Semaglutide’s Surprisingly Unexamined Effects
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Semaglutide’s Surprisingly Big Research Gap
GLP-1 receptor agonists like Ozempic, Wegovy, and other semaglutide drugs. are fast becoming a health industry standard go-to tool in the weight loss toolbox. When it comes to recommending that patients lose weight, “Have you considered Ozempic?” is the common refrain.
Sometimes, this may be a mere case of kicking the can down the road with regard to some other treatment that it can be argued (sometimes even truthfully) would go better after some weight loss:
How weight bias in health care can harm patients with obesity: Research
…which we also covered in fewer words in the second-to-last item here:
But GLP-1 agonists work, right?
Yes, albeit there’s a litany of caveats, top of which are usually:
- there are often adverse gastrointestinal side effects
- if you stop taking them, weight regain generally ensues promptly
For more details on these and more, see:
…but now there’s another thing that’s come to light:
The dark side of semaglutide’s weight loss
In academia, “dark” is often used to describe “stuff we don’t have much (or in some cases, any) direct empirical evidence of, but for reasons of surrounding things, we know it’s there”.
Well-known examples include “dark matter” in physics and the Dark Ages in (European) history.
In the case of semaglutide and weight loss, a review by a team of researchers (Drs. Sandra Christenen, Katie Robinson, Sara Thomas, and Dominique Williams) has discovered how little research has been done into a certain aspect of GLP-1 agonist’s weight loss effects, namely…
Dietary changes!
There’s been a lot of popular talk about “people taking semaglutide eat less”, but it’s mostly anecdotal and/or presumed based on parts of the mechanism of action (increasing insulin production, reducing glucagon secretions, modulating dietary cravings).
Where studies have looked at dietary changes, it’s almost exclusively been a matter of looking at caloric intake (which has been found to be a 16–39% reduction), and observations-in-passing that patients reported reduction in cravings for fatty and sweet foods.
This reduction in caloric intake, by the way, is not significantly different to the reduction brought about by counselling alone (head-to-head studies have been done; these are also discussed in the research review).
However! It gets worse. Very few studies of good quality have been done, even fewer (two studies) actually had a registered dietitian nutritionist on the team, and only one of them used the “gold standard” of nutritional research, the 24-hour dietary recall test. Which, in case you’re curious, you can read about what that is here:
Dietary Assessment Methods: What Is A 24-Hour Recall?
Of the four studies that actually looked at the macros (unlike most studies), they found that on average, protein intake decreased by 17.1%. Which is a big deal!
It’s an especially big deal, because while protein’s obviously important for everyone, it’s especially important for anyone trying to lose weight, because muscle mass is a major factor in metabolic base rate—which in turn is much important for fat loss/maintenance than exercise, when it comes to how many calories we burn by simply existing.
A reasonable hypothesis, therefore, is that one of the numerous reasons people who quit GLP-1 agonists immediately put fat back on, is because they probably lost muscle mass in amongst their weight loss, meaning that their metabolic base rate will have decreased, meaning that they end up more disposed to put on fat than before.
And, that’s just a hypothesis and it’s a hypothesis based on very few studies, so it’s not something to necessarily take as any kind of definitive proof of anything, but it is to say—as the researchers of this review do loudly say—more research needs to be done into this, because this has been a major gap in research so far!
Any other bad news?
While we’re talking research gaps, guess how many studies looked into micronutrient intake changes in people taking GLP-1 agonists?
If you guessed zero, you guessed correctly.
You can find the paper itself here:
What’s the main take-away here?
On a broad, scoping level: we need more research!
On a “what this means for individuals who want to lose weight” level: maybe we should be more wary of this still relatively new (less than 10 years old) “wonder drug”. And for most of those 10 years it’s only been for diabetics, with weight loss use really being in just the past few years (2021 onwards).
In other words: not necessarily any need to panic, but caution is probably not a bad idea, and natural weight loss methods remain very reasonable options for most people.
See also: How To Lose Weight (Healthily!)
Take care!
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Coughing/Wheezing After Dinner?
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The After-Dinner Activities You Don’t Want
A quick note first: our usual medical/legal disclaimer applies here, and we are not here to diagnose you or treat you; we are not doctors, let alone your doctors. Do see yours if you have any reason to believe there may be cause for concern.
Coughing and/or wheezing after eating is more common the younger or older someone is. Lest that seem contradictory: it’s a U-shaped bell-curve.
It can happen at any age and for any of a number of reasons, but there are patterns to the distribution:
Mostly affects younger people:
Allergies, asthma
Young people are less likely to have a body that’s fully adapted to all foods yet, and asthma can be triggered by certain foods (for example sulfites, a common preservative additive):
Adverse reactions to the sulphite additives
Foods/drinks that commonly contain sulfites include soft drinks, wines and beers, and dried fruit
As for the allergies side of things, you probably know the usual list of allergens to watch out for, e.g: dairy, fish, crustaceans, eggs, soy, wheat, nuts.
However, that’s far from an exhaustive list, so it’s good to see an allergist if you suspect it may be an allergic reaction.
Affects young and old people equally:
Again, there’s a dip in the middle where this doesn’t tend to affect younger adults so much, but for young and old people:
Dysphagia (difficulty swallowing)
For children, this can be a case of not having fully got used to eating yet if very small, and when growing, can be a case of “this body is constantly changing and that makes things difficult”.
For older people, this can can come from a variety of reasons, but common culprits include neurological disorders (including stroke and/or dementia), or a change in saliva quality and quantity—a side-effect of many medications:
Hyposalivation in Elderly Patients
(particularly useful in the article above is the table of drugs that are associated with this problem, and the various ways they may affect it)
Managing this may be different depending on what is causing your dysphagia (as it could be anything from antidepressants to cancer), so this is definitely one to see your doctor about. For some pointers, though:
NHS Inform | Dysphagia (swallowing problems)
Affects older people more:
Gastroesophagal reflux disease (GERD)
This is a kind of acid reflux, but chronic, and often with a slightly different set of symptoms.
GERD has no known cure once established, but its symptoms can be managed (or avoided in the first place) by:
- Healthy eating (Mediterranean diet is, as usual, great)
- Weight loss (if and only if obese)
- Avoiding trigger foods
- Eating smaller meals
- Practicing mindful eating
- Staying upright for 3–4 hours after eating
And of course, don’t smoke, and ideally don’t drink alcohol.
You can read more about this (and the different ways it can go from there), here:
NICE | Gastro-oesophageal reflux disease
Note: this above page refers to it as “GORD”, because of the British English spelling of “oesophagus” rather than “esophagus”. It’s the exact same organ and condition, just a different spelling.
Take care!
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Counterclockwise – by Dr. Ellen Langer
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We’ve written previously about Dr. Langer’s famous “Counterclockwise” study that saw reversals in biological markers of aging after a one-week intervention that consisted only of a (albeit rather intensive) mental reframe with regard to their age.
This book, as you might expect from the title, refers to that experiment a lot—but it doesn’t stop there. While the Counterclockwise experiment remains Dr. Langer’s most well-known, it’s not her most recent, and she draws from a wealth of research (her own and that of her colleagues in the field) to show the extent and limit of psychosomatic effect on aging.
Note:
- psychosomatic effect does not mean: “imagining it”
- psychosomatic effect means: “your brain regulates almost everything else in your body, directly or indirectly, including your autonomic functions, which includes immune function, tissue replacement, and more”
And as for when it comes to aging? Aging, like cancer, is in large part a problem of immune dysfunction; in both cases cells (be they senescent or cancerous, respectively) are not being killed when they are supposed to be, and in both cases, better instructions will improve the matter.
Many larger-scale markers of aging, such as mobility, are a case of the body only being able to do what the tissues allow, and the tissues are being constantly rebuilt (for better or for worse) according to autonomically-implemented specifications, and cells’ ability to carry out those orders.
Beyond the cellular physiology, this book discusses (a lot) the brain-down mechanisms by which the most powerful organ in our body can tell the rest of the body how old to be.
Dr. Langer also discusses the matter of “priming”, that is to say, how external factors prime us to believe certain things about our age and, with it, our health. These things can include popular media, conversations with friends and family, and healthcare providers’ framing of certain issues.
For example, a person just under a certain age and a person just over a certain age could both go to the doctor with the same complaint—a pain in a certain joint, let’s say. The doctor may refer the slightly younger patient for an x-ray because “let’s see what’s going on here”, and prescribe the slightly older patient some painkillers because “this is perfectly normal at your age”. One resultant problem is obvious: a difference in the standard of care. But the other resultant problem is less obvious: the older patient has now been primed to believe, by a confident authority figure, “it is natural for my body to be in a state of decline now, and this is what to expect”.
Thus, Dr. Langer prescribes mindfulness, not in the mindfulness meditation sense (though sure, do that too), but rather in the sense of consciously interacting with the world and making our own decisions about our own health and, yes, our own age. Because after all, our body neither knows nor cares how many times it has flown around the sun, and merely responds to physiological stimuli—including those we can influence with psychological reframing.
The book is not, per se, a “how-to” guide, rather it is an explanatory treatise, but it contains more than enough information to put it into practice, and indeed, she does also provide some exercises to do along the way.
The style is… Vivacious, without being especially upbeat. Dr. Langer is enthused about her work, yes, but she’s also angry at how many people are having their health sabotaged on the daily, and calls for a more health-first approach (as opposed to illness-first).
Bottom line: this is the book on our brain’s power over aging, so if that topic interests you, this book absolutely belongs on your bookshelf. Well, in your hands, and then on the bookshelf, and then back in your hands from time to time.
Click here to check out Counterclockwise, and age counterclockwise as her experimental subjects did!
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Cupping: How It Works (And How It Doesn’t)
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Good Health By The Cup?
In Tuesday’s newsletter, we asked you for your opinion of cupping (the medical practice), and got the above-depicted, below-described, set of responses:
- About 40% said “It may help by improving circulation and stimulating the immune system”
- About 26% said “I have never heard of the medical practice of cupping before this”
- About 19% said “It is pseudoscience and/or placebo at best, but probably not harmful
- About 9% said “It is a good, evidence-based practice that removes toxins and stimulates health”
- About 6% said “It is a dangerous practice that often causes harm to people who need medical help”
So what does the science say?
First, a quick note for those unfamiliar with cupping: it is the practice of placing a warmed cup on the skin (open side of the cup against the skin). As the warm air inside cools, it reduces the interior air pressure, which means the cup is now (quite literally) a suction cup. This pulls the skin up into the cup a little. The end result is visually, and physiologically, the same process as what happens if someone places the nozzle of a vacuum cleaner against their skin. For that matter, there are alternative versions that simply use a pump-based suction system, instead of heated cups—but the heated cups are most traditional and seem to be most popular. See also:
National Center for Complementary and Integrative Health | Cupping
It is a dangerous practice that often causes harm to people who need medical help: True or False?
False, for any practical purposes.
- Directly, it can (and usually does) cause minor superficial harm, much like many medical treatments, wherein the benefits are considered to outweigh the harm, justifying the treatment. In the case of cupping, the minor harm is usually a little bruising, but there are other risks; see the link we gave just above.
- Indirectly, it could cause harm by emboldening a person to neglect a more impactful treatment for their ailment.
But, there’s nothing for cupping akin to the “the most common cause of death is when someone gets a vertebral artery fatally severed” of chiropractic, for example.
It is a good, evidence-based practice that removes toxins and stimulates health: True or False?
True and False in different parts. This one’s on us; we included four claims in one short line. But let’s look at them individually:
- Is it good? Well, those who like it, like it. It legitimately has some mild health benefits, and its potential for harm is quite small. We’d call this a modest good, but good nonetheless.
- Is it evidence-based? Somewhat, albeit weakly; there are some papers supporting its modest health claims, although the research is mostly only published in journals of alternative medicine, and any we found were in journals that have been described by scientists as pseudoscientific.
- Does it remove toxins? Not directly, at least. There is also a version that involves making a small hole in the skin before applying the cup, the better to draw out the toxins (called “wet cupping”). This might seem a little medieval, but this is because it is from early medieval times (wet cupping’s first recorded use being in the early 7th century). However, the body’s response to being poked, pierced, sucked, etc is to produce antibodies, and they will do their best to remove toxins. So, indirectly, there’s an argument.
- Does it stimulate health? Yes! We’ll come to that shortly. But first…
It is pseudoscience and/or placebo at best, but probably not harmful: True or False?
True in that its traditionally-proposed mechanism of action is a pseudoscience and placebo almost certainly plays a strong part, and also in that it’s generally not harmful.
On it being a pseudoscience: we’ve talked about this before, but it bears repeating; just because something’s proposed mechanism of action is pseudoscience, doesn’t necessarily mean it doesn’t work by some other mechanism of action. If you tell a small child that “eating the rainbow” will improve their health, and they believe this is some sort of magical rainbow power imbuing them with health, then the mechanism of action that they believe in is a pseudoscience, but eating a variety of colorful fruit and vegetables will still be healthy.
In the case of cupping, its proposed mechanism of action has to do withbalancing qi, yin and yang, etc (for which scientific evidence does not exist), in combination with acupuncture lore (for which some limited weak scientific evidence exists). On balancing qi, yin and yang etc, this is a lot like Europe’s historically popular humorism, which was based on the idea of balancing the four humors (blood, yellow bile, black bile, phlegm). Needless to say, humorism was not only a pseudoscience, but also eventually actively disproved with the advent of germ theory and modern medicine. Cupping therapy is not more scientifically based than humorism.
On the placebo side of things, there probably is a little more to it than that; much like with acupuncture, a lot of it may be a combination of placebo and using counter-irritation, a nerve-tricking method to use pain to reduce pain (much like pressing with one’s nail next to an insect bite).
Here’s one of the few studies we found that’s in what looks, at a glance, to be a reputable journal:
Cupping therapy and chronic back pain: systematic review and meta-analysis
It may help by improving circulation and stimulating the immune system: True or False?
True! It will improve local circulation by forcing blood into the area, and stimulate the immune system by giving it a perceived threat to fight.
Again, this can be achieved by many other means; acupuncture (or just “dry needling”, which is similar but without the traditional lore), a cold shower, and/or exercise (and for that matter, sex—which combines exercise, physiological arousal, and usually also foreign bodies to respond to) are all options that can improve circulation and stimulate the immune system.
You can read more about using some of these sorts of tricks for improving health in very well-evidenced, robustly scientific ways here:
The Stress Prescription (Against Aging!)
Take care!
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The Power of Hormones – by Dr. Max Nieuwdorp
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First a quick note on the author: he’s an MD & PhD, internist, endocrinologist, and professor. He knows his stuff.
There are a lot of books with “the new science of” in the title, and they don’t often pertain to science that is actually new, and in this case, for the most part the science contained within this book is quite well-established.
A strength of this book is that it’s not talking about hormones in just one specific aspect (e.g. menopause, pregnancy, etc) but rather, in the full span of human health, across the spectra of ages and sexes—and yes, also covering hormones that are not sex hormones, so for example also demystifying the different happiness-related neurotransmitters, as well as the hormones responsible for hunger and satiety, weight loss and gain, sleep and wakefulness, etc.
Which is all very good, because there’s a lot of overlap and several hormones fall into several categories there.
Moreover, the book covers how your personal cocktail of hormones impacts how you look, feel, behave, and more—there’s a lot about chronic health issues here too, and how to use the information in this book to if not outright cure, then at least ameliorate, many conditions.
Bottom line: this is an information-dense book with a lot of details great and small; if you read this, you’ll come away with a much better understanding of hormones than you had previously!
Click here to check out The Power of Hormones, and harness that power for yourself!
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How To Set Anxiety Aside
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How To Set Anxiety Aside
We’ve talked previously about how to use the “release” method to stop your racing mind.
That’s a powerful technique, but sometimes we need to be calm enough to use it. So first…
Breathe
Obviously. But, don’t underestimate the immediate power of focusing on your breath, even just for a moment.
There are many popular breathing exercises, but here’s one of the simplest and most effective, “4–4 breathing”:
- Breathe in for a count of four
- Hold for a count four
- Breathe out for a count of four
- Hold for a count of four
- Repeat
Depending on your lung capacity and what you’re used to, it may be that you need to count more quickly or slowly to make it feel right. Experiment with what feels comfortable for you, but the general goal should breathing deeply and slowly.
Identify the thing that’s causing you anxiety
We’ve also talked previously about how to use the RAIN technique to manage difficult emotions, and that’s good for handling anxiety too.
Another powerful tool is journaling.
Read: How To Use Journaling to Challenge Anxious Thoughts
If you don’t want to use any of those (very effective!) methods, that’s fine too—journaling isn’t for everyone.
You can leverage some of the same benefits by simply voicing your worries, even to yourself:
There’s an old folk tradition of “worry dolls”; these are tiny little dolls so small they can be kept in a pocket-size drawstring purse. Last thing at night, the user whispers their worries to the dolls and puts them back in their bag, where they will work on the person’s problem overnight.
We’re a health and productivity newsletter, not a dealer of magic and spells, but you can see how it works, right? It gets the worries out of one’s head, and brings about a helpful placebo effect too.
Focus on what you can control
- Most of what you worry about will not happen.
- Some of what you worry about may happen.
- Worrying about it will not help.
In fact, in some cases it may bring about what you fear, by means of the nocebo effect (like the placebo effect, but bad). Additionally, worrying drains your body and makes you less able to deal with whatever life does throw at you.
So while “don’t worry; be happy” may seem a flippant attitude, sometimes it can be best. However, don’t forget the other important part, which is actually focusing on what you can control.
- You can’t control whether your car will need expensive maintenance…
- …but you can control whether you budget for it.
- You can’t control whether your social event will go well or ill…
- …but you can control how you carry yourself.
- You can’t control whether your loved one’s health will get better or worse…
- …but you can control how you’re there for them, and you can help them take what sensible precautions they may.
…and so forth.
Look after your body as well!
Your body and mind are deeply reliant on each other. In this case, just as anxiety can drain your body’s resources, keeping your body well-nourished, well-exercised, and well-rested and can help fortify you against anxiety. For example, when it comes to diet, exercise, and sleep:
- Read: Fruit and vegetable intake is inversely associated with perceived stress across the adult lifespan
- Read: Exercise and anxiety: physical activity appears to be protective against anxiety disorders in clinical and non-clinical populations
- Read: Sleep problems predict and are predicted by generalized anxiety/depression
Don’t know where to start? How about the scientifically well-researched, evidence-based, 7-minute workout?
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The voice in your head may help you recall and process words. But what if you don’t have one?
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Can you imagine hearing yourself speak? A voice inside your head – perhaps reciting a shopping list or a phone number? What would life be like if you couldn’t?
Some people, including me, cannot have imagined visual experiences. We cannot close our eyes and conjure an experience of seeing a loved one’s face, or imagine our lounge room layout – to consider if a new piece of furniture might fit in it. This is called “aphantasia”, from a Greek phrase where the “a” means without, and “phantasia” refers to an image. Colloquially, people like myself are often referred to as having a “blind mind”.
While most attention has been given to the inability to have imagined visual sensations, aphantasics can lack other imagined experiences. We might be unable to experience imagined tastes or smells. Some people cannot imagine hearing themselves speak.
A recent study has advanced our understanding of people who cannot imagine hearing their own internal monologue. Importantly, the authors have identified some tasks that such people are more likely to find challenging.
fizkes/Shutterstock What the study found
Researchers at the University of Copenhagen in Denmark and at the University of Wisconsin-Madison in the United States recruited 93 volunteers. They included 46 adults who reported low levels of inner speech and 47 who reported high levels.
Both groups were given challenging tasks: judging if the names of objects they had seen would rhyme and recalling words. The group without an inner monologue performed worse. But differences disappeared when everyone could say words aloud.
Importantly, people who reported less inner speech were not worse at all tasks. They could recall similar numbers of words when the words had a different appearance to one another. This negates any suggestion that aphants (people with aphantasia) simply weren’t trying or were less capable.
Hearing our own imagined voice may play an important role in word processing. sutadimages/Shutterstock A welcome validation
The study provides some welcome evidence for the lived experiences of some aphants, who are still often told their experiences are not different, but rather that they cannot describe their imagined experiences. Some people feel anxiety when they realise other people can have imagined experiences that they cannot. These feelings may be deepened when others assert they are merely confused or inarticulate.
In my own aphantasia research I have often quizzed crowds of people on their capacity to have imagined experiences.
Questions about the capacity to have imagined visual or audio sensations tend to be excitedly endorsed by a vast majority, but questions about imagined experiences of taste or smell seem to cause more confusion. Some people are adamant they can do this, including a colleague who says he can imagine what combinations of ingredients will taste like when cooked together. But other responses suggest subtypes of aphantasia may prove to be more common than we realise.
The authors of the recent study suggest the inability to imagine hearing yourself speak should be referred to as “anendophasia”, meaning without inner speech. Other authors had suggested anauralia (meaning without auditory imagery). Still other researchers have referred to all types of imagined sensation as being different types of “imagery”.
Having consistent names is important. It can help scientists “talk” to one another to compare findings. If different authors use different names, important evidence can be missed.
We’re starting to broaden our understanding of the senses and how we imagine them. Napat Chaichanasiri/Shutterstock We have more than 5 senses
Debate continues about how many senses humans have, but some scientists reasonably argue for a number greater than 20.
In addition to the five senses of sight, smell, taste, touch and hearing, lesser known senses include thermoception (our sense of heat) and proprioception (awareness of the positions of our body parts). Thanks to proprioception, most of us can close our eyes and touch the tip of our index finger to our nose. Thanks to our vestibular sense, we typically have a good idea of which way is up and can maintain balance.
It may be tempting to give a new name to each inability to have a given type of imagined sensation. But this could lead to confusion. Another approach would be to adapt phrases that are already widely used. People who are unable to have imagined sensations commonly refer to ourselves as “aphants”. This could be adapted with a prefix, such as “audio aphant”. Time will tell which approach is adopted by most researchers.
Why we should keep investigating
Regardless of the names we use, the study of multiple types of inability to have an imagined sensation is important. These investigations could reveal the essential processes in human brains that bring about a conscious experience of an imagined sensation.
In time, this will not only lead to a better understanding of the diversity of humans, but may help uncover how human brains can create any conscious sensation. This question – how and where our conscious feelings are generated – remains one of the great mysteries of science.
Derek Arnold, Professor, School of Psychology, The University of Queensland
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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