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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  • Buckwheat vs Oats – Which is Healthier?

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    Our Verdict

    When comparing buckwheat to oats, we picked the oats.

    Why?

    First of all, for any thinking about the health concerns sometimes associated with wheat: buckwheat is not a kind of wheat, nor is it even in the same family; it’s not a grain, but a flowering plant. Buckwheat is to wheat as a lionfish is to lions.

    That said, while these are both excellent foods, one of them is so good it makes the other one look bad in comparison:

    In terms of macros, oats have more carbs, but also more protein and more fiber.

    When it comes to vitamins, a clear winner emerges: oats have more of vitamins B1, B2, B5, B6, and B9, while buckwheat is higher in vitamin K and choline.

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    All in all: as ever, enjoy both, but if you’re picking one, oats cannot be beaten.

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    The Best Kind Of Fiber For Overall Health?

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    Some books on longevity are science-heavy and heavy-going; others are glorified manifestos with much philosophy but little practical.

    This one’s a sciencey-book written for a lay reader. It’s heavily referenced, but not a challenging read.

    This book is divided into three parts:

    1. What we know (the past)
    2. What we’re learning (the present)
    3. Where we’re going (the future)

    Let us quickly mention: the last part is principally sociology and economics, which are not the author’s wheelhouse. Some readers may enjoy his thoughts regardless, but we’re going to concentrate on where we found the real value of the book to be: in the first and second parts, where he brings his expertise to bear.

    The first part lays the foundational knowledge that’s critical for understanding why the second part is so important.

    Basically: aging is a genetic disease, and diseases can be cured. No disease has magical properties, even if sometimes it can seem for a while like they do, until we understand them better.

    The second part covers a lot of recent and contemporary research into aging. We learn about such things as NAD-agonists that make elderly mice biologically young again, and the Greenland shark that easily lives for 500 years or so (currently the record-holder for vertebrates). And of course, biologically immortal jellyfish.

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    Other recommendations pertain to lifestyle; the usual five things (diet, exercise, sleep, no alcohol, no smoking), as well as intermittent fasting and cryotherapy (cold showers/baths).

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    Get your copy of “Lifespan: Why We Age—And Why We Don’t Have To” from Amazon today!

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  • Stuck in fight-or-flight mode? 5 ways to complete the ‘stress cycle’ and avoid burnout or depression

    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.

    Can you remember a time when you felt stressed leading up to a big life event and then afterwards felt like a weight had been lifted? This process – the ramping up of the stress response and then feeling this settle back down – shows completion of the “stress cycle”.

    Some stress in daily life is unavoidable. But remaining stressed is unhealthy. Chronic stress increases chronic health conditions, including heart disease and stroke and diabetes. It can also lead to burnout or depression.

    Exercise, cognitive, creative, social and self-soothing activities help us process stress in healthier ways and complete the stress cycle.

    What does the stress cycle look like?

    Scientists and researchers refer to the “stress response”, often with a focus on the fight-or-flight reactions. The phrase the “stress cycle” has been made popular by self-help experts but it does have a scientific basis.

    The stress cycle is our body’s response to a stressful event, whether real or perceived, physical or psychological. It could be being chased by a vicious dog, an upcoming exam or a difficult conversation.

    The stress cycle has three stages:

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    Different people will respond to stress differently based on their life experiences and genetics.

    Unfortunately, many people experience multiple and ongoing stressors out of their control, including the cost-of-living crisis, extreme weather events and domestic violence.

    Remaining in stage 2 (the flight-or-flight response), can lead to chronic stress. Chronic stress and high cortisol can increase inflammation, which damages our brain and other organs.

    When you are stuck in chronic fight-or-flight mode, you don’t think clearly and are more easily distracted. Activities that provide temporary pleasure, such as eating junk food or drinking alcohol are unhelpful strategies that do not reduce the stress effects on our brain and body. Scrolling through social media is also not an effective way to complete the stress cycle. In fact, this is associated with an increased stress response.

    Stress and the brain

    In the brain, chronic high cortisol can shrink the hippocampus. This can impair a person’s memory and their capacity to think and concentrate.

    Chronic high cortisol also reduces activity in the prefrontal cortex but increases activity in the amygdala.

    The prefrontal cortex is responsible for higher-order control of our thoughts, behaviours and emotions, and is goal-directed and rational. The amygdala is involved in reflexive and emotional responses. Higher amygdala activity and lower prefrontal cortex activity explains why we are less rational and more emotional and reactive when we are stressed.

    There are five types of activities that can help our brains complete the stress cycle. https://www.youtube.com/embed/eD1wliuHxHI?wmode=transparent&start=0 It can help to understand how the brain encounters stress.

    1. Exercise – its own complete stress cycle

    When we exercise we get a short-term spike in cortisol, followed by a healthy reduction in cortisol and adrenaline.

    Exercise also increases endorphins and serotonin, which improve mood. Endorphins cause an elated feeling often called “runner’s high” and have anti-inflammatory effects.

    When you exercise, there is more blood flow to the brain and higher activity in the prefrontal cortex. This is why you can often think more clearly after a walk or run. Exercise can be a helpful way to relieve feelings of stress.

    Exercise can also increase the volume of the hippocampus. This is linked to better short-term and long-term memory processing, as well as reduced stress, depression and anxiety.

    2. Cognitive activities – reduce negative thinking

    Overly negative thinking can trigger or extend the stress response. In our 2019 research, we found the relationship between stress and cortisol was stronger in people with more negative thinking.

    Higher amygdala activity and less rational thinking when you are stressed can lead to distorted thinking such as focusing on negatives and rigid “black-and-white” thinking.

    Activities to reduce negative thinking and promote a more realistic view can reduce the stress response. In clinical settings this is usually called cognitive behaviour therapy.

    At home, this could be journalling or writing down worries. This engages the logical and rational parts of our brain and helps us think more realistically. Finding evidence to challenge negative thoughts (“I’ve prepared well for the exam, so I can do my best”) can help to complete the stress cycle.

    Young person draws in notebook
    Journalling could help process stressful events and complete the stress cycle. Shutterstock/Fellers Photography

    3. Getting creative – a pathway out of ‘flight or fight’

    Creative activities can be art, craft, gardening, cooking or other activities such as doing a puzzle, juggling, music, theatre, dancing or simply being absorbed in enjoyable work.

    Such pursuits increase prefrontal cortex activity and promote flow and focus.

    Flow is a state of full engagement in an activity you enjoy. It lowers high-stress levels of noradrenaline, the brain’s adrenaline. When you are focussed like this, the brain only processes information relevant to the task and ignores non-relevant information, including stresses.

    4. Getting social and releasing feel-good hormones

    Talking with someone else, physical affection with a person or pet and laughing can all increase oxytocin. This is a chemical messenger in the brain that increases social bonding and makes us feel connected and safe.

    Laughing is also a social activity that activates parts of the limbic system – the part of the brain involved in emotional and behavioural responses. This increases endorphins and serotonin and improves our mood.

    5. Self-soothing

    Breathing exercises and meditation stimulate the parasympathetic nervous system (which calms down our stress responses so we can “reset”) via the vagus nerves, and reduce cortisol.

    A good cry can help too by releasing stress energy and increasing oxytocin and endorphins.

    Emotional tears also remove cortisol and the hormone prolactin from the body. Our prior research showed cortisol and prolactin were associated with depression, anxiety and hostility.

    man jogs outside
    Getting moving can help with stress and its effects on the brain. Shutterstock/Jaromir Chalabala

    Action beats distraction

    Whether it’s watching a funny or sad movie, exercising, journalling, gardening or doing a puzzle, there is science behind why you should complete the stress cycle.

    Doing at least one positive activity every day can also reduce our baseline stress level and is beneficial for good mental health and wellbeing.

    Importantly, chronic stress and burnout can also indicate the need for change, such as in our workplaces. However, not all stressful circumstances can be easily changed. Remember help is always available.

    If you have concerns about your stress or health, please talk to a doctor.

    If this article has raised issues for you, or if you’re concerned about someone you know, call Lifeline on 13 11 14 or Kids Helpline on 1800 55 1800.

    Theresa Larkin, Associate professor of Medical Sciences, University of Wollongong and Susan J. Thomas, Associate professor in Mental Health and Behavioural Science, University of Wollongong

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

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  • ‘I keep away from people’ – combined vision and hearing loss is isolating more and more older Australians

    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 ageing population brings a growing crisis: people over 65 are at greater risk of dual sensory impairment (also known as “deafblindness” or combined vision and hearing loss).

    Some 66% of people over 60 have hearing loss and 33% of older Australians have low vision. Estimates suggest more than a quarter of Australians over 80 are living with dual sensory impairment.

    Combined vision and hearing loss describes any degree of sight and hearing loss, so neither sense can compensate for the other. Dual sensory impairment can occur at any point in life but is increasingly common as people get older.

    The experience can make older people feel isolated and unable to participate in important conversations, including about their health.

    bricolage/Shutterstock

    Causes and conditions

    Conditions related to hearing and vision impairment often increase as we age – but many of these changes are subtle.

    Hearing loss can start as early as our 50s and often accompany other age-related visual changes, such as age-related macular degeneration.

    Other age-related conditions are frequently prioritised by patients, doctors or carers, such as diabetes or heart disease. Vision and hearing changes can be easy to overlook or accept as a normal aspect of ageing. As an older person we interviewed for our research told us

    I don’t see too good or hear too well. It’s just part of old age.

    An invisible disability

    Dual sensory impairment has a significant and negative impact in all aspects of a person’s life. It reduces access to information, mobility and orientation, impacts social activities and communication, making it difficult for older adults to manage.

    It is underdiagnosed, underrecognised and sometimes misattributed (for example, to cognitive impairment or decline). However, there is also growing evidence of links between dementia and dual sensory loss. If left untreated or without appropriate support, dual sensory impairment diminishes the capacity of older people to live independently, feel happy and be safe.

    A dearth of specific resources to educate and support older Australians with their dual sensory impairment means when older people do raise the issue, their GP or health professional may not understand its significance or where to refer them. One older person told us:

    There’s another thing too about the GP, the sort of mentality ‘well what do you expect? You’re 95.’ Hearing and vision loss in old age is not seen as a disability, it’s seen as something else.

    Isolated yet more dependent on others

    Global trends show a worrying conundrum. Older people with dual sensory impairment become more socially isolated, which impacts their mental health and wellbeing. At the same time they can become increasingly dependent on other people to help them navigate and manage day-to-day activities with limited sight and hearing.

    One aspect of this is how effectively they can comprehend and communicate in a health-care setting. Recent research shows doctors and nurses in hospitals aren’t making themselves understood to most of their patients with dual sensory impairment. Good communication in the health context is about more than just “knowing what is going on”, researchers note. It facilitates:

    • shorter hospital stays
    • fewer re-admissions
    • reduced emergency room visits
    • better treatment adherence and medical follow up
    • less unnecessary diagnostic testing
    • improved health-care outcomes.

    ‘Too hard’

    Globally, there is a better understanding of how important it is to maintain active social lives as people age. But this is difficult for older adults with dual sensory loss. One person told us

    I don’t particularly want to mix with people. Too hard, because they can’t understand. I can no longer now walk into that room, see nothing, find my seat and not recognise [or hear] people.

    Again, these experiences increase reliance on family. But caring in this context is tough and largely hidden. Family members describe being the “eyes and ears” for their loved one. It’s a 24/7 role which can bring frustration, social isolation and depression for carers too. One spouse told us:

    He doesn’t talk anymore much, because he doesn’t know whether [people are] talking to him, unless they use his name, he’s unaware they’re speaking to him, so he might ignore people and so on. And in the end, I noticed people weren’t even bothering him to talk, so now I refuse to go. Because I don’t think it’s fair.

    older woman looks down at table while carer looks on
    Dual sensory loss can be isolating for older people and carers. Synthex/Shutterstock

    So, what can we do?

    Dual sensory impairment is a growing problem with potentially devastating impacts.

    It should be considered a unique and distinct disability in all relevant protections and policies. This includes the right to dedicated diagnosis and support, accessibility provisions and specialised skill development for health and social professionals and carers.

    We need to develop resources to help people with dual sensory impairment and their families and carers understand the condition, what it means and how everyone can be supported. This could include communication adaptation, such as social haptics (communicating using touch) and specialised support for older adults to navigate health care.

    Increasing awareness and understanding of dual sensory impairment will also help those impacted with everyday engagement with the world around them – rather than the isolation many feel now.

    Moira Dunsmore, Senior Lecturer, Sydney Nursing School, Faculty of Medicine and Health, University of Sydney, University of Sydney; Annmaree Watharow, Lived Experience Research Fellow, Centre for Disability Research and Policy, University of Sydney, and Emily Kecman, Postdoctoral research fellow, Department of Linguistics, University of Sydney

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

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