Sunday, March 12, 2017

Dr. Salim Yusuf and the PURE study

The PURE study is the Prospective Urban and Rural Epidemiology study, chaired by co-investigators Drs. Salim Yusuf and Koon Teo of McMaster University in Hamilton, Ontario, Canada.  PURE is the largest global study looking at environmental, societal and biological influences on obesity and chronic health conditions such as heart disease, diabetes and cancer.  The PURE Study consists of over 150,000 participants from 17 countries of low, middle and high income.

A side track around here is that a dear friend of ours has been in and out of hospitals most of the last month.  He had been having some shortness of breath, and some swelling in his legs, so went to see his primary care doctor.  The PCP did an EKG, took one look and told him to get to the ER.  To keep this short, over the course of the next three weeks he was in and out of two hospitals, home and back to an ER a few times, eventually getting a pacemaker and oxygen at home.  He has been home for about a week, now and we went by today, finding him looking much better than earlier in the week.  There are many more doctor visits and tests in the near future.

His discharging physician (not his regular doctor) told him to eat a heart healthy, low sodium diet.  Right away, most of you have a picture in your mind of what that is.  I invite you to watch this video of Dr. Salim Yusuf describing their results.  Yes, it's a 22 minute video.  It's important to underline that Dr. Yusuf is about as mainstream as it gets.  He's the president of the World Heart Federation and the Department Chair in Cardiovascular Disease at McMaster University Medical School.  This is not "quack alert" time.

[EDIT 03/22/17 1030 EDT - The video has had embedding turned off.  You may still watch it at this link.  SiG] 

Note that the ideal sodium consumption for minimization of cardiac events was in the range of 3-5 grams of salt/day.  3 grams is approximately twice the MDR of salt and twice what my friend's discharging physician recommended for salt consumption.  Sodium was especially interesting because for some people there was a "check mark" shaped curve of cardiovascular disease (CVD) vs sodium intake; that is, when the sodium intake got too low or too high, CVD went up. 

Now - some important stuff.  Studies like the PURE and virtually everything you get on the evening news are observational studies, and I maintain my belief that when most of those stories break, like last week's buzz story about gluten, they're not worth much attention.  Observational studies are essentially not able to distinguish cause and effect, but are useful for determining what needs to be studied in randomized, controlled studies.  There's somewhat of an exception to this, the Bradford Hill criteria, which basically say that if the effect is "ginormous" like it was with smoking (smokers got lung cancer something like 15 times more frequently than non-smokers), and if there's a plausible mechanism, and if a few other criteria are met, then you can attribute causality.  On the other hand, lack of correlation in an observational study can prove lack of causality.  If something causes another they have to be correlated, but being correlated itself doesn't prove anything.  (Easy example: there's a 100% correlation between people that breathed and people that died so that dying and breathing are correlated, but breathing doesn't cause dying). 

The conclusions through the 9th year of the PURE study are shown below:
  • CVD = cardiovascular disease.
  • MUFA = monounsaturated fatty acids - monounsaturated fat as found in olive oil, some nuts (e.g. almonds), and famously recommended in the "Mediterranean Diet"
  • PUFA = polyunsaturated fatty acids - typically found in vegetable oils, and in some nuts (e.g. walnuts) and recommended for years.  This is saying that despite at least 30 years of promoting vegetable oils - margarine over butter - there is no data showing it's protective
  • CHO = carbohydrate.  No distinction is made between complex sugars (starches) and simple sugars.  Restrict to less than 50% of caloric intake.  For the last 30 years, authorities have been recommending more like 65%. 
Not clear from the conclusion chart is that there was some evidence that saturated fat is protective; certainly not harmful.  There is no evidence that drinking 1% or 2% milk instead of full fat milk is protective; in fact, dairy fats appear protective.  All of which shows, according to this study, that a bacon cheeseburger - without the bun - might be the best food you can eat.  Do you like a salad with that?  Dr. Yusuf says "you have to eat something - if you like vegetables, eat vegetables".  So go have some bacon!


  1. I wish it were that simple. If your genetic predisposition is to have problems with salt than indeed consuming too much salt will cause you problems. But about 85% of the human population there is no health risk to salt and consuming too much salt will just result is peeing it out. How does this then affect the stats which uses all the people in the study? Well there will be this small increase in salt related problems significant enough to be important but not by any means all the people or even a majority of the population. No matter it’s stats it’s there so it’s no gospel; salt is bad for you. This works for fat being good and some fats being better or worse and carbs being bad, etc. etc.

    So seriously are carbs bad for you? Probably for 15% of the population replacing fat calories with carb calories is bad. For the other 85% it isn’t. But stats are insidious. In other words it shows a tendency for lowering carbs and increasing fats to be “better” statistically so therefore it becomes gospel (again) and settled science. Are carbs “bad”? Obviously not. The real proof is most modern societies eat a lot of carbs and the overall health has been improving or in some cases staying the same.

    What causes most heart attacks? Mostly it’s genetic. Can they be prevented? Sure, to some extent. If you have a genetic predisposition to heart disease then follow the best medical advice. If you don’t have a predisposition for heart disease it makes no difference.

    Here is the thing. We all die from something. In the 3rd world most die from diseases we can prevent or cure. In the 1st world we don’t generally die young from these curable illnesses so we die of natural causes. And what are natural causes for humans in the West? Heart attacks, cancer and stroke. This skews the stats and can be used intentionally or unintentionally to prove pretty much anything. For example most people in America die from heart disease so the press makes abig deal about it and makes it appear we all have one foot in the grave. But in fact most people in America (or the West in general) die at age 77-87 or so while in all those countries where heart disease isn’t even in the top ten their average life expectancy is 45-55. Ditto with cancer. You are 4 times more likely to get cancer by age 65 then you are at age 35.

    The bottom line on this is it becomes fertile ground for the quacks, the hucksters and the well meaning statistics challenged doctors. There is a certain amount of validity though. That is if you do not know if salt is bad for you or high carbs are bad for you then follow the best advice and it will maybe improve your odds. But, wouldn’t it be better to know based on your genetics what might harm you or help you?

    1. (1) The salt question ("How does this then affect the stats which uses all the people in the study?") is addressed in the video. Obviously more detail than I can get into.

      (2) The promise of genetic medicine, at least for me, is in the same category as "where's my flying car"? When human DNA was first sequenced, the science press proclaimed the dawn of personalized, genetic-based medicine. I haven't seen a thing other than the standard flow chart medicine: "You're over 50, you're male, and your lipid ratios are wrong: here's your statins".

    2. The salt question ("How does this then affect the stats which uses all the people in the study?

      It's difficult to put in 1000 words or less but please let me try: If any population had 15% who were sensitive to some food or chemical and scientists did a study using a diverse group to test the safety or effect of that particular food or chemical then they would indeed find a statistically significant effect. They could simply conclude that the food/chemical in question is generally unsafe for the entire population and should be limited or cut out completely. But it wouldn't be accurate. Statistically provable but not correct (like so many things with statistics). The accurate fact is that for people with a "salt problem" too much salt is indeed harmful. For the rest of us, the other 85%, excess salt consumption is not harmful. So to say to the population as a whole to cut back salt to what is an unrealistic level is foolish and quite probably risky. People today do fall ill and die from too little salt. But the results are accurate and provable, right? Yes! But what was actually proved is not what is claimed was proved.
      This same statistical anomaly applies to fats/oils, carbs, meats, and all the additives and various other non-food items we consume. What we are getting from science and medical experts is incorrect conclusions from legitimate tests. Why? IMHO it is because medical experts do not major in statistics and they simply put the data into a "black box" and get something out and they accept that as gospel.

  2. What is seldom discussed/studied as it relates to heart disease, obesity, diabetes etc. is our modern society. Meaning the world created by the industrial revolution. The two factors most likely to be the biggest reason for the huge increase in the above diseases are
    A: the creation of modern transportation, meaning people now walk MUCH LESS than they did in the past. Studies show that in places like New York where private vehicle ownership is much lower than elsewhere the incidence of heart disease and obesity is lower. This is because New Yorkers walk....A LOT.

    The second factor in the increase of "first world diseases" is the success of modern health care. In the past century the advent of antibiotics, successful surgeries of all types and other modern innovations that allow us to diagnose and treat many illnesses that used to cause early mortality and has allowed a far greater number of people to live long enough to develop these diseases. In the past you often didn't live long enough to get die from heart attacks, diabetes etc. because something else killed you first.

    It is a combination of modern technology that makes mobility almost irrelevant ( we don't even walk across the room to change the TV channel anymore), poor diets deficient in real nutrients (think fruits and vegetables and other NON processed foods) and the ability of modern medicine to keep you alive for YEARS with what would otherwise be terminal diseases. It's a 'perfect storm' of conditions that results in a massive increase in subterminal illnesses that require massive amounts of dollars to treat but which in reality we are NEVER going to "cure" because the "disease" is actually a symptom of our lifestyle and culture.

  3. It is very interesting how some of these dietary restrictions/mandates change over time, as new research is done. Separating out the studies done with an agenda from true, repeatable scientific results can be difficult. Like with polyunsaturated fats, salt, etc. I am definitely not a vegan, and I am fairly ignorant of the current mainstream thoughts concerning nutrition, but I tend to believe that natural food, prepared without _too_ much "denaturing (cooked rather than burnt, for example ;-), is healthier than most "food" which has been chemically denatured or processed.

    It is my understanding that cholesterol in food only affects a small number of people. Most cholesterol in the body is created in the body, _by_ the body, not a product of what has been consumed, other than in those folks with the genetic predisposition to translate dietary cholesterol into physiologic cholesterol. When I kept 37 Rhode Island Red chickens on my little ranch, I ate a _lot_ of eggs. As a very unscientific experiment, I had my coronary risk panel (lab testing for total cholesterol, HDL, LDL, triglycerides and the ratios thereof) checked, stopped eating eggs in any form for a month (no other dietary cholesterol excluded, though) and had my blood tested again. No change in the numbers, not even a small amount.

    While that certainly isn't proof of anything, it suggested that my coronary risk wasn't being affected by my consumption of eggs, which we have been told for many years _would_ raise your cholesterol levels, hence egg-white omelets, and other "heart healthy" menu items.

    Also, along with what SiG was saying about milk, when I had BPH (benign prostatic hyperplasia - an enlarged prostate _not_ caused by cancer), I was told that whole milk was safer than 2%, 1%, or non-fat. Supposedly, whole milk did not encourage the abnormal growth of prostate tissue (hyperplasia), but the milk with artificially lowered amounts of fat _did_ encourage such growth. I don't know if that was due to the methods used to lower the fat content or some other reason, but I've stuck to whole milk since I was told of the difference. Again, natural vs processed food.

    1. The egg question was resolved in the late 90s by Stanford University. They did the gold standard test on eggs: a crossover test that eliminates possible confounding variables in the two groups. They showed no problems with eating eggs.

      The larger problem is addressed in the video and I really recommend watching it: the use of surrogate end points. Much of cardiac statistical research was based on the end point of raising cholesterol and especially LDL, not actual "cardiac events". It says, "we "know" that LDL cholesterol is bad so anything that raises LDL is bad". It turns out LDL or total cholesterol may not be that bad, or at least LDL numbers don't contain enough information, and if those statistics look at actual cardiac events and not the surrogate, the results come out very different.

  4. SiG, I got distracted and forgot to ask - was your friend checked for DVTs (deep vein thomboses)? I was hospitalized with shortness of breath and _one_ leg that was swollen, gowing to the ER because I was pretty sure I had a clot (DVT) in my lower leg, and parts of that clot in my left lung, causing a PE - pulmonary embolism(s). In my case a large number of tiny clots/pieces of a clot that were blocking the circulation in my lung, seriously reducing my access to oxygen.

    Was that part of the issue for your friend, or were the shortness of breath (SOB) and swollen legs caused by something else?

    1. His swelling is bilateral and DVT hasn't been mentioned, but I know more tests are coming this week. I think congestive heart failure/cardiomyopathy is on the short list of probable causes. The response to cut salt was for the swelling (and what led me to stumble across this) which is probably due to some loss of function in his kidneys which he believes (or was told) is from the metformin he's been taking for type 2 diabetes.

    2. Metformin does not harm kidneys. Generally the only drug Metformin is prescribed for is adult onset of type II diabetes..More accurately called acquired insulin resistance.
      People with this condition invariably have chronically high blood sugar levels...Often even maximum doses of multiple meds cannot bring A1C down to "normal". Free sugar in the bloodstream damages blood vessels, the smallest ones first. Kidneys are especially susceptible as they are highly vascularized. This causes changes in blood serum volume and "third space" fluid volumes resulting in swelling of extremities. In addition the heart can be involved leading to early CHF...And leg swelling. While bilateral leg DVT is not impossible it is vanishingly rare. Bilateral leg swelling is most often a symptom of fluid imbalance secondary to conditions such as CHF or Renal Insufficiency.
      Diabetes, both type 1 and 2 are terrible diseases...Among the worst a person can be afflicted with as there is no true cure and treatments are not always effective. The most effective treatment is prevention via weight control and a diet low in sugar and carbohydrates along with adequate exercise.

    3. Diabetes is inherited, you get it from your parents not carbs/sugar. People of Northern European descent tend to have half the rate of diabetes that people of African or native American have. It's in their genes. Diabetes is not a disease that is exactly the same in everyone who has it. If you are diabetic a low carb diet, weight control and exercise can reduce the symptoms and the damage of the disease. But if you do not have diabetes ignoring that prescription will NOT give you diabetes.

    4. Diabetes like MANY "diseases" has both a genetic and an environmental component. Certain groups of American Indians are much more likely to have diabetes than other groups. However EVERYBODY is at risk of developing type II diabetes if they eat the wrong food and engage in the wrong lifestyle. Eating properly and exercising is not a guarantee you won't develop diabetes....just as eating anything you want and watching TV doesn't guarantee you will get it. EVERYTHING in life has "exceptions"....people who are outliers that don't match the general guidelines. But this number is so small as to be irrelevant. So as I stated...MANY diseases of modern society including diabetes are a result of our chosen lifestyle. And before Mr. Anonymous decides to preach some more he needs to bring along his bona fides to prove he knows what he is talking about. ME.....I graduated from Loma Linda University (a school that teaches ONLY medical related disciplines) and have decades of experience in health care.

  5. If the bacon sits in the fridge long enough to turn green, does that make it a vegetable?

    Surely you remember your days in college as an undergraduate student and the first time you found out that if it was in your fridge and was green, it wasn't that color when it went in. And eating it was an opportunity to win the Darwin award...

    And do note that a significant portion of medical "research" today is done by entities which have an interest in how that research turns out. I think the latest figure I saw said that less than 30% of medical "research" is reproducible. Turns out the "scientists" involved play with the configuration until they get the results their source of funding wants. And then they only publish THOSE results and ignore the other ten studies where that wasn't the case. Quelle surprise!

    1. I think it was Eddie Murphy who did the bit on "Red meat isn't bad for you. Green meat is bad for you"

      And yeah, I've done a couple of columns on the problems with science. My favorite story is the one where the researcher couldn't replicate someone else's experiment and eventually contacted them. "I explained that we re-did their experiment 50 times and never got their result. He said they'd done it six times and got this result once, but put it in the paper because it made the best story."

      Story? Story??!!?? Since there's a good chance we taxpayers are paying for it, I WANT MY MONEY BACK.

  6. Dan I respect doctors and all of the medical personnel. I also respect facts and common sense. What I said about statistical studies is absolutely true and provable. Some people intentionally use statistics to defraud and misinform and some people fail to understand the shortcomings of statistics and inadvertently misinform. If my exposing that offends anyone I can only say they need to take some classes in statistics and get back to me.

    99% of type II diabetes is genetic, simple as that. What most people think is diabetes is discovering their symptoms. Long before they had symptoms they had diabetes, usually. Because of this it is common for people, including doctors, to believe that, gee you were diabetes free for 30 years and now you have it about the same time you put on an extra 30 lbs. Well there you go the extra weight and lack of excercise must have "given" you diabetes. Conveniently ignoring the 95% of the population that also puts on an extra 30 lbs by age 30 and stops exercising regularly after having a family and dealing with all of the constraints on their life and does not get diabetes. How could that be??? If a Western diet and lack of exercise and extra weight causes diabetes how can it possibly be that 95% of us don't get diabetes??? And if that is the cause but blacks get it at twice the rate and Hispanics get it at three times the rate and many American Indians get it at 5-10 times the rate and Australian indigenous people all get it how can it be diet or lifestyle or weight gain??? Surely it must be some genetic tendency that causes so many more American Indians to acquire diabetes than people of Northern European extraction. Surely you are not going to try to convince someone that the reason American Indians get diabetes at three times the rate of whites is because they eat three times as much junk food or are three times fatter or get 1/3rd the exercise of whites? No! It's genetic. If you do not have the genetic predisposition to get diabetes that you can eat sugar by the spoonful, never exercise and gain 30 extra lbs and you still won't get diabetes. You may not believe it. It may not be what was taught to you, nut it is true. I am sure that you hate hearing this from someone who did not graduate from Loma Linda but I can only hope that your learning did not end with your diploma and that you might think, I wonder if he is right?

    1. Anon - you seem to be saying that 5% of the population will get diabetes here: how can it possibly be that 95% of us don't get diabetes???. Do you have a source for that number?

      I'd think quite a bit more than that based on observations.

  7. The actual percentage of people with diabetes is complex. There are two essential reasons for this: 1. about half the people who actually have diabetes don't know it. 2. different ethnicities have different rates of diabetes. So while the rate of diabetes for people of Northern European extraction might be about 5% the rate for people of native Mexican and South American extraction is about twice that or 10%. Ditto for American Indians and blacks. These numbers may in fact be slightly higher because some percentage of diabetics are not yet identified.

    There is a third factor in this as well. Certain groups have a vested interest in inflating and conflating the data. I don't ascribe a terrible motive to this simply that they feel their group and agenda is best served if more people worry about or fear diabetes so they kinda hype the numbers. Gets more attention, more funding and better treatment. To be perfectly honest I think they believe that a little bit of fudging on the data equals positive results for a serious illness so the end justifies the means.

    When you take the U.S. population as a whole the actual rate of known diabetes is said to be 8% with an assumption that a smaller percentage of unknown diabetes exists as well. Again this is largely because of the large percentage of our population of various ethnicities with a high genetic predisposition to diabetes. The bottom line is no one really knows the exact percentage and it may be unknowable.

    What is knowable is the round numbers and the dramatic difference between different ethnic groups. What is also significant is the tendency for diabetes to be discovered after the age of 20-30. Part of this is that diabetes symptoms can be controlled by diet and exercise. We have all been children and teens and we know that teen tend to skip meals, are very active and in general don't put on the kind of weight that they are likely to maintain through out their adult life. This lifestyle masks and somewhat controls the illness. So commonly a diabetic discovers that they have the disease after they marry and settle down. This is significant because it contributes to the misinformation and misunderstanding of the disease.

    Why is this important? Because diabetes is very serious and early treatment can be very effective in reducing the negative complications and extending life. If someone has diabetes then absolutely follow the doctors advice adopt a diabetic diet, get regular exercise, maintain a normal weight, etc. If you don't know if you might have diabetes then get tested for it. I am a believer in healthy living I am simply asking for better information.