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:

Shedding Some Obesity Myths

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:

Semaglutide For Weight Loss?

…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:

Dietary intake by patients taking GLP-1 and dual GIP/GLP-1 receptor agonists: A narrative review and discussion of research needs

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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  • Welcoming the Unwelcome – by Pema Chödrön

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    There’s a lot in life that we don’t get to choose. Some things we have zero control over, like the weather. Others, we can only influence, like our health. Still yet others might give us an illusion of control, only to snatch it away, like a financial reversal or a bereavement.

    How, then, to suffer those “slings and arrows of outrageous fortune” and come through the other side with an even mind and a whole heart?

    Author Pema Chödrön has a guidebook for us.

    Quick note: this book does not require the reader to have any particular religious faith to enjoy its benefits, but the author is a nun. As such, the way she describes things is generally within the frame of her religion. So that’s a thing to be aware of in case it might bother you. That said…

    The largest part of her approach is one that psychology might describe as rational emotive behavioral therapy.

    As such, we are encouraged to indeed “meet with triumph and disaster, and treat those two imposters just the same”, and more importantly, she lays out the tools for us to do so.

    Does this mean not caring? No! Quite the opposite. It is expected, and even encouraged, that we might care very much. But: this book looks at how to care and remain compassionate, to others and to ourselves.

    For Chödrön, welcoming the unwelcome is about de-toothing hardship by accepting it as a part of the complex tapestry of life, rather than something to be endured.

    Bottom line: this book can greatly increase the reader’s ability to “go placidly amid the noise and haste” and bring peace to an often hectic world—starting with our own.

    Click here to check out Welcoming the Unwelcome, and learn what’s practically a superpower in this sometimes crazy world.

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  • Fitness In Our Fifties

    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.

    It’s Q&A Day at 10almonds!

    Have a question or a request? We love to hear from you!

    In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!

    As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!

    So, no question/request too big or small

    Q: What’s a worthwhile fitness goal for people in their 50s?

    A: At 10almonds, we think that goals are great but habits are better.

    If your goal is to run a marathon, that’s a fine goal, and can be very motivating, but then after the marathon, then what? You’ll look back on it as a great achievement, but what will it do for your future health?

    PS, yes, marathon-running in one’s middle age is a fine and good activity for most people. Maybe skip it if you have osteoporosis or some other relevant problem (check with your doctor), but…

    Marathons in Mid- and Later-Life ← we wrote about the science of it here

    PS, we also explored some science that may be applicable to your other question, on the same page as that about marathons!

    The thing about habits vs goals is that habits give ongoing cumulative (often even: compounding) benefits:

    How To Really Pick Up (And Keep!) Those Habits

    If you pressingly want advice on goals though, our advice is this:

    Make it your goal to be prepared for the health challenges of later life. It may seem gloomy to say that old age is coming for us all if something else doesn’t get us first, but the fact is, old age does not have to come with age-related decline, and the very least, we can increase our healthspan (so we’re hitting 90 with most of the good health we enjoyed in our 70s, for example, or hitting 80 with most of the good health we enjoyed in our 60s).

    If that goal seems a little wishy-washy, here are some very specific and practical ideas to get you started:

    Train For The Event Of Your Life!

    As for the limits and/or extents of how much we can do in that regard? Here are what two aging experts have to say:

    And here’s what we at 10almonds had to say:

    Age & Aging: What Can (And Can’t) We Do About It?

    Take care!

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  • Ashwagandha: The Root of All Even-Mindedness?

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    Ashwagandha: The Root Of All Even-Mindedness?

    In the past few years, Ashwagandha root has been enjoying popular use in consumer products ranging from specialist nootropic supplement stacks, to supermarket teas and hot chocolates.

    This herb is considered to have a calming effect, but the science goes a lot deeper than that. Let’s take a look!

    Last summer, a systematic review was conducted, that asked the question:

    Does Ashwagandha supplementation have a beneficial effect on the management of anxiety and stress?

    While they broadly found the answer was “yes”, they expressed low confidence, and even went so far as to say there was contradictory evidence. We (10almonds) were not able to find any contradictory evidence, and their own full article had been made inaccessible to the public, so we couldn’t double-check theirs.

    We promptly did our own research review, and we found many studies this year supporting Ashwaghanda’s use for the management of anxiety and stress, amongst other benefits.

    First, know: Ashwagandha’s scientific name is “Withania somnifera”, so if you see that (or a derivative of it) mentioned in a paper or extract, it’s the same thing.

    Onto the benefits…

    A study from the same summer investigated “the efficacy of Withania somnifera supplementation on adults’ cognition and mood”, and declared that:

    “in conclusion, Ashwagandha supplementation may improve the physiological, cognitive, and psychological effects of stress.”

    We notice the legalistic “may improve”, but the data itself seems more compelling than that, because the study showed that it in fact “did improve” those things. Specifically, Ashwagandha out-performed placebo in most things they measured, and most (statistically) significantly, reduced cortisol output measurably. Cortisol, for any unfamiliar, is “the stress hormone”.

    Another study that looked into its anti-stress properties is this one:

    Ashwagandha Modulates Stress, Sleep Dynamics, and Mental Clarity

    This study showed that Ashwagandha significantly outperformed placebo in many ways, including:

    • sleep quality
    • cognitive function
    • energy, and
    • perceptions of stress management.

    Ashwagandha is popular among students, because it alleviates stress while also promising benefits to memory, attention, and thinking. So, this study on students caught our eye:

    The Perceived Impact of Ashwagandha on Stress, Sleep Quality, Energy, and Mental Clarity for College Students: Qualitative Analysis of a Double-Blind Randomized Control Trial

    Their findings demonstrated that Ashwagandha increased college students’ perceived well-being through supporting sustained energy, heightened mental clarity, and enhanced sleep quality.

    That was about perceived well-being and based on self-reports, though

    So: what about hard science?

    A later study (in September) found supplementation with 400 mg of Ashwagandha improved executive function, helped sustain attention, and increased short-term/working memory.

    Read the study: Effects of Acute Ashwagandha Ingestion on Cognitive Function

    ❝But aside from the benefits regarding stress, anxiety, sleep quality, cognitive function, energy levels, attention, executive function, and memory, what has Ashwagandha ever done for us?

    Well, there have been studies investigating its worth against depression, like this one:

    Can Traditional Treatment Such as Ashwagandha Be Beneficial in Treating Depression?

    Their broad answer: Ashwagandha works against depression, but they don’t know how it works.

    They did add: “Studies also show that ashwagandha may bolster the immune system, increase stamina, fight inflammation and infection, combat tumors*, reduce stress, revive the libido, protect the liver and soothe jangled nerves.

    That’s quite a lot, including a lot of physical benefits we’ve not explored in this research review which was more about Ashwagandha’s use as a nootropic!

    We’ve been focusing on the more mainstream, well-studied benefits, but for any interested in Ashwagandha’s anti-cancer potential, here’s an example:

    Evaluating anticancer properties of [Ashwagandha Extract]-a potent phytochemical

    In summary:

    There is a huge weight of evidence (of which we’ve barely skimmed the surface here in this newsletter, but there’s only so much we can include, so we try to whittle it down to the highest quality most recent most relevant research) to indicate that Ashwagandha is effective…

    • Against stress
    • Against anxiety
    • Against depression
    • For sleep quality
    • For memory (working, short-term, and long-term)
    • For mental clarity
    • For attention
    • For stamina
    • For energy levels
    • For libido
    • For immune response
    • Against inflammation
    • Against cancer
    • And more*

    *(seriously, this is not hyperbole… We didn’t even look at its liver-protective functions, for instance)

    Bottom line:

    You’d probably like some Ashwagandha now, right? We know we would.

    We don’t sell it (or anything else, for that matter), but happily the Internet does:

    Try Out Ashwagandha For Yourself Here!

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  • Brown Rice vs Wild Rice – Which is Healthier?

    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.

    Our Verdict

    When comparing brown rice to wild rice, we picked the wild.

    Why?

    It’s close! But there are important distinctions.

    First let’s clarify: despite the name and appearance, wild rice is botanically quite different from rice per se; it’s not the same species, it’s not even the same genus, though it is the same umbrella family. In other words, they’re about as closely related as humans and gorillas are to each other.

    In terms of macros, wild rice has considerably more protein and a little more fiber, for slightly lower carbs.

    Notably, however, wild rice’s carbs are a close-to-even mix of sucrose, fructose, and glucose, while brown rice’s carbs are 99% starch. Given the carb to fiber ratio, it’s worth noting that wild rice also has lower net carbs, and the lower glycemic index.

    In the category of vitamins, wild rice leads with more of vitamins A, B2, B9, E, K, and choline. In contrast, brown rice has more of vitamins B1, B3, and B5. So, a moderate win for wild rice.

    When it comes to minerals, brown rice finally gets a tally in its favor, even if only slightly: brown rice has more magnesium, manganese, phosphorus, and selenium, while wild rice has more copper, potassium, and zinc. They’re equal in calcium and iron, by the way. Still, this category stands as a 4:3 win for brown rice.

    Adding up the categories makes a modest win for wild rice, and additionally, if we had to consider one of these things more important than the others, it’d be wild rice being higher in fiber and protein and lower in total carbs and net carbs.

    Still, enjoy either or both, per your preference!

    Want to learn more?

    You might like to read:

    Take care!

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  • Why are tall people more likely to get cancer? What we know, don’t know and suspect

    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.

    People who are taller are at greater risk of developing cancer. The World Cancer Research Fund reports there is strong evidence taller people have a higher chance of of developing cancer of the:

    • pancreas
    • large bowel
    • uterus (endometrium)
    • ovary
    • prostate
    • kidney
    • skin (melanoma) and
    • breast (pre- and post-menopausal).

    But why? Here’s what we know, don’t know and suspect.

    Pexels/Andrea Piacquadio
    A tall woman and her partner are silhoutted against the sunset.
    Height does increase your cancer risk – but only by a very small amount. Christian Vinces/Shutterstock

    A well established pattern

    The UK Million Women Study found that for 15 of the 17 cancers they investigated, the taller you are the more likely you are to have them.

    It found that overall, each ten-centimetre increase in height increased the risk of developing a cancer by about 16%. A similar increase has been found in men.

    Let’s put that in perspective. If about 45 in every 10,000 women of average height (about 165 centimetres) develop cancer each year, then about 52 in each 10,000 women who are 175 centimetres tall would get cancer. That’s only an extra seven cancers.

    So, it’s actually a pretty small increase in risk.

    Another study found 22 of 23 cancers occurred more commonly in taller than in shorter people.

    Why?

    The relationship between height and cancer risk occurs across ethnicities and income levels, as well as in studies that have looked at genes that predict height.

    These results suggest there is a biological reason for the link between cancer and height.

    While it is not completely clear why, there are a couple of strong theories.

    The first is linked to the fact a taller person will have more cells. For example, a tall person probably has a longer large bowel with more cells and thus more entries in the large bowel cancer lottery than a shorter person.

    Scientists think cancer develops through an accumulation of damage to genes that can occur in a cell when it divides to create new cells.

    The more times a cell divides, the more likely it is that genetic damage will occur and be passed onto the new cells.

    The more damage that accumulates, the more likely it is that a cancer will develop.

    A person with more cells in their body will have more cell divisions and thus potentially more chance that a cancer will develop in one of them.

    Some research supports the idea having more cells is the reason tall people develop cancer more and may explain to some extent why men are more likely to get cancer than women (because they are, on average, taller than women).

    However, it’s not clear height is related to the size of all organs (for example, do taller women have bigger breasts or bigger ovaries?).

    One study tried to assess this. It found that while organ mass explained the height-cancer relationship in eight of 15 cancers assessed, there were seven others where organ mass did not explain the relationship with height.

    It is worth noting this study was quite limited by the amount of data they had on organ mass.

    A tall older man leans against a wall while his bicycle is parked nearby.
    Is it because tall people have more cells? Halfpoint/Shutterstock

    Another theory is that there is a common factor that makes people taller as well as increasing their cancer risk.

    One possibility is a hormone called insulin-like growth factor 1 (IGF-1). This hormone helps children grow and then continues to have an important role in driving cell growth and cell division in adults.

    This is an important function. Our bodies need to produce new cells when old ones are damaged or get old. Think of all the skin cells that come off when you use a good body scrub. Those cells need to be replaced so our skin doesn’t wear out.

    However, we can get too much of a good thing. Some studies have found people who have higher IGF-1 levels than average have a higher risk of developing breast or prostate cancer.

    But again, this has not been a consistent finding for all cancer types.

    It is likely that both explanations (more cells and more IGF-1) play a role.

    But more research is needed to really understand why taller people get cancer and whether this information could be used to prevent or even treat cancers.

    I’m tall. What should I do?

    If you are more LeBron James than Lionel Messi when it comes to height, what can you do?

    Firstly, remember height only increases cancer risk by a very small amount.

    Secondly, there are many things all of us can do to reduce our cancer risk, and those things have a much, much greater effect on cancer risk than height.

    We can take a look at our lifestyle. Try to:

    • eat a healthy diet
    • exercise regularly
    • maintain a healthy weight
    • be careful in the sun
    • limit alcohol consumption.

    And, most importantly, don’t smoke!

    If we all did these things we could vastly reduce the amount of cancer.

    You can also take part in cancer screening programs that help pick up cancers of the breast, cervix and bowel early so they can be treated successfully.

    Finally, take heart! Research also tells us that being taller might just reduce your chance of having a heart attack or stroke.

    Susan Jordan, Associate Professor of Epidemiology, The University of Queensland and Karen Tuesley, Postdoctoral Research Fellow, School of Public Health, The University of Queensland

    This article is republished from The Conversation under a Creative Commons license. Read the original article.

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  • Ikigai – by Héctor García and Francesc Miralles

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    Ikigai is the Japanese term for what in English we often call “raison d’être”… in French, because English is like that.

    But in other words: ikigai is one’s purpose in life, one’s reason for living.

    The authors of this work spend some chapters extolling the virtues of finding one’s ikigai, and the health benefits that doing so can convey. It is, quite clearly, an important and relevant factor.

    The rest of the book goes beyond that, though, and takes a holistic look at why (and how) healthy longevity is enjoyed by:

    • Japanese people in general,
    • Okinawans in particular,
    • Residents of Okinawa’s “blue zone” village with the highest percentage of supercentenarians, most of all.

    Covering considerations from ikigai to diet to small daily habits to attitudes to life, we’re essentially looking at a blueprint for healthy longevity.

    For a book whose title and cover suggests a philosophy-heavy content, there’s a lot of science in here too, by the way! From microbiology to psychiatry to nutrition science to cancer research, this book covers all bases.

    In short: this book gives a lot of good science-based suggestions for adjustments we can make to our lives, without moving to an Okinawan village!

    Click Here To Check Out Ikigai on Amazon Today!

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