How to Live Longer And Exercise Shorter?

Let's face it, if exercise was really that much fun, everybody would do it and we wouldn't be fat, diabetic or die of heart disease. So when your doctor tells you that you better start exercising, your immediate question might be: how much do I have to do? The answer is, it depends. It depends on whether you want to hear the polite version or the truth.  [tweet this].


The polite version goes something like this:  As long as you do some exercise, you will see some health benefits. When your doctor gives you this advice, he probably has studies in mind like the one performed by Hamer and colleagues [1]. They show us that as few as 1-2 exercise sessions per week protect against heart disease. I don't really buy it, and neither should you. Here is why:

The researchers took data from 23,747 people of the English and Scottish health surveys and grouped them into one of two groups, depending on the status of their metabolic health. The latter was defined along the risk markers of high blood pressure, low good cholesterol, diabetes status, high waist circumference and inflammatory status. People who had less than 2 of those risk factors made it into the metabolically healthy group, the rest into the unhealthy group. 

Since these surveys had also asked people to self-report their physical activity levels, the researchers were able to investigate, how exercise volume correlates with health outcome. And, lo and behold, over the average follow-up period of 7 years those among the metabolically unhealthy people, who reported exercising just once or twice a week, had the same risk of developing heart disease as the metabolically healthy people. I'm not trying to discredit this study. It is a valid method to look at associations between exercise and health. But we have to keep in mind that it only answers the question whether PA, at this low volume of 1-2 times per week, is associated with heart health. What the study doesn't tell us is, whether this association is of a causal nature. In other words, it really does not tell us whether low-volume PA "...is protective in men and women with clustered metabolic abnormalities" as the authors suggest.

If studies like the one of Hamer and colleagues are used to entice the couch potatoes to pick up exercise, even if it is only once or twice a week, then, by all means, that's a good start. In public health we love this type of message for a simple reason:  We can throw it at the media in the hope of encouraging sedentary people to take up exercise. If the message is effective, there will be fewer heart attacks and early deaths. What we deliberately do not tell you, though, is how effective this exercise is for YOU. We have a number for that. It is called the 'number needed to expose' (NNE). It tells you how many couch potatoes need "to be exposed" to a change in exercise habits in order to prevent one single case of heart attack or death. In the case of Hamer's study that number stands at more than 40. Meaning, for every 40 people, which we convince, we can prevent 1 death from any cause. Good for us. But probably not good enough for you. If you take up our advice, the 1 in 40 simply means a 2.5% chance that this avoided death would have been yours. Not very motivating. Which is why you don't read so much about these numbers.

Now, if you were my client, I would ask you, whether you were interested in getting the best out of the limited time you are willing to invest in exercise. Which brings us to the second version of the answer, which I promised you in the beginning of this post: the truth.

Evidence is accumulating that the intensity at which you exercise is far more important for your health than the total volume of exercise. In an earlier post (Shortcut to Longevity) I introduced the results of the Copenhagen City Heart Study, which showed an association between heart disease mortality and the intensity, but not the volume, of habitual cycling. Of course, what applies to the Hamer study, applies to this study too. An association is not necessarily of a causative nature. But if we take it as an indication that exercise intensity is so important, isn't that bad news and bad news for the couch potato? Not only does he have to exercise, he also has to exercise hard? No, this is where the good news are: There is method of milking this high-intensity effect to the point where it saves you oodles of time.

It is called high intensity interval training, or HIT for short. This acronym should get you excited, because it super-charges the benefit:time ratio of exercising. In fact, if done correctly, you can expect to improve your fitness and endurance to the same extent as you would with traditional continuous endurance exercise while spending 90% less time on exercise [2]! But let's take it a step at a time.

What is HIT? As the name implies, HIT sessions consist of alternating intervals of vigorous and moderate intensity exercise. One-minute intervals of sprinting, interspersed with 3 minutes of jogging at a moderate pace, would be one of a virtually infinite number of variations of HIT. Do this for 16 or 20 minutes thrice a week and I promise you, within 2 weeks, you'll be excited about the noticeable progress you make. That's 60 minutes a week! Should be possible for the tightest of time budgets. After all, time is the most often cited obstacle to taking up exercise. Understandably, because there are only 24 hours in a day, of which statistically, every German spends 4 hours in front of the TV and every American 6 hours. Which really leaves us so little time to do something meaningful, aside from working and sleeping. If that comes across as sarcastic, I'm guilty as charged.

Anyway, I haven't answered the next logical question, whether HIT also translates into real health benefits. You bet it does. In fact those benefits are so profound, that even heart attack and heart failure patients are now being put on HIT routines. Wisloff and colleagues randomized 27 heart failure patients into 3 training groups [3]: a HIT group which walked three times a week four 4-minute intervals at close to maximal heart rate, with 3-minute intervals of walking at 50% to 70% of maximal heart rate between the high intensity intervals; a moderate-intensity exercise group which walked thrice weekly continuously for 47 minutes at 70% to 75% of maximal heart rate; and a control group which met every 3 weeks for a 47-minute walk. After 12 weeks, the control group showed no improvement in fitness, measured as maximal oxygen uptake. The moderate-intensity group had improved fitness by 14%, whereas the HIT group, which had spent 50% less time on exercise, had an improvement of 54%. Moreover HIT improved arterial function, cholesterol and heart function, significantly better than the continuous moderate-intensity exercise protocol.

In another study, diabetics were put on a HIT protocol consisting ten 60-s sprints interspersed with 60-s moderate-intensity cycling. After only 6 sessions, participants' glucose metabolism had improved substantially and so had their muscles' oxidative capacity [4]. Unfortunately, this study was not controlled, meaning there was no control group to compare the relative benefits of HIT vs. continuous moderate intensity exercise. Which shows, we are still in the early days of finding our ways to optimal protocols for different people with different health issues.

In my lab, we wanted to know whether the high benefit:time ratio of HIT, together with its quickly noticeable results, would entice couch potatoes to do more than a prescribed weekly minimum of three 20-minute hit sessions. After 6 months 76% of our 120 study participants had acquired the habit of exercising more than 150 minutes per week. When they started on our program they had all been sedentary and mostly overweight, but they were otherwise healthy. Over the 6 months they not only improved their fitness substantially but also reduced their weight and improved their risk factors for heart diseases and diabetes [5].

I prefer telling a couch potato that, to gain a health benefit,  (a) he or she has to do exercise, that (b) the exercise has to be of sufficient intensity, and that (c) this benefit can be his or hers at a modicum of time spent on exercise. I prefer that to making polite noises about the benefits of very little exercise, no matter what intensity and volume, because the benefit I would be talking about wouldn't be the benefit she or he is thinking of. 

In the next post I will show you how to design your own HIT routine, how to find the optimal intensities and what to keep in mind when you bring such a routine into a hitherto sedentary life.

Seeing you again coming Monday.


1.    Hamer, M. and E. Stamatakis, Low-Dose Physical Activity Attenuates Cardiovascular Disease Mortality in Men and Women With Clustered Metabolic Risk Factors. Circulation: Cardiovascular Quality and Outcomes, 2012.

2.    Kent, W., The effects of sprint interval training on aerobic fitness in untrained individuals: a systematic review. British Journal of Sports Medicine, 2011. 45(15): p. A8.

3.    Wisloff, U., et al., Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation, 2007. 115(24): p. 3086-94.

4.    Little, J.P., et al., Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. Journal of Applied Physiology, 2011. 111(6): p. 1554-1560.

5.    Kraushaar, L., Improving the Efficiency of Lifestyle Change Interventions for the Prevention of Cardiometabolic Disease, in School of Public Health Medicine2010, University of Bielefeld: Bielefeld. p. 239.


Hamer, M., & Stamatakis, E. (2012). Low-Dose Physical Activity Attenuates Cardiovascular Disease Mortality in Men and Women With Clustered Metabolic Risk Factors Circulation: Cardiovascular Quality and Outcomes DOI: 10.1161/CIRCOUTCOMES.112.965434

Kent, W. (2011). The effects of sprint interval training on aerobic fitness in untrained individuals: a systematic review British Journal of Sports Medicine, 45 (15) DOI: 10.1136/bjsports-2011-090606.26

Wisloff, U., Stoylen, A., Loennechen, J., Bruvold, M., Rognmo, O., Haram, P., Tjonna, A., Helgerud, J., Slordahl, S., Lee, S., Videm, V., Bye, A., Smith, G., Najjar, S., Ellingsen, O., & Skjaerpe, T. (2007). Superior Cardiovascular Effect of Aerobic Interval Training Versus Moderate Continuous Training in Heart Failure Patients: A Randomized Study Circulation, 115 (24), 3086-3094 DOI: 10.1161/CIRCULATIONAHA.106.675041

Little, J., Gillen, J., Percival, M., Safdar, A., Tarnopolsky, M., Punthakee, Z., Jung, M., & Gibala, M. (2011). Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes Journal of Applied Physiology, 111 (6), 1554-1560 DOI: 10.1152/japplphysiol.00921.2011

Will Work For A Family

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The Butler kids in Washington decided they wanted to ‘Adopt A Family’ in our Adoption Ministry 1:27 program.  So their dad (who just happens to be the program director) gave them a job to do to earn one month’s support!

Thanks to those hard-working Butler kids for their big hearts and excellent car-washing skills!  Is there a line forming down the street?



If you’d also like to sponsor a family in Ethiopia  - either a guardian family or an at-risk family – for $40 per month, be sure to visit our Adoption Ministry 1:27 webpage.  Join us in addressing the orphan crisis in Ethiopia through our orphan prevention program.
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Setting an example

Rachel Gallegos 209 for water filters

As is the case with so many of our adoptive families, their children have a heart for the people of Ethiopia and they want to DO something to help!

Thirteen-year-old Rachel Gallegos recently gave a presentation at her AWANA group and took a two week collection of spare change to buy water filters for Ethiopia from our YWAM Gift Catalog.  The children brought in over $200 in that short time!  They were such cheerful givers, too – they gave all they had in their pockets!  These donations will buy 5 portable water filters which will be delivered through our in-country representative to several communities where clean water is not available.

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Rachel’s mom, Michelle, said “We had no idea what God was going to do in our hearts through adoption.  We did not know He was going to break our hearts for the widows and orphans of this country or that He was going to give us such a love for Ethiopia and a desire to advocate for the needs we saw.  We also did not know what God was and is doing in the lives of our children through adoption – especially our oldest daughter.  We have witnessed God using her to bless the people of Ethiopia in many ways.  It all started with God calling us to adopt and it is amazing to watch the UNEXPECTED things God does, molding us and our children.”

1 Timothy 4:12  Don't let anyone look down on you because you are young, but set an example for the believers in speech, in life, in love, in faith and in purity.

THANK YOU to Rachel and to her Awana group.  Many families will now have clean water to drink and avoid getting diseases like Typhoid that are spread through dirty water.



Be sure to visit our YWAM Gift Catalog to find ways you too can make a difference in the lives of widows and children in Ethiopia.
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Mattress Delivery in Korah

The mission team from the University of Kentucky spent their last day serving in Ethiopia bringing much needed beds to several families in Adoption Ministry 1:27’s program in the community of Korah in Addis Ababa.  Here are a few photos from Friday.  


Some of the homes in Korah…

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Tesfaye told the team about several of the families they would be delivering mattresses and bedframes to before they began.

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Stepping into these homes is an extremely humbling experience.  These are truly deplorable living conditions.

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People sleep on cardboard, tarps or share one bed for many adults and children.

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You can’t drive down the narrow paths to some of these homes so everything has to be carried in.

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As always, there are children who come to watch…

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“But just as you excel in everything—in faith, in speech, in knowledge, in complete earnestness and in your love for us —see that you also excel in this grace of giving.”  2 Corinthians 5:12


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We are so grateful for this team of folks who came to serve and to give!   Thank you Jason, Joker, Leslie, Larry, Mike and Matt – you guys were awesome!

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For $40 a month, you can sponsor a family in our Adoption Ministry 1:27 program and make a huge difference in the lives of Ethiopia's poorest.  Please visit our website here to find out more!
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3 Ways to Spot Their Lies About Healthy Recipes

Briefly: If I had to name the one word, that is most often used to label something as what it is not, my vote would go to "healthy". Whether it's the issue of sugar vs. honey, of butter vs. oil or of calories vs. nutrients, science and evidence are clearly not playing the lead role in the culinary theater of the world wide web. Judging by its popularity, that's a missed opportunity.
I recently gave a talk on the lies and deceptions the food industry uses in labeling and marketing their products. A German corporate health insurance had asked me to give that presentation to their clients. Naturally, a large percentage of the audience were women. Judging from the lively and entertaining discussion, which followed my presentation, almost all women prefer home cooked food for their families to take-out or eat-out. The most often cited reason was that home cooked food is the healthier choice. I'm not convinced that they get it. Not if they get their food information from where they professed to search for it: the internet.
I know this, because in preparation for my talk I followed my wife on one of her culinary search trips through the web.
The number of recipe sites is staggering. So is the degree of misinformation disseminated by them. Most of it in the form of labeling something as healthy when it clearly isn't. Let's look at three commonly encountered mis-perceptions on randomly chosen recipe sites. I won't give you the links, because to single them out would be unfair. What I found there is so ubiquitous, that you will encounter it virtually everywhere once you start surfing the culinary side of the web.

Honey vs. Sugar

A self-proclaimed holistic health counselor shares her recipe for a "Healthier Flourless Chocolate Cake". Which immediately begs the question: healthier compared to what? The answer comes in brackets directly behind the title, where it says "refined-sugar free". Reducing sugar in our daily diet is certainly a big step towards better health. But you won't get there by replacing sugar with honey. The difference between sugar and honey is simple: Sugar is 100% sugar, honey is 80% sugar. Admitted, that's a little oversimplified. Honey does have ingredients which sugar doesn't. But these are not an issue when it comes to reducing calories or the metabolic impact of sugar. Whether you sprinkle granulated sugar into the dough or fold honey into it, what your metabolism has to deal with is their common denominator, the breakdown molecule, which ends up in your blood - glucose. Of the recipe's remaining 4 ingredients - butter, eggs, cocoa powder and baking chocolate - the butter is evidence that our holistic health counselor has missed out on another common diet mis-perception:

Butter vs. Oil

On another website we find the "Best Ever Healthier Chocolate Brownies". Honey isn't an issue for this lady. Her claim to healthiness is based on the conviction that other recipes use "... butter rather than olive oil", and that "olive oil contains healthier fats". This butter vs. oil issue is not as straight forward as the glucose theme. So let's look at it in greater detail.
The fats for human nutrition come either from animal or plant sources, and you can think of them in 3 major categories: saturated fats, and mono- and poly-unsaturated fats. We don't need to go into the molecular details of the fats - or fatty acids (FA), as they are more correctly called. Suffice it to say, that the "unsaturated" part of the descriptor refers to one (mono) or more (poly) carbon atoms of the fatty acid molecule having less than the maximally possible number of hydrogen atoms linked to them. Depending on the position of the first "unsaturated" atom in the chain of carbon atoms, the poly-unsaturated fats are called omega-3 or omega-6 poly-unsaturated fatty acids (PUFA). There is one more thing you should be aware of: the human body can manufacture most of the fatty acids which it needs for its metabolism and maintenance. But there are two, which we need to supply through our food intake. These two are alpha linolenic acid (ALA), an omega-3 FA, and linoleic acid (LA), an omega-6 FA. Our organism uses them to produce other fatty acid variants which are essential for our health.
Armed with this knowledge we can now ask ourselves an obvious question: What's the health issue with fats? You have probably heard that a high fat diet promotes high levels of cholesterol in your blood (partly true) and that high cholesterol is the cause of heart disease (not true). You have also heard that saturated fats, such as butter, are bad for you and that replacing it with olive oil is good for your health.
Now let's hear the facts as we know them today: Dietary trials in which saturated fat, such as butter, was replaced by PUFA lead to a reduction in risks for cardiovascular disease [1]. However, when those PUFAs were mainly of the omega-6 version, there was no reduction, or even a slight increase in risk for heart disease. Looks like replacing saturated fats with oils isn't going to do you any good if you don't chose the oils for their content of omega-3 FAs.
These observations match nicely with what we know from evolutionary biology. Comparing the fat intake between our hunter/gatherer ancestors and us, we notice that the ratio of omega-6 to omega-3 fatty acids has undergone a dramatic change. While that ratio stood at 1:1 or even lower throughout most of human evolution, our modern western diet has upped that ratio to a whopping 16:1 [2], and even greater than that, depending on where you live. When I now tell you that the downstream products of your omega-6 FA intake are pro-inflammatory whereas the products of ALA have the opposite effects, you might begin to see the picture. With heart disease and stroke being the late-stage consequences of chronic inflammation of the arteries, as I highlighted in my earlier post "Your Shortcut To Longevity", the type of fat appears to have an effect on your arterial health. And therefore on your risk of heart disease.
How large this effect really is, remains unclear. In a recently updated review of randomized clinical trials the Cochrane Collaboration came to the conclusion that reducing the content of saturated fat in favor of unsaturated fats had some effect on cardiovascular disease events in men only (not in women) and only if such dietary habit change lasted at least 2 years [3]. There was no detectable effect on the risk of dying from cardiovascular disease. Importantly, it was unclear whether the reduction in disease events was due to poly- or mono-unsaturated fatty acids.
There is another issue I have with that song and dance about olive oil. Its omega-6:omega-3 ratio is around 13, which doesn't exactly make it heart healthy. In comparison, the much maligned coconut oil has no omega-3 FAs only omega-6. But it delivers only a third of the omega-6 FA of olive oil. In contrast, sunflower oil also has no omega-3 component but delivers almost 6 times as much omega-6 as olive oil. The only really stand-up guy in the vegetable oil department is flaxseed oil: its omega6:omega3 ratio is 0.3, which makes it as good as any of the fish oils, which are considered healthy. But don't get too excited about flaxseed oil taking over your kitchen anytime soon. It can't hide it's similarity with fish oil. I tried it. It's OK in a salad, and so are the seeds. Heat up the oil, though, and you think you are frying a cod liver. That taste doesn't go too well with a chocolate cake, or many other dishes.
So, what's the point? Of course, you can read the evidence as you like, but I wouldn't call a brownie or chocolate cake healthier when the only merit to this claim is its oil content. To me, the excess in calories is what by far outweighs the relative merits of the carriers of theses calories. Which brings me to the third issue:

Calorie Density vs. Nutrient Density

When I added up the calories for the brownie and the cake, the calorie-to-weight ratio was in excess of 4. That is, every 100 grams of these buggers deliver more than 400 calories. This nutrient density of 4 is way in excess of what man was exposed to through most of evolution. Think about it: fruits come with a ratio of 0.6, on average, vegetables with a ratio of 0.3 and game meat, the only meat available to our cave dwelling ancestors, delivers on average 200 calories for every 100 gram. We can reasonably assume that our ancestors had to survive on an overall calorie-to-weight ratio of less than 2. Add to this the fact that they expended far more calories than we do today. Just to maintain calorie balance our ancestors had to eat a much larger quantity of food than we do today. And that food, while low in calories, was packed with nutrients. So, their nutrient:calorie ratio was certainly far more favorable than ours is today.
There are many more issues which plague much of the web's culinary universe. By right, the word healthy shouldn't be anywhere near most of its places. Particularly when those places are all about eating and nothing about exercise. You can eat as healthy as you like, if you fail to exercise at the right frequency, intensity and volume, then pay-back day is almost inevitable.
How your arteries benefit from exercise, and how you can make that exercise exactly right for you with the least possible effort, that will be an issue of my next post. Until then, don't get hooked too much on the culinary web. I worked up a hell of an appetite during my recipe surfing exercise with my wife. Didn't do any good to my waist line and probably not to my arteries. But, what the hell, we need to enjoy sometimes, too.    


Kuipers RS, de Graaf DJ, Luxwolda MF, Muskiet MH, Dijck-Brouwer DA, & Muskiet FA (2011). Saturated fat, carbohydrates and cardiovascular disease. The Netherlands journal of medicine, 69 (9), 372-8 PMID: 21978979

Simopoulos, A. (2008). The Importance of the Omega-6/Omega-3 Fatty Acid Ratio in Cardiovascular Disease and Other Chronic Diseases Experimental Biology and Medicine, 233 (6), 674-688 DOI: 10.3181/0711-MR-311

Hooper L, Summerbell CD, Thompson R, Sills D, Roberts FG, Moore HJ, & Davey Smith G (2012). Reduced or modified dietary fat for preventing cardiovascular disease. Cochrane database of systematic reviews (Online), 5 PMID: 22592684

Awards Day

I promise to start enjoying my three day weekend....right after I post, lol. I have three more school days for the year. I'm going to try to keep Tuesday as fun *and regimented* as I can. On Wednesday we have field day and a volunteers luncheon. Throughout the year we have so many volunteers (moms, dads, friends of staff, grandparents, and even retired teachers) that our school provides a luncheon for them to come and see our gratitude. I'll post more on that later. Thursday is our last day. In the morning each grade level has a small, short, sweet awards ceremony. It's nothing big but we try to make sure everyone walks away with something. The school provides some awards but I try to add a few extra. I have used Word templates in the past and they were okay. I decided to try my hand at making some and I like how they turned out so I decided to share. Just click here to download.


For those of you that have a few days left like myself I wish you luck. For those of you already finished enjoy your break and get a fruity drink ready for me because I'll be there soon.

A Day to Play

A mission team from the University of Kentucky spent the last two days in the village of Gutumuma, conducting sports camps for children in the government school there.  Here is a photo diary of their time there…

Just a ‘few’ kids showed up for the sports camp day!  T-shirts were handed out, teams were assigned (kind of) and lines were formed.

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The team also made some repairs to the faucets at the compound…

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and everyone enjoyed the cool, clean water!

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Coming up next:  A day spent at Korah visiting several sponsored families in our Adoption Ministry 1:27 program.
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Day 176

As I'm sure most of you do we have a Morning Meeting board where we go over the date, months, and a few other math things. (Yes, I have also downloaded Cara Carroll's Calendar Companion and it works great)(click on pic to check it out, it's fabulous and supplements math things in a great way)
Well, today our Number of the Day is day 176. Can you believe it?! Four more school days and we'll be done. I have such a grreat group of sweet (hilarious) kiddos. The younger grades add a straw, or dot on a tens frame, or tally mark to show a new day...every single day. Believe you me the school year seems daunting when you are only on day 25. Whooo. Now it's all gone by so quickly. Don't get me wrong I am R.E.A.D.Y. for break. I definitely need it. I should probably insert a picture of my haphardly organized desk or my stack of papers that need graded and input by next week but since I'm still a newbie I'll safe myself a little embarassment.

Each year in first grade (for at least the last 20 years) our school has put on a First Grade Circus. Each kid is assigned an act and we have volunteers that help us teachers 'train' the kids to do their act. Yesterday was CIRCUS DAY!! This year I trained the jump rope group and the basketball all-stars. This is my third year doing and I really do like it. A lot goes into and my co-teacher is fabulous and organizing it all and being patient while remindnig me or teaching how to do certain things. We decorate the gym, paint faces, make posters, have costumes, do hair, and do an intro song. It's really neat. I'm a little jealous that I didn't get to be in one in first grade. The other first grade teacher's husband is kind enough to record it and edit it. We all send home a DVD copy with each kid. The parents really like it.


I'll try to see if I can edit some pics to post.

The Death Of Good Cholesterol

Briefly

There were always two types of cholesterol, the good and the bad. Until now. A large new study tells us that good cholesterol might have been an impostor. That's food for the media types. For those who think before they type, the real news is that we are finally getting closer to uncovering the impostors. Thanks to the genetics revolution which seems to be paying off in an unexpected area.  

 

 

HDL - The Knight in Shining Armor

In the cholesterol universe there are two camps: good cholesterol, also known as HDL, and bad cholesterol, often referred to as non-HDL cholesterol. The latter comes in a variety of flavors, of which LDL is the most prominent and best known. From many large observational studies we know that high levels of LDL and low levels of HDL associate with an elevated risk for heart disease and stroke. Certain limits have been derived from these studies, above which your LDL shouldn't rise and below which your HDL shouldn't fall. The magic level for HDL is 60 mg/dL blood. Above that limit, we are assured, HDL will even offset some other risk factor, such as age or being of the male persuasion. Given that a large percentage of people fail to achieve these desirable levels, researchers have been eagerly sourcing for pharmaceutical means to increase HDL. Now a new study tells us, that HDL might have to be stripped off its White-Knight title, much for the same reason as "Dr." Karl-Theodor zu Guttenberg, the former German defense minister, had to be stripped off his doctorate last year: for being an impostor.

Epidemiology 101

If you have been following biomedical research for a couple of years, you will have noticed that results are often conflicting. So, you might discount the findings of one study if hundreds of others come to a different conclusion. Only in this case you should pay closer attention, because what Voight and colleagues have produced strikes at the foundation of how we do research in epidemiology, the science which studies the health of populations [1].  To appreciate the gravity of the situation, I need to familiarize you with a basic concept of epidemiological studies: Confounding. I'll use a very simple and hypothetical example. 
Let's say we are interested to know the causes of health and disease in children in the hypothetical and impoverished state of Maladipore. The figure to the left represents our astonishing finding that children growing up in a household which owns a TV are significantly less likely to die during childhood than children growing up without the boob tube. The correlation between TV ownership status and survival are very strong and compelling. 
On the face of it we could now recommend the prime minister to improve the health of the nation by simply installing a TV in every household in which there are children. If we know that this is nonsense, we take our epidemiology tools and look for another factor which has an influence on TV ownership AND on survival rate. 
And so we discover that wealth is this third factor. We call it a confounder. Wealth has confounded our original finding because the wealthy can afford a TV and they can also afford medical care and immunization for their children. Whereas the inability to buy a TV certainly reflects the inability to buy medical care, too. When we repeat our analysis of the data, which we gathered during our observational study, we find that the link between TV ownership and survival disappears once we bring the third variable, wealth, into the equation. Clearly, providing every household with a TV wouldn't have reduced the rate of child deaths. Greater wealth however will.
In the case of Maladipore, common sense is all it takes to suspect and find the confounder. In real life it is almost never as simple. When we find an association between cholesterol and heart disease, then we typically have some idea about the way cholesterol might contribute to heart disease. At that stage our ideas are merely hypothetical. The classic way of investigating them is through clinical trials in which we randomize participants into 2 groups, one in which we lower (bad) cholesterol and another in which we don't, the control group. Then we observe them for a period and note the rate at which people in both groups develop heart disease or die from it. If we find that the control group, the one which didn't receive the benefit of having its cholesterol lowered, has a significantly higher rate of falling ill, we conclude that lowering cholesterol is the way to go. Sounds easy, but it isn't. For several reasons. In the case of cholesterol, the time between developing high bad, or low good, cholesterol and suffering a heart attack or stroke is measured in decades rather than in years. We also cannot just experiment with people as we would like to in the name of science. Ethics boards look very closely at the potential risks and benefits associated with what we do in trials. We cannot simply withhold treatment from a control group, with scientific curiosity as the motivation. With these obstacles, we had  to draw our conclusions from observational studies, which tell us a lot about associations but nothing about cause and effect. Until now, we simply had no other choice. But not any more:

It's Mendel All Over Again

With larger and larger databases being developed from genetic research we can now do something else: Mendelian randomization studies. Which is what Voight and colleagues did. The concept behind it is amazingly simple and elegant, though not as brand new as you might think. It has been named after Gregor Mendel, the father of modern genetics, who first observed and described how traits are inherited. As always, a concept is best understood using an example. In the 1980s some researchers thought that very low cholesterol levels might increase the risk of cancer. There was definitely an association being observed between cancer and low cholesterol, but nobody knew which was the cause and which the effect. Or whether there was a third confounding variable, as yet unknown. Now, you can't make a study in which you lower the cholesterol in some people, just to see whether they will develop cancer.  Go and find volunteers for that one.
So, Martjin Katan had another idea [2]. In 1986 he pointed out that there existed a certain variation in one gene (the gene which encodes the apolipoprotein E), which, if you had that variation, would give you extremely low cholesterol levels. He also knew, of course, that we inherit our genes from our mother and our father in a random way. That means, your hodgepodge of genes and my hodgepodge of genes are not systematically different from each other. Both are just random assemblies of genes from among all possible variations. In case you inherited that low-cholesterol gene, and I didn't, then it was just the luck of the draw. The important point is, that there is no room for confounding the random selection of genes. 
So, if the "unconfoundable" low-cholesterol gene directly affects cholesterol levels and nothing else, then people who carry this gene should be found more often among patients with cancer than among people who are free from cancer. That was Katan's suggestion for a study design to test this cholesterol-cancer hypothesis.
Unfortunately, in 1986 it was impossible to realize this study design. The required genetic data were not yet available. That is changing. While, to the best of my knowledge, Katan's proposal has not been carried out yet, Voight and colleagues used his proposed design to investigate the HDL-heart disease theory.

The Death of Cholesterol?

They looked at a rare gene variant, which, as far as we know today, correlates strongly with HDL concentration, but not with any other cholesterol type. That's important, because we need to disentangle the effects of HDL from those of LDL. In their analysis, using data from 21,000 heart disease patients and 95,000 controls (people free of heart disease), the researchers could not find any association between HDL level and risk of heart disease. But Voight and colleagues didn't leave it at that. They also formulated a genetic risk score using 14 common gene variants with known effects on HDL (but not on LDL) and examined the score's association with heart disease in over 12,000 patients and over 41,000 controls. Again, nothing. Elevated HDL did not show up as the cherished knight in shining armor.
What do we make of this? First, that raising HDL cholesterol may not be a way to reduce the risk of heart disease. Therefore, secondly, let's not think that treating a so-called risk factor will reduce risk (more on that in my post "when risk factors for heart disease really suck"). Third, let's hope Pfizer & Co. get this message, too. Because drugs, which treat risk factors but not risk, are like impostors: they never deliver.



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