Will The Polypill Prevent Your Heart Attack?

Giving the polypill to everybody above the age of 55 kills two birds with one stone: cardiovascular risk and preventive medicine. That's what the proponents of the polypill say. The medical establishment is in uproar. Here is why you should be, too. But for a different reason. [tweet this].

   

We are typically sold on the notion, that heart disease and stroke have become today's major killer, for one simple reason: We live far longer than our ancestors of a hundred years ago, whose major cause of death were infectious diseases. Their eradication has brought upon us the blessings of longer lives, and with it the detriments of aging related cardiovascular disease. It's root cause is elevated cholesterol, a theory enshrined in the so-called lipid hypothesis. Questioning it is to the medical establishment what Galileo's theories were to the catholic church: plain heresy. After all, cholesterol lowering drugs, the statins, are a blessing to mankind and substantial reducer of cardiovascular death. 

    

This is what nearly everyone believes.

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To hell with exercise

Who says that exercise is medicine? For one, the American College of Sports Medicine (ACSM) of which I'm a professional member. Then, how can I say it isn't?

Let's look first at the conventional view of the benefits of exercise. There is a large and increasing amount of evidence which clearly tells us that exercise prevents today's number 1 killer: cardiovascular disease. That is, heart attack, stroke and peripheral vascular disease. Mind you, what is common knowledge today emerged only some 50 years ago when Morris and colleagues discovered that UK bus conductors, the guys climbing up and down the double-decker London buses, had better fitness and fewer heart attacks than their all-day-seated driver colleagues [1].

In the years since then our knowledge about the effects of physical activity on cardiovascular, metabolic and mental health has virtually exploded. From this evidence the U.S. Dept. of Health and Human Services (HHS) concluded in 2008 that the most active people of the population have a 35% reduced risk of dying from cardiovascular disease compared to the least active people [2]. The WHO lists insufficient physical activity (PA) as the 4th leading cause of death world wide after high blood pressure, tobacco use and high blood glucose. What's wrong with this picture? High blood pressure and high blood glucose are known consequences of a sedentary lifestyle. So is obesity, which ranks 5th place on the WHO killer list. Which is why physical inactivity deserves top spot on that list.

What most people don't know is the way lack of physical activity causes all those diseases, from insulin resistance and diabetes to arterial dysfunction and atherosclerosis, and from there to heart attack, stroke, kidney failure. The mechanisms are extremely complex, and, while we have untangled quite some of them, there are probably a lot more to discover. I'll try to make this the subject of one of the next blog posts. 

Now you are probably asking yourself, how the hell, with all this evidence, will I ever be able to make my point that physical activity is not a medicine. Ok, here it comes: it's a matter of viewpoint. The one I'm taking is the one of evolutionary biology. Let me play its advocate and present as evidence a couple of insights.

First, our human ancestors, who had roamed this Earth as hunter/gatherers for the most part of human existence, had, by necessity, a much more physically active lifestyle. A lifestyle which required at least 1.7 to 2 times the normal resting energy expenditure [3]. [To get an idea about resting energy expenditure and physical activity levels and how they are calculated, simply follow the links to the videos.] Those ancestors' genes are what we have inherited. And these genes are exposed to a lifestyle which is vastly different from the ones under which these genes evolved. Specifically with a view to physical activity, which brings me to evidence no 2:

What we typically observe today are physical activity levels with factors of somewhere between 1.2 and 1.4 of our resting energy expenditure. That's true for most people.

Even if you were to follow the ACSM's recommendation of 30 minutes of moderate to vigorous exercise on at least 5 days per week, would you NOT reach the level of 1.7 if you are working in a typical office job or doing house work. Which means, the physical activity levels which we recommend today, do not add a behavioral type of medicine into our lives, they merely reduce the extent of a "poisonous" behavior called sedentism. It's like cutting down from 2 packs of cigarettes per day to 1 pack. Would you call this a "medicine"? Would the ACSM call that a medicine? With respect to exercise they do.

So, OK, if you had been attracted to this post in the hope of finding some excuse for not doing exercise, or some argument to get those exercise evangelists, like myself, off your back, I'm sorry to have disappointed you. No, actually, I'm not sorry. And neither will you be, if you get your physical activity level above those 1.7. Then you may just start calling exercise a medicine. Until then, chances are you will still go to hell with exercise, because you get too little of it. Certainly too little to stay out of that hell of heart disease, stroke, diabetes and many cancers.

1.           Morris, J.N. and P.A. Raffle, Coronary heart disease in transport workers; a progress report. Br J Ind Med, 1954. 11(4): p. 260-4.

2.           Physical Activity Guidelines Advisory Committee, Physical Activity Guidelines Advisory Committee Report, 2008, U.S. Department of Health and Human Services: Washington, D.C.

3.           Eaton, S.B. and S.B. Eaton, An evolutionary perspective on human physical activity: implications for health. Comp Biochem Physiol A Mol Integr Physiol, 2003. 136(1): p. 153-9.

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MORRIS JN, & RAFFLE PA (1954). Coronary heart disease in transport workers; a progress report. British journal of industrial medicine, 11 (4), 260-4 PMID: 13208943
Eaton, S., & Eaton, S. (2003). An evolutionary perspective on human physical activity: implications for health Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology, 136 (1), 153-159 DOI: 10.1016/S1095-6433(03)00208-3 PrintPDF

Screw Your Health?!

So, what's your excuse for not exercising enough, for smoking, for not watching your diet, for getting fatter every year, and therefore having high blood pressure, and too much glucose and cholesterol in your blood?

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Do vitamin supplements make you healthier?

The (non-)sense of vitamin supplementation?

Almost one in two American adults is a regular user of vitamin and mineral supplements, either in the form of single- or multivitamin/mineral formulations (MVMS). It all adds up to a market of US$ 9 Billion annually, or one third of the total US supplements market. Does all the pill-popping help their users to achieve better health or longevity? 

That's one question raised by Björn, one of the readers of my blog. Thanks, Björn, I wanted to write on this subject for some time. You just got me going on this a little earlier than I would have otherwise. And also thanks for the second question: Does the latest technology of delivering the drug (not to your house, but within your body to your organism's cells) via "nano-encapsulation" improve that health effect in any way? Let me try to answer these questions one by one.

When you talk about vitamins, you talk about essential micronutrients, for which the human organism has either no or only a very limited ability to produce (e.g. Vitamin D) on its own. If you want to group vitamins according to their solubility you'll find that they come in two flavors: water soluble and fat soluble. Of course, you could group them for any other biochemical characteristic, but grouping them according to their solubility makes immediate sense when you keep in mind that the fat soluble ones (A, D, E and K) can accumulate in your body's tissues, whereas the water soluble Vitamins typically can't. Whatever can accumulate, can also accumulate to the point where there is too much of it in a body's tissue. So, yes, too much of a good thing may turn into a not so good thing, as is the case for vitamins A and E for example. Or, too much of a good thing may just be flushed out of the body, as is the case with water-soluble vitamin C.

The supplement industry certainly does a good job convincing the public that supplementing one's diet with additional vitamin formulations is good for one's health. It's certainly good for the industry's bank accounts. In such cases it always pays to ask one simple question: Where is the evidence?  

In a meta-analysis of randomized clinical trials (RCT, the gold standard of clinical research methodology), the authors investigated the effects of vitamins E and A on the risk of cardiovascular disease and death in altogether 220,000 patients [1]. The effects? Zilch. The authors recommendation? The evidence does not support any recommendation for the use of Vitamins E and A. On the contrary, they found a slight increase in all-cause and cardiovascular disease mortality associated with vitamin A supplementation.

In another 2007 review on the subject, published in the American Journal of Clinical Nutrition, its author came to the same conclusion, stating that "Results to date are not compelling concerning a role for MVMs in preventing morbidity or mortality from cancer or CVD." [2] The two largest trials on Vitamin A and E supplementation in smokers, the Finnish Alpha-Tocopherol Beta-Carotene (ATBC Trial) and the US Carotene and Retinol Efficacy Trial (CARET) enrolled 29,000 and 18,000 smokers. In the Finnish trial, supplementation with Vitamin A increased the risk for lung cancers by 18% within a 5 to 8-year observation period [3]. And the US trial was halted after 2 years for the same reason: a 28% increase in lung cancer risk, a 26% increase in risk for dying from cardiovascular disease [4]. In 22,000 healthy men who had been observed for 12 years, supplementation with vitamin A showed neither benefit nor harm [5].  

So where is the evidence for you to believe that buying Vitamin E and A supplements will make you healthier and live longer? Maybe I'm blinded by a perverse distrust of everything a sales man tells me, but I can't see it.

So, how about multi-vitamins? In the group of people with the highest take-up rate of multivitamins: post-menopausal women? Again, the authors of a study which pooled the data from the Women's Health Initiative trial and observational study cohorts, come to the same conclusion "the WHI CT and OS cohorts provide convincing evidence that multivitamin use has little or no influence on the risk of cancer or CVD in postmenopausal women." [6].

Not even for infections is there any evidence that MVMS have any protective effect on those most vulnerable, the elderly [7]. 

Of course, keeping all this in mind, the nagging question remains: would there be an effect if only the delivery of the drug in the human body was improved? After all, if vitamins are essential for survival, and if vitamin supplementation does not improve health, then there are several possible reasons for this observation. For instance, we might get enough vitamins from our food, and adding vitamins has simply no effect. Or, maybe we have vitamin deficiencies but the supplements are ineffective in delivering their vitamin loads.

Which brings us to Björn's second question: "Does nano-encapsulation improve the effect of MVMS?

And may I add my nagging question: Or is "nano-whatever" just a cool gimmick of the industry to push a market, which currently grows only moderately? In the next post (Monday 16. April) I'll try to answer this question. So, stay tuned. 

1.           Vivekananthan, D.P., et al., Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet, 2003. 361(9374): p. 2017-23.

2.           Prentice, R.L., Clinical trials and observational studies to assess the chronic disease benefits and risks of multivitamin-multimineral supplements. American Journal of Clinical Nutrition, 2007. 85(1): p. 308S-313S.

3.           The Effect of Vitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers. New England Journal of Medicine, 1994. 330(15): p. 1029-1035.

4.           Omenn, G.S., et al., Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med, 1996. 334(18): p. 1150-5.

5.           Hennekens, C.H., et al., Lack of Effect of Long-Term Supplementation with Beta Carotene on the Incidence of Malignant Neoplasms and Cardiovascular Disease. New England Journal of Medicine, 1996. 334(18): p. 1145-1149.

6.           Neuhouser, M.L., et al., Multivitamin Use and Risk of Cancer and Cardiovascular Disease in the Women's Health Initiative Cohorts. Archives of Internal Medicine, 2009. 169(3): p. 294-304.

7.           El-Kadiki, A. and A.J. Sutton, Role of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomised controlled trials. BMJ, 2005. 330(7496): p. 871.

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