We, human beings in Western society, make over 200 food choices each day (1). That’s a lot! Fortunately (or, according to others, unfortunately), we don’t actually have to think about each and every one of them, or at least not consciously. If our food choices are not so much a conscious decision, then how do we make them? A lot has been written about external factors influencing our food choices, for instance, alluring displays in supermarkets or the availability of unhealthy foods in our day-by-day environment. In this blog, I will address the potential role of genetics on food choices: to what extent do our genes determine what we eat?

Eating behaviours are complex, i.e. they are very diverse and influenced by many different factors. When we investigate complex behaviours, we are unlikely to find simple explanations. In other words: we do not expect to find one gene that makes me prefer pizza margarita over pizza fungi, nor will we find a single gene responsible for my triple-chocolate ice cream consumption. There are, however, some instances in which specific genes have relatively simple and straightforward effects on our food choices. This is the case when genetic variants code for food sensitivities.

A famous example is the LCT gene (or, more precisely, the C>T change at 13910 bases upstream of the LCT gene in the 13th intron of the MCM6 gene). The LCT gene codes for lactase persistence, or lactose tolerance after childhood. Worldwide, the majority of people (and most other mammals, for that matter) no longer tolerate dairy products after childhood. For them, consuming milk products causes nausea, bloating and cramping within 2-3 hours. As a result, they will soon learn not to consume dairy products. Those who have the lactase persistence gene, however, don’t have any problems digesting dairy products and, thus, are more likely to consume them (2). Geographical region is important here: while in Northern European countries such as the UK and Finland, 90-100% of people tolerate dairy products, in South-East Asia and Australia this number is close to 0% (3).

A similar situation seems to occur for genes coding for certain taste receptors on the tongue. The TAS2R38 gene, for instance, makes some people extremely sensitive to bitter taste. This, of course, will cause them to avoid bitter foods such as cruciferous vegetables (4). A recent study has even identified a small number of genes that together cause people to either love or hate marmite (5)! Another gene variant (CYP1A1), coding for caffeine clearance from the body, causes carriers to drink less or more coffee and tea (6).

Thus, when food sensitivities are involved, food choices can be driven by specific genes. Most food choices, however, have very little to do with food sensitivities and are much more complex. Pizza Margarita or Pizza Funghi? Triple-chocolate ice cream today or maybe tomorrow? While for such complex food choices there is no single gene responsible, our genetic make-up still does have influence. Typically, for complex behaviours, many different genes can be identified. While each gene individually contributes only a little bit, together they can actually have quite an effect on your food choices. For instance, a recent study identified seven genetic variants each having a small effect on carbohydrate intake. Taken together, genes explained 8% of the variation in carbohydrate intake between individuals (7).

In conclusion: while some genetic variants have rather drastic effects on our food choices, by giving us a physical adverse reaction to certain foods, there are only few of them. Most of our food choices are much more complex. These are influenced by multiple genes at the same time, and even together these genes have only limited influence.

REFERENCES
1. Wansink, B., & Sobal, J. (2007). Mindless eating: The 200 daily food decisions we overlook. Environment and Behavior, 39(1), 106-123. doi: 10.1177/0013916506295573

2. Szilagyi, A. (2015). Adaptation to Lactose in Lactase Non Persistent People: Effects on Intolerance and the Relationship between Dairy Food Consumption and Evolution of Diseases. Nutrients, 7(8):6751-79. doi: 10.3390/nu7085309

3. Itan, Y., Jones, B.L., Ingram, C.J.E., Swallow, D.M. & Thomas, M.G. (2010). A worldwide correlation of lactase persistence phenotype and genotypes. BMC Evol Biol, 10:36. doi: 10.1186/1471-2148-10-36

4. Feeney, E., O’Brien, S., Scannell, A., Markey, A. & Gibney, E.R. (2011). Genetic variation in taste perception: does it have a role in healthy eating? Proc Nutr Soc, 70(1):135-43. doi: 10.1017/S0029665110003976.

5. Roos, T.R., Kulemin, N.A., Ahmetov, I.I., Lasarow, A. & Grimaldi, K. (2017). Genome-Wide Association Studies Identify 15 Genetic Markers Associated with Marmite Taste Preference. BioRxiv (preprint). doi: 10.1101/185629

6. Josse, A.R., Da Costa, L.A., Campos, H. & El-Sohemy, A. (2012). Associations between polymorphisms in the AHR and CYP1A1-CYP1A2 gene regions and habitual caffeine consumption. Am J Clin Nutr, 96(3):665-71. doi: 10.3945/ajcn.112.038794.

7. Meddens, S.F.W., de Vlaming, R., Bowers, P., Burik, C.A.P., Karlsson Linnér, R., Lee, C., et al. (2018). Genomic analysis of diet composition finds novel loci and associations with health and lifestyle. BioRxiv (preprint). doi: 10.1101/383406

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Our body is colonized by trillions of microorganisms that are important for vital processes. Gut microbiota are the microorganisms living in the intestinal gut and play an essential role in digestion, vitamin synthesis and metabolism, among others. The mouth and the large intestine contain the vast majority of gut microbiota whether the stomach only contains few thousands of microorganisms, especially due to the acidity of its fluids. Microbiota composition is constantly changing, affecting the well-being and health of the individual.

Each individual has a unique microbiota composition, and it depends on several factors including diet, diseases, medication and also the genetics of the individual (host) (Figure). Some medicines, especially antibiotics, reduce bacterial diversity. Strong and broad spectrum antibiotics can have longer effects on gut microbiota, some of them up to several years. Genetic variation of an individual also affects the microbiota composition, and the abundance of certain microorganisms is partly genetically determined by the host.

The main contributor to gut microbiota diversity is diet, accounting for 57% of variation. Several studies have demonstrated that diet’s composition has a direct impact on gut microbiota. For example, an study performed on mice showed that “Western diet” (high-fat and sugar diet), alters the composition of microbiota in just one day! On the other hand, vegetarian and calorie restricted diet can also have an effect on gut microbiota composition.

Prebiotics and probiotics are diet strategies more used to control and reestablish the gut microbiota and improve the individual’s health. Probiotics are non-pathogenic microorganisms used as food ingredients (e.g. lactobacillus present in yoghurt) and prebiotics are indigestible food material (e.g. fibers in raw garlic, asparagus and onions), which are nutrients to increase the growth of beneficial microorganisms.

In the last years the new term psychobiotics has been introduced to define live bacteria with beneficial effects on mental health. Psychobiotics are of particular interest for improving the symptomatology of psychiatric disorders and recent preclinical trials have show promising results, particularly in stress, anxiety and depression.

Overall, these approaches are appealing because they can be introduced in food and drink and therefore provide a relatively non-invasive method of manipulating the microbiota.

AUTHORS:
Judit Cabana-Domínguez and Noèlia Fernàndez-Castillo

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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopment disorder characterized by inattention or hyperactivity–impulsivity, or both. It might seem paradoxical, but many studies indicate that individuals with a diagnosis of ADHD suffer from overweight and obesity. Therefore, it is important to understand the underlying mechanism that put individuals with ADHD at risk for obesity.

 Evidence from within-individual study
A systematic review and meta-analysis (1) based on 728,136 individuals from 42 studies, suggested a significant association between ADHD and obesity both in children/adolescents and adults. The pooled prevalence of obesity was increased by about 70% in adults with ADHD and 40% in children with ADHD compared with individuals without ADHD. However, due to the lack of longitudinal and genetically-informative studies, the meta-analysis was unable to explain the exact direction of association and the underlying etiologic mechanisms. There are several potential explanations:

  • ADHD causing obesity: The impulsivity and inattention components of ADHD might lead to disordered eating patterns and poor planning lifestyles, and further caused weight gain.
  • Obesity causing ADHD: Factors associated with obesity, for example dietary intake, might lead to ADHD-like symptoms through the microbiota-gut-brain axis.
  • ADHD and obesity may share etiological factors: ADHD and obesity may share dopaminergic dysfunctions underpinning reward deficiency processing. So the same biological mechanism may lead to both ADHD and obesity. This is difficult to investigate within individuals, but family studies can help to test this hypothesis.

We will further investigate these possibilities in the Eat2beNICE research project by using both perspective cohort study and twin studies.

Evidence from a recent within-family study
Recently, a population-based familial co-aggregation study in Sweden (2) was conducted to explore the role of shared familial risk factors (e.g. genetic variants, family disease history) in the association between ADHD and obesity. They identified 523,237 full siblings born during 1973–2002 for the 472,735 index males in Sweden, and followed them until December 3, 2009. The results suggest that having a sibling with overweight/obesity is a risk factor for ADHD. This makes it likely that biological factors (that are shared between family members) increase the risk for both ADHD and obesity.

Evidence from across-generation study
Given that both ADHD and obesity are highly heritable complex conditions, across-generation studies may also advance the understanding of the link between ADHD and obesity.

A population-based cohort study (3) based on a Swedish nationwide sample of 673,632individuals born during 1992-2004, was performed to explore the association between maternal pre-pregnancy obesity and risk of ADHD in offspring. The sibling-comparison study design was used to test the role of shared familial factors for the potential association. The results suggest that the association between maternal pre-pregnancy obesity and risk of ADHD in offspring might be largely explained by shared familial factors, for example, genetic factors transmitted from mother to child that contribute to both maternal pre-pregnancy obesity and ADHD.

Together, based on previous evidence from various study designs, there is evidence to suggest that the association between ADHD and obesity mainly is caused by shared etiological factors. However, future studies on different population are still needed to further test these findings.

REFERENCES:
1. Cortese S, Moreira-Maia CR, St Fleur D, Morcillo-Penalver C, Rohde LA, Faraone SV. Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis. The American journal of psychiatry. 2016;173(1):34-43.

2. Chen Q, Kuja-Halkola R, Sjolander A, Serlachius E, Cortese S, Faraone SV, et al. Shared familial risk factors between attention-deficit/hyperactivity disorder and overweight/obesity – a population-based familial coaggregation study in Sweden. J Child Psychol Psychiatry. 2017;58(6):711-8.

3. Chen Q, Sjolander A, Langstrom N, Rodriguez A, Serlachius E, D’Onofrio BM, et al. Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design. Int J Epidemiol. 2014;43(1):83-90.

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Why 12 genetic markers for ADHD are exciting news for New Brain Nutrition

We are finally here: for the first time, genome-wide significant markers are identified that increase the risk for Attention Deficit / Hyperactivity Disorder (ADHD). This research was conducted by an international consortium of more than 200 experts on genetics and ADHD, and includes several researchers that are also involved in our Eat2beNICE project (the scientific basis of this New Brain Nutrition website). The findings were recently published in the prestigious journal “Nature Genetics” and will greatly advance the field of ADHD genetics research.

Why is this finding so important?

The genetics of ADHD are very complex. While ADHD is highly heritable, there are likely to be thousands of genes that contribute to the disorder. Each variant individually increases the risk by only a tiny fraction. To discover these variants, you therefore need incredibly large samples. Only then can you determine which variants are linked to ADHD. The now published study by Ditte Demontis and her team combined data from many different databases and studies, together including more than 55,000 individuals of whom over 22,000 had an ADHD diagnosis.

We can now be certain that the twelve genetic markers contribute to the risk of developing ADHD. Their influence is however very small, so these markers by themselves can’t tell if someone will have ADHD. What’s interesting for the researchers is that none of these markers were identified before in much smaller genetic studies of ADHD. So this provides many new research questions to further investigate the biological mechanisms of ADHD. For instance, several of the markers point to genes that are involved in brain development and neuronal communication.

Why are our researchers excited about this?

A second important finding from the study is that the genetic variants were not specific to ADHD, but overlapped with risk of lower education, higher risk of obesity, increased BMI, and type-2 diabetes. If genetic variants increase both your risk for mental health problems such as ADHD, and for nutrition-related problems such as obesity and type-2 diabetes, then there could be a shared biological mechanism that ties this all together.

We think that this mechanism is located in the communication between the gut and the brain. A complex combination of genetic and environmental factors influence this brain-gut communication, which leads to differences in behaviour, metabolism and (mental) health.genetic markers for adhd

The microorganisms in your gut play an important role in the interaction between your genes and outside environmental influences (such as stress, illness or your diet). Now that we know which genes are important in ADHD, we can investigate how their functioning is influenced by environmental factors. For instance, gut microorganisms can produce certain metabolites that interact with these genes.

The publication by Ditte Demontis and her co-workers is therefore not only relevant for the field of ADHD genetics, but brings us one step closer to understanding the biological factors that influence our mental health and wellbeing.

Further Reading

Demontis et al. (2018) Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics. https://www.nature.com/articles/s41588-018-0269-7

The first author of the paper, Ditte Demontis, also wrote a blog about the publication. You can read it here: https://mind-the-gap.live/2018/12/10/the-first-risk-genes-for-adhd-has-been-identified/

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Is there any evidence for using micronutrients for the treatment of mental illness?

The notion that good nutrition is good for the brain is not a new idea. What is relatively new is that, until recently, there were very few well conducted studies examining whether a broad spectrum approach using doses of nutrients higher than what you could get out of a daily diet, could treat a mental disorder.

At my lab at the University of Canterbury, we have been studying the impact of micronutrients (vitamins and minerals) on mental health for the last decade. With more and more people suffering from a mental illness and not enough people getting better with conventional treatments, we need to investigate new ideas. We appear to have reached an impasse improving outcomes for mental health, despite improvements in other areas of medicine.

Mental illness and micronutrientsFor the past several decades, this idea that nutrients might treat mental illness was received with great scepticism and even ridiculed. Some continue to believe that vitamins kill us, despite evidence(1) to the contrary.

And why would this approach even work? Many readers might consider the idea is too simple to be taken seriously. But the general premise is that our brains need nutrients to function and chemicals that are essential for good mental health, like dopamine and serotonin, require micronutrients, like vitamins and minerals. Agricultural practices have changed dramatically over the last 50 years such that our food is just not as nourishing as it was for our ancestors. Perhaps some people are genetically prone to need more nutrients than what they can get out of their food. Maybe giving nutrients in higher doses than what is present in the diet can correct metabolic errors that some people may have inherited. It isn’t that farfetched an idea; don’t forget, a million sailors died from scurvy in the 18th century, before Vitamin C was introduced as a treatment.

Scientific advancements in knowledge of micronutrients

Over the last decade the field has grown substantially. No single study should be interpreted in isolation. There are now over 30 double blind randomised controlled trials (RCT) using a variety of combinations of nutrients and doses across a variety of mental health conditions showing that we can induce a substantial and clinically meaningful change in symptoms just by using nutrients.

It takes two RCTs to put a drug on the market. There are enough RCTs completed internationally that this approach should already be mainstream for the treatment of stress, anxiety, low mood and aggression in prisoners. Sadly, good nutrition and additional nutrients are not on the menu in prisons and if you present to your GP with stress or low mood, chances are pretty good that you will be put on a medication. Most data across the world consistently show that about 10% of the populations are taking an anti-depressant. In some countries, this number is even higher.

There is a long way to go to improve the effectiveness of this approach. More research is required to determine if we can enhance outcomes with a more tailored approach. We are in the infancy of figuring out the mechanism of action. Can we use genetic and nutrient testing to determine the optimal dose and nutrients that someone may require to get better, based on their individual profile? Can we use microbiome analyses to determine what microbial strains are required to best heal the gut to optimise absorption of nutrients? Current and future technologies should allow us to greatly expand the number of people who benefit from a nutritional approach. Eat2BeNice plans to investigate all these mechanism of action.

It is encouraging that some people can have better mental health and more fulfilling lives simply by ensuring their brains receive adequate nutrients and that they will not have to experience the side effects associated with so many medications. Perhaps mental illness will be viewed as being at least partially caused by improper nutrition. Could such a shift influence the stigma associated with mental illness?

We could continue to ignore the data. Or we can embrace the idea, properly fund it, and see how far it can take us in curbing the national trends. Valuing the role of nutrition as part of addressing our mental health statistics must become part of our future. Thanks to the European Commission, this might just happen.

(1) Helen Macpherson, Andrew Pipingas, Matthew P Pase; Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials, The American Journal of Clinical Nutrition, Volume 97, Issue 2, 1 February 2013, Pages 437–444, https://doi.org/10.3945/ajcn.112.049304

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