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 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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What Most People Don’t Know About HIV
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What To Know About HIV This World AIDS Day
Yesterday, we asked 10almonds readers to engage in a hypothetical thought experiment with us, and putting aside for a moment any reason you might feel the scenario wouldn’t apply for you, asked:
❝You have unprotected sex with someone who, afterwards, conversationally mentions their HIV+ status. Do you…❞
…and got the above-depicted, below-described, set of responses. Of those who responded…
- Just over 60% said “rush to hospital; maybe a treatment is available”
- Just under 20% said “ask them what meds they’re taking (and perhaps whether they’d like a snack)”
- Just over 10% said “despair; life is over”
- Two people said “do the most rigorous washing down there you’ve ever done in your life”
So, what does science say about it?
First, a quick note on terms
- HIV is the Human Immunodeficiency Virus. It does what it says on the tin; it gives humans immunodeficiency. Like many viruses that have become epidemic in humans, it started off in animals (called SIV, because there was no “H” involved yet), which were then eaten by humans, passing the virus to us when it one day mutated to allow that.
- It’s technically two viruses, but that’s beyond the scope of today’s article; for our purposes they are the same. HIV-1 is more virulent and infectious than HIV-2, and is the kind more commonly found in most of the world.
- AIDS is Acquired Immunodeficiency Syndrome, and again, is what it sounds like. When a person is infected with HIV, then without treatment, they will often develop AIDS.
- Technically AIDS itself doesn’t kill people; it just renders people near-defenseless to opportunistic infections (and immune-related diseases such as cancer), since one no longer has a properly working immune system. Common causes of death in AIDS patients include cancer, influenza, pneumonia, and tuberculosis.
People who contract HIV will usually develop AIDS if untreated. Untreated life expectancy is about 11 years.
HIV/AIDS are only a problem for gay people: True or False?
False, unequivocally. Anyone can get HIV and develop AIDS.
The reason it’s more associated with gay men, aside from homophobia, is that since penetrative sex is more likely to pass it on, then if we go with the statistically most likely arrangements here:
- If a man penetrates a woman and passes on HIV, that woman will probably not go on to penetrate someone else
- If a man penetrates a man and passes on HIV, that man could go on to penetrate someone else—and so on
- This means that without any difference in safety practices or promiscuity, it’s going to spread more between men on average, by simple mathematics.
- This is why “men who have sex with men” is the generally-designated higher-risk category.
There is medication to cure HIV/AIDS: True or False?
False so far (though there have been individual case studies of gene treatments that may have cured people—time will tell).
But! There are medications that can prevent HIV from being a life-threatening problem:
- PrEP (Pre-Exposure Prophylaxis) is a medication that one can take in advance of potential exposure to HIV, to guard against it.
- This is a common choice for people aren’t sure about their partners’ statuses, or people working in risky environments.
- PEP (Post-Exposure Prophylaxis) is a medication that one can take after potential exposure to HIV, to “nip it in the bud”.
- Those of you who were rushing to hospital in our poll, this is what you’re rushing there for.
- ARVs (Anti-RetroVirals) are a class of medications (there are different options; we don’t have room to distinguish them) that reduce an HIV+ person’s viral load to undetectable levels.
- Those of you who were asking what meds your partner was taking, these will be those meds. Also, most of them are to be taken in the morning with food, so that’s what the snack was for.
If someone is HIV+, the risk of transmission in unprotected sex is high: True or False?
True or False, with false being the far more likely. It depends on their medications, and this is why you were asking. If someone is on ARVs and their viral load is undetectable (as is usual once someone has been on ARVs for 6 months), they cannot transmit HIV to you.
U=U is not a fancy new emoticon, it means “undetectable = untransmittable”, which is a mathematically true statement in the case of HIV viral loads.
See: NIH | HIV Undetectable=Untransmittable (U=U)
If you’re thinking “still sounds risky to me”, then consider this:
You are safer having unprotected sex with someone who is HIV+ and on ARVs with an undetectable viral load, than you are with someone you are merely assuming is HIV- (perhaps you assume it because “surely this polite blushing young virgin of a straight man won’t give me cooties” etc)
Note that even your monogamous partner of many decades could accidentally contract HIV due to blood contamination in a hospital or an accident at work etc, so it’s good practice to also get tested after things that involve getting stabbed with needles, cut in a risky environment, etc.
If you’re concerned about potential stigma associated with HIV testing, you can get kits online:
CDC | How do I find an HIV self-test?
(these are usually fingerprick blood tests, and you can either see the results yourself at home immediately, or send it in for analysis, depending on the kit)
If I get HIV, I will get AIDS and die: True or False?
False, assuming you get treatment promptly and keep taking it. So those of you who were at “despair; life is over” can breathe a sigh of relief now.
However, if you get HIV, it does currently mean you will have to take those meds every day for the rest of your (no reason it shouldn’t be long and happy) life.
So, HIV is definitely still something to avoid, because it’s not great to have to take a life-saving medication every day. For a little insight as to what that might be like:
HIV.gov | Taking HIV Medication Every Day: Tips & Challenges
(as you’ll see there, there are also longer-lasting injections available instead of daily pulls, but those are much less widely available)
Summary
Some quick take-away notes-in-a-nutshell:
- Getting HIV may have been a death sentence in the 1980s, but nowadays it’s been relegated to the level of “serious inconvenience”.
- Happily, it is very preventable, with PrEP, PEP, and viral loads so low that they can’t transmit HIV, thanks to ARVs.
- Washing will not help, by the way. Safe sex will, though!
- As will celibacy and/or sexual exclusivity in seroconcordant relationships, e.g. you have the same (known! That means actually tested recently! Not just assumed!) HIV status as each other.
- If you do get it, it is very manageable with ARVs, but prevention is better than treatment
- There is no certain cure—yet. Some people (small number of case studies) may have been cured already with gene therapy, but we can’t know for sure yet.
Want to know more? Check out:
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Kava vs Anxiety
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Kava, sometimes also called “kava kava” but we’re just going to call it kava once for the sake of brevity, is a heart-shaped herb that
bestows the powers of the Black Pantheris popularly enjoyed for its anxiolytic (anxiety-reducing) effects. Despite the similarity of the name in many languages, it is unrelated to coffee (except insofar as they are both plants), and its botanical name is Piper methysticum.Does it work?
Yes! At least in the short-term; more on that later.
Firstly, you may be wondering how it works; it works by its potentiation of GABA receptors in the brain. GABA (or gamma-aminobutyric acid, to give it its full name), as you may recall, is a neurotransmitter that is associated with feelings of calm; we wrote about it here:
So, what does “potentiation of GABA receptors” mean? It means… Scientists don’t for 100% sure know how it works yet, but it does make GABA receptors fire more. It’s possible that to some degree GABA fits the “molecular lock” of the receptors and causes them to say “GABA is here”; it’s also possible that they just make them more sensitive to the real GABA that is there, or there could be another explanation as yet undiscovered. Either way, it means that taking kava has a similar effect to having increased GABA levels in the brain:
As for how much to use, 20–300mg appears to be an effective dose, and most sources recommend 80–250mg:
Kava as a Clinical Nutrient: Promises and Challenges
This review of clinical trials found that it was more effective than placebo in only 3 of 7 trials; specifically, it was beneficial in the short-term and not in the long-term. For these reasons, the researchers concluded:
❝Kava Kava appears to be a short-term treatment for anxiety, but not a replacement for prolonged anti-anxiety use. Although not witnessed in this review, liver toxicity is especially possible if taken longer than 8 weeks.❞
Another review of clinical trials found better results over the course of 11 clinical trials, though again, short-term treatment only was considered to be where the “safe and effective” claim can be placed:
❝Compared with placebo, kava extract appears to be an effective symptomatic treatment option for anxiety. The data available from the reviewed studies suggest that kava is relatively safe for short-term treatment (1 to 24 weeks), although more information is required. Further rigorous investigations, particularly into the long-term safety profile of kava are warrant❞
Source: Kava extract for treating anxiety
Is it safe?
Nope! It has been associated with liver damage:
The likely main mechanism of toxicity is that it simply monopolizes the liver’s metabolic abilities, meaning that while it’s metabolizing the kava, it’s not metabolizing other things (such as alcohol or other medications), which will then build up, and potentially overwhelm the liver:
Constituents in kava extracts potentially involved in hepatotoxicity: a review
However, traditionally-prepared kava has not had the same effect as modern extracts; at first it seemed the difference was the traditional aqueous extracts vs modern acetonic/ethanolic extracts, but eventually that was found not to be the case, as toxicity occurred with industrial aqueous extracts too. The conclusion so far is that it is about the quality of the source ingredients, and the problems inherent to mass-production:
Meanwhile, short-term use doesn’t seem to have this problem, if you’re not drinking alcohol or taking medications that affect the liver:
Mechanisms/risk factors – kava-associated hepatotoxicity ← you’ll need to scroll down to 4.2.4 to read about this
Want to try it?
If the potential for hepatotoxicity doesn’t put you off, here’s an example product on Amazon ← we do not recommend it, but we are not the boss of you, and maybe you’re confident about your liver and want to use it only very short-term?
Take care!
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Crispy Tempeh & Warming Mixed Grains In Harissa Dressing
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Comfort food that packs a nutritional punch! Lots of protein, fiber, vitamins, minerals, and healthy fats, and more polyphenols than you can shake a fork at.
You will need
- 1 lb cooked mixed whole grains (your choice what kind; gluten-free options include buckwheat, quinoa, millet)
- 7 oz tempeh, cut into ½” cubes
- 2 red peppers, cut into strips
- 10 baby plum tomatoes, halved
- 1 avocado, pitted, peeled, and diced
- 1 bulb garlic, paperwork done but cloves left whole
- 1 oz black olives, pitted and halved
- 4 tbsp extra virgin olive oil
- 2 tbsp harissa paste
- 2 tbsp soy sauce (ideally tamari)
- 1 tbsp nutritional yeast
- 1 tbsp chia seeds
- 2 tsp black pepper, coarse ground
- 1 tsp red chili flakes
- 1 handful chopped fresh flat-leaf parsley
- ½ tsp MSG or 1 tsp low-sodium salt
Method
(we suggest you read everything at least once before doing anything)
1) Preheat the oven to 400℉ / 200℃.
2) Combine the red pepper strips with the tomatoes, garlic, 2 tbsp of the olive oil, and the MSG/salt, tossing thoroughly to ensure an even coating. Spread them on a lined baking tray, and roast for about 25 minutes. Remove when done, and allow to cool a little.
3) Combine the tempeh with the soy sauce and nutritional yeast flakes, tossing thoroughly to ensure an even coating. Spread them on a lined baking tray, and roast for about 25 minutes, tossing regularly to ensure it is crispy on all sides. If you get started on the tempeh as soon as the vegetables are in the oven, these should be ready only a few minutes after the vegetables.
4) Whisk together the remaining olive oil and harissa paste in a small bowl, to make the dressing,
5) Mix everything in a big serving bowl. By “everything” we mean the roasted vegetables, the crispy tempeh, the mixed grains, the dressing, the chia seeds, the black pepper, the red chili flakes, and the flat leaf parsley.
6) Serve warm.
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
- Grains: Bread Of Life, Or Cereal Killer?
- Tempeh vs Tofu – Which is Healthier?
- Our Top 5 Spices: How Much Is Enough For Benefits?
Take care!
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What is a virtual emergency department? And when should you ‘visit’ one?
10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.
For many Australians the emergency department (ED) is the physical and emblematic front door to accessing urgent health-care services.
But health-care services are evolving rapidly to meet the population’s changing needs. In recent years, we’ve seen growing use of telephone, video, and online health services, including the national healthdirect helpline, 13YARN (a crisis support service for First Nations people), state-funded lines like 13 HEALTH, and bulk-billed telehealth services, which have helped millions of Australians to access health care on demand and from home.
The ED is similarly expanding into new telehealth models to improve access to emergency medical care. Virtual EDs allow people to access the expertise of a hospital ED through their phone, computer or tablet.
All Australian states and the Northern Territory have some form of virtual ED at least in development, although not all of these services are available to the general public at this stage.
So what is a virtual ED, and when is it appropriate to consider using one?
Shutterstock/Nils Versemann How does a virtual ED work?
A virtual ED is set up to mirror the way you would enter the physical ED front door. First you provide some basic information to administration staff, then you are triaged by a nurse (this means they categorise the level of urgency of your case), then you see the ED doctor. Generally, this all takes place in a single video call.
In some instances, virtual ED clinicians may consult with other specialists such as neurologists, cardiologists or trauma experts to make clinical decisions.
A virtual ED is not suitable for managing medical emergencies which would require immediate resuscitation, or potentially serious chest pains, difficulty breathing or severe injuries.
A virtual ED is best suited to conditions that require immediate attention but are not life-threatening. These could include wounds, sprains, respiratory illnesses, allergic reactions, rashes, bites, pain, infections, minor burns, children with fevers, gastroenteritis, vertigo, high blood pressure, and many more.
People with these sorts of conditions and concerns may not be able to get in to see a GP straight away and may feel they need emergency advice, care or treatment.
When attending the ED, they can be subject to long wait times and delayed specialist attention because more serious cases are naturally prioritised. Attending a virtual ED may mean they’re seen by a doctor more quickly, and can begin any relevant treatment sooner.
From the perspective of the health-care system, virtual EDs are about redirecting unnecessary presentations away from physical EDs, helping them be ready to respond to emergencies. The virtual ED will not hesitate in directing callers to come into the physical ED if staff believe it is an emergency.
The doctor in the virtual ED may also direct the patient to a GP or other health professional, for example if their condition can’t be assessed visually, or if they need physical treatment.
The results so far
Virtual EDs have developed significantly over the past three years, predominantly driven by the COVID pandemic. We are now starting to slowly see assessments of these services.
A recent evaluation my colleagues and I did of Queensland’s Metro North Virtual ED found roughly 30% of calls were directed to the physical ED. This suggests 70% of the time, cases could be managed effectively by the virtual ED.
Preliminary data from a Victorian virtual ED indicates it curbed a similar rate of avoidable ED presentations – 72% of patients were successfully managed by the virtual ED alone. A study on the cost-effectiveness of another Victorian virtual ED suggested it has the potential to generate savings in health-care costs if it prevents physical ED visits.
Only 1.2% of people assessed in Queensland’s Metro North Virtual ED required unexpected hospital admission within 48 hours of being “discharged” from the virtual ED. None of these cases were life-threatening. This indicates the virtual ED is very safe.
The service experienced an average growth rate of 65% each month over a two-year evaluation period, highlighting increasing demand and confidence in the service. Surveys suggested clinicians also view the virtual ED positively.
The right advice could tell you whether you need to visit hospital in person or not. 1st footage/Shutterstock What now?
We need further research into patient outcomes and satisfaction, as well as the demographics of those using virtual EDs, and how these measures compare to the physical ED across different triage categories.
There are also challenges associated with virtual EDs, including around technology (connection and skills among patients and health professionals), training (for health professionals) and the importance of maintaining security and privacy.
Nonetheless, these services have the potential to reduce congestion in physical EDs, and offer greater convenience for patients.
Eligibility differs between different programs, so if you want to use a virtual ED, you may need to check you are eligible in your jurisdiction. Most virtual EDs can be accessed online, and some have direct phone numbers.
Jaimon Kelly, Senior Research Fellow in Telehealth delivered health services, The University of Queensland
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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The Longevity Diet – by Dr. Valter Longo
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Another book with “The New Science” in its subtitle, so, is this one a new science?
Yes and no; some findings are new, many are not, what really sets this book apart from many of its genre though is that rather than focusing on fighting aging, it focuses on retaining youth. While this may seem like one and the same thing, there is a substantive difference beyond the ideological, which is: while anti-aging research focuses on what causes people to suffer age-related decline and fights each of those things, Dr. Longo’s research focuses on what is predominant in youthful bodies, cells, DNA, and looks to have more of that. Looking in a slightly different place means finding slightly different things, and knowledge is power indeed.
Dr. Longo bases his research and focus on his “5 pillars of longevity”. We’ll not keep them a mystery; they are:
- Juventology research
- Epidemiology
- Clinical studies
- Centenarian studies
- Study of complex systems
The first there (juventology research) may sound like needless jargon, but it is the counterpoint of the field of gerontology, and is otherwise something that didn’t have an established name.
You may wonder why “clinical studies” gets a separate item when the others already include studies; this is because many studies when it comes to aging and related topics are population-based studies, cohort studies, observational studies, or (as is often the case) multiple of the above at once.
Of course, all this discussion of academia is not itself practical information for the reader (unless we happen to work in the field), but it is interesting and does give confidence in the conclusions upon which the practical parts of the book are based.
And what are they? As the title suggests, it’s about diet, and specifically, it’s about Dr. Longo’s “fast-mimicking diet”, which boasts the benefits of intermittent fasting without intermittent fasting. This hinges, of course, on avoiding metabolic overload, which can be achieved with a fairly simple diet governed by the principles outlined in this book, based on the research referenced.
In the category of subjective criticism, there is quite a bit of fluff, much of it self-indulgently autobiographical and very complimentary, but its presence does not take anything away from the excellent content contained in the book.
Bottom line: if you’d like a fresh perspective on regaining/retaining youthfulness, then this is a great book to read.
Click here to check out The Longevity Diet, and stay younger!
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Avocado, Coconut & Lime Crumble Pots
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This one’s a refreshing snack or dessert, whose ingredients come together to make a very good essential fatty acid supplement. Coconut is a good source of MCTs, avocados are rich in omega 3, 6, and 9, while chia seeds are a great ALA omega 3 food, topping up the healthy balance.
You will need
- flesh of 2 large ripe avocados
- grated zest and juice of 2 limes
- 3 tbsp coconut oil
- 1 tbsp chia seeds
- 2 tsp honey (omit if you prefer a less sweet dish)
- 1 tsp desiccated coconut
- 4 low-sugar oat biscuits
Method
(we suggest you read everything at least once before doing anything)
1) Blend the avocado, lime juice, coconut oil, honey, and half the desiccated coconut, in a food processor.
2) Scoop the mixture into 4 ramekins (or equivalent-sized glasses), making sure to leave a ½” gap at the top. Refrigerate for at least 2–4 hours (longer is fine if you’re not ready to serve yet).
3) Assemble, by crumbling the oat biscuits and sprinkling on top of each serving, along with the other half of the desiccated coconut, the lime zest, and the chia seeds.
4) Serve immediately:
Enjoy!
Want to learn more?
For those interested in some of the science of what we have going on today:
Take care!
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