Category Archives: fertility

Circadian rhythms, sleep deprivation, and human performance

“Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance (Goel et al., 2013).”

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Acute and chronic sleep restriction degrade neurobehavioral functions, attention, cognitive speed, and memory. Strictly according to the studies (not your n=1), < 5.5 hours is bad, < 7 hours is suboptimal, and ~ 9.5 hours may be optimal. Seems like a lot; who has time to sleep 9.5 hours?!

Above image shows cerebral blood flow (orange) in the same person’s brain during a Psychomotor Vigilance Test performed in the morning and afternoon. Interestingly, most participants perform better in the afternoon and this is associated with more blood going to a different part of the brain.

“Sleep is a ubiquitous biological imperative that appears to be evolutionarily conserved across species.” Mandatory for optimal attention and cognitive performance.

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calories proper

 

It STARTS with Sleep.

Social jet lag.

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Poor sleep, “dietary disinhibition,” and weight gain

“Dietary disinhibition”

In school, the concept was taught like this: recruit a bunch of people and tell them it’s for a cookie taste-testing project. Give them a form with a bunch of questions about cookie quality (taste, texture, sweetness, etc.) and a plate of cookies.

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SWITCHAROO!

They aren’t there for a cookie taste-test. It turns out that some people experience “dietary disinhibition” wherein if they eat one cookie, they think something like “well, I’ve blown my diet for the day, so might as well just eat the whole plate of cookies” (actually, I’m pretty sure it’s way more complicated than that, but I learned it in a nutrition class, not a psychology class).

It’s not a lot of people — most would just take a bite and fill out the questionnaire — but it’s been replicated in enough settings that it’s probably a real phenomenon.

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Carb early but not often

*if you’re going to carb, that is

 

 

The Sofer study was uniquely insightful in that they compared 3 carb-rich meals per day with the same amount of carbs but restricted to 1 meal.  Both groups ate 3 times per day.  Tl;dr: one carb meal is modestly better than three even when total carbs are controlled.  Since the carb-meal happened to be dinner, #fakenews reported that “carbs at night” are superior… but we saw right through that – the real conclusion was carb frequency not carb timing.

 

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What or When to Eat

Artificial light at night, crappy sleep, and skipping breakfast are major contributors to poor circadian rhythms.  Some bro’s insist WHAT you eat is infinitely more important than WHEN you eat.  I beg to differ, at least in part – nix the refined & processed foods and it doesn’t really matter if you prefer low fat or low carb (P<0.05).  Evidence: Hunger-free diet(s).

 

Exhibit A.  On the other hand, feed two people identical diets but induce circadian disruption in one and whammo – big difference in outcome.

 

 

Significantly less fat loss and more muscle loss in the circadian disrupted group.

Interindividual variability? Yes.  Statistical significance? YES.

 

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LIGHT, Leptin, and Environmental Mismatch

For a long time, the melanocortin system was basically thought to control the color of skin and hair.  It still does, and many redheads are redheaded due to polymorphisms in one of the melanocortin receptors.

Fast forward to 2015: to make a long story short, melanocortins are HUGE players in circadian biology.

 

POMC ACTH a-MSH

 

Brief background (also see figure above):

Fed state -> high leptin -> a-MSH -> MC4R (the receptor for a-MSH) = satiety, energy production, fertility, etc.

Fasted state -> low leptin -> AgRP blocks MC4R = hunger, energy conservation, etc.

MC4R polymorphisms in humans are associated with obesity.  Melanotan II causes skin darkening (marketed as “photoprotection” [no bueno, imo]), enhanced libido, and appetite suppression.

 

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Low carbohydrate diets favorably impact testosterone levels.

It is known.  Carbohydrate restriction improves (lowers) testosterone in women with PCOS.  It works for men, too… but by “works” I mean “increases.”

Decrease of serum total and free testosterone during a low-fat high fibre diet (Hamalainen et al., 1982) 

Intervention pseudo-crossover study: 30 healthy Finnish men in their 40’s were studied on their habitual high fat diet (40%  fat), then put on a low-fat (25%) high fibre diet for 6 weeks, then switched back to high fat.  The high fat diet was also higher in saturates, P:S ratio 0.15 vs. 1.25.

free T

 

Free testosterone levels declined on the low fat diet, but they recovered after 6 weeks of going back to their high [saturated] fat dieting (p < 0.01).

Some observational data: Testosterone and cortisol in relationship to dietary nutrients and resistance exercise (Volek et al., 1997)

…fat, and in particular saturated fat, is associated with increased testosterone levels [in men]:

observational

 

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Circadian biology: jet lag, mood, & potential role of BP regulatory peptides

There are enough connections here to suggest it’s an interesting rabbit hole.  Besides the effects of ARBs & desmopressin on mood and cognition, blood pressure regulation is not interesting <– fact.  But if it ties into fertility, circadian biology, and seasonal changes in how we should be doing things…

Way back in 1998 when I was graduating high school, Murphy and colleagues were screwing with “light-entrainable” and “food-entrainable” oscillators of circadian rhythmicity (1998).  They did this in two lines of rats, one with intact vasopressin signaling and one without.  With little mechanistic work, they showed vasopressin mediates circadian effects driven by light; and rats without vasopressin were more entrainable by meal timing.  N.B. in addition to the posterior pituitary, vasopressin is also found in the famous circadian light-regulated SCN neurons (Rosving 2010).

While it is speculated to play a role in social behaviors and sexual motivation, vasopressin is primarily known for its anti-hypotensive effects.  When plasma volume drops, vasopressin is secreted to decrease urinary water loss and increase blood pressure.  This is antagonized by alcohol, which is thought to be one reason why alcohol can dehydrate you.

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It’s paleo: Hypothyroidism impairs reproductive success in bitches.

Kisspeptin was discovered in Hershey, Pennsylvania, and was named after Hershey’s Kisses.  It has 776 pubmed citations going back to 2001, and may (or may not) play a key part integrating circannual reproduction patterns and seasonal thyroid function.

Kisspeptin was originally identified as a protein that inhibited breast cancer and melanoma.  This might also provide insight into the WHO’s recent declaration of shift work as a “probable” carcinogen.

Exhibit A. TSH restores a summer phenotype in photoinhibited mammals via the RF-amides RFRP3 and kisspeptin (Klosen 2013)

In this study, TSH infusion in short-day adapted hamsters (who are in winter non-breeding mode) induced summer phenotype & kisspeptin.  It also fattened them up a bit.  These TSH secreting neurons express melatonin receptors, but not those for TRH or T3 (Klosen 2002), so it is said to go something like this:Kisspeptin feedback diagram

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Paleo breeding: mating in the wild.

I’ve adapted much of this chart from Howell-Skalla (2002)  and Tsubota (1998).

Canadian polar bears: bona fide seasonal breeders.circannual hormones

The light cycle increases until June, then decreases until December.  Melatonin goes in the exact opposite direction. Testosterone peaks around the onset of breeding season (springtime, April/May), coinciding with LH (as expected). There is also a lot of bear-on-bear violence at this time due to: 1) testosterone-induced aggression; and 2) the high female:male ratio –-> females rear their cubs and are thus out of the game for about 3 years, but males like to breed every year.

Females followed a similar pattern, with estrogen peaking around breeding season and prolactin following the light cycle.

The authors mentioned that prolactin levels mirrored day length, and according to Wiley this would be the prolactin peak that normally occurs when you’re sleeping, but has spilled over into the daytime due to short sleep / long light cycle… not total prolactin levels (24h AUC?), which should be highest in winter (see below).

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