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.

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.