Why a common asthma drug will now carry extra safety warnings about depression
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Australia’s Therapeutic Goods Administration (TGA) recently issued a safety alert requiring extra warnings to be included with the asthma and hay fever drug montelukast.
The warnings are for users and their families to look for signs of serious behaviour and mood-related changes, such as suicidal thoughts and depression. The new warnings need to be printed at the start of information leaflets given to both patients and health-care providers (sometimes called a “boxed” warning).
So why did the TGA issue this warning? And is there cause for concern if you or a family member uses montelukast? Here’s what you need to know.
First, what is montelukast?
Montelukast is a prescription drug also known by its brand names which include Asthakast, Lukafast, Montelair and Singulair. It’s used to manage the symptoms of mild-to-moderate asthma and seasonal hay fever in children and adults.
Asthma occurs when the airways tighten and produce extra mucus, which makes it difficult to get air into the lungs. Likewise, the runny nose characteristic of hay fever occurs due to the overproduction of mucus.
Leukotrienes are an important family of chemicals found throughout the airways and involved in both mucus production and airway constriction. Montelukast is a cysteinyl leukotriene receptor antagonist, meaning it blocks the site in the airways where the leukotrienes work.
Montelukast can’t be used to treat acute asthma (an asthma attack), as it takes time for the tablet to be broken down in the stomach and for it to be absorbed into the body. Rather, it’s taken daily to help prevent asthma symptoms or seasonal hay fever.
It can be used alongside asthma puffers that contain corticosteriods and drugs like salbutamol (Ventolin) in the event of acute attacks.
What is the link to depression and suicide?
The possibility that this drug may cause behavioural changes is not new information. Manufacturers knew this as early as 2007 and issued warnings for possible side-effects including depression, suicidality and anxiousness.
The United Kingdom’s Medicines and Healthcare products Regulatory Agency has required a warning since 2008 but mandated a more detailed warning in 2019. The United States’ Food and Drug Administration has required boxed warnings for the drug since 2020.
Montelukast is known to potentially induce a number of behaviour and mood changes, including agitation, anxiety, depression, irritability, obsessive-compulsive symptoms, and suicidal thoughts and actions.
Initially a 2009 study that analysed data from 157 clinical trials involving more than 20,000 patients concluded there were no completed suicides due to taking the drug, and only a rare risk of suicide thoughts or attempts.
The most recent study, published in November 2024, examined data from more than 100,000 children aged 3–17 with asthma or hay fever who either took montelukast or used only inhaled corticosteroids.
It found montelukast use was associated with a 32% higher incidence of behavioural changes. The behaviour change with the strongest association was sleep disturbance, but montelukast use was also linked to increases in anxiety and mood disorders.
In the past ten years, around 200 incidences of behavioural side-effects have been reported to the TGA in connection with montelukast. This includes 57 cases of depression, 60 cases of suicidal thoughts and 17 suicide attempts or incidents of intentional self-injury. There were seven cases where patients taking the drug did complete a suicide.
This is of course tragic. But these numbers need to be seen in the context of the number of people taking the drug. Over the same time period, more than 200,000 scripts for montelukast have been filled under the Pharmaceutical Benefits Scheme.
Overall, we don’t know conclusively that montelukast causes depression and suicide, just that it seems to increase the risk for some people.
And if it does change behaviour, we don’t fully understand how this happens. One hypothesis is that the drug and its breakdown products (or metabolites) affect brain chemistry.
Specifically, it might interfere with how the brain detoxifies the antioxidant glutathione or alter the regulation of other brain chemicals, such as neurotransmitters.
Why is the TGA making this change now?
The new risk warning requirement comes from a meeting of the Australian Advisory Committee on Medicines where they were asked to provide advice on ways to minimise the risk for the drug given current international recommendations.
Even though the 2024 review didn’t highlight any new risks, to align with international recommendations, and help address consumer concerns, the advisory committee recommended a boxed warning be added to drug information sheets.
If you have asthma and take montelukast (or your child does), you should not just stop taking the drug, because this could put you at risk of an attack that could be life threatening. If you’re concerned, speak to your doctor who can discuss the risks and benefits of the medication for you, and, if appropriate, prescribe a different medication.
If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14.
Nial Wheate, Professor of Pharmaceutical Chemistry, Macquarie University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Sciatica Exercises & Home Treatment – by Dr. George Best
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Dr. Best is a doctor of chiropractic, but his work here is compelling. He starts by giving an overview of the relevant anatomy, and then the assorted possible causes of sciatica, before moving on to the treatments.
As is generally the case for chiropractic, nothing here will be “cured”, but it will give methods for ongoing management to keep you pain-free—which in the case of sciatica, is usually the single biggest thing that most people suffering from it most dearly want.
We get to read a lot about self-massage and exercises, of the (very well-evidenced; about the most well-evidenced thing there is for back pain) McKenzie technique exercises, as well as assorted acupressure-based techniques that are less well-evidenced but have good anecdotal support.
He also writes about preventing sciatica—which if you already have it, that doesn’t mean it’s too late; it just means, in that case do these things (along with the aforementioned exercises) to gradually reverse the harm done and get back to where you were pre-sciatica.
Lastly, he does also speak on when signs might point to your problems being beyond the scope of this book, and seeking professional examination if you haven’t already.
The style throughout is straight to the point, informative, and instructional. There is zero fluff or padding, and no sensationalization. There are diagrams and illustrative photos where appropriate.
Bottom line: if you have, or fear the threat of, sciatica, then this is an excellent book to have and use its exercises.
Click here to check out Sciatica Exercises & Home Treatment, and live pain-free!
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Rapamycin Can Slow Aging By 20% (But Watch Out)
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Rapamycin’s Pros & Cons
Rapamycin is generally heralded as a wonderdrug that (according to best evidence so far) can slow down aging, potentially adding decades to human lifespan—and yes, healthspan.
It comes from a kind of soil bacteria, which in turn comes from the island of Rapa Nui (a Chilean territory best known for its monumental moai statues), hence the name rapamycin.
Does it work?
Yes! Probably! With catches!
Like most drugs that are tested for longevity-inducing properties, research in humans is very slow. Of course for drugs in general, they must go through in vitro and in vivo animal testing first before they can progress to human randomized clinical trials, but for longevity-inducing drugs, it’s tricky to even test in humans, without waiting entire human lifetimes for the results.
Nevertheless, mouse studies are promising:
Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
(“Easter Island” is another name given to the island of Rapa Nui)
That’s not a keysmash in the middle there, it’s a reference to rapamycin’s inhibitory effect on the kinase mechanistic target of rapamycin, sometimes called the mammalian target of rapamycin, and either way generally abbreviated to “mTOR”—also known as “FK506-binding protein 12-rapamycin-associated protein 1” or “FRAP1“ to its friends, but we’re going to stick with “mTOR”.
What’s relevant about this is that mTOR regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription.
Don’t those words usually get associated with cancer?
They do indeed! Rapamycin and its analogs have well-demonstrated anti-cancer potential:
❝Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo.
Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer.❞
…and as such, gets used sometimes as an anticancer drug—especially against renal cancer. See also:
Research perspective: Cancer prevention with rapamycin
What’s the catch?
Aside from the fact that its longevity-inducing effects are not yet proven in humans, the mouse models find its longevity effects to be sex-specific, extending the life of male mice but not female ones:
Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects
One hypothesis about this is that it may have at least partially to do with rapamycin’s immunomodulatory effect, bearing in mind that estrogen is immune-enhancing and testosterone is immunosuppressant.
And rapamycin? That’s another catch: it is an immunosuppressant.
This goes in rapamycin’s favor for its use to avoiding rejection when it comes to some transplants (most notably including for kidneys), though the very same immunosuppressant effect is a reason it is contraindicated for certain other transplants (such as in liver or lung transplants), where it can lead to an unacceptable increase in risk of lymphoma and other malignancies:
Prescribing Information: Rapamune, Sirolimus Solution / Sirolimus Tablet
(Sirolimus is another name for rapamycin, and Rapamune is a brand name)
What does this mean for the future?
Researchers think that rapamycin may be able to extend human lifespan to a more comfortable 120–125 years, but acknowledge there’s quite a jump to get there from the current mouse studies, and given the current drawbacks of sex-specificity and immunosuppression:
Advances in anti-aging: Rapamycin shows potential to extend lifespan and improve health
Noteworthily, rapamycin has also shown promise in simultaneously staving off certain diseases associated most strongly with aging, including Alzheimer’s and cardiac disease—or even, starting earlier, to delay menopause, in turn kicking back everything else that has an uptick in risk peri- or post-menopause:
Effect of Rapamycin in Ovarian Aging (Rapamycin)
👆 an upcoming study whose results are thus not yet published, but this is to give an idea of where research is currently at. See also:
Pilot Study Evaluates Weekly Pill to Slow Ovarian Aging, Delay Menopause
Where can I try it?
Not from Amazon, that’s for sure!
It’s still tightly regulated, but you can speak with your physician, especially if you are at risk of cancer, especially if kidney cancer, about potentially being prescribed it as a preventative—they will be able to advise about safety and applicability in your personal case.
Alternatively, you can try getting your name on the list for upcoming studies, like the one above. ClinicalTrials.gov is a great place to watch out for those.
Meanwhile, take care!
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Natural Remedies and Foods for Osteoarthritis
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It’s Q&A Day at 10almonds!
Have a question or a request? You can always hit “reply” to any of our emails, or use the feedback widget at the bottom!
In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!
As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!
So, no question/request too big or small
❝Natural solutions for osteoarthritis. Eg. Rosehip tea, dandelion root tea. Any others??? What foods should I absolutely leave alone?❞
We’ll do a main feature on arthritis (in both its main forms) someday soon, but meanwhile, we recommend eating for good bone/joint health and against inflammation. To that end, you might like these main features we did on those topics:
- We Are Such Stuff As Fish Are Made Of (collagen for bone and joint health)
- The Bare-Bones Truth About Osteoporosis (eating for bone health generally)
- Keep Inflammation At Bay (dietary tips for minimizing inflammation—also, our all-time most popular article to date!)
Of these, probably the last one is the most critical, and also will have the speediest effects if implemented.
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Do Hard Things – by Steve Magness
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It’s easy to say that we must push ourselves if we want to achieve worthwhile things—and it’s also easy to push ourselves into an early grave by overreaching. So, how to do the former, without doing the latter?
That’s what this book’s about. The author, speaking from a background in the science of sports psychology, applies his accumulated knowledge and understanding to the more general problems of life.
Most of us are, after all, not sportspeople or if we are, not serious ones. Those few who are, will get benefit from this book too! But it’s mostly aimed at the rest of us who are trying to work out whether/when we should scale up, scale back, change track, or double down:
- How much can we really achieve in our career?
- How about in retirement?
- Do we ever really get too old for athletic feats, or should we keep pressing on?
Magness brings philosophy and psychological science together, to help us sort our way through.
Nor is this just a pep talk—there’s readily applicable, practical, real-world advice here, things to enable us to do our (real!) best without getting overwhelmed.
The style is pop-science, very easy-reading, and clear and comprehensible throughout—without succumbing to undue padding either.
Bottom line: this is a very pleasant read, that promises to make life more meaningful and manageable at the same time. Highly recommendable!
Click here to check out Do Hard Things, and get the most out of life!
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Beet “Kvass” With Ginger
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Kvass is a popular drink throughout Eastern Europe, with several countries claiming it, but the truth is, kvass is older than nations (as in: nations, in general, any of them; nation states are a newer concept than is often realized), and its first recorded appearance was in the city state of Kyiv.
This one is definitely not a traditional recipe, as kvass is usually made from rye, but keeping true to its Eastern European roots with (regionally popular) beetroot, it’s nevertheless a great fermented drink, full of probiotic benefits, and this time, with antioxidants too.
It’s a little saltier than most things we give recipes for here, so enjoy it on hot sunny days as a great way to replenish electrolytes!
You will need (for 1 quart / 1 liter)
- 2¾ cups filtered or spring water
- 2 beets, roughly chopped
- 1 tbsp chopped fresh ginger
- 2 tsp salt (do not omit or substitute)
Method
(we suggest you read everything at least once before doing anything)
1) Sterilize a 1-quart jar with boiling water (carefully please)
2) Put all the ingredients in the jar and stir until the salt dissolves
3) Close the lid tightly and store in a cool dark place to ferment for 2 weeks
4) Strain the beets and ginger (they are now pickled and can be enjoyed in a salad or as a kimchi-like snack), pouring the liquid into a clean jar/bottle. This can be kept in the fridge for up to a month. Next time you make it, if you use ¼ cup of this as a “starter” to replace an equal volume of water in the original recipe, the fermentation will take days instead of weeks.
5) Serve! Best served chilled, but without ice, on a hot sunny day.
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
- Making Friends With Your Gut (You Can Thank Us Later)
- What To Eat, Take, And Do Before A Workout
- Ginger Does A Lot More Than You Think
Take care!
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Astaxanthin: Super-Antioxidant & Neuroprotectant
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Think Pink For Brain Health!
Astaxanthin is a carotenoid that’s found in:
- certain marine microalgae
- tiny crustaceans that eat the algae
- fish (and flamingos!) that eat the crustaceans
Yes, it’s the one that makes things pink.
But it does a lot more than that…
Super-antioxidant
Move over, green tea! Astaxanthin has higher antioxidant activity than most carotenoids. For example, it is 2–5 times more effective than alpha-carotene, lutein, beta-carotene, and lycopene:
Antioxidant activities of astaxanthin and related carotenoids
We can’t claim credit for naming it a super-antioxidant though, because:
Astaxanthin: A super antioxidant from microalgae and its therapeutic potential
Grow new brain cells
Axtaxanthin is a neuroprotectant, but that’s to be expected from something with such a powerful antioxidant ability.
What’s more special to astaxanthin is that it assists continued adult neurogenesis (creation of new brain cells):
❝The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis.
Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation.
By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging. ❞
That first part is very important, by the way! There are so many things that our brain needs, and we can eat, but the molecules are unable to pass the blood-brain barrier, meaning they either get wasted, or used elsewhere, or dismantled for their constituent parts. In this case, it zips straight into the brain instead.
See also:
How To Grow New Brain Cells (At Any Age)
(Probably) good for the joints, too
First, astaxanthin got a glowing report in a study we knew not to trust blindly:
…and breathe. What a title that was! But, did you catch why it’s not to be trusted blindly? It was down at the bottom…
❝Conflict of interest statement
NOVAREX Co., Ltd. funded the study. Valensa International provided the FlexPro MD® ingredients, and NOVAREX Co., Ltd. encapsulated the test products (e.g., both FlexPro MD® and placebo)❞
Studies where a supplement company funded the study are not necessarily corrupt, but they can certainly sway publication bias, i.e. the company funds a bunch of studies and then pulls funding from the ones that aren’t going the way it wants.
So instead let’s look at:
Astaxanthin attenuates joint inflammation induced by monosodium urate crystals
and
Astaxanthin ameliorates cartilage damage in experimental osteoarthritis
…which had no such conflicts of interest.
They agree that astaxanthin indeed does the things (attenuates joint inflammation & ameliorates cartilage damage).
However, they are animal studies (rats), so we’d like to see studies with humans to be able to say for sure how much it helps these things.
Summary of benefits
Based on the available research, astaxanthin…
- is indeed a super-antioxidant
- is a neuroprotective agent
- also assists adult neurogenesis
- is probablygood for joints too
How much do I take, and is it safe?
A 2019 safety review concluded:
❝Recommended or approved doses varied in different countries and ranged between 2 and 24 mg.
We reviewed 87 human studies, none of which found safety concerns with natural astaxanthin supplementation, 35 with doses ≥12 mg/day.❞
Source: Astaxanthin: How much is too much? A safety review
In short: for most people, it’s very safe and well-tolerated. If you consume it to an extreme, you will likely turn pink, much as you would turn orange if you did the same thing with carrots. But aside from that, the risks appear to be minimal.
However! If you have a seafood allergy, please take care to get a supplement that’s made from microalgae, not one that’s made from krill or other crustaceans, or from other creatures that eat those.
Where can I get it?
We don’t sell it, but here’s an example product on Amazon, for your convenience
Enjoy!
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