Is vitamin D really a cure-all and how should we get our fix?

Evidence is growing that the sunshine vitamin helps protect against a wide range of conditions including cancers

Vitamin D is having quite a moment. In the past few months, evidence has been growing that the sunshine vitamin not only has an important role in bone and muscle health, but might also help prevent a range of cancers, reduce the chance of developing rheumatoid arthritis, protect against multiple sclerosis and cut the risk of colds and flu.

But is vitamin D truly a cure-all? And if the benefits are real, should we all be taking vitamin D supplements or even fortifying our foods?

Vitamin D is not one chemical, but a label that covers a group of substances, including vitamin D2 and D3. The latter is the form made when sunlight hits your skin and is also found in other animals. Non-animal sources such as fungi and yeasts primarily produce the D2 form. Once in the body, these substances are converted into biologically active steroids that circulate in the blood.

One area where the impact on health appears to be clear is vitamin Ds role in keeping bones and teeth healthy and improving muscle strength.

The musculoskeletal stuff is really good and really strong, said Helen Bond, a spokesperson for the British Dietetic Association, pointing out that vitamin D is important in calcium and phosphate absorption.

Too little vitamin D can be serious: the skeletal disorders osteomalacia and rickets are known to be caused by a vitamin D deficiency, and the latter is on the rise in the UK, a finding some put down to the impact of poverty on poor nutrition.

But do the wider health claims stand up?

Intuition suggests that it cant all be right, said Julia Newton-Bishop, professor of dermatology and vitamin D expert from the University of Leeds. But while a recent review of evidence by the scientific advisory committee on nutrition only found strong evidence in the case of bone and muscle health, Newton-Bishop says a growing body of research is exploring other conditions.

Newton-Bishop says the fact that receptors for vitamin D are present on a huge array of body cells suggests the substance might indeed play a central role in our health, adding that human history offers further evidence: as humans moved to higher latitudes, skin tone became paler. [One] explanation is that vitamin D was so important that that was a selective pressure, she said. The fact that Inuits arent pale-skinned and for millennia they have had an exclusively fish diet is an argument for the fact that vitamin D was a driver, because why would they be different to everyone else?

Martin Hewison, professor of molecular endocrinology at the University of Birmingham, who carried out the recent study into vitamin D and rheumatoid arthritis, said evidence from cell studies backs up the idea that the vitamin is important.

In most of the models, vitamin D appears to have quite a positive effect, he said. If you are using cancer cell lines or cancer cells, vitamin D has anti-cancer effects, and likewise in cells that have been used for models for infection and immune disorders, vitamin D has quite clear antibacterial and anti-inflammatory effects.

But when it comes to studies in humans, the picture is far from clear-cut. While some studies find links to diseases, others do not.

That, say experts, could be partly down to the way they are conducted for example, not all studies take into account the starting levels of vitamin D in participants, or they may have been carried out in populations with different genetic factors that might affect the impact of vitamin D.

Other experts have doubts about vitamin Ds influence. Prof Tim Spector, author of The Diet Myth, wrote in the Independent: The evidence so far suggests (with the possible exception of multiple sclerosis and some cancers) that low vitamin D levels are either irrelevant or merely a marker of the disease.

Hewison says that while vitamin D might help prevent certain conditions such as tuberculosis, respiratory infections and autoimmune diseases,it should not be seen as a cure for them. It is good at protecting against things, he said, but once a disease is settled in, it is unlikely you are going to be able to give somebody who has got prostate cancer vitamin D and it is going to get dramatically better.

What about the case for supplements? With some having previously been found to cause more harm than good, Newton-Bishop says caution towards this apparent panacea is unsurprising. Everyone within the cancer world is nervous about supplements, she said. I would say to patients dont take supplements, with the exception of avoiding a low vitamin D level.

But how low is low? With the amount of sunlight needed varying with genetics, skin colour, time of day, how much one covers up and a host of other factors, the scientific advisory committee on nutrition said it was too difficult to say how much sun we need to make sure our vitamin D levels are up to scratch. In any case, from October until March the sun in the UK isnt strong enough to do the job.

The upshot is that national guidelines now recommend that during the autumn and winter at least, individuals should consider taking supplements or boosting their intake of vitamin-D-rich foods to get an intake of 10 micrograms a day, with higher-risk individuals such as some ethnic minority groups advised to follow the guidelines all year round.

However, Bond says it is hard to get enough from diet alone.

There are very few naturally rich sources of vitamin D, and most really good sources are of animal origin, which doesnt bode well for vegans and vegetarians, she said. A serving of oily fish like mackerel will give you easily your 10 micrograms of vitamin D a day, but if you drop down to a tin of canned tuna, you are only getting 1.5 micrograms.

And as Adrian Martineau, clinical professor of respiratory infection and immunity at Queen Mary University of London, points out, even in the summer, sunshine isnt going to be the answer, especially because there is an associated risk of skin cancer.

If you are considering taking supplements, it might be worth checking which form of vitamin D they contain. Some people dont want an animal form of vitamin D, said Hewison. However, What studies have shown is that if you want to raise your blood vitamin D levels, vitamin D3 is much more efficient at doing that.

Dr Benjamin Jacobs, a consultant paediatrician and spokesperson for the Royal College of Paediatrics and Child Health, says supplements are not enough as it is hard to make sure people actually take them. Instead, he suggests the UK consider food fortification.

Some countries, including Canada and Finland, have embraced fortification of milk. But although infant formula and some breakfast cereals, plant-based milks and fruit juices are already fortified in the UK, most foods are not.

Hewison believes the government should consider a national fortification plan and that the risks of it resulting in dangerously high vitamin D intake are negligible: I think most people in the field agree that if you want to have a large-scale improvement in peoples vitamin D levels then it can only really be done through fortified foods.

Read more: https://www.theguardian.com/science/2018/mar/09/is-vitamin-d-really-a-cure-all-and-how-should-we-get-our-fix

Even one cigarette a day greatly raises cardiovascular risk, experts warn

Impact of one daily cigarette on risk of heart disease and stroke greater than previously thought

Even one cigarette a day greatly raises cardiovascular risk, experts warn

Impact of one daily cigarette on risk of heart disease and stroke greater than previously thought

Read more: https://www.theguardian.com/society/2018/jan/24/even-one-cigarette-a-day-greatly-raises-cardiovascular-risk-experts-warn

Afternoon heart surgery has lower risk of complications, study suggests

Heart attacks and heart failure less common in patients having heart operations in the afternoon as opposed to the morning, say researchers

Patients undergoing open heart surgery in the afternoon have a lower risk of potentially fatal complications than those undergoing operations in the morning, new research suggests.

The study found that events including heart attacks and heart failure were less common among those who had undergone a valve replacement operation in the afternoon.

The finding appears to be linked to the ability of the heart tissue to recover after being starved of blood supply during surgery an effect the researchers say is influenced by the cells biological or circadian clock.

While the study suggests patients might fare better if they undergo afternoon surgery, Professor David Montaigne, first author of the research from the University of Lille in France, said it also highlighted another approach to reduce complications.

We have to find a drug that can alter the circadian clock to induce a jet lag, he said, noting that it could also help to improve patient outcomes for heart attacks and organ transplantation.

Writing the in Lancet, Montaigne and colleagues report how they looked at the outcomes of 596 patients, half of whom had valve surgery in the morning, and half in the afternoon. While 18% of morning surgery patients experienced a major cardiac event such as a heart attack or heart failure in the following 500 days, only 9% of those who had afternoon surgery experienced such events.

The team then randomly assigned 88 valve surgery patients to either morning or afternoon operations and monitored levels of a protein in their blood linked to heart tissue damage.

The results reveal that afternoon surgery patients had lower levels of the protein after their operation, suggesting about 20% less damage to the heart than those who underwent morning surgery.

Delving deeper, the team took biopsies from 14 morning surgery patients and 16 afternoon surgery patients, finding that tissue from the latter recovered better after being deprived of oxygen.

Further analysis found 287 genes within the cells that showed different levels of activity depending on whether the cells were from morning or afternoon patients genes which have, in many cases, previously been linked to the circadian clock.

With a time-of-day effect also found in the recovery of mouse heart tissue, the team explored the impact of tinkering with the activity linked to one of the body clock genes, both using drugs and by looking at mice without the gene. Both approaches improved the recovery of the heart tissue at the time of day when it was typically worse.

Dr John ONeill, an expert in circadian rhythms from the MRC Laboratory of Molecular Biology, said the research backed up previous work in mice and fruitflies that had explored the genes involved in the body clock work which scooped a trio of scientists the Nobel prize for medicine earlier this month.

The biological clock, the circadian rhythm, is in every single cell of the body, therefore it affects the biological activity of each cell type, commensurate with the function of those cells, he said, adding that in healthy humans the heart is known to follow a daily pattern of activity and is not at its optimum performance in the morning.

But, he noted, since systems including that of inflammation are also influenced by circadian rhythms, they too might play a role in the different outcomes for morning and afternoon surgeries.

Whats more, said ONeill, the study did not consider whether the surgeons performed the operation better in the afternoon, adding that more work was need to explore whether the findings would hold for patients at other hospitals, or for other types of surgery.

It is not the case that every single medical intervention is necessarily going to be best dealt with in the afternoon, he said, adding that the research did not mean that patients should try to jet lag themselves before surgery.

Professor Bryan Williams, chair of medicine at University College London, described the new research as fascinating and elegant, adding that the study builds on the fact that cardiovascular events, such as heart attacks, are more common in the morning. What this research suggests is that an intrinsic body clock within cells of the heart may render these cells more susceptible to injury during cardiac surgery in the morning versus the afternoon, he said.

But Williams agreed that it was too soon to consider rescheduling heart surgeries to the afternoon, and that large-scale, robust clinical trials would be needed to probe the effect further. This would be needed to change practice because the logistical implications of doing so would be huge and require definitive proof that there is a real benefit, he said.

Read more: https://www.theguardian.com/science/2017/oct/26/afternoon-heart-surgery-has-lower-risk-of-complications-study-suggests

Blood-thinning drugs ‘can reduce risk of dementia by up to 48%’

Research strongly suggests that patients taking anticoagulants for irregular heartbeat could be protected against dementia and stroke

Blood-thinning drugs could protect against dementia and stroke in people with an irregular heartbeat, research suggests.

A study found that patients being treated for atrial fibrillation (AF) were less likely to develop dementia if they were taking anticoagulants. Their risk was reduced by up to 48% compared with others with the same condition who were not prescribed the drugs.

Scientists analysed health record data from more than 444,000 Swedish AF patients.

While the findings could not prove cause and effect, they strongly suggested blood-thinning pills protect against dementia in patients with the condition, the team said.

Atrial fibrillation increases the risk of stroke and blood clots, which some experts think may appear in the brain and help trigger dementia.

Dr Leif Friberg from the Karolinska Institute in Stockholm, Sweden, who co-led the study, said: As a clinician I know there are AF patients who have a fatalistic view on stroke. Either it happens or it does not. Few patients are fatalistic about dementia, which gradually makes you lose your mind.

No brain can withstand a constant bombardment of microscopic clots in the long run. Patients probably want to hang on to as many of their little grey cells for as long as they can.

In order to preserve what youve got, you should take care to use anticoagulants if you are diagnosed with AF, as they have been proved to protect against stroke and, which this study indicates, also appear to protect against dementia.

The researchers identified everyone in Sweden who had been given a diagnosis of AF between 2006 and 2014. Monitoring each persons progress provided 1.5m years of follow-up during which 26,210 patients were diagnosed with dementia.

Prescribed blood thinners include the drugs warfarin, apixaban, dabigatran, edoxaban and rivaroxaban. Their protective effect was greater the earlier treatment started after a diagnosis of AF, the scientists found.

Friberg said patients should begin taking the drugs as soon as possible and continue using them.

He added: Doctors should not tell their patients to stop using oral anticoagulants without a really good reason. To patients, I would say dont stop unless your doctor says so.

The study, published in the European Heart Journal, found no difference in dementia prevention between the older blood-thinning drug warfarin and newer anticoagulants.

Prof Jeremy Pearson, associate medical director at the British Heart Foundation, said: Strokes caused by a clot blocking the blood vessels in the brain are a major cause of dementia, and atrial fibrillation is an important risk factor as it increases the chances of these clots forming.

By treating AF patients with blood-thinning drugs, you reduce the risk of both stroke and dementia.

Dr Carol Routledge, head of science at Alzheimers Research UK, said: The findings highlight a need to investigate this link further, but the nature of the study prevents us from firmly concluding that anticoagulants reduce the risk of dementia.

It will be important to see the results of other ongoing studies in this area, as well as teasing apart the exact relationship between anticoagulants and the risk of different types of dementia.

Read more: https://www.theguardian.com/science/2017/oct/25/blood-thinning-pills-irregular-heartbeat-patients-dementia-stroke

How your blood may predict your future health

New research into bloodstream biomarkers aims to unlock the full impact of social status on peoples lifetime health outcomes. The key is exposure to stress

Health is a well-known inequality issue. While ageing is inevitable and most of us will get sick at some point, the rate of your decline is likely to be faster the lower down the socioeconomic ladder you started.

The intriguing thing is, nobody exactly knows why. Tempting though it is to blame the usual suspects poor diet, obesity, smoking they dont account for the whole story.

If you exactly knew somebodys diet, exercise level, smoking habit or alcohol consumption, you would be about 30 to 40% likely to accurately predict how long they are going to live, says Mel Bartley, professor emerita of medical sociology at University College London, who has dedicated her career to understanding the links between society and health. But whats the rest? Thats the big question.

Unpicking the biological connections between external socioeconomic forces and an individuals health is no easy task. But Bartley and others in her field believe important clues can be found in the very lifeblood of a nation.

The idea that measurable biological markers (biomarkers) in the bloodstream can reflect an individuals underlying health status and even offer some kind of prediction of their life expectancy gained popularity in the 1950s, as scientists started searching for tell-tale markers linked to the epidemic of heart disease spreading through the US.

High blood pressure was the obvious one, but they also discovered that the level of bad cholesterol in the bloodstream was a good indicator of risk. By monitoring blood cholesterol levels in healthy people before they show any outward signs of heart disease, doctors can predict who is most at risk. The resulting medical interventions, such as dietary changes and statin drugs, can demonstrably improve those peoples long-term health.

Now, researchers are using the same approach to measure the impact of social status on the body, in the hope of developing policies that can reduce the health toll on societys most deprived section (on average, the poorest people in the UK miss out on more than a decade of life compared with the richest).

One of the most ambitious projects, currently being undertaken by the University of Essexs Institute for Social and Economic Research (ISER), is looking at blood biomarkers from some of the 40,000 UK households taking part in its Understanding Society study, which covers the entire socioeconomic spectrum.

A biomarker is an objective measure of health, explains Professor Meena Kumari, the epidemiologist leading the study along with health economist Dr Apostolos Davillas. These chemicals are like molecular flags: they allow us to see what happens inside people as theyre going through their life course which they themselves might not be so aware of.

According to Kumari, Whats happened historically is that social scientists have tended to measure health in a simple way just asking people: How do you rate your health right now? But we wanted to bring together the biology and the social science.

Published in the journal Scientific Reports, the ISER teams initial analysis focused on measuring the levels of two molecules, fibrinogen and C-reactive protein (CRP), that are produced by inflammation the bodys response to infections, stress and other harmful stimuli. Chronic long-term inflammation is linked to poorer health outcomes including heart disease, diabetes and cancer.

According to Davillas and Kumari, measuring an individuals CRP and fibrinogen levels and matching them against their socioeconomic position starts to reveal the hidden mechanisms connecting social inequality and health. And the missing link appears to be stress.

The impact of chronic stress

When we experience something stressful, we activate the hypothalamic pituitary adrenal axis: a convoluted network involving the brain and the pituitary and adrenal glands. This results in the release of cortisol and other stress hormones such as adrenaline, which have a range of effects on the body.

The complex biological conversation between this stress response and the bodys inflammatory processes actually damps down inflammation in the short term. But this careful balance seems to shift in the face of chronic stress, resulting in more inflammation over time. Thus the levels of CRP and fibrinogen, as markers of chronic inflammation, are a proxy for the impact of long-term stress on a persons body.

CRP
CRP levels at different ages by household income, left, and education. Photograph: Davillas et al/Scientific Reports

For Kumari and Davillass biomarker study, blood samples were gathered from nearly 8,000 adults in the Understanding Society cohort. While CRP and fibrinogen levels increase in all of us as we age, the ISER team found that differences in the levels of CRP and fibrinogen between socioeconomic groups begin to show relatively early in life and on average rise faster and peak sooner in poorer people.

The research shows differences in CRP levels start around 30 years old and peak around the age of 55, Davillas says. Then the gap starts to narrow again theres not so much difference between the lowest and highest socio-economic groups in later life, although of course the social inequalities are still there. People in both groups end up with similar CRP readings by their mid-70s.

The analysis suggested people in lower socioeconomic groups have a demonstrably longer exposure to chronic inflammation with all its knock-on impacts on long-term health even once the team corrected for the usual suspects of health inequality, including diet and smoking. Theres clearly something else at work.

If you ask people about their health, you dont really see differences early in life people tend to become unhealthy later in life, Kumari says. But were starting to see these underlying biomarker differences in people in their 30s; so whats that about?

Fibrinogen
Fibrinogen levels at different ages by household income, left, and education. Photograph: Davillas et al/Scientific Reports

Kumari and Davillas are now considering the causes of chronic stress that might contribute to the patterns they have found, starting with employment or lack of it and the associated issues of poor pay, job insecurity, long hours and the burgeoning gig economy.

You have stressful life events such as bereavement or divorce, but were talking about understanding chronic long-term stresses, Kumari says. One of the things we think about is why is disadvantage stressful? For something like low income, it could be because you dont have the same levels of control over your life. Maybe you can manage it for a little while, but over the long term it becomes a chronic stress. These things are hard to measure and capture.

Bartley agrees more needs to be done to understand the financial causes of stress across society. Debt is deadly for people its the ultimate lack of control, she says. Housing is also a huge issue and it doesnt get researched enough living in poor situations is depressing, especially if youre bringing up children. People in poverty can end up in social isolation, and thats known to be associated with all kinds of unhealthy outcomes.

Changes in policy

Its all very well to be able to measure levels of inflammatory biomarkers, and link them to stress and worse health outcomes but the big question is what to do about it. If its as simple as lowering inflammation, then maybe we should just hand out anti-inflammatory drugs such as aspirin to poorer people?

I dont believe thats the answer, says Bartley. We need to understand what it is about living in a tougher social and economic situation that causes this underlying stress, in order to argue for more effective changes in policy.

From a policy perspective, if you know when health inequalities begin and when they peak, this can help you target these age groups and allocate resources more effectively, says Davillas, pointing to the example of retirement timing. If youre doing a stressful job and this impacts your health more compared to someone in a less stressful occupation, this is an important issue to consider from a public health perspective. Perhaps people in more stressful jobs should retire earlier.

Measuring biomarkers across society could also give researchers a way of monitoring the impact of policy interventions. But to do that effectively will require a lot more data. While the ISER teams findings suggest a link between inflammation, stress and poor health outcomes in the most disadvantaged sectors of society, the study is only a snapshot of biomarker levels in individuals of different ages at one point in time. Whats really needed is detailed, long-term research, monitoring and following people over decades as their lives change.

If we have 30-year-olds with high CRP, we want to know what happens to them five years later, says Bartley. We need to study people over their whole life course to find out if that early high CRP reading is fixed, and does high CRP at age 30 condemn someone to get sicker faster later on or does their health outcome change if they improve their situation and lower their stress levels?

The challenge with this long-term approach is finding ways of measuring biomarkers in large numbers of people across the full spectrum of society. It would be good if we could collect them by some electronic means, instead of having to stick needles in people for blood samples, Bartley speculates. Theres a lot of scope for improvements in technology such as mobile phones, in terms of understanding how society gets under the skin.

The ISER study also highlights another striking issue: the general lack of research focuses on people in midlife a time when life paths can become entrenched.

There are a lot of studies looking at older age groups, because thats when people get sick, and lots involving children because child development is interesting, but theres not a lot going on in the middle of the age span, Kumari says. And yet we found the difference between biomarker levels was biggest in working age groups, where we have the least amount of data.

Understanding the underlying biological pathways will help us to target what it is we should be focusing on. Our data suggest that it might be stress that we need to be thinking about, particularly for working age people. But this is just the beginning theres still a lot to do.

Share your experiences by emailing inequality.project@theguardian.com, or follow the Guardians Inequality Project on Twitter here

Read more: https://www.theguardian.com/inequality/2017/oct/10/how-your-blood-may-predict-your-future-health-biomarkers

More than 25 million people dying in agony without morphine every year

Concern over illicit use and addiction is putting morphine out of reach for millions of patients globally who need it for pain relief

More than 25 million people, including 2.5 million children, die in agony every year around the world, for want of morphine or other palliative care, according to a major investigation.

Poor people cannot get pain relief in many countries of the world because their needs are overlooked or the authorities are so worried about the potential illicit use of addictive opioids that they will not allow their importation.

Staring into this access abyss, one sees the depth of extreme suffering in the cruel face of poverty and inequity, says a special report from a commission set up by the Lancet medical journal.

In Haiti, for instance, says the report, there are no nursing homes or hospices for the dying and most have to suffer without pain relief at home.

Patients in pain from trauma or malignancy are treated with medications like ibuprofen and acetaminophen, says testimony from Antonia P Eyssallenne of the University of Miami School of Medicine. Moreover, nurses are uncomfortable giving high doses of narcotics even if ordered to do so for fear of being responsible for the patients death, even if the patient is terminal.

Death in Haiti is cruel, raw, and devastatingly premature. There is often no explanation, no sympathy, and no peace, especially for the poor.

A doctor in Kerala, India, which has a palliative care service, told of the arrival of a man in agony from lung cancer. We put Mr S on morphine, among other things. A couple of hours later, he surveyed himself with disbelief. He had neither hoped nor conceived of the possibility that this kind of relief was possible, said Dr M R Rajagopal.

But when he returned, morphine stocks were out. Mr S told us with outward calm, I shall come again next Wednesday. I will bring a piece of rope with me. If the tablets are still not here, I am going to hang myself from that tree. He pointed to the window. I believed he meant what he said.

The commissions three-year inquiry found that nearly half of all deaths globally 25.5 million a year involve serious suffering for want of pain relief and palliative care. A further 35.5 million people live with chronic pain and distress. Of the 61 million total, 5.3 million are children. More than 80% of the suffering takes place in low and middle-income countries.

Jim Yong Kim, president of the World Bank, said things had to change. Failure of health systems in poor countries is a major reason that patients need palliative care in the first place. More than 90% of these child deaths are from avoidable causes. We can and will change both these dire situations.

Morphine is hard to obtain in some countries and virtually unobtainable in others. Mexico meets 36% of its need, China meets 16%, India 4% and Nigeria 0.2%. In some of the worlds poorest countries, such as Haiti, Afghanistan and many countries in Africa, oral morphine in palliative care is virtually non-existent.

Oral and injectable morphine is out of patent, but costs vary widely and it is cheaper in affluent countries like the USA than in poor countries. A second issue is opiophobia the fear that allowing the drugs to be used in hospitals will lead to addiction and crime in the community.

The world suffers a deplorable pain crisis: little to no access to morphine for tens of millions of adults and children in poor countries who live and die in horrendous and preventable pain, says Professor Felicia Knaul, co-chair of the commission from the University of Miami, calling it one of the worlds most striking injustices.

Knaul says she only realised that many people suffered without pain relief when she was working to improve access to cancer treatment in low-income countries. I was shocked. I had no idea. When people were showing me the data I thought it cant be in this world, she told the Guardian.

She had also experienced the need for morphine herself after a mastectomy for breast cancer. When I woke up I couldnt breathe because the pain was so bad. If they hadnt arrived with the morphine I dont know how I would have got through it. And as a young girl in Mexico, she had to watch her father suffer as he died without pain relief.

I dont think that we have cared enough about poor people who have pain, she said. It doesnt make them live any longer. It doesnt make them more productive. It is simply the human right of not suffering any more pain and we dont care about that for people who are poor.

The commission recommends that all countries put in place a relatively inexpensive package of effective palliative care for end of life conditions that cause suffering, including HIV, cancers, heart disease, injuries and dementia.

One of their most emphatic recommendations, says Knaul, is that immediate-release, off-patent, morphine that can cost just pennies should be made available in both oral and injectable formulations for any patient with medical need. The disparity and access abyss between the haves and have-nots is a medical, public health and moral injustice that can be effectively addressed by the commissions recommendations.

Read more: https://www.theguardian.com/science/2017/oct/12/more-than-25-million-people-dying-in-agony-without-morphine-every-year

‘Western society is chronically sleep deprived’: the importance of the body’s clock

The 2017 Nobel prize for medicine was awarded for the discovery of how our circadian rhythms are controlled. But what light does it shed on the cycle of life?

The cycle of day and night on our planet is age-old and inescapable, so the idea of an internal body clock might not sound that radical. In science, though, asking the questions why? and how? about the most day-to-day occurrences can require the greatest leaps of ingenuity and produce the most interesting answers.

This was the case for three American biologists, Jeffrey Hall, Michael Rosbash and Michael Young, who earlier this week were awarded the Nobel in medicine or physiology, for their discovery of the master genes controlling the bodys circadian rhythms.

The first hints of an internal clock came as early as the 18th century when the French scientist Jean-Jacques dOrtous de Mairan noticed that plants kept at a steady temperature in a dark cupboard unexpectedly maintained their daily rhythm of opening and closing their leaves. However, De Mairan himself concluded this was because they could sense the sun without ever seeing it.

It was only when Hall, Rosbash and Young used fruit flies to isolate a gene that controls the rhythm of a living organisms daily life that scientists got the first real glimpse at our time-keeping machinery that explains how plants, animals and humans adapt their biological rhythm so that it is synchronised with the Earths revolutions, the Nobel prize committee said.

Using fruit flies, the team identified a period gene, which encodes a protein within the cell during the night which then degrades during the day, in an endless feedback cycle.

Prof Robash, 73, a faculty member at Brandeis University in Waltham, Massachussetts, said that when his paper was published in the 1980s he had no grandiose thoughts about the importance of the discovery. During the intervening years, the picture has changed.

Its [now] pretty clear that it has its fingers in all kinds of basic processes by influencing an enormous fraction of the genome, he said.

Scientists discovered the same gene exists in mammals and that it is expressed in a tiny brain area called the suprachiasmatic nucleus, or SCN. On one side, it is linked to the retina in the eye, and on the other side it connects to the brains pineal gland, which pumps out the sleep hormone melatonin.

Modern lifestyles may no longer be constrained by sunrise and sunset, but light remains one of the most powerful influences on our behaviour and wellbeing. This realisation has fuelled a sleep hygiene movement, whose proponents point out that bright lights before bedtime and spending the whole day in a dimly lit office can dampen the natural circadian cycle, leaving people in a continual mental twilight dozy in the morning, and too alert to fall asleep promptly at night.

Rosbash welcomes this new awareness. Its been overlooked for a long time as a real public health problem, he said. All of western society is a little bit sleep deprived and, when I say a little bit, I mean chronically.

There is growing evidence that this decoupling from the natural circadian cycle can have long-term health consequences much more far-reaching than tiredness.

At first, it was assumed that the brains master clock was the bodys only internal timekeeper. In the past decade, though, scientists have shown that clock genes are active in almost every cell type in the body. The activity of blood, liver, kidney and lung cells in a petri dish all rise and fall on a roughly 24-hour cycle. Scientists have also found that the activity of around half our genes appear to be under circadian control, following undulating on-off cycles.

In effect, tiny clocks are ticking inside almost every cell type in our body, anticipating our daily needs. This network of clocks not only maintains order with respect to the outside world, but it keeps things together internally.

Virtually everything in our body, from the secretion of hormones, to the preparation of digestive enzymes in the gut, to changes in blood pressure, are influenced in major ways by knowing what time of day these things will be needed, said Clifford Saper, a professor of neuroscience at Harvard Medical School. The most common misconception is that people think that they do not have to follow the rules of biology, and can just eat, drink, sleep, play, or work whenever they want.

This discovery explains why jet lag feels so grim: the master clock adapts quickly to changing light levels, but the the rest of your body is far slower to catch up and does so at different speeds.

Jet lag is so awful because youre not simply shifted, but the whole circadian network is not aligned to each other, said Prof Russell Foster, chair of circadian neuroscience at the University of Oxford. If you were completely aligned but just five hours shifted you wouldnt feel so crappy.

It is also helps explain the extensive range of health risks experienced by shift workers, who are more likely to suffer from heart disease, dementia, diabetes and some cancers. Theyre having to override their entire biology, said Foster.

Obesity is also more common among those with irregular sleep patterns. Sapers team has found that animals that dont get enough sleep, but keep their circadian pattern, do not gain weight. But when they are placed on a 20-hour light-dark cycle, they eat more impulsively and develop glucose intolerance.

I would suggest that for humans, staying up late, watching video screens with high levels of blue light and eating high fat foods, is potentially a major cause of obesity and diabetes, said Saper.

Evidence is also emerging that our risk of acute illness rises and falls with a predictable regularity. People are 49% more likely to suffer a stroke between 6am and 12 noon than at any other time of the day and a similar pattern is true for heart attacks. This is linked to a circadian rise in blood pressure in the early morning, which happens even if youre lying in bed not doing anything.

As a result, it makes sense to take certain blood pressure medications first thing, before getting out of bed. By contrast, cholesterol is made more rapidly by the liver at night. So, statins, which lower cholesterol, work best if taken before going to bed.

Foster said that a failure to consider the circadian influence in past animal experiments may even have led to promising drug candidates being shelved. Toxicity can change from 20% to 80% depending on the time of the day you test a drug, he said.

As the impact of scientific advance slowly trickles down, the medical profession and society at large are waking up to the power of the biological clock.

A paper last year showing that jet lag impairs baseball performance, prompted some professional sports teams to take on circadian biologists as consultants on schedules for training and travel. The US Navy has altered its shift system to align it with the 24-hour clock, rather than the 18-hour day used in the old British system. Schools are experimenting with later school days, better aligned with the teenage body clock, which runs several hours later than that of adults.

As circadian rhythms have journeyed from obscure corner of science to part of the zeitgeist, companies are launching an increasing number of products on the back of a new anxiety around sleep and natural cycles. This is the western world; if somebody can make a buck theyre going to try to do it, said Rosbash.

The 73-year-old, who describes his own relationship with sleep as borderline problematic, prefers low- tech remedies, however.

I havent quite figured out how to do better, he said. I try not to take sleep medication. I dont drink alcohol too late in the evening, I read a good book. The common sense things, I think they help.

Read more: https://www.theguardian.com/science/2017/oct/06/western-society-is-chronically-sleep-deprived-the-importance-of-the-bodys-clock

Could a drug that mimics a zero-carb diet help us live longer, healthier lives?

Researchers hope to develop a medication that mimics a diet stripped of carbohydrate, after two studies showed clear benefits in mice

A drug that mimics a zero-carbohydrate diet could help people live longer, healthier lives and have better memories in old age, US researchers claim.

Scientists hope to develop a medication after two independent studies showed that mice fed on a diet stripped of all carbohydrate lived longer and performed better on a range of physical and mental tasks than those that had regular meals.

Because the diet is hard to stick to, the researchers are working on a compound that aims to deliver the same benefits for humans. If they are successful, it would amount to an extra seven to ten years of life on average, and protection against the weakening muscles and faltering memories that are defining aspects of human ageing.

Im excited about this, and its hard not to be after what weve seen that it does. These are pretty profound effects, said Eric Verdin, a physician who led one of the studies at the Buck Institute for Research on Aging in California.

The zero carb diet was designed to induce a dramatic change in metabolism, by fooling the mice into thinking they were fasting. When deprived of carbohydrate, the body shifts from using glucose as its main energy source to burning fat and producing chemicals in the liver known as ketone bodies.

In 2013, Verdin showed that a ketone body called BHB served as fuel in the body and might also protect animals against the microscopic damage that builds up in cells as part of the natural ageing process.

In a new study published in the journal Cell Metabolism, Verdin and his colleagues describe how they fed one-year-old mice either a normal high-carbohydrate diet; a high-fat, low-carb diet; or a high-fat, zero-carb diet, also known as a ketogenic diet. They found that mice on the zero-carb diet were more likely to reach old age and scored better on memory tasks than those on the other diets.

Similar benefits of the ketogenic diet were seen in a separate study by scientists at the University of California in San Diego. Megan Roberts and others found that mice fed on a zero-carbohydrate diet lived 13% longer, reaching an average age of 1,003 days compared with 886 days for mice given standard meals.

But while the zero-carb diet appeared to benefit mice, its health effects have yet to be proven in humans. To make up the calories, the mouse diet contained 90% fat, which could be dangerous for humans to adopt.

Stephen ORahilly, director of the Metabolic Research Laboratories at Cambridge University, said high-fat diets drive up LDL or bad cholesterol in humans, and so raise the risk of heart disease. Mice dont really use LDL cholesterol in the first place, so it doesnt have that bad impact on them, he said.

The work could still lead to valuable insights though. We may be able to learn from these studies what some of the pathways are that this sort of diet influences to keep mice somewhat generally healthier as they age. But for it to be useful in humans we would have to somehow dissociate these effects from the adverse effects on circulating LDL cholesterol, ORahilly added.

Verdin said that the difficulty of sticking to the diet was a major reason his team was searching for drugs to mimic the its effects. Tests are underway on a compound that produces BHB in the body in the hope that it could be taken as a supplement, he said.

The biggest problem with the diet is that it is difficult to maintain as a lifestyle, Verdin said. Its an antisocial diet. You can hardly eat anything that most of us like.

Read more: https://www.theguardian.com/science/2017/sep/05/could-a-drug-that-mimics-a-zero-carb-diet-help-us-live-longer-healthier-lives

New heart treatment is biggest breakthrough since statins, scientists say

US researchers find heart attack survivors given anti-inflammatory injections have fewer future episodes and lower cancer risk

Anti-inflammatory injections could lower the risk of heart attacks and may slow the progression of cancer, a study has found, in what researchers say is the biggest breakthrough since the discovery of statins.

Heart attack survivors given injections of a targeted anti-inflammatory drug called canakinumab had fewer attacks in the future, scientists found. Cancer deaths were also halved in those treated with the drug, which is normally used only for rare inflammatory conditions.

Statins are the mainstay drugs for heart attack prevention and work primarily by lowering cholesterol levels. But a quarter of people who have one heart attack will suffer another within five years despite taking statins regularly. It is believed this is because of unchecked inflammation within the hearts arteries.

The research team, led from Brigham and Womens hospital in Boston, tested whether targeting the inflammation with a potent anti-inflammatory agent would provide an extra benefit over statin treatment.

The researchers enrolled more than 10,000 patients who had had a heart attack and had a positive blood test for inflammation into the trial, known as the Cantos study. All patients received high doses of statins as well as either canakinumab or a placebo, both administered by injection every three months. The trial lasted for four years.

For patients who received the canakinumab injections the team reported a 15% reduction in the risk of a cardiovascular event, including fatal and non-fatal heart attacks and strokes. Also, the need for expensive interventional procedures, such as bypass surgery and inserting stents, was cut by more than 30%. There was no overall difference in death rates between patients on canakinumab and those given placebo injections, and the drug did not change cholesterol levels.

Dr Paul Ridker, who led the research team, said the study ushers in a new era of therapeutics.

For the first time, weve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk, he said.

This has far-reaching implications. It tells us that by leveraging an entirely new way to treat patients targeting inflammation we may be able to significantly improve outcomes for certain very high-risk populations.

The hospital said the reductions in risk were above and beyond those seen in patients who only took statins.

Ridker said the study showed that the use of anti-inflammatories was the next big breakthrough following the linkage of lifestyle issues and then statins.

In my lifetime, Ive gotten to see three broad eras of preventative cardiology, he said. In the first, we recognised the importance of diet, exercise and smoking cessation. In the second, we saw the tremendous value of lipid-lowering drugs such as statins. Now, were cracking the door open on the third era. This is very exciting.

But there were some downsides to the treatment. The researchers reported an increase in the chances of dying from a severe infection of about one for every 1,000 people treated, although this was offset by an unexpected halving of cancer deaths across all cancer types. In particular, the odds of succumbing to lung cancer were cut by over 75%, for reasons the team do not yet understand. The researchers are planning further trials to investigate canakinumabs potentially protective effect against cancer.

Prof Martin Bennett, a cardiologist from Cambridge who was not involved in the study, said the trial results were an important advance in understanding why heart attacks happen. But, he said, he had concerns about the side effects, the high cost of the drug and the fact that death rates were not better in those given the drug.

Treatment of UK patients is unlikely to change very much as a result of this trial, but the results do support investigation of other drugs that inhibit inflammation for cardiovascular disease, and the use of this drug in cancer, he said.

Prof Jeremy Pearson, associate medical director at the British Heart Foundation, was optimistic about the trial opening the door to new types of treatment for heart attacks.

Nearly 200,000 people are hospitalised due to heart attacks every year in the UK, Pearson said. Cholesterol-lowering drugs like statins are given to these people to reduce their risk of another heart attack and this undoubtedly saves lives. But we know that lowering cholesterol alone is not always enough.

These exciting and long-awaited trial results finally confirm that ongoing inflammation contributes to risk of heart disease, and [lowering it] could help save lives.

Read more: https://www.theguardian.com/science/2017/aug/27/anti-inflammatory-drugs-may-lower-heart-attack-risk-study-finds

We can cure Alzheimers if we stop ignoring it | Joseph Jebelli

Given focus and funding, Alzheimers will yield to science and reason, writes neuroscientist and author Joseph Jebelli

The terror of Alzheimers is that it acts by degrees, and can therefore bewilder family members as much as its victims. Those who first notice the onset of Alzheimers in a loved one tell of forgotten names and unsettling behaviour, of car keys found in the fridge and clothing in the kitchen cabinet, of aimless wanderings.

Naturally, they want to understand the boundaries of normal ageing and whether these are being crossed. Often, the answer arrives when theyre greeted as complete strangers, when the patients mind becomes irrevocably unmoored from its past. The disease is terrifying for its insidiousness as well as its long-term manifestations.

Fear partly explains why Alzheimers has been ignored for so long. Yet it is now the leading cause of death among the oldest people, and according to Professor Sir Michael Marmot, an expert in health inequalities, it could be an important part of the stagnation in increases in life expectancy since 2010 that he has identified.

As a researcher, I have been struck by how many patients speak openly about their condition only after receiving a diagnosis. I knew something wasnt right. Sometimes I dont know what day of the week it is or what I have to do, one newly diagnosed patient told me. I look in my calendar but then I think: why am I looking at this? My husband was the one who made me see a GP. I was too frightened. I thought I might have it but I didnt want to hear it.

My grandfather suppressed his concerns and agreed to see a doctor only after being hassled by his five children. By that point he had forgotten where he lived and was mistaking his wife, Afsana, for his first wife, Parry. Raising the issue with him wasnt easy; hed insist his memory was fine, and then happily discuss the health concerns of others. When faced with the stark reality of dementia, patients can retreat into themselves and some opt for silence.

But another factor is undoubtedly at work. For most of history, Alzheimers was a deeply taboo subject; those who had it were mad or just foolish. Although we think of Alzheimers as a modern disease, early accounts of dementia were described by the Roman philosopher Cicero and the Greek physician Galen. And yet only in the past two decades have we begun to realise Alzheimers is an affliction no less urgent than cancer or stroke.

And if people with other diseases of old age deserve recognition and action, then so do people with Alzheimers. The crisis around the funding of social care, and the attention focused on this during the general election campaign, has only increased the sense of urgency.

Where memory used to be viewed as a spectral, intangible quality, impossible to pin down, Alzheimers research now demonstrates the precise opposite that memory is a material phenomenon, an exquisite product of healthy brain cells that appears to reside in a network of durable connections between those brain cells. To say that this needs protecting is an understatement. Memory forms an individuals autobiography. It defines who we are. As the noted cognitive neuroscientist Michael Gazzaniga once said: Everything in life is memory, save for the thin edge of the present.

Worried
We know now that a therapy must be given in the very early stages of the disease, before symptoms appear. Photograph: Alamy

This is why the more I consider the governments approach to Alzheimers the more frustrated I become. Alzheimers costs the UK an estimated 26bn a year the combination of spending on healthcare, social care and lost earnings and taxes from people who have taken up caring roles in place of paid employment.

This is more than cancer, heart disease and stroke combined. And yet, astonishingly, only a fraction of 1% of that amount is spent on research. A hallmark of the NHS constitution is to improve health and wellbeing. In his 1939 address as president of the American Psychiatric Association, Richard Hutchings warned: Our institutions promise to become in time vast infirmaries with relatively small departments for younger patients with curable disorders.

Indeed, if things continue this way, epidemiologists estimate that the total number of Alzheimers cases will double every 20 years, making dementia the next global pandemic. In that event, the current 850,000 patients in the UK would represent no more than the tip of a vast, society-crippling iceberg.

Increasing the overall health budget is an option. A smarter strategy would be to reassess how funding is allocated in the first place. Cancer now causes fewer deaths each year than Alzheimers, but receives on average 13 times more funding. Eliminating cancer is vital, but we shouldnt pour all our efforts into one pandemic only to then be met by another. Given the advances made in understanding Alzheimers the signs and symptoms, the causes and risk factors, the genetics and neurobiology the number of therapies awaiting discovery is limitless.

The task of developing such therapies lies with the pharmaceutical industry. The problem is that many in the industry feel uneasy: between 2000 and 2012, in more than 400 clinical trials, only one drug was approved (Namenda, a drug similar to the Aricept generation of drugs, and similarly insufficient). In total, Alzheimers drug candidates have racked up a lamentable 99.6% failure rate even higher than cancer, at 81%. The recent failure of Eli Lillys solanezumab and Merck & Cos verubecestat hasnt helped.

But things are changing. We know now that a therapy must be given in the very early stages of the disease, before symptoms appear. And so Lilly, Merck and other companies are now testing drugs on patients in the newly defined preclinica phase of Alzheimers, with results expected by 2025. The role of academic researchers and patient advocates in all this is to keep championing the issue, to keep applying pressure as well as encouragement.

The word incurable is often used to describe Alzheimers. I have never liked the term because it is freighted with hopelessness. And it is wrong. Alzheimers will yield to science and reason; it will one day be as treatable as diabetes and HIV. The choice in front of us is how many generations we are willing to lose before that day comes.

The remarkable patients I met during my research, each teaching us something new and profound about the disease, deserve our action, not our sorrow. It is time to abolish their fear and silence. Its time to foster a seriousness of purpose that defeats Alzheimers once and for all.

Read more: https://www.theguardian.com/commentisfree/2017/jul/19/alzheimers-disease-death-old-people-science