Supplements: Nutrition Science Or Nutrition Crap?

Nutritionists claim they are doing science, consumers buy it, and the supplements industry makes a healthy living from it. Only you probably won't. Here is why: 

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One of the enduring diet questions is whether supplements are a good tool to (a) improve health, and (b) compensate for nutritional deficits of an enjoyable but less than healthy dietary habit.  

To most people, the answer seems to be a resounding "Yes". In the U.S. more than 65% of the population are regular supplement users. They spend north of 28 Billion US$ annually on their pills and potions. To put this into perspective:  28 Billion is more than the gross domestic product of Cyprus - the latest EU country in need of being bailed out. While Cyprus circles the drain, the supplement industry doesn't. In fact it is growing by 10% annually. A growth, which, in 2008, Dr. Daniel Fabricant, then vice president of the Natural Products Association (NPA), had correctly predicted. He knew the drivers of that growth: "...the products that grow are the ones with science behind them. When there’s good science like there is behind ... vitamin D and omega 3s, that’s really where the dollar is going to be spent.” So, let's have a look at how good that science really is.  

Remember the time when Vitamin E and beta Carotene - the thing in veggies and fruits, which your body turns into Vitamin A - were found to be associated with decreased risk of lung cancer. The year was 1981 and the knowledge of that time had been summarized in the journal Nature [1]. You must keep in mind: if it's in Nature, it's like God's gospel.  Also keep in mind, that those studies were observational by design, that is, they observed an association between increased beta-carotene intake and lower incidence of lung cancers. Such observations do not allow us to say that one causes the other, even though the media types are typically quick in doing just that.  So, the natural conclusion from these association studies was: give smokers, those people who have the highest risk of getting lung cancer, a Vitamin supplement to reduce their risk. 

Then, in 1985, a group of Finnish researchers (The Alpha-Tocopherol, Beta Carotene Cancer Prevention Group, ATBC) did the one and only thing, which can establish a cause-effect relationship: a study in which male smokers, the people at highest risk for lung cancer, were given the supplement and another group wasn't [2]. In fact, the 29,000 participants had been randomized into one of 4 equal-sized groups, with group A receiving Vitamin E, group B receiving Vitamin A , group C receiving both Vitamins and group D getting simply a placebo. In 1994 the results came out. Certainly not in favor of the supplement. The guys on beta-carotene had an 18% higher rate of developing lung cancer than their peers who did not get this Vitamin. Actually, this rate was seen accelerating over time.

Another large trial, the beta-carotene and retinol efficacy trial (CARET) did essentially the same thing. It investigated the effect of beta-carotene on lung cancer risk in more than 18,000 participants at elevated risk due to their being smokers or having been exposed to asbestos. CARET was done in the U.S., and it delivered more sobering results: A 28% increase in lung cancer risk among those who had been randomized to receive the beta-carotene supplement [3]. The trial was halted, and follow-up observations showed a gradual reversal of elevated risk. That's a clear indication that the increased risk of lung cancer was attributable to the supplementation with beta-carotene and vitamin E. 

While these results certainly put a damper on the enthusiasm for vitamin A & E, the truly interesting finding is often overlooked and underreported: For the placebo guys in the ATCB study, there was a clear inverse relationship between intake of FOODS high in Vitamin E & A and the risk of lung cancer. The group with the lowest intake of those veggies and fruits, which deliver Vitamin E & A, had a 50% higher risk of developing lung cancer compared to those guys with the highest intake of fruits and veggies. 

These observation have been confirmed in the EPIC study which investigated the effects of diet on cancer. Also here, a high intake of fruit and vegetables, not supplements, was found to reduce smokers' risk of lung cancer considerably [4]. 

With these facts about nutrition science, and how the supplement industry uses it, I simply wanted to set the mood. Now, let's look at how this science is doing in the vitamin D and omega-3 department as emphasized by Dr. Fabricant.

Vitamin D supplements are believed to improve or maintain bone health in older adults, particularly in women. Indeed, what comes out of science labs seems to support this notion. Dr. Bischoff-Ferrari and her colleagues evaluated 11 randomized controlled trials to answer the question whether vitamin D supplementation reduces fracture risk in women aged 65 and older. It does. But only in those with the highest daily intake, more than 800IU. Good news for the supplement industry? You bet. But is it good news for you, too? Maybe not. Vitamin D needs to be taken with calcium to be effective. But high calcium intake by way of supplements appears to increase the risk for heart attacks, whereas dietary calcium intake, say from milk and cheese, does not [5]. 

In view of all this evidence the United States Preventive Services Task Force (USPSTF) recently issued its draft recommendation, which says that there is insufficient evidence to "...to assess the balance of the benefits and harms of combined vitamin D and calcium supplementation...". But rest assured, the supplement industry has all the evidence and science, which the USPSTF has not. Or so they want you to believe. 

Let's move over to the famous fish oils and their Omega-3s.

The Omega-3 fatty acids are often praised as the constituents of fish oil, which protect against heart disease. At least that's what the supplement industry says. Science says something else. A double-blind prospective study of 2500 men and women aged 45 to 80, who had experienced a heart attack or stroke, investigated whether omega3- supplementation would prevent further cardiovascular events [6]. It didn't. 

You might ask, why this study looked only at people who had already cardiovascular disease. Maybe they are so far down the drain, that fish oil can't do its trick any more. Wouldn't it be nice to know whether omega-3 is protective in people who do not have cardiovascular disease? Yeah, it would. It would also be nice for you to tell me how to run such a study. Realistically. You would have to enroll thousands of healthy people, randomize them into those who MUST NOT EVER get their hands on omega-3 supplements and those who MUST take it every day for many years. Go find those people. Then, after many years, you would have to compare the outcome between the two groups. And you also would have to rule out those outcomes to be affected by such factors as physical activity and all the different food habits those thousands of people have. Of course, you would need funding for this type of research. Only, who will give you the funds? Certainly not the pharmaceutical industry. It pumps billions into research, yes, but only for proprietary chemicals. There is nothing proprietary about a vitamin, which every Tom, Dick and Harry can put into a pill. Which is why even the supplements industry won't give you a single dollar for your research. Now you know why such studies are not being performed. And why nutrition science is so fickle with its results. 

What's the taking home point: When it comes to nutrient-health interactions, it is obviously not as simple as boiling down the effects of food to an individual vitamin or other nutrient. Neither is it as simple as stuffing this nutrient into a pill and shoving it down your throat. In the words of Einstein: "Make things as simple as possible, but not simpler." Reducing the effects of food to individual vitamins or other nutrients is obviously an oversimplification. When, as a result of oversimplification, nutrition science makes you jump from one supplement to the next, what does the supplement industry do? They are laughing their way to the bank. And, as we have seen, Mr Fabricant knows why. He is no more with the NPA, though. He has switched sides to work now for the FDA as director of its Dietary Supplement Programs division. Let's hope the FDA's view on nutrition science remains as skeptical as it ought to be. In the interest of your health. [tweet this].

1. Peto R, Doll R, Buckley JD, Sporn MB: Can dietary beta-carotene materially reduce human cancer rates? Nature 1981, 290(5803):201-208.

2. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994, 330(15):1029-1035.

3. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL, Jr., Omenn GS, Valanis B, Williams JH, Jr.: The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 2004, 96(23):1743-1750.

4. Gonzalez CA, Riboli E: Diet and cancer prevention: Contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Eur J Cancer 2010, 46(14):2555-2562.

5. Li K, Kaaks R, Linseisen J, Rohrmann S: Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Heidelberg). Heart 2012, 98(12):920-925.

6. Galan P, Kesse-Guyot E, Czernichow Sb, Briancon S, Blacher J, Hercberg S: Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ, 341.

Peto R, Doll R, Buckley JD, & Sporn MB (1981). Can dietary beta-carotene materially reduce human cancer rates? Nature, 290 (5803), 201-8 PMID: 7010181

The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group (1994). The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The New England journal of medicine, 330 (15), 1029-35 PMID: 8127329

Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, Valanis B, & Williams JH Jr (2004). The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. Journal of the National Cancer Institute, 96 (23), 1743-50 PMID: 15572756

Gonzalez CA, & Riboli E (2010). Diet and cancer prevention: Contributions from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. European journal of cancer (Oxford, England : 1990), 46 (14), 2555-62 PMID: 20843485

Li K, Kaaks R, Linseisen J, & Rohrmann S (2012). Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition study (EPIC-Hei Heart (British Cardiac Society), 98 (12), 920-5 PMID: 22626900

Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S, & SU.FOL.OM3 Collaborative Group (2010). Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ (Clinical research ed.), 341 PMID: 21115589

Nano-encapsulated supplements. Ballyhoo or miracle drug?

When humble supplements meet ultra cool nano-technology.

I'm going to continue where I left off in my previous post: With the question:

Does nano-encapsulation improve the effect of multi-vitamin multi-mineral supplements?

When I was confronted with this question my immediate reaction was: What is wrong with old-fashioned natural delivery of vitamins, from eating fruit, and vegetables, and, yeah, eggs and meat and drinking milk, all of which are the natural carriers of vitamins and more? Is this "nano-whatever" just a cool gimmick of an industry pushing a market, which "suffers" from only moderate growth? I admit it, I have a bias.  A bias for evidence. 

And as a health scientist I also have to admit that nano-encapsulation appeared, until now, only on the very fringes of the radar screen with which I observe the thousands of studies published each year on the subject of preventable, lifestyle-dependent chronic diseases. Literally thousands! Now go to PubMed, where the US National Library of Medicine and the National Institute of Health collect and archive all of those millions of studies and papers written on anything related to biomedicine and search for the combination of the terms "nano-encapsulation" and "vitamin" and you will find the stupendous number of ...

10 papers. None of them related to the oral administration of vitamins. That settled my initial fear, that my radar might have had a blind spot. The drawback was, I can't argue the case, for or against the usefulness of nano-encapsulation, based on published evidence. That leaves me no choice than to do what we scientists are supposed to do: to come up with testable hypotheses on subjects of which we have no, or not enough, knowledge. Which is why my answer to Björn's question will admittedly, be a highly subjective one. But then, there is no clear-cut answer anywhere else to get. Beware of the types who claim to have that answer!

Now let's get the technicalities out of the way first. What does nanoencapsulation mean? It simply means to coat one substance with another at sizes ranging from 1 to 1000 nm. The purpose of doing that is to

·       deliver a drug to a specific tissue or site in an organism, where the drug is then released

·       slow down or time the release of a drug. Which is a good way of delivering Insulin via a nasal spray, a very new technique, which has shown some promise in reducing food intake in overweight women.

·       adding certain micro-nutrients, such as omega-3 fatty acids, to foods without altering the foods' textures or tastes, and to prevent degradation of the otherwise volatile micro-nutrient

·       increase the shelf-life of vitamins

·       increase the bioavailability of anti-oxidants and to prevent unwanted reactions with other food items.

There are lots of other uses in the food and cosmetics industry, but they do not concern us here.

What we want to know is, whether a nano-encapsulated vitamin supplement does its job any different from, and possibly better than, a supplement that is not so encapsulated. 

Now when you take in vitamins, with your food or with supplements, these vitamins need to travel from the mouth through your esophagus and stomach to the small intestine where they will be absorbed through the intestine's membrane. Water-soluble vitamins are typically transported via some sort of a carrier, with the exception of vitamin B12, for which specific receptors do that job. Fat-soluble vitamins require the presence of the same enzymes which fat itself requires for being absorbed. All this happens in the small intestine, the one into which the stomach empties its content. These processes are complex but well researched and known in great detail. Now, just for laughs, let's look at what the geniuses at one of the nano-encapsulation supplement producers have to say about the point where nano-encapsulated vitamins meet the small intestine.

And I quote from here (http://livethesource.com/index.php/products/dailymultivitamin):

"livethesource® nanotechnology creates a particle size small enough to be efficiently absorbed, yet not so small as to be counterproductively absorbed by the body. We use all natural plant lipids as the basis of our nano encapsulation material. The importance of this cannot be overstated. The food grade material not only is absorbed and recognized as a safe substance, but also delivers its payload in a quick, safe and efficient manner."

"small enough to be efficiently absorbed" - as opposed to what? In the intestine water-soluble vitamins are transported molecule by molecule across the intestinal barrier and fat soluble vitamins are integrated into the micelles, which are small enough to pass through this barrier. That's what happens to the vitamins in your food. No nanoencapsulation required here. I also fail to understand what could possibly be a counterproductive absorption. Either vitamins are absorbed, or they are not, but counterproductive absorption is an oxymoron.

What really throws me off is the "natural plant lipids" which form the "basis of our nanoencapsulation material". If water-soluble vitamins are encased in lipids (another term for fat, or fatty acids) they are not available for transport as these vitamins' carriers and receptors will not recognize them. If the nanocapsules, thanks to their fat-soluble exterior, are integrated wholly into the micelles, which transport fat and fat-soluble vitamins, then the water soluble vitamins end up in the blood in a different pathway. If the nanocapsules are dissolved in the intestine prior to their absorption, then what difference does nanoencapsulation make to the absorption process. And with "difference" I mean the difference to naturally delivered vitamins of an apple or an egg yolk which you eat.

The rest of this quote is, like most of their page, a lot of ballyhoo.

Now it's time to return to our initial question: Does nano-encapsulation improve the effect of multi-vitamin multi-mineral supplements? You probably have guessed my answer: If I had to form a hypothesis, it would be something along the line of "nano-encapsulation in itself is not expected to improve a supplement based delivery of vitamins. The potential benefit of nanoencapsulating vitamins in supplements is the potentially longer shelf life of so encapsulated products."

But this longer shelf life benefits exclusively the manufacturer, not you, the consumer. Encapsulation or not, you'll only buy a bottle of vitamin pills which you can consume before it's use-by date. Don't you?

Now that you have read my point of view on vitamin supplementation (my yesterday's post) and on nano-encapsulation of supplements, I need to tell you why my arguments may not apply to you, personally. This is an issue which plagues medicine and public health, and it is hardly recognized or being talked about. This issue is at the heart of personalized medicine and personalized prevention. Stay tuned, because I will tell you in my next post, why you should be skeptical of the interpretation of the results of any study, regardless of who interprets the results. Whether it's me or anybody else.

Stay tuned.

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.