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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  • How to Think More Effectively – by Alain de Botton

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    Our brain is our most powerful organ, and our mind is an astonishing thing. So why do we sometimes go off-piste?

    The School of Life‘s Alain de Botton lays out for us a framework of cumulative thinking, directions for effort, and unlikely tools for cognitive improvement.

    The book especially highlights the importance of such things as…

    • making time for cumulative thinking
    • not, however, trying to force it
    • working with, rather than in spite of, distractions
    • noting and making use of our irrationalities
    • taking what we think/do both seriously and lightly, at once
    • practising constructive self-doubt

    The style is as clear and easy as you may have come to expect from Alain de Botton / The School of Life, and yet, its ideas are still likely to challenge every reader in some (good!) way.

    Bottom line: if you would like what you think, say, do to be more meaningful, this book will help you to make the most of your abilities!

    Click here to check out How To Think More Effectively, and upgrade your thought processes!

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  • Hummus vs Guacamole – Which is Healthier?

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    Our Verdict

    When comparing hummus to guacamole, we picked the guacamole.

    Why?

    First up, let’s assume that the standards are comparable, for example that both have been made with simple whole foods. The hummus is mostly chickpeas with tahini and a little olive oil and some seasoning; the guacamole is mostly avocado with a little lime juice and some seasoning.

    In terms of macronutrients, hummus has slightly more protein and fiber, 2x the carbohydrates (but they are healthy carbs), and usually slightly less fat (but the fats are healthy in both cases).

    In terms of micronutrients, the hummus is rich in iron and B vitamins, and the guacamole is rich in potassium, magnesium, vitamins C, E, and K.

    So far, it’s pretty much tied. What else is there to consider?

    We picked the guacamole because some of its nutrients (especially the potassium, magnesium, and vitamin K) are more common deficiencies in most people’s diets than iron and B vitamins. So, on average, it’s probably the one with the nutrients that you need more of at any given time.

    So, it was very very close, and it came down to the above as the deciding factor.

    However!

    • If you like one and not the other? Eat that one; it’s good.
    • If you like both but feel like eating one of them in particular? Eat that one; your body is probably needing those nutrients more right now.
    • If you are catering for a group of people? Serve both!
    • If you are catering for just yourself and would enjoy both? Serve both! There’s nobody to stop you!

    Want to read more?

    You might like: Avocado Oil vs Olive Oil – Which is Healthier?

    Enjoy!

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  • Hawthorn For The Heart (& More)

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    Hawthorn, The Heart-Healthy Helper

    Hawthorn, a berry of the genus Crataegus (there are many species, but they seem to give more or less the same benefits), has been enjoyed for hundreds of years, if not thousands, as a herbal remedy for many ailments, mostly of the cardiovascular, digestive, and/or endocrine systems:

    Crataegus pinnatifida: Chemical Constituents, Pharmacology, and Potential Applications

    Antioxidant & Anti-inflammatory

    Like most berries, it’s full of helpful polyphenols, with antioxidant and anti-inflammatory properties. Indeed, as Dr. Nabavi et al. wrote,

    Crataegus monogyna Jacq. (hawthorn) is one of the most important edible plants of the Rosaceae family and is also used in traditional medicine.

    Growing evidence has shown that this plant has various interesting physiological and pharmacological activities due to the presence of different bioactive natural compounds.

    In addition, scientific evidence suggests that the toxicity of hawthorn is negligible. ❞

    ~ Dr. Nabavi et al.

    Read in full: Polyphenolic Composition of Crataegus monogyna Jacq.: From Chemistry to Medical Applications

    While “the toxicity of hawthorn is negligible” may be reasonably considered a baseline for recommending an edible plant, it’s still important as just that: a baseline. It’s good to know that berries are safe, after all!

    More positively, about those antioxidant and anti-inflammatory properties:

    Polyphenols from hawthorn peels and fleshes differently mitigate dyslipidemia, inflammation and oxidative stress

    This one was a mouse study, but it’s important as it about modulating liver injury after being fed a high fructose diet.

    In other words: it a) helps undo the biggest cause of non-alcoholic fatty liver disease, b) logically, likely guards against diabetes also (by the same mechanism)

    Anti-Diabetes Potential

    Curious about that latter point, we looked for studies, and found, for example:

    Noteworthily, those studies are from the past couple of years, which is probably why we’re not seeing many human trials for this yet—everything has to be done in order, and there’s a lengthy process between each.

    We did find some human trials with hawthorn in diabetes patients, for example:

    Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial

    …but as you see, that’s testing not its antidiabetic potential, so far demonstrated only in mice and rats (so far as we could find), but rather its blood pressure lowering effects, using diabetic patients as a sample.

    Blood pressure benefits

    Hawthorn has been studied specifically for its hypotensive effect, for example:

    Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension

    As an extra bonus, did you notice in the conclusion,

    ❝Furthermore, a trend towards a reduction in anxiety (p = 0.094) was also observed in those taking hawthorn compared with the other groups.

    These findings warrant further study, particularly in view of the low dose of hawthorn extract used.❞

    ~ Dr. Ann Walker et al.

    …it seems that not a lot more study has been done yet, but that is promising too!

    Other blood metrics

    So, it has antidiabetic and antihypertensive benefits, what of blood lipids?

    Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles

    And as for arterial plaque?

    Clinical study on treatment of carotid atherosclerosis with extraction of polygoni cuspidati rhizoma et radix and crataegi fructus: a randomized controlled trial

    here it was tested alongside another herb, and performed well (also against placebo).

    In summary…

    Hawthorn (Crataegus sp.) is…

    • a potent berry containing many polyphenols with good antioxidant and anti-inflammatory effects
    • looking promising against diabetes, but research for this is still in early stages
    • found to have other cardioprotective effects (antihypertensive, improves lipid profiles), too
    • considered to have negligible toxicity

    Where can I get it?

    As ever, we don’t sell it, but here for your convenience is an example product on Amazon

    Enjoy!

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  • How to be kind to yourself (without going to a day spa)

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    “I have to be hard on myself,” Sarah told me in a recent telehealth psychology session. “I would never reach my potential if I was kind and let myself off the hook.”

    I could empathise with this fear of self-compassion from clients such as Sarah (not her real name). From a young age, we are taught to be kind to others, but self-kindness is never mentioned.

    Instead, we are taught success hinges on self-sacrifice. And we need a healthy inner critic to bully us forward into becoming increasingly better versions of ourselves.

    But research shows there doesn’t have to be a trade-off between self-compassion and success.

    Self-compassion can help you reach your potential, while supporting you to face the inevitable stumbles and setbacks along the way.

    What is self-compassion?

    Self-compassion has three key ingredients.

    1. Self-kindness

    This involves treating yourself with the same kindness you would extend towards a good friend – via your thoughts, feelings and actions – especially during life’s difficult moments.

    For instance, if you find yourself fixating on a minor mistake you made at work, self-kindness might involve taking a ten-minute walk to shift focus, and reminding yourself it is OK to make mistakes sometimes, before moving on with your day.

    2. Mindfulness

    In this context, mindfulness involves being aware of your own experience of stress or suffering, rather than repressing or avoiding your feelings, or over-identifying with them.

    Basically, you must see your stress with a clear (mindful) perspective before you can respond with kindness. If we avoid or are consumed by our suffering, we lose perspective.

    3. Common humanity

    Common humanity involves recognising our own experience of suffering as something that unites us as being human.

    For instance, a sleep-deprived parent waking up (for the fourth time) to feed their newborn might choose to think about all the other parents around the world doing exactly the same thing – as opposed to feeling isolated and alone.

    It’s not about day spas, or booking a manicure

    When Sarah voiced her fear that self-compassion would prevent her success, I explained self-compassion is distinct from self-indulgence.

    “So is self-compassion just about booking in more mani/pedis?” Sarah asked.

    Not really, I explained. A one-off trip to a day spa is unlikely to transform your mental health.

    Instead, self-compassion is a flexible psychological resilience factor that shapes our thoughts, feelings and actions.

    It’s associated with a suite of benefits to our wellbeing, relationships and health.

    Massage therapist massaging woman's back
    A one-off trip to a day spa is unlikely to transform your mental health.
    baranq/Shutterstock

    What does the science say?

    Over the past 20 years, we’ve learned self-compassionate people enjoy a wide range of benefits. They tend to be happier and have fewer psychological symptoms of distress.

    Those high on self-compassion persevere following a failure. They say they are more motivated to overcome a personal weakness than those low on self-compassion, who are more likely to give up.

    So rather than feeling trapped by your inadequacies, self-compassion encourages a growth mindset, helping you reach your potential.

    However, self-compassion is not a panacea. It will not change your life circumstances or somehow make life “easy”. It is based on the premise that life is hard, and provides practical tools to cope.

    It’s a factor in healthy ageing

    I research menopause and healthy ageing and am especially interested in the value of self-compassion through menopause and in the second half of life.

    Because self-compassion becomes important during life’s challenges, it can help people navigate physical symptoms (for instance, menopausal hot flushes), life transitions such as divorce, and promote healthy ageing.

    I’ve also teamed up with researchers at Autism Spectrum Australia to explore self-compassion in autistic adults.

    We found autistic adults report significantly lower levels of self-compassion than neurotypical adults. So we developed an online self-compassion training program for this at-risk population.

    Three tips for self-compassion

    You can learn self-compassion with these three exercises.

    1. What would you say to a friend?

    Think back to the last time you made a mistake. What did you say to yourself?

    If you notice you’re treating yourself more like an enemy than a friend, don’t beat yourself up about it. Instead, try to think about what you might tell a friend, and direct that same friendly language towards yourself.

    2. Harness the power of touch

    Soothing human touch activates the parasympathetic “relaxation” branch of our nervous system and counteracts the fight or flight response.

    Specifically, self-soothing touch (for instance, by placing both hands on your heart, stroking your forearm or giving yourself a hug) reduces cortisol responses to psychosocial stress.

    Middle-aged man hugging himself
    Yes, hugging yourself can help.
    http://krakenimages.com/Shutterstock

    3. What do I need right now?

    Sometimes, it can be hard to figure out exactly what self-compassion looks like in a given moment. The question “what do I need right now” helps clarify your true needs.

    For example, when I was 37 weeks pregnant, I woke up bolt awake one morning at 3am.

    Rather than beating myself up about it, or fretting about not getting enough sleep, I gently placed my hands on my heart and took a few deep breaths. By asking myself “what do I need right now?” it became clear that listening to a gentle podcast/meditation fitted the bill (even though I wanted to addictively scroll my phone).The Conversation

    Lydia Brown, Senior Lecturer in Psychology, The University of Melbourne

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

    Don’t Forget…

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  • Why You Can’t Just “Get Over” Trauma

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    Time does not, in fact, heal all wounds. Sometimes they even compound themselves over time. Dr. Tracey Marks explains the damage that trauma does—the physiological presentation of “the axe forgets but the tree remembers”—and how to heal from that actual damage.

    The science of healing

    Trauma affects the mind and body (largely because the brain is, of course, both—and affects pretty much everything else), which can ripple out into all areas of life.

    On the physical level, brain areas affected by trauma include:

    • Amygdalae: becomes hyperactive, keeping a person in a heightened state of vigilance.
    • Hippocampi: can shrink, causing fragmented or missing memories.
    • Prefrontal cortex: reduces in activity, impairing decision-making and emotional regulation.

    Trauma also activates the body’s fight or flight response, releasing stress hormones like cortisol and adrenaline. These are great things to have a pinch, but having them elevated all the time is equivalent to only ever driving your car at top speed—the only question becomes whether you’ll crash and burn before you break down.

    However, there is hope! Neuroplasticity (the brain’s ability to rewire itself) can make trauma recovery possible through various interventions.

    Evidence-based therapies for trauma include:

    • Eye Movement Desensitization and Reprocessing (EMDR): this can help reprocess traumatic memories and reduce emotional intensity.
    • Trauma-focused Cognitive Behavioral Therapy (CBT): this can help change unhelpful thought patterns and includes exposure therapy.
    • Somatic therapies: these focus on the body and nervous system to release stored tension.

    In this latter category, embodiment is key to trauma recovery—this may sound “wishy-washy”, but the evidence shows that reconnecting with the body does help manage emotional stress responses. Mind-body practices like mindfulness, yoga, and breathwork help cultivate embodiment and reduce trauma-related stress.

    In short: you can’t just “get over” it, but with the right support and interventions, it’s possible to rewire the brain and body toward resilience and healing.

    For more on all of this from Dr. Marks, 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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  • Pumpkin Protein Crackers

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    Ten of these (give or take what size you make them) will give you the 20g protein that most people’s body’s can use at a time. Five of these plus some of one of the dips we list at the bottom will also do it:

    You will need

    • 1 cup chickpea flour (also called gram flour or garbanzo bean flour)
    • 2 tbsp pumpkin seeds
    • 1 tbsp chia seeds
    • 1 tsp baking powder
    • ¼ tsp MSG or ½ tsp low-sodium salt
    • 2 tbsp extra virgin olive oil

    Method

    (we suggest you read everything at least once before doing anything)

    1) Preheat the oven to 350℉ / 180℃.

    2) Combine the dry ingredients in a mixing bowl, and mix thoroughly.

    3) Add the oil, and mix thoroughly.

    4) Add water, 1 tbsp at a time, mixing thoroughly until the mixture comes together and you have a dough ball. You’ll probably need 3–4 tbsp in total, but do add them one at a time.

    5) Roll out the dough as thinly and evenly as you can between two sheets of baking paper. Remove the top layer of the paper, and slice the dough into squares or triangles. You could use a cookie-cutter to make other shapes if you like, but then you’ll need to repeat the rolling to use up the offcuts. So we recommend squares or triangles at least for your first go.

    6) Bake them in the oven for 12–15 minutes or until golden and crispy. Enjoy immediately or keep in an airtight container.

    Enjoy!

    Want to learn more?

    For those interested in some things to go with what we have going on today:

    Take care!

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