The Circadian Rhythm: Far More Than Most People Know

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The Circadian Rhythm: Far More Than Most People Know

This is Dr. Satchidananda (Satchin) Panda, the scientist behind the discovery of the blue-light sensing cell type in the retina, and the many things it affects. But, he’s discovered more…

First, what you probably know (with a little more science)

Dr. Panda discovered that melanopsin, a photopigment, is “the primary candidate for photoreceptor-mediated entrainment”.

To put that in lay terms, it’s the brain’s go-to for knowing approximately what time of day or night it is, according to how much light there is (or isn’t), and how long it has (or hasn’t) been there.

But… the brain’s “go-to” isn’t the only method. By creating mice without melanopsin, he was able to find that they still keep a circadian rhythm, even in complete darkness:

Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting

In other words, it was a helpful, but not completely necessary, means of keeping a circadian rhythm.

So… What else is going on?

Dr. Panda and his team did a lot of science that is well beyond the scope of this main feature, but to give you an idea:

  • With jargon: it explored the mechanisms and transcription translation negative feedback loops that regulate chronobiological processes, such as a histone lysine demathlyase 1a (JARID1a) that enhances Clock-Bmal1 transcription, and then used assorted genomic techniques to develop a model for how JARID1a works to moderate the level of Per transcription by regulating the transition between its repression and activation, and discovered that this heavily centered on hepatic gluconeogenesis and glucose homeostasis, facilitated by the protein cryptochrome regulating the fasting signal that occurs when glucagon binds to a G-protein coupled receptor, triggering CREB activation.
  • Without jargon: a special protein tells our body how to respond to eating/fasting at different times of day—and conversely, certain physiological responses triggered by eating/fasting help us know what time of day it is.
  • Simplest: our body keeps on its best cycle if we eat at the same time every day

This is important, because our circadian rhythm matters for a lot more than sleeping/waking! Take hormones, for example:

  • Obvious hormones: testosterone and estrogen peak in the mornings around 9am, progesterone peaks between 10pm and 2am
  • Forgotten hormones: cortisol peaks in the morning around 8:30am, melatonin peaks between 10pm and 2am
  • More hormones: ghrelin (hunger hormone) peaks around 10am, leptin (satiety hormone) peaks 20 minutes after eating a certain amount of satiety-triggering food (protein does this most quickly), insulin is heavily tied to carbohydrate intake, but will still peak and trough according to when the body expects food.

What does this mean for us in practical terms?

For a start, it means that intermittent fasting can help guard against metabolic and related diseases (including inflammation, and thus also cancer, diabetes, arthritis, and more) a lot more if we practice it with our circadian rhythm in mind.

So that “8-hour window” for eating, that many intermittent fasting practitioners adhere to, is going to do much, much better if it’s 10am to 6pm, rather than, say, 4pm to midnight.

Additionally, Dr. Panda and his team found that a 12-hour eating window wasn’t sufficient to help significantly.

Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges

Some other take-aways:

  • For reasons beyond the scope of this article, it’s good to exercise a) early b) before eating, so getting in some exercise between 8.30am and 10am is ideal
  • It also means it’s beneficial to “front-load” eating, so a large breakfast at 10am, and smaller meals/snacks afterwards, is best.
  • It also means that getting sunlight (even if cloud-covered) around 8.30am helps guard against metabolic disorders a lot, since the light remains the body’s go-to way of knowing the time.
    • We realize that sunlight is not available at 8.30am at all latitudes at all times of year. Artificial is next-best.
  • It also means sexual desire will typically peak in men in the mornings (per testosterone) and women in the evenings (per progesterone), but this is just an interesting bit of trivia (albeit sometimes an inconvenient one if you’re heterosexual), and not so relevant to metabolic health

What to do next…

Want to stabilize your own circadian rhythm in the best way, and also help Dr. Panda with his research?

His team’s (free!) app, “My Circadian Clock”, can help you track and organize all of the body’s measurable-by-you circadian events, and, if you give permission, will contribute to what will be the largest-yet human study into the topics covered today, to refine the conclusions and learn more about what works best.

Check out the iOS app here | Check out the Android app here

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  • Gut-Healthy Sunset Soup

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    So-called for its gut-healthy ingredients, and its flavor profile being from the Maghreb (“Sunset”) region, the western half of the N. African coast.

    You will need

    • 1 can chickpeas (do not drain)
    • 1 cup low-sodium vegetable stock
    • 1 small onion, finely chopped
    • 1 carrot, finely chopped
    • 2 tbsp sauerkraut, drained and chopped (yes, it is already chopped, but we want it chopped smaller so it can disperse evenly in the soup)
    • 2 tbsp tomato paste
    • 1 tbsp harissa paste (adjust per your heat preference)
    • 1 tbsp ras el-hanout
    • ¼ bulb garlic, crushed
    • Juice of ½ lemon
    • ¼ tsp MSG or ½ tsp low-sodium salt
    • Extra virgin olive oil
    • Optional: herb garnish; we recommend cilantro or flat-leaf parsley

    Method

    (we suggest you read everything at least once before doing anything)

    1) Heat a little oil in a sauté pan or similar (something suitable for combination cooking, as we’ll be frying first and then adding liquids), and fry the onion and carrot until the onion is soft and translucent; about 5 minutes.

    2) Stir in the garlic, tomato paste, harissa paste, and ras el-hanout, and fry for a further 1 minute.

    3) Add the remaining ingredients* except the lemon juice. Bring to the boil and then simmer for 5 minutes.

    *So yes, this includes adding the “chickpea water” also called “aquafaba”; it adds flavor and also gut-healthy fiber in the form of oligosaccharides and resistant starches, which your gut microbiota can use to make short-chain fatty acids, which improve immune function and benefit the health in more ways than we can reasonably mention as a by-the-way in a recipe.

    4) Stir in the lemon juice, and serve, adding a herb garnish if you wish.

    Enjoy!

    Want to learn more?

    For those interested in some of the science of what we have going on today:

    Take care!

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  • Exercise… In A Pill?

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    Exercise is, of course, vitally important for many aspects of health. So, can it be replaced by a pill?

    And the answer is: in part, at least!

    Here’s how…

    Trick the muscles; trick the brain

    First, what this won’t do:

    • Give all the cardiovascular benefits of exercise
    • Give all the strength (muscular or skeletal) benefits of exercise

    You may be thinking: isn’t that everything then?

    And no it isn’t, because the word “all” was doing a fair bit of heavy-lifting (so to speak) in those bullet points.

    For example, there are a lot of physiological benefits, such as to muscle metabolism and knock-on effects in brain health (not just due to improved circulation, but also due to assorted chemicals being released too).

    Researchers (Dr. Bernard Jasmin et al.) noted that in cases of depression, exercise can be similarly effective to first-line treatments such as medication and psychotherapy, but adherence is often lower and drop-out rates are higher than with antidepressants despite their side effects.

    It’s not laziness, either; symptoms such as low energy, lack of motivation, and anhedonia—along with socio-economic pressures, co-morbidities, inexperience, time constraints, older age, stroke history, and functional limitations—can prevent people from starting or maintaining exercise.

    You can learn more about this here, by the way: Laziness Is A Scooby-Doo Villain ← which means: to tackle it requires doing a Scooby-Doo unmasking. You know, when the mystery-solving gang has the “ghost” or “monster” tied to a chair, and they pull the mask off, to reveal that there was no ghost etc, and in fact it was a real estate scammer or somesuch. So it is with “laziness” too; there’s always something else underneath (e.g. the debilitating factors we mentioned in the previous paragraph)

    Social psychologist Dr. Devon Price wrote about this (not with that metaphor though) in his book: Laziness Does Not Exist – by Dr. Devon Price

    So the trick that Dr. Jasmin et al. went for is making use of muscle as a signalling organ that communicates with the brain.

    This is because of the muscle–brain axis: skeletal muscle makes up approximately 40–50% of adult body mass and releases cehmicals collectively known as a myosecretome during contraction, which can reduce inflammation and increase neurotrophic factors that support brain health.

    Sounds like a job for exercise mimetics!

    What exercise mimetics are: exercise mimetics—which can be called “exercise pills”—are natural or synthetic compounds that activate key endurance-related signalling pathways in skeletal muscle, shifting fibres towards slower, more oxidative properties without physical training.

    For example, compounds such as AICAR, GW501516, metformin, resveratrol, NAD+ boosters, and urolithin A, all of which may alter muscle metabolism and the composition of molecules released into the bloodstream. We wrote about several of these, by the way, in: Dr. Greger’s Anti-Aging Eight

    Which can help a lot in this case too, as you can see in the paper itself: Exercise mimetics as unexplored therapeutics for treating depression

    Want to learn more?

    If you like this, then you’ll love the already-available…

    Mediterranean Diet… In A Pill?

    Take care!

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  • Brothy Beans & Greens

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    “Eat beans and greens”, we say, “but how”, you ask. Here’s how! Tasty, filling, and fulfilling, this dish is full of protein, fiber, vitamins, minerals, and assorted powerful phytochemicals.

    You will need

    • 2½ cups low-sodium vegetable stock
    • 2 cans cannellini beans, drained and rinsed
    • 1 cup kale, stems removed and roughly chopped
    • 4 dried shiitake mushrooms
    • 2 shallots, sliced
    • ½ bulb garlic, crushed
    • 1 tbsp white miso paste
    • 1 tbsp nutritional yeast
    • 1 tsp rosemary leaves
    • 1 tsp thyme leaves
    • 1 tsp black pepper, coarse ground
    • ½ tsp red chili flakes
    • Juice of ½ lemon
    • Extra virgin olive oil
    • Optional: your favorite crusty bread, perhaps using our Delicious Quinoa Avocado Bread recipe

    Method

    (we suggest you read everything at least once before doing anything)

    1) Heat some oil in a skillet and fry the shallots for 2–3 minutes.

    2) Add the nutritional yeast, garlic, herbs, and spices, and stir for another 1 minute.

    3) Add the beans, vegetable stock, and mushrooms. Simmer for 10 minutes.

    4) Add the miso paste, stirring well to dissolve and distribute evenly.

    5) Add the kale until it begins to wilt, and remove the pot from the heat.

    6) Add the lemon juice and stir.

    7) Serve; we recommend enjoying it with crusty wholegrain bread.

    Enjoy!

    Want to learn more?

    For those interested in some of the science of what we have going on today:

    Take care!

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  • What is AuDHD? 5 important things to know when someone has both autism and ADHD

    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 seen some new ways to describe when someone is autistic and also has attention-deficit hyperactivity disorder (ADHD). The terms “AuDHD” or sometimes “AutiADHD” are being used on social media, with people describing what they experience or have seen as clinicians.

    It might seem surprising these two conditions can co-occur, as some traits appear to be almost opposite. For example, autistic folks usually have fixed routines and prefer things to stay the same, whereas people with ADHD usually get bored with routines and like spontaneity and novelty.

    But these two conditions frequently overlap and the combination of diagnoses can result in some unique needs. Here are five important things to know about AuDHD.

    Kosro/Shutterstock

    1. Having both wasn’t possible a decade ago

    Only in the past decade have autism and ADHD been able to be diagnosed together. Until 2013, the Diagnostic and Statistical Manual of Mental Disorders (DSM) – the reference used by health workers around the world for definitions of psychological diagnoses – did not allow for ADHD to be diagnosed in an autistic person.

    The manual’s fifth edition was the first to allow for both diagnoses in the same person. So, folks diagnosed and treated prior to 2013, as well as much of the research, usually did not consider AuDHD. Instead, children and adults may have been “assigned” to whichever condition seemed most prominent or to be having the greater impact on everyday life.

    2. AuDHD is more common than you might think

    Around 1% to 4% of the population are autistic.

    They can find it difficult to navigate social situations and relationships, prefer consistent routines, find changes overwhelming and repetition soothing. They may have particular sensory sensitivities.

    ADHD occurs in around 5–8% of children and adolescents and 2–6% of adults. Characteristics can include difficulties with focusing attention in a flexible way, resulting in procrastination, distraction and disorganisation. People with ADHD can have high levels of activity and impulsivity.

    Studies suggest around 40% of those with ADHD also meet diagnostic criteria for autism and vice versa. The co-occurrence of having features or traits of one condition (but not meeting the full diagnostic criteria) when you have the other, is even more common and may be closer to around 80%. So a substantial proportion of those with autism or ADHD who don’t meet full criteria for the other condition, will likely have some traits.

    3. Opposing traits can be distressing

    Autistic people generally prefer order, while ADHDers often struggle to keep things organised. Autistic people usually prefer to do one thing at a time; people with ADHD are often multitasking and have many things on the go. When someone has both conditions, the conflicting traits can result in an internal struggle.

    For example, it can be upsetting when you need your things organised in a particular way but ADHD traits result in difficulty consistently doing this. There can be periods of being organised (when autistic traits lead) followed by periods of disorganisation (when ADHD traits dominate) and feelings of distress at not being able to maintain organisation.

    There can be eventual boredom with the same routines or activities, but upset and anxiety when attempting to transition to something new.

    Autistic special interests (which are often all-consuming, longstanding and prioritised over social contact), may not last as long in AuDHD, or be more like those seen in ADHD (an intense deep dive into a new interest that can quickly burn out).

    Autism can result in quickly being overstimulated by sensory input from the environment such as noises, lighting and smells. ADHD is linked with an understimulated brain, where intense pressure, novelty and excitement can be needed to function optimally.

    For some people the conflicting traits may result in a balance where people can find a middle ground (for example, their house appears tidy but the cupboards are a little bit messy).

    There isn’t much research yet into the lived experience of this “trait conflict” in AuDHD, but there are clinical observations.

    4. Mental health and other difficulties are more frequent

    Our research on mental health in children with autism, ADHD or AuDHD shows children with AuDHD have higher levels of mental health difficulites than autism or ADHD alone.

    This is a consistent finding with studies showing higher mental health difficulties such as depression and anxiety in AuDHD. There are also more difficulties with day-to-day functioning in AuDHD than either condition alone.

    So there is an additive effect in AuDHD of having the executive foundation difficulties found in both autism and ADHD. These difficulties relate to how we plan and organise, pay attention and control impulses. When we struggle with these it can greatly impact daily life.

    5. Getting the right treatment is important

    ADHD medication treatments are evidence-based and effective. Studies suggest medication treatment for ADHD in autistic people similarly helps improve ADHD symptoms. But ADHD medications won’t reduce autistic traits and other support may be needed.

    Non-pharmacological treatments such as psychological or occupational therapy are less researched in AuDHD but likely to be helpful. Evidence-based treatments include psychoeducation and psychological therapy. This might include understanding one’s strengths, how traits can impact the person, and learning what support and adjustments are needed to help them function at their best. Parents and carers also need support.

    The combination and order of support will likely depend on the person’s current functioning and particular needs. https://www.youtube.com/embed/pMx1DnSn-eg?wmode=transparent&start=0 ‘Up until recently … if you had one, you couldn’t have the other.’

    Do you relate?

    Studies suggest people may still not be identified with both conditions when they co-occur. A person in that situation might feel misunderstood or that they can’t fully relate to others with a singular autism and ADHD diagnosis and something else is going on for them.

    It is important if you have autism or ADHD that the other is considered, so the right support can be provided.

    If only one piece of the puzzle is known, the person will likely have unexplained difficulties despite treatment. If you have autism or ADHD and are unsure if you might have AuDHD consider discussing this with your health professional.

    Tamara May, Psychologist and Research Associate in the Department of Paediatrics, Monash University

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

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  • LSD vs Anxiety!

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    We’ve written before about how psychedelics can have lasting (beneficial!) effects, here:

    Psychedelics: Yes Even Once?

    However, after a lot of research into psilocybin (the active compound in “magic mushrooms”) and some other psychedelics, the “yes even once” part of that was in reference to a study using the psychedelic compound 25CN-NBOH, a selective serotonin 2A receptor agonist (which honestly does not have a snappier name than that or else we’d use it), and how it improved cognitive flexibility (albeit: in mice) in a lasting fashion.

    You can read that paper in full (and see graphs!) here:

    Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks* after administration

    *About “weeks”; the experiment ran for 20 days and that was that. It is not known how long the benefits would have persisted, only that in the first 20 days, they showed no signs of disappearing.

    Suffice it to say, an LSD trip does not last for weeks. So, it seems the changes have been made to the brain and that’s that.

    So, what about LSD and anxiety?

    A “chill pill” with safe, lasting effects?

    We previously shared this study:

    Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline

    However, that was (once again) mice. And, as the study title suggests, repeated LSD use, not just a single dose.

    Today, we’ll be looking at a study into the effects of LSD vs anxiety in humans, from a single dose.

    Researchers (Dr. Reid Robinson et al.) found that a single LSD dose eased anxiety symptoms for up to 3 months* in 198 patients with moderate to severe anxiety

    *This is a case of the study running for three months, so the researchers can’t comment on what how long it lasts after the three months, because the research grant didn’t have enough for a crystal ball for them to use to write about the future and what will happen with the study participants after the study period. After all, at some point one needs to draw a line under it and publish the results.

    About that timeline:

    • at baseline, all patients had moderate to severe anxiety
    • at four weeks, those who took higher doses significantly lowered anxiety scores compared to smaller doses or placebo
    • at 12 weeks, 65% of patients who took 100 mg still showed improvements and 48% were in remission

    One thing that set this study apart from many is that it unlike most psychedelic studies paired with therapy, this trial tested LSD alone under supervision to isolate the drug’s effect vs placebo, rather than the effect drug+therapy and being unsure whether it would have helped without the therapy.

    About that placebo: it was noted as a limitation of the study that that many patients correctly guessed whether they took LSD or placebo (weakening blinding). The resultant high dropout rate (because it’s not very motivating to keep at something where you’re almost certain you received the placebo) reduced the final data set. Still, the researchers did what they could under the circumstances.

    You can find the paper itself, here: Single Treatment With MM120 (Lysergide D-Tartrate) in Generalized Anxiety Disorder

    On which note, with regard to “lysergide D-tartrate”; that is a form of LSD (it’s a salt of LSD, which is then metabolized as such, so one could argue that it’s essentially a pro-drug), and/but since it is far from the only form of LSD, it cannot be said for sure whether the effects will be the same with any/all LSD. It seems likely that the results will translate just the same to other forms of LSD, but we can’t say that confidently without the science actually being done for it.

    Want to learn more?

    With regard to psychedelics in general, see:

    Taking A Trip Through The Evidence On Psychedelics

    Take care!

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  • HRT Cycling: Should You Do It?

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    It’s Q&A Day at 10almonds!

    Have a question or a request? We love to hear from you!

    In cases where we’ve already covered something, we might link to what we wrote before, but will always be happy to revisit any of our topics again in the future too—there’s always more to say!

    As ever: if the question/request can be answered briefly, we’ll do it here in our Q&A Thursday edition. If not, we’ll make a main feature of it shortly afterwards!

    So, no question/request too big or small 😎

    ❝I started HRT about 6 months ago, I take it every day, but now I’m reading there may be some benefits to skipping days like with birth control, to simulate a cycle. What does science say about this?❞

    We will start by assuming that you began HRT at clinical menopause, that is to say, one year after your last period, or else that you began it after that point, not before. We realize this assumption may be incorrect, but it affects the answer, as we will explain, so it’s necessary to state this assumption up-front.

    With that in mind…

    The quickest and easiest answer is that if everything is fine as it is, there’s no need to fix what isn’t broken! That is to say, if you are not experiencing menopause symptoms, your serum hormone levels are equivalent to a normal premenopausal average, and you are not experiencing vaginal bleeding, then probably all is well.

    With regard to “vaginal bleeding”, we do use those words and not “menstruation” in this case, because not all vaginal bleeding is menstruation.

    Within the first 6 months or so postmenopause, it’s very common to have a brief, light, reprise of menstruation. There’s no egg involved, but your uterus (assuming you have one) will be cued to shed its lining as before. Obviously, this won’t happen if you’ve had a hysterectomy—but you may still get other period symptoms, including cramps in the uterus you don’t have.

    You may be wondering how this latter happens: hormones are just messengers, and will deliver their message as best they can. In the case of having an important message to deliver to the uterus, and there being no uterus there to receive it, the message will be left with the nearest tissue resembling the uterus, which is the very similar (almost identical, in fact) smooth muscle of the gut. Which will then cramp, because it got instructions saying “cramp now”.

    For more on that, see: HRT Side Effects & Troubleshooting

    Later postmenopause, you should not be bleeding down there, at all, ever, and if you are, it’s cause for concern. Not cause for panic though; just, concern. The reason for such bleeding may be anything from fibroids to endometrial cancer, and it’s worth getting check out.

    For more information about that, see: When A Period Is Very Late (Post-Menopause)

    Non-bleeding period symptoms can (and often will) still occur in the case of taking menopausal HRT, even without cycling (i.e., skipping a few consecutive days each month; exact number of days may vary from prescriber to prescriber, but is invariably 3–7 days, with 5 days being common).

    The reason for this is because even if you’re taking the hormones at the same amounts each day, your hypothalamus can and will influence the body’s use of those hormones (e.g. how much to metabolize). Premenopause, it is your hypothalamus, and not your uterus, your ovaries, or the phase of the moon, that regulates the monthly hormonal cycle. So, it can (and often will) do that in cases of treated menopause, just the same. Your hypothalamus neither knows nor cares whether your estrogen came from your ovaries or the pharmacy, and will treat it just the same.

    That said, just because the hypothalamus regulates hormone metabolism doesn’t mean that you can just give it any amount because the hypothalamus will regulate it; it can still get overwhelmed if you do give it far too much to work with. See for example: What Happens If Your Estrogen Gets Too High? ← but this is much, much rarer than having too little

    What if I began HRT pre-menopause?

    Including: if pre-menopause you had hormonal birth control, and now have shifted your HRT up a gear into full menopausal HRT (the doses for this are typically orders of magnitude higher than the doses for birth control).

    In this case, yes, regretfully (because it’s not fun), there is a case for hormone cycling, just as there was during birth control. The reason for this is less because it’s important to get the symptoms, and more because it’s best to not impede the body’s natural process of menstruation, as stopping it while it still has eggs to send forth can increase the risks of various things going wrong (including PCOS and endometriosis).

    You can read more about that, here: Contraception meets HRT: seeking optimal management of the perimenopause

    However, once you find you have stopped menstruation (i.e. even if other period symptoms persist, there is no more monthly bleeding), there should be no reason not to just take your HRT daily.

    Last thing: good HRT management involves regular testing of your hormone levels. You should have a blood test done before any change to your HRT regime, and 1–3 months after the change to it, to check the difference. And if you’re not making any changes to your HRT regime (i.e. you have been taking the same dose with acceptable blood levels for many months and are just staying on this now), then you should still get a blood test every 6 months or so, just to be sure that nothing’s going off-piste and everything’s still working the same.

    Want to learn more?

    You might like this excellent book that we reviewed a while back:

    The Menopause Manifesto – by Dr. Jen Gunter

    Take care!

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