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insomnia image

Is sleep the balm of hurt minds? It should be. Happily, sleep usually comes easily to me. There are some exceptions: the night before having to wake early for a long plane flight being one, but these events are few and far between.

Many people complain of insomnia, and this is a private disorder, in that it is rarely on public view. What could be more personal than to be stranded in wakeful isolation while the rest of the world is soundly asleep? However, if you have the great fortune to share a bed with someone else, you can sometimes judge whether the other person slept well, just by noting their regular breathing. You might even try a whispered “Are you awake?” to check whether you are judging their state of somnolence correctly. Then, if in the morning your partner claims not to have slept a wink, you can counter with your own observations about them having slept soundly for at least part of the night.

There are other methods to measure whether people are really awake for hours, or just exaggerating on the basis that any unwanted wakefulness at night can feel as if it lasted for ages. For example, having a bedside timer that has to be responded to every time a little light comes on is one such method used by sleep researchers. If you are wakeful you can do this monitoring task for a long while. Once you fall asleep you can no longer monitor the signals. To some extent, the perception of not having had a full night’s sleep can be measured objectively.

Be all this as it may, to rise from bed in the morning feeling you have not slept properly is a burden. What causes insomnia? A long list of foods and drinks usually follow, plus bad habits about getting too agitated prior to going to bed. “Sleep hygiene” is recommended by psychologists, and often works. You probably know the advice: prepare for sleep by following a sequence. Avoid bright lights and noise and troubling activities. Go through a ritual that calms you down and gently reminds you of comforting topics, and casts away troubling thoughts. If all that doesn’t work, get up and do some of the tasks that are worrying you, or at least write down a to-do list, and then go back to bed and try again.

Now Danielle Posthuma and colleagues have looked at the genetic angle. Are some people more prone to this disorder? So it would seem.

Genome-wide Analysis of Insomnia (N=1,331,010) Identifies Novel Loci and Functional Pathways
Philip R Jansen, Kyoko Watanabe, Sven Stringer, Nathan Skene, Julien Bryois, Anke R Hammerschlag, Chrstiaan A de Leeuw, Jeroen Benjamins, Ana B Munoz-Manchado, Mats Nagel, Jeanne E Savage, Henning Tiemeier, Tonya White, Joyce Y Tung, David A Hinds, Vladimir Vacic, Patrick F Sullivan, Sophie van der Sluis, Tinca JC Polderman, August B Smit, Jens Hjerling-Leffler, Eus JW van Someren, Danielle Posthuma
doi: https://doi.org/10.1101/214973

https://drive.google.com/file/d/1KHT_vTLjTvNqCsvDvtrA9rbi4cWdNMcn/view?usp=sharing

It is not often that one gets sent a paper with a 1.3 million sample size. I move in refined circles, it would seem.

Abstract
Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available. Despite a substantial role of genetic factors, only a handful of genes have been implicated and insight into the associated neurobiological pathways remains limited. Here, we use an unprecedented large genetic association sample (N=1,331,010) to allow detection of a substantial number of genetic variants and gain insight into biological functions, cell types and tissues involved in insomnia. We identify 202 genome-wide significant loci implicating 956 genes through positional, eQTL and chromatin interaction mapping. We show involvement of the axonal part of neurons, of specific cortical and subcortical tissues, and of two specific cell-types in insomnia: striatal medium spiny neurons and hypothalamic neurons. These cell-types have been implicated previously in the regulation of reward processing, sleep and arousal in animal studies, but have never been genetically linked to insomnia in humans. We found weak genetic correlations with other sleep-related traits, but strong genetic correlations with psychiatric and metabolic traits. Mendelian randomization identified causal effects of insomnia on specific psychiatric and metabolic traits. Our findings reveal key brain areas and cells implicated in the neurobiology of insomnia and its related disorders, and provide novel targets for treatment.

Well, at first glance these authors are on to something. These are brain areas one might have imagined would be implicated in sleep disorders. Also, the disorder picks up the nexus of psychiatric disorders, long suspected of having some biological roots. Let us read further.

They say:

Insomnia complaints were measured using questionnaire data, and the 36 specific questions were validated to be good proxies of insomnia disorder, using an independent sample (The Netherlands Sleep Register, NSR) in which we had access to 38 similar question data, as well as clinical interviews assessing insomnia disorder.

So, they seem to be measuring insomnia, which increases with age, and is more common among women. They pick up real genetic signals, not spurious associations.

We confirm previously reported genetic correlations between insomnia and neuropsychiatric and metabolic traits, and also identify several GWS SNPs for 249 insomnia that have previously been associated with these traits. The strongest correlations were with depressive symptoms (rg=0.64, SE=0.04 P=1.21×10-71 250 ), followed by anxiety disorder (rg=0.56, SE=0.11 P=1.40×10-7 251 ), subjective well-being (rg=−0.51, SE=0.03 P=4.93×10-52), major depression (rg=0.50, SE=0.07 P=8.08×10-12 252 ) and neuroticism (rg=0.48, SE=0.02 P=8.72×10-80 253 ).

Since a similar high reliability has been reported for both sleep and psychiatric phenotypes, the findings suggest that genetically insomnia more closely resembles neuropsychiatric traits than it resembles other sleep-related traits.

In addition, insomnia was bidirectionally associated with educational attainment, with a stronger effect from insomnia on educational attainment (bxy=−0.32, SE=0.02, P=1.68×10-77 265 ) (i.e. a higher risk for insomnia leads to lower educational attainment) than vice versa (bxy=−0.10, SE=0.01, P=2.27×10-23 266 ), the same pattern was observed for intelligence.

insomnia genetic correlations

This is an extremely detailed paper, and I have only given you the very basic points. Yet, in another way, the results are very familiar. A pattern is beginning to emerge. If you take a behavioural problem, like being unable to get restful sleep, you find a genetic nexus of psychiatric disorders with deleterious effects on intellectual ability.

Dryden, whom I revere, intoned: Great wits are sure to madness near allied, and thin partitions do their bounds divide.

Far from that being the case, wit is diminished by mental disorders. When literary tradition collides with empiricism, woe to tradition.

 
• Category: Science • Tags: Deep Sleep, Sleep 
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  1. Duxide says:

    I am not an expert on Mendelian randomization but I think one of its core assumptions is that the genetic markers are correlated to exposure have no direct effect on the effect phenotype. So we don’t know if the effect is due to insomnia exposure (lack of sleep causing certain deficits) or to the direct effect of the insomnia-associated polymorphisms on the other traits. I guess Mendelian randomization works better with smaller sets of genes which we know are causally related only to the instrument (exposure affecting SNPs) variable. Conversely if we use thousands of SNPs, we lose track of pleiotropy but most importantly any potential direct effects, hence incur the risk of misattributing them to environmental exposure. However, this study apparently controlled for pleiotropy so this risk is reduced.

    • Replies: @ploni almoni
  2. anon • Disclaimer says:

    Elimination of sonic and light disturbances in the bedroom are also very important to good sleep. Make sure the room is completely dark – even digital clock displays can interfere with restful sleep.
    Perhaps most important to this subject is the fact that a huge number of us are afflicted with sleep disordered breathing problems of varying severity, which can repeatedly wake us from restful sleep without bringing us to full consciousness – thus causing a multitude of symptoms that we’re unable to connect to the actual time we spent sleeping. It has downstream effects which are debilitating and life threatening.
    I suffered with sleep apnea for many years without knowing it until it became so detrimental to my health that I tracked down the problem and fixed it. The problem is quite well understood now, and more and more doctors are becoming proficient in diagnosing and treating it. If you feel you’re not getting enough good sleep, get tested. There are take-home computers which you wear overnight to see if you have a breathing restriction which only manifests itself when you’re unconscious – something you can’t discern for yourself.

    • Replies: @FKA Max
  3. dearieme says:

    “if in the morning your partner claims not to have slept a wink, you can counter with your own observations about them having slept soundly for at least part of the night”: thank God you’re not a marriage counsellor, doc.

    “Insomnia is the second-most prevalent mental disorder”: I do dislike the imperialism that medicalises more and more of life.

    Anyway, chamomile tea. Just the job.

  4. dearieme says:

    Twenty-three authors – enough for two football sides and a referee – and yet nobody can render “we had access to 38 similar question data” into good English.

    Onwards: “Are some people more prone to this disorder?” That’s the way to bet.

    “insomnia, which increases with age, and is more common among women”: does the menopause make much of a difference, doc?

    • Replies: @Alden
    , @Old fogey
  5. Imsonia is a stuttering of circadian cycle. So what is sttutering**

    To talk, for most humans, it is automatic, they don’t think manually how to talk, they just learn it and use it in very [de vecchio] intuitive/faster way.

    But maybe virtually all stutter people believe, intuitively/instinctively, ”to talk” is manual and not automatically used. Instead just toss sounding words they try miserably, step by step, how to start to talk in fluent way.

    The secret of most true learnings is: never think too much about it. If you no have real or factually-certified facility to learn something it’s may mean you no have super-capacity to learn it, you no have motivation enough to do it or both.

    ”To sleep” is also, as well for most if not all activities, at very intuitive procedure. We don’t learn how to sleep, we just lie down in the bed and without our conscious attention we sleep. The same for stuttering.

    More worried/anxious the imsone is to sleep more time s/he will spend trying to sleep, truly. More worried s/he is, more s/he will try to do it in automatic/wrong way, step by step, something which happens without our conscious consent or command.

  6. FKA Max says: • Website
    @anon

    Elimination of sonic and light disturbances in the bedroom are also very important to good sleep.

    Insomnia is more common in Caucasians and I believe light eye pigmentation is the reason:

    In my opinion and according to my research, selection for blue/light eyes (low melanin levels in the iris) in/among Northern Europeans has to do with melatonin secretion suppression by light, which, as lighter skin (low melanin levels in the skin) allows for increased Vitamin D production, is evolutionaryily advantageous in cloudy latitudes far away from the equator.This melatonin secretion suppression by light leads to insomnia and hyperactivity (good for non-stop foraging during the short summers in Northern Europe) during the light summer months, and ensures one does not become lethargic, unproductive, and depressed ( e.g., seasonal affective disorder (SAD)) during the dark winter months in extreme northern or southern latitudes.
    [...]
    Our group has previously noted three effects of light iris pigmentation in patients with seasonal affective disorder (summarized in Goel et al., 2002): (a) a larger summertime increase in photopic sensitivity than patients with darker pigmentation; (b) lower depression and fatigability scores in winter; and (c) earlier awakening during dawn simulation therapy

    http://www.unz.com/gnxp/the-2000-year-selection-of-the-british/#comment-1415671 Effect of Iris Pigmentation and Latitude on Chronotype and Sleep Timing White et al. (2003)
    [...]
    In contrast, other studies have found that minorities are at lower risk of insomnia. A survey of over 17,000 adults revealed that Whites reported more trouble falling asleep and staying asleep than did Blacks and Hispanics.(51) Similar findings were reported in a diary study examining self-reported chronic insomnia in 769 adults.(52)

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824366/ Kingsbury et al. (2013)

    http://www.unz.com/jthompson/isteve-metrics/#comment-1830062

    Personally, I am sleeping inclined:

    http://inclinedbedtherapy.com/

  7. songbird says:

    I’ve been a pretty light sleeper at least since adolescence. I’ve wondered whether maybe I got it from some ancestor, who survived either a nighttime raid or a prowling carnivore.

    One night I developed a fever and had the strangest pattern of sleep. I woke up, it seems at least a dozen times, maybe dozens of times. Each time I woke up, I felt better rested. Like I was experiencing a different mix of stages of sleep. Perhaps pure REM. At daybreak, I felt really great mentally. Only my body was so violently ill I didn’t really get a chance to test my brain on my normal routine.

  8. Alden says:
    @dearieme

    Age insomnia usually starts in the late sixties. It’s as natural as graying hair. And old men also have it.

    • Replies: @dearieme
    , @Anon
  9. “Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available.”
    Liberalism is the first-most prevalent mental disorder, but sufficient treatment is, sadly, unlawful.

  10. There’s some research suggesting people with depression may benefit from controlled sleep deprivation:

    https://www.sciencedaily.com/releases/2017/09/170919140416.htm

    In general though, the effects of sleep deprivation are pretty negative. For example, if you’re someone who experiences a lot of generalised anxiety you’re mood swings can intensify quite dramatically if you go for a number of nights without getting a decent night’s sleep.

    • Agree: Sollipsist
  11. Anonymous • Disclaimer says:

    When “literary tradition collides with empiricism”, I’m inclined to suspect that the empiricists are “educated” illiterates who cannot describe what they perceive. That would at least accord with my experience.

    • Replies: @Santoculto
  12. My sleep was troubled for many years. Then a doctor suggested I probably was missing an enzyme that breaks down stimulants like the caffeine in coffee, the theophylline in tea, or the theobromine in chocolate. For you the normal three hour half-life of these stimulants may well be thirty hours, using other enzymes to eventually break stimulants down. That was the key. I sleep fairly well now as long as I never drink more than one cup of coffee every few days and limit even green tea to a single cup in a day.

    • Replies: @dearieme
  13. Renoman says:

    Take Phenabut, you’ll sleep like the dead.
    .

  14. Old fogey says:
    @dearieme

    “[D]oes the menopause make much of a difference, doc?”

    Sure does. Trouble sleeping was the one and only secondary effect to the menopause that I noticed. Previously, I had gloriously out-slept everyone I knew. Now, it has all turned around.

    • Replies: @dearieme
  15. @Anonymous

    ”Tradition” also can be translated as

    a mix between beautiful architecture and horrible ethics…

  16. Che Guava says:

    This is an old song with the title Insomnia.

    Recommended, althnugh I am unable to check the link now, data plan, etc. A good song of the time.

    To classify insomnia as a mental disorder, even further, as genetic in origin, seems nonsense to me.

    Old fogey above gives just one example where it is not so.

    In my own case, environmental factors were the main ones, firstly my parents fighting well after I should have been asleep, recovered from that, bad experiences (partly recovered), most recently, arsehole neighbours who trained their yappy toy dog to yap just inside their door, opposite mine, at all hours of the night.

    Sounded like it was in my room. That was for several years.

    I have moved away, but one never fully recovers from such a psychological attack.

    Dr. or Mr. Thompson, I appreciate your articles, bui have no trouble with insomnia that does not have an external cause.

    Sure, taking Tokyo as an example, many people asleep on the trains, but they are generally not really asleep, just making a show of it. In any case, many of them are so tired because of noisy environment, or because of a nasty spouse, or the interrupted sleep involved in looking after a baby.

  17. dearieme says:
    @Alden

    Thanks.

    Note to Mr Unz: a “thanks” button would be a welcome improvement to your excellent website.

  18. dearieme says:
    @Old fogey

    Thanks. Have you tried chamomile tea? It works a treat for me.

    Note to Mr Unz: a “thanks” button would be a welcome improvement to your excellent website.

  19. dearieme says:
    @Mike Garrett

    Allow me to recommend chamomile tea. It’s not really “tea” of course but what the French would call an “infusion”. Roibos (Red Bush) “tea” from South Africa might also be worth a try.

    • Replies: @Mike Gerrett
  20. Insomnia is the second-most prevalent mental disorder, with no sufficient treatment available.

    There are actually numerous treatments available such as taking Benadryl, Melatonin, Ambien, or vari0us other sedative drugs such as Trazodone or Seroquel, but for most people doing plenty of hard physical work and/or taking physical exercise such as running 3 miles or swimming 1/2 mile will help.

    Caffeine drinks should be avoided for 5 hours before bed time, and alcohol consumption is of dubious benefit and may lead to having to get up in the night to take a piss. Naps during the daytime should be avoided.

    The room should be dark and quiet and the temperature should be at a comfortable level so that you are neither shivering nor sweating. A comfortable bed also helps.

    If all else fails, reading a book of classic literature will put most people out in a few minutes.

    Of course, the most common mental disorder in America is hypochondria.

    • Replies: @YetAnotherAnon
    , @Anonymous
  21. I agree — this is a significant sample size. In reading through the questionnaire, it’s very detailed and expansive.

    What thought was missing from it evaluation were questions pertaining to diet and physical activity as well as weight (fat distribution), blood sugar levels etc. I may have missed it, but questions about environment; exercise, single, stressers, kids, income . . . might have been helpful.

    I think it is safe to say that our genetics plays a role in almost everything, the real challenge is discovering how much and whether any adjustment would have a desired outcome.

    Interesting to say the least – very.

  22. “Wit” consists of several things, some of which play perfectly well with mental disorders. I doubt there’s ever been a perfectly healthy comedian in the history of the world.

    Well, maybe Bob Newhart.

    • Replies: @Wizard of Oz
  23. @Jonathan Mason

    When single I used to sleep with the window open and bedroom heating off no matter what time of year. I would sleep all night if the room was sub-zero but the bed was warm.

    For the first year of marriage I actually persuaded my wife (raised in a warm, centrally-heated home) of the virtues of this practice, but when our first child arrived the window was closed in winter and the radiator on.

    Our central heating is currently broken, England is in a lengthy cold spell, the kids are away and I’m sleeping really well in a bedroom maybe five degrees above zero.

    • Replies: @dearieme
  24. I am still waiting to read of the research which would establish the prima facie highly probable fact that we do not all ideally need 7.5 to 8.5 hours sleep in 24 but that our needs are normally distributed as one would expect from the product of many genes.

    My guess is an average of about 7.25 hours with a sd of about 1 hour – very approximate.

    A complication is that sleep serves several functions so that it might be hard to find a single equivalent like g – or at any rate one that didn’t grossly neglect the importance of one or more functiona of sleep that were out of line in their time requirements with others. Thus there may well be people whose brains can function well on 4 hours sleep but whose heart, lungs and livers kill them young. N’est-ce pas?

    • Replies: @middle aged vet . . .
  25. Clonidine is an old blood pressure pill now used for a few other conditions that will certainly help one get to sleep at night. It is very useful for those with “sympathetic overload”. It is not marketed as a sleeping pill but it is always very effective. Get your blood pressure and heart rate and other parameters reviewed by a savvy, open minded clinician and see how it works.

  26. I would like to change my name to the original Lostamerican or a different name but when I try to do so I get blocked. This is why I have to use Anon. If someone can tell me how to give myself a name other than Anon I will be glad to do so.

    • Replies: @Ron Unz
  27. Ron Unz says:
    @Lost american

    Your comments have all been merged into “Lost american,” which was the handle you had regularly used:

    http://www.unz.com/comments/all/?commenterfilter=Lost+american

    • Replies: @Wizard of Oz
  28. Ron yours is the kind of scientific mind I would like to comment on the (surely wellfounded) speculation I proffered in #25. Every second week one can find health advice from respectable sources that says most of us don’t get enough sleep (and need 8 hours approx) but without more it strikes me as rubbish. I once asked the then 98 year old mother of one of the world’s most successful and energetic media moguls what *her* average number of hours sleep had been in her adult life and she said “five and a half” without a pause. I believed her though I had thought it might less.

  29. @Sollipsist

    Bob Hope? Ģeorge Burns? Charlie Chaplin? They certainly enjoyed physical health. What about the Marx Brothers?

    John Cleese is bipolar, so is Stephen Fry, Barry Humphries is merely a dry alcoholic so I don’t know if he counts. Rolf Harris…. oh dear!

  30. Anon • Disclaimer says:
    @Alden

    And if they don’t start having an insomnia problem what should or might be inferred?

  31. @Ron Unz

    My earlier version hadn’t appeared but please leave this in place for the China reference.

    Just taking advantage of the opportunity to ask the most acute sceptical and scientific mind to consider my #25. Isn’t it prima facie absurd that everyday health punditry says nearly all of us aren’t getting enough sleep? My guess is that most are stressed in a competitive world by pressure created by the reasonably high IQ 5 and 6 hour a night sleepers. It would be interesting to apply your theorising about the rise of Chinese peasant intelligence equally to their stamina. I wonder if there are any stats.

  32. Anonymous • Disclaimer says:
    @Jonathan Mason

    Anticholinergics have a strong link to dementia. Too bad it took decades to determine the link.

    Seroquel is used to treat symptoms listed in the psychiatric comedy manual DSM-5. What the hell let’s use it to help people sleep. Criminally toxic but a real money maker.

    If you have trouble sleeping and are considering talking to a shrink, try experimenting with cannabis and alcohol first as those can be much safer.

  33. dearieme says:
    @YetAnotherAnon

    Ditto: no heating and window open. I often have a hot water bottle though, both for the warmth and because it relieves the ache of arthritis in my hands. Better an hwb than a painkiller.

    • Replies: @YetAnotherAnon
  34. @dearieme

    I must say an electric blanket is pretty good when you first get in. Not tempted?

    • Replies: @dearieme
  35. dearieme says:
    @YetAnotherAnon

    We had electric heating pads at one time which we’d bought for relieving back pains. They worked. I’ve no idea what became of them. Thanks for the reminder.

    On particularly cold nights I wear knee socks. They work too.

  36. @Wizard of Oz

    Wizard – I agree completely. The only thing that wears us down at differential rates is “responsibility” for others. Thus, a general will get worn down at a higher rate than a colonel, and so on.

    The reason the powers that be always claim we are not getting enough sleep is because they want to convince the sergeants that they are generals. They (we) are not.

    In modern days, many of the intellectually gifted people who used to get by on 4 hours sleep now need a few more due to all the flashing lights of the computers they spend so much of the day on.

    Also, if you have a demanding spouse, you need 8 hours of sleep because – let us be honest, spouses are often hard on each other – and for some of us, those 8 hours are the only hours of freedom we truly experience, due to demands of our spouses. Sad, but often true. And even the most deluded and subjugated of us are never so deluded that we can live for very long without, say, 8 hours a day of freedom. (it is easier for the rich who live in a world where they are considered valuable and gifted – believe me, they do not stare long at computer screens with those imperious flashing lights, and they have plenty of time in their 20 wakeful hours to refresh every biological function that needs refreshing….) Why 8 hours, as a minimum for even the poorest among the average among us? I don’t know. If we were born measuring things at Babylonian rates, instead of the inhuman decimal rates later and more degraded civilizations left to us as our inheritance, it might be more clear.

    • Replies: @Sparkon
  37. Dryden, whom I revere, intoned: Great wits are sure to madness near allied, and thin partitions do their bounds divide.

    Far from that being the case, wit is diminished by mental disorders. When literary tradition collides with empiricism, woe to tradition.

    Just because a condition is deleterious doesn’t mean it can’t correlate with high intelligence. Both psychological disorder and genius skew heavily toward the male sex.

    Also, the “thin partition” may often simply be success. Step out of bounds, and your theory pans out, you’re a genius. If it doesn’t, you’re just another nut.

    The Chinese are the smartest major nation on the planet, yet they fell for Maoist Marxism, a bastardization of a bastardization. Pythagoras thought you could fart your soul away. And every halfway-sane person knows to ignore the political and other views of major intellectual figures away from their area of study.

  38. There are two types of sanity

    current one or DOMESTICATED

    and

    ideal one or WISE

    Because human selection for tamed people, this selective pressure have inter-related both domestication and emotional stability.

  39. Sparkon says:
    @middle aged vet . . .

    In modern days, many of the intellectually gifted people who used to get by on 4 hours sleep now need a few more due to all the flashing lights of the computers they spend so much of the day on.

    I don’t know how you’d qualify your term “get by,” or if it relates to a single night, or a regular habit.

    I can only speak for myself, but very many nights in a row of just 4 hours sleep would leave me a wreck, although I could probably “get by” and probably did when I was younger, a little more foolish, and meeting more dames than I had time or money to chase, but fortunately, I didn’t let that stop me.

    Is there some kind of award in this thread for being the first to mention the connection between the title of James Thompson’s article here, and the inspiration for Blade Runner ?

    Do Androids Dream of Electric Sheep? by Philip K. Dick. 10 to 1 says James Thompson knew that, and is poised even now to bestow upon me the Deckard Prize.

    Well, if the ability to get by on 4 hours sleep is a valid indicator of intellectually gifted people, I didn’t make the cut.

    In fact, I don’t even have a computer with all the flashing lights, but rather a solitary soft amber light on a USB drive running a live Linux session, that does start winking and blinking on those rare occasions when I do something especially spectacular.

    Getting back to sawing logs, catching Zzzzzs, or being enchanted by the Sandman, please let me recommend a little soothing white noise for your dreamy slumbers:

    For do-it-yourself white noise, tune static on your FM receiver, or try an electric fan.

  40. Yep, Androids dreaming. Prize is a good night’s sleep.

  41. @dearieme

    Yes, Daerieme, I drink roibos all the time, but my body has never liked chamomile. Also, in my 70s I have stopped drinking any herb teas with mints or licorich, which are known to suppress testosterone production.

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