The Science of Magnesium and Its Role in Aging and Disease | Dr. Rhonda Patrick (2024)

In this solo episode, I'm taking an in-depth look at magnesium – a critical yet frequently underestimated mineral in our health. Magnesium stands tall among vital nutrients for its significant role in multiple aspects of human physiology. During this podcast, we'll delve into the widespread negative health effects caused by low magnesium intake and discuss why increasing your magnesium intake might be key to achieving optimal health.

Here are some of the key takeaways:

• 00:01:05 - Why the effects of magnesium are far-reaching
• 00:03:25 - Why athletes need at least 10-20% more magnesium than the RDA
• 00:07:30 - Why magnesium deficiency & insufficiency are common
• 00:08:56 - How to determine if you're getting enough magnesium
• 00:09:02 - The problem with magnesium blood tests
• 00:11:52 - Magnesium supplements
• 00:14:28 - The effectiveness of epsom salt baths (see also 01:09:19)
• 00:14:55 - Is magnesium threonate better at crossing the blood-brain barrier?
• 00:21:46 - Why magnesium threonate shouldn't count toward your RDA goal
• 00:22:42 - What magnesium supplement do I take?
• 00:23:09 - The effect of stress on magnesium balance
• 00:26:53 - Why the energy demands of workouts affect magnesium balance
• 00:29:34 - Does magnesium supplementation improve sleep?
• 00:30:42 - Why trials in the field of nutrition are often misleading
• 00:34:04 - Does higher magnesium intake improve cognition?
• 00:35:45 - Does magnesium have a role in preventing Alzheimer's disease?
• 00:38:47 - The effect of creatine on the brain (and its relationship to magnesium)
• 00:39:20 - Why magnesium may prevent excitotoxicity in the brain
• 00:40:10 - Magnesium's potential for managing migraines
• 00:43:19 - The role of magnesium in aging
• 00:44:17 - Why magnesium deficiency impairs DNA repair
• 00:45:51 - Magnesium's role in cancer prevention
• 00:47:52 - Why magnesium is intertwined in genomic stability
• 00:50:42 - Why we shouldn't disregard observational data in nutrition
• 00:51:30 - How magnesium intake affects mortality risk and cancer
• 00:54:27 - Magnesium in osteoporosis prevention
• 00:55:59 - Why magnesium intake in early life affects bone accretion
• 00:57:44 - The effect of magnesium on vitamin D metabolism
• 01:03:14 - Does magnesium treat high blood pressure?
• 01:06:50 - Does magnesium help manage muscle cramps?
• 01:09:19 - Is transdermal absorption of magnesium effective?

Active lifestyles increase magnesium needs.

The recommended magnesium intake varies according to age, sex, and life stage – topping out at roughly 320 milligrams for women and 420 milligrams for men. However, for people who engage in regular physical activity, the body's demand for magnesium escalates (as much as 20 percent) due to increased loss through sweat and the stress of physical activity, which depletes magnesium. This elevated requirement underscores the mineral's pivotal role in muscle function, energy metabolism, and maintaining electrolyte balance – essential aspects of athletic performance and recovery.

Dietary factors can impair magnesium absorption.

Unfortunately, many of the foods richest in magnesium contain components that hinder magnesium's absorption, such as the phytates found in plant-based foods like whole grains and legumes. Phytates bind to magnesium in the gut, reducing the mineral's bioavailability. In addition, high doses of supplemental zinc can compete with magnesium for absorption. Understanding these dietary interactions is critical to optimizing magnesium intake through diet and supplementation.

Alcohol consumption depletes magnesium levels.

Drinking alcohol can exacerbate magnesium deficiency by promoting the mineral's excretion in urine. This effect is particularly problematic given the widespread insufficiency in magnesium intake, highlighting the need for people who consume alcohol to consider supplementation to mitigate loss.

Plasma levels aren't necessarily the best way to know how much magnesium you're getting.

Much of the body's magnesium is sequestered in the bones and muscles, so determining whether you're getting enough is tough. Blood tests aren't particularly accurate and are best for identifying severe deficiencies. Tracking dietary intake is the best option, ensuring you eat plenty of leafy greens (like spinach and kale), nuts, and legumes, as well as supplementing to meet needs.

Choose the right magnesium supplement for optimal benefits.

"For optimal bioavailability of magnesium supplements, it’s also generally more effective to take the total daily dose in divided smaller amounts, rather than a single large dose."- Dr. Rhonda Patrick Click To Tweet

When it comes to supplementation, organic magnesium salts like magnesium glycinate and taurate offer superior bioavailability and are generally gentler on the digestive system. These forms are recommended for effective supplementation, contributing significantly to meeting daily magnesium needs. Aiming for smaller, more frequent doses will likely provide the greatest benefits.

Magnesium threonate may not be the best choice for overall needs.

Magnesium threonate has gained attention for its ability to cross the blood-brain barrier, suggesting it provides cognitive benefits. However, the science supporting this idea is still developing. In addition, magnesium threonate's low elemental magnesium content makes it a less desirable choice for fulfilling overall magnesium requirements. Its use should complement, not replace, other more bioavailable magnesium supplements.

Adequate magnesium intake is crucial for brain health and cognitive function.

Magnesium is a coenzyme for many biochemical processes, particularly those related to brain function. Magnesium intake is linked to improved cognitive function and has shown potential in managing migraine symptoms, likely due to its role in regulating neurotransmitters and protecting against neuroinflammation. These associations underscore the importance of adequate magnesium levels for brain health and cognitive function.

Stress depletes magnesium, underscoring its importance in stress management.

Stress – both mental and physical – can lead to a significant decrease in magnesium levels, with stress hormones such as cortisol accelerating the mineral's depletion. This loss highlights magnesium's crucial role in the body's stress response and underscores the importance of increased magnesium intake during stressful periods to maintain physiological balance.

Magnesium holds promise for improving sleep quality – but the data don't support it yet.

Some research suggests that magnesium may improve sleep quality by regulating neurotransmitters involved in the sleep cycle. While promising, the evidence is not yet definitive, and further studies may clarify magnesium's role in sleep enhancement, especially for people with magnesium deficiency.

Magnesium deficiency affects cancer risk.

Magnesium deficiency has high stakes, affecting crucial biological processes like DNA repair, replication, and transcription. When these processes are compromised due to insignificant magnesium, cancer-causing mutations can develop. Magnesium's role in DNA repair and its antioxidant properties suggest a protective effect against age-related diseases, including cancer. This highlights the role of adequate nutrition throughout the lifespan and supports the "micronutrient triage theory" – the idea that the body prioritizes the utilization of micronutrients for metabolic pathways needed for survival and reproduction over those used for long-term health. Ensuring adequate magnesium intake is crucial for minimizing DNA damage and supporting longevity, emphasizing the mineral's importance in healthy aging.

Insufficient magnesium intake leads to the depletion of magnesium stores in the bones.

Magnesium is essential for bone health, influencing bone density and the risk of osteoporosis. It works synergistically with calcium and vitamin D, emphasizing the need for sufficient magnesium levels to support bone health and reduce the risk of bone-related diseases in older adults. Early-life magnesium intake is like an investment in your later-in-life bone health.

Magnesium is cardioprotective, reducing blood pressure and maintaining heart health.

Magnesium contributes significantly to cardiovascular health by regulating blood pressure and supporting heart function. Adequate magnesium intake is associated with a lower risk of hypertension and cardiovascular diseases, reinforcing the mineral's role in maintaining heart health and preventing heart-related conditions.

Achieving optimal health necessitates adequate magnesium intake.

The multifaceted roles of magnesium in health, from supporting muscle and brain function to contributing to bone health and cardiovascular wellness, underscore its vital nature. Ensuring sufficient magnesium intake through a balanced diet and appropriate supplementation is paramount for overall health and longevity.

In this podcast, I cover these and many other magnesium-related topics, including my personal magnesium regimen.

Thanks for watching!

People mentioned:

• Dr. Bruce Ames

Relevant publications:

• Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences - Higher dietary magnesium consumption - about 550 milligrams per day - seemed to correlate with larger grey matter and hippocampal volumes than the average intake of about 350 milligrams per day.
• An evidence-based review of oral magnesium supplementation in the preventive treatment of migraine - Individuals who suffer from migraines are often found to be deficient in magnesium.
• Adrenergic control of plasma magnesium in man - When adrenaline was infused into people, it didn't just temporarily lower magnesium levels; these levels stayed significantly reduced even an hour after stopping the infusion.
• Role of magnesium in genomic stability - Magnesium is essential for the proper functioning of DNA repair enzymes.
• Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality - Men with the highest magnesium levels had a 40% lower all-cause mortality and a 50% decrease in cancer deaths compared to those with the lowest magnesium levels.
• Magnesium intake and incidence of pancreatic cancer: the VITamins and Lifestyle study - Every 100 mg per day decrease in magnesium intake was linked to a 24% increase in pancreatic cancer incidence.
• Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III - High intake of magnesium, whether from diet, supplements, or both, was linked to a lower risk of having low levels of vitamin D.
• Effects of Magnesium Supplementation on Blood Pressure - Magnesium supplementation at an average dose of 368mg/day notably lowers both systolic and diastolic blood pressures.
• Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women - Magnesium-rich diets in pre-adolescence positively affect bone density in young adulthood, particularly in the heel bone.
• Alterations in magnesium and oxidative status during chronic emotional stress - Young adults undergoing persistent or intermittent stress like anticipating military conflict) experienced substantial decreases in their overall and plasma magnesium concentrations over three months.

Episodes & Clips:

• 3 Mechanisms for Magnesium Deficiency
• Best magnesium to supplement (based on current evidence) | Rhonda Patrick
• The Dangers of Magnesium Deficiency (and Rhonda Patrick's preferred dietary & supplement sources)
• Effects of magnesium L-threonate on the brain: animal vs. human evidence | Rhonda Patrick

Other related links:

• The Cognitive Enhancement Blueprint (bdnfprotocols.com) - This guide is your tactical checklist for better brain aging. Expect to learn specific exercise, omega-3, and heat stress protocols for boosting BDNF.

If a person's magnesium intake is adequate, this can enhance the body's ability to maintain healthy levels of vitamin D. On the other hand, if magnesium intake is low, like 45% or half the population, roughly, of the US, that may hinder the body's ability to utilize vitamin D effectively. Even if vitamin D intake is sufficient, I would say a really important takeaway from this section is magnesium threonate is not the best option for meeting daily magnesium needs.

It shouldn't be included as contributing to your recommended daily allowance of magnesium. And that is because magnesium threonate contains a very low amount of elemental magnesium. So if you are considering supplementing with magnesium threonate for its potential brain health benefits, which I would say have not been established, do not count that magnesium dose towards your RDA goal.

Welcome to the Found my fitness podcast. I'm your host Rhonda Patrick. There is a lever you can pull every day to significantly enhance your body's ability to repair damage to your DNA, potentially reducing cancer risk in a dose dependent manner.

This is the power of magnesium, a mineral that plays a foundational role in our health, yet is often overlooked. The stakes of magnesium deficiency are high, affecting crucial biological processes like DNA repair, replication and transcription. When these processes are compromised due to insufficient magnesium, it can lead to development of potentially cancer causing mutations.

More alarmingly, recent studies indicate a potential link between insufficient magnesium levels and accelerated brain volume loss, which could hasten the onset of dementia as we age. I'm here to unpack the science behind magnesium, often termed as the most prevalent micronutrient deficiency, and its profound implications for nearly 45% of the US population who is falling short. Nearly half of the population of the United States doesn't get enough magnesium, primarily because our diets lack sufficient dark, leafy greens, where magnesium is abundantly found, hidden within the chlorophyll that gives plants their vibrant green color.

That means that roughly half of you watching or listening to this episode right now have inadequate magnesium intake. In the landscape of essential nutrients, magnesium is a giant. It's part of a triad of micronutrients that, when deficient, have far reaching impacts on our health.

Let's dive deep into the reasons that make magnesium a key player in maintaining our well being, and how boosting your intake could be a critical step towards optimal health. Magnesium is a cofactor for about 300 different enzymes in our bodies, which are special proteins that perform functions. Magnesium is required for these enzymes to work properly.

So to put that into perspective, our bodies have around 75,000 types of enzymes, so the enzymes that need magnesium make up about 0.4% of all the enzymes in our body. This shows that while magnesium's role is specific, it's crucial for a wide range of bodily functions which we are going to discuss today.

So adult women generally need about 310 to 320 milligrams a day, which increases to about 360 milligrams a day during pregnancy. Adult men require about 400 to 420 milligrams a day, and athletes and those that have high physical activity, including people that are also regular sauna users, may need additionally about 10 to 20% above the recommended dietary allowance due to their greater magnesium loss through urine and sweat.

There's data from nutritional surveys like NHANES revealing that the average intake of magnesium in the US falls below the RDA. So the typical intake for women is around 230 milligrams per day, while men consume about 320 milligrams per day. So this deficit is more pronounced in female athletes who are at a higher risk of magnesium deficiency.

Such deficiency can potentially lead to serious health issues, including arrhythmias like atrial fibrillation, as well as muscle spasms and other complications. What makes the situation worse is that the RDA value is based on the absolute minimum amount necessary in order to prevent severe diseases associated with magnesium deficiency. So even if you're meeting that 300 to 400 milligrams per day threshold, you are still only running at the bare minimum necessary to function.

Magnesium plays a really important role in maintaining healthy electrolyte balance and preventing dehydration. It helps regulate the body's balance of electrolytes, which are pretty important for conducting nerve impulses, contracting muscles, also maintaining a healthy heart rhythm. So when the body is deficient in magnesium, it can disrupt this balance and that can potentially lead to dehydration and other related complications.

So this aspect of magnesium's role is particularly important for athletes and those, again with high physical activity, as they're more susceptible to these electrolyte imbalances due to increased sweat and fluid loss. Good dietary sources of magnesium include dark leafy greens, legumes, nuts, seeds, whole grains, brown rice and fish like mackerel. The net absorption of magnesium in the diet is only about 50%.

It's even lower with high fiber diets. But most of the studies that have found this are studies where they feed people super high amounts of fiber, which most people aren't getting even when they have a high plant-rich diet. So a big reason for poor magnesium biobailability in plant sources is because magnesium is bound to phytate in plants.

And there are ways to increase bioavailability of magnesium from plants and that is by activating phytases. These are enzymes that break down phytate. So for example, if you heat up oats or you cook your leafy greens or legumes, or you germinate or you sprout your grains and seeds, all of these things decrease phytate levels because they activate those enzymes that are called phytases.

So as it turns out, both wheat and yeast also have strong phytase activity during the baking process. So there are ways that again, just heat itself, but also germination and sprouting and heating up oats, cooking leafy greens, these are all ways that we increase magnesium bioavailability from plant sources because of deactivation of the phytases. The other really important factor that can limit the bioavailability of magnesium is excessive supplemental zinc at doses higher than 124 milligrams a day, which is quite high.

That's well above the RDA. And people should not be taking that much zinc on a daily basis because it can also inhibit the absorption of other trace elements, for example copper. There is an exception.

So the exception of people doing a little bit of a mega-, sort of a higher dose of zinc would be during illness or the onset of illness, where higher zinc dose supplementation, like in the order of, for example, 80 milligrams a day, has been shown to lessen respiratory illness symptoms and decrease duration of illness as well. So I would say that taking high, high doses of zinc on a very, very short term basis, where it's just a couple of days, is different than someone who's daily supplementing with a high dose of zinc because it can inhibit magnesium absorption. Diet composition is the main reason magnesium insufficiency and deficiency are so common.

The typical standard American diet is high in calories. It's low in micronutrients, including magnesium. So eating a calorically dense meal full of processed foods, meats, dairy products, these are poor sources of magnesium.

In contrast, green vegetables like dark leafy greens are rich in magnesium because of their chlorophyll content. Magnesium is at the center of a chlorophyll molecule. Another reason is bioavailability, which we just discussed.

Magnesium is only so bioavailable from certain foods like the plant sources. And so ways of increasing their bioavailability, like heating up greens or sprouting and germination like we discussed, also improves magnesium bioavailability. And the last reason that magnesium insufficiency and deficiency are common is because there are certain health conditions and lifestyle choices that can lead to increased magnesium excretion.

So, for example, diabetes leads to this, as well as alcohol consumption. So alcohol can increase the rate at which the body excretes magnesium despite normal absorption rates in the gut because it acts like a diuretic. So it leads to increased urine production and then losses of magnesium through urine. So this diuretic effect contributes to a higher rate of magnesium being filtered out by the kidneys and expelled in urine, rather than being absorbed and used in the body.

I think the logical question is, how do you know if you're getting enough magnesium? Well, naturally, one would think a blood test might help shed some light.

But unfortunately, most of the time it does not. And the reason for this is because magnesium levels are assessed in plasma. And I'm going to take a moment to explain this because I think it's important.

So the average person has slightly less than 1 ounce of magnesium in their body. Roughly 60% of all the magnesium is found in the skeleton. So most of our magnesium is found in our bones.

About 27% is found in the muscle. And six to 7% is found in other cells. Less than 1% is found outside of our cells.

About one-third of the magnesium in the bones is exchangeable. In other words, the bones are serving as a reservoir, so that the body can draw from it in times of need.

So when magnesium levels are low, the body will draw from the bones to get that magnesium. Because it's so, so important. So most of the time, magnesium will be pulled from the bones into plasma to maintain optimal levels.

The body regulates plasma magnesium concentrations within a very narrow range. So typically around 0.7 to one millimolar per liter.

If plasma magnesium levels drop below this range, it could lead to hypomagnesemia, which can cause all sorts of problems: muscle weakness, tremors, seizures, abnormal heart rhythms, and other potentially serious complications.

So our body will just continually pull from our bones. To prevent magnesium levels from going below 0.7 millimole per liter. For this reason, plasma magnesium is not a good indicator of magnesium status for most healthy adults.

Similarly, a red blood cell magnesium test, which measures magnesium inside red blood cells. While it might provide a better indication of magnesium status than plasma levels, it still may not fully represent total body magnesium content. So both tests are more likely to identify, I would say, more severe magnesium deficiency, rather than a mild or moderate deficiency or something that we would call magnesium insufficiency.

So, really, to ensure adequate magnesium intake, the most practical approach is to track and calculate the magnesium content in your diet. This involves being a little more mindful of the magnesium-rich foods you consume, such as green vegetables like leafy greens, nuts, seeds, grains, fish. The USDA's Food Data Central is a good resource for estimating the micronutrient and macronutrient content in various foods.

So that would include magnesium. I personally think it's still a good idea to get a plasma or a red blood cell magnesium test just to rule out severe deficiency, but not to use it as a guide of whether or not you have optimum levels of magnesium or you have sufficient magnesium levels. It's really just to rule out severe deficiency.

So naturally, the next question on people's minds are what about magnesium supplements? Where do they fit in? What if I don't get enough magnesium from dietary sources? Can I supplement? So let's start with supplemental magnesium doses. So how much is too much? The US Institute of Medicine's Food and Nutrition Board has set the upper safe limit for daily supplemental magnesium intake at 350 milligrams per day. So this is the level considered that it's unlikely to cause diarrhea or gastrointestinal issues.

For most people, diarrhea is the first sign of excessive magnesium supplementation. It's often used therapeutically as a laxative, but this is a bit of a conservative dose. It does not include magnesium from dietary sources.

So in other words, there's no evidence that going above the RDA for magnesium is harmful. In fact, some evidence suggests that it may even be beneficial, particularly if the magnesium is mostly coming from dietary sources. For optimal bioavailability of magnesium supplements, it's also generally more effective to take the total daily dose in divided smaller amounts rather than a single large dose.

So this approach allows for more efficient absorption by the body. It can also minimize the potential Gi discomfort. So smaller spaced out doses, they're processed better by the digestive system and this also ensures maximum absorption, utilization of the magnesium. The bioavailability of different magnesium supplements does vary and it's not fully standardized in studies clinical research on organic magnesium salts. So these include magnesium citrate, magnesium glycinate, magnesium taurate. These indicate…magnesium malate is also in there.

These organic salt forms of magnesium are generally more bioavailable and effectively raise plasma magnesium levels compared to inorganic forms of magnesium like magnesium oxide, magnesium chloride, magnesium sulfate. So organic magnesium salts are better absorbed in the digestive tract. It can lead to more significant increase in magnesium levels in the blood and I think for this reason it makes them more effective choices for supplementing magnesium and also, of course, addressing deficiencies.

But just to eliminate any confusion, the term organic in this context refers to the presence of carbon being in the acid molecule. So we're not talking about agricultural standard of being organically grown here. It's a different term.

Magnesium sulfate can be taken orally, and this is an inorganic form, but it's often more commonly used as Epsom salt for transdermal through the skin applications. When it's taken orally, it can act as a laxative and it's used therapeutically as a laxative. The effectiveness of Epsom salt, particularly in baths, is unclear.

We'll talk about this a little bit later because the transdermal absorption of magnesium through Epsom salt baths really hasn't been conclusively proven. But let's talk about another form of magnesium called magnesium threonate. Magnesium threonate is a form of magnesium that has garnered a lot of attention because of its potential impact on brain function.

So generally, only a small portion of the magnesium ingested in a supplement form reaches the brain. And this is due to the intricate active transport systems that control the progression of magnesium from the digestive tract into the bloodstream, and then subsequently from the bloodstream across the blood brain barrier. The body establishes and manages a very tight concentration gradient.

It creates a higher magnesium level in the blood compared to the cerebral spinal fluid, and that allows a very controlled quantity of magnesium that can actually get transported into the brain. This precise regulation is really important to maintaining this equilibrium of magnesium necessary for optimal brain function. So in humans, it's been found that even an increase up to 300% in blood magnesium results in less than 19% change in the cerebrospinal fluid magnesium content.

And I think this really highlights the significant role that physiological processes in maintaining magnesium balance play, which then influence the brain health and function. So some animal evidence suggests that magnesium threonate can easily get across the blood brain barrier and at a human equivalent dose of 8.1 milligrams per kilogram body weight, so that would be around 662 milligrams for 180-pound person, can improve cognition and decrease amyloid-beta plaques.

Now, this is in the brains of mice, and it's thought that the magnesium threonate is uniquely effective in crossing the blood brain barrier due to its specific molecular structure. So this form of magnesium is chelated to thoronic acid, and that is a metabolite of vitamin C. So this chelation enhances its ability to pass through the blood brain barrier, or so it's thought.

The precise mechanism by which magnesium threonate bypasses this tightly regulated concentration gradient between the blood and the brain is not fully understood. It is believed, though, that its molecular structure does somehow facilitate easier entry into the brain, thereby increasing concentration of magnesium in the brain more effectively than other forms of magnesium.

That is solely based on a very small and limited number of animal studies. When we turn to human studies, only a couple have explored the effects of magnesium threonate. So these studies are, I want to point out, industry funded, which does invite us to consider a potential conflict of interest.

So the initial study that I think garnered a lot of attention was published in 2016. It was a small scale study that only had 44 participants total. Those in the treatment group took daily doses of about 1500 to 2000 milligrams of magnesium threonate.

So this is marketed as Magtine and they took it for over twelve weeks. So this was based on their body weight, that's why there's a range in dose.

The findings of this study, I personally think, are underwhelming. So the treatment group only achieved a marginal increase in plasma magnesium levels, with no elevation noted in red blood cell magnesium levels compared to the placebo group. Additionally, there was a significant increase in urinary magnesium, which suggests that most of the supplemented magnesium threonate was actually being excreted through urine.

There were some cognitive tests that were also done. There was no significant difference observed when each of these four different measured cognitive tests were looked at in isolation compared to the placebo group. But if the data was all pooled together, so all four cognitive tests were then pooled together, then there was a statistically significant difference in cognitive function compared to the placebo group.

Obviously this suggests a degree of statistical uncertainty in the study's conclusions, whether or not it was just due to a small sample size – I said there's only 44 people in this study – perhaps if there were 444 people, there would have been more of a stronger signal and the data wouldn't have had to have been pooled together.

Or maybe there really isn't much of an effect. There's no telling.

The second study was also industry funded, which I think is important to keep in mind. This study was published in 2022 and it involved 100 participants and the treatment group was given 400 milligrams of magnesium, threonate, along with vitamins C, D, B-6, and phosphotidal serine. In contrast, the placebo group received only 2 grams of a starch capsule. So despite the absence of any elevation of serum or brain magnesium levels, the treatment group did have improved cognitive test performance compared to the placebo group.

I would say this study raises pretty significant questions around causations, because the treatment group was not just given magnesium threonate, they were given a variety of vitamins. They were given vitamin C, the B vitamins, vitamin D, B-6, but they were also given phosphatidal serine. So I think to be able to establish a solid conclusion that magnesium threonate is responsible for improving cognitive function, the placebo group should have gotten all those other vitamins and the phosphatidal serine, but not the magnesium threonate.

However, that was not the way the study was done. So in my opinion, I think it's an interesting study, but really no conclusions can be stated directly about magnesium threonate itself. So I think a concluding statement with respect to supplemental magnesium, there's a few concluding statements.

One, to enhance bioavailability, it's advisable to take smaller, frequent doses of magnesium supplements. Organic magnesium salts like magnesium glycinate or magnesium taurate are generally more readily absorbed than inorganic forms like magnesium oxide. I also think there's some added benefits of these organic salts.

For example, taking magnesium glycinate also gives you some accompanying compounds like glycine. So glycine could potentially be beneficial, at least according to some studies. Also, magnesium taurate would give you taurine, which also may have some health advantages.

But that's the subject of another podcast. There is some caution that should be taken without not wanting to exceed super high doses of magnesium. So 350 milligrams per day is the safe upper limit.

And that is for either organic or inorganic magnesium supplements. If you go above that, you may get GI side effects. So that's something to keep in mind.

I would say a really important takeaway from this section is magnesium threonate is not the best option for meeting daily magnesium needs as outlined by the RDA. It shouldn't be included as contributing to your recommended daily allowance of magnesium. And that is because magnesium threonate contains a very low amount of elemental magnesium.

So if you are considering supplementing with magnesium threonate for its potential brain health benefits, which I would say have not been established, do not count that magnesium dose towards your RDA goal. So, to ensure you're getting enough magnesium, you need to calculate what you're getting from your foods. But also consider supplementing with other organic magnesium forms like magnesium glycinate, which does have a higher amount of elemental magnesium content.

As you can tell, there are many different forms of magnesium available. A natural question is what do I take? The answer is I hedge my bets. I take a supplement that has many different forms of magnesium salts, which seems logical to me.

There are not many products I have found that offer that. One of them is Magnesi-Om by Moonjuice. The other one I sometimes take at night is magnesium glycinate by Pure Encapsulations.

There are many different brands. I'm not affiliated with either of those, but I know many of you want to know what I take. So there you have it.

The other area I want to kind of dive into, and I find very interesting with respect to where magnesium plays a role in physiology, is the stress response. So the stress response that your body experiences involves the production of hormones – stress hormones like adrenaline, cortisol.

Those stress hormones can potentially lead to a reduction or depletion of magnesium levels in the body. So these hormones are released during times of stress and then subsequently your body uses up more magnesium to try to help manage the stress reactions. So what ends up happening is this can reduce overall amounts of magnesium available for other functions of the body.

So to better understand how stress hormones like adrenaline can lead to magnesium deficiency or lower magnesium levels and its clinical implications, there was a study by White et al that looked at how adrenaline, which is a well known stress hormone, affects our magnesium levels. And what they found, I personally thought was an interesting study. They found when adrenaline was infused into people, it didn't just temporarily lower magnesium levels.

These levels stayed significantly reduced even an hour after stopping the adrenaline infusion without showing any immediate signs of bouncing back. So in other words, the adrenaline immediately lowered magnesium levels and those levels stayed low for quite some time. There have been a range of studies that have found that stress exposure, things that are stressful and are known to increase cortisol, adrenaline, can influence magnesium levels both in blood and urine.

So for example, young adults undergoing persistent or even intermittent stress, like for example anticipating a military conflict, they experienced substantial decreases in their overall and plasma magnesium concentrations over three months. And there were similar results or outcomes found when the impact of short term, so this is a one day and also a long term, which would be like a month of sleep deprivation on magnesium levels was examined. So this was done in healthy men.

And both short term and long term sleep deprivation caused reduction in magnesium red blood cells. So the magnesium levels in red blood cells with the long term sleep deprivation having the most robust impact. Another study found an increase in anxiety levels and a corresponding rise in urinary magnesium excretion in university students during exam time.

So that would indicate if you're excreting more magnesium in your urine, that you are not absorbing it and using it in your body. In another related study, this was done over the course of four weeks. This was post exams.

Researchers found a significant reduction in the concentration of magnesium in red blood cells among college students, yet again sort of solidifying how the stress response will lower magnesium levels. So yet another study confirmed this. This was done in people that were impacted – they were affected by noise exposure. So they had been subjected to noise exposure and their magnesium levels of course went down after the noise exposure and their urinary excretion peaked after a few hours and it continued for up to two days. So it seemed like there was some sort of long term effect with respect to excreting more magnesium through urine, which is something I mentioned that alcohol also does just from that stress response, from the very loud noise exposure.

It's interesting how our body magnesium levels respond not only to mental stress, but also physical stress, like exercise. So acute or short term stress can lead to a brief spike in our blood magnesium levels. This is a phenomenon known as transient hypermagnesemia.

This has been observed in the aftermath of like short, intense exercise sessions lasting around 20 minutes. But after pushing your body hard, it appears it rallies the magnesium resources, probably to aid in the energy production and other vital functions. But when you start to engage in a more prolonged, let's say 1-hour session, that initial elevation in magnesium is not found.

And it seems like there's a threshold after which your body does not respond in that way. And magnesium levels then have been noted to go below what your baseline resting levels are. So exercise does deplete magnesium, but let's talk briefly about why mental and physical stress can decrease magnesium.

So the body's neuroendocrine system responds to stress through a process that many will recognize as the fight or flight response. So this is primarily activated by the adrenal glands. The hormones adrenaline and cortisol rapidly increase during this response.

They're responsible for preparing the body for action. Now, part of this preparation involves the mobilization of magnesium, which is a crucial cofactor for enzymes that drive energy production and utilization in the form of ATP. So during this stress response, the body rapidly pulls magnesium from the cells, causes a temporary surge in serum magnesium levels.

But the catch is this mobilization of magnesium is not an infinite resource. So as the stress continues, it's extracting magnesium and then expelling it through the body through urination, which then gradually depletes our overall body store of magnesium. And then there's the role of cortisol, which is often considered the body's primary stress hormone.

So when cortisol levels rise, it signals to the kidneys that they need to kick into turbo mode and start expelling more magnesium out of the body. This action further reduces our body's total magnesium supply. And then on top of all this, stress also triggers certain hormones that can affect the balancing act of magnesium in our body, especially in organs like the gut, kidneys and the bones.

So these hormones can result in less magnesium getting absorbed in the intestines, more getting expelled from the kidneys, as I just mentioned, leading to this downward spiral in magnesium levels if we don't replenish it properly.

Let's move on to another area that has gained popularity, the role of magnesium in sleep. So the role of magnesium in sleep has recently become a topic of interest.

We know that sleep deprivation can deplete magnesium levels, but does this create a cycle affecting sleep quality? Observational studies have shown that adults with higher dietary magnesium intake often report better sleep quality. However, this could be the healthy user bias, right? People with higher magnesium intake might also have other healthy habits contributing to good sleep. Now, when we look at randomized control trials, the picture gets more complex.

A meta analysis of some trials suggests that magnesium supplementation can improve some sleep metrics, including scores on the Pittsburgh Sleep Quality Index, and also can improve sleep efficiency and duration. Yet the results across different studies are very, very mixed. There's quite a few studies out there showing that magnesium supplementation has no effect on sleep.

So it really highlights the need for more research in this field. I'm not going to say that magnesium supplementation will not improve sleep, but I will say there is not strong evidence that magnesium supplementation will improve sleep. I do think this, I have to go on a little bit of tangent here because randomized controlled trials in this field of nutrition are very different than the gold standard of randomized controlled trials that are used with pharmaceutical drugs.

So we know that 45% of the population has insufficient magnesium intake. Okay? So 55% have sufficient levels of magnesium. So when you're starting a clinical trial in nutrition with something like magnesium, half the population in that trial are going to need that magnesium supplement and the other half really aren't because they've already got sufficient magnesium intake.

This is very different from a drug trial. Everyone at the start of a drug trial has the same amount of drug in their system, which is zero. So you either give the person the drug or a placebo.

And it's very clear that if there is an effect that it's because of the drug and that if there is not an effect, it's because the drug did not have an effect. But in the case of magnesium, if you are not identifying who is deficient or has insufficient magnesium at the start of the trial, then you're not going to know whether or not giving them a supplement really is important or going to make any difference because they might already have sufficient magnesium. So I think this really illustrates why it's so important for nutritional randomized control trials to account and to measure, or at least, at the very least look at dietary intake and magnesium and figure out who at the start of this trial is deficient in this nutrient that we are investigating.

Let's start with that population. Because essentially what you're looking at is giving some, you're trying to avoid deficiency, right? And that's the real important thing here, to avoid deficiency. So with that said, when I say there is a lot of mixed results in these randomized controlled trials with respect to magnesium and sleep, or with respect to magnesium and fill in the blank effect, right.

Whatever outcome we are looking at, I think it is very important for people to keep in mind, particularly people that are doing clinical trials in the medical field that have this mentality that randomized controlled trials are the gold standard because they are coming from this pharmaceutical background. Keep in mind that nutrition is different because we all have different starting levels of nutrients and it is very, very important to measure these nutrients or in some way figure out at the start of the trial if our starting population is low in that nutrient. If they're not, then that's another question that would be is supplementing supra levels going to do anything right? That's a completely different question than avoiding deficiency.

All right, so sorry for that tangent, but I do think it's very important because until we address these trial flaws, these fundamental methodological oversights, we are going to continue to have conflicting data in the field of nutrition. So I think we need to improve study designs. We need to consider individual nutritional baselines and until we do that, we're going to continue facing confusion, uncertainty and a lot of conflicting data with respect to nutritional trials.

Okay, so on that note, let's dive into brain health. There's some pretty recent research that suggests there's a potential association between dietary magnesium intake and brain health. So this was an observational study using data from over 6000 participants.

They were aged 40 to 73. It was UK Biobank data and those who reported a higher magnesium intake had on average, larger brain volumes which could convey up to approximately one year of reduced brain aging compared to those with lower magnesium intakes. So the results revealed that the higher dietary magnesium consumption, this was about 550 milligrams per day, seemed to correlate with larger gray matter in hippocampal volumes than the average intake of about 350 milligrams per day, which is actually closer to the RDA.

This was actually particularly notable in women. I would say this is an intriguing link. Obviously, interpretation of these results have to recognize that these are observational studies, so they really can't provide a cause and effect relationship, only suggest a possible association.

So the data is based on self reported dietary intake. That could be influenced by other overall dietary patterns or other factors like lifestyle habits or health conditions. To really, I would say, conclusively say, state that magnesium is improving brain health by increasing brain volume, particularly gray matter, in the hippocampal regional of the brain. We would need clinical trials to substantiate that potential relationship.

Those probably aren't going to be done, so kind of just have to look at this data and make what you want out of it. Magnesium has been linked to the development and progression of various age related brain disorders. Higher cerebral magnesium levels have been shown to decrease oxidative stress and inflammation and improve synaptic plasticity, also counteract other mechanisms leading to neurodegeneration.

So there was a recent systematic review that revealed individuals with Alzheimer's disease also have significantly lower plasma magnesium levels compared to healthy controls. So researchers looked at a lot of data from different sources, like blood, serum, plasma, the fluid around the brain, the cerebrospinal fluid, which helped them sort of be more confident about their findings. However, when they specifically checked the fluid, the cerebrospinal fluid, it wasn't entirely clear.

So there was a hint that Alzheimer's patients might have lower magnesium in the cerebrospinal fluid, but it wasn't as clear cut as in the plasma in the blood, for example, in serum. In a study that followed over 1000 middle aged adults for 17 years, researchers found that those who ate the most magnesium, so they were getting at least 196 milligrams per day, had a 37% lower chance of getting dementia when they got older compared to those who ate the least magnesium. So they were getting 174 milligrams per day or less.

There was another study in people aged 60 and above who did not have dementia, also showed that eating more magnesium, so this was at least 434 milligrams, might help them from getting mild cognitive impairment, which is the stage before dementia. The numbers from this study suggest that the risk was much lower for those who ate more magnesium. And again, another observational study, this was over 2500 older adults who were mentally healthy, again found higher magnesium intake – this was over 407 milligrams per day – was also linked to overall better brain function. But this benefit was actually only seen in women. So again, all these studies are observational.

They're really only showing associations. They really can't prove that higher magnesium intake directly causes these health benefits. We need more controlled trials, clinical research, to really establish that definitive link.

But we do know that magnesium is a vital coenzyme that plays a crucial role in a variety of biochemical processes in the brain. So it serves as the key factor in a variety of brain-specific enzymes. So adenosine triphosphatases, these are ATPases, they're crucial enzymes that control our ability to hydrolyze ATP, which is the major energy source for all of our cells, very important in the brain.

So magnesium is a cofactor, it's essential for those enzymes to properly function. And this is really important for the sodium potassium ATPase and the calcium ATPase, which help establish this electrochemical gradient across our cellular membranes in our brain. It's essential for neuronal function.

Another enzyme would be involved with creatine. So everyone, you guys have heard of creatine, most people think about it in the context of bodybuilding muscle mass, but it also is important in the brain as well. So creatine passes phosphate groups from phosphocreatine to ADP to make ATP that energy currency.

And so the enzymes that are doing this, again require magnesium to do it. So another reason why magnesium would be important for the brain, it's also important for another enzyme called glutamine synthetase. So this enzyme, it enables the conversion of glutamate into ammonia and glutamine, and magnesium is required for the appropriate function of this enzyme.

And this is really critical because maintaining that glutamate-to-glutamine balance in the brain is important for preventing excitotoxicity. So this could potentially lead to neuronal damage. If you're not maintaining that balance, you might have too much glutamate, which could lead to that excitotoxicity and neurotoxicity.

Right? So too much excitatory activity from glutamate, you could end up with neuronal damage. So magnesium plays, this is just three examples of enzymes in the brain where magnesium plays a critical function and why magnesium is so crucial for brain function. I would say one area with respect to the brain, where the data is a bit stronger, is migraines.

So magnesium might play a role in managing migraines, which is a condition that affects many people worldwide. There's recent randomized controlled trials that have really shed some light on magnesium's potential benefits for those suffering from migraines. So what is happening in the brain during a migraine? One key element is something called cortical spreading depression.

So it's a kind of wave of brain activity that leads to visual and sensory changes we often associate with migraine auras. So, interestingly, magnesium supplementation seems to help prevent these waves. But there's a little more to it.

Magnesium may also decrease the release of certain chemicals in the brain, like substance P and glutamate, which are known to transmit pain signals. So by reducing their release, magnesium could play a role in lessening the pain associated with migraines. Also, it might prevent the further narrowing of brain blood vessels caused by serotonin, another neurotransmitter involved in migraines.

So, as it turns out, individuals who suffer from migraines are often found to be deficient or have insufficient magnesium. Now this might not be entirely surprising when we consider that nearly half the US population doesn't get enough magnesium in their diet. But it does highlight a potential link between widespread nutritional gaps and specific health conditions like migraines.

Understanding these connections can offer us insights, I think, into simple yet impactful ways to improve our health. So there's results of randomized controlled trials that we're going to discuss. There were five randomized controlled trials that indicate that magnesium supplementation can effectively reduce the frequency and intensity of migraine relapses.

So magnesium is believed to work by preventing cortical spreading depression, the brain-signaling waves often responsible for migraine aura we just talked about. And additionally, magnesium reduces the release of those pain transmitting chemicals like substance P and glutamate. The effective magnesium dose for preventing migraines seems to be around 600 milligrams per day, which is almost twice the suggested upper limit.

To minimize gastrointestinal discomfort, I think it's advisable to divide the dose into smaller amounts, such as 200 milligrams taken three times throughout the day. This can really help minimize the irritation on the digestive tract while still providing an effective dose for migraine management. So I mentioned this data comes from five different randomized controlled trials.

I do think that while there's only a few studies, the implications could be significant. Migraines, they're not just headaches, they're really complex neurological events. So understanding how something as accessible as a magnesium supplement, for some people, could mitigate these symptoms, I think is really it offers new hope and a potential new avenue for relief for some people.

So it's a great example of how diving deep into some of the brain science and understanding magnesium's role and looking at some of the clinical studies can kind of help lead to some practical, everyday health benefits.

Let's move on to aging. Magnesium depletion is a slow process, so marginally low intake would likely take years to manifest, but it would still take a toll.

It's likely a factor in aging and the development of chronic disease. So I want to take a moment to discuss a concept that has been a significant focus in the field of nutrition, particularly a theory put forth by my mentor, Dr. Bruce Ames, who has introduced what is known as the triage theory and published several studies on it.

It's really a fascinating way to understand how our bodies deal with micronutrient scarcity, like with magnesium. So Dr. Ames has published several papers on this topic highlighting how nature has possibly evolved a mechanism to prioritize certain biological processes over others when micronutrient resources are limited.

So magnesium, for example, is a key player in numerous biological functions. Some of these are critical for immediate survival and preventing diseases that could lead to acute life-threatening conditions. However, magnesium is also pivotal for long term health processes like DNA repair.

So deficiencies in DNA repair might not cause immediate harm, but they can lead to a gradual accumulation of DNA damage – mutations that over time can then become oncogenic or cancer causing. So the triage theory posits that in the face of limited magnesium, the body will prioritize its use for enzymes involved in essential short term survival, such as enzymes like energy production. This means that other processes that are vital for long term health, like DNA repair, might get less of this magnesium.

What's the end result? Well, we might not be getting enough magnesium. We might be getting enough to avoid acute deficiency, even pulling it from our bones to maintain levels in our muscles and other tissues. We could be setting the stage for chronic health issues like osteoporosis down the line.

So I think this inadequate intake of magnesium and micronutrients in general, can accumulate its insidious damage over time. In the context of magnesium, when DNA repair and replication, which both do require magnesium to properly function, they aren't functioning optimally due to those inadequate levels. The accumulation of this damage can lead to these mutations, cell dysfunction and potentially cancer development.

And it's a clear example of how subtle long term effects of micronutrient inadequacy, or magnesium inadequacy, in this case, can contribute to the aging process and the development of chronic disease. So we're talking about cancer. Let's dive in a little bit more into that topic.

Magnesium does play a crucial role in DNA repair, and this has implications for cancer prevention. So every day, our DNA is facing damage from both internal sources, like metabolism, and external forces, things like UV, radiation, pollution, things like that. As we age, our DNA repair mechanisms naturally slow down, like everything else.

But when we're also low in magnesium, it's kind of like throwing gasoline on a fire. The risk of DNA damage escalates. Magnesium is essential for the proper functioning of DNA repair enzymes.

So consider the sheer frequency of cell division in our bodies. Millions of cells divide daily with some tissues, like our skin and intestinal lining, they have exceptionally high turnover rates.

So DNA replication, which is necessary to make a new cell, is really vital for that process of making a new cell. And magnesium plays a role in DNA replication as well. It's essential for the proper functioning of those enzymes called DNA polymerases.

These are essentially the workhorses of cell division. Without adequate magnesium, these processes can be compromised, and this could lead to potential errors and mutations when you are making new DNA. Now, let's dive a little bit into the role of magnesium in what's called matrix metalloproteinases, or MMPs.

So these are enzymes. They're more like agents of extracellular matrix breakdown. They're involved in critical processes like tissue remodeling, wound healing, and magnesium deficiency can upset the delicate balance here with the activity of these MMP enzymes.

That also could potentially aid in cancer cell invasion and progression. So it plays a little downstream role in cancer progression and cell invasion. But again, I think it really highlights the sort of broader impact of magnesium on cellular health, cancer prevention.

And it's really an important micronutrient that is just fundamentally intertwined with our body's ability to maintain what's called genetic integrity and to prevent the formation of oncogenic cells, which are cancer cells. So let's talk about a study that followed about over 66,000 men and women aged 50 to 76 years old. So this was part of the Vitamins and Lifestyle study, or the VITAL study.

It was from the year 2000 to 2008. Among the 151 participants who ended up developing pancreatic cancer, those with magnesium intake below the RDA had a significantly higher risk of pancreatic cancer, specifically those getting 75% to 99% of the RDA. The risk was increased by 42%.

And for those with less than 75% of the RDA, that risk jumped to 76%. But what was even more striking about that study was that for every 100 milligram per day decrease in magnesium intake, there was an increase – a 24% increase – in pancreatic cancer incidence. So this was in a dose dependent manner.

Every 100 milligram decrease was associated with a 24% increase in pancreatic cancer incidence. And what's particularly interesting here is also the role of magnesium supplementation. So the inverse association between magnesium intake and pancreatic cancer risk seemed to be more pronounced among those who took magnesium supplements, either from a multivitamin or even as an individual supplement.

So in other words, what I'm saying is that within that cohort, it wasn't just dietary intake, it was also supplemental intake and people that were also supplementing with magnesium that was associated with a stronger decreased risk in pancreatic cancer. Obviously, it's important to approach findings with a very nuanced understanding, right? This is still observational data still means correlation; can't really establish causation. There could be a variety of other factors that could influence this as well. So that's always important to keep in mind when we're talking about observational data.

There was another study, this was the Paris Prospective Study 2, which followed about 4000 men aged 30 to 60 over 18 years old. And that study found that men with the highest magnesium levels, that was associated with a 40% lower all cause mortality and a 50% lower decrease in cancer death compared to those with the lowest magnesium levels.

Yet again, all the caveats I just mentioned, this was also an observational study. I think the beauty of observational studies, honestly, is in their ability to reveal these patterns, these associations, in large populations over extended periods. So that is really the beauty of observational data.

And then once you get that observational data, you kind of need to approach it with a little bit more of a critical eye and sort of also try to turn to some interventional studies as well with respect to cancer incidence. That's going to be very challenging because cancer takes decades to develop. So having a randomized control trial with a supplement like magnesium is going to be challenging, if not impossible to do. So that's also something to keep in mind.

But let's dive a little deeper into a meta-analysis that examined both dietary and supplemental magnesium intake and their effects on mortality risks. So dietary magnesium intake was linked to a significantly lower risk of both all cause mortality and cancer mortality.

So specifically, for every additional 100 milligrams per day of dietary magnesium, there was a 6% reduction in all cause mortality and a 5% reduction in cancer mortality. And again, this was in a dose dependent manner. So for each 100 milligram increase per day, you got those reductions.

So I do want to point out that this was from dietary sources and not from supplemental sources. So it really could be that there's just a barrage of things going on because you're talking about getting magnesium from sources of healthy foods. So what I'm trying to say is because foods that are high in magnesium, like leafy greens, they're packed with a plethora of other vital micronutrients and phytonutrients.

So these components collectively contribute to overall health. They're also a part of a food matrix that enhances their benefits. The analysis also looked at supplemental magnesium intake. And here's where things get intriguing. The supplemental magnesium intake showed a non-significant positive association with cancer mortality risk based on three studies. It's important to note that non-significant doesn't mean that there was no effect.

In fact, the p-value that's used to determine significance can actually be quite arbitrary. But that's a whole other tangent. But I do think it highlights the complexity of interpreting data.

Similarly, there was a total magnesium intake which looked at both dietary and supplemental sources, and that really didn't show any significant association with cancer mortality or all cause mortality. But there was a lot of what's called heterogeneity between studies. In other words, some studies did see an effect, other studies saw no effect.

And so again, it comes down to that mixed data, really, those sorts of differences come down to differences in study design, population, other factors that can just add all these layers of complexity to our understanding. I think these findings reinforce the idea that getting magnesium from dietary sources might be the most beneficial approach. They also underscore the nuanced nature of nutritional research.

Right. The variation in these studies, the arbitrary nature of statistical significance, the heterogeneity between studies, they all really point to this careful interpretation, a deeper understanding of how nutrients like magnesium are impacting our health, and again, to how trials in nutrition, and just how complex trials in nutrition are, and the need to sort of standardize some of these trials as well so that we can get better data. I do want to shift gears and talk a little bit about osteoporosis.

So magnesium also plays a role in bone health. We already discussed how roughly 60% of the body's magnesium is stored in the bones. It serves as a reservoir during times when you need magnesium, your body will pull it from your bones to get that source of magnesium.

As a person ages, magnesium losses from the bones increase. And this is partly because the body strives to maintain a very narrow, stable range of magnesium in the plasma. When our dietary intake is insufficient, the body compensates again by pulling magnesium from the bones, which is a reservoir.

I know I'm being repetitive here, but it's important to understand that just like the muscle is a reservoir for amino acids, our body pulls amino acids out of muscle when we need amino acids when we're low on protein, which is not a good thing because then you end up losing muscle mass. Well, the same concept here. Your body is pulling magnesium from your bones.

That's a reservoir for magnesium, but pulling from the bones, especially when you're talking about over a lifetime, right? You're talking about in older adults, this can contribute to a decrease in a very large decrease in bone magnesium content. In fact, over a lifetime, nearly half of the magnesium content of bone is lost in people.

And there's some evidence that suggests that this magnesium loss in the bones over decades contributes to osteoporosis. So adequate magnesium intake early in life, really honestly, is like an investment in your long term bone health, right? Because if you are getting enough magnesium from your diet and supplemental sources, your body's not going to have to pull on the magnesium from your bones to get it what it needs. So studies have shown that magnesium rich diets in pre adolescence positively affect bone density in young adulthood, particularly in the heel bone.

There's been a year long magnesium supplementation study that found that magnesium supplementation for one year can enhance bone mass in the hips of peripubertal girls. And I think this highlights, again, magnesium's crucial role beyond just calcium in building strong bones and preventing osteoporosis. A lot of people think about the role of calcium, also very important for bone health.

But getting enough magnesium early in life is, I think, really important. So I'm not talking about supplementing with magnesium later in life when you already have osteoporosis. I'm talking about preventing your body from pulling that magnesium out of your bones so that you lower your risk of osteoporosis later in life.

So magnesium is important for ensuring stronger bones as you age. And I think, again, think of it as an investment strategy. Earlier in life, you're going to make sure that your body's not going to pull that magnesium from your bones year after year after year after decade after decade, eventually depleting 40% of your body's bones' reservoir of magnesium.

I think on a very similar note, let's get into vitamin D and vitamin D metabolism. Vitamin D also plays a role in bone health, but I think even more important here is the role magnesium plays in vitamin D metabolism. So it's just another layer of connection that magnesium has to our bone health, because we know vitamin D plays a role in bone health as well.

So vitamin D is important for calcium absorption and bone health. Magnesium, by acting as a cofactor for several enzymes that metabolize vitamin D, then helps make sure that we're getting vitamin D and using it effectively. Magnesium directly contributes to bone density because it makes up the bone, right.

But it also plays an important role in bone health indirectly by contributing to vitamin D metabolism, which is a key player in bone health. So this synergy between magnesium and vitamin D metabolism I think is a perfect example of how interconnected our nutrient intake is with overall bodily functions, and how some of these micronutrients are sort of working together and synergizing, and why some trials where you're just giving one micronutrient may not be enough because another one is needed because they work in concert. So let's discuss this a little bit.

High intake of magnesium, whether from the diet or supplements or both, is linked to a lower risk of having low levels of vitamin D. There's also a notable interaction between magnesium and vitamin D intakes that influence the risk of vitamin D deficiency and insufficiency.

So what do I mean? For example, if a person's magnesium intake is adequate, this can enhance the body's ability to maintain healthy levels of vitamin D. On the other hand, if magnesium intake is low, like 45% or half the population, roughly, of the US, that may hinder the body's ability to utilize vitamin D effectively, even if vitamin D intake is sufficient.

So this study found that the benefits of having higher vitamin D levels in reducing the risk of death, especially from cardiovascular disease and colorectal cancer, were more significant in individuals that had above average intake of magnesium. Building on the insights of those observational studies I just mentioned, a randomized controlled trial helped shed further light on how magnesium supplementation influences vitamin D status.

So magnesium is key for enzymes that convert vitamin D-3 into 25-hydroxy vitamin D, which is the main circulating form of vitamin D in our bodies. It's what we typically measure on a vitamin D blood test. So this trial showed that for people with low 25-hydroxy vitamin D levels, which usually can indicate vitamin D deficiency, magnesium supplementation effectively increased these levels. It appears that magnesium is aiding in the conversion of vitamin D-3 into this more stable form of vitamin D, which is 25-hydroxy vitamin D.

So what this tells us is that magnesium's influence on vitamin D status is not a one size fits all. It really varies based on your existing vitamin D levels. It's playing a critical role in either helping stabilize vitamin D in the body, converting that vitamin D-3 into that stable, circulating form, or it's also activating that circulating stabilized form, 25-hydroxy vitamin D, into the active steroid hormone, depending on your individual needs.

I think this study, really, I like this study. It offers a deeper understanding of the intricate relationship between magnesium and vitamin D. They're both crucial micronutrients, although vitamin D actually functions as a steroid hormone in the body.

But it also adds layers of complication to randomized controlled trials using vitamin D. And perhaps there's a negative result where you're getting no effect after giving a vitamin D supplement. Well, if half the US population is not getting enough magnesium, and magnesium is required to make vitamin D function as an active steroid hormone, then you're going to have a problem.

Those trials, they're going to be flawed at the get-go. And again, it highlights the important role of thinking about nutrition differently than pharmaceutical drug trials. We have to think about not only the varying levels and different levels people have of these nutrients at the start of the trial, but how these nutrients are interacting with each other.

And if a deficiency in one is going to affect the function of another, then giving that supplement of the other isn't going to do much if you're still deficient in the important micronutrient that is needed to make that other one properly function. So again, I just want you guys to understand why nutritional trials are so complicated and why there's so much mixed data out there. It's incredibly hard to design the trial properly and to think of all these things and to get enough funding to do them as well.

So, lots of things to keep in mind when it comes to interpreting the results of a trial. Okay, let's shift gears and talk now about blood pressure, hypertension, the role of magnesium in lowering blood pressure. So hypertension or high blood pressure, it's actually a pretty prevalent issue.

So it affects nearly half of US adults, including 20% of young adults age 18 to 39, which, wow, that's kind of important. Twenty percent of young adults aged 18 to 39 have hypertension. It's really crucial for people, those young adults, people in their twenties and thirties to be aware of their blood pressure.

Elevated blood pressure is not only going to increase the risk of cardiovascular diseases, but it also significantly raises the risk of dementia later in life. And what's the most important factor for that is the cumulative exposure to high blood pressure. So the earlier in life you get high blood pressure, the more the risk you have of dementia later in life.

And this is because sustained high blood pressure can lead to damage in the small vessels of the brain, and that impairs cognitive functions and potentially leads to conditions like dementia as a person ages. So monitoring and managing blood pressure from a young age, I think, is really important and can be crucial for mitigating these dementia risk, these cardiovascular disease risk. So where does magnesium come into this? Well, magnesium helps control blood pressure by boosting the production of substances like prostacycline and nitric oxide, which relax blood vessels and improve overall cardiovascular health.

It also aids in the widening of blood vessels, which reduces blood pressure. So vasodilation, it makes it easier for the heart to pump blood. Also, magnesium's ability to fight inflammation and protect against damage to blood vessels also is another way that it can support cardiovascular health.

And I think this shows there's a lot of different ways that magnesium plays a vital role in helping maintain and keep the cardiovascular system healthy.

So there was a comprehensive meta analysis involving 34 different randomized controlled trials. There was over 2000 participants, and researchers discovered that magnesium supplementation at an average dose of 368 milligrams per day notably lowers both systolic and diastolic blood pressures.

This effect, which is slightly influenced by the dose and duration of magnesium, I think does underscore the potential for magnesium to play a role in blood pressure management, perhaps in some people. There are laboratory studies that also back this up that have found magnesium's ability to adjust vascular smooth muscle function. It can reduce vascular resistance, it can combat hypertension, prevent vasoconstriction.

Also, it's been shown to have antioxidant properties in the vascular system. I think all these things help mitigate vascular damage caused by oxidative stress and other factors as well. And I think this latest research, including a comprehensive meta analysis of randomized control trials, really does highlight that magnesium could play a role in help managing blood pressure effectively in some people.

Also, integrating magnesium-rich foods into the diet also is an important way as well. And there's been a lot of studies out there showing things like a DASH diet, which include a lot of foods that are rich in magnesium, is another great way to manage hypertension or high blood pressure as well.

So let's move on to an area that has really, I would say, garnered significant interest, and that is the effect of magnesium supplementation for the prevention and treatment of muscle cramps. This interest really, I think, stems from magnesium's role in muscle function. It's essential for muscle contractions, relaxation.

Deficiencies in magnesium could potentially lead to increased muscle excitability and cramps, making supplementation an area of interest for those with low magnesium levels, or those prone to muscle cramps, such as athletes or elderly individuals, or those with certain medical conditions. However, when we look at the data surrounding magnesium supplementation and its effect on muscle cramps, it's really a mixed bag. Some studies suggest benefits, especially in pregnant women, but the broader picture is a little more complex.

I think this complexity likely stems from the fact that not all studies check if participants were deficient in magnesium or had insufficient magnesium at the start of the trial, as we've already discussed. Also, another layer of complexity is the fact that muscle cramps have a diverse array of causes, so not are all related to magnesium levels. So considering only about half the US population might actually have a low magnesium intake, supplementation would only affect perhaps the half of the population that would not be getting enough magnesium.

And so you might expect that there would be some mixed data with respect to some of these trials. Again, based on those facts, I would say overall the data is not very strong supporting magnesium supplementation and its effects on reducing muscle cramps. But that doesn't mean that it doesn't have any effect.

Again, like I've been really sort of trying to drive home throughout this podcast is that the nutritional trials in nutrition, micronutrients, things like magnesium, are flawed at the get-go. And so in a way, you're almost setting yourself up for failure. And when you actually get a positive result, in my opinion, it's kind of like almost just amazing because of all the hurdles that need to be overcome with respect to designing randomized control trials in nutrition.

The other area that I think with respect to muscle cramps and magnesium that's got a lot of interest is the Epsom salt baths. And we talked a little bit about this earlier in the podcast, and this is where I think we really go into scientifically uncharted waters. There's a debate on whether or not magnesium, so magnesium from Epson salt is in the form of magnesium sulfate, and there's a debate on whether or not the skin can effectively absorb magnesium and sulfates from these kinds of baths to influence muscle and tissue health.

I would say there are some studies that suggest a pathway for magnesium penetration via the sweat glands and hair follicles. They're representing a very small fraction of the skin's overall surface area, so the clinical significance of absorption remains a question. Not to mention that there's never been any indication that Epsom salt – soaking in Epsom salts can actually increase any plasma magnesium levels.

I have not seen that study showing that. I would say there have at least been some studies showing that Epsom salt, particularly Dead Sea salt. So Dead Sea salt is high in magnesium.

It can improve skin barrier function and hydration as well. But with respect to muscle crampings, I would say that there's no real scientific validation that Epsom salts are going to improve muscle cramps.

Nonetheless, I would say that ultimately, if you find relaxation and a sense of well being by taking an Epsom salt bath, as I do, then you should continue to do that, because at the end of the day, that's what's most important.

As we wrap up today's deep dive into the world of magnesium and its myriad of roles in health and disease prevention, I think it's clear that magnesium holds a pivotal place in the intersection of neuroscience, physical health, and longevity. Magnesium's contribution extends far beyond its role in muscle function and bone health. It's touching on crucial aspects of metabolic health, cardiovascular function, and even cognitive processes.

For individuals aiming for longevity and peak performance, I think understanding the subtleties of magnesium's effects, particularly in the context of dietary intake, potential supplementation, is important. The evidence suggests that a tailored approach, recognizing that while some may benefit significantly from increased magnesium, others, particularly those with already sufficient levels, may not see much of an effect or improvement with increased magnesium intake or supplementation. And this really highlights the importance of a sort of personalized, data driven approach to nutrition, one that considers individual health statuses and goals.

So that brings us to the end of today's discussion.

Friends, I really appreciate your tuning in and sharing this deep dive into the fascinating realm of magnesium and its pivotal role in evidence-based nutrition. Thank you for your curiosity and commitment to understanding how this essential mineral influences our health.