What pathogen might spark the next pandemic? How scientists are preparing for ‘disease X’
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Before the COVID pandemic, the World Health Organization (WHO) had made a list of priority infectious diseases. These were felt to pose a threat to international public health, but where research was still needed to improve their surveillance and diagnosis. In 2018, “disease X” was included, which signified that a pathogen previously not on our radar could cause a pandemic.
While it’s one thing to acknowledge the limits to our knowledge of the microbial soup we live in, more recent attention has focused on how we might systematically approach future pandemic risks.
Former US Secretary of Defense Donald Rumsfeld famously talked about “known knowns” (things we know we know), “known unknowns” (things we know we don’t know), and “unknown unknowns” (the things we don’t know we don’t know).
Although this may have been controversial in its original context of weapons of mass destruction, it provides a way to think about how we might approach future pandemic threats.
Influenza: a ‘known known’
Influenza is largely a known entity; we essentially have a minor pandemic every winter with small changes in the virus each year. But more major changes can also occur, resulting in spread through populations with little pre-existing immunity. We saw this most recently in 2009 with the swine flu pandemic.
However, there’s a lot we don’t understand about what drives influenza mutations, how these interact with population-level immunity, and how best to make predictions about transmission, severity and impact each year.
The current H5N1 subtype of avian influenza (“bird flu”) has spread widely around the world. It has led to the deaths of many millions of birds and spread to several mammalian species including cows in the United States and marine mammals in South America.
Human cases have been reported in people who have had close contact with infected animals, but fortunately there’s currently no sustained spread between people.
While detecting influenza in animals is a huge task in a large country such as Australia, there are systems in place to detect and respond to bird flu in wildlife and production animals.
It’s inevitable there will be more influenza pandemics in the future. But it isn’t always the one we are worried about.
Attention had been focused on avian influenza since 1997, when an outbreak in birds in Hong Kong caused severe disease in humans. But the subsequent pandemic in 2009 originated in pigs in central Mexico.
Coronaviruses: an ‘unknown known’
Although Rumsfeld didn’t talk about “unknown knowns”, coronaviruses would be appropriate for this category. We knew more about coronaviruses than most people might have thought before the COVID pandemic.
We’d had experience with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS) causing large outbreaks. Both are caused by viruses closely related to SARS-CoV-2, the coronavirus that causes COVID. While these might have faded from public consciousness before COVID, coronaviruses were listed in the 2015 WHO list of diseases with pandemic potential.
Previous research into the earlier coronaviruses proved vital in allowing COVID vaccines to be developed rapidly. For example, the Oxford group’s initial work on a MERS vaccine was key to the development of AstraZeneca’s COVID vaccine.
Similarly, previous research into the structure of the spike protein – a protein on the surface of coronaviruses that allows it to attach to our cells – was helpful in developing mRNA vaccines for COVID.
It would seem likely there will be further coronavirus pandemics in the future. And even if they don’t occur at the scale of COVID, the impacts can be significant. For example, when MERS spread to South Korea in 2015, it only caused 186 cases over two months, but the cost of controlling it was estimated at US$8 billion (A$11.6 billion).
The 25 viral families: an approach to ‘known unknowns’
Attention has now turned to the known unknowns. There are about 120 viruses from 25 families that are known to cause human disease. Members of each viral family share common properties and our immune systems respond to them in similar ways.
An example is the flavivirus family, of which the best-known members are yellow fever virus and dengue fever virus. This family also includes several other important viruses, such as Zika virus (which can cause birth defects when pregnant women are infected) and West Nile virus (which causes encephalitis, or inflammation of the brain).
The WHO’s blueprint for epidemics aims to consider threats from different classes of viruses and bacteria. It looks at individual pathogens as examples from each category to expand our understanding systematically.
The US National Institute of Allergy and Infectious Diseases has taken this a step further, preparing vaccines and therapies for a list of prototype pathogens from key virus families. The goal is to be able to adapt this knowledge to new vaccines and treatments if a pandemic were to arise from a closely related virus.
Pathogen X, the ‘unknown unknown’
There are also the unknown unknowns, or “disease X” – an unknown pathogen with the potential to trigger a severe global epidemic. To prepare for this, we need to adopt new forms of surveillance specifically looking at where new pathogens could emerge.
In recent years, there’s been an increasing recognition that we need to take a broader view of health beyond only thinking about human health, but also animals and the environment. This concept is known as “One Health” and considers issues such as climate change, intensive agricultural practices, trade in exotic animals, increased human encroachment into wildlife habitats, changing international travel, and urbanisation.
This has implications not only for where to look for new infectious diseases, but also how we can reduce the risk of “spillover” from animals to humans. This might include targeted testing of animals and people who work closely with animals. Currently, testing is mainly directed towards known viruses, but new technologies can look for as yet unknown viruses in patients with symptoms consistent with new infections.
We live in a vast world of potential microbiological threats. While influenza and coronaviruses have a track record of causing past pandemics, a longer list of new pathogens could still cause outbreaks with significant consequences.
Continued surveillance for new pathogens, improving our understanding of important virus families, and developing policies to reduce the risk of spillover will all be important for reducing the risk of future pandemics.
This article is part of a series on the next pandemic.
Allen Cheng, Professor of Infectious Diseases, Monash University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The BAT-pause!
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When Cold Weather & The Menopause Battle It Out
You may know that (moderate, safe) exposure to the cold allows our body to convert our white and yellow fat into the much healthier brown fat—also called brown adipose tissue, or “BAT” to its friends.
If you didn’t already know that, then well, neither did scientists until about 15 years ago:
The Changed Metabolic World with Human Brown Adipose Tissue: Therapeutic Visions
You can read more about it here:
Cool Temperature Alters Human Fat and Metabolism
This is important, especially because the white fat that gets converted is the kind that makes up most visceral fat—the kind most associated with all-cause mortality:
Visceral Belly Fat & How To Lose It ← this is not the same as your subcutaneous fat, the kind that sits directly under your skin and keeps you warm; this is the fat that goes between your organs and of which we should only have a small amount!
The BAT-pause
It’s been known (since before the above discovery) that BAT production slows considerably as we get older. Not too shocking—after all, many metabolic functions slow as we get older, so why should fat regulation be any different?
But! Rodent studies found that this was tied less to age, but to ovarian function: rats who underwent ovariectomies suffered reduced BAT production, regardless of their age.
Naturally, it’s been difficult to recreate such studies in humans, because it’s difficult to find a large sample of young adults willing to have their ovaries whipped out (or even suppressed chemically) to see how badly their metabolism suffers as a result.
Nor can an observational study (for example, of people who incidentally have ovaries removed due to ovarian cancer) usefully be undertaken, because then the cancer itself and any additional cancer treatments would be confounding factors.
Perimenopausal study to the rescue!
A recent (published last month, at time of writing!) study looked at women around the age of menopause, but specifically in cohorts before and after, measuring BAT metabolism.
By dividing the participants into groups based on age and menopausal status, and dividing the post-menopausal group into “takes HRT” and “no HRT” groups, and dividing the pre-menopausal group into “normal ovarian function” and “ovarian production of estrogen suppressed to mimic slightly early menopause” groups (there’s a drug for that), and then having groups exposed to warm and cold temperatures, and measuring BAT metabolism in all cases, they were able to find…
It is about estrogen, not age!
You can read more about the study here:
“Good” fat metabolism changes tied to estrogen loss, not necessarily to aging, shows study
…and the study itself, here:
Brown adipose tissue metabolism in women is dependent on ovarian status
What does this mean for men?
This means nothing directly for (cis) men, sorry.
But to satisfy your likely curiosity: yes, testosterone does at least moderately suppress BAT metabolism—based on rodent studies, anyway, because again it’s difficult to find enough human volunteers willing to have their testicles removed for science (without there being other confounding variables in play, anyway):
Testosterone reduces metabolic brown fat activity in male mice
So, that’s bad per se, but there isn’t much to be done about it, since the rest of your (addressing our male readers here) metabolism runs on testosterone, as do many of your bodily functions, and you would suffer many unwanted effects without it.
However, as men do typically have notably less body fat in general than women (this is regulated by hormones), the effects of changes in BAT metabolism are rather less pronounced in men (per testosterone level changes) than in women (per estrogen level changes), because there’s less overall fat to convert.
In summary…
While menopausal HRT is not necessarily a silver bullet to all metabolic problems, its BAT-maintaining ability is certainly one more thing in its favor.
See also:
Dr. Jen Gunter | What You Should Have Been Told About The Menopause Beforehand
Take care!
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Death by Food Pyramid – by Denise Minger
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This one is less about “here’s the perfect way of eating” or even “these specific foods are ontologically evil”, but more about teaching science literacy.
The author explores various health trends from the 70s until time of writing (the book was published in 2014), what rationales originally prompted them, and what social phenomena either helped them to persist, or caused them to get dropped quite quickly.
Of course, even in the case of fads that are societally dropped quite quickly, on an individual level there will always be someone just learning about it for the first time, reading some older material, and thinking “that sounds like just the miracle life-changer I need!”
What she teaches the reader to do is largely what we do a lot of here at 10almonds—examine the claims, go to the actual source material (studies! Not just books about studies!), and see whether the study conclusions actually support the claim, to start with, and then further examine to see if there’s some way (or sometimes, a plurality of ways) in which the study itself is methodologically flawed.
Which does happen sometimes, do actually watch out for that!
The style is quite personal and entertaining for the most part, and yet even moving sometimes (the title is not hyperbole; deaths will be discussed). As one might expect of a book teaching science literacy, it’s very easy to read, with copious footnotes (well, actually they are at the back of the book doubling up as a bibliography, but they are linked-to throughout) for those who wish to delve deeper—something the author, of course, encourages.
Bottom line: if you’d like to be able to sort the real science from the hype yourself, then this book can set you on the right track!
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You can now order all kinds of medical tests online. Our research shows this is (mostly) a bad idea
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Elena.Katkova/Shutterstock Many of us have done countless rapid antigen tests (RATs) over the course of the pandemic. Testing ourselves at home has become second nature.
But there’s also a growing worldwide market in medical tests sold online directly to the public. These are “direct-to-consumer” tests, and you can access them without seeing a doctor.
While this might sound convenient, the benefits to most consumers are questionable, as we discovered in a recent study.
What are direct-to-consumer tests?
Let’s start with what they’re not. We’re not talking about patients who are diagnosed with a condition, and use tests to monitor themselves (for example, finger-prick testing to monitor blood sugar levels for people with diabetes).
We’re also not talking about home testing kits used for population screening, such as RATs for COVID, or the “poo tests” sent to people aged 50 and over for bowel cancer screening.
Direct-to-consumer tests are products marketed to anyone who is willing to pay, without going through their GP. They can include hormone profiling tests, tests for thyroid disease and food sensitivity tests, among many others.
Some direct-to-consumer tests allow you to complete the test at home, while self-collected lab tests give you the equipment to collect a sample, which you then send to a lab. You can now also buy pathology requests for a lab directly from a company without seeing a doctor.
We’ve all become accustomed to RATs during the pandemic.
Ground Picture/ShutterstockWhat we did in our study
We searched (via Google) for direct-to-consumer products advertised for sale online in Australia between June and December 2021. We then assessed whether each test was likely to provide benefits to those who use them based on scientific literature published about the tests, and any recommendations either for or against their use from professional medical organisations.
We identified 103 types of tests and 484 individual products ranging in price from A$12.99 to A$1,947.
We concluded only 11% of these tests were likely to benefit most consumers. These included tests for STIs, where social stigma can sometimes discourage people from testing at a clinic.
A further 31% could possibly benefit a person, if they were at higher risk. For example, if a person had symptoms of thyroid disease, a test may benefit them. But the Royal Australian College of General Practitioners does not recommend testing for thyroid disease in people without symptoms because evidence showing benefits of identifying and treating people with early thyroid disease is lacking.
Some 42% were commercial “health checks” such as hormone and nutritional status tests. Although these are legitimate tests – they may be ordered by a doctor in certain circumstances, or be used in research – they have limited usefulness for consumers.
A test of your hormone or vitamin levels at a particular time can’t do much to help you improve your health, especially because test results change depending on the time of day, month or season you test.
Most worryingly, 17% of the tests were outright “quackery” that wouldn’t be recommended by any mainstream health practitioner. For example, hair analysis for assessing food allergies is unproven and can lead to misdiagnosis and ineffective treatments.
More than half of the tests we looked at didn’t state they offered a pre- or post-test consultation.
Ordering medical tests online probably isn’t a good idea.
fizkes/ShutterstockProducts available may change outside the time frame of our study, and direct-to-consumer tests not promoted or directly purchasable online, such as those offered in pharmacies or by commercial health clinics, were not included.
But in Australia, ours is the first and only study we know of mapping the scale and variety of direct-to-consumer tests sold online.
Research from other countries has similarly found a lack of evidence to support the majority of direct-to-consumer tests.
4 questions to ask before you buy a test online
Many direct-to-consumer tests offer limited benefits, and could even lead to harms. Here are four questions you should ask yourself if you’re considering buying a medical test online.
1. If I do this test, could I end up with extra medical appointments or treatments I don’t need?
Doing a test yourself might seem harmless (it’s just information, after all), but unnecessary tests often find issues that would never have caused you problems.
For example, someone taking a diabetes test may find moderately high blood sugar levels see them labelled as “pre-diabetic”. However, this diagnosis has been controversial, regarded by many as making patients out of healthy people, a large number of whom won’t go on to develop diabetes.
2. Would my GP recommend this test?
If you have worrying symptoms or risk factors, your GP can recommend the best tests for you. Tests your GP orders are more likely to be covered by Medicare, so will cost you a lot less than a direct-to-consumer test.
3. Is this a good quality test?
A good quality home self-testing kit should indicate high sensitivity (the proportion of true cases that will be accurately detected) and high specificity (the proportion of people who don’t have the disease who will be accurately ruled out). These figures should ideally be in the high 90s, and clearly printed on the product packaging.
For tests analysed in a lab, check if the lab is accredited by the National Association of Testing Authorities. Avoid tests sent to overseas labs, where Australian regulators can’t control the quality, or the protection of your sample or personal health information.
4. Do I really need this test?
There are lots of reasons to want information from a test, like peace of mind, or just curiosity. But unless you have clear symptoms and risk factors, you’re probably testing yourself unnecessarily and wasting your money.
Direct-to-consumer tests might seem like a good idea, but in most cases, you’d be better off letting sleeping dogs lie if you feel well, or going to your GP if you have concerns.
Patti Shih, Senior Lecturer, Australian Centre for Health Engagement, Evidence and Values, University of Wollongong; Fiona Stanaway, Associate Professor in Clinical Epidemiology, University of Sydney; Katy Bell, Associate Professor in Clinical Epidemiology, Sydney School of Public Health, University of Sydney, and Stacy Carter, Professor and Director, Australian Centre for Health Engagement, Evidence and Values, University of Wollongong
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The Seven Principles for Making Marriage Work – by Dr. John Gottman
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A lot of relationship advice can seem a little wishy-washy. Hardline clinical work, on the other hand, can seem removed from the complex reality of married life. Dr. Gottman, meanwhile, strikes a perfect balance.
He looks at huge datasets, and he listens to very many couples. He famously isolated four relational factors that predict divorce with 91% accuracy, his “Four Horsemen”:
- Criticism
- Contempt
- Defensiveness
- Stonewalling
He also, as the title of this book promises (and we get a chapter-by-chapter deep-dive on each of them) looks at “Seven principles for making marriage work”. They’re not one-word items, so including them here would take up the rest of our space, and this is a book review not a book summary. However…
Dr. Gottman’s seven principles are, much like his more famous “four horsemen”, deeply rooted in science, while also firmly grounded in the reality of individual couples. Essentially, by listening to very many couples talk about their relationships, and seeing how things panned out with each of them in the long-term, he was able to see what things kept on coming up each time in the couples that worked out. What did they do differently?
And, that’s the real meat of the book. Science yes, but lots of real-world case studies and examples, from couples that worked and couples that didn’t.
In so doing, he provides a roadmap for couples who are serious about making their marriage the best it can be.
Bottom line: this is a must-have book for couples in general, no matter how good or bad the relationship.
- For some it’ll be a matter of realising “You know what; this isn’t going to work”
- For others, it’ll be a matter of “Ah, relief, this is how we can resolve that!”
- For still yet others, it’ll be a matter of “We’re doing these things right; let’s keep them forefront in our minds and never get complacent!”
- And for everyone who is in a relationship or thinking of getting into one, it’s a top-tier manual.
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Algorithms to Live By – by Brian Christian and Tom Griffiths
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As humans, we subconsciously use heuristics a lot to make many complex decisions based on “fuzzy logic”. For example:
Do we buy the cheap shoes that may last us a season, or the much more expensive ones that will last us for years? We’ll—without necessarily giving it much conscious thought—quickly weigh up:
- How much do we like each prospective pair of shoes?
- What else might we need to spend money on now/soon?
- How much money do we have right now?
- How much money do we expect to have in the future?
- Considering our lifestyle, how important is it to have good quality shoes?
How well we perform this rapid calculation may vary wildly, depending on many factors ranging from the quality of the advertising to how long ago we last ate.
And if we make the wrong decision, later we may have buyer’s (or non-buyer’s!) remorse. So, how can we do better?
Authors Brain Christian and Tom Griffiths have a manual for us!
This book covers many “kinds” of decision we often have to make in life, and how to optimize those decisions with the power of mathematics and computer science.
The problems (and solutions) run the gamut of…
- Optimal stopping (when to say “alright, that’s good enough”)
- Overcoming cognitive biases
- Scheduling quandaries
- Bayes’ Theorem
- Game Theory
- And when it’s more efficient to just leave things to chance!
…and many more (12 main areas of decision-making are covered).
For all it draws heavily from mathematics and computer science, the writing style is very easy-reading. It’s a “curl up in the armchair and read for pleasure” book, no matter how weighty and practical its content.
Bottom line: if you improve your ability to make the right decisions even marginally, this book will have been worth your while in the long run!
Order your copy of “Algorithms To Live By” from Amazon today!
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Statins: His & Hers?
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The Hidden Complexities of Statins and Cardiovascular Disease (CVD)
This is Dr. Barbara Roberts. She’s a cardiologist and the Director of the Women’s Cardiac Center at one of the Brown University Medical School teaching hospitals. She’s an Associate Clinical Professor of Medicine and takes care of patients, teaches medical students, and does clinical research. She specializes in gender-specific aspects of heart disease, and in heart disease prevention.
We previously reviewed Dr. Barbara Roberts’ excellent book “The Truth About Statins: Risks and Alternatives to Cholesterol-Lowering Drugs”. It prompted some requests to do a main feature about Statins, so we’re doing it today. It’s under the auspices of “Expert Insights” as we’ll be drawing almost entirely from Dr. Roberts’ work.
So, what are the risks of statins?
According to Dr. Roberts, one of the biggest risks is not just drug side-effects or anything like that, but rather, what they simply won’t treat. This is because statins will lower LDL (bad) cholesterol levels, without necessarily treating the underlying cause.
Imagine you got Covid, and it’s one of the earlier strains that’s more likely deadly than “merely” debilitating.
You’re coughing and your throat feels like you gargled glass.
Your doctor gives you a miracle cough medicine that stops your coughing and makes your throat feel much better.
(Then a few weeks later, you die, because this did absolutely nothing for the underlying problem)
You see the problem?
Are there problematic side-effects too, though?
There can be. But of course, all drugs can have side effects! So that’s not necessarily news, but what’s relevant here is the kind of track these side-effects can lead one down.
For example, Dr. Roberts cites a case in which a woman’s LDL levels were high and she was prescribed simvastatin (Zocor), 20mg/day. Here’s what happened, in sequence:
- She started getting panic attacks. So, her doctor prescribed her sertraline (Zoloft) (a very common SSRI antidepressant) and when that didn’t fix it, paroxetine (Paxil). This didn’t work either… because the problem was not actually her mental health. The panic attacks got worse…
- Then, while exercising, she started noticing progressive arm and leg weakness. Her doctor finally took her off the simvastatin, and temporarily switched to ezetimibe (Zetia), a less powerful nonstatin drug that blocks cholesterol absorption, which change eased her arm and leg problem.
- As the Zetia was a stopgap measure, the doctor put her on atorvastatin (Lipitor). Now she got episodes of severe chest pressure, and a skyrocketing heart rate. She also got tremors and lost her body temperature regulation.
- So the doctor stopped the atorvastatin and tried rosovastatin (Crestor), on which she now suffered exhaustion (we’re not surprised, by this point) and muscle pains in her arms and chest.
- So the doctor stopped the rosovastatin and tried lovastatin (Mevacor), and now she had the same symptoms as before, plus light-headedness.
- So the doctor stopped the lovastatin and tried fluvastatin (Lescol). Same thing happened.
- So he stopped the fluvastatin and tried pravastatin (Pravachol), without improvement.
- So finally he took her off all these statins because the high LDL was less deleterious to her life than all these things.
- She did her own research, and went back to the doctor to ask for cholestyramine (Questran), which is a bile acid sequestrent and nothing to do with statins. She also asked for a long-acting niacin. In high doses, niacin (one of the B-vitamins) raises HDL (good) cholesterol, lowers LDL, and lowers tryglycerides.
- Her own non-statin self-prescription (with her doctor’s signature) worked, and she went back to her life, her work, and took up running.
Quite a treatment journey! Want to know more about the option that actually worked?
Read: Bile Acid Resins or Sequestrants
What are the gender differences you/she mentioned?
Actually mostly sex differences, since this appears to be hormonal (which means that if your hormones change, so will your risk). A lot of this is still pending more research—basically it’s a similar problem in heart disease to one we’ve previously talked about with regard to diabetes. Diabetes disproportionately affects black people, while diabetes research disproportionately focuses on white people.
In this case, most heart disease research has focused on men, with women often not merely going unresearched, but also often undiagnosed and untreated until it’s too late. And the treatments, if prescribed? Assumed to be the same as for men.
Dr. Roberts tells of how medicine is taught:
❝When I was in medical school, my professors took the “bikini approach” to women’s health: women’s health meant breasts and reproductive organs. Otherwise the prototypical patient was presented as a man.❞
There has been some research done with statins and women, though! Just, still not a lot. But we do know for example that some statins can be especially useful for treating women’s atherosclerosis—with a 50% success rate, rather than 31% for men.
For lowering LDL itself, however, it can work but is generally not so hot in women.
Fun fact:
In men:
- High total cholesterol
- High non-HDL cholesterol
- High LDL cholesterol
- Low HDL cholesterol
…are all significantly associated with an increased risk of death from CVD.
In women:
…levels of LDL cholesterol even more than 190 were associated with only a small, statistically insignificant increased risk of dying from CVD.
So…
The fact that women derive less benefit from a medicine that mainly lowers LDL cholesterol, may be because elevated LDL cholesterol is less harmful to women than it is to men.
And also: Treatment and Response to Statins: Gender-related Differences
And for that matter: Women Versus Men: Is There Equal Benefit and Safety from Statins?*
Definitely a case where Betteridge’s Law of Headlines applies!
What should women do to avoid dying of CVD, then?
First, quick reminder of our general disclaimer: we can’t give medical advice and nothing here comprises such. However… One particularly relevant thing we found illuminating in Dr. Roberts’ work was this observation:
The metabolic syndrome is diagnosed if you have three (or more) out of five of the following:
- Abdominal obesity (waist >35″ if a woman or >40″ if a man)
- Fasting blood sugars of 100mg/dl or more
- Fasting triglycerides of 150mg/dl or more
- Blood pressure of 130/85 or higher
- HDL <50 if a woman or <40 if a man
And yet… because these things can be addressed with exercise and a healthy diet, which neither pharmaceutical companies nor insurance companies have a particular stake in, there’s a lot of focus instead on LDL levels (since there are a flock of statins that can be sold be lower them)… Which, Dr. Roberts says, is not nearly as critical for women.
So women end up getting prescribed statins that cause panic attacks and all those things we mentioned earlier… To lower our LDL, which isn’t nearly as big a factor as the other things.
In summary:
Statins do have their place, especially for men. They can, however, mask underlying problems that need treatment—which becomes counterproductive.
When it comes to women, statins are—in broad terms—statistically not as good. They are a little more likely to be helpful specifically in cases of atherosclerosis, whereby they have a 50/50 chance of helping.
For women in particular, it may be worthwhile looking into alternative non-statin drugs, and, for everyone: diet and exercise.
Further reading: How Can I Safely Come Off Statins?
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