The Sardinian Cholesterol Paradox

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Broadly speaking, low-density lipoprotein (LDL), or “bad” cholesterol, is generally considered to be… Well… Bad. Specifically because of how it can functionally narrow arteries, causing bits of floating detritus to get stuck in it, narrow it further, and eventually harden into atherosclerotic plaque, at which point it becomes even harder for the body to clear out.

We wrote about the process here: Demystifying Cholesterol

When it comes to cholesterol, the most common lay understanding (especially under a certain age) is “it’s bad”.

A more informed view (and more common after a certain age) is “LDL cholesterol is bad; HDL cholesterol is good”.

A more nuanced view is “LDL cholesterol is established as significantly associated with (and almost certainly a causal factor of) atherosclerotic cardiovascular disease and related mortality in men; in women it is less strongly associated and may or may not be a causal factor”

We wrote more about that, here: Statins: His & Hers? ← despite most research being on men, statins have very different effects (and side effects) for women, often being relatively less useful, and more dangerous. There are exceptions (for some women’s specific profiles they can still be worthwhile), but the trend is certainly troubling.

What, then, of Sardinia?

Sardinia is well-known for being one of the “Supercentenarian Blue Zones”, a place whose inhabitants enjoy (on average, statistically) unusually healthy longevity. These places have been looked to for clues as to how to live the healthiest life.

For example: From Blue To Green: News From The Centenarian Blue Zones

However, researchers recently were investigating life in a region of Sardinia where a lot of people are aged 90+, and followed the health of 168 of them for up to 6 years (because in the case of those who died during that time, obviously the time was less than 6 years).

Note: because this was specifically a Blue Zones study, they only included participants of whom all four grandparents were born within the Blue Zone—so not, for example, looking at the health of someone who just moved there from New York, say.

They collected a lot of interesting data (of course), but what we’re talking about today is that they found that participants with LDL levels above 130 mg/dL had a significantly longer average survival than those with LDL levels below this threshold. Specifically, a 40% lower mortality risk.

This is interesting, because LDL levels ≥130 mg/dL are considered moderate hypercholesterolemia (i.e., the LDL levels are a bit too high).

However, if the same participants had total cholesterol levels over 250mg/dL, they got no extra survival benefits, and very high cholesterol was still linked with shorter survival.

You can read the paper here: The Cholesterol Paradox in Long-Livers from a Sardinia Longevity Hot Spot (Blue Zone)

But before you reach for the butter…

The researchers have several hypotheses about why these results could be so, including:

  • The longevity has less to do with LDL itself, and more to do with the diet, with the ratio of grain to olive oil.
  • Most of the participants with higher LDL cholesterol were on antihypertensive drugs, which a) will obviously have a cardioprotective effect, and b) means that their heart health is probably enjoying greater scrutiny, and medical scrutiny can also have a protective effect (indeed, that’s the point of it).
  • It was also speculated that the locals of that region may have a genetic defense against the harm of moderate hypercholesterolemia, due to historical exposure to malaria meaning that naturally slightly higher cholesterol levels without increased cardiovascular risk may have been naturally selected-for (i.e. those without it were more likely to die of malaria and not pass on their genes).

Thus, it may be that it’s not so applicable more generally. However, it is still reason to at least re-examine how bad LDL cholesterol actually is, and whether for some demographics it could have a protective factor (much like “overweight” BMI is a protective factor for people over 65).

Still, if you’d like to keep on top of your cholesterol levels, check out:

How To Lower Cholesterol Naturally, Without Statins

Enjoy!

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  • Mammography AI Can Cost Patients Extra. Is It Worth It?

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    As I checked in at a Manhattan radiology clinic for my annual mammogram in November, the front desk staffer reviewing my paperwork asked an unexpected question: Would I like to spend $40 for an artificial intelligence analysis of my mammogram? It’s not covered by insurance, she added.

    I had no idea how to evaluate that offer. Feeling upsold, I said no. But it got me thinking: Is this something I should add to my regular screening routine? Is my regular mammogram not accurate enough? If this AI analysis is so great, why doesn’t insurance cover it?

    I’m not the only person posing such questions. The mother of a colleague had a similar experience when she went for a mammogram recently at a suburban Baltimore clinic. She was given a pink pamphlet that said: “You Deserve More. More Accuracy. More Confidence. More power with artificial intelligence behind your mammogram.” The price tag was the same: $40. She also declined.

    In recent years, AI software that helps radiologists detect problems or diagnose cancer using mammography has been moving into clinical use. The software can store and evaluate large datasets of images and identify patterns and abnormalities that human radiologists might miss. It typically highlights potential problem areas in an image and assesses any likely malignancies. This extra review has enormous potential to improve the detection of suspicious breast masses and lead to earlier diagnoses of breast cancer.

    While studies showing better detection rates are extremely encouraging, some radiologists say, more research and evaluation are needed before drawing conclusions about the value of the routine use of these tools in regular clinical practice.

    “I see the promise and I hope it will help us,” said Etta Pisano, a radiologist who is chief research officer at the American College of Radiology, a professional group for radiologists. However, “it really is ambiguous at this point whether it will benefit an individual woman,” she said. “We do need more information.”

    The radiology clinics that my colleague’s mother and I visited are both part of RadNet, a company with a network of more than 350 imaging centers around the country. RadNet introduced its AI product for mammography in New York and New Jersey last February and has since rolled it out in several other states, according to Gregory Sorensen, the company’s chief science officer.

    Sorensen pointed to research the company conducted with 18 radiologists, some of whom were specialists in breast mammography and some of whom were generalists who spent less than 75% of their time reading mammograms. The doctors were asked to find the cancers in 240 images, with and without AI. Every doctor’s performance improved using AI, Sorensen said.

    Among all radiologists, “not every doctor is equally good,” Sorensen said. With RadNet’s AI tool, “it’s as if all patients get the benefit of our very top performer.”

    But is the tech analysis worth the extra cost to patients? There’s no easy answer.

    “Some people are always going to be more anxious about their mammograms, and using AI may give them more reassurance,” said Laura Heacock, a breast imaging specialist at NYU Langone Health’s Perlmutter Cancer Center in New York. The health system has developed AI models and is testing the technology with mammograms but doesn’t yet offer it to patients, she said.

    Still, Heacock said, women shouldn’t worry that they need to get an additional AI analysis if it’s offered.

    “At the end of the day, you still have an expert breast imager interpreting your mammogram, and that is the standard of care,” she said.

    About 1 in 8 women will be diagnosed with breast cancer during their lifetime, and regular screening mammograms are recommended to help identify cancerous tumors early. But mammograms are hardly foolproof: They miss about 20% of breast cancers, according to the National Cancer Institute.

    The FDA has authorized roughly two dozen AI products to help detect and diagnose cancer from mammograms. However, there are currently no billing codes radiologists can use to charge health plans for the use of AI to interpret mammograms. Typically, the federal Centers for Medicare & Medicaid Services would introduce new billing codes and private health plans would follow their lead for payment. But that hasn’t happened in this field yet and it’s unclear when or if it will.

    CMS didn’t respond to requests for comment.

    Thirty-five percent of women who visit a RadNet facility for mammograms pay for the additional AI review, Sorensen said.

    Radiology practices don’t handle payment for AI mammography all in the same way.

    The practices affiliated with Boston-based Massachusetts General Hospital don’t charge patients for the AI analysis, said Constance Lehman, a professor of radiology at Harvard Medical School who is co-director of the Breast Imaging Research Center at Mass General.

    Asking patients to pay “isn’t a model that will support equity,” Lehman said, since only patients who can afford the extra charge will get the enhanced analysis. She said she believes many radiologists would never agree to post a sign listing a charge for AI analysis because it would be off-putting to low-income patients.

    Sorensen said RadNet’s goal is to stop charging patients once health plans realize the value of the screening and start paying for it.

    Some large trials are underway in the United States, though much of the published research on AI and mammography to date has been done in Europe. There, the standard practice is for two radiologists to read a mammogram, whereas in the States only one radiologist typically evaluates a screening test.

    Interim results from the highly regarded MASAI randomized controlled trial of 80,000 women in Sweden found that cancer detection rates were 20% higher in women whose mammograms were read by a radiologist using AI compared with women whose mammograms were read by two radiologists without any AI intervention, which is the standard of care there.

    “The MASAI trial was great, but will that generalize to the U.S.? We can’t say,” Lehman said.

    In addition, there is a need for “more diverse training and testing sets for AI algorithm development and refinement” across different races and ethnicities, said Christoph Lee, director of the Northwest Screening and Cancer Outcomes Research Enterprise at the University of Washington School of Medicine. 

    The long shadow of an earlier and largely unsuccessful type of computer-assisted mammography hangs over the adoption of newer AI tools. In the late 1980s and early 1990s, “computer-assisted detection” software promised to improve breast cancer detection. Then the studies started coming in, and the results were often far from encouraging. Using CAD at best provided no benefit, and at worst reduced the accuracy of radiologists’ interpretations, resulting in higher rates of recalls and biopsies.

    “CAD was not that sophisticated,” said Robert Smith, senior vice president of early cancer detection science at the American Cancer Society. Artificial intelligence tools today are a whole different ballgame, he said. “You can train the algorithm to pick up things, or it learns on its own.”

    Smith said he found it “troubling” that radiologists would charge for the AI analysis.

    “There are too many women who can’t afford any out-of-pocket cost” for a mammogram, Smith said. “If we’re not going to increase the number of radiologists we use for mammograms, then these new AI tools are going to be very useful, and I don’t think we can defend charging women extra for them.”

    KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.

    Subscribe to KFF Health News’ free Morning Briefing.

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  • Wakefulness, Cognitive Enhancement, AND Improved Mood?

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    Old Drug, New Tricks?

    Modafinil (also known by brand names including Modalert and Provigil) is a dopamine uptake inhibitor.

    What does that mean? It means it won’t put any extra dopamine in your brain, but it will slow down the rate at which your brain removes naturally-occuring dopamine.

    The result is that your brain will get to make more use of the dopamine it does have.

    (dopamine is a neutrotransmitter that allows you to feel wakeful and happy, and perform complex cognitive tasks)

    Modafinil is prescribed for treatment of excessive daytime sleepiness. Often that’s caused by shift work sleep disorder, sleep apnea, restless leg syndrome, or narcolepsy.

    Read: Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

    Many studies done on humans (rather than rats) have been military experiments to reduce the effects of sleep deprivation:

    Click Here To See A Military Study On Modafinil!

    They’ve found modafinil to be helpful, and more effective and more long-lasting than caffeine, without the same “crash” later. This is for two reasons:

    1) while caffeine works by blocking adenosine (so you don’t feel how tired you are) and by constricting blood vessels (so you feel more ready-for-action), modafinil works by allowing your brain to accumulate more dopamine (so you’re genuinely more wakeful, and you get to keep the dopamine)

    2) the biological half-life of modafinil is 12–15 hours, as opposed to 4–8 hours* for caffeine.

    *Note: a lot of sources quote 5–6 hours for caffeine, but this average is misleading. In reality, we are each genetically predetermined to be either a fast caffeine metabolizer (nearer 4 hours) or a slow caffeine metabolizer (nearer 8 hours).

    What’s a biological half-life (also called: elimination half-life)?

    A substance’s biological half-life is the time it takes for the amount in the body to be reduced by exactly half.

    For example: Let’s say you’re a fast caffeine metabolizer and you have a double-espresso (containing 100mg caffeine) at 8am.

    By midday, you’ll have 50mg of caffeine left in your body. So far, so simple.

    By 4pm you might expect it to be gone, but instead you have 25mg remaining (because the amount halves every four hours).

    By 8pm, you have 12.5mg remaining.

    When midnight comes and you’re tucking yourself into bed, you still have 6.25mg of caffeine remaining from your morning coffee!

    Use as a nootropic

    Many healthy people who are not sleep-deprived use modafinil “off-label” as a nootropic (i.e., a cognitive enhancer).

    Read: Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review

    Important Note: modafinil is prescription-controlled, and only FDA-approved for sleep disorders.

    To get around this, a lot of perfectly healthy biohackers describe the symptoms of sleep pattern disorder to their doctor, to get a prescription.

    We do not recommend lying to your healthcare provider, and nor do we recommend turning to the online “grey market”.

    Such websites often use anonymized private doctors to prescribe on an “informed consent” basis, rather than making a full examination. Those websites then dispense the prescribed medicines directly to the patient with no further questions asked (i.e. very questionable practices).

    Caveat emptor!

    A new mood-brightener?

    Modafinil was recently tested head-to-head against Citalapram for the treatment of depression, and scored well:

    See its head-to-head scores here!

    How does it work? Modafinil does for dopamine what a lot of anti-depressants do for serotonin. Both dopamine and serotonin promote happiness and wakefulness.

    This is very promising, especially as modafinil (in most people, at least) has fewer unwanted side-effects than a lot of common anti-depressant medications.

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  • Nature Valley Protein Granola vs Kellog’s All-Bran – Which is Healthier?

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

    Our Verdict

    When comparing Nature Valley Protein Granola to Kellog’s All-Bran, we picked the All-Bran.

    Why?

    While the Protein Granola indeed contains more protein (13g/cup, compared to 5g/cup), it also contains three times as much sugar (18g/cup, compared to 9g/cup) and only ⅓ as much fiber (4g/cup, compared to 12g/cup)

    Given that fiber is what helps our bodies to absorb sugar more gently (resulting in fewer spikes), this is extremely important, especially since 18g of sugar in one cup of Protein Granola is already most of the recommended daily allowance, all at once!

    For reference: the AHA recommends no more than 25g added sugar for women, or 32g for men

    Hence, we went for the option with 3x as much fiber and ⅓ of the sugar, the All-Bran.

    For more about keeping blood sugars stable, see:

    10 Ways To Balance Blood Sugars

    Enjoy!

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  • White Potato vs Sweet Potato – Which is Healthier?

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

    Our Verdict

    When comparing white potatoes to sweet potatoes, we picked the sweet potatoes.

    Why?

    In terms of macros, sweet potatoes are a little lighter on carbs and calories, though in the case of sugar and fiber, sweet potato has a few grams more of each, per potato. However, when an average sweet potato’s 7g of sugar are held against its 4g of fiber, this (much like with fruit!) not a sugar you need to avoid.

    See also: Which Sugars Are Healthier, And Which Are Just The Same?

    The glycemic index of a sweet potato is also lower than that of a white potato, so the sugars it does have are slower-release.

    Sweet potatoes famously are good sources of vitamin A and beta-carotene, which important nutrients white potatoes cannot boast.

    Both plants are equally good sources of potassium and vitamin C.

    Summary

    Both are good sources of many nutrients, and any nutritional health-hazards associated with them come with the preparation (for example, frying introduces unhealthy fats, and mashing makes the glycemic index skyrocket, and cooking with salt increases the salt content).

    Baking either is great (consider stuffing them with delicious well-seasoned beans and/or tomatoes; if you make it yourself, pesto can be a great option too, as can cheese if you’re so-inclined and judicious with choice and quantity) and preserves almost all of their nutrients. Remember that nearly 100% of the fiber is in the skin, so you do want to eat that.

    The deciding factor is: sweet potatoes are good sources of a couple more valuable nutrients that white potatoes aren’t, and come out as the overall healthiest for that reason.

    Enjoy!

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  • The Simple Six – by Clinton Dobbins

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    We at 10almonds don’t believe in keeping things a mystery, so…

    “The Simple Six” are:

    1. the squat
    2. the goblet squat
    3. the hinge
    4. the kettlebell swing
    5. the push
    6. the push-up
    7. the kettle-bell press
    8. the pull
    9. the chin-up
    10. the gait, and
    11. walking.

    Ok, we’re being a little glib here because to be fair, those are chunked into six groups, but the point is: don’t let the title fool you into thinking the book could have been an article; there’s plenty of valuable content here.

    That said, it is a short book (64 pages), but with an average of 10 pages per exercise type, it’s a lot more than for example we could ever put into our newsletter.

    Bottom line: we know that 10almonds readers like simple, clear, evidence-based, to-the-point health information, and that’s what this book is, so we do recommend it.

    Click here to check out The Simple Six, and streamline your workouts!

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  • Get Rid Of Female Facial Hair Easily

    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.

    Dr. Sam Ellis, dermatologist, explains:

    Hair today; gone tomorrow

    While a little peach fuzz is pretty ubiquitous, coarser hairs are less common in women especially earlier in life. However, even before menopause, such hair can be caused by main things, ranging from PCOS to genetics and more. In most cases, the underlying issue is excess androgen production, for one reason or another (i.e. there are many possible reasons, beyond the scope of this article).

    Options for dealing with this include…

    • Topical, such as eflornithine (e.g. Vaniqa) thins terminal hairs (those are the coarse kind); a course of 6–8 weeks continued use is needed.
    • Hormonal, such as estrogen (opposes testosterone and suppresses it), progesterone (downregulates 5α-reductase, which means less serum testosterone is converted to the more powerful dihydrogen testosterone (DHT) form), and spironolactone or other testosterone-blockers; not hormones themselves, but they do what it says on the tin (block testosterone).
    • Non-medical, such as electrolysis, laser, and IPL. Electrolysis works on all hair colors but takes longer; laser needs to be darker hair against paler skin* (because it works by superheating the pigment of the hair while not doing the same to the skin) but takes more treatments, and IPL is a less-effective more-convenient at-home option, that works on the same principles as laser (and so has the same color-based requirements), and simply takes even longer than laser.

    *so for example:

    • Black hair on white skin? Yes
    • Red hair on white skin? Potentially; it depends on the level of pigmentation. But it’s probably not the best option.
    • Gray/blonde hair on white skin? No
    • Black hair on mid-tone skin? Yes, but a slower pace may be needed for safety
    • Anything else on mid-tone skin? No
    • Anything on dark skin? No

    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 to read:

    Too Much Or Too Little Testosterone?

    Take care!

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