Die Sucht aufs Essen. Warum wir dick werden obwohl wir es nicht wollen.

Unser Essverhalten wird weniger vom freien Willen und der Vernunft gesteuert, als vielmehr von autonomen Mechanismen. Den Verhaltensforschern sind sie bekannt. Den Akteuren unseres Gesundheitswesens sind sie ein Dorn im Auge. Ein Dorn, der sie mit einer selektiven Blindheit geschlagen hat für...

Die Sucht aufs Essen

Neurohormonale Mechanismen treiben den Drogensüchtigen zu seiner Droge, obwohl er die Konsequenzen seines Verhaltens kennt und fürchtet. Den Verhaltensbiologen sind diese Mechanismen seit einigen Jahren bekannt. Und auch dass Zucker dieselben Hirnzentren und Mechanismen aktiviert. Evolutionsbiologisch wichtige Mechanismen, wie wir heute wissen. Denn die Lust auf Süßes trieb unsere Urahnen zu der einzigen Nahrung, die diese Lust befriedigte: Obst und Früchte. Diese Lust war aus zwei Gründen wichtig: erstens sind unsere Speicher für Kohlehydrate, anders als die fürs Fett, sehr klein und innerhalb von spätestens 48 Stunden aufgezehrt. Zweitens liefern Obst und Früchte lebenswichtige Mikronährstoffe. Ganz im Gegensatz zu jenen Colas, Kuchen und Keksen, mit denen wir die Lust auf Süßes heute befriedigen. Für diese Lust sollten wir uns also nicht deshalb schämen, weil wir sie erst mit der Erforschung eines moralisch verpönten Verhaltens, der Drogensucht, entschlüsselt haben. Das erklärt, warum die Nahrungsmittelindustrie Zucker in allen möglichen Nahrungsmitteln versteckt, in denen wir ihn nicht vermuten. So wie die Zigarettenindustrie  ihre Tabake mit zusätzlichem Nikotin anreichert, einem der stärksten Suchtmittel überhaupt. Die Konsequenz dieser Sucht auf's Essen ist das Übergewicht. Womit wir beim zweiten Grund für das Scheitern des Abnehmens sind:

Entgleiste Hormone

Wer lange genug zu viel isst und sich zuwenig bewegt, verwandelt nicht nur seine Figur sondern auch seinen Organismus. Gemeint ist damit jene komplexe neurohormonale Vernetzung von Verdauungsapparat, Fettgewebe, Muskelzellen und jenen Hirnzentren, die Appetit, Sättigung und den Drang auf Bewegung regeln. Wer nach einem Essen, das eine vierköpfige Familie in Bangladesh ernährt hätte, der Lust auf ein Tiramisu nicht widerstehen kann, hat das auch diesem neurohormonalen Netzwerk zu verdanken. Es ist resistent geworden gegen Sättigungssignale. Wenig hilfreich ist auch, dass der Anblick des Tiramisu einen Verhaltensreflex auslöst, den wir von Boris Becker in der Besenkammer kennen. Erst mal vernaschen, bereuen kommt später. Verhaltenswissenschaftler nennen dieses Phänomen...

Hyperbolic discounting

Discounting heißt Abzinsung. Was der Verhaltensforscher darunter versteht, ist die Art, wie unser Gehirn intuitiv den Gegenwartswert eines erwarteten zukünftigen Nutzens ermittelt. Vor die Wahl gestellt, entweder 120 Euro in 6 Monaten geschenkt zu bekommen oder 100 Euro in 5 Monaten, entscheiden sich die meisten Menschen für die 120 Euro. Was aber, wenn ich Ihnen 100 Euro jetzt bar auf die Hand biete oder 120 Euro in einem Monat? Die meisten Probanden ziehen die sofort verfügbaren 100 Euro vor. In beiden Fällen ist die Differenz die Gleiche, nur Sie bewerten sie intuitiv anders. Dieser Effekt ist mit dem Wörtchen "hyperbolisch" beschrieben, einer mathematischen Formel die sich von der exponentiellen Form der Abzinsung unterscheidet, auf der wir unser Banken- und Wirtschaftssystem aufgebaut haben.

Dank der hyperbolischen Abzinsung greifen Sie morgen doch wieder zum Tiramisu, obwohl Sie heute Stein und Bein schwören, dass Ihnen der Gesundheitsgewinn in der ferneren Zukunft wirklich mehr wert sei als der Lustgewinn nach dem Mittagessen morgen. Und genauso funktioniert nicht nur das menschliche Gehirn sondern auch das von Tauben, Mäusen und Affen. Das zeigt, im Laufe der Evolution muss sich die hyperbolische Abzinsung als wirksames Werkzeug fürs Überleben bewährt haben. Andernfalls hätte Mutter Natur es nicht über Millionen Jahre in die Hirne ihrer Spezies programmiert. Heute müssen wir mit diesem Erbe in einer Umwelt zurechtkommen, deren Gestaltung wir Mutter Natur aus der Hand genommen haben. 

Dem Aberglauben an die Vernunft und den freien Willen als Treiber unseres Ess- und Bewegungsverhaltens hätten diese Erkenntnisse schon seit mehr als 10 Jahren den Wind aus den Segeln nehmen müssen. Haben sie aber nicht. Wohl weil es einfacher ist, den Dicken und chronisch Kranken die Schuld für ihren Zustand zu geben, als sich zu fragen, wie das Produktions- und Werbeverhalten einer Nahrungsmittelindustrie, von Nestle bis zu MacDonalds, zu reglementieren sei.

Und wie kann ich nun behaupten, dass das Zeitalter der chronischen Gesundheit greifbar ist?

Aus drei Gründen: weil sich die Börsen für das Thema zu interessieren beginnen, weil wir unser Hirn überlisten können, und weil wir die notwendigen Werkzeuge aus den Gesundheitswissenschaften haben. 
Dazu mehr im nächsten Beitrag. Und falls es Ihnen bis dahin langweilig werden sollte, können Sie ja schon mal einen Blick auf unser Navi zur chronischen Gesundheit werfen.   PrintPDF

Chronisch gesund geht. Aber nicht mit unserem Gesundheitssystem.

So versagt unser Gesundheitswesen

Das Faszinierende an unserem Gesundheitssystem ist, dass es 8 von 10 Deutschen an chronischen Krankheiten leiden und sterben lässt, obwohl wir genau wissen, wie wir diese Krankheiten verhüten können. Also warum tun wir's nicht?

Als Gesundheitswissenschaftler arbeite ich seit 15 Jahren an der Beantwortung dieser Frage. Viele meiner Kollegen warnen mit immer dunkler werdenden Zukunftsvisionen vor einem Tsunami aus Behandlungs- und Pflegekosten für unsere zunehmend älter, kränker und dementer werdende Bevölkerung. 

Dabei könnten wir das Zeitalter der chronischen Gesundheit bereits jetzt einläuten. Ein Zeitalter in dem  Herzinfarkt, Schlaganfall und viele Krebsarten ihre Bedeutung in der Sterbestatistik verloren haben werden. So wie die ansteckenden Krankheiten nach der Einführung der Hygiene.  Aber so, wie wir Prävention bislang machen, funktioniert sie nicht. Die Entscheidungsträger unseres Gesundheitssystems kämen zum gleichen Schluss, wären sie nicht mit einer selektiven Blindheit gegenüber unbequemen Fakten geschlagen.

Das Versagen der Prävention

Die Akteure unseres Gesundheitswesens verweisen gerne auf große staatlich finanzierte Studien, wie das US amerikanische Diabetes Prevention Program und die Look AHEAD Studie, die zeigen, wie wirksam simple Lebensstiländerungen für die Prävention der chronischen Erkrankungen sind. Worüber sie nicht gerne reden ist, wie flüchtig diese Erfolge sind. Für die meisten Teilnehmer sind anfängliche Gewichtsverluste spätestens nach 3 bis 4 Jahren wieder "aufgezehrt", und Risikofaktoren sind wieder auf dem Stand vor Studieneintritt.

Wie kann man behaupten Prävention funktioniert, wenn das Übergewicht zum Rauchen des 21. Jahrhunderts geworden ist? Wenn für jeden US Bürger, der 2011 das Rauchen aufgegeben hat, ein anderer adipös (BMI > 30) wurde? Wenn zum ersten Mal in der Menschheitsgeschichte es mehr übergewichtige als unterernährte Menschen auf dieser Welt gibt? Deren Lebensstil aus zu viel Essen und zu wenig Bewegung ist der größte Risikofaktor für die vermeidbaren kardiometabolen Erkrankungen und ihre klinischen Endpunkte: Diabetes, Herzinfarkt, Schlaganfall, Herzversagen.

Wenn also die Änderung des Gesundheitsverhaltens Krankheit verhindert, was verhindert dann die Änderung des Gesundheitsverhaltens? 

Der Aberglaube an ein willensgesteuertes Gesundheitsverhalten.

Wir alle wissen, dass Übergewicht und Bewegungsarmut ungesund sind. Trotzdem sind zwei von drei Deutschen übergewichtig und weniger als jeder fünfte bewegt sich ausreichend. Die logische Schlussfolgerung: Wenn Sie einen Lebensstil wählen, von dem Sie wissen, dass er Ihnen Krankheit und vorzeitigen Tod bringt, dann treffen Sie diese Wahl entweder mit Ihrem freien Willen, oder es ist nicht Ihr freier Wille, der Ihr Gesundheitsverhalten treibt.

Offensichtlich ist letzteres der Fall. Wie sonst können wir erklären, dass übergewichtige Kinder ihr Ess- und Bewegungsverhalten beibehalten, obwohl sie ihren Leidensdruck aus Übergewicht und Stigmatisierung als genauso schwer empfinden wie  ihre krebskranken Altersgenossen den einer Chemotherapie. Wie sonst können wir erklären, dass adipöse Erwachsene nicht abspecken, obwohl ihre Aussichten eine akademische Ausbildung, einen Job und einen Geschlechtspartner zu finden deutlich schlechter sind, als die ihrer normalgewichtigen Altersgenossen? Wie sonst können wir erklären, dass der Prozentsatz der Adipösen unter den US Bürgern in den letzten 20 Jahren um 60% gestiegen ist, während sie im gleichen Zeitraum ihre Ausgaben für Abnehmprodukte auf jährlich 60 Milliarden Dollar verdoppelt haben? Sie alle WOLLEN abnehmen, aber sie schaffen es nicht. Aus drei Gründen. 

Über die Sucht aufs Essen, über entgleiste Hormone und über hyperbolische Verzinsung in unseren Hirnen geht's in meinem nächsten Blogbeitrag. Und bis dahin, schauen Sie sich doch mal an, wie Sie bereits jetzt auf den Weg zur chronischen Gesundheit und guten Figur kommen.

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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.

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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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How to get those vegetarian zealots off your back.

Does red meat kill you? Only in a vegetarian's dream!

Red meat is the favorite enemy of nutritionists nowadays. Their studies and publications are often (ab-)used by those evangelical vegetarian types who would love to impose their no-meat religion on the rest of us. Don't buy it. Now let me show you how you can profess your love for steak AND support it with the data from the same studies which the zealots use for their vegetarian crusades.

Earlier this year Pan et al. published a study titled "Red meat consumption and mortality" [1]. They had pooled the data of two large prospective studies, the Nurses' Health Study and the Health Professionals' Follow-up Study. Collectively these studies had followed 121,000 people, who were free of cardiovascular diseases at baseline, for more than 20 years. Altogether, the participants accumulated close to 3 million person years for observation. During the observation period close to 24,000 deaths occurred of which 6,000 were of cardiovascular causes, that is heart attack, stroke, heart failure.

The researchers discovered that for every increase of 1 serving of unprocessed red meat per day the hazard ratio of dying from any cause was 1.13 and the hazard ratio of dying from a cvd-cause was 1.2. That means for every increase of a serving of red meat per day the chances of dying from any cause and from a cvd-cause increased by 13% and 20% respectively. Those rates were a little higher for processed red meat. To put this into perspective the researchers also calculated that if all participants had eaten less than half a serving of red meat per day (42g/d), 9% of deaths in men and 7.6% of deaths in women could have been prevented. Wonderful. Sounds impressive, but it isn't for one simple reason:

Unreliable data acquisition. Just ask one question: how did the researchers know how much red meat those people ate? This question cuts to the heart of many, if not most, studies on diet-disease associations. Data on food consumption are typically acquired through food frequency questionnaires (FFQ). These FFQs ask you about your consumption of food items over the past days, weeks or even months. And as you can imagine, such recall can be terribly unreliable. So much so, that other researchers wanted to quantify this effect. So they used FFQs and compared the results with objective quantitative measurement of energy intake and protein intake [2]. And lo and behold, they discovered that if relative risks (such as the hazard ratio mentioned above) were calculated from FFQs they overestimate the true diet-disease association very severely. In fact so severe, that a hazard ratio of, say, 2 would in reality be around 1.3.

What does that mean for a hazard ratio which is, as in the study of Pan and colleagues, less than 1.3 to begin with? It means possibly nothing. You certainly can't conclude from these data that red meat kills you. That's what it means.  And mind you, this inaccuracy of FFQs shows up with recall periods of a few weeks. Pan and colleagues had to rely on FFQs which were conducted YEARS apart. In fact,  data acquisition based on FFQs is so flawed, that the question been raised "is it time to abandon the food frequency questionnaire?" [3]. And the authors state: "We should be very circumspect about analyses of current studies that have used FFQs for dietary assessment." That was 7 years ago. We still have those FFQs and you  still have the media telling you  how bad red meat is for you.

And I'm going to have a real nice steak now. How about you?

1.           Pan, A., et al., Red Meat Consumption and Mortality: Results From 2 Prospective Cohort Studies. Archives of Internal Medicine, 2012: p. archinternmed.2011.2287.

2.           Kipnis, V., et al., Structure of dietary measurement error: results of the OPEN biomarker study. American Journal of Epidemiology, 2003. 158(1): p. 14-21; discussion 22-6.

3.           Kristal, A.R., U. Peters, and J.D. Potter, Is it time to abandon the food frequency questionnaire? Cancer Epidemiology, Biomarkers and Prevention, 2005. 14(12): p. 2826-8.

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