Dr. Oliver M Shannon, Human Nutrition & Exercise Research Centre, Newcastle University

When I was young, I loved to spend time with my grandad.  He was full of energy, had a wicked sense of humour, and was always there when you needed him.  He was in great health throughout most of his life, and he was still running half marathons well into his 70’s. However, when he was 85, my grandad had a stroke.  Shortly after, he was diagnosed with dementia and his short-term memory began to decline. Over time, other bodily functions did too, and he sadly passed away in January of this year. 

This is a short-hand version of my own personal experience of dementia.  Millions of other people have a similar story.  You may do too.  Indeed, right now there are over 55 million people in the world living with dementia, placing a huge and unsustainable burden on individuals, their families and society at large.

Although promising findings are starting to emerge, at present, there are very few options available for treating dementia.  As such, many researchers are focused on identifying ways to help people reduce their risk of developing this condition. 

The 2020 Lancet Commission Report on dementia prevention outlined 12 modifiable risk factors, which collectively account for around 40% of dementia cases worldwide, and could be targeted by policy makers and individuals to help reduce dementia risk.  These risk factors include low education levels, hearing loss, brain injury, high blood pressure, high intake of alcohol, obesity, smoking, depression, social isolation, physical inactivity, air pollution, and diabetes. 

Although this report identifies a high intake of alcohol (a dietary factor) and conditions such as obesity and diabetes (which may be linked with diet) as key dementia risk factors, it is notable that consumption of an unhealthy diet as a whole is absent from the list of modifiable risk factor for dementia.  This is despite mounting evidence that what we eat can impact brain health throughout the life course. 

There are a few reasons why diet might not play a more prominent role in the Lancet Commission report.  This includes the difficulties in defining what a healthy/unhealthy diet looks like, and the fact that not all studies have shown convincing links between diet and brain health.    There is therefore a need for more research to help us understand whether what we eat can have a meaningful effect on dementia risk.  Likewise, it is important to identify whether there are certain people who might benefit more or less from making changes to their diet. 

For some time, we (and many others) have been interested in the potential health benefits of eating a Mediterranean-like diet, which is rich in healthy plant-based foods like fruits and vegetables, pulses, nuts, olive oil and also includes plenty of fish.  Numerous studies, including the influential PREDIMED trial in Spain, have shown that eating a Mediterranean diet can improve cognitive (brain) function in older adults.  Similarly, a handful of studies have suggested that eating a Mediterranean diet could help reduce the risk of developing dementia.  However, the links between a Mediterranean diet and dementia risk are far from conclusive.  Moreover, most studies to date have been fairly small and have provided limited insight into whether certain individuals (for example, those with different genetics) might respond differently to consumption of a Mediterranean diet. 

To address some of these issues, we recently explored the associations between adherence to a Mediterranean diet and dementia risk in over 60,000 participants from the UK Biobank.  Using dietary data from the participants, we were able to give each individual a score ranging from 0 to 15 to define how closely their diet matched the key features of a Mediterranean diet (those with higher scores had a more Mediterranean-like diet).  We then used a statistical technique known as Cox proportional hazard regression to explore associations between the level of Mediterranean diet adherence and risk of developing dementia over a ~9 year period, whilst controlling for potential differences in factors such the education level and physical activity status of participants. 

We found that individuals with higher adherence to the Mediterranean diet, as defined by one of the Mediterranean diet scores known as the MEDAS continuous score, had a 23% lower risk of developing dementia than those with lower adherence to a Mediterranean diet. 

Interestingly, there were similar associations between Mediterranean diet adherence and dementia risk in individuals with higher and lower genetic risk for this condition.  This suggests that, even for those with higher genetic risk, having a more Mediterranean-like diet could help reduce the likelihood of developing dementia. 

Our study has a number of strengths, not least it’s size and the comprehensive way in which we defined genetic risk for dementia (using an approach called a polygenic risk score).  However, no study is without limitations. Most notably, as this was an observational study, we cannot infer cause and effect from our findings. 

Much more research is needed to identify the best diet that people could follow to try and reduce their risk of dementia.  However, the findings from our study contribute towards a growing body of evidence to suggest that following a more Mediterranean-like diet could be an effective way to help ‘oil your cogs’ and reduce your risk of developing dementia. 

Anyone who has spent time in research will tell you that some of the most important and highly skilled members of the research team are the laboratory technicians, without whom university research would grind to a halt.

In this blog we provide an insight into a day in the life of the Sport and Exercise Science Technicians within the HNERC.

5/6am: Our alarms go off bright and early to make sure we get to the gym/go out for a run before we start work (some of us are more committed than others!).

7am: After a sleepy walk/ metro journey into work, we get to the gym at around 7am and train for around an hour.

8am: Time for a quick shower, hair done, and we are ready to start the morning!

8am-12 (dinner): Mornings are usually our busiest time in the labs. We have UG and MSc classes scheduled most days throughout Semester 1 and 2, (usually a 9am start) and ensuring equipment and facilities are prepared is a major part of our role. We enable, check and calibrate all of the equipment that is needed for the day to ensure it’s ready to go for the students and our academic colleagues to use. We have at least 2/3 repeats of a class each day so as soon as one is done, equipment is cleaned, recalibrated, and reset ready for the next students coming in. As well as taught classes, we support staff and student research projects. It is here that our lab skills are utilised the most, we provide training, demonstrations and more recently, some of us have completed training in both venepuncture and cannulation and therefore provide phlebotomy support to a range of projects across the whole faculty.

Dinner time (most important part of the day!): We are all a bit obsessed with asking what we have for lunch, so dinner time is a very important part of our day! We catch up with one another/ other colleagues and try and have some downtime before the afternoon starts.

12:30-3pm: After lunch we catch up with any emails/lab booking forms and get ready for any classes scheduled on the afternoons.  The team have their own roles and responsibilities, and this time of day is generally used to fulfil these. For example…

• Alex is currently working on his application to gain his HEA Associate Fellowship qualification
• Jordan is supporting two projects, the first of which is investigating appetite responses to different protein sources in older adults, and the second is looking to determine the necessary centrifugation required to ensure acellular plasma.
• Will is preparing for his PhD in neuromuscular physiology, looking at the concept of durability and fatigue in endurance sports.
• Steve is currently working on setting up a consultancy service to perform biomechanical analysis on elite level golfers. Also, Steve is learning how to code using MatLab which will be beneficial for when he starts his PhD, looking at translating motion capture into real world settings using inertial measurement units.
• Ross leads both the SES and Nutrition technical teams and has recently completed his professional services development programme. Ross is also the school health and safety officer, so he is always keeping us on our toes!

As technicians, we have to be very adaptable and flexible; students and staff can need help with equipment/ anything lab based at any point in the day so we usually have to prioritise tasks as and when they arise and work around this.

3 -5 pm: We try to plan ahead and make sure we are as prepared as possible for the next day so we check the calendar and get everything ready for the next morning.

Home time – we head off home to relax and spend time with our friends and family ?

By Giorgia Perri

My PhD within the Human Nutrition & Exercise Research Centre is now coming to an end which has allowed for reflection on my learning and understanding during the programme. My PhD focused on the effect of nutrition, specifically selenium, on musculoskeletal ageing. Before I embarked the PhD programme, like many others, I did not know a whole lot about selenium. I’d noticed it on some multivitamins I was taking, but after reading about this essential micronutrient, it soon became clear how important selenium is for human health, and how it could be involved in the ageing processes of muscle and bone. Selenium is incorporated into the human body as selenoproteins which exert different effects. Most selenoproteins have antioxidant effects that can mitigate the negative effects of excessive reactive oxygen species such as DNA damage. With age there is an increase in these reactive oxygen species which is thought to contribute to the ageing phenotype and disease, including reduced musculoskeletal function. It’s crucial that research is maintained in this area as populations are on the rise and living longer, but not necessarily in good health. One major issue older adults face is a decline in their musculoskeletal function, which can be associated with osteoporosis and sarcopenia. The rationale behind my PhD was further enhanced as experiments involving animal models had found effects of selenium deficiency or supplementation on musculoskeletal function. For example, in selenium-deficient rats, studies have found abnormal skeletal growth and poor bone health ^1,2 and lower bone mineral density and femur ash weight ³.

Despite these experimental findings, the research was, and still is, lacking in human studies. A handful of promising observational studies have found associations between low serum selenium and markers of musculoskeletal strength like hand grip strength ⁴ and bone mineral density in older women ⁵ and older men ⁶. However, none of these studies to date have explored the long-term effects of selenium, analysed a variety of selenium doses or biomarkers of status or studied very old adults (≥ 85 years). This is what my PhD involved through exploring the effect of selenium on MSK ageing using two different study designs, observational (prospective) and experimental (randomised controlled trial).

The prospective analyses of my PhD used data obtained from the Newcastle 85+ Study. This was a large, longitudinal, single-birth year cohort residing in Newcastle upon Tyne. The study set out to explore the health trajectories of very old adults (≥ 85 years) and factors influencing these. During my MRes analyses I used the same data exploring the effect of dietary selenium intake on musculoskeletal function. Over half of the participants were consuming below the lower reference nutrient intake, a recommended intake to meet the needs of 2.5 % of a population, which equates to 40 µg/d ⁷. At baseline, those with lower intakes were associated with lower hand grip strength, but the association was not maintained during the 5 year follow up. This initial analysis was helpful in discovering that, as suspected, selenium intakes were suboptimal in very old adults, however, there are some limitations to dietary nutrient estimations, therefore, serum biomarkers of selenium status were measured as part of my PhD in 757 samples. These were analysed at Charité University, Berlin in Prof Lutz Schomburg’s lab that I also got to visit and found really interesting. The biomarkers of selenium status were serum selenium and two selenoproteins, glutathione peroxidase 3 (GPx3) and selenoprotein P (SePP).

Like the suboptimal selenium intake, this population also had suboptimal selenium status for serum selenium, however, surprisingly, GPx3 activity was considered adequate. It was also found that the selenoproteins were correlated linearly with serum selenium, further suggesting a lack of full selenoprotein expression. Taking this further, the associations between the biomarkers of selenium status and musculoskeletal function were explored. At baseline, there was no association between biomarkers of selenium status and hand grip strength or physical performance. However, there were negative associations between each of the selenium biomarkers and disability and GPx3 activity at baseline was negatively associated with change in prevalence of sarcopenia after 3-year follow-up.

The experimental analyses of my PhD used data obtained from the PRECISE study. This was a large, placebo-controlled randomised controlled trial using selenium-yeast supplementation in different doses (100, 200, 300 µg/d) for 5 years in 481 participants. In this study, plasma selenium was measured and retrospectively, biomarkers of bone turnover were measured. Selenium increased plasma selenium in a dose-dependent manner, suggesting good compliancy to the supplementation. However, supplementation had no significant effect on the bone turnover markers. This may be since the populations baseline selenium was 86.5 µg/l which is considered adequate whereby supplementing on top of this may provide no additional benefit. This was published in Journal of Bone and Mineral Research, see the link here https://pubmed.ncbi.nlm.nih.gov/36093566/

My PhD contributed to the field of research in selenium and musculoskeletal function by enhancing previous knowledge for example using longer study durations or more biomarkers of selenium. Despite the lack of significant findings it is still important to note the suboptimal selenium status in very old adults which requires attention for health optimisation. I would like to explore this further looking at other musculoskeletal outcomes, such as falls and fractures.

References

1. Moreno-Reyes, R., Egrise, D., Nève, J., Pasteels, J. L., Schoutens, A. (2001) ‘Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia’, Journal of Bone and Mineral Research, 16, pp. 1556-1563.
2. Hurt, H. D., Cary, E. E. and Visek, W. J. (1971) ‘Growth, reproduction, and tissue concentrations of selenium in the selenium-depleted rat’, J Nutr, 101(6), pp. 761-6.
3. Sasaki, S., Iwata, H., Ishiguro, N., Habuchi, O., & Miura, T. (1994) ‘Low-selenium Diet, Bone, and Articular Cartilage in Rats’, Nutrition, 10(6) pp. 538-543.
4. Beck, J., Ferrucci, L., Sun, K., Walston, J., Fried, L. P., Varadhan, R., Guralnik, J. M. and Semba, R. D. (2007) ‘Low serum selenium concentrations are associated with poor grip strength among older women living in the community’, BioFactors, 29(1), pp. 37-44.
5. Hoeg, A., Gogakos, Apostolos, Murphy, Elaine, Mueller, Sandra, Köhrle, Josef, Reid, David M., Glüer, Claus C., Felsenberg, Dieter, Roux, Christian, Eastell, Richard, Schomburg, Lutz, Williams, Graham R. (2012) ‘Bone turnover and bone mineral density are independently related to selenium status in healthy euthyroid postmenopausal women’, The Journal of clinical endocrinology and metabolism, 97, pp. 4061-4070.
6. Beukhof, C. M., Medici, M., van den Beld, A. W., Hollenbach, B., Hoeg, A., Visser, W. E., de Herder, W. W., Visser, T. J., Schomburg, L. and Peeters, R. P. (2016) ‘Selenium Status Is Positively Associated with Bone Mineral Density in Healthy Aging European Men’, PLoS One, 11(4), pp. e0152748.
7. Perri, G., Mendonça, Nuno., Jagger, Carol., Walsh, Jennifer., Eastell, Richard., Mathers, John C., Hill, Tom R. (2020) ‘Dietary selenium intakes and musculoskeletal function in very old adults: Analysis of the newcastle 85+ study’, 12, Nutrients, pp. 1-22.