Can Chocolate Save You From Heart Attack?

The media says yes. Science says maybe. In the end, you decide. Here are the facts:


A truffle treatment for heart disease is imminent. That's what a recent article suggests, headlined in the New York Daily News as: "Dark chocolate cuts heart deaths; Study shows benefits for high risk cardiac patients." 

The funny thing is, the cited  study does not show what the media geniuses claim it does. So, let's look at this master piece of research journalism and ...
do a little fact check. [tweet this].

The cited study was performed by Ella Zomer and colleagues in Australia [1]. The researchers wanted to answer the question, what the daily consumption of dark chocolate would do to the heart health of a given population. Contrary to what you might believe, the researchers didn't pit chocolate eaters against abstainers. They simply ran an algorithmic model on the computer. In this case, a 10-year forward projection of what might happen, heart-wise, in a given population. Nothing wrong with that, as long as we keep in mind that such models are based purely on assumptions. You need to know those assumptions before you start investing a part of your daily food budget into chocolate.  So, let's take a more detailed look than the anonymous AFP writer did, whose master piece the NYDN bought to educate their readers.

The researchers selected the data sets of 2013 AusDiab study participants who were free from cardiovascular disease and diabetes, but who had the metabolic syndrome. The latter is not a disease in itself but an arbitrary risk definition along 5 risk factors: abdominal obesity, elevated triglycerides, blood sugar and blood pressure, and low "good" cholesterol (high-density lipoprotein, HDL). Have any three of those 5, and you are said to have the metabolic syndrome. 

To calculate the risk of suffering a heart attack or stroke, the researchers used the algorithms developed from the Framingham study. Those risk calculations are widely used in clinical practice. They inform your doctor about the need and urgency of treating you to prevent a heart attack or stroke. I have written about the sense and nonsense of such risk factors in my earlier post "When risk factors for heart attack really suck!".  Now, in order to calculate what the blissful consumption of chocolate will do to prevent such heart attacks, we need some more data. The researchers took those from 13 studies, which investigated the effects of chocolate consumption on blood pressure and on cholesterol levels.  

Now here is the first problem: While the Framingham study's algorithms have been tuned on the correlation of risk factors with with hard outcomes (real heart attacks and strokes) for more than half a century, the longest clinical trial on the effects of chocolate lasted just 18 weeks. Meaning, for the effects of chocolate consumption, we don't have anything remotely equivalent to the Framingham data. And we will probably never have, because it is difficult to imagine a study in which we expose half the participants to a daily chocolate load for many years, while the other half doesn't get any, with us waiting and watching what happens in terms of heart disease. Which is to say, the 13 studies used by the researchers are the next best choice. It informs us about the effects of chocolate consumption on blood pressure and cholesterol. The researchers plugged those data into the mathematical model, together with the Framingham algorithms and the life tables available for their Australian population. The entire model is based on a so-called "Markov model", which is simply a probability-based simulation of processes over time. 

  

Now that we are clear about the methods and assumptions, let's look at what you read in the article: 

"Australian researchers have found that eating a block of chocolate daily over 10 years has 'significant' benefits for high risk cardiac patients and could prevent heart attacks and strokes." Well, didn't I just tell you that the participants' data sets had been selected such that only those who were not cardiac patients, were considered in the model? Yep, that's what it says in the methods section of the study. But methods are tedious to read and, admittedly, a bit difficult to understand sometimes, so we forgive our writer for this little slip-up. Also, none of the participants had eaten a chocolate bar daily for 10 years, so really nobody could "have found" what that would have done for heart risk. But let's not dwell on such trifles. On to the next paragraph:

"A study .... found that the consumption of ... chocolate ... was an effective measure to reduce risk." Whoa, that one we can't forgive. What we do have are 13 studies, which show that a daily chocolate consumption of about 100 grams (3.5 ounces) reduces systolic blood pressure in hypertensive people by 5 mmHg on average, and total cholesterol by 0.21 mmol/L (8mg/dL). What these studies do not show, is a reduction of risk for heart disease, that is, a reduction of real heart attacks and strokes. 

Given the size of the improvements, I have serious doubts about those effects anyway. What I observe as blood pressure measurements in the daily clinical practice, a 5mmHg difference is within the error margin of many physicians' and nurses' measurement skills. And a 0.21 mmol/L difference in cholesterol is deep within the bandwidth of variations, which most people would see if they were to measure their cholesterol levels for a few days in a row. We have done that in our lab, and found the intra-individual variability to be way above those 0.21 mmol/L. In other words, if your cholesterol level is measured today, and tomorrow, and day after tomorrow, the values will vary by more than those 0.21 mmol/L, even if your blood was drawn at the same time of day, and always after an overnight fast.  

On to the next paragraph: "Lead researcher Ella Zomer said the team found 70 fatal and 15 non-fatal cardiovascular events per 10,000 people could be prevented over 10 years if patients at risk of having a heart attack or stroke ate dark chocolate." Throwing out numbers always looks good, but what do these numbers mean for YOU? I operate under the assumption that you are not interested in the 85 events among the 10,000 people, but that your interest is with the ONE possible event in YOU, right? 


OK, let's look at that. Of course, I don't have the data set of Zomer and colleagues, but we can make quite an educated calculation using the Framingham risk algorithm, the average risk profile of the participant and the researchers' statement of the effect size: 85 prevented events per 10,000 people. And here is what it means to you: 

If your profile is that of the average participant (that is, you are 53 years old, have a systolic blood pressure of 141 mmHg, total cholesterol of 6.1 mmol/L and HDL-cholesterol of 1.2 mmol/L), your chance of suffering a heart attack or stroke over the next 10 years would be roughly 10%. 

Eating chocolate every day would reduce this risk by a whopping 0.3% to 9.7%. Wow. 

So, over to you: do you agree with the article's next paragraph, where it quotes the researchers as saying that "Our findings indicate dark chocolate therapy could provide an alternative to or be used to complement drug therapeutics in people at high risk of cardiovascular disease."? I can already hear people telling their friends about the chocolate therapy they are on. Sounds fully compliant with the researchers' next statement "... here is a dietary alternative which may be quite appealing to a lot of people. In fact, chocolate studies have shown really good compliance rates." 

Well, except for the morsel about compliance rate, I don't buy it. Think about it. 100 grams of chocolate pump 550 kcal into your body (coincidentally the same as a Big Mac), delivered by  50 grams of sugar and 36 grams of fat, most of it saturated. And one more thing: the ingredient which, we believe, is the cause of chocolate's beneficial effect is the flavanol content. I won't go into details about this member of the flavonoid family, but suffice it to say, you'll find it in effective doses only in chocolates with at least a 70% cocoa. That is bitter chocolate. Also known as dark chocolate. But the latter name is already a potential for deception by the manufacturer. The flavanols are inherently bitter, which is where bitter chocolate originally got its name. To make it more pleasant to your taste buds, manufacturers can take the flavanols out and compensate by making the chocolate darker by other means. The end effect is a dark chocolate, which delivers all the sugar and fat and calories but none of the benefits for which you might have chosen it. 

Also, the flavanol content of cocoa can vary substantially, depending on where it comes from. No wonder, you find nothing written about your favorite chocolate's flavanol content on its nutrition label. And by the way, you encounter the flavonoid superfamily, of which chocolate's flavanols are a member, in virtually all fruits and vegetables. Often in concentrations which far exceed what chocolate has to offer. 

So here is what we see in this article of the New York Daily News: there is public health, there is you and then there is the media. To public health, 85 avoided heart attacks and strokes per 10,000 people is worth something, particularly when public health doesn't need to pay for it. Because you do, by buying your "chocolate therapy". Public health couldn't care less whether your 0.3% risk reduction is meaningful for YOU. But you care, I presume. Which is why I find it regrettable that you have to deal with the degree of misinformation doled out by those media geniuses, who, like public health, are not interested in YOU. They are interested in your subscription and your dollar. 


So, if you think that some of your friends would benefit from knowing about this, then send them this post. If you or they have an elevated risk for heart disease, there are many proven ways to reduce that risk. Eating chocolate is not one of them. [tweet this].  

1. Zomer, E., et al., The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model. BMJ, 2012. 344(may30 3): p. e3657-e3657.

Zomer, E., Owen, A., Magliano, D., Liew, D., & Reid, C. (2012). The effectiveness and cost effectiveness of dark chocolate consumption as prevention therapy in people at high risk of cardiovascular disease: best case scenario analysis using a Markov model BMJ, 344 (may30 3) DOI: 10.1136/bmj.e3657

Can A Genetic Test Say Why You Are Fat?

With the decoding of the human genome came the hope of getting a lever on the chronic diseases, which kill most of us today: heart disease, stroke, diabetes and many cancers. And since overweight and obesity are a common cause of those diseases, many obese people were, and still are, yearning for that exculpatory headline: "It's all in your genes!" Why and how this headline is unlikely to ever appear in any serious media, was a subject of my earlier post "It's not your genes, stupid!".

Now, a group of researchers have looked at the data of a 30-year investigation of health and behavior, ...
which you might call the New Zealand equivalent of the famous U.S. Framingham study [1]. If you ever wondered whether it would make sense to get your children, or yourself, tested for your genetic risk of obesity, you will be surprised to learn what this study tells you. But one step at a time. Let's first have a look at this outstanding piece of research. [tweet this].

The study population consists of all the 1037 babies born in Dunedin, New Zealand, between 1st April 1972 and 31st March 1973 at the Queen Mary Maternity Hospital. Comprehensive health assessments were done at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38. These investigations will be extended into the future and into the next generation. This is a massive and admirable effort. With data having been collected about virtually all aspects of health and behavior, this project provides a rare opportunity to match those data with genetic information. While genetic profiling wasn't possible in the seventies, it is possible and feasible now. And since study participants' genetic make-up hasn't changed since the time of their conception, we can retrospectively look at the correlation of biomarkers and genes, in this case those that correlate with obesity. To understand this study let me familiarize you with some facts and terms first.

So-called genome-wide association studies (GWAS) have thrown up more than 30 individual single-nucleotide polymorphisms (SNP, pronounced 'snip'), that's geneticists' speak for a variation of a single building block (nucleotide) of a gene. The draw-back: Those SNPs individually correlate only very weakly with obesity. That is, while there is a statistical correlation with obesity, there are obese people who don't carry the SNP, and there are carriers of the SNP who are not obese. To complicate matters a little further, not all SNPs which show statistical correlations in one population, say the U.S., do so in another, say New Zealand. Which is why the Dunedin researchers developed a risk score from the 32 SNPs known from other studies. Of those 32 they could find 29 in their study cohort, and so they developed their score from those 29 SNPs. Participants were grouped according to their score into either high- or low-risk.

The next step was to look at how the participants' genetic risk score (GRS) correlated with BMI in each decade, starting from 15-18 years of age, followed by 21-26 years, and then from 32-38 years. In the second decade (ages 15-18), people with a high risk score had 2.4 times the risk of being obese than those who scored low on the GRS. Had this been you, having a high risk score would have made you almost two and a half times more likely to be obese as a teenager compared to your buddies of the low-risk persuasion. That sounds like a lot, and you might be tempted to think that screening your child for genetic risk would help you to be more vigilant in watching over his or her BMI while he or she is still under your care.

The authors certainly seem to think so when they say that "These findings have implications for clinical practice..." and that "the results suggest promise for using genetic information in obesity risk assessments." I respectfully disagree, and so might you.

Let's simply take your point of view for a moment, and not the one of public health, where we are interested in one patient only, the population under our care. In contrast, the only patient you are interested in is you, or maybe your child. This value of a relative risk of 2.4 doesn't tell you much. What you rather want to know is, what a high- or low-risk score means to you. And the right question to ask would be along the line of "what are the chances of becoming obese when my risk score is high?". And also, "what are my chances of not becoming obese when my risk score is low?". The answers to these 2 questions come in the shape of values, which we call positive predictive value (PPV) and negative predictive value (NPV). Unfortunately the Dunedin researchers don't report those values. But we can calculate them, which I did.

And here is the surprising answer: if you had a high score, your risk of being obese as an adolescent is just about 10%. In other words, even with a high-risk score, you stand a 90% chance of not being obese as an adolescent. And if your risk score had been low you would have a 95% chance of not becoming obese. Beats me, but I can't see the benefit of genetic testing.

I deliberately talk only about the risk at the age of adolescence. There is a simple reason for this. The researchers found that the relative risk of obesity between the high- and low-risk categories diminished progressively from 2.4 in the second decade to 1.6 in the fourth (ages 32-38). That means, our looking at adolescents affords us a look at a time when study participants' exposure to environmental and behavioral influences had been relatively short. Over the years, environment and behavior further diminish the predictive power of the genetic score. Which is akin to saying: your lifestyle choices give you a greater power over your BMI than your genes. And by extension, the choices you make for your children's lifestyle beats their genes easily, too. In other words, it's not so much the luck of the draw, which determines your body weight, but rather your skill of playing the deck of (genetic) cards, which we have been dealt at the moment of conception. The study's data say the same thing just in other words: At birth the high-risk babies were not any heavier than their low-risk peers. Only once they were exposed to the outside world, did BMI careers begin to divert. For some of them.

This tells us one thing: when it comes to obesity, habits and environment are the key, not a potpourri of SNPs. Of course, if you are in the business of peddling genetic tests, you will disagree. And also when selling guilt-free conscience to obese readers is what pays your bills. Which is why I'm curious to see how the media will portray this study. Let's stay tuned. [tweet this].

1.    Belsky, D.W., et al., Polygenic Risk, Rapid Childhood Growth, and the Development of ObesityEvidence From a 4-Decade Longitudinal StudyPolygenic Risk for Adult Obesity. Archives of Pediatrics and Adolescent Medicine, 2012. 166(6): p. 515-521.

Belsky DW, Moffitt TE, Houts R, Bennett GG, Biddle AK, Blumenthal JA, Evans JP, Harrington H, Sugden K, Williams B, Poulton R, & Caspi A (2012). Polygenic Risk, Rapid Childhood Growth, and the Development of Obesity: Evidence From a 4-Decade Longitudinal StudyPolygenic Risk for Adult Obesity. Archives of pediatrics & adolescent medicine, 166 (6), 515-21 PMID: 22665028

No Time To Exercise? You Are Not Alone!

Lack of time is the most often cited excuse for not exercising. I deliberately chose the word "excuse" over its less judgmental alternative "obstacle". Simply because I cannot see an "obstacle" when I compare two simple metrics: the hours people spend watching TV and the minutes needed to maintain one's health with exercise. With high intensity interval training, or HIT, health enhancing exercise can be compressed into an amazingly short amount of time. When done right. [tweet this].

According to the Nielsen "Three Screen Report" Americans spend 5.1 hours daily in front of their TV. But they admit to "only" half that time, according to a survey of the Bureau of Labor Statistics. To be fair, I take the survey's figure of 2.7 hours for the comparison with the American College of Sports Medicine (ACSM) current guidelines for quantity and quality of exercise [1]. The ACSM's recommendations of 2.5 hours exercise PER WEEK vs. 2.7 hours in front of the TV PER DAY. Cut your 162 minutes of daily TV watching by just 21 minutes, and it still leaves you with more than 2 hours for mind numbing soaps.  

On a cautionary note to my fellow German readers: don't think for one minute that our TV habits are in any way better than those of our U.S. friends. According to statista's "Daten & Fakten zur Mediennutzung" we spend on average 220 minutes in front of the dumb tube. So, either we have, for once, outdone our U.S. friends, or their self-admitted 2.7 hours are an understatement. Anyway, those figures tell you why I talk about excuses and not obstacles.

But I'm a realist. Whatever my view on the issue of having time, it won't change other people's views. Which is why my colleagues in public health have begun to look into ways of how to get the same health punch out of dramatically shorter exercise routines. And, as I mentioned in my previous post, the solution might have been found. It is called high intensity interval training, or HIT.

HIT is an exercise routine, which consists of brief bouts of vigorous activity, alternating with "active recovery" periods of more moderate intensity.  Until very recently, researchers focused on the comparison of HIT with the conventional continuous endurance exercise of moderate-to-vigorous intensity, which is what those public health guidelines are all about. Most studies comparing those two exercise alternatives matched them for energy expenditure. Since energy expenditure is higher during the intense bout the overall time needed to expand the same amount of energy is shorter in HIT than in continuous exercise. 

Latest research efforts, however, try to answer the question whether those high-intensity bouts might even compensate for an overall lesser energy volume. In other words, could we reduce not only the time spent on exercise but also the total exercise volume simply by doing HIT? Which means, reducing the time required for doing exercise even further? The latest study, conducted by Katharine D. Currie and her colleagues seems to suggest just that [2]. Before I go into the details, let me explain why I find her line of investigation very appealing and important.

The overall purpose of exercise is to maintain functional health. The reason why exercise is key to human functional health is because humans are made to move. Only, today they don't move anymore. That's why my primary interest in exercise is about its link to health. Anything else, such as weight loss, is secondary. Because, if I can improve health by exercising, I have achieved my objective.  Regardless of whether weight loss has materialized as a side effect or not. Weight loss for its own sake without any improvement in health is a purely cosmetic issue, which doesn't interest me that much.

One of the main health issues attached to exercise is arterial function. It's impairment is the first step that leads to atherosclerotic plaque build-up in your arteries and ultimately to heart attack or stroke. The entire process typically lasts decades, and our current portfolio of risk factors, such as high cholesterol, alert us way too late to this situation. I have written about this in my earlier post "When Risk Factors For Heart Attack Really Suck". Which is why I believe that arterial function is THE benchmark for testing the efficacy of exercise: It's an extremely sensitive early warning signal and a reliable tool to measure the effect of your exercise efforts. This is what Currie and colleagues had in mind. They wanted to see how a low-volume HIT routine affected the arterial function and fitness of 10 participants with existing heart disease.

Participants were tested individually for their fitness on a cycle ergometer. The researchers used the results of the fitness test to set the parameters for the two exercise routines, which all participants had to perform. The endurance protocol was set at 55% of each participant's peak power output as determined during the fitness test. In the endurance exercise bout, participants had to cycle at this intensity for 30 consecutive minutes.

The HIT protocol consisted of 10 1-minute bouts of exercise at 80% of peak power output, separated by 1-minute bouts at 10% of peak power output. That's 30 minutes of continuous exercise vs. 19 minutes of HIT, not considering warm-up and cool-down which were the same for both protocols.
Interestingly, while all participants completed the HIT protocol, 2 participants were unable to last through the endurance protocol. Arterial function improved after both exercise protocols similarly, despite the fact that the total work performed in the endurance protocol was significantly greater than in the HIT protocol.

Now, 10 participants is a rather small number of subjects for such a study. The problem with a small number is insufficient statistical power to detect a difference in arterial function between the two protocols, if there was a difference. Which is why we will be looking forward to seeing larger trials investigating this question using more participants.

The researchers also show one thing which is always close to my heart but which is rarely reported in study publications: the very different outcomes between individuals. After the endurance exercise one participant saw a dramatic improvement in arterial function, 4 participants had a more modest improvement, and the remaining 5 no improvement. Following the HIT routine, there were 2 participants with a dramatic improvement of arterial function, 2 with a more moderate improvement, 1 whose arterial function actually got worse and the remaining 5 with no change. Unfortunately the researchers do not tell us whether those who improved or didn't improve in one routine showed corresponding effects in the other routine. My guess is, for at least some of the participants, the reaction will have been different. But even if that was not the case, we can see again, that the presentation of group results masks the fact that different people react very differently to the same type of intervention. I have presented an example of this effect in my earlier post "Am I shittin' you? Learn to be a skeptic".

A similar degree of inter-individual difference was seen in a study which used the same protocol of low-volume HIT, but this time on healthy sedentary adults. The question was whether 2 weeks of performing the HIT routine 3 times per week would improve the participants' ability to burn fat instead of carbohydrates. This so called oxidative capacity is a marker of metabolic health and gives you a clue about your diabetes risk. True enough, the results support the idea, that this minimal amount of exercise can substantially improve metabolic function. But again, the wide standard deviation of the group results points at substantial differences between the individuals [3].  

These inter-individual differences make prescription of exercise always a trial-and-error effort. As much as you would like to hear from your coach or doctor that a specific type of exercise will have a specific effect on your health, nobody can give you that certainty. In fact, if you encounter a coach who talks certainty, you know a coach whose knowledge is too limited to make him recognize his own limitations. That's something to be wary about.

Now, what if you would like to try HIT for yourself? How would you design a HIT routine? Before I give you a few pointers, let me warn you first: Do not take my advice as a medical recommendation. You follow it at your own risk. If you have been sedentary, and you have any doubt as to whether exercise at high intensity is good for you, seek medical advice first.

Obviously the best way of designing a maximally effective HIT routine is to go through a fitness test first. Ideally, one which tests things like your maximal oxygen consumption. The gold standard is the cardiopulmonary exercise test during which gas exchange is measured together with heart rate or ECG. The measured values will allow your coach to tailor the intensity of the intervals to maximum effect. But there is a simple do-it-yourself way, too. Here is how it works:

In exercise research we know that people's perception of exertion correlates quite reliably and closely with biomarkers of exertion (e.g. heart rate, oxygen consumption). We call this subjective perception the "rate of perceived exertion" or RPE. And we have scales for you to express this RPE. The most commonly used one is the Borg scale of perceived exertion. I personally prefer the OMNI version because its 0-10 scale is so much more intuitive than Borg's 6-20 scale. 

The picture to the right is a copy of the OMNI scale.

It doesn't matter whether you run or cycle or do any other type of endurance exercise. What you would describe as "extremely hard" (9-10) is the most strenuous intensity at which you can currently perform your exercise. Regardless of your personal maximal oxygen capacity. That means, an Olympic marathon runner has his 100% max at 10 and so do you as a couch potato. Even though both of you have vastly different capacities. Since we want to exercise at 80% of that capacity it doesn't matter what it's absolute value is. The only thing that matters is that we hit the 80%. Which is what these scales are so good for.

At the left end (0) of the scale you find the descriptor "extremely easy", which is the way you would describe an exercise that you could perform for very long durations without any distress. The point is to get your exercise intensity during the high-intensity intervals to where you would describe the feeling as "hard", that is, at a 7-8 out of 10. That point correlates pretty closely with the 80-85% of maximal effort used by the researchers. The period of active recovery, which separates two high-intensity intervals, should get you to a perception in the range of 4-6.

Keeping this scale in mind you can now perform your own interval training with whatever exercise you fancy, whether its cycling, running, skating, swimming, or whatever. From experience with our own study participants I find a HIT routine of 1-minute high-intensity intervals, separated by 4-minute active recovery intervals, the most agreeable to start with. If that's too tough, cut the high-intensity interval down to 45 or 30 seconds. Try to get 3 to 4 high interval bouts into one exercise. And don't be frustrated if initially you can manage only two. Do this 3 times a week, always with one day between 'HIT days', and you'll find your fitness level responding very fast to this minimal effort. Increasing this effort will be no problem. You can play around with different ways of doing that. Shortening the active recovery period is one way. Stringing more intervals into your exercise bout is another. The variations are limitless.

If there is one particular biomarker which you want to improve, be it blood pressure, blood sugar or arterial function, get it tested before you start and then a couple of weeks after you have persisted with the weekly HIT routine. To see the health effects of your efforts can be a strong motivator to go on, or to do even more. To get from 20 minutes three times a week to 20 minutes daily will be a huge improvement. It still leaves you with plenty of TV time, and probably with enough time to wonder how you could have ever thought of time being an obstacle to exercise.

You'll probably not be tempted to do what I did 10 years ago: I threw out my TV and never replaced it. Which is why I can now work, study, exercise and write a blog. Which also means that to compensate for my zero TV time, somebody must spend a lot longer in front of the TV than the average 2.7 hours. Could that be you? Or someone you know, who would benefit from reading this?  [tweet this].

1.    Garber, C.E., et al., Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Apparently Healthy Adults: Guidance for Prescribing Exercise. Medicine & Science in Sports & Exercise, 2011. 43(7): p. 1334-1359 10.1249/MSS.0b013e318213fefb.

2.    Currie, K.D., R.S. McKelvie, and M.J. Macdonald, Flow-Mediated Dilation Is Acutely Improved following High-Intensity Interval Exercise. Medicine and Science in Sports and Exercise, 2012.

3.    Hood, M.S., et al., Low-volume interval training improves muscle oxidative capacity in sedentary adults. Medicine and Science in Sports and Exercise, 2011. 43(10): p. 1849-56.

Garber, C., Blissmer, B., Deschenes, M., Franklin, B., Lamonte, M., Lee, I., Nieman, D., & Swain, D. (2011). Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory, Musculoskeletal, and Neuromotor Fitness in Apparently Healthy Adults Medicine & Science in Sports & Exercise, 43 (7), 1334-1359 DOI: 10.1249/MSS.0b013e318213fefb

Currie KD, McKelvie RS, & Macdonald MJ (2012). Flow-Mediated Dilation Is Acutely Improved following High-Intensity Interval Exercise. Medicine and science in sports and exercise PMID: 22648341

Hood MS, Little JP, Tarnopolsky MA, Myslik F, & Gibala MJ (2011). Low-volume interval training improves muscle oxidative capacity in sedentary adults. Medicine and science in sports and exercise, 43 (10), 1849-56 PMID: 21448086