Starting up the Inuit diet intervention study

Grønlandsbilled

Last month I arrived in Nuuk ready to start up our project of examining the Inuit diet.

As you can read in an earlier blog post, we are examining the effect of this diet and how it could potentially be used to prevent the rising type 2 diabetes prevalence among the Greenland Inuit population.

Setting up a trial is always a bit chaotic and stressful since a lot of unknowns needs to come together. We started by sending a bunch of letters to potential participants. This was done manually, so Else, our Greenlandic project employee (it’s hard to find a good name for her position – basically she is essential in all parts of the project from examinations, recruitment to the handling of everyday project related activities) had her work cut out for her.

Next up we went buying foods for the participants. We have a deal with one of the local supermarkets, Brugseni, which has a large selection of both Danish and Inuit foods and who helps us with handing out the foods. Since we did not have enough freezer storage at our examination site this was a huge help leaving one of the logistic unknowns solved. We ended up providing the participants with a wide range of foods. For the traditional Inuit diet, this included a selection of fish (cod, halibut, salmon, trout, etc.), seafood (shrimps) and sea mammals (whale, seal). For the westernized diet we provided a 28-day box with frozen imported meats (incl. beef, lamb, pig, sausages, chicken and cold cuts of meat), various pasta, cereals, and bread (both rye bread and white bread). We went for providing foods for the participants covering around 25% of their daily energy intake and thus the participants need to cover some of the foods themselves. They got a detailed pamphlet on which foods to consume and which foods to avoid when being on the different diets. Luckily the participants were very enthusiastic about the study, especially the traditional Inuit diet.

Indkøb grønland

Mads fisk

One of the traditional ways of living in a hunter-gatherer society is collecting your own food. Fishing is still a big part of society in Greenland and for the period where the participants are encouraged to eat an Inuit diet, they are encouraged to eat locally caught fish. I got to try this out while being on a local boating trip, where our guide asked whether we would like to try to fish. In Denmark, this can be a lengthy process taking hours with very little success. However, our guide assured us that we would, of course, catch something; it would take a maximum of 30 min. I was skeptical, but went along with it, even though I have only tried fishing once or twice. To my amazement, I was able to pick up 8 sizeable codfish and another tourist from the boat trip picked up 9 codfish – all in 30 min. Here you see a picture of me getting it ready for consumption – an amazing dinner – really showing the amazing tastes of the Greenland Inuit cuisine.

Of course, we also need to examine the participants and a special focus for this trial is to test how the diet affects the blood sugar regulation in order to understand whether it can ultimately prevent the participants from developing type 2 diabetes. We do this in multiple ways. First, we examine the participant’s blood sugar when they arrive at the examinations, also called fasting blood sugar. If this is elevated you will have a higher risk of developing type 2 diabetes. Furthermore, we examine their HbA1c or glycated hemoglobin. This is a marker of longer-term average blood glucose levels (8-12 weeks). Hemoglobin is normally what carries oxygen in the blood, however, when hemoglobin is exposed to glucose in the blood, it can also bind glucose and we can measure if the hemoglobin has been exposed to higher levels of glucose over the preceding weeks. To further test how well the participants handle their blood glucose we also do an oral glucose tolerance test. In this test, the participants consume 75 gram of glucose in 150 ml of water within 5 min (yes it’s very sweet!) and then we measure their blood sugar over the next two hours. This tells us something about how well they can handle a large amount of sugar – the better they can do this (with lower blood sugar) the lower the risk of developing type 2 diabetes. One last way we assess their blood sugar regulation in this study is providing the participants with a small glucose monitor, which we place on their upper arm. This can measure their blood sugar continuously for 14 days in a row (!) and provide very detailed data on how their blood sugar is behaving during the two diet periods. Below you can see an example of how it looks when we have measured the blood sugar for 14 days. We hope that this can make us much more knowledgeable about how we can use the diet to regulate blood sugar, something which can be both of importance when preventing but also treating type 2 diabetes. Besides looking into the blood sugar regulation of the participants, we also examine various other markers in their blood such as their cholesterol level and level of inflammation, but that will be a story for another time.

CGM — Here you see the individual glucose measurements (dots) throughout the day with a clear top at breakfast, lunch, and dinner. At the y-axis, you can see glucose concentration and the x-axis shows the time.

For now, the study is up and running and we are looking forward to seeing the first results. However, there is still a lot of work to do and we need to plan for the next two study sites in Qaanaaq (the northwest of Greenland) and in Qasigiannguit in the Disco Bay (west Greenland). Hope you enjoyed the update on the Greenland Inuit diet project and I look forward to writing the next update on the project.

Nutrition in Greenland – A first glance

Last month I landed in Nuuk, Greenland full of excitement to get started on our dietary study examining a traditional Inuit diet vs a westernized diet on blood sugar and other cardiovascular health markers in the Greenland Inuit population.

As almost everyone landing in Greenland for the first time, the first thing you notice is the stunning nature which is everywhere and breathtaking. I heard about it and was told to expect something special, but it is really something you should experience in person. Incredible.

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However, as someone with a special interest in nutrition, the foods and dietary culture are also of special interest. So one of the first things, after landing and getting settled in our AirBnB, was to visit the local supermarkets. As always, a top attraction for someone with a nutrition background. One of the things you obviously notice (and somewhat expect) is the large assortment of fish, seafood and sea mammals (such as whale and seal) and also local meats such as reindeer and musk ox. However, it is also evident that a lot of imported foods have found their way here – as exemplified with the cereal aisle. What was also striking, but not surprising, was that the price of fresh fruits and vegetables is 4-6 times more expensive compared to Denmark. No wonder this is probably not a stable food at the family dinners.

The trip to the supermarkets gave the first indication of why this population has experienced a rapid increase in obesity and type 2 diabetes prevalence since transitioning from a traditional hunter-gatherer way of living.

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The second indication came when I tried out the local cafés and eating places. First thing I noticed was the big selection of ice coffee with various taste, caramel, ice cream and just loads of whipped cream in general. Apparently, ice coffee is still delicious even if its -10 °C outside… Besides this people also add a substantial amount of sugar to their coffee (we are not just talking one or two scoops). This explained why there is also a separate point just for sugar added to hot drinks in our dietary assessment method, something I found a bit strange to start with. This coffee often comes with cakes with cream. A lot of cream. While I agree that you need something to keep you warm up here, even I found that there is such a thing as too much whipped cream…

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As part of my interest in nutrition, I also enjoy food and trying out local specialties and fine dining. For our Easter dinner, my girlfriend and I tried out Sarfalik where I got to try out the musk soup, reindeer filet and lumpfish roe (aka caviar of the north). An amazing experience to try out the local cuisine at the highest level. This really gave an impression on how one could use the local foods for creating healthy dishes – something that is very central for our dietary study.

When experiencing the cold weather one can understand why the traditional diet of the Inuit was very high fat, high protein as you would want a high fat intake to get enough calories for surviving the winters. Together with the high level of physical activity in the traditional hunter-gather society, this makes a lot of sense. However, in modern societies where physical activity levels are also dropping and simple carbohydrate intake is increasing this does seem to be a recipe for the rapid increase in obesity and type 2 diabetes prevalence.

Obviously, Nuuk is not typical of all of Greenland but it does home a substantial amount of the total population. From a nutritional perspective, there seems to be quite some room for improvement, but also a very high potential for including local foods in a healthy Greenlandic diet. Hopefully, our new research project can uncover some of the potentials of using local foods.

New Project – The Greenland Inuit diet intervention

Nuuk_city_below_Sermitsiaq I’m happy to announce that I’m working on a new project which is centered around a dietary intervention study in Greenland. The overall objective of the study is to investigate a traditional Inuit diet compared to a westernized diet in Greenland Inuit. The reason we are examining this is that the lifestyle of Inuit in Greenland is undergoing a transition from a fisher-hunter society, with a physically active lifestyle and a diet based on the food available from the natural environment, to a westernized society. Parallel to this, a rapid increase in the prevalence of lifestyle diseases such as type 2 diabetes and obesity has been observed[1]. What we are especially interested in is whether switching to a more traditional Inuit diet could improve glycemic control and thus prevent the development of type 2 diabetes.

Studies of Greenland Inuit before the 1980s found a low prevalence of type 2 diabetes compared to Western populations, however, recent population studies in Greenland have found a higher prevalence of pre-diabetes and type 2 diabetes[2,3]. This might in part be explained by the transition in lifestyle, but in addition, a genetic variant increasing the susceptibility to type 2 diabetes have been found to be prevalent in the Greenland Inuit [4], thus further increasing their risk of type 2 diabetes. Therefore, the objective of our study is also to assess whether this gene modifies the effect of following a traditional Inuit diet.

What is a traditional Inuit diet? This is of course hard to examine but multiple studies have tried to assess this in Greenland throughout the last 100 years. They have found that the traditional food of the Greenland Inuit included sea mammals, fish, seafood, and to a lesser degree terrestrial animals and game birds. The sea mammals include walrus, seal meat and blubber, dried whale meat and skin. Fish are local and include halibut, cod, char, salmon and trout, and seafood such as mussels, shrimps, or crab. The terrestrial animals and game birds include lamb, caribou, musk ox, hare, guillemot, eider duck, and eggs from these birds[5–8]. This result is the traditional Inuit diet being higher in fat and protein and lower in carbohydrate compared to a westernized/Danish diet. We have designed the traditional western diet so that it will contain meat from chicken, cow, and pig, as well as having a high amount of cereal products, bread, pasta and rice (carbohydrate).

The study is designed to be a 4-week cross-over intervention study, meaning that each participant has to follow both dietary interventions for 4 weeks in a random order. The study is expected to provide relevant information in relation to whether diet has a role in preventing type 2 diabetes in Greenland and also whether this might be dependent on which genes you have. We have obtained ethical approval for the project and we are currently working on getting all the practical stuff in order so we can begin recruiting participants. The project will start in Nuuk this April, fingers crossed.

The study was initiated by Marit Eika Jørgensen, Lotte Lauritzen and I. The project is a collaboration between researchers at the University of Copenhagen, Steno Diabetes Center Copenhagen, University of Southern Denmark and University of Greenland. It is funded by The Novo Nordisk Foundation who plays no role in the design, methods, data management and analysis or in the decision to publish the results of the study.

References

[1] Hansen JC, Deutch B, Odland JØ. Dietary transition and contaminants in the Arctic: emphasis on Greenland. Int J Circumpolar Health 2008;67:1–98. doi:10.1080/22423982.2007.11864604.

[2] Jørgensen ME, Bjeregaard P, Borch-Johnsen K. Diabetes and impaired glucose tolerance among the inuit population of Greenland. Diabetes Care 2002;25:1766–71.

[3] Jørgensen ME, Borch-Johnsen K, Witte DR, et al. Diabetes in Greenland and its relationship with urbanization. Diabet Med 2012;29:755–60. doi:10.1111/j.1464-5491.2011.03527.x.

[4] Moltke I, Grarup N, Jørgensen ME, et al. A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature 2014;512:190–3. doi:10.1038/nature13425.

[5] Bjerregaard P, Jeppesen C. Inuit dietary patterns in modern Greenland. Int J Circumpolar Health 2010;69:13–24.

[6] Deutch B, Dyerberg J, Pedersen HS, et al. Traditional and modern Greenlandic food — Dietary composition, nutrients and contaminants. Sci Total Environ 2007;384:106–19. doi:10.1016/j.scitotenv.2007.05.042.

[7] Bang HO, Dyerberg J, Hjøorne N. The composition of food consumed by Greenland Eskimos. Acta Med Scand 1976;200:69–73.

[8] Jeppesen C, Bjerregaard P, Jørgensen ME. Dietary patterns in Greenland and their relationship with type 2 diabetes mellitus and glucose intolerance. Public Health Nutr 2014;17:462–70. doi:10.1017/S136898001300013X.

Should you take folate supplements to reduce the risk of type 2 diabetes?

diabetes folate folic acid

I recently published an article in the American Journal of Clinical Nutrition[1], which is kind of a big deal for me since this is one of the first articles where I really feel ownership of the idea. One of my main research interests and what I also did my PhD work on is one-carbon metabolism (yes, nerd alert big time). Basically, this is a pathway centered around folate designed to transfer carbon units for all kinds of biological processes, so if things go wrong here it has a major impact on the whole system. This is partly why inhibitors (blockers) of this pathway are widely used as antibiotics and chemotherapeutics[2]. I could (and probably will) write multiple blog posts on this fascinating and complex biological system, but for now, I will tell you a bit more about the new study.

Actually, this study began with me doing the literature review for my PhD thesis where I wanted to cover pretty much all intervention studies with nutrients related to one-carbon metabolism (I soon realized that this was impossible in the timeframe I had, but did a fair job and ended up with 539 references)[3]. I did cover quite a lot of folate studies and thought that it was strange that no one had noticed the marked decreases in insulin resistance (Insulin and HOMA-IR) values, so I asked my supervisor how hard it was to do a meta-analysis of them. “Easy”, she replied; should have known better. All of the work started in spring 2016 and has finally been published in the American Journal of Clinical Nutrition – almost 3 years later. This tells you something about the speed of science sometimes. Of course, I did not do all the work by myself and have to give a big shout out to especially the last author Jane for providing some much-needed structure and a more clinical angle on the discussion.

The findings in the study were quite interesting as we found that folate supplementation lowered fasting insulin and HOMA-IR indicating that subjects taking folate were less insulin resistant (better of) compared to a control (placebo) group. Another funny finding was that changes in homocysteine were linked to clear changes in both fasting glucose and glycated hemoglobin (HbA1c), and also tended to be associated with changes in insulin and HOMA-IR. Homocysteine is a molecule that is linked with detrimental health outcomes (here insulin resistance), and homocysteine is lowered by folic acid supplementation, which is hypothesized to be a benefit for health. So long story short, we found that the more you can lower homocysteine the larger improvements we see on insulin resistance. This would normally mean that we would also lower the risk of type 2 diabetes… However, we did not find many studies examining the effect on type 2 diabetes (only 2) and overall this did not show marked effects on risk – probably due to the limited number of studies and the modest (if any) effect. Disappointing… That would have been a really good story.

So, should you then take an extra vitamin pill with folic acid to prevent type 2 diabetes? Well, no. First of all the improvements in insulin resistance was not translated into a clear reduction in risk of type 2 diabetes. Meaning that we cannot see clear effects on the disease we were hypothesizing to prevent. Furthermore, there are some concerns around potential increased risk of cancer and thus uncritically supplementing with folate cannot at present be recommended[4](https://hawcproject.org/assessment/public/). However, our results are still interesting since there might be some remarkable prospects for people already at high risk of developing type 2 diabetes or have type 2 diabetes, with regards to cardiovascular risk (stroke). One very large study has shown that for people with high plasma glucose values or diabetes have a marked reduction (34%) in stroke risk when receiving folic acid[5]. This link between folic acid, type 2 diabetes, and stroke might explain some of the large differences earlier studies of folic acid supplementation found with regards to CVD risk reduction. Thus, as always, more research is needed. Moreover, folate is just one of the components of one-carbon metabolism and the balance/optimal functioning of this pathway depends upon a number of nutrients including other B-vitamins such as B₁₂[6]. And this is what I spend much of my research time on and untangling this complex link between folate and disease is probably going to keep me busy for a while…

References

[1] Lind MV, Lauritzen L, Kristensen M, et al. Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2019. doi:10.1093/ajcn/nqy234.

[2] Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell Metab 2017;25:27–42. doi:10.1016/j.cmet.2016.08.009.

[3] Lind MV. The role of diet in one-carbon metabolism and epigenetics, a metabolic syndrome perspective. University of Copenhagen, Faculty of Science, Department of Nutrition, Exercise and Sports, 2016. PhD thesis.

[4] House AA, Eliasziw M, Cattran DC, et al. Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy. JAMA 2010;303:1603. doi:10.1001/jama.2010.490.

[5] Xu RB, Kong X, Xu BP, et al. Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention. Am J Clin Nutr 2017;105:564–70. doi:10.3945/ajcn.116.145656.

[6] Paul L, Selhub J. Interaction between excess folate and low vitamin B12 status. Mol Aspects Med 2017;53:43–7. doi:10.1016/j.mam.2016.11.004.

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.