Researchers from TwinsUK have found that rather than being protective, high protein intake is associated with loss of muscle mass in healthy over-60s.
This surprising finding comes from a study of 3,302 twins from the TwinsUK cohort.
Sarcopenia is associated with ageing and occurs when there is an accelerated loss of skeletal muscle mass and function. This can lead to negative outcomes such as frailty, reduced function in day-to-day activities, and increased risk of falls. The study aimed to investigate factors linked with skeletal muscle strength, mass and sarcopenia, particularly intake of protein, and to evaluate if shared twin characteristics are important.
The team studied twins who consumed the optimal recommended protein intake as the reference group (1.0–1.3 g/kg/day) and found that there was no significant link between protein intake (neither high nor low) and low muscle strength, or between low intake of protein and sarcopenia.
Results showed that high protein intake on the other hand was associated with decreased muscle mass, while low protein intake was protective. High protein intake was also linked with sarcopenia, even after adjusting for demographic, anthropometric (physical measures of a person’s size, form, and functional capacities) and dietary factors.
The study also found that the strength of muscles is linked with age, education, income, diet, appetite and diversity in the gut microbiome. However, the link between muscle strength and weight, body mass index, healthy eating index, protein intake, and gut microbiome diversity were not significantly influenced by shared twin factors. This means that treatments targeting these factors may be effective in preventing or treating sarcopenia.
First author Dr Mary Ni Lochlainn explains:
“We know high quality protein intake is essential for muscle health, however, it is important to consider that not all sources of protein contain the full range of essential amino acids, and that it may be important to eat some sources of protein in moderation.”
“While our participants were healthy volunteers, the results give valuable insight into the link between diet and sarcopenia. Further research is needed to investigate this further, including looking at longitudinal data in cohorts with an increased number of participants who live with sarcopenia.”
Researchers from TwinsUK have found that taking proton pump inhibitors is linked with decreased hip bone density and this effect is partly mediated through plasma metabolites.
This could put people at increased risk of fractures.
Proton pump inhibitors (PPI) are common drugs used to treat gastric disorders and are one of the most used drugs in the UK. They decrease the release of acids in the stomach by blocking an enzyme which controls the production of acids. Acids in the gut microbiome are important for the absorption of a variety of nutrients like vitamins, iron, and calcium. Several studies have suggested that the use of PPI causes a lower absorption of intestinal calcium that could then lead to a decrease in bone mineral density (BMD) and increased fracture risk.
The team wanted to investigate if PPI could modulate BMD by altering gut environment by using data from over 5,000 British male and female participants from the TwinsUK cohort.
They observed a decrease in total hip BMD in individuals who used PPI. This effect however was not mediated through the gut microbiome, suggesting that the gut microbiome does not play a role in PPI’s effect on BMD.
PPI users have lower plasma level of androgen sulfates, which belong to the sex hormone pathways. Besides, plasma androgen sulfate levels were associated with total hip BMD. Mediation analysis suggested that PPI could affect hip BMD indirectly through these plasma metabolites, providing a possible new mechanism.
First author Xinyuan Zhang said:
“In this study we showed that plasma metabolites could play a role in one of PPI’s major side effects, which is lowering BMD and increasing fracture risks. Our observation on the potential involvement of the androgen pathways in bone loss deserve additional investigations.”
Scientists have found the “booster” COVID-19 vaccine programme led to a large boost in the antibodies that help protect against coronavirus. High levels of antibodies is associated with lower risk of severe infection.
The study, which is part of the National Core Study for Longitudinal Health and Wellbeing, is published today in the scientific journal eLife. Researchers from King’s College London, Bristol University, UCL and several other institutions around the UK teamed up to work on the project.
Researchers analysed blood samples from 9,361 participants from two UK population cohorts, with 4,739 participants from TwinsUK and 4,622 from Children of the 90s (also known as the Avon Longitudinal Study of Parents and Children). Samples were tested to measure antibodies generated by vaccination, and examine whether certain groups were more likely to have lower levels of antibodies. Lower levels are known to be linked to higher risk of coronavirus infection.
Similar to previous research, the study found higher infection rates among participants with lower levels of antibodies after a first vaccination. However, researchers also found large increases in antibodies with each round of vaccination. The level of antibodies was around 10 times higher in the first weeks after a third vaccine compared to those who had only received two vaccinations an average of six months earlier.
Some groups of individuals had consistently lower levels of antibodies after vaccination. In particular, people advised to “shield” in the first year of the COVID-19 pandemic because of an increased risk of complication due to COVID-19 were more likely to have fewer antibodies. The good news was that even these individuals mounted a strong response to the booster.
Researchers also found a third dose appeared to eliminate a key difference in antibody levels based on the type of vaccine received. While people who received the Oxford/AstraZeneca vaccine were more likely to have lower antibody levels than those who received Pfizer-BioNTech after one or two vaccinations, this difference was no longer present after a third vaccination.
Findings also showed people who had a confirmed coronavirus infection before vaccination were more likely to have higher levels of antibodies, compared to those without confirmed infection.
First author Dr Nathan Cheetham explained:
“ Our findings support a policy of a third (and now fourth) COVID-19 vaccination to boost antibodies and protect against COVID-19. This is especially true for people who had the Oxford/AstraZeneca vaccine for their first and second jabs. ”
“ Our results also showed that some people are more likely to have a weaker response to vaccination than others, which we hope will be useful for policy-makers when considering any future COVID-19 vaccinations. In particular, we saw in participants from both TwinsUK and Children of the 90s cohorts that the “Shielded Patient List” criteria were an effective means to identify those with lower response to vaccination, despite the guidance to shield no longer being in place. ”
Professor Claire Steves said:
“We were particularly pleased to see that individuals at higher risk of severe infection still responded well to the booster vaccination. This is further evidence that coming forward for a booster vaccination is a good idea as COVID is still very much around.”
Your X chromosome contains clues as to whether or not you might develop cancer and heart disease, according to latest research from TwinsUK.
Chromosomes are lengths of DNA that contain genes on them. Human males have both an X and a Y chromosome, and females have two X chromosomes (XX). We only need one dose of the genes on the X chromosome, so in females, one of the X chromosomes in every cell is switched off so they do not get double the dose.
This process of X-inactivation is meant to happen at random, but researchers have identified that in some people as they age, one X is more likely to be inactivated than the other. In this study, the team identified that skew in X-inactivation (XCI) is associated with chronic health outcomes. They found that XCI-skew in older females can pick up on changes that occur in a population of blood cells and can be used as a potential biomarker to recognise the risk of developing chronic conditions.
Ageing is a complex process that involves different cellular and molecular features, which includes alteration to blood cells and makes an individual more susceptible to developing chronic conditions.
The team studied 1,575 female TwinsUK members to examine XCI skew and its link with ageing, risk of developing heart disease, and cancer diagnoses.
Researchers also found that XCI-skew is linked with the number of years an individual has lived and increases over someone’s life span. The changes in the frequency of XCI-skew were examined across increasing ages and identified 12% of participants below 40 years old displaying XCI-skew, 28% of 40–59-year old’s; 37% of 60–69-year old’s; and 44% of those over 70-year-old.
Furthermore, results showed that a skewed XCI can predict future cancer detection in a 10-year follow-up. They found that using a heart disease risk score, picked up on specific risk factors, and can predict the risk of a major heart disease event in the next 10 years, with a heart disease risk score greater than 7.5% characterizing an intermediate-risk, and a heart disease risk score greater than 20% characterizing substantial risk.
A limitation of the study was that the sample sizes restricted the chances of carrying out investigations on specific deaths or cancer types.
First author Dr Amy Roberts explained:
“This study provides a better understanding of the link between X chromosome inactivation and our health and might help explain why some twins develop chronic diseases even if their co-twin does not. Further research is needed to convert the biological usefulness of skewed XCI into clinical applications for investigating the link between blood cell changes as someone ages and association with chronic disease, despite chromosomal sex.”
This paper is part of a broader programme of work investigating how the X chromosome affects our health.
In a world first, a team of researchers led by TwinsUK has found that people with high blood pressure take longer and work harder to clear fats from the blood after meals and have higher levels of inflammation after eating.
The research, published today in Nutrients, identified that this link is in large part due to visceral fat – the kind that wraps around your organs in your belly.
This suggests that reducing belly fat could be particularly important in improving the body’s responses to food in people with high blood pressure.
“People with high blood pressure are more likely to have higher levels of visceral fat than people with normal blood pressure. Our study found that this visceral fat is indeed responsible for a considerable amount of the difference we see in blood fats and insulin levels between these two groups after meals.”
The research was part of ongoing analysis of data collected during the PREDICT study, where 1,000 participants – including several hundred TwinsUK members – had their bodies’ responses to food measured over a two-week period.
Previous studies have shown that people with high blood pressure have higher baseline levels of blood fats, insulin and inflammation compared with people with normal blood pressure, and higher blood fats following a fatty meal. The present study however was the first to investigate and compare responses between the two groups following a nutritionally balanced meal.
“We’d like to thank all of the participants who spent a full day in clinic and then two weeks meticulously logging their meals and collecting blood samples at home. It’s because of your dedication that we are able to advance health research.”
Having symptoms of COVID-19 has been associated with worse mental health and lower life satisfaction.
The study, which is part of the COVID-19 Longitudinal Health and Wellbeing National Core Study, is published today in The Lancet Psychiatry. It is led by researchers from King’s and University College London in collaboration with several UK institutions.
Data was taken from 11 longitudinal studies between April 2020 and April 2021, in which there were 54,442 participants with and without self-reported COVID-19. The study looked at the impact of COVID-19 infection on subsequent mental health and well-being.
Researchers found that rises in psychological distress, depression, anxiety, and lower life satisfaction were associated with prior self-reported COVID-19. The associations with poorer mental health did not lessen over time after infection, highlighting the potential enduring impacts of the disease and the need for a longer follow-up process from healthcare providers.
Self-reported COVID-19 was consistently associated with psychological distress, regardless of whether people tested positive for antibodies to the virus. These effects of infection were felt similarly in different groups of gender, ethnicity, and socio-economic circumstances.
The study suggests that the infection of COVID-19 might impact mental health most in older people as people with self-reported infection aged 50 years and older showed a stronger association with poorer mental health. This might reflect that older people are more likely to experience more severe COVID-19 symptoms, greater worry around infection, and increased risk of blood vessel (microvascular) or brain (neurological) changes after infection. This contrasts with the effect of the pandemic overall on mental health, where previous studies have shown that women and adults aged 25-44 have had the greatest adverse impacts.
Joint first author Dr Ellen Thompson from The School of Life Course & Population Sciences said:
“These findings suggest that there were prolonged mental health consequences of COVID-19 infection for some people at the beginning of this pandemic. Understanding why this is the case will be key to finding treatment strategies for those affected as well as preventing such effects in future pandemic waves.”
Senior author Prof Praveetha Patalay from University College London said:
“This study brings together many of the UK’s longitudinal studies to provide a comprehensive overview of the impacts of COVID-19 infection on population mental health. Compared to most studies to-date that have focussed on more severe and hospitalised cases, this study demonstrates the impact of infection during a pandemic on overall population mental health and wellbeing.”
A recent study has found that brain-age could help with early detection of dementia in patients. The team, which included TwinsUK Clinical Director Professor Claire Steves, found that patients who visited memory clinics with brains that appeared to look older had a higher risk of dementia.
Dementia is a general term for loss of memory, language, problem-solving and other thinking abilities that are severe enough to affect everyday activities.
Some years ago, members from TwinsUK took part in an MRI brain study which was used to define a brain-age score – a way of marking the age of a person from the structure of their brain. This data was used to develop a way of determining whether someone’s brain looks older or younger than their years. In the present study, the team analysed MRI brain scans from patients referred to memory clinics to determine their brain-age, and tracked which patients developed dementia through linking to their electronic health records in the years that followed.
The researchers found that patients with higher brain-age were more likely to receive a subsequent dementia diagnosis. The results from this study show that neuroimaging biomarkers like brain-age are useful clinically in managing people with memory problems. The next stage is for doctors to put this into practice regularly, so that everyone affected by memory issues can benefit from it.
Professor Claire Steves said:
“I would like to sincerely thank the twins who contributed to this study by being willing to have MRI scans, as the study shows the potential of using quantitative techniques to study the structure and function of the central nervous system in closing the gap between basic research and it being applied in clinical settings.”
The number of people with dementia around the world is increasing, and this is driving research to improve ways of identifying earlier individuals at greatest risk of being diagnosed with the disease. Being able to identify dementia in patients early on has important significance for planning future care, interventions, and clinical trials.
TwinsUK researchers have found that your B cell and T cell responses are linked to COVID-19 infection.
The immune system is made up of lots of different cells and organs that help your body fight off infections. B cells create antibodies, which neutralise viruses, with the help of T cells. Doctors and scientists have been using antibody tests to find people with previous COVID-19 infections, particularly for research. The TwinsUK team wanted to see if T-Cell tests would be a helpful addition, or replacement, for antibody tests. This is particularly important now many people cannot access PCR (swab) tests from the NHS when they think they have COVID-19.
The study looked at T-cell responses in participants who did or did not have a positive antibody response to the virus that causes COVID-19 (SARS-CoV-2) in participants who were symptomatic and asymptomatic during the COVID-19 pandemic.
The team gathered data from the TwinsUK cohort who participated in the home visit study and the COVID Symptom Study cohort. They were put into groups based on if they presented symptoms associated with COVID or not, and if they had taken part in TwinsUK’s antibody testing during the first wave in the UK in Spring 2020.
There were 32 participants who were part of the final analysis. None of the 17 participants without antibodies showed a T cell response, when their blood was tested against peptides specific to the virus. 14 out of the 15 participants who had antibodies against COVID-19 experienced a T cell response. Therefore, the study found that there was a strong correlation between antibody responses, and T cell responses to the peptides specific to SARS-CoV-2. Also, individuals who were symptomatic, but didn’t have antibodies after the infection wave in Spring 2020, had no proof of T cell memory of COVID-19 infection either.
The researchers also found no evidence of cellular immunity suggestive of COVID-19 infection in individuals with COVID-19-like symptoms but negative antibodies.
First author Dr Marc Österdahl said:
“Now that access to COVID-19 PCR testing is restricted, it is important for the public, doctors and researchers to know how we can pick-up previous COVID-19 infection. The standard is IgG Spike antibody testing, but not everyone who had symptoms that looked like COVID-19 showed antibodies.
We wanted to know if T-Cell testing, which is more expensive and complicated, would be needed to pick up all cases. However, in people who had symptoms in recent months, antibody and T-Cell responses are strongly linked, and T-Cell testing didn’t add any benefit. This suggests that the established IgG Spike test is best, and that symptoms in antibody negative people might be from another similar illness.”
Changes that occur in the body in response to an increase in belly fat have been put under the microscope as part of a study from TwinsUK, offering new insight into the cause of metabolic disease.
The study, led by King’s College London researchers Dr Jordana Bell and Colette Christiansen and published in the medical journal Genome Medicine, looked at how epigenetic marks (measures of how the human body reads DNA to affect the way genes work) in fat tissue change as belly fat accumulates.
Using samples from 538 TwinsUK participants and combining genetic, gene function, diet, and health data, the researchers examined epigenetic marks across the genome (the complete set of a person’s genetic material) and found nine genes that are highly relevant to metabolic disease risk.
Among these was a gene where the identified epigenetic changes were recognised as a potential mechanism through which diet can affect belly fat accumulation, as well as other epigenetic marks that translate genetic risk effects on metabolic health.
The findings also allowed the researchers to characterise the molecular changes that occur because of an increase in belly fat and the impact these changes have on gene function and insulin resistance.
Dr Jordana Bell, reader in Epigenomics in the School of Life Course & Population Sciences said:
“With rapidly rising rates of obesity worldwide, it is important that we understand how elevated body fat affects us at the molecular level and how this translates to metabolic disease risk,”
Metabolic diseases – the most common of which is diabetes – disrupt normal metabolism or the process of converting food to energy on a cellular level.
While previous studies in this field have explored the role of epigenetic marks in overall obesity using body mass index (BMI), the build-up of belly fat deep within the abdomen is known to be a greater risk factor for metabolic disease than BMI alone.
Dr Jordana Bell added:
“Our study brings us one step closer to this goal by identifying an epigenetic signature of excess belly fat, understanding its genetic and dietary triggers, and characterising its functional impacts and clinical consequences for insulin resistance,”
Based on the results of the study, the researchers also developed an epigenetic predictor of insulin resistance, relating their findings to the clinical consequences of elevated belly fat.
Colette Christiansen, PhD researcher in the School of Life Course & Population Sciences said:
“It is exciting to see that when we combine many different layers of biological information, we can start to unravel the mechanisms which drive the state of our biological health.”
One in six (17%) middle-aged people who report being infected by SARS-CoV-2 also report long COVID symptoms, while this falls to one in 13 (7.8%) among younger adults who reported having Covid-19, according to a new study led by King’s and UCL which is now published in Nature.
The preliminary findings, part of the UKRI-NIHR funded multi-institution CONVALESCENCE study and submitted to the preprint server medRxiv, also found that women were 50% more likely to report long COVID than men, and that the risk for long COVID symptoms increases with age, is linked to poorer pre-pandemic mental and physical health and is associated with a previous diagnosis of asthma. Non-white ethnic minority groups had lower odds of reporting long COVID (about 70% less likely).
Using a stricter definition of long COVID as impacting routine daily activities, the researchers found that it affected 1.2% of 20-year-olds who had Covid-19, but 4.8% of people in middle age.
The researchers analysed anonymised data from 1.2 million primary health records across the UK together with 10 population-based cohort studies with 45,096 participants. Using existing cohort studies, whose participants are surveyed regularly, allowed the research team to include cases not reported to the GP and to look at people’s health before the pandemic.
Knowing which factors increase the risk of long COVID is an important first step in understanding how best to prevent and treat this condition.
Professor Nishi Chaturvedi (MRC Unit for Lifelong Health and Ageing at UCL), who leads the ongoing CONVALESCENCE study, said: “Getting consistent findings from this combination of many different studies gives us greater confidence that our findings are robust, which is critical given that we know so little about long COVID.”
First author Dr Ellen Thompson, of King’s College London, said:
“It’s really important to identify risk factors in the population so we can prepare and devise prevention strategies, protecting people at increased risk of poor outcomes from COVID-19.”
First author Dr Dylan Williams (MRC Unit for Lifelong Health & Ageing at UCL) said:
“Amassing this body of evidence would usually take many months or years to assemble but we achieved this more quickly through massive, constant collaboration by researchers at many different institutions.
Dr Claire Steves from the School of Life Course Sciences said:
“Our findings hint at the mechanisms behind long COVID. Next, we need to identify the predispositions that might explain, for example, why women or individuals with asthma appear to be at higher risk. Could a liability to suffer from autoimmunity or allergies play a role? Establishing concrete research avenues to go down will eventually lead to benefits for people with long COVID.”
The study forms part of the larger COVID-19 Longitudinal Health and Wellbeing National Core Study, which is investigating the health, social and economic impacts of the COVID-19 pandemic by combining rich pre-COVID data collected from participants of numerous national research studies with national anonymised electronic health records.
The researchers investigated if the risks of developing long-term Covid symptoms differed by several pre-pandemic socioeconomic and health characteristics. Coordinated analyses of the longitudinal studies and health records data showed consistently that female sex and increasing age (up to 70 years) were associated with increased odds of long COVID.
Pre-existing adverse mental health was associated with a 50% increase in the odds of reporting long COVID, while asthma was the only specific prior medical condition consistently associated with greater risk of developing lasting Covid-19 symptoms (a 32% increase). Participants were identified as having pre-existing adverse mental health if they had been diagnosed with one of a number of conditions such as depression and bipolar disorder, or their responses to questionnaires indicated they had a mental health condition before the pandemic.
Analysis was conducted on 6,899 individuals self-reporting COVID-19 from 45,096 surveyed adult participants of ongoing longitudinal studies in the UK, and on 3,327 cases assigned a long COVID code in primary care electronic health records out of 1,199,812 adults diagnosed with acute COVID-19. Long COVID, identified as Post-COVID-19 syndrome in the study, is defined as symptoms persisting for longer than 12 weeks after the initial infection.
The research team included researchers at the Universities of Bristol, Edinburgh, Glasgow, and Oxford, as well as the London School of Hygiene & Tropical Medicine, and the Bradford Royal Infirmary.
Dr Fiona Glen, programme director for the NICE Centre for Guidelines, said:
“There is still much we do not know about the long-term effects of COVID-19. We continue to monitor and assess the latest evidence on the long-term effects allowing us to continuously update our guideline recommendations. We welcome this new research which will ensure we have a better understanding of how to manage the care and treatment of patients with prolonged symptoms of COVID-19.”
