What’s autophagy? It’s the ultimate detox that doesn’t yet live up to the hype

What’s autophagy? It’s the ultimate detox that doesn’t yet live up to the hype

January 12, 2022 6.12am AEDT

Authors

  1. Tim Sargeant Head, Lysosomal Health in Ageing research group, South Australian Health & Medical Research Institute
  2. Julien Bensalem Postdoctoral researcher, Lysosomal Health in Ageing research group, South Australian Health & Medical Research Institute

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TJS and JB are listed as inventors on a related patent, PCT/AU2020/050908 for measurement of autophagy in humans.

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“The anti-aging MIRACLE.” “Strengthen your immune system.” “Lose weight fast.”

These are some of the promises of autophagy, the silver bullet wellness influencers are saying is backed by Nobel-winning science.

In many cases, influencers say the best way to boost autophagy – the body’s way of recycling molecules – is with a product available from their online store.

While autophagy sounds too good to be true, the scientific reality may cross over with the hype – at least in laboratory mice and some other organisms.

Get your news from people who know what they’re talking about.

Here’s where the science is up to and what we still need to find out to see if boosting autophagy helps humans.


Read more: Research Check: can eating aged cheese help you age well?


Autophagy is the ultimate detox

Autophagy is a vital process that removes and recycles unwanted or damaged molecules from your cells.

The process begins with the cell marking unwanted or damaged organelles (made from molecules like proteins, carbohydrates, lipids, and DNA or RNA) for removal.

These marked organelles are enveloped by a membrane, sealing them inside like a garbage bag, becoming what scientists call an autophagosome.

The autophagosome then moves closer to another organelle called a lysosome, a small acidic bag filled with powerful enzymes. When the two fuse, their contents mix. The enzymes break down the rubbish into recycled nutrients your cells can re-use.

It is the ultimate detox, and you’re doing it right now.

How autophagy works in the body. Created with BioRender.com. Author provided

Mice benefit, but do humans?

Removing these waste products can potentially affect age-related diseases. For example, genetically engineered mice with less autophagy are more likely to develop tumours. Decreased autophagy also accelerates signs of dementia and heart disease in mice.

Autophagy degrades cellular components to re-use as an energy source during advanced stages of starvation in mice. And because autophagy is crucial for survival during starvation, it is sensitive to nutrient and energy levels. If we decrease nutrition in laboratory cells and laboratory animals, autophagy increases to compensate. This means diet can potentially modify autophagy.

It all sounds promising. But, and this is the big stumbling block, we don’t really know how it acts in humans.


Read more: Of mice and men: why animal trial results don’t always translate to humans


How would we know if it’s the same in humans?

For us to know if fasting, taking a pill or some other activity affects autophagy in humans (and our health), we need to be able to measure if autophagy is increasing or decreasing.

And our group has developed the first test of its kind to measure how autophagy activity varies in humans. But even that is limited to blood samples. We’re still not sure about the levels of autophagy in tissues like the brain or whether the autophagy activity we see in the blood matches elsewhere in the body. We are working on it.


Read more: There’s no magic way to boost your energy. But ‘perineum sunning’ isn’t the answer


How about those diets or pills then?

We simply do not understand enough about autophagy in humans, and there has not been enough time to test whether autophagy-boosting diets or supplements actually work in people. At best this makes various claims of boosting autophagy and its benefits premature, and at worst, completely incorrect.

Given the positive results in animals, and because autophagy is sensitive to nutrition, it is not surprising there is no end of advice and nutritional supplements that promise to increase autophagy for healthy ageing.

These tend to be books or material that explain how to diet your way to more autophagy (using intermittent fasting or keto-diets for example). Or, you can buy supplements claiming to increase autophagy with ingredients such as citrus bergamot.

Woman holding up dietary supplement
There is no end of advice and nutritional supplements that promise to increase autophagy for healthy ageing. Shutterstock

As dubious as these claims might seem, a lot of them do tend to stem from a grain of truth. Indeed, work on the mechanisms of autophagy really did win the Nobel Prize in 2016.

But influencers’ claims wildly extrapolate from preliminary data without context. For example, a mouse can only go without food for two to three days before dying, while a human can go without food for weeks.

So exactly how much fasting is required to increase autophagy in humans is completely unknown: influencer claims of 16, 24 or 48 hours are stabs in the dark.

This is equally true for supplements. One prominent product for sale is spermidine, which can increase autophagy in the laboratory, such as in yeast and cultured human cells. However, nothing directly shows it can increase autophagy in humans.

Autophagy has only been widely studied for around 15 years. So far, we know it can slow biological ageing in laboratory animals. Because of this, it has the potential to address some of the biggest health issues our society currently faces. This includes dementia, cancer and heart disease.

But, at the moment, we just don’t know enough about autophagy in humans to make any claims about what we can do to increase it, or any health benefits.


Ben Lewis, science writer and communicator at the South Australian Health and Medical Research Institute, co-authored this article.

Natural sleep-enhancement methods physicians can use tonight

Natural sleep-enhancement methods physicians can use tonight

Richard Chachowski|January 4, 2022

Few things are more restorative than a quality night of sleep. The recommended 7-9 nightly hours of shuteye are essential for attention acuity, cognitive adroitness, swift reaction times, and mood stabilization—all qualities you’d probably prefer to have in spades as an HCP. 

Research has shown that exercise helps to calibrate the body’s natural ebb and flow of energy levels.

Unfortunately, many of you are working overtime. According to the Physicians Foundation’s 2018 Survey of American Physicians, doctors work anywhere from 41-60 hours a week, while the national average stands at 34.7 hours. That extra work often translates to sleep deprivation. According to a 2018 Journal of Community Health study, about 45% of healthcare workers sleep fewer than 7 hours nightly. Healthcare was second only to protective service and military, of which 50% sleep fewer than 7 hours.

Not getting enough sleep can take a serious toll on your health, with a 2016 Current Opinion in Cardiology study showing that inadequate sleep is associated with weight gain, inflammation, cardiovascular disease, diabetes, and early mortality. It can also undermine judgment, mood, and cognitive abilities, and cause heightened stress. A 2020 JAMA Network Open study found that physicians with high levels of sleep deprivation were 97% more likely to self-report a serious medical error. And, according to a Sleep Health study, nurses who slept fewer than 7 hours before a work day were similarly found to have lower ratings of quality of care and patient safety.

The case is clear: If you want to be a more effective HCP, you need to improve the quality and duration of your sleep. While pharmaceuticals are an option, some may prefer to first try more natural methods. The following natural approaches are clinically validated. 

Exercise regularly

Physical activity is obviously important for a variety of reasons, but exercising on a regular basis can also affect how tired you feel at the end of the day, paving the way for restorative, uninterrupted sleep when you finally turn in.

A 2017 Advances in Preventive Medicine review found a correlation between people with higher levels of regular physical activity and better sleep, especially for older individuals. That raises the question of what types of physical activity benefit sleep. For people diagnosed with insomnia, a 2019 Brazilian Journal of Psychiatry study found that moderate resistance training and stretching led to objective and subjective sleep improvements, lengthier sleep durations, decreased waking episodes during the night, and generally less stress and tension overall.

Drink herbal or decaffeinated tea

It’s impossible to pinpoint one simple explanation for why many HCPs receive insufficient sleep, but it’s likely some combination of stress and variable hours/shift work. Some herbal or decaffeinated tea may take the edge off both.

A 2020 Complementary Therapies in Medicine study found that lavender tea reduced anxiety and depression scores among the elderly (an at-risk group for depression and anxiety), making it an effective tea choice to unwind with. Chamomile is another option. A 2019 Phytotherapy Research meta analysis found that chamomile extract also improves overall sleep quality, with a limited 2016 Phytomedicine study reporting long-term chamomile consumption was effective in combating moderate to severe generalized anxiety disorder. 

No matter your tea choice, be sure you choose herbal or decaffeinated. According to the American Academy of Sleep, caffeine has a half-life of 3-5 hours, meaning a cup of late afternoon coffee could affect your ability to fall asleep at night. To make it easier to sleep at the end of the day, avoid caffeine or sugar before bed—including caffeinated teas, sodas, chocolate, and other sweets.

Read or listen to music before bed

A relaxing evening routine can ease the transition into sleep. Try reserving an hour before bed for “quiet time,” wherein you avoid strenuous exercises and artificial light. A 2017 Chronobiology International study found that bright screens—from phones, TVs, and computers—negatively affected melatonin secretion, disrupted sleep patterns and morning attention, and resulted in daytime drowsiness.

To avoid that wakefulness, turn off screens before bed and opt for reading a book, listening to calming music, or doing yoga or breathing exercises to reach a relaxed state of mind that will help you slip more easily into la-la-land.

Take a hot shower or bath

Cold and hot showers each have their own benefits—cold water being beneficial for circulation, boosting metabolism and improving recovery—but in terms of getting ready for bed, we suggest a hot shower an hour or so before lights out.

A 2019 meta-analysis in Sleep Medicine Reviews found that taking a hot shower or bath improved overall sleep quality, and that those who showered/bathed 1-2 hours before bed had shorter sleep onset latency (SOL). A 2021 Journal of Clinical Sleep Medicine study similarly found that older adults who took a hot bath 1-3 hours before bed had decreased SOL rates as well.

Researchers behind a 2020 study in Current Opinion in Physiology have attributed hot showers to aiding the body’s thermoregulation process. By immersing yourself in hot water, you’re speeding this process along, meaning shortened SOL levels and an easier time falling asleep (a phenomenon known as the “warm bath effect”).

Set a strict sleep schedule

HCPs may have chaotic work schedules, but it’s critical that you maintain a healthy balance between wakefulness and sleep. To do so, you can start by supporting your natural circadian rhythm.

Evidence-backed ways to cut dementia

Evidence-backed ways to cut dementia

Naveed Saleh, MD, MS|June 2, 2021

On the surface, dementia statistics are harrowing. Globally, about 50 million people live with dementia. By 2050, this number is projected to rise—especially in low- and middle-income countries in which two-thirds of those with dementia currently live. Furthermore, the financial impact is expected to be about $1 trillion annually.

Exercising regularly is just one of a dozen modifiable risk factors for dementia, according to new research.

These numbers are staggering, according to the authors of a 2020 update of the 2017 Lancet Commission on dementia prevention. The good news is that dementia is not necessarily a foregone conclusion as we age. In fact, neurocognitive health is highly dependent on many lifestyle decisions that we can control.  

The Lancet study authors point to 12 modifiable risk factors fleshed out by the research—an increase from the nine cited in 2017. Let’s take a closer look.

What can be done?

According to the Commission, the 12 modifiable risk factors account for about 40% of worldwide dementia that can be prevented or delayed.

The authors categorize prevention strategies as: 1) reduced pathological damage (eg, amyloid-/tau-mediated, vascular, or inflammatory mechanisms), and 2) increased/maintained cognitive reserve.

The authors cite the following interventions:

  • Reduce diabetes
  • Reduce hypertension (ie, systolic pressure of 130 mm Hg at 40 years or older via antihypertensive medications)
  • Avoid head injury
  • Stop (or don’t start) smoking 
  • Decrease exposure to air pollution (including second-hand smoke)
  • Decrease midlife obesity

Additionally, the authors recommend the following for maintaining/boosting cognitive reserve:

  • Treatment of hearing impairment (ie, use of hearing aids and avoidance of excessive noise levels)
  • Develop and maintain social contact
  • Attain higher levels of education

As for factors that relate to pathological damage and cognitive reserve, the authors recommended the following:

  • Engage in frequent exercise
  • Address depression
  • Avoid excessive levels of alcohol

Of note, the three new modifiable risk factors added in 2020 were excessive alcohol consumption, head injury, and air pollution.

The authors wrote, “We recommend keeping cognitively, physically, and socially active in midlife and later life although little evidence exists for any single specific activity protecting against dementia …. Although behaviour change is difficult and some associations might not be purely causal, individuals have a huge potential to reduce their dementia risk.”

They added, “Well-being is the goal of much of dementia care. People with dementia have complex problems and symptoms in many domains. Interventions should be individualised and consider the person as a whole, as well as their family carers. Evidence is accumulating for the effectiveness, at least in the short term, of psychosocial interventions tailored to the patient’s needs, to manage neuropsychiatric symptoms. Evidence-based interventions for carers can reduce depressive and anxiety symptoms over years and be cost-effective.”

Other recent research suggests that sleep deprivation can lead to certain types of dementia. Read more about it on MDLinx.

Do these preventive strategies work?

Results of a prospective study published in the BMC reflected whether the 12 aforementioned modifiable risk factors decreased the incidence of dementia diagnosis in 1,100 participants within the study period (mean follow-up, 82.3 months). The researchers also controlled for nonmodifiable risk factors including age, sex, and APOE ε4 genotype.

Overall, 10.1% of the sample developed dementia, with APOE ε4, diabetes, heart disease, stroke, and delirium all independently correlated with risk of dementia. In the present study, nearly 40% of dementia cases were secondary to comorbid diseases.

It’s Just Not Fair.

A year ago medicare stopped giving rebates for telephone consultations. To qualify for a rebate you must have seen the doctor face-to-face (FTF) within the year before the telephone consultation. This is totally unfair to people who live in regional/rural areas, who are patients of doctors like myself, who have skill not available locally. If you live near here, Caloundra or North Lakes say, it is not too difficult to make a FTF appointment. If you live at Chinchilla, or Mackay for example, it is not so easy. You may be facing an 8 hour journey one way. How wise is this in the time of Covid, anyway, when we are encouraged to stay home. Some of my regional patients have been seeing me for more than 20 years. So again, country people are being punished again. What bureaucrat thought up this dumb policy.

I suggest rural people contact their local representatives and point out how unfair this is. There is an election coming up, so this may be a good time to get noticed. If enough people complain, this unjust rule may be corrected.

You should care about your doctor’s health, because it matters to yours

This is my first post of the new year. Unfortunately, Covid is still very much present and we will just have to get on with it. I continue to work as usual. I am not taking any new patients at present (Avoiding burnout) but hope this will be able to change in the near future. Jeff, the pharmacist at the Compounding Clinic next door has left for greener pastures, and we wish him well. My fees have gone up slightly, which is the first time in 4 years. This is due to the cost of running a medical practice having escalated (Like most other things). I wish you all well and hope this will be a good, healthy and Covid free year.

You should care about your doctor’s health, because it matters to yours

June 8, 2017 12.27pm AEST Updated February 28, 2019 9.15am AEDT

Author

  1. Alex Broom Professor of Sociology, UNSW

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Alex Broom receives funding from the Australian Research Council

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Doctors’ health tends to be broadly high compared to the general population. This is expected given their relative privilege. Health operates according to a social gradient – those with more, say, money and education, generally do better and live longer. Yet, among doctors, suicide rates are disproportionately high and mental illness is common.

Our society tends to consider certain people or roles as privileged and resilient. Doctors, above all, are helpers: they care for us, rather than us caring for them. Large salaries, influence and cultural deference lead us to assume they are not in need of care themselves.

Such assumptions are not helpful if we want to address the problem of poor well-being in the medical profession. Research shows doctors are prone to burnout, depression, anxiety, substance abuse problems, and dysfunctional personal relationships.

And when doctors struggle, the human side of the care they are trained to give suffers, and so do we as patients. Ensuring doctor wellness should be seen as ensuring quality in the Australian health-care system, promoting competence, reducing medical errors and, in turn, ensuring health system cost-effectiveness.

Get your news from people who know what they’re talking about.

Doctors who feel better will make fewer mistakes and solve problems faster. Our public investment in their careers will pay off with quality care.

Doctors’ well-being and patient health

There are many examples of the impacts of a doctor’s health on the patient. Empathy, for example, is crucial to clinical competence. We know people have more empathy when they are feeling better themselves.

The current environment may in many cases promote the reverse – what is often referred to as decreased presenteeism, or on-the-job productivity. Doctors may be present (in the clinic) but not engaging with their patients.


Read more: Are our busy doctors and nurses losing empathy for patients?


Medicine is a quickly evolving science. Doctors are required to constantly absorb new and complex information. A recent review of studies, for example, showed participation in continuing education improves professional practice and, crucially, patient outcomes.

Further, there is a known negative relationship between participation in professional education and burnout. This means the more stressed the doctor, the less motivated they will be to learn new things, and the less capable they will be to care for us.

In many other professions, time in the job reduces the risk of burnout. After an adjustment period that might be stressful, people settle down. In medicine, being in the job longer actually increases risks. The long hours, work-life imbalances, workplace pressure and even recent changes in employment opportunities fundamentally bring into question the assumed privilege of doctors.

Our study of cancer doctors

Our recent study revealed how cancer specialists experience some of these issues.

A junior cancer specialist told of the pressures cascading through medical school to training:

… you get through medical school, you do your internship residency, you get through and you don’t fail, and that’s one … then you do your physician training … it kind of takes over your life … and then you find yourself in a medical oncology advanced training position, then you’re like, ooh, everyone’s talking about there being no job, and you just think, ‘Gosh, I’ve just put myself through the wringer for the last ten years of medical school and then physician exams and everything’ … You just think, ‘Oh my god, it doesn’t end.’

Another said:

…If you’re skating on the edge of burnout, then it is very difficult to have patience with patients and their families … you’re not going to have that reserve and resilience…

A medical culture of not talking about emotional problems was also evident:

There’s not very many clear avenues of people that we can talk to about when there are difficult situations … that is something which has the ability to affect your mental health in a detrimental way … It still becomes hard for any individual to admit that they’re struggling with something because that may come across as a form of weakness.

And an early-career cancer specialist talked of how on-the-job pressures affected patient care:

I think you need to be able to commit that time [to patients] in order to be doing an effective job and if [treatment] becomes a box-ticking exercise … it dehumanises the relationship, which I find a struggle … When there isn’t time to see everyone and you have to rush them out, I think that really wears down that important part of the patient-doctor dynamic.

Not just ‘doctors’ personalities’

A classic opt-out in this debate is that doctors are type-A personalities, which means they are competitive, self-critical, high achievers and so on.

While this may be true for some, viewing the problem through this lens places the responsibility on doctors themselves rather than focusing on systemic cultural and organisational issues in medicine. It also contributes to the cultural tendency to individualise mental health issues, rather than see them as deeply embedded in broader professional and health service problems.

Medical care is rarely straightforward. It involves listening to patients’ stories, putting together complex histories and, in many cases, managing the difficult emotions of patients and families.

If we want doctors to listen, be empathetic, solve complex problems and maybe even save the health system money, we need to invest seriously in clinician well-being. Healthy doctors understand us better, make good decisions and offer us the best chance of good health.

Half of women over 35 who want a child don’t end up having one, or have fewer than they planned

Half of women over 35 who want a child don’t end up having one, or have fewer than they planned

December 7, 2021 6.06am AEDT

Author

  1. Karin Hammarberg Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University

Disclosure statement

Karin Hammarberg receives funding from The Australian Government Department of Health. She is a Senior Research Officer at the Victorian Assisted Reproductive Treatment Authority.

Monash University provides funding as a founding partner of The Conversation AU.

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At age 35, one in four Australian women and one in three men were hoping to have a child or more children in the future. But by age 49, about half report they haven’t yet had the number of children they hoped for.

That’s according to the Household, Income and Labour Dynamics in Australia (HILDA) 2021 report, released today. Over 20 years, HILDA has tracked more than 17,500 people in 9,500 households.

While some of the 49-year-old men may still father a child later in life, this is unlikely to be the case for women at that age.

In Australia and other high-income countries, there has been a long-term downward trend in the fertility rate: the average number of births per woman. In 2019, Australia hit a record-low of 1.66 babies per woman.

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Read more: Australians want more children than they have, so are we in the midst of a demographic crisis?


Low fertility rates are partly a result of more people not having children, either by choice or through circumstance. About a quarter of Australian women in their reproductive years are likely to never have children.

Why are women having fewer children?

There are many reasons why people have no or fewer children than planned towards the end of their reproductive years.

One contributing factor is the average age when women have their first child has increased in the last few decades and is now almost 30 years. This is in part explained by women spending more time in education and the workforce than they used to.


Read more: Balancing work and fertility demands is not easy – but reproductive leave can help


Another reason is some women don’t find a suitable partner or have a partner who is unwilling or “not ready” to commit to parenthood.

It’s also possible limited knowledge about the factors affecting fertility leads to missed opportunities to have the number of children originally planned.

But whatever the reason, having children later in life will inevitably affect the number of children people ultimately have. While most women who try for a baby will succeed, some won’t, and some will have fewer children than they had planned to have.

Fertility declines with age – so does IVF success

The risk of not achieving pregnancy increases as a woman gets older because the number and quality of her eggs decline.

By 40, a woman’s fertility is about half the level it was when she was 30. And sperm quality decreases with age too, starting at around age 45.

Man leans against a bike while looking at his phone.
Men’s sperm quality also declines with age. Unsplash

Increasingly, people who struggle to conceive turn to assisted reproductive technology (ART) such as in-vitro fertilisation (IVF).

There was a 27% increase in the number of treatment cycles in the 2020–2021 financial year compared to the previous year, according to data released today by the Victorian Assisted Reproductive Treatment Authority (VARTA).

But unfortunately, IVF is not a good back-up plan for age-related infertility.

On behalf of VARTA, researchers at the University of New South Wales tracked thousands of women who started IVF in Victoria in 2016 to see what had happened to them by June 30, 2020. The graph below shows the proportions of women who had a baby after one, two or three stimulated IVF cycles, including the transfer of all fresh and frozen embryos that resulted from these.

Victorian Assisted Reproductive Treatment Authority

Women who started IVF when they were 30 years old had a 48% chance of a baby after one stimulated cycle, a 62% chance after two cycles and a 67% chance after three cycles.

But for a woman who started IVF at age 40, there was only a 13% chance of a baby after one stimulated cycle, a 21% chance after two cycles and a 25% chance after three cycles.

Fertility options for over-35s

So, what are the options for women in their mid-30s who want to have a child or more children?

The Victorian Assisted Reproductive Treatment Authority data reveal some women aren’t waiting to find a partner. Over four years, there has been a 48% increase in single women using donor sperm to have a child, and a 50% increase among same-sex couples.

But the number of men who donate sperm in Victoria has remained the same, so there is now a shortage of donor sperm.

Woman sits reading in a medical waiting room.
Single women are increasingly using donor sperm to have a baby. Shutterstock

The option of freezing eggs for later use is also used by more and more women. Almost 5,000 women now have frozen eggs in storage in Victoria, up 23% on the previous year.

But it’s important to remember that although having stored eggs offers the chance of a baby, it’s not a guarantee.

For women in their 40s, using eggs donated by a younger woman increases their chance of having a baby. Our study showed women aged 40 and over who used donor eggs were five times more likely to have a live birth than women who used their own eggs.

But finding a woman who is willing to donate her eggs can be difficult. Most women who use donated eggs recruit their donor themselves and some use eggs imported from overseas egg banks.

So while people might think pregnancy will happen as soon as they stop contraception, having a baby is not always easy.


Read more: Egg freezing won’t insure women against infertility or help break the glass ceiling

Can Prozac treat COVID? Perhaps, but a related drug may be better

Shutterstock

Can Prozac treat COVID? Perhaps, but a related drug may be better

December 9, 2021 6.21am AEDT

Authors

  1. Jennifer Martin Professor of Medicine and Chair of Clinical Pharmacology, University of Newcastle
  2. Richard John Head Emeritus Professor, University of South Australia

Disclosure statement

The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.

University of South Australia and University of Newcastle provide funding as members of The Conversation AU.

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  • The rise of Omicron, the latest SARS-CoV-2 variant of concern, reminds us how quickly things can change during the pandemic.

Only a few weeks ago, we were hearing about a range of potential new COVID-19 antiviral drugs and antibody treatments. Now researchers are asking if such drugs will still work to treat Omicron, with its multiple new mutations. We’ll be hearing more about this in coming weeks.

However, another approach to treating COVID is to “treat the host”. Rather than target the virus itself, this involves treating the body’s overwhelming response to the virus. This approach is less susceptible to new viral variants.

And for this, we have some progress with, at first glance, an unlikely group of drugs to treat COVID-19 – antidepressants. These include fluoxetine (for example, Prozac) and the related drug fluvoxamine (for example, Luvox). It’s early days yet. But here’s what we know so far.

Experts have never been more important. Help us raise their voices.

Read more: Why an antidepressant could be used to treat COVID-19


How could antidepressants treat COVID?

The antidepressants under investigation are SSRIs or selective serotonin reuptake inhibitors. These commonly prescribed mood-altering drugs block “reuptake” of the naturally occurring chemical messenger, serotonin, by nerve cells in the brain; some antidepressants stop serotonin being broken down. These mechanisms leave more serotonin available to pass messages between nearby nerve cells.

There are two ways SSRIs could have an effect on COVID-19.

First, human biology is frugal

Biological “frugality” sets the scene. It takes a lot of effort for the body to make a single important molecule and a huge undertaking if you need hundreds of them. So, biology directs important molecules to multi-task.

For example, we all make serotonin by introducing a few changes to the chemical structure of the essential amino acid tryptophan, commonly present in food.

Serotonin is then tasked with being:

  • a messenger in the brain
  • a molecule to cause contraction in the gut
  • an inducer of platelet clotting, and
  • a modulator of how blood vessels work, including how they constrict and how they interact with the immune system.

The virus responsible for COVID-19 drives a devastating hyperinflammation in serious disease. This involves many of the systems serotonin strongly regulates – inflammation, platelet clotting and proper functioning of blood vessels.

So there’s a potential link between drugs that influence serotonin, and COVID-19.


Read more: Diarrhoea, stomach ache and nausea: the many ways COVID-19 can affect your gut


Second, drugs can open different locks

Drugs often act as a “key” to open certain locks in the body. However, in some cases, the “key” is not that specific and can surprise us by opening additional, unrelated locks.

This is called a pleiotropic response and is the basis of using existing drugs for new purposes (repurposing).

This may also explain why a mood-altering drug may be effective in serious infection. As we’ll see later, it may open the lock to influence inflammation.

Key in lock of old, antique wooden door
Sometimes drugs act as ‘keys’ that open different, unrelated locks. Shutterstock

Read more: Explainer: how do drugs work?


Have people tried SSRIs for COVID?

There have been a number of clinical trials showing favourable COVID-19 outcomes for people taking SSRIs.

In a preliminary study, outpatients with COVID-19 symptoms treated with fluvoxamine were less likely to deteriorate over 15 days compared with those taking the placebo.

Another study found patients hospitalised for COVID-19 who took antidepressants – including the SSRI fluoxetine, and non-SSRI antidepressants – within 48 hours of admission were less likely to be intubated or die than those who didn’t take an antidepressant.

The latest evidence comes from a major independent study published online in late October. This found people diagnosed with COVID-19 who took fluvoxamine reduced their chance of symptoms deteriorating or needing to go to hospital, compared to those who took the placebo.

Although few studies have directly compared fluvoxamine with fluoxetine to treat COVID-19, the bulk of the best quality evidence suggests to date suggests fluvoxamine may have the greatest promise.

However, there are a number of studies on broader effects of other SSRIs including fluoxetine.


Read more: We can expect more COVID drugs next year. But we’ve wasted so much time getting here


What could be happening?

It is likely our frugal biology is at work, in particular the influence of serotonin on platelets and blood clotting.

SSRIs may be reducing the incidence or size of blood clots, heart attacks and strokes we’d usually see in severe COVID-19.

SSRIs could also switch on anti-inflammatory pathways in the body, independent of any serotonin effect. Different SSRIs have different capacities to do this, which may explain why some SSRIs seem to have a greater effect on COVID-19 than others.

For instance, fluvoxamine is a more powerful key to unlock the sigma-1 receptor, which has a significant role in controlling inflammation. Fluvoxamine may also increase melatonin, which has anti-inflammatory effects.

What we still want to find out

Despite promising clinical trials, in particular for fluvoxamine, researchers still want to know:

  • is this a class effect? In other words, would all SSRIs work? Although fluvoxamine is widely available, it is not on the World Health Organization’s list of essential medicines, whereas fluoxetine is. So we need to know if these drugs are interchangeable within the class of SSRIs, or even with antidepressants more broadly
  • we still don’t know the precise mechanism behind why these drugs seem to work. But how much more data would we need before we start treating these patients in hospital?
  • could fluvoxamine work for vaccinated people? Or is the potential mainly for those unvaccinated, and more likely to have severe disease?
  • we need further information on possible side-effects of using SSRIs in COVID-19 patients, particularly if we are using doses different to the standard antidepressant dose. However, since SSRIs are existing and commonly used drugs, we already know a lot about how they work in the body, and any possible adverse reactions.

That said, based on the results to date with fluvoxamine in particular, we consider it needs to be added to the list of candidate COVID-19 drugs for further testing and evaluation.

Omicron may not be the last variant of concern. And by “treating the host” with existing drugs – SSRIs being just one example – we can offer patients options that are not at the mercy of future, unknown variants.


SSRIs can be dangerous if used in a dose that is too high for a particular person. These drugs should only be prescribed by your doctor. The drugs also have a number of potential drug interactions, increasing the risk of serotonin syndrome, which can be life-threatening.

Dentists admit feeling pressured to offer unnecessary treatments

Do I really need this crown? Dentists admit feeling pressured to offer unnecessary treatments

November 2, 2020 12.34pm AEDT

Author

  1. Alexander Holden Senior Lecturer in Dental Ethics, University of Sydney

Disclosure statement

Alexander Holden has received funding from the Dental Council of NSW, the research reported in this article being supported by an Education and Research Grant. He is also a director of the Australian Dental Association, both at a National and NSW state level and is a director of Filling the Gap, a charity providing pro-bono dental care to vulnerable members of society. Alexander is also a member of the NSW Registrations Committee of the Dental Board of Australia.

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If your dentist recommends a crown, your wisdom teeth extracted, or some other common treatment, you may wonder whether it’s really necessary.

We don’t know how common such over-servicing is. However, our research, which includes interviews with Australian dentists in private practice, published today, shows it is an issue.

Not only is this a problem for patients, some dentists say they feel pressured to recommend unnecessary treatments. And the way dentists are paid for their services actually encourages it.


Read more: How often should I get my teeth cleaned?

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What is over-servicing in dentistry?

Over-servicing can occur in many types of health care, with various definitions. But in dentistry, our research defines over-servicing as when dental treatments are provided over and above what’s clinically justified, or where there is no justification for that care at all.

Over-servicing in dentistry is reported internationally and discussed online.

And we’ve known about it in Australia for some time. In 2012, a Sydney dentist went to court and was fined more than A$1.7 million for performing almost $75,000 worth of treatment on one patient, knowing it was unnecessary and would be ineffective.

In 2013, another Sydney dentist was found guilty of over-servicing elderly nursing home patients, some of whom had dementia. He filed down their teeth to fit them for crowns they did not need, without anaesthesia.

However, over-servicing can be less extreme than revealed in these landmark court cases. Dentists we interviewed said they often felt pressured to over-service as part of their day-to-day practice.


Read more: Five commonly over-diagnosed conditions and what we can do about them


What we found

We analysed interviews with, and diary entries from, 20 Australian dentists working in private practice, the first study of its kind to include their perspectives on over-servicing.

Most dentists we interviewed had felt pressure to provide unnecessary care. Pressure came from practice owners, or their own need to meet financial commitments.

They spoke about a culture in some practices of “finding treatment” to do, rather than simply treating the issues patients had:

I quit my first job because they were overly commercial and I figured that out about two weeks in because there it was very much a matter of, “how many crowns are you doing per week? We expect our clinicians to be doing at least a crown a day” and there was no real care factor towards, what does the patient actually need? It was very much a matter of, “Okay, you’re seeing a new patient, see if you can get this much revenue out of that one”.

Why does this happen?

Most private dentists in Australia earn their wage linked to how much treatment they provide. So this fee-for-service model provides an incentive for them to provide more treatment, rather than less.

However, over-servicing isn’t inevitable. Some participants said their professional identities as dentists helped them place patients before profit:

Look, I’d always put my professionalism first. There’s been a couple of times when I’ve recommended a crown and I sort of thought “OK, am I doing this because the crown is a high-end item or because I really believe it’s the best thing for the patient?”, and I always go with what I believe is the best thing for the patient.

The dentists we spoke to also said they spent a lot of time considering how they managed patient care in a system inherently skewed to promote over-servicing.

So what happens when you shift away from purely a fee-for-service model? This might include a monthly fee for having a patient registered with a practice or service, as trialled in the United Kingdom.

The amount of clinical treatment reduced, with patients noting little change in the service they received.


Read more: Two million Aussies delay or don’t go to the dentist – here’s how we can fix that


How do we tackle this?

We could address the culture of over-servicing by changing the way dentists are paid, away from a pure fee-for-service model. Payments could be linked to measurable improvements in oral health, rather than purely just how much dentists do.

However, with fee-for-service being so entrenched in Australian dentistry, we admit this would be a difficult task, despite the increased awareness of the topic that research like ours brings.


Read more: 50 shades whiter: what you should know about teeth whitening


If you’re not sure why your dentist is recommending a certain treatment, ask. You can also ask about the pros and cons of other options, including doing nothing for now and keeping an eye on things.

If you’re not satisfied with the answer, you can ask for a second opinion. One thing to consider is that you’ll need to ask your dentist for a copy of your clinical records and x-rays (to avoid these needing to be taken again). And if visiting another dentist, you probably will need to pay for another consultation.

If you’re unhappy with your care, the best place to complain to first is your treating clinician; dentists really value receiving feedback and the opportunity to put things right.


Could marijuana break your heart?

Featured Articles in Internal Medicine In the News

Could marijuana break your heart?

Naveed Saleh, MD, MS, for MDLinx | January 23, 2020

It’s easy to get caught up in the marijuana hype. After all, everywhere you turn, there seems to be a new weed-based gummy or marijuana-infused tea. And more states are legalizing marijuana for both medicinal and recreational uses. Some of the most popular and common therapeutic uses for marijuana include relief for anxiety, nausea, and chronic pain. Keep in mind, however, that smoking marijuana produces many of the same toxins, irritants, and carcinogens as cigarette smoke, which have been shown to increase the risks of cancer and heart disease.

Advertisementmarijuana and EKG

Emerging research has linked marijuana use to adverse cardiovascular effects.

Although more studies on the health effects of marijuana need to be done, emerging research has linked marijuana use to adverse cardiovascular effects.

Physiologic effects

In new users, marijuana increases heart rate, slightly raises blood pressure levels, and can result in orthostatic hypertension. Over time, users become habituated, blood pressure drops, orthostatic hypotension dissipates, and heart rate slows. This habituation results from reduced sympathetic tone and increased parasympathetic tone.

“Marijuana’s cardiovascular effects are not associated with serious health problems for most young, healthy users, although occasional myocardial infarction, stroke, and other adverse cardiovascular events are reported,” wrote the authors of a review article published in The Journal of Clinical Pharmacology.

However, they cautioned that “[m]arijuana smoking by people with cardiovascular disease poses health risks because of the consequences of the resulting increased cardiac work, increased catecholamine levels, carboxyhemoglobin, and postural hypotension.”

Myocardial infarction

Cannabis is a rare trigger of myocardial infarction, according to the results of an oft-cited study that was supported by the National Heart, Lung, and Blood Institute and the American Heart Association. Notably, of 3,882 study participants with acute myocardial infarction, 124 (3.2%) reported marijuana use in the prior year. Of these patients, 37 said they smoked within 24 hours of a heart attack, and 9 said they did it within 1 hour of a heart attack. On a related note, these users were more commonly men, were more likely to also smoke cigarettes, and were less likely to exhibit a history of angina or high blood pressure.

Importantly, among these patients, the risk of heart attack was 4.8 times higher within the first hour of smoking and rapidly dropped thereafter. 

Cannabis arteritis

Making its first appearance in the literature in the 1960s, the phenomenon of cannabis arteritis has been described in 50-plus cases ever since. This condition, which is similar tothromboangiitis obliterans, develops in young adults who smoke pot.

Thromboangiitis obliterans, or Buerger disease, is a rare disorder that causes the blood vessels of the arms and legs to inflame, swell, and thrombose. Of note, tetrahydrocannabinol (THC)—the primary psychoactive cannabinoid found in cannabis—is hypothesized to trigger the clotting cascade, which leads to thrombus formation. 

Unlike thromboangiitis obliterans, people with cannabis arteritis are more often younger and male. Furthermore, limb involvement is more commonly unilateral. 

Although the cause of cannabis arteritis remains to be elucidated, experts hypothesize that it could be due to arsenic byproducts that result in inflammation of the endothelium.

Vasospasm

The most frequent cause of vascular events secondary to marijuana seems to be reversible arterial vasospasm. Furthermore, THC has been linked to coronary vasospasm-induced cardiomyopathy.

Although the mechanisms underlying such vasospasms are unclear, autonomic nervous system dysfunction could play a role, thus resulting in waves of vasoconstriction-dilation. Furthermore, in chronic pot smokers, THC could irritate the vascular endothelium, resulting in an increased risk of vasospasm.

Atherosclerosis

Some researchers have suggested that marijuana could contribute to atherosclerosis.

“Stimulation of the [cannabinoid 1]  and [cannabinoid 2] receptors has also been shown to modulate the function of cytoskeletal elements in the vessel wall, which may elicit an inflammatory cascade, resulting in atheroma formation. Because pulmonary and [cardiovascular systems] are populated with [cannabinoid 1] and [cannabinoid 2] receptors, marijuana use has been hypothesized to be involved in the progression of atherosclerotic disease,” wrote the authors of a review article published in Missouri Medicine.

However, more research on this subject is required.

Stroke and heart failure

According to high-powered research presented at the American College of Cardiology’s 66th Annual Scientific Session, marijuana use is linked to a 26% increased risk of stroke and a 10% increased risk of heart failure—even after adjusting for demographics, health conditions like obesity and hypertension, and lifestyle risk factors such as smoking and alcohol use.

Bottom line

Marijuana is a difficult drug to study because it’s still classified as a Schedule I substance by the federal government. Nevertheless, some researchers have shown that it can negatively impact the cardiovascular system. Although these effects may be minimal in otherwise healthy people, those with heart disease are at increased risk.

Postnatal psychosis is rare, but symptoms can be brushed aside as ‘normal’ for a new mum

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Postnatal psychosis is rare, but symptoms can be brushed aside as ‘normal’ for a new mum

November 11, 2021 2.10pm AEDT

Author

  1. Diana Jefferies Senior lecturer, Western Sydney University

Disclosure statement

Diana Jefferies does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Republish our articles for free, online or in print, under Creative Commons licence.

The period after birth of a child is supposed to be a time of great happiness for women. However, a significant number of new mothers will experience a mental illness at this time.

One is postnatal psychosis (also known as postpartum or puerperal psychosis). It’s not related to postnatal depression.

Postnatal psychosis affects one to two in every 1,000 new mothers, or about 600 women each year in Australia.

But our interviews with women who have been diagnosed with this rare but serious condition show their symptoms were often dismissed as a normal part of adjusting to motherhood.

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What is postnatal psychosis?

Postnatal psychosis affects women across all cultures and geographic areas.

The condition can put a woman at risk of self-harm or suicide and, on rare occasions, of harming others including her new baby or other children.

We don’t know what causes it. But contributing factors may include sleep deprivation, and rapid hormone changes associated with pregnancy and childbirth.

The risk of postnatal psychosis increases if a woman has a history of bipolar disorder or has had postnatal psychosis before. One woman tells her story.

What are the symptoms?

Symptoms can begin in the first few days after giving birth but may not appear until up to 12 weeks afterwards.

Some women have manic symptoms

  • manic symptoms include feeling they do not need to sleep, and are powerful and strong
  • women may have unusual experiences, such as seeing or hearing things others cannot. They may believe things that are not true
  • they can also make unrealistic and impulsive plans, can be disorganised or forgetful, and talk very quickly
  • their moods may change rapidly or they may seem excessively happy.

Others have depressive symptoms

  • depressive symptoms include a loss of energy and an inability to sleep or eat
  • women may have thoughts or auditory hallucinations that they are a bad mother and they may say they wish to die. Hallucinations or delusions (false beliefs) point to postnatal psychosis rather than to postnatal depression
  • women may find it difficult to complete activities, such as caring for themselves or their baby, or attending to other tasks in the home
  • they may believe they are helpless, hopeless and worthless, especially as a mother
  • they can become isolated and no longer enjoy activities.

Women say it’s traumatic

Women say postnatal psychosis is traumatic, especially if they do not get help when they first report symptoms. But it can be challenging to diagnose because of the stigma surrounding mental illness around the time of giving birth.

Women say they are reluctant to disclose unusual symptoms as they feel ashamed they are finding motherhood difficult and worry they may lose custody of their baby

When we interviewed ten women, who had experienced an episode of postnatal psychosis in the past ten years, we discovered another barrier to diagnosis.

Women said they knew they had unusual symptoms, such as not being able to sleep or changes in the way they thought or behaved, but they found it difficult to get help. Often, they were told these symptoms were a normal part of adjusting to motherhood.

Their postnatal psychosis was not identified until their only option was admission to an acute mental health unit and separation from their baby.

So we need more education about the condition for health-care workers. By identifying the condition earlier, this gives women more treatment options.

There are treatments

Once diagnosed, the condition can be treated with antipsychotic and mood stabilising medication, prescribed by a psychiatrist or other treating doctor.

This is very effective but medication is often not started until the symptoms have become very severe and the woman requires hospitalisation in an acute mental health unit, without her baby. This separation can compromise the developing bond between them.

So early diagnosis can potentially reduce the time a woman may spend in an acute mental health unit.


Read more: Postpartum psychosis: as we work to find causes, mothers still aren’t getting the support they need


Admission to a mother-baby unit

Best practice is to admit women and their babies to a mother-baby unit, which is usually linked to a hospital. This allows women to continue to care for their babies with the support of child and family health-care professionals.

However, publicly funded units are only available in Victoria, South Australia, Western Australia and Queensland. In New South Wales, two public mother-baby units are being built. In NSW, the only existing one is a private facility, which many families cannot afford.


Read more: Historical hospital records can show us what not to do in helping psychosis patients


Helping others

The women we interviewed said they developed support networks with each other. One woman told us:

You feel like, okay, that was such a hard experience, is there a way that we could make that a little less hard for the women who are going to go through it next time?

Women wanted to tell their stories so others would better understand postnatal psychosis and could find it easier to get help.


If this article has raised issues for you, or if you’re concerned about someone you know, contact the following organisations for more information or support: Perinatal Anxiety & Depression Australia (PANDA), 1300 726 306; Centre of Perinatal Excellence; Beyondblue, 1300 22 4636; Lifeline, 13 11 1