Tag: supplements

SIMBA project update

I was recently asked to do a small newsletter for the SIMBA project shortly describing the intervention and where we were in the process of getting it started. I thought it would be a good idea to update you as well on the project process.

We have been working hard on getting the ethical approval and on the 16th of September we got the go-ahead. We have just hired Simon, a Ph.D. student, to help out with the practical work on the project. There will be a lot to do with recruitment, running examinations and other practical parts of running a human trial.

The newsletter also contains a short description of the major hypothesis and a bit about the design of the study. Hope you enjoy the news! (continues after the picture)

SIMBA project

SIMBA newsletter

Globally, the incidence of obesity and related metabolic diseases are steeply increasing, and this has major consequences both for individuals as well as the health care system worldwide. This urgently calls for early preventive strategies, but also for treatments targeting the early developing stages of diseases such as metabolic syndrome. The gastrointestinal system and the gut microbiome, in particular, have been proposed as a key target for such interventions. A dysbiotic, or altered, gut microbiome has been associated with increased metabolic and immune disorders in humans, affecting insulin secretion, fat accumulation, energy homeostasis and plasma cholesterol levels and initially manifests as metabolic syndrome, a health condition that places people at a higher risk of cardiovascular diseases, type 2 diabetes and some cancers. Therefore, the gut microbiome may serve as a potential therapeutic target for metabolic syndrome. However, only a few potential candidates for alleviating metabolic syndrome via gut microbiome manipulation have been tested in humans.

This is about to change with the SIMBA project. As part of Work Package 5, a novel, sustainable, fermented plant-based dietary supplement will be tested on humans. The product, developed by our partner FermBiotics, is a fermented canola-seaweed product that is produced via a lactic acid bacteria driven fermentation of canola (rapeseed) and seaweed. The product is rich in glycosinolates and putatively prebiotic oligosaccharides, and it’s projected to have a huge impact on the human gut microbiota, and thereby human health.

The intervention study will be carried out as a double-blinded, placebo-controlled randomized controlled trial using a parallel design, with 100 obese participants consuming 5 grams/day of fermented seaweed and canola, or a rye cereal placebo. The participants will be instructed to maintain their daily routines throughout the six-week study, and thus potential changes would be mediated only by the supplement.

We will study the effects of the fermented canola-seaweed product on glucose handling and related cardiometabolic traits such as dyslipidemia and low-grade systemic inflammation. At each visit, an oral glucose tolerance test will be conducted to investigate insulin sensitivity by measuring 30- and 120-min blood glucose. Moreover, a small number of participants will also be included in a sub-study where they will have blood glucose levels monitored with a 24-hour continuous glucose monitoring for 14 days. We will also measure anthropometry and blood pressure. Finally, we will examine the gut microbiota and the metabolic phenotype of the subjects to explore molecular mechanisms related to the potential improvements.

Recruitment of participants has started in October 2019 and the final participants are expected to finish the trial in March 2020. The study will provide a better understanding of how a sustainable, fermented plant-based dietary supplement could be used as a potential supplement to alleviate obesity-related metabolic disorders in a population at high risk of developing type 2 diabetes and cardiovascular disease. Furthermore, the study will examine whether the product can affect obesity-related metabolic disorders through modulation of the gut microbiota and host metabolome. We expect this study to enhance our insight into useful and valuable interventions for future development of microbiota-based interventions for patients with obesity and related metabolic disorders.

New Project – Sustainable European food systems using microorganisms – the SIMBA Project

SIMBA project

I’m happy to present another new project, SIMBA, not too long after introducing the Greenland Inuit dietary intervention study.

In a recent press release, the overall aim of the project was nicely presented. “SIMBA is a project funded by the European Union that will explore the potential of using microorganisms in plants and animals to improve food security and promote sustainable food production. This is to tackle the growing challenge of supplying food to a growing global population amidst the climate change crisis, through innovative activities around food systems using microorganisms.”

The research in this project is structured around studying microbiome applications in food systems to achieve sustainable innovative solutions for the growing demand for food and for agricultural production around the world. What I’m involved in is a minor part of the larger project. Here we are to test a product that lives up to the above description. Since this involves a company, I cannot reveal too much about the product yet, but this will involve conducting a human intervention study, which I look forward to beginning in Autumn 2019.

As the world population increases and the global climate is changing, we need to find suitable solutions for the supply of food so that it will not become a problem in the future. Worldwide, the demand for food and for agricultural produce is predicted to increase by up to 70% by 2050. Thus, there is an urgent need to improve and be innovative in our food production systems, which needs to meet this increasing demand for food. Here we hope that the SIMBA project will show the potential of microorganisms in this process.

You can follow the project on twitter @SIMBAproject_EU or follow my blog for specific updates on my little part of this huge 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.