Gluten – The root of all evil?

So, you’ve probably heard about gluten – it has been linked to all kinds of diseases including autism, type 1 & 2 diabetes, and cancer. So what is gluten exactly and is it really the cause of so many diseases?

Wheat gluten gluten-free

Gluten is a much-discussed entity, which has been hyped for quite a while now. As mentioned above, it has been linked to of all sorts of diseases including autism, type 1 & 2 diabetes, various cancer types, osteoporosis, dementia & Alzheimer’s. Well, these postulations have been largely based on anything else than science – but there has been quite considerably advances in the research within this area in the past years which I will try to shed some light on taking my own research as an example.

But first, what is gluten? And celiac disease? These are important things to clear up since there seem to be some major misconceptions. Gluten is found in grains such as wheat, barley, and rye. Gluten is a mixture of proteins but the two major ones are gliadin and glutenin and these are responsible for some of the nice baking properties of bread made from these grains. Celiac disease is a condition in which gluten triggers immune system activity that damages the lining of the small intestine, which, over time, damages the intestine so much it prevents the absorption of nutrients from food.

No one seems to disagree upon the fact that people with celiac disease need to be following a gluten-free diet to avoid damages to the intestine and gastrointestinal symptoms. Not following a gluten-free diet for people with celiac disease has been linked to increased risk of cardiovascular diseases [1]. However, a more widespread belief is that everyone should be following a gluten-free diet despite not having celiac disease as this could have wide health benefits and thus following diets limiting gluten although being non-celiac gluten sensitive have gained huge popularity.

We recently published the results of a dietary study where we examined a low-gluten diet (2 grams/day) compared to a high-gluten diet (18 grams/day) in 60 overweight or obese adults without celiac disease over 8 weeks in a cross-over design (meaning they tried both diets in a random order)[2]. The hypothesis was that following a low-gluten diet compared to a high-gluten diet would change the gut microbiota/bacteria composition (which bacteria are present) and functional potential (how the bacteria work). We hypothesized that this would cause less subjective gastrointestinal discomfort, such as feeling bloated and would positively affect host metabolic and inflammatory markers[3]. In short, we tested the assumption that you would have a better gut feeling and become healthier by following a low-gluten diet and that this is caused by beneficial changes to your intestinal microbiota. We provided the participants with matched grain products, which were either gluten-free or containing gluten. For example, in one period, they got ciabatta wheat bread (high in gluten) and in the other period, they got a gluten-free bread (buckwheat, sunflower seeds etc.). We did thorough examinations of the participants in the beginning and end of each period. This sounds relatively simple when I write it, but in total, these examinations took over 1.5 years to complete and involved multiple people (including the 52 authors on the paper), so a substantial amount of time and effort went into this.

What did the dietary change do then? We found that people actually felt less bloated on a low-gluten diet compared to a high-gluten diet. This change was probably related to changes in the fermentation and gas production of the intestinal microbiota, which we found was lowered after being on the low-gluten diet. The participants also reported a higher well-being after a standard breakfast meal. We did find a minor weight loss of about 800 grams when following a low-gluten diet (Hardly anything you could sell in a magazine stating “Loose 800 grams in 8 weeks”) and some selective changes in the inflammatory markers, which were quite hard to interpret.

So was this caused by gluten? Well, changing the grain types to gluten-free also changed major parts of the dietary fiber types. The difference in fiber types, as well as the absence of gluten itself, might explain the changes in subjective gastrointestinal feeling. One of the reasons we think that the dietary fiber change is the cause of the changes in gastrointestinal feeling was that we found changes in the gut microbiome composition and functionality which seems to be related to the carbohydrate/fiber metabolism of the gut bacteria. Another reason is that an earlier study has shown that when giving gluten to people with self-reported non-celiac gluten sensitivity on top of a low FODMAP diet (a diet low in fermentable carbohydrates) no gastrointestinal effects were shown[4]. They showed that it was when changing to a low FODMAP diet that their gastrointestinal symptoms were lowered. So, my interpretation is that some people are sensitive to certain fiber/fermentable carbohydrates causing gastrointestinal discomfort and that this is not related to gluten. But who these people are and why they are sensitive to fiber/fermentable carbohydrates is less clear – at least to me.

Should you begin following a gluten-free diet, if you don’t have celiac disease? More and more research seems to be showing that there might be some downsides to choosing a gluten-free diet. One example of this is that higher gluten intake has been associated with lower risk of type 2 diabetes[5]. Others have shown that Americans reporting that they follow a gluten-free diet were exposed to higher levels of arsenic and mercury[6]. Some have shown that gluten intake is not associated with risk of coronary heart disease, but following a gluten-free diet may result in avoidance of whole grain, which lowers the risk of coronary heart disease[7].

Therefore, in my opinion, gluten is not your enemy or the root of all evil. It might just have been mixed in with fiber/fermentable carbohydrates that cause gastrointestinal discomfort in some people. And this should not keep you from getting some very valuable whole grains.

But this blog post is probably not going to end the discussion on gluten and nor should it. As always, more research is probably needed as some people might actually benefit and improve their quality of life substantially by altering their diet. Also special diets, following principles like FODMAPs, is an important research area as it might be useful for patients with chronic gastrointestinal disorders such as ulcerative colitis and Crohn’s Disease (Link). Furthermore, gluten-free diets are important for people with celiac disease, and having products with high nutritional value for this group of people is important.

Disclosure
As I have already written in my about page I have a possible conflict of interest as I was partly supported by an unrestricted grant from Cereal Partners Worldwide; a joint venture between Nestlé SA and General Mills Ltd which manufactures and sells grain products. They covered the last 1/3 of my PhD funding which was actually the reason for me being able to do a PhD. They played no role in the design, methods, data management, and analysis nor in the decision to publish in any of the studies.

References

[1]         Ludvigsson JF, James S, Askling J, et al. Nationwide Cohort Study of Risk of Ischemic Heart Disease in Patients With Celiac Disease. Circulation 2011;123:483–90. doi:10.1161/CIRCULATIONAHA.110.965624.

[2]         Hansen LBS, Roager HM, Søndertoft NB, et al. A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults. Nat Commun 2018;9:4630. doi:10.1038/s41467-018-07019-x.

[3]         Ibrügger S, Gøbel RJ, Vestergaard H, et al. Two Randomized Cross-Over Trials Assessing the Impact of Dietary Gluten or Wholegrain on the Gut Microbiome and Host Metabolic Health. J Clin Trials 2014;4. doi:10.4172/2167-0870.1000178.

[4]         Biesiekierski JR, Peters SL, Newnham ED, et al. No Effects of Gluten in Patients With Self-Reported Non-Celiac Gluten Sensitivity After Dietary Reduction of Fermentable, Poorly Absorbed, Short-Chain Carbohydrates. Gastroenterology 2013;145:320–328.e3. doi:10.1053/j.gastro.2013.04.051.

[5]         Zong G, Lebwohl B, Hu FB, et al. Gluten intake and risk of type 2 diabetes in three large prospective cohort studies of US men and women. Diabetologia 2018;61:2164–73. doi:10.1007/s00125-018-4697-9.

[6]         Bulka CM, Davis MA, Karagas MR, et al. The Unintended Consequences of a Gluten-free Diet. Epidemiology 2017;28:e24–5. doi:10.1097/EDE.0000000000000640.

[7]         Lebwohl B, Cao Y, Zong G, et al. Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study. BMJ 2017;357:j1892. doi:10.1136/bmj.j1892.

Measuring diet without asking – can we rely on biomarkers as our only source of information?

biomarkers as diet measurement

Recently I was asked if I would do a short article for the magazine BestPractice – general practitioners in Denmark mostly read it. I was going to cover a subject called dietary biomarkers and risk of type 2 diabetes which I found quite remarkable that general practitioners could find interesting.  Anyway, I chose to accept the challenge and tried to cover this with an example of our own research where we did an assessment of dietary intake without relying on people to report their diet – How you ask? (Or at least I hope the general practitioners ask that and don’t turn the page thinking that this is anything but interesting!)

Well, this was based on an article I co-authored with my former supervisor and good colleagues at Chalmers University of Technology and University of Gothenburg, Sweden.  Otto (the first author) deserves most of the credit for this one since he developed the awesome method used for analysis of the samples, as well as did a lot of statistics work and writing to make this happen. The study was published in American Journal of Clinical Nutrition (2017) and was called “Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women” (link to the original study)[1].

The idea was that we had a cohort of 64-year-old women who only had blood samples taken, with no dietary assessment. Could we really find out what they ate simply using biomarkers in a blood sample?

What is a biomarker?

Well, it can be almost any type of molecule, which is related to the body that reflects some kind of biological condition or state. For example, anything you can measure in blood, urine, faecal, saliva, hair, adipose tissue, semen, teardrop, nose drip, earwax or other biological fluid or tissue you can get your hands on (and who doesn’t like to get their hands on lots and lots of earwax?)[2]. Sometimes people even use the term on other bodily measurements such as waist circumference, limp length or other more exotic anthropometric measurements as biomarkers [3]. However, most often it is a biological molecule found in body fluid or tissue.

In our case, we measured a wide range of molecules present in a blood sample to try to assess markers related to dietary intake using a really cool method on a very expensive machine[4]. E.g., we tried to assess whether you ate a lot of whole grain, fish, meat or bananas from a blood sample (unfortunately, we were not able to cover the last one otherwise you would have already heard about it in some newspaper or blog stating: “Bananas cure diabetes”).

So, what did we find? Well, if I simplify the findings a bit we found that markers of beef intake (β-alanine) were higher in women with type 2 diabetes and impaired glucose tolerance (on the way to type 2 diabetes) while markers of wholegrain wheat and rye (alkylresorcinols), as well as fatty fish (eicosapentaenoic acid, EPA) and vitamin E status (α-tocopherol), were lower. We also found that a higher fish intake (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, CMPF) and vitamin E status (α-tocopherol) were associated with a lower risk of developing type 2 diabetes over a 5-year period.

So, can we rely on biomarkers as our only source of information for dietary assessment? Well, in my honest opinion, no, at least not yet. There is great potential in using such advanced methods for gathering complex biomarker information regarding dietary intake [5](shamelessly citing myself), but for now the current methods do not cover enough dietary markers to cover the entire diet sufficiently. Furthermore, there are other limitations and barriers to overcome related to how far back they cover dietary intake or how specific such markers can be… But that will be the topic for another blog post 😉 Thank you for reading along – feel free to leave a comment.

References

[1]         Savolainen O, Lind MV, Bergström G, et al. Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women. Am J Clin Nutr 2017;106. doi:10.3945/ajcn.117.152850.

[2]         Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework. Clin Pharmacol Ther 2001;69:89–95. doi:10.1067/mcp.2001.113989.

[3]         Gunnell D. Commentary: Can adult anthropometry be used as a ‘biomarker’ for prenatal and childhood exposures? Int J Epidemiol 2002;31:390–4. doi:10.1093/ije/31.2.390.

[4]         Savolainen OI, Sandberg A-S, Ross AB. A Simultaneous Metabolic Profiling and Quantitative Multimetabolite Metabolomic Method for Human Plasma Using Gas-Chromatography Tandem Mass Spectrometry. J Proteome Res 2015. doi:10.1021/acs.jproteome.5b00790.

[5]         Lind MV, Savolainen OI, Ross AB. The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples. Eur J Epidemiol 2016;31. doi:10.1007/s10654-016-0166-2.

Smoking vitamins!?

I recently discovered that you can get e-cigarettes/vapors with vitamins to “boost your health”. This made me think – Can you really smoke your vitamins? Is there a health benefit to this? Or is it another health hype that is more healthy to avoid than participate in?

vitamins vapor

A few weeks ago I joined Twitter (and started a blog) partly to share my own research and partly to keep up with other’s research (I have to give huge credit to my girlfriend for convincing me and helping me get started).

I stumbled over an article from the New York Post on trendy healthy vitamin vaping which caught my eye since 1. I had never heard about it and 2. it involved vitamin B12 which I’m very interested in from a research perspective (see earlier blog post). The basic idea is to add vitamins (mainly water soluble) and other “health compounds” to the vapor-liquid which can then get vaporized and inhaled through your E-cigarettes, Vapes, E-Cigs or whatever you want to call it (cute child has many names, as we say in Danish). Apparently, these companies have been around since 2014 so maybe this is old news but keeping up with health trends, especially while doing your Ph.D. can be a bit of a hassle. Also, my girlfriend says I should avoid it since new health trends seem to cause me high blood pressure, cursing and furiously shaking of my head.

Anyway, one of my first questions when hearing about this were, can you really absorb vitamins by inhaling them? Well, I tried to find some evidence for this, and while I did find some old experiments that show that it could be possible to inhale vitamin B12 [1,2], these do not seem to be very cited suggesting that the research within this field is limited. Even though some have suggested nasal spray as a delivery method[3] as well, the reason for the limited research is probably that the absorption through the oral route is very sufficient for getting adequate amounts of vitamins (with some exceptions for older people). Furthermore, other scientists have expressed concern that there is very limited inhalation safety research which makes me think that vaping is probably not the way to go for your daily vitamin needs.

The bigger question might be whether vaping is safe at all, although it might aid in smoking cessation, to my knowledge there seems to be very little evidence on the long-term outcomes of using these[4]. Finally, some of the vapor vitamin products include very low amounts of some vitamins (e.g. 1% of recommended daily intake of vitamin C) and an oral supplement seems to be the best option if you want to get additional vitamins in addition to your dietary intake. Imagine how many times a day, you would need to puff on your vaporizer to get your daily dose!

In my opinion, research within the area of vaping (and vapor vitamins) should be conducted before widespread public use. Even though research is a very slow progress (sometimes dauntingly slow) for some things it is better to be safe than sorry. The vapor vitamins seem to be a hype with very limited benefit and potentially with harm. As always, if you suspect you have a vitamin deficiency consult your doctor to get it checked out, especially before you decide to start E-smoking.

References

[1]         Shinton NK, Singh AK. Vitamin B 12 Absorption by Inhalation. Br J Haematol 1967;13:75–9. doi:10.1111/j.1365-2141.1967.tb08696.x.

[2]         Smith FJ, Monto RW, Rebuck JW. B12 inhalation therapy in pernicious anemia. Trans Am Clin Climatol Assoc 1952;64:27–39.

[3]         Kurtz S. Use of methylcobalamin nasal spray to treat disorders – Patent application 2008. https://patents.google.com/patent/US20090012039A1/en (accessed October 28, 2018).

[4]         Stratton K, Kwan LY, Eaton DL, editors. Public Health Consequences of E-Cigarettes. Washington, D.C.: National Academies Press; 2018. doi:10.17226/24952.

Vitamin B12 for brainy children

Vitamin B12 for brainy childrenSo, tomorrow we are having a journal club at work (no, we are not sitting around reading each other’s diaries) where I have chosen an article, which we are going to discuss.

Kvestad et al. 2017 “Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children”[1]. https://www.ncbi.nlm.nih.gov/pubmed/28330909

I’m currently doing research on Vitamin B12, cognition and metabolism in early life (0-3 years of age) and the reason I’m interested in vitamin B12 during this period of life is that it is essential for the brain and the intellectual development of the child.

The study in the article shows some very convincing associations between higher vitamin B12 status at age 2-12 months and better cognitive outcomes in 5-year-old children. They also use the ASQ (Age and Stages Questionnaire) score [2] as an outcome –it measures five subscales of development including communication, problem-solving, gross and fine motor development and personal-social development. I’m also going to be using the ASQ score as a measure of child development in my research.

One of the things I look forward to investigate in my project is if we see similar associations in our population, which have a much higher intake of vitamin B12 in their diet and thus should have a much higher status. This could enlighten us (here I mean mankind) further and possibly shed some light on what levels of vitamin B12 are sufficient for optimal brain and intellectual development. This can aid in establishing guidelines and design potential interventions for improving status among children with low vitamin B12 status. Something it looks like the same group is currently doing in an intervention study as well which I’m looking forward to very much[3].

Hopefully, this will be one step in the right direction for getting super brainy children in the future.

References

[1]         Kvestad I, Hysing M, Shrestha M, et al. Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children. Am J Clin Nutr 2017;105:1122–31. doi:10.3945/ajcn.116.144931.

[2]         Squires J, Bricker D. Ages & Stages Questionaires. Third Edit. Baltimore: Brooks Publishing; 2009.

[3]         Strand TA, Ulak M, Chandyo RK, et al. The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial. Trials 2017;18:187. doi:10.1186/s13063-017-1937-0.

Welcome!

Mads Vendelbo LindSo, nutrition and especially nutrition science is a popular field, where there is an endless amount of information (some more useful than others). So, you might think, why do I want to read another blog about it?

Well, you do! Because this blog is about how science is actually performed using my own research as an example. This will not be a blog about the super-duper-health-effects of some unknown plant/seed coming out of central Fantasyland. As I’m quite a foodie myself, I tend to believe that all foods are good, happy and comforting superfoods – we just need to eat them in appropriate amounts (and I must admit, I struggle with finding the appropriate amount of cake).

I have a bachelor’s degree in Food Science and a master’s degree in Human Nutrition, both from the University of Copenhagen. I did my PhD as a double degree working at Chalmers University of Technology, Sweden at the Department of Food Science and Nutrition as well as at the University of Copenhagen, Department of Nutrition, Exercise and Sports. The latter is where I currently work, which involves doing research and teaching for bachelors, masters and PhD students.

As with all research, my research has to be funded (since before mentioned Fantasyland doesn’t seem to exist). Either by companies, private investors, NGOs or government funding programs – or others (feel free to send me your advice…or a check). I have received funding from both companies and government funding programs – which for some means I cannot be trusted. I will try to update my potential conflict of interest so you can decide yourself whether you trust the things I write or not.

I hope that you find the blog interesting and if you have any questions, feel free to send them to me through the contact page.

Welcome on board and let’s eat some science…and cake!