to set a control population and a study
population. In this study population, you would have to make these people obese.
You’d have to randomize between the two and you’d have to keep people blinded to
whether or not they became obese, them and their doctors. Well that’s never
gonna happen. Neither one of those – you’re not gonna
make people, you’re not gonna select people at random
and make them obese; and you’re certainly not going to be able to blind people or
their Doc’s to the fact that they’ve become obese. So how do we deal with this?
There is a type of epidemiology that has begun to blossom in this age of genetics.
And it’s based on the fact that, there are genes associated with certain
medical outcomes. For example, there are genes for blue – blue eyes, green eyes, etc. Well,
there’s also a random mix. We have – we’re assuming in Mendelian randomization, that
there’s a random mix of genes. So whether you got blue-eyed genes from your mom or
dad or brownout genes for your mom and dad, basically, for the most part occurs
at random. So, let’s go back and look at something that we know we’ve heard of
c-reactive protein. There are genes that cause elevated c-reactive protein. Basically what they do, it appears that
some of them create more cause the – you to create more CRP, other ones just cause
you to not break down CRP. So they’ve looked at that using Mendelian
randomization. And the evidence is, that CRP doesn’t cause heart disease, it’s a
marker for heart disease. Now, how did they know that? Well they took a
population, a large population and separated them out. The people that have
genetic reasons for a high CRP and they look to see if they tend to have higher
heart attack rate risk. They did not. Then they looked at the people that did not
have the genetic – genetically high CRP. They had the same heart attack risk as
the first. However, we know and again if you don’t
know this then you need to see some of our other videos then you need to take
the inflammation panel or the inflammation course. We know that when
CRP increases in somebody, their risk for heart attack and stroke is increasing.
And that’s what you see in this – this image right here- circulating usual
concentrations of CRP. If those are increased, adjusted for age, sex, ethnicity
and other adjustments. If those are increased, you have an increased risk
beyond normal for a heart attack. Now, how about people that have
genetically raised concentrations of CRP? They don’t have that increased risk for
heart attacks. So yes, CRP is associated with it but something else is causing
the elevated CRP in these people up top because – causing you to have an increase
beyond your normal CRP. It’s also causing heart attack and stroke risk.
Well again, you should – we should know that, That’s inflammation. Inflammation
can cause both elevated CRP and it causes heart attack and stroke risk. So
if you have genetic elevation of CRP, that’s not going to cause the risk.
That’s the basics of Mendelian randomization. So let’s go back like this
study and apply that whole concept to obesity and heart attacks. That’s exactly
what they did here, and in fact they did a meta-analysis. They ended up finding
several studies that actually did this activity. Sources they used for data
where MEDLINE and Scopus study selections as you can imagine, as we’ve
talked about, they wanted to find studies that link to both that study
the linkage between obesity and heart attack and stroke; and also looked for
obesity related genes and there are obesity related genes, just like there
are CRP related genes. At the – at the end, they had about the studies themselves.
There were 406 – 4660 potentially relevant articles. Only 2500 titles were given
proper screening; seven studies were included and five studies at the end of
this actually covered all that we needed to see or all that the authors needed to
see to look at Mendelian randomization. You may say, well five studies that’s not
very many but again we’re talking about large population Genome-Wide Association
Studies (GWAS). So huge number of people, 881, 692 participants. Now, here’s what they found. Obesity is
associated with type two diabetes and coronary heart disease. It did not show
that same linkage for strokes. Now how could that be? Well we have already seen,
there are some, there’s a huge overlap in terms of risk for stroke versus risk for
heart of – heart attack in type two diabetes; and we know that type two
diabetes is a risk for both heart attack and stroke. We also know however that
there is not 100% overlap between the two. Atria fib for example, it tends to
have more of a risk for stroke. Hypertension tends to drive more stroke
risk. So again, there’s not a 100% overlap between heart attack and stroke. So that
certainly may be a real item or it may have just been something that washed out.
It’s just are looking at the articles. Now, we got
into a lot of detail. Again, a lot of the geeks, a lot of people that are fairly
sophisticated in this area and that’s a lot of my viewers. They’re going to be
very interested to see that and I’ll provide you the links so you can go read
that yourself; but let’s go back. We talked about bottom line. I get a lot of
grief about bottom line at Brewer so let’s do just that and I’m trying to
find that. Okay, so this is back to the Levere – is it Lavie? The – yeah – the Lavie
article. He did go into some key points and I think it’s worth going over those
key points because the last one is the bottom line.
First, the prevalence of obesity has increased in most of the world, past few
decades. Patients with obesity have more cardiovascular risk and metabolic risk
and it’s being driven by the fat mass, fat cells have an impact. They tend to
drive insulin resistance. Data suggests that metabolically healthy of – obesity
especially with combat – when combined with a high level of fitness is
associated with at most (excuse me) a minimal increase in overall risk for
cardiovascular disease and mortality. In patients with – with established
cardiovascular diseases and other chronic conditions such as kidney
disease, severe arthritis. Those with overweight, overweight in class one
obesity, in other words a little bit of obesity, tend to have a better prognosis.
Does that mean that if you’re staying in shape, you’re thin, you have a couple of
these you want to gain weight? No it doesn’t mean that and again we’ll talk
about that in just a minute. Fitness is more important than fatness
for a long term prognosis. In the obesity paradox, fitness markedly alters the
relationship between adiposity or in other words being obese and long-term
health outcomes. In other words, metabolically having
fat mass does drive things like insulin resistance. However, being in shape
exercise is a – is a huge antidote vaccine for that, basically. And here’s the bottom
line, here’s the last comment: “Despite accumulating evidence on the obesity
paradox, the available data still support purposeful weight loss for long-term
health. Particularly when combined with increased physical activity, muscular
strength and fitness.” For those of you who are interested in some of these a
little bit deeper more nuanced debates and – and discussions, this reminds me of a
book called, “The Sports Gene”. In The Sports Gene, the author basically deals
with Malcolm Gladwell’s comment about the 10,000 hour rule. Malcolm Gladwell
said in the 10,000 hour rule, look, if you play a sport for 10,000 hours you can
get to professional level. It’s practice, practice, practice.
And there’s – there’s a lot of truth to that but the author of the sports gene
shows case after case after case where it’s both. So for example, I could
practice 10,000 hours of basketball. I’m still not gonna become a LeBron James.
Now, I just don’t have the genetics. I’m 5’10” not 6’10” ain’t – I’m not gonna get
there! However, there are also people that have genetics compatible and competitive
with somebody like LeBron or another basketball star but they’re not
basketball dominating basketball stars. Why is that? Because they didn’t practice
10,000 hours or 15 or 20,000 hours. So the bottom line is, it takes both. How
about the obesity paradox? Should we lose weight or should we exercise? Bottom line,
both! Thank you!

7 thoughts on “Managing Your Risk: The Obesity Paradox – Can Genetics Provide a Clue?”

  1. Dr. Brewer, this is another very educational video. Thank you for introducing us to the "Mendelian Randomization" concept. This is the first time hearing of it and it makes perfect sense. Is there a catalogue or reference document listing SNP with typical biomarkers? It could be quite helpful when discussing labs with physicians. Maybe this would be a good project for a "retired" doc. 🙂

  2. Hi Doc, could you review this book “The New Testosterone Treatment: How You and Your Doctor Can Fight Breast Cancer, Prostate Cancer, and Alzheimer' ”

  3. I was getting pretty ripped last November or December. But, however, I could not loose the love handles, so I looked into lipo costs. Then, fortunately, I saw the video by "Stuff I learned", YT channel, on the Japanese diabetes paradox. This got the liposuction desire out of my head. I now look at my- impossible to loose- love handle fat as a vital body organ to store excess sugar, in an emergency. Much better than stuffing it between the organs in the abdomin. The visceral, organ fat is the bad guy….. You know my recent experience with watching the end game of a few decades of sugar spikes (encouraged by diabetic dieticians) , and my horror.

  4. A timely video. At 65 yo with a number of metabolic syndrome issues, at the beginning of the year, I started to do Keto to reduce mass and BG. That has worked to a point. Dropped 230 to 210lbs, A1c is 5.1 w/500 Metformin x2 and Berberine 1000 /day from 6.0-6.5. Just as I was about to do my quarterly BW, I did the 23&me DNA and ran it through Dr. Patrick's genetic assessment. Genetics says I'm not a good match for saturated fat, and the BW shows a good kick up in the Cholesterol panel including TG. 10k of daily Vit D w/K7 isn't as effective per genetics and BW, D is 49. Genetics says morning fast BG is a challenge, and I can go to bed and wake up with +15. Genetics says I need Vit E.

    I need to look at the Genetics in more depth!

  5. I used to weigh 425 and I’m down to 371. My a1c was 7.9 now it’s down to 5.8. I do have chf and on entresto. It actually saved my life. I’m 5’11”. I went in Atkins and my kidney function was really bad. I lost weight but I think the high protein hurt my kidneys. My kidney disease was 3 now it’s one. I had to decrease my protein and increase carbs to 60 to 100. I started going to the gym and I’m up to 3 miles threetimed a week I told my sister n law and she told me to quit telling her lies. No encouragement whatsoever. She goes to the gym 7 days a week and just eats salads. I hate lettuce but can tolerate it a couple times a week. I’ve cut my red meat to twice a week. Some chicken and tuna or cod once a week. I’m not a seafood person. I do eat a lot of beans , navy, pinto, red, great northern, purple hull peas,?red beans. Only use olive or coconut oil. Cut my sugars. I’m down one size in my clothes. It’s frustrating when your own family is not supportive. My kids are, but my wife’s family is not. I wish my wife was , it really hurts my feelings when I feel like I’m trying and nothing.

  6. That lecture I linked the other day by that US expert noted that if you are going to eat carbs, then eat them last, because of the way the body's insulin response mechanism works.

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