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Hey everyone, it's Mikki here. You're listening to Mini Mikkipedia on a Monday. I want to chat about when supplements don't do what you think they should do. And everyone talks about certain supplements to be so helpful for things like sleep, for strength and recovery, improving inflammation and a whole host of other things, including ones that I recommend, but they don't always have the intended effects.

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And it's not necessarily that they don't work at all, but there are certain reasons why, for example, magnesium, which is the first one I talk about, isn't having that calming sedative effect on sleep that you expect it to do because it is always recommended as being a sleep supplement. And actually, let's go right there to magnesium. So magnesium is involved in 300 different enzymatic processes.

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in the body. And it is one of the first supplements to be recommended if you're having trouble falling asleep. And not just magnesium per se, but magnesium glycinate, often recommended, and magnesium threonate for the specific reason that these potentially or do cross the blood-brain barrier. So they're going to actively work on the neurotransmitters and help support either falling asleep or staying asleep. Here's the thing though, magnesium threonate has developed

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a reputation both as a sleep game changer and something that can feel oddly stimulating. The first reason is that magnesium 3N8 is not a sedative. It doesn't work like melatonin or even magnesium citrate, which is taken for muscle relaxation. Magnesium 3N8 is specifically designed to raise magnesium levels inside neurons in the brain. And that matters because magnesium plays a critical role in regulating NMDA receptors,

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glutamate activity and overall neural excitability. In people whose sleep problem is driven by a busy brain, racing thoughts, rumination, light-fragmented sleep, frequent waking, magnesium-3-nate can dramatically improve sleep quality, not by knocking them out, but by reducing this background neural noise. The brain can become quieter, sleep becomes deeper, and waking is more stable. That's why some people describe it as the first time their brain shuts up at night.

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However, that same brain active effect explains why others find it stimulating. If someone already has elevated nighttime cortisol, is under-fuelled, training hard, or living in a chronic stress state, increasing neuronal efficiency can initially feel like increasing alertness rather than calm. The supplement isn't creating stimulation, it's removing this inefficiency. And if the nervous system is already running hot, that clarity can feel activating.

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So this is why timing in the dose matters so much. Magnesium threonate often works best when started at a low dose, taken earlier in the day initially, used consistently rather than a one-off sleep aid. Many people who find it stimulating at first will move it to the afternoon for a week or two, then gradually shift it back towards evening once the nervous system adapts. When that happens, the sleep benefits often emerge clearly. So the key distinction here is that magnesium threonate

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improve sleep architecture, not sedation. So it's a powerful tool for the right person, especially those with brain-driven sleep disruption, but it's not universally calming the way marketing often suggests. So if your problem is a loud brain, magnesium-3 and 8 can be transformative. If your problem is stress hormones, under recovery or under eating, it may initially feel stimulating, and that's quite useful information. So you just have a different path.

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to actually get the benefits from the threonate. I see the same though for magnesium glycinate. Magnesium glycinate is the most commonly recommended calming for magnesium and I recommend it all the time, but it can feel surprisingly stimulating for some, particularly when taken at night. And the key here is glycine. Again, another sleep supplement. It's often described as a calming amino acid glycine and it is partly true. In the spinal cord,

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Glycine is inhibitory and supports muscle relaxation. That's why magnesium glycinate can help with physical tension, restlessness, and the feeling of not being able to settle in the body. But in the brain, glycine has a second role. It acts as a co-agonist at the NMDA receptor, meaning it helps activate a receptor involved in learning, memory, and alertness. For some nervous systems, particularly those already prone to cognitive hyperarousal, that extra glycine can

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increase mental activity rather than quiet it. This is why magnesium glycinate can help some people fall asleep faster while others experience racing thoughts, vivid dreams, early awakening, or a feeling of being tired but mentally switched on. It's because the glycinate is interacting with a nervous system that doesn't need more NMDA support. Magnesium glycinate also tends to unmask what's already there. So in people who are under-fuelled,

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who might be low carb, lower carb than ideal, who may be training hard or running on elevated cortisol, glycine can act as a metabolic signal that nudges alertness rather than relaxation. Dose and timing matter here as well. Magnesium glycinate is more likely to feel stimulating when taken in higher doses, taken late in the evening, or combined with other amino acids like

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more glycine or glutamate. So for people who don't tolerate it well at night, moving to an earlier in the day or lowering the dose often resolves the issues. But others simply do better with a different form of magnesium altogether, such as magnesium citrate or magnesium malate. So the important takeaway is that magnesium glycinate is better at relaxing the body than quieting the brain. So it makes it a great option for people whose sleep issue is physical restlessness or muscle tension.

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But again, like threonate, those with a noisy overactive mind, it can sometimes make things worse rather than better. So what about supplements beyond magnesium? Malatonin is another one. It can be even more unpredictable. So, malatonin is a hormone, as you know. It is released by the pineal gland in response to darkness. Supplementing it should help with sleep onset, shift work, jet lag, and for some people it absolutely does.

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It's actually quite effective for circadian rhythm disorders. But in practice, the responses can be all over the map. Some people take 0.5 milligrams and sleep wonderfully. Others take 10 milligrams and nothing happens. And actually, some people can sleep worse on melatonin. Vivid disturbing dreams, morning grogginess that lasts for hours, feeling hungover. And some people develop tolerance really quickly where it works for a few weeks, then it stops working. The dose-response relationship.

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can seem a bit out of whack actually. We have this more as better mentality with supplements, but with melatonin, research suggests that lower doses, 0.3 to 1 milligrams, might actually be more effective than the mega doses you can buy at the pharmacy. And we actually don't see these low doses at the pharmacy. Those 10 milligram tablets may be creating these supraphysiological levels that could be disrupting your natural melatonin production or receptor sensitivity.

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There's also an issue with timing. Malatonin isn't a sleeping pill, it's a darkness signal. Taking it right before bed might not be optimal. Some people do better taking it two to three hours before they decide bedtime to properly shift their circadian rhythm. And, malatonin can interact with sex hormones, immune function, and blood sugar regulation. For some women, particularly in perimenopause, malatonin supplementation may be problematic from those viewpoints. So, it's a supplement that is

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obviously safe, evidence-based, widely recommended, but can be pretty over the map with regards to whether it will be helping you, whether it will do nothing, or whether it will even make things worse. And the last supplement I think it's worth chatting about, or group of supplements, is probiotics. There is a lot of marketing hype that taking a probiotic will improve your gut health regardless, boost immunity, enhance mood, and fix digestive issues.

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The reality is, well, all of these things can be true. It's actually can be far more complicated than that. And don't get me wrong, clearly, think gut health is super important and there are some very good probiotics and very good reasons for taking probiotics out there. There are a number of factors whereby you can take probiotics and actually end up worse off than when you started. The first issue may be that strain specificity. Different bacterial strains have different effects.

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Lactobacillus rhamnosus GG does different things than Bifidobacterium longum, which does different things to Saccharomyces borlades. A general gut health probiotic with 15 different strains and billions of colony forming units isn't really targeted to anything specific. It's a shotgun approach that might hit something useful or it might not. Second issue is the transient colonization.

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Most probiotic bacteria don't permanently colonize your gut, as you know. They pass through, potentially having beneficial effects while they're there, but they may not last once you stop taking the supplement if you don't work at seeding the bacteria when they're there, i.e. prebiotics. The third issue is individual microbiome variation. Your baseline gut microbiome is unique to you. What you might need might be completely different from what someone else needs. uh

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probiotic that helps someone with one pattern of dysbiosis might do nothing or make things worse for someone with a different pattern. And the delivery and viability. Are bacteria actually alive when they reach your gut? Do they need to be alive when they reach your gut to modulate their immune system? Are they surviving stomach acid? Is the dose sufficient? Is the strain what the label says it is? All of these questions just, I guess, pose a number of different challenges. If you're looking at probiotics to

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effectively understand what you need and what you don't. My advice around probiotics for gut related issues is to work with a practitioner who understands gut health, such as a naturopath, to help figure out what you need rather than just spending a lot of money on products that may not be beneficial for you. Because you may need probiotics, you may need a particular type of probiotic to resolve a particular challenge.

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You might need prebiotics to help support the environment of your gut, or you may need nothing like that. And you may need some other gut related support. You may need some testing to understand better what it is you truly need. So there's just so many issues there that cannot be resolved just by going to the pharmacy to grabbing and grabbing a probiotic. Again, I do think probiotics are great, but you've got to know what you're working with. And the last supplement I just want to address is creatine. I love creatine.

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As you know, but what I'm seeing, and it's not a lot of this in the research, is that creatine can genuinely be problematic for a subset of people, particularly perimenopausal women and women who might already have symptoms in their luteal phase. And the symptoms I hear about, worsening bloating, significantly heavier and more tender breasts, and sleep disruption are enhanced when creatine is on board. Whilst the research might not be there around this, uh

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does make mechanistic sense. Creating increases intracellular water retention. That is in part how it works, pulling water into the muscle cells, which contributes to strength and performance benefits. But for some with stable hormones, the water retention is a non-issue. It's intracellular. It's not bloat. But if you're already dealing with luteal phase fluid shifts, that second half of your cycle where progesterone should be high, but it might not be, oh

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Estrogen can be relatively dominant when your body is already retaining more fluid and in creatine's water retention on top is amplifying in an already comfortable situation. Same thing in perimenopause. When you have these fluctuating estrogen levels that are three times higher than they otherwise would be, with fluid retention and breast tenderness already common complaints, creatine can be like throwing fuel on that fire. And then sleep disruption is super interesting because it

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can point to creatine's effects on brain energy metabolism. Creatine isn't a stimulant, there's no caffeine in it obviously, but it's increasing ATB availability in the brain. It's enhancing cellular energy production. And it has been studied for its effects on helping keep us alert in times of sleep deprivation, which of course for most people this is great, better cognitive function, mental clarity,

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possibly even better mood effects. But if you're struggling with tired but wired, that's already a common thing in perimenopause when you're exhausted but you can't settle down to sleep. Enhanced brain energy availability might be pushing you further in the wrong direction. And in your luteal phase, when progesterone should be promoting a calming gap or activity but might not be doing its job effectively, having your brain running on high octane fuel from creatine

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be interfering with sleep onset or sleep quality. But I will say, while the mechanism makes sense, the research isn't there. We have research on benefits for muscle mass preservation, potentially bone density alongside resistance training, cognitive function, mood support, but not here with cognition. So in my practice, when I see these patterns, I typically suggest one or two things. For women who struggle with their luteal phase, with

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these symptoms, I tell them to pull creatine out for two weeks or four. Creatine works through the saturation of muscle cells. So you won't fully deplete those cells within two weeks or 10 days. It'll just take gradually longer to saturate the cells, but it's worth trying to see where this eliminates the symptoms entirely. Similarly with perimenopausal woman, if your cycles all over the place, I do actually just say, take it out.

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because the reality is creatine is a cherry on top of the other foundations of health. It is not the be all and end all. So you're not losing everything if you can't take creatine. So, you know, this is just a perfect example where there's an evidence base for a supplement that has real benefits for most people, but can be counterproductive for some. As is the case, obviously, with magnesium and melatonin and probiotics.

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where there is that population level evidence, but there's that individual response that we need to account for. And we have to remember that randomized controlled trials, where there are beneficial effects in a study population, may not be indicative of your individual response, because that study population has inclusion and exclusion criteria, has specific characteristics. It controls for other variables, and often they put the average response as

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the overall finding rather than looking at those individual responses, which is what you are. So that means that these responses don't always translate because when we go out into the real world, we've got real people with their individual variability, their complex health histories, their hormone fluctuations, genetic differences, and existing supplement regimes. So what does this mean? It means a few things. One.

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We need to understand that evidence-based doesn't mean universally effective. It means that it has been shown to work in certain populations under certain conditions. It's a starting point, not a guarantee. Two, we need to pay attention to individual response. Just because a supplement should work doesn't mean it's working for you. Track your symptoms. Be honest about whether you're seeing benefits. Be willing to pull the plug if something isn't helping or making things worse. Three, consider the context.

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your whole hormonal status, your life stage, your existing health conditions, your other supplements and medications, all of these things matter. A supplement that's perfect for one person at one life stage might be problematic for the same person at a different life stage. Four, be willing to troubleshoot. Sometimes it's not that a supplement doesn't work, it's that the dose is wrong, the timing is wrong, the form is wrong, or it needs to be combined with other interventions to be effective. And five,

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Don't keep taking supplements just because you're quote unquote supposed to. I see this all the time. And of course I recommend it myself, people taking something because experts say these are their non-negotiable compulsories, even though they're not necessarily seeing any actual benefits. So I do say take magnesium, take fish oil, take creatine, but always know that there's always caveats around that. Are you getting the benefit you're supposed to be getting? And if not,

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should you reconsider. So the bottom line is that the evidence matters, research matters, mechanisms matter, but they never override your individual experience and response. And that is the art of applied nutrition, taking the science and translating that into individualized recommendations that account for all the messy, complicated variables that are pretty much just living life in the real world. So that's it from me. Let me know your thoughts. I'm at

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Instagram threads and X @mikkiwilliden, Facebook @mikkiwillidenNutrition, or head on to my website, mikkiwilliden.com and sign up to the Mondays Matter wait list because things are happening in the next couple of weeks there to get you off into a really great start for 2026. Pretty much no supplements required. All right, team, you have the best week. See you later.