An Accessible New Development Against Alzheimer’s

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Dopamine vs Alzheimer’s

One of the key hallmarks of Alzheimer’s disease is the formation of hardened beta-amyloid plaques around neurons. The beta-amyloid peptides themselves are supposed to be in the brain, but the hardened pieces of them that form the plaques are not.

While the full nature of the relationship between those plaques and Alzheimer’s disease is not known for sure (there are likely other factors involved, and “the amyloid hypothesis” is at this stage nominally just that, a hypothesis), one thing that has been observed is that increasing or reducing the plaques increases or reduces (respectively) Alzheimer’s symptoms such as memory loss.

Neprilysin

There is an enzyme, neprilysin, that can break down those plaques.

Neprilysin is made naturally in the brain, and/but we cannot take it as a supplement or medication, because it’s too big to pass through the blood-brain barrier.

A team of researchers led by Dr. Takaomi Saido genetically manipulated mice to produce more neprilysin, and those mice resultantly experienced fewer beta-amyloid plaques and better memory in their old age.

However wonderful for the mice (and a great proof of principle) the above approach is not useful as a treatment for humans whose genomes weren’t modified at our conception in a lab.

Since (as mentioned before) we also can’t take it as a medication/supplement, that leaves one remaining option: find a way to make our already-existing brains produce more of it.

The team’s previous research allowed them to narrow this down to “there is probably a hormone made in the hypothalamus that modulates this”, so they began experimenting with making the mice produce more hormones there.

The DREADD switch

DREADDs, or Designer Receptors Exclusively Activated by Designer Drugs, were the next tool in the toolbox. The scientists attached these designer receptors to dopamine-producing neurons in the mice, so that they could be activated by the appropriate designer drugs—basically, allowing for a “make more dopamine” button, without having to literally wire up the brains with electrodes. The “button” gets triggered instead by a chemical trigger, the designer drug. You can read more about them here:

DREADDs for Neuroscientists: A Primer

The result was positive; when the mice made more dopamine, the result was that they also made more neprilysin. So far, the hypothesis is that the presence of dopamine upregulates the production of neprilysin. In other words, the increased neprilysin levels were caused by the increased dopamine levels (the alternatives would have been: they were both caused by the same thing—in this case that’d be the DREADD activation—or the increase was caused by something else entirely that hadn’t been controlled for).

As to how the causal relationship was determined…

“But I don’t have (or want) a DREADD switch in my head”

Happily for us (and probably happily for the mice too, because dopamine causes feelings of happiness), the experiments continued.

This time, instead of using the DREADD system, they tried simply supplementing the mouse food with l-dopa, a dopamine precursor. L-dopa is often used in the treatment of Parkinson’s disease, because the molecules are small enough to pass through the blood-brain barrier, and can be converted to full dopamine inside the brain itself. So, taking l-dopa normally raises dopamine levels.

The results? The mice who were given l-dopa enjoyed:

  • higher dopamine levels
  • higher neprilysin levels
  • lower beta-amyloid plaque levels
  • better memory in tests

The next step for the researchers is to investigate how exactly dopamine regulates neprilysin in the brain, but for now, the relationship between l-dopa consumption and the reduction of Alzheimer’s symptoms seems clear.

You can read about the study here:

The dopaminergic system promotes neprilysin-mediated degradation of amyloid-β in the brain

Is there a catch?

L-dopa has common side effects that are not pleasant; the list begins with nausea and vomiting, and continues with things that one might expect from having “too much of a good thing” when it comes to dopamine, such as dyskinesia (extra movements) and hallucinations.

You can read about it more here at the Parkinson’s Foundation:

Parkinson’s Foundation | Levodopa

However! All is not lost. Rather than reaching for the heavy guns by taking l-dopa unnecessarily, there are other dopamine precursors that don’t have those side effects (and are consequently less restricted, to the point they can be purchased as supplements, or indeed, enjoyed where they occur naturally in some foods).

Top of the list of such safe* and readily-available dopamine precursors is…

N-Acetyl L-Tyrosine (NALT): The Dopamine Precursor & More

If you’d like to try that, here’s an example product on Amazon… Or you could eat fish, white beans, tofu, natto, or pumpkin seeds 😉

*Quick note on safety: “safe” is a relative term and may vary from person to person. Please speak with your own doctor to be sure, check with your pharmacist in case of any meds interactions, and be especially careful taking anything that increases dopamine levels if you have bipolar disorder or are otherwise prone to psychosis of any kind. For most people, this shouldn’t be an issue as our brains have a built-in mechanism for scrubbing excess dopamine and ensuring we don’t end up with too much, but for some people whose dopamine regulation is not so good in that regard, it can cause problems. So again, speak with your doctor to be sure, because we are not doctors, let alone your doctor.

Lastly…

If you’d like an entirely drug-free approach, that’s skipping even the “nutraceuticals”, you might enjoy:

Short On Dopamine? Science Has The Answer

Take care!

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  • How To Stay Lean All Year (3 Rules To Live By)

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    It’s common for weight (and specifically: adiposity, i.e. how much fat we carry) to fluctuate throughout the year. This is reasonable; we are, after all, mammals—and so will naturally tend towards putting on a few pounds for the winter, if food is available to do so.

    However, as we’re no longer living with the seasonal food scarcity of tens of thousands of years ago and earlier, it’s nowadays all too easy to put on significantly more weight for winter, and then it’s either a) an arduous challenge to lose it in spring, or b) it gets set as our new base weight, to which we will now add even more weight in the following winter, and repeat each year.

    So… Is there a third option? Cori Lefkowitz, of “Redefining Strength” and “Strong at every age”, shows how to keep the weight off for as long as you want:

    In for the long run

    With the caveat that this is for maintenance (and not any initial fat loss you might want to do first) her three principles are as follows:

    1. Sustainability evolves: true change doesn’t feel sustainable at first—because it isn’t yet, in the sense of being self-sustaining, at least. Habit takes 3–4 months, lifestyle 16–18 months, and identity 3–4 years to form. Over time, habits become as automatic as brushing your teeth—you just have to get there!
    2. Adaptability remains critical: one strategy won’t work forever; your lifestyle should evolve with seasons and circumstances. Doing less perfectly is infinitely better than doing nothing when you can’t do it all. Build a strong foundation (like tracking food or regular workouts), then adjust the smaller details (such as macros and specific exercises) as needed.
    3. Mindset matters most: no perfect macro or workout exists—your mindset is what makes the single biggest difference. Generally speaking, people are held back more by unrealistic expectations, guilt, and self-sabotage than by a lack of tools or knowledge. Progress isn’t about avoiding setbacks completely (though by all means, do try to avoid them); what’s most important if and when they do occur, however, is recovering from them quickly.

    PS: you might not want to be as lean as Cori! That’s fine. This very healthy writer usually has a body fat percentage around 21% or a little under, which is a) the level I prefer to maintain; I consider it optimal for me personally, and b) rather more than we see Cori with here. So all this to say, while the above method is presented as a way to stay lean all year, it’s up to you to define what body composition you want to “lock in” and then maintain.

    For more on all of this, enjoy:

    Click Here If The Embedded Video Doesn’t Load Automatically!

    Want to learn more?

    You might also like:

    Is A Visible Six-Pack Obtainable Regardless Of Genetic Predisposition?

    Take care!

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  • Children can be more vulnerable in the heat. Here’s how to protect them this summer

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    Extreme heat is increasingly common in Australia and around the world and besides making us uncomfortable, it can harm our health. For example, exposure to extreme heat can exacerbate existing medical conditions, or cause problems such as heat stroke.

    Due to a combination of physiology and behaviour, children are potentially more vulnerable to severe heat-related illness such as heat stroke or heat exhaustion.

    But these are not the only heat-related health issues children might experience on a very hot day. In a new study, we looked at emergency department (ED) visits and unplanned hospital admissions among children in New South Wales on heatwave days.

    We found a significant increase in children attending hospital compared to milder days – with a range of health issues.

    maxim ibragimov/Shutterstock

    Why are children more vulnerable in the heat?

    Sweating is the main way we lose heat from our bodies and cool down.

    Children have a greater skin surface area to body mass ratio, which can be an advantage for sweating – they can lose more heat through evaporation for a given body mass. But this also means children can lose fluids and electrolytes faster through sweating, theoretically making them more susceptible to dehydration.

    Meanwhile, younger children, particularly babies, can’t sweat as much as older children and adults. This means they can’t cool down as effectively.

    Children in general also tend to engage in more outdoor physical activity, which might see them more exposed to very hot temperatures.

    Further, children may be less in-tune to the signals their body is giving them that they’re overheating, such as excessive sweating or red skin. So they might not stop and cool down when they need to. Young children especially may not recognise the early signs of heat stress or be able to express discomfort.

    A boy drinking from a drink bottle, appears hot and bothered.
    Children may not easily be able to communicate that they’re hot and bothered. christinarosepix/Shutterstock

    Our study

    We wanted to examine children’s exposure to extreme heat stress and the associated risks to their health.

    We measured extreme heat as “heatwave days”, at least two consecutive days with a daily maximum temperature above the 95th percentile for the relevant area on a universal thermal climate index. This ranged from 27°C to 45°C depending on the area.

    We assessed health outcomes by looking at ED visits and unplanned hospital admissions among children aged 0–18 years from NSW between 2000 and 2020. This totalled around 8.2 million ED visits and 1.4 million hospital admissions.

    We found hospital admissions for heat-related illness were 104% more likely on heatwave days compared to non-heatwave days, and ED visits were 78% more likely. Heat-related illness includes a spectrum of disorders from minor conditions such as dehydration to life-threatening conditions such as heat stroke.

    But heat-related illness wasn’t the only condition that increased on heatwave days. There was also an increase in childhood infections, particularly infectious enteritis possibly related to food poisoning (up 6% for ED visits and 17% for hospital admissions), ear infections (up 30% for ED visits and 3% for hospital admissions), and skin and soft tissue infections (up 6% for ED visits and 4% for hospital admissions).

    A boy standing in front of a sprinkler.
    Kids can be more vulnerable in the heat because of their behaviour and physiology. K-FK/Shutterstock

    We know many infectious diseases are highly seasonal. Some, like the flu, peak in winter. But heat and humidity increase the risk of certain infections caused by bacterial, viral and fungal pathogens.

    For example, warmer weather and higher humidity can increase the survival of bacteria, such as Salmonella, on foods, which increases the risk of food poisoning.

    Hot weather can also increase the risk of ear infections. Children may be at greater risk during hot weather because they often swim or play at the beach or pool. Water can stay in the ear after swimming and a moist environment in the ear canal can cause growth of pathogens leading to ear infections.

    Which children are most vulnerable?

    During heatwaves, we found infants aged under one were at increased risk of ED visits and hospital admission for any reason compared to older children. This is not surprising, because babies can’t regulate their body temperature effectively and are reliant on their caregivers to keep them cool.

    Our study also found children from the most disadvantaged areas were more vulnerable to heat-related illness on heatwave days. Although we don’t know exactly why, we hypothesised families from poorer areas might have limited access to air-conditioning and could be more likely to live in hotter neighbourhoods.

    Keeping kids cool: tips for parents

    The highest levels of heat exposure on hot days for young children is usually when they’re taken outside in prams and strollers. To protect their children from direct sunlight, parents often instinctively cover their stroller with a cloth such as a muslin.

    However, a recent study from our group showed this actually increases temperatures inside a stroller to as much as 3–4˚C higher than outside.

    But if the cloth is wet with water, and a small fan is used to circulate the air close to the child, stroller temperatures can be 4–5˚C lower than outside. Wetting the cloth every 15–20 minutes (for example, with a spray bottle) maintains the cooling effect.

    When young children are not in a stroller, and for older children, there are a few things to consider to keep them cool and safe.

    Remember temperatures reported on weather forecasts are measured in the shade, and temperatures in the sun can be up to 15˚C higher. So sticking to the shade as much as possible is important.

    Exercise generates heat inside the body, so activities should be shortened, or rescheduled to cooler times of the day.

    Sunscreen and hats are important when outdoors, but neither are especially effective for keeping cool. Spraying water on the child’s skin – not just the face but arms, legs and even the torso if possible – can help. Wetting their hats is another idea.

    Proper hydration on hot days is also essential. Regular water breaks, including offering water before, during and after activity, is important. Offering foods with high water content such as watermelon and orange can help with hydration too.

    Wen-Qiang He, Research Fellow in Biostatistics and Epidemiology, Faculty of Medicine and Health, University of Sydney; James Smallcombe, Post-doctoral Research Associate, Faculty of Medicine and Health, University of Sydney; Natasha Nassar, Professor of Paediatric and Perinatal Epidemiology and Chair in Translational Childhood Medicine, University of Sydney, and Ollie Jay, Professor of Heat & Health; Director of Heat & Health Research Incubator; Director of Thermal Ergonomics Laboratory, University of Sydney

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

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  • Asparagus vs Bamboo – Which is Healthier?

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    Our Verdict

    When comparing asparagus to bamboo, we picked the asparagus.

    Why?

    Both are great! But asparagus does distinguish itself on nutritional density.

    In terms of macros, bamboo starts strong with more protein and fiber, but it’s not a huge amount more; the margins of difference are quite small.

    In the category of vitamins, asparagus wins easily with more of vitamins A, B2, B3, B5, B9, C, E, and K. In contrast, bamboo boasts only more vitamin B6. A clear win for asparagus.

    The minerals line-up is closer; asparagus has more calcium, iron, magnesium, and selenium, while bamboo shoots have more manganese, phosphorus, potassium, and zinc. That’s a 4:4 tie, but asparagus’s margins of difference are larger, and if we need a further tiebreaker, bamboo also contains more sodium, which most people in the industrialized world could do with less of rather than more. So, a small win for asparagus.

    In other considerations, asparagus is much higher in polyphenols, especially quercetin, and thus wins this round too.

    Adding up the sections shows clearly that bamboo shoots, but asparagus scores, and wins the day. As ever, do enjoy either or both, of course, but if making a pick, then asparagus has more bang-for-buck nutritionally.

    Want to learn more?

    You might like to read:

    Don’t Be Bamboozled By Bamboo! ← including how to eat bamboo, for those unfamiliar with such, as we have been asked about it 🙂

    Take care!

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  • Herring vs Sardines – Which is Healthier?

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    Our Verdict

    When comparing herring to sardine, we picked the sardines.

    Why?

    In terms of macros, they are about equal in protein and fat, but herring has about 2x the saturated fat and about 2x the cholesterol. So, sardines win this category easily.

    When it comes to vitamins, herring has more of vitamins B1, B2, B6, B9, and B12, while sardines have more of vitamins B3, E, and K. That’s a 5:3 win for herring, although it’s worth mentioning that the margins of difference are mostly not huge, except for that sardines have 26x the vitamin K content. Still, by the overall numbers, this one’s a win for herring.

    In the category of minerals, herring is not richer in any minerals*, while sardines are richer in calcium, copper, iron, manganese, phosphorus, and selenium, meaning a clear win for sardines.

    *unless we want to consider mercury to be a mineral, in which case, let’s mention that on average, herring is 6x higher in mercury. However, we consider that also a win for sardines.

    All in all, sardines are better for the heart (much lower in cholesterol), bones (much higher in calcium), and brain (much lower in mercury).

    Want to learn more?

    You might like to read:

    Farmed Fish vs Wild Caught: Antibiotics, Mercury, & More

    Take care!

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  • How To Engage Your Whole Brain

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    The Stroke Of Insight That Nobody Wants

    This is Dr. Jill Bolte Taylor. She’s a neuroanatomist, who, at the age of 37 (when she was a post-doctoral fellow at Harvard Medical School), had what she refers to as her “stroke of insight”.

    That is to say, she had a massive stroke, and after a major brain surgery to remove a clot the size of a golf ball, she spent the next 8 years re-learning to do everything.

    Whereas previously she’d been busy mapping the brain to determine how cells communicate with each other, now she was busy mapping whether socks or shoes should go on first. Needless to say, she got an insight into neuroplasticity that few people would hope for.

    What does she want us to know?

    Dr. Taylor (now once again a successful scientist, lecturer, and author) advocates for “whole brain living”, which involves not taking parts of our brain for granted.

    About those parts…

    Dr. Taylor wants us to pay attention to all the parts regardless of size, ranging from the two hemispheres, all the way down to the billions of brain cells, and yet even further, to the “trillions of molecular geniuses”—because each brain cell is itself reliant on countless molecules of the many neurochemicals that make up our brain.

    For a quick refresher on some of the key players in that latter category, see our Neurotransmitter Cheatsheet 😎

    When it comes to the hemispheres, there has historically been a popular belief that these re divided into:

    • The right brain: emotional, imaginative, creative, fluid feeling
    • The left brain: intellectual, analytical, calculating, crystal thinking

    …which is not true, anatomically speaking, because there are cells on both sides doing their part of both of these broad categories of brain processes.

    However, Dr. Taylor found, while one hemisphere of her brain was much more damaged than the other, that nevertheless she could recover some functions more quickly than others, which, once she was able to resume her career, inspired her model of four distinct ways of cogitating that can be switched-between and played with or against each other:

    Meet The Four Characters Inside Your Brain

    Why this matters

    As she was re-learning everything, the way forward was not quick or easy, and she also didn’t know where she was going, because for obvious reasons, she couldn’t remember, much less plan.

    Looking backwards after her eventual full recovery, she noted a lot of things that she needed during that recovery, some of which she got and some of which she didn’t.

    Most notably for her, she needed the right kind of support that would allow all four of the above “characters” as she puts it, to thrive and grow. And, when we say “grow” here we mean that literally, because of growing new brain cells to replace the lost ones (as well as the simple ongoing process of slowly replacing brain cells).

    For more on growing new brain cells, by the way, see:

    How To Grow New Brain Cells (At Any Age)

    In order to achieve this in all of the required brain areas (i.e., and all of the required brain functions), she also wants us to know… drumroll please

    When to STFU

    Specifically, the ability to silence parts of our brain that while useful in general, aren’t necessarily being useful right now. Since it’s very difficult to actively achieve a negative when it comes to brain-stuff (don’t think of an elephant), this means scheduling time for other parts of our brain to be louder. And that includes:

    • scheduling time to feel (emotionally)
    • scheduling time to feel (gut feelings)
    • scheduling time to feel (kinesthetically)

    …amongst others.

    Note: those three are presented in that order, from least basic to most basic. And why? Because, clever beings that we are, we typically start from a position that’s not remotely basic, such as “overthinking”, for example. So, there’s a wind-down through thinking just the right amount, thinking through simpler concepts, feeling, noticing one’s feelings, noticing noticing one’s feelings, all the way down to what, kinesthetically, are we actually physically feeling.

    ❝It is interesting to note that although our limbic system fucntions throughout our lifetime, it does not mature. As a result, when our emotional “buttons” are pushed, we retain the ability to react to incoming stimulation as though we were a two-year-old, even when we are adults.❞

    ~ Dr. Jill Taylor

    Of course, sometimes the above is not useful, which is why the ability to switch between brain modes is a very important and useful skill to develop.

    And how do we do that? By practising. Which is something that it’s necessary to take up consciously, and pursue consistently. When children are at school, there are (hopefully, ideally) curricula set out to ensure they engage and train all parts of their brain. As adults, this does not tend to get the same amount of focus.

    “Children’s brains are still developing”—indeed, and so are adult brains:

    The Brain As A Work-In-Progress

    Dr. Taylor had the uncommon experience of having to, in many ways, neurologically speaking, redo childhood. And having had a second run at it, she developed an appreciation of the process that most of us didn’t necessarily get when doing childhood just the once.

    In other words: take the time to feel stuff; take the time to quiet down your chatty mind, take the time engage your senses, and take it seriously! Really notice, as though for the first time, what the texture of your carpet is like. Really notice, as though for the first time, what it feels like to swallow some water. Really notice, as though for the first time, what it feels like to experience joy—or sadness, or comfort, or anger, or peace. Exercise your imagination. Make some art (it doesn’t have to win awards; it just has to light up your brain!). Make music (again, it’s about wiring your brain in your body, not about outdoing Mozart in composition and/or performance). Make changes! Make your brain work in the ways it’s not in the habit of doing.

    If you need a little help switching off parts of your brain that are being too active, so that you can better exercise other parts of your brain that might otherwise have been neglected, you might want to try:

    The Off-Button For Your Brain

    Enjoy!

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  • Soybeans vs White Beans – Which is Healthier?

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    Our Verdict

    When comparing soybeans to white beans, we picked the soy.

    Why?

    Both are great! But…

    In terms of macros, soy has 2x the protein while white beans have 3x the carbs, and they’re equal on fiber. We’ll prioritize the protein over the carbs, and call this round a win for soybeans.

    In the category of vitamins, soy has more of vitamins B1, B2, B3, B6, C, K, and choline, while white beans have more of vitamins B5, B7, B9, and E, adding up to a 7:4 win for soy.

    Looking at minerals, soybeans have more calcium, copper, iron, magnesium, manganese, phosphorus, and selenium, while white beans have more potassium and zinc; thus, a 7:2 win for soy.

    Adding up the sections makes for a clear overall win for soy, but by all means enjoy either or both, as diversity is good (unless you have a soy allergy, in which case, don’t do that)!

    Want to learn more?

    You might like:

    Why You Can’t Skimp On Amino Acids

    Enjoy!

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