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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  • What Omega-3 Fatty Acids Really Do For Us

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    What Omega-3 Fatty Acids Really Do For Us

    Shockingly, we’ve not previously covered this in a main feature here at 10almonds… Mostly we tend to focus on less well-known supplements. However, in this case, the supplement may be well known, while some of its benefits, we suspect, may come as a surprise.

    So…

    What is it?

    In this case, it’s more of a “what are they?”, because omega-3 fatty acids come in multiple forms, most notably:

    • Alpha-linoleic acid (ALA)
    • Eicosapentaenoic acid (EPA)
    • Docosahexanoic acid (DHA)

    ALA is most readily found in certain seeds and nuts (chia seeds and walnuts are top contenders), while EPA and DHA are most readily found in certain fish (hence “cod liver oil” being a commonly available supplement, though actually cod aren’t even the best source—salmon and mackerel are better; cod is just cheaper to overfish, making it the cheaper supplement to manufacture).

    Which of the three is best, or do we need them all?

    There are two ways of looking at this:

    • ALA is sufficient alone, because it is a precursor to EPA and DHA, meaning that the body will take ALA and convert it into EPA and DHA as required
    • EPA and DHA are superior because they’re already in the forms the body will use, which makes them more efficient

    As with most things in health, diversity is good, so you really can’t go wrong by getting some from each source.

    Unless you have an allergy to fish or nuts, in which case, definitely avoid those!

    What do omega-3 fatty acids do for us, according to actual research?

    Against inflammation

    Most people know it’s good for joints, as this is perhaps what it’s most marketed for. Indeed, it’s good against inflammation of the joints (and elsewhere), and autoimmune diseases in general. So this means it is indeed good against common forms of arthritis, amongst others:

    Read: Omega-3 fatty acids in inflammation and autoimmune disease

    Against menstrual pain

    Linked to the above-referenced anti-inflammatory effects, omega-3s were also found to be better than ibuprofen for the treatment of severe menstrual pain:

    Don’t take our word for it: Comparison of the effect of fish oil and ibuprofen on treatment of severe pain in primary dysmenorrhea

    Against cognitive decline

    This one’s a heavy-hitter. It’s perhaps to be expected of something so good against inflammation (bearing in mind that, for example, a large part of Alzheimer’s is effectively a form of inflammation of the brain); as this one’s so important and such a clear benefit, here are three particularly illustrative studies:

    Against heart disease

    The title says it all in this one:

    A meta-analysis shows that docosahexaenoic acid from algal oil reduces serum triglycerides and increases HDL-cholesterol and LDL-cholesterol in persons without coronary heart disease

    But what about in patients who do have heart disease?

    Mozaffarian and Wu did a huge meta-review of available evidence, and found that in fact, of all the studied heart-related effects, reducing mortality rate in cases of cardiovascular disease was the single most well-evidenced benefit:

    Read more: Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events

    How much should we take?

    There’s quite a bit of science on this, and—which is unusual for something so well-studied—not a lot of consensus.

    However, to summarize the position of the academy of nutrition and dietetics on dietary fatty acids for healthy adults, they recommend a minimum of 250–500 mg combined EPA and DHA each day for healthy adults. This can be obtained from about 8 ounces (230g) of fatty fish per week, for example.

    If going for ALA, on the other hand, the recommendation becomes 1.1g/day for women or 1.6g/day for men.

    Want to know how to get more from your diet?

    Here’s a well-sourced article about different high-density dietary sources:

    12 Foods That Are Very High in Omega-3

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  • Spinach vs Kale – Which is Healthier?

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    Our Verdict

    When comparing spinach to kale, we picked the spinach.

    Why?

    In terms of macros, spinach and kale are very similar. They are mostly water wrapped in fiber, with very small amounts of carbohydrates and protein and trace amounts of fat.

    Spinach has a lot more vitamins and minerals—a wider variety, and in most cases, more of them.

    Kale is notably higher in vitamin C, though. Everything else, spinach is higher or close to equal.

    Spinach is especially notably a lot higher in B vitamins, as well as iron, calcium, magnesium, and zinc.

    One downside to spinach, though, which is that it’s high in oxalates, which can increase the risk of kidney stones. If your kidneys are in good health and you eat spinach in moderation, this is not a problem for most people—but if your kidneys aren’t in good health (or you are, for whatever reason, consuming Popeye levels of spinach), you might consider switching to kale.

    While spinach swept the board in most categories, kale remains a very good option too, and a diet diverse in many kinds of plants is usually best.

    Want to learn more?

    Spinach and kale are very both good sources of carotenoids; check out:

    Brain food? The Eyes Have It!

    Enjoy!

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  • Natto vs Tempeh – Which is Healthier?

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    Our Verdict

    When comparing nattō to tempeh, we picked the nattō.

    Why?

    Both are great, but in the battle of fermented soybeans vs fermented soybeans with extra steps, it turns out that the simplest option is the best, even if tempeh was a close runner-up:

    In terms of macros, nattō has more carbs and fiber for the same protein and fat; we’ll call this category a tie or a marginal win for nattō.

    In the category of vitamins, nattō has more of vitamins B1, C, E, K, and choline, while tempeh has more of vitamins B2, B3, B6, and B9. A clearer, yet still modest, win for nattō.

    Minerals, however, are what really set them apart: nattō has more calcium, copper, iron, magnesium, manganese, potassium, selenium, and zinc, while tempeh has more phosphorus. An overwhelming win for nattō this time.

    In short: enjoy either or both, but nattō is the more nutritionally dense option!

    Want to learn more?

    You might like:

    21% Stronger Bones in a Year at 62? Yes, It’s Possible (No Calcium Supplements Needed!) ← nattō is featured as part of the diet 😎

    Enjoy!

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  • Stand Up For Your Health (Or Don’t)

    10almonds is reader-supported. We may, at no cost to you, receive a portion of sales if you purchase a product through a link in this article.

    You may have heard the phrase “sitting is the new smoking”, and while the jury’s out on whether that’s accurate or not in terms of exactly how damaging it is, one thing that is universally agreed-upon is that sitting is indeed very bad.

    It’s especially bad for your spine (because of being folded in ways it shouldn’t be), your muscles and associated nerves of the lower back and hip area, your abdominal organs (because of being compressed in ways they shouldn’t be), and your heart (because of arteries and veins being squashed up in ways they shouldn’t be), and if you remember how “what’s good for your heart is good for your brain”, the inverse is true, and what’s bad for your heart is also bad for your brain, which won’t get nourished with oxygen and nutrients and which won’t have its detritus removed as efficiently as it should; that’ll be left to build up in the brain instead.

    First, elephant in the room: not everybody can stand, and of those who can, not everybody can stand for long. So obviously, work within what’s attainable for you.

    Also note that while sitting is the disease-bringer/worsener, standing isn’t the only solution, for example:

    • Walking is better than standing. You may be wondering: “who can’t stand but can walk?” and the answer is, a lot of people with certain kinds of chronic pain, for whom walking is less chronic-pain-exacerbating than standing, because the human body is built for movement and inactivity can worsen things even more than movement.
    • Lying down is better than sitting. One of the major problems with sitting is that your organs are all bunched up in ways they shouldn’t be. Lying down is, in this regard, closer to standing than sitting, because your body has a nice straight line to it.
    • Sitting can be made less bad! For example:
      • Sitting in a recliner chair in the reclined position is… Not great, if you’re then tilting your skull forwards to compensate, but if you’re just sitting back and relaxing, this is a lot better than sitting in the usual seated position, because again, it’s closer to lying down, which is closer to standing.
      • Sitting in seiza (the traditional Japanese kneeling position) is, provided you do it correctly and with good posture, better than sitting in the traditional Western manner. The reason for this is simple: instead of having your torso and legs at 90°, they are at 120°ish, give or take the size of your thighs and butt (bigger being better in this regard), and even that angle can be made even better if you use a meditation bench like this one ← we’re eyeballing it and didn’t get out a protractor, but if you look at the model’s torso and thighs, that’s about 135° difference, which is huge improvement over the 90° you get while sitting Western-style.

    For most of us a lot of the time though, we can stand to sit less. Think about the places you most often sit, and what can be done to reasonably minimize those, for example:

    • Car: minimize driving (or being a passenger in a car); walk where reasonably possible. Public transport, if available, may have standing options.
    • Office: a standing desk is, of course, the way to go. You can even use a standing desk converter, like this one. Just make sure to set it at the correct height, both in terms of where the keyboard and mouse go (the same height as your elbows are when your arms are dropped to your sides), and where the monitor goes (center of the monitor should be at eye-level).
      • Note: laptops will never be right for this, unless the natural resting distance between your elbows and your eyes is about 4½ inches, which will only be the case if your total height is approximately 1 foot and 2 inches. For anyone taller than that, laptops are still great to have when on the move and as a backup, but not great for ergonomics.
      • Workaround: if for some reason you must use a laptop for your day-to-day work, consider using a bluetooth keyboard so that you can still set them the appropriate height-distance apart and thus not have to hunch over them.
    • Dining room: sitting to eat a main meal is reasonable, but consider standing options for lighter bites; a standing-height “brunch bar” is great if you can arrange one.
    • Lounge: let it live up to its name, and actually lounge: if you’re not going to stand, then horizontal lounging is an improvement over sitting—as is sitting on the floor, and changing your position frequently. Who knew, kids had it right in that regard!
      • Note: if, like this writer, you do a lot of reading, the same applies regardless of which room you’re doing it in.
    • Bedroom: a culprit for many will be sitting while doing a beauty routine and/or possibly make-up. Easily avoided if you set a well-lit mirror at the correct height to use while standing.
      • Note: at the correct height though! While hunching up over a wall-mounted mirror is an improvement over hunching up at a seated vanity, it’s not a great improvement. You want to be able to stand with good posture and do it comfortably.
    • Bathroom: leave your phone outside—which is also a good approach for avoiding hemorrhoids! See also: Half Of Americans Over 50 Have Hemorrhoids, But They Can Be Prevented!

    Want to know more?

    We reviewed this book recently, which goes into all of the above in much more detail than we have room for here, plus also discusses a lot of social reframes that can be used (since a lot of sitting is a matter of social expectations, not actual need). It’s a very useful read:

    Death by Sitting: The Hidden Health Risks of a Sedentary Life and How to Stand Up for Your Well-Being – by Carolyne Thompson

    Take care!

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  • Can We Do Fat Redistribution?

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    The famous answer: no

    The truthful answer: yes, and we are doing it all the time whether we want to or not, so we might as well know what things affect our fat distribution in various body parts.

    There’s a kernel of truth in the “no”, though, and where that comes from is that we cannot exclusively put fat on in a certain area only, and nor can we do “spot reduction”, i.e., intentionally lose fat from only one place.

    How, then, do we do fat redistribution?

    Your body is a living organism, not a statue

    It’s easy to think “I’ve been carrying this fat in this place for 20 years”, but during that time the fat has been replaced several times and moved often; in fact, the cells containing the fat have even been replaced. Because: fat can seem like a substance that’s alien to your body because it doesn’t respond like muscles, isn’t controllable like muscles, doesn’t have the same sensibility as muscles, etc. But, every bit of fat stored in your body is stored inside a fat cell; it’s not one big unit of fat; it’s lots of tiny ones.

    In reality, any given bit of fat on your body has probably been there for 18–24 months at most:

    Fat turnover in obese slower than average

    …and there are assorted factors that can modify the rate at which our body deals with fat storage:

    Human white adipose tissue: A highly dynamic metabolic organ

    So, how do I get rid of this tummy?

    There are plenty of stories of people who try to lose weight from one part of their body, and lose it from somewhere else instead. Say, a person wants to lose weight from her hips, and with careful diet and exercise, she loses weight—by dropping a couple of bra cup sizes while keeping the hips.

    So, we must figure out: why is fat stored in certain places? And the main driving factors are:

    • hormones
    • metabolic health
    • stress

    Hormones affect fat distribution insofar as estrogen and progesterone will favor the hips, thighs, butt, breasts, and testosterone will favor a more central (but still subcutaneous, not visceral) distribution. Additionally, estrogen and progesterone will favor a higher body fat percentage, while testosterone will favor a lower one.

    This is particularly relevant later in life, when suddenly the hormone(s) you’ve been relying on to keep your shape, are now declining, meaning your shape does too. This goes for everyone regardless of sex.

    See:

    Metabolic health affects fat distribution insofar as poor metabolic health will result in more fat being stored in the viscera, rather than in the usual subcutaneous places. This is a serious health risk.

    See: Visceral Belly Fat & How To Lose It

    Stress affects fat distribution insofar as chronically elevated cortisol levels see more fat sent to the stomach, face, and neck. This fat redistribution isn’t dangerous itself, but it can be indicative of the chronic stress, which does pose more of a general threat to health.

    See: Lower Your Cortisol! (Here’s Why & How)

    What this means in practical terms

    Assuming that you would like the fat distribution that says “this is a healthy woman” or “this is a healthy man”, respectively, then you might want to:

    • Check your sex hormone levels and get them adjusted if appropriate
    • Improve your overall metabolic health—without necessarily trying to lose weight, just, take care of your blood sugars for example, and they will take care of you in terms of fat storage.
    • Manage your stress (which includes any stress you are experiencing about your body not being how you’d like it to be).

    If you are doing these things, and you don’t have any major untreated medical abnormalities that affect these things, then your fat will go to the places generally considered healthiest.

    Can we speed it up?

    Yes, we can! Firstly, we can speed up our overall metabolism:

    Let’s Burn! Metabolic Tweaks And Hacks

    Secondly, we can encourage our body to “move” fat by intentionally “yo-yoing”, something usually considered bad in dieting when people just want to lose weight and instead are going up and down, but: if you lose weight healthily, it comes off everywhere evenly, and if you gain weight healthily, it goes mostly to the places where it should be.

    So, a sequence of lose-gain-lose-gain might look like “lose a bit from everywhere, put it back in the good place, lose a bit more from everywhere, put it back in the good place”, etc.

    So, you might want to gently cycle these a few months apart, for example:

    How To Lose Fat (Healthily!) | How To Gain Fat (Healthily!)

    You can also cheat a little, if it suits your purpose! By this we mean: if you’d like a little extra where you already have a little fat, then you can put muscle on underneath it, it will pad it up, and (because of the layer of actual fat on top) nobody will know the difference unless you flex it with their hand on it.

    Let’s put it this way: people doing squats for a bubble-butt aren’t doing it to put on fat; they’re putting muscle on under the fat they have.

    So, check out: How To Gain Muscle (Healthily!)

    And finally, for all your body-sculpting needs, we present these excellent books:

    Women’s Strength Training Anatomy Workouts – by Frédéric Delavier

    Strength Training Anatomy (For Men) – by Frédéric Delavier

    Enjoy!

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  • 10 Oft-Ignored Symptoms Of Diabetes

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    Due in part to its prevalence and manageability, diabetes is often viewed as more of an inconvenience than an existential threat. While very few people in countries with decent healthcare die of diabetes directly (such as by diabetic ketoacidosis, which is very unpleasant, and happens disproportionately in the US where insulin is sold with a 500%–3000% markup in price compared to other countries), many more die of complications arising from comorbidities, and as for what comorbidities come with diabetes, well, it increases your risk for almost everything.

    So, while for most people diabetes is by no means a death sentence, it is something that means you’ll now have to watch out for pretty much everything else too. On which note, Dr. Siobhan Deshauer is here with things to be aware of:

    More than your waistline

    Some of these are early symptoms (even appearing in the prediabetic stage, so can be considered an early warning for diabetes), some are later risks (it’s unlikely you’ll lose your feet from diabetic neuropathy complications before noticing that you are diabetic), but all and any of them are good reason to speak with your doctor sooner rather than later:

    1. Polyuria: waking up multiple times at night to urinate due to excess glucose spilling into the urine.
    2. Increased thirst: dehydration from frequent urination leads to excessive thirst, creating a cycle.
    3. Acanthosis nigricans: dark, velvety patches on areas like the neck, armpits, or groin, signalling insulin resistance.
    4. Skin tags: multiple skin tags in areas of friction may indicate insulin resistance.
    5. Recurrent Infections: high blood sugar weakens the immune system, making skin infections, UTIs, and yeast infections more common.
    6. Diabetic stiff hand syndrome: stiffness in hands, limited movement, or a “positive prayer sign” caused by sugar binding to skin and tendon proteins.
    7. Frozen shoulder and trigger finger: pain and limited movement in the shoulder or fingers, with a snapping sensation when moving inflamed tendons.
    8. Neuropathy: numbness, tingling, or pain in hands and feet due to nerve and blood vessel damage, often leading to foot deformities like Charcot foot.
    9. Diabetic foot infections: poor sensation, weakened immune response, and slow healing can result in severe infections and potential amputations.
    10. Gastroparesis: damage to stomach nerves causes delayed digestion, leading to bloating, nausea, and erratic blood sugar levels.

    For more on all of these, plus some visuals of the things like what exactly is a “positive prayer sign”, enjoy:

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

    Want to learn more?

    You might also like to read:

    Cost of Insulin by Country 2024 ← after the US, the next most expensive country is Chile, at around 1/5 of the price; the cheapest listed is Turkey, at around 1/33 of the price.

    Take care!

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    Learn to Age Gracefully

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