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!)
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Nicotine pouches are being marketed to young people on social media. But are they safe, or even legal?
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Flavoured nicotine pouches are being promoted to young people on social media platforms such as TikTok and Instagram.
Although some viral videos have been taken down following a series of reports in The Guardian, clips featuring Australian influencers have claimed nicotine pouches are a safe and effective way to quit vaping. A number of the videos have included links to websites selling these products.
With the rapid rise in youth vaping and the subsequent implementation of several reforms to restrict access to vaping products, it’s not entirely surprising the tobacco industry is introducing more products to maintain its future revenue stream.
The major trans-national tobacco companies, including Philip Morris International and British American Tobacco, all manufacture nicotine pouches. British American Tobacco’s brand of nicotine pouches, Velo, is a leading sponsor of the McLaren Formula 1 team.
But what are nicotine pouches, and are they even legal in Australia?
Like snus, but different
Nicotine pouches are available in many countries around the world, and their sales are increasing rapidly, especially among young people.
Nicotine pouches look a bit like small tea bags and are placed between the lip and gum. They’re typically sold in small, colourful tins of about 15 to 20 pouches. While the pouches don’t contain tobacco, they do contain nicotine that is either extracted from tobacco plants or made synthetically. The pouches come in a wide range of strengths.
As well as nicotine, the pouches commonly contain plant fibres (in place of tobacco, plant fibres serve as a filler and give the pouches shape), sweeteners and flavours. Just like for vaping products, there’s a vast array of pouch flavours available including different varieties of fruit, confectionery, spices and drinks.
The range of appealing flavours, as well as the fact they can be used discreetly, may make nicotine pouches particularity attractive to young people.
Vaping has recently been subject to tighter regulation in Australia.
Aleksandr Yu/ShutterstockUsers absorb the nicotine in their mouths and simply replace the pouch when all the nicotine has been absorbed. Tobacco-free nicotine pouches are a relatively recent product, but similar style products that do contain tobacco, known as snus, have been popular in Scandinavian countries, particularly Sweden, for decades.
Snus and nicotine pouches are however different products. And given snus contains tobacco and nicotine pouches don’t, the products are subject to quite different regulations in Australia.
What does the law say?
Pouches that contain tobacco, like snus, have been banned in Australia since 1991, as part of a consumer product ban on all forms of smokeless tobacco products. This means other smokeless tobacco products such as chewing tobacco, snuff, and dissolvable tobacco sticks or tablets, are also banned from sale in Australia.
Tobacco-free nicotine pouches cannot legally be sold by general retailers, like tobacconists and convenience stores, in Australia either. But the reasons for this are more complex.
In Australia, under the Poisons Standard, nicotine is a prescription-only medicine, with two exceptions. Nicotine can be used in tobacco prepared and packed for smoking, such as cigarettes, roll-your-own tobacco, and cigars, as well as in preparations for therapeutic use as a smoking cessation aid, such as nicotine patches, gum, mouth spray and lozenges.
If a nicotine-containing product does not meet either of these two exceptions, it cannot be legally sold by general retailers. No nicotine pouches have currently been approved by the Therapeutic Goods Administration as a therapeutic aid in smoking cessation, so in short they’re not legal to sell in Australia.
However, nicotine pouches can be legally imported for personal use only if users have a prescription from a medical professional who can assess if the product is appropriate for individual use.
We only have anecdotal reports of nicotine pouch use, not hard data, as these products are very new in Australia. But we do know authorities are increasingly seizing these products from retailers. It’s highly unlikely any young people using nicotine pouches are accessing them through legal channels.
Health concerns
Nicotine exposure may induce effects including dizziness, headache, nausea and abdominal cramps, especially among people who don’t normally smoke or vape.
Although we don’t yet have much evidence on the long term health effects of nicotine pouches, we know nicotine is addictive and harmful to health. For example, it can cause problems in the cardiovascular system (such as heart arrhythmia), particularly at high doses. It may also have negative effects on adolescent brain development.
The nicotine contents of some of the nicotine pouches on the market is alarmingly high. Certain brands offer pouches containing more than 10mg of nicotine, which is similar to a cigarette. According to a World Health Organization (WHO) report, pouches deliver enough nicotine to induce and sustain nicotine addiction.
Pouches are also being marketed as a product to use when it’s not possible to vape or smoke, such as on a plane. So instead of helping a person quit they may be used in addition to smoking and vaping. And importantly, there’s no clear evidence pouches are an effective smoking or vaping cessation aid.
A Velo product display at Dubai airport in October 2022. Nicotine pouches are marketed as safe to use on planes.
Becky FreemanFurther, some nicotine pouches, despite being tobacco-free, still contain tobacco-specific nitrosamines. These compounds can damage DNA, and with long term exposure, can cause cancer.
Overall, there’s limited data on the harms of nicotine pouches because they’ve been on the market for only a short time. But the WHO recommends a cautious approach given their similarities to smokeless tobacco products.
For anyone wanting advice and support to quit smoking or vaping, it’s best to talk to your doctor or pharmacist, or access trusted sources such as Quitline or the iCanQuit website.
Becky Freeman, Associate Professor, School of Public Health, University of Sydney
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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See what other 10almonds subscribers are asking!
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It’s Q&A Day at 10almonds!
Q: I would be interested in learning more about collagen and especially collagen supplements/powders and of course if needed, what is the best collagen product to take. What is collagen? Why do we need to supplement the collagen in our body? Thank you PS love the information I am receiving in the news letters. Keep it up
We’re glad you’re enjoying them! Your request prompted us to do our recent Research Review Monday main feature on collagen supplementation—we hope it helped, and if you’ve any more specific (or other) question, go ahead and let us know! We love questions and requests
Q: Great article about the health risks of salt to organs other than the heart! Is pink Himalayan sea salt, the pink kind, healthier?
Thank you! And, no, sorry. Any salt that is sodium chloride has the exact same effect because it’s chemically the same substance, even if impurities (however pretty) make it look different.
If you want a lower-sodium salt, we recommend the kind that says “low sodium” or “reduced sodium” or similar. Check the ingredients, it’ll probably be sodium chloride cut with potassium chloride. Potassium chloride is not only not a source of sodium, but also, it’s a source of potassium, which (unlike sodium) most of us could stand to get a little more of.
For your convenience: here’s an example on Amazon!
Bonus: you can get a reduced sodium version of pink Himalayan salt too!
Q: Can you let us know about more studies that have been done on statins? Are they really worth taking?
That is a great question! We imagine it might have been our recent book recommendation that prompted it? It’s quite a broad question though, so we’ll do that as a main feature in the near future!
Q: Is MSG healthier than salt in terms of sodium content or is it the same or worse?
Great question, and for that matter, MSG itself is a great topic for another day. But your actual question, we can readily answer here and now:
- Firstly, by “salt” we’re assuming from context that you mean sodium chloride.
- Both salt and MSG do contain sodium. However…
- MSG contains only about a third of the sodium that salt does, gram-for-gram.
- It’s still wise to be mindful of it, though. Same with sodium in other ingredients!
- Baking soda contains about twice as much sodium, gram for gram, as MSG.
Wondering why this happens?
Salt (sodium chloride, NaCl) is equal parts sodium and chlorine, by atom count, but sodium’s atomic mass is lower than chlorine’s, so 100g of salt contains only 39.34g of sodium.
Baking soda (sodium bicarbonate, NaHCO₃) is one part sodium for one part hydrogen, one part carbon, and three parts oxygen. Taking each of their diverse atomic masses into account, we see that 100g of baking soda contains 27.4g sodium.
MSG (monosodium glutamate, C₅H₈NO₄Na) is only one part sodium for 5 parts carbon, 8 parts hydrogen, 1 part nitrogen, and 4 parts oxygen… And all those other atoms put together weigh a lot (comparatively), so 100g of MSG contains only 12.28g sodium.
Q: Thanks for the info about dairy. As a vegan, I look forward to a future comment about milk alternatives
Thanks for bringing it up! What we research and write about is heavily driven by subscriber feedback, so notes like this really help us know there’s an audience for a given topic!
We’ll do a main feature on it, to do it justice. Watch out for Research Review Monday!
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Menopause, & When Not To Let Your Guard Down
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This is Dr. Jessica Shepherd, a physician Fellow of the American College of Obstetricians & Gynecologists, CEO at Sanctum Medical & Wellness, and CMO at Hers.
She’s most well-known for her expertise in the field of the menopause. So, what does she want us to know?
Untreated menopause is more serious than most people think
Beyond the famous hot flashes, there’s also the increased osteoporosis risk, which is more well-known at least amongst the health-conscious, but oft-neglected is the increased cardiovascular disease risk:
What Menopause Does To The Heart
…and, which a lot of Dr. Shepherd’s work focuses on, it also increases dementia risk; she cites that 60–80% of dementia cases are women, and it’s also established that it progresses more quickly in women than men too, and this is associated with lower estrogen levels (not a problem for men, because testosterone does it for them) which had previously been a protective factor, but in untreated menopause, was no longer there to help:
Alzheimer’s Sex Differences May Not Be What They Appear
Treated menopause is safer than many people think
The Women’s Health Initiative (WHI) study, conducted in the 90s and published in 2002, linked HRT to breast cancer, causing fear, but it turned out that this was quite bad science in several ways and the reporting was even worse (even the flawed data did not really support the conclusion, much less the headlines); it was since broadly refuted (and in fact, it can be a protective factor, depending on the HRT regimen), but fearmongering headlines made it to mainstream news, whereas “oopsies, never mind, we take that back” didn’t.
The short version of the current state of the science is: breast cancer risk varies depending on age, HRT type, and dosage; some kinds of HRT can increase the risk marginally in those older than 60, but absolute risk is low compared to placebo, and taking estrogen alone can reduce risk at any age in the event of not having a uterus (almost always because of having had a hysterectomy; as a quirk, it is possible to be born without, though).
It’s worth noting that even in the cases where HRT marginally increased the risk of breast cancer, it significantly decreased the risk of cancers in total, as well fractures and all-cause-mortality compared to the placebo group.
In other words, it might be worth having a 0.12% risk of breast cancer, to avoid the >30% risk of osteoporosis, which can ultimately be just as fatal (without even looking at the other things the HRT is protective against).
However! In the case of those who already have (or have had) breast cancer, increasing estrogen levels can indeed make that worse/return, and it becomes more complicated in cases where you haven’t had it, but there is a family history of it, or you otherwise know you have the gene for it.
You can read more about HRT and breast cancer risk (increases and decreases) here:
…and about the same with regard to HMT, here:
The Hormone Therapy That Reduces Breast Cancer Risk & More
Lifestyle matters, and continues to matter
Menopause often receives the following attention from people:
- Perimenopause: “Is this menopause?”
- Menopause: “Ok, choices to make about HRT or not, plus I should watch out for osteoporosis”
- Postmenopause: “Yay, that’s behind me now, back to the new normal”
The reality, Dr. Shepherd advises, is that “postmenopause” is a misnomer because if it’s not being treated, then the changes are continuing to occur in your body.
This is a simple factor of physiology; your body is always rebuilding itself, will never stop until you die, and in untreated menopause+postmenopause, it’s now doing it without much estrogen.
So, you can’t let your guard down!
Thus, she recommends: focus on maintaining muscle mass, bone health, and cardiovascular health. If you focus on those things, the rest (including your brain, which is highly dependent on cardiovascular health) will mostly take care of itself.
Because falls and fractures, particularly hip fractures, drastically reduce quality and length of life in older adults, it is vital to avoid those, and try to be sufficiently robust so that if you do go A over T, you won’t injure yourself too badly, because your bones are strong. As a bonus, the same things (especially that muscle mass we talked about) will help you avoid falling in the first place, by improving stability.
See also: Resistance Is Useful! (Especially As We Get Older)
And about falls specifically: Fall Special: Be Robust, Mobile, & Balanced!
Want to know more from Dr. Shepherd?
You might like this book of hers that we reviewed not long back:
Generation M – by Dr. Jessica Shepherd
Take care!
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Thriving Beyond Fifty – by Will Harlow
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We’ve featured this author sometimes in our video section; he’s an over-50s specialist physiotherapist with a lot of very functional advice to offer.
In this book, Harlow focusses heavily on three things: mobility, strength, endurance.
You may not want to be a gymnast, powerlifter, or marathon-runner, but these things are important for us all to maintain to at least a fair degree:
- Mobility can be the difference between tweaking one’s shoulder getting something from a high shelf, or not
- Strength can be the difference between being able to get back up, or not
- Endurance can be the difference between coming back from a long day on your feet and thinking “that was a good day; I’m looking forward to tomorrow now”, or not
One of the greatest strengths of this book is its comprehensive troubleshooting aspect; if you have a weak spot, chances are this book has the remedy.
As for the style, it’s quite casual/conversational in tone, but without skimping on science and detail. It’s clear, explanatory, and helpful throughout.
Bottom line: if you’d like to maintain/improve mobility, strength, and endurance, then this book is a very recommendable resource.
Click here to check out Thriving Beyond Fifty, and keep thriving at every age!
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Doctors From 15 Specialties Tell The Worst Common Mistakes People Make
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Whatever your professional background, you probably know many things about it that are very obvious to you, but that most people don’t know. So it is for doctors too; here are the things that doctors from 15 specialties would never do, and thus advise people against doing:
Better safe than sorry
We’ll leap straight into it:
- General Surgery: avoid rushing into musculoskeletal or spinal surgery unless absolutely necessary; conservative treatments like physical therapy are often effective.
- Interventional Gastroenterology: avoid long-term, around-the-clock use of anti-inflammatory pain medications (e.g. Ibuprofen and friends) to prevent stomach ulcers.
- Podiatry: never place feet on the car dashboard due to the risk of severe injuries from airbag deployment.
- Rheumatology: avoid daily use of high heels to prevent joint and foot deformities, bunions, and pain.
- Otorhinolaryngology: never smoke, as it can lead to severe consequences like laryngectomy and other life-altering conditions.
- Pediatrics: avoid dangerous activities for children, such as swimming alone, eating choking hazards, biking or skiing without a helmet, or consuming raw meat/fish/dairy. Also, be cautious with firearms in homes.
- Orthopedic Surgery: avoid riding motorcycles and handling fireworks due to high risks of accidents.
- Emergency Medicine: never drink and drive or ride ATVs. Always use eye protection during activities like woodworking.
- Ophthalmology: always wear safety glasses during activities like grinding metal or woodworking. Sunglasses are essential to prevent UV damage even on cloudy days.
- Urology: avoid shaving pubic hair if diabetic or immunocompromised to prevent severe infections like Fournier’s gangrene.
- Gastroenterology: do not use gut health supplements as they lack proven efficacy and are often a waste of money*
- Plastic Surgery: avoid contour threads (barbed sutures for facial rejuvenation) and butt implants due to risks like infection, complications, and poor outcomes.
- Psychiatry: never take recreational drugs from unknown sources to avoid accidental overdoses, especially from substances laced with fentanyl. Carry Narcan for emergencies.
- Dermatology: use sunscreen daily to prevent skin cancer, aging, pigmentation issues, and texture problems caused by UV exposure.
- Cardiology: avoid the carnivore diet as it increases heart disease risks due to its negligible fiber content and high saturated fat intake.
*We had an article about this a while back; part of the problem is that taking probiotics without prebiotics can mean your new bacteria just die in about 20 minutes, which is their approximate lifespan in which to multiply or else die out. Similar problems arise if taking them with sugar that feeds their competitors instead. See: Stop Sabotaging Your Gut!
For more on each of these, in the words of the respective doctors, enjoy:
Click Here If The Embedded Video Doesn’t Load Automatically!
Want to learn more?
You might also like to read:
Take care!
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Protein Immune Support Salad
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How to get enough protein from a salad, without adding meat? Cashews and chickpeas have you more than covered! Along with the leafy greens and an impressive array of minor ingredients full of healthy phytochemicals, this one’s good for your muscles, bones, skin, immune health, and more.
You will need
- 1½ cups raw cashews (if allergic, omit; the chickpeas and coconut will still carry the dish for protein and healthy fats)
- 2 cans (2x 14oz) chickpeas, drained
- 1½ lbs baby spinach leaves
- 2 large onions, finely chopped
- 3 oz goji berries
- ½ bulb garlic, finely chopped
- 2 tbsp dessicated coconut
- 1 tbsp dried cumin
- 1 tbsp nutritional yeast
- 2 tsp chili flakes
- 1 tsp black pepper, coarse ground
- ½ tsp MSG, or 1 tsp low-sodium salt
- Extra virgin olive oil, for cooking
Method
(we suggest you read everything at least once before doing anything)
1) Heat a little oil in a pan; add the onions and cook for about 3 minutes.
2) Add the garlic and cook for a further 2 minutes.
3) Add the spinach, and cook until it wilts.
4) Add the remaining ingredients except the coconut, and cook for another three minutes.
5) Heat another pan (dry); add the coconut and toast for 1–2 minutes, until lightly golden. Add it to the main pan.
6) Serve hot as a main, or an attention-grabbing side:
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
- Cashew Nuts vs Coconut – Which is Healthier?
- What Matters Most For Your Heart?
- Beyond Supplements: The Real Immune-Boosters!
- Goji Berries: Which Benefits Do They Really Have?
- Our Top 5 Spices: How Much Is Enough For Benefits?
Take care!
Don’t Forget…
Did you arrive here from our newsletter? Don’t forget to return to the email to continue learning!
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