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Carbohydrates for Fertility and Health

Posted by on May 31, 2012 in Blog, HPA axis, Hypothalamic Amenorrhea, PCOS, Sleep | 109 comments

Carbohydrates for Fertility and Health

I spend a disproportionate amount of my time telling women to eat carbohydrates (read: “safe starches”–see below).  The thing is, a low carbohydrate diet (<50g/day) can do wonderful things for people.   This we all know well.  It’s a quick way to lose weight, to sharpen insulin sensitivity, and to reduce appetite in the short term, and it can be hugely therapeutic for people with cancer, migraines,and  chronic infections or psychological disorders.

On the other hand, low carbohydrate diets can be a significant tax on people, women especially.

Because low carbohydrate diets are so popular for weight loss, it is common for women trying to lose weight and to “look good” to exercise often, eat very few carbohydrates, fast, and restrict food intake.  The more of these restrictions a woman undertakes at once, the more and more her body reads this as living in a starved, stressed state.   The results are significant.  Her adrenals fire heavily, her liver gets tired from performing so much gluconeogenesis, her insulin sensitivity drops, her body fat levels fluctuate, her leptin signalling gets off, she stops sleeping soundly, and she stops menstruating regularly.

I cannot say that this applies to everyone.  Many women undertake low-carb diets–Peggy the Primal Parent comes to mind as a fierce advocate (recently, however, she has, in her own words “scrutinized” and weighed evidence against the diet)–and feel great energy, life, and liberation from symptoms of their previous lifestyles.  But women who are experiencing low-thyroid symptoms, menstrual dysregulation, sleep and or mood and mental health related issues may find significant relief from adding carbohydrates back into their diets.

Here’s why:

-Glucose is necessary for the conversion of T4 to T3 in the liver.  Certainly, the liver is capable of producing its own glucose with gluconeogenesis, but that process can become taxed over time, particularly if the woman’s liver is already taxed from poor eating habits in the past, mineral deficiencies, stress, or caloric restriction.   Instead, when a woman ingests glucose, she assures that her liver does not have to work overtime.  She provides the glucose that her brain needs, rather than forcing her body to make its on its own.  This helps the body function more efficiently and with less stress in general, but it also specifically optimizes thyroid activity.  Hypothyroidism is implicated in mood disorders, reproductive irregularities such as PCOS and amenorrhea, in skin conditions, and in weight gain, among other things.   Many women, contrary to popular paleo belief, in fact lose weight once they add carbohydrates back into their diets.

This is true of clinical hypothyroidism, as well as sub-clinical hypothyroidism.  Note that in many studies, women with cystic ovaries and sublicinical hypothyroidism see the resumption of regular ovulation when they correct their thyroid issues.

-Glucose elicits an insulin response, which in turn spikes leptin levels in the blood.     This is a short-term spike, so eating carbohydrates should not be used as a replacement for body fat, which is the primary long-term secretor of leptin.  However, moderate, regular consumption of carbohydrate spikes leptin frequently enough to help signal to the hypothalamus that the body is being fed.   Recall that leptin is absolutely crucial for reproductive function.  Without leptin, the hypothalamus does not tell the pituitary to produce sex hormones.   At all.

-Moderate carbohydrate intake is associated with better mood, stress-reduction, and sleep, pretty well across the board.   I see this in my work and in anecdotes, as well as in many controlled studies.    The carbohydrate-well-being connection also plays out decently in biochemical theory.  Carbohydrate intake (via insulin and albumin) boosts tryptophan levels in the brain, and tryptophan is the protein precursor to serotonin.  Presumably, then, carbohydrate intake helps with the vast array of issues associated with serotonin deficiency which include moodiness, stress, and insomnia.  For a look at the details and complexities of the issue, see Emily Deans  here and here. The primary takeaway of this point being that while the exact mechanism of carbohydrates boosting mood and sleep quality is unknown, carbohydrates still appear to be a healthy, and in many cases necessary, macronutrient.

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The whole point being that carbohydrates are not just okay but important.  For women who have appetite control problems, sugar addictions, and a lot of weight to lose, absolutely I believe a low-carbohydrate diet can do them wonders.  For women who struggle with menstruation, fertility, stress, exercise performance, or stress, along with any other hormonal oddities, carbohydrates help assure the woman’s body that she is healthy and fed.  This is crucial for reproductive health.  

In all cases, diet is a matter of personal physiology and experimentation.  If a woman’s body works better on carbs, she should eat them, and delight in those joys rather than worry needlessly.  At the very least, they are not harmful, and at their best, they are life saving.

Carbohydrates to eat:

I recommend glucose-containing carbohydrates rather than fructose for a wide variety of reasons, least of which are appetite control, liver function, and the prevention of metabolic syndrome.  Many studies seem to be indicating that fructose is the real culprit in all of these problems.  Glucose, on the other hand, when eaten absent of fructose has real satiating power.

I also recommend starchy glucose, since it is a “complex carbohydrate” and is broken down more slowly during digestion, which prevents blood sugar from rising or dropping too sharply.

Of course, grain-based carbohydrates are a no.

Finally, I recommend carbohydrates that contain nutrients over empty carbohydrates.

This means that I recommend eating:

Starchy tubers such as sweet potatoes, batata, jerusalem artichoke, cassava, tarot, and bamboo.  Regular potatoes are fine, too, but they contain fewer vitamins than their sweet counterparts.  Of the sweet potatoes, Japanese sweet potatoes are the most delicious, in my opinion, followed by white sweet potatoes and then yams and regular orange sweet potatoes.

For fruits, I recommend berries and cherries, which contain more glucose than fructose, and also bananas, which are pure 100 calorie glucose bombs.

Both white and brown rice are fine, but are fairly nutrient-poor.  Brown rice contains anti-nutrients in it’s shell, so white rice is more innocuous in terms of nutrient absorption.

Vegetables of course are great, but they do not count for carbohydrate consumption.  I know that much of carbohydrate content is indeed processed as glucose, but much of it is also tied up in fiber, which is broken down and turned into short-chain fatty acids by gut bacteria.  For this reason, vegetables alone cannot make up a woman’s carbohydrate consumption.  Instead, starchy tubers and low-fructose fruits work the best.

How much to eat: 

For a woman recovering from stress, metabolic distress, and hypothalamic amenorrhea, I recommend eating between 100-200 g/day.  That goes for athletes as well.  And for pregnant women.  At least 100 g/day.

Moreover, carbohydrates taken later in the day help with insulin sensitivity (since that gives the body the longest amount of time throughout a 24 hour period to operate at low insulin and leptin levels).  They also, anecdotally, help put people to sleep.

Carbohydrates elsewhere in the paleo blogosphere:

Chris Kresser and Chris Masterjohn: Cholesterol, mostly, also: Telltale signs you need more carbs

Jimmy Moore: Is there any such thing as a safe starch?

Jamie Scott: A Week of It

Paul Jaminet: Higher Carb Dieting Pros and Cons (includes a discussion of the “longevity trade-off”)

Cheeseslave: Why I ditched low carb

Beth Mazur: Why I don’t eat low carb

Julianne Taylor: Okay, People, Carb’s Don’t Kill

Melissa McEwen (always a badass on women and fertility): What the bleep do we know about carbs

While you’re at it, go read Melissa’s post on Why Women Need Fat.  Now.

Still afraid of carbohydrates and insulin?  Read Weightology’s take on insulin, or, better yet, Stephan Guyunet’s thoughts on fructose being the sole driver of insulin resistance, rather than glucose.

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The GABA Neurotransmitter: Another Link Between Diet, Hormones, Mental Health, and Sleep

Posted by on May 8, 2012 in Blog, Mental Health, Sleep | 13 comments

The GABA Neurotransmitter: Another Link Between Diet, Hormones, Mental Health, and Sleep

Neurotransmitters: Exciting and Inhibiting

Gamma-Amino-Butyric-Acid, or GABA, is the chief inhibitory neurotransmitter in the human brain.  Along with serotonin, dopamine, glutamate, glycine, histamine,  and norepinephrine, among dozens of other neurotransmitters, GABA regulates brain function.     Different neurotransmitters are in relationship with different types of receptors, and these receptors signal excitation or inhibition.  For this reason, neurotransmitters are commonly classified by their excitatory or inhibitory activity.  Some neurotransmitters signal to both kinds of receptors and play both excitatory and inhibitory roles.  Others are just one or the other.  GABA is one of these.  It is powerfully inhibitory.

GABA: Calm, Resilience, and Sleep

The GABA neurotransmitter tells the brain to be quiet.   The vast majority of inhibitory synapses in the brain employ GABA.   For people who are depressed and fatigued, therefore, GABA might seem like a problematic molecule.  But that ends up not being the case.  GABA malfunctioning has been shown to play a role in almost all mood disorders, including depression.  GABA is strongly associated with well-being, calmness, proper memory function, proper circadian rhythms, and good sleep.  GABA inhibits amygdala activity, too, so it has also been shown to inhibit pain and fear.  For this reason, people have talked about GABA as being a molecule that promotes resilience and personal strength.

GABA is well known to be a prominent factor in mental well-being and feelings of calm.  Officially it results in “sedative, hypnotic (sleep-inducing), anxiolytic (anxiety reducing!), anticonvulsant, muscle relaxant and amnesic” effects.  For this reason, a whole host of drugs that mimic GABA, called benzodiazepines, have been designed and proscribed prolifically.  Valium is one of them.  The long-term effects of these drugs are unpleasant, as they almost always result in withdrawal.  The symptoms of benzodiazepine withdrawal parallel GABA deficiency.  These iclude anxiety, tension, high blood pressure, insomnia, agitation, seizures, muscle spasms, and panic disorders.  For example, GABA-inhibited mice tested for anxiety demonstrate “a model of anxiety characterized by harm avoidance behavior and an explicit memory bias for threat cues, resulting in heightened sensitivity to negative associations.”

GABA is also one of the prominent molecules involved in sleep.  During sleep, many parts of the brain need to be quieted, and they need to do it all at once.  This is, in part, GABA’s job.    Without GABA, excitatory neurotransmitters continually keep different parts of the brain and the body firing, such that it can never shut down fully enough for deep sleep.   Valerian root, a natural herb and supplement, “encourages” the production of GABA.  It’s one of the most successful sleep aids one can use.  Melatonin is also powerful and is bio-identical, but it’s effects wane more markedly over time as the body becomes more and more used to higher levels of melatonin.   Over-the-counter and prescription drugs, while knocking people out, also inhibit the deep restfulness of REM sleep.  Valerian does not replace, but instead stimulates GABA production.  This is why it is so naturally (and without causing addiction) effective in promoting deep sleep.

GABA and The Pituitary

GABA, even while it inhibits frenetic activity in the brain, also stimulates activity in the anterior pituitary.  The anterior pituitary is where most of an individual’s hormone production takes place.  GABA, therefore, is crucial for people who would like to boost hormone production.  ACTH, TSH, FSH, LH, prolactin, and Human Growth Hormone are all secreted from the anterior pituitary.   Low TSH is profoundly implicated in hypothyroidism; having low FSH, LH, and prolactin levels is the root biological cause of hypothalamic amenorrhea; and growth hormone is one of the primary molecules responsible for healthy metabolism.  It’s activities include up-regulating fat utilization, protein sparing, and glucose-insulin sensitivity.  One study at the University of Milan found that 90 minutes after 5 grams of GABA supplementation, HGH levels increased 5-fold.

Increasing GABA with diet

-GABA itself is not present in foods, but one of its key constituents — glutamic acid/glutamate — is available in a wide array of readily available foods.    Glutamate-containing foods are plants and vegetables.  Examples include: broccoli, spinach, lentils, walnuts, citrus, tomatoes, cheese, corn, and mushrooms.   There are other foods in this category, such as wheat, wheat bran, soy, and cottonseed flour, and peanuts, but I do not recommend eating them.   High glutamic acid containg foods are generally animal products.  they include eggs, particularly the whites, many varieties of cheese, cod, gelatin, whitefish, and chicken, beef, and scallops.

-L-theanine also increases GABA activity. This amino acid is found in high doses in green tea.

-Foods rich in B-complex vitamins, particularly inositol, also prompt GABA production.  In fact, B-vitamins are necessary for the functioning of nearly all brain processes and chemicals.  Foods containing B-vitamins comprise a rich and varied list.  They include: fruits such as bananas, figs, cantaloupe oranges and figs, and vegetables, particularly cruciferous vegetables, such as beets, broccoli, kale, and spinach, and nuts, and seafood, and beef and beef liver, chicken liver, all organ meats, and all game/ruminant meats.

-A lower protein diet in general is associated with increased GABA activity.

-Finally, exercise and meditation can enhance GABA activity.  GABA is a lot like other body systems and muscles in that it has positive feedback effects.  The calmer someone is, the more likely it is that he will be able to produce proper amounts of GABA.  Some physical activities allow the mind and body to enter into calmed and relaxed state.   For this reason, many natural health practitioners recommend yoga as a means of increasing GABA.  Meditation and light forms of exercise such as walking also fit into that recommendation.

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Night Eating Syndrome: An Effect of HPA axis and Appetite Dysregulation (among other things)

Posted by on May 2, 2012 in Blog, Neurobiology of Eating, Sleep | 2 comments

Night Eating Syndrome: An Effect of HPA axis and Appetite Dysregulation (among other things)

Night Eating Syndrome isn’t something that gets talked about very often. But disordered eating researchers are hyper aware of it.  It’s also an enlightening topic for a variety of reasons, least of which being the relationship between the endocrine system, circadian rhythms, and feeding schedules.

The diagnosis and experience of night eaters is now well-parameterized, though the causal factors are not.  Night eaters usually eat very little in the mornings, eat more snacks during the day time than others, and wake up often several times each evening in order to eat.  They usually sleep at normal times, but their sleep is disturbed by their need to eat.   Night eaters experience lower levels of leptin both at night and during the day, lower levels of growth hormone, and higher levels of TSH.  In general, insulin and glucose are elevated, and rates of depression are also higher.   But still the crux of the night eating problem is timing:  Leptin and insulin are delayed between 1 and 3 hours.   Melatonin is delayed by a couple of hours.   Ghrelin, the primary hormone that stimulates food intake, is phased forward by as much as five hours.   Glucose rhythms are almost entirely reversed.   Night eaters also experience several “amplitude” attenuations.  What this means is that both the spikes and the troughs of different cycles are minimized, such that hormone levels flatten out and disrupt the endocrine system’s ability to hit the triggers for normal functioning.

Researchers are not sure what causes night eating syndrome.  Metabolic dysregulation for sure, but “obesity” still doesn’t provide the answers.    What is clear is that the central timing of circadian rhythms (via the suprachiasmatic nucleus in the brain) undergoes some kind of disconnect with other clocks located throughout the body, particularly those found in the stomach and the liver.  Many researchers recommend using lighting and other environmental triggers to get NES sufferer’s clocks back on schedule, but that only addresses one portion of what controls timing.  The SCN is the ruler of the circadian system, but it cannot force peripheral organs into line.  I believe liver and stomach signalling need to be addressed independently.  For an excellent discussion of what mechanisms may be at play in peripheral clock signalling, check out this review.

The mechanism by which these clocks become de-coupled is not quite known.  First, it is generally assumed that a switch in feeding times tells the body to expect different signals, such that moving meals around really can phase shift organs.  Yet it goes deeper; most everyone with night eating syndrome still eats at regular mealtimes.  Something must account for what’s making them so hungry at nighttime.  In investigating the link, some researchers injected the glucose-receptor agonist dexamethasone into mice at different times during the day.  Dexamethasone is a synthetic glucocorticoid, stronger than cortisol.   With the dexamethasone in their systems, the mice’s livers became phase-shifted within a day or so.  With less, it took longer.  What this demonstrates is that the presence of cortisol in a system accelerates whatever phase changes might be occurring.   The SCN is capable of arousing CRH (a precursor to cortisol) production.  Many researchers speculate that this is a mechanism by which the SCN generally attempts to modulate peripheral organ activity.  Yet if cortisol runs amok, the effects can occur absent the usually cause.

The same goes for people.  One study tested CRH levels in night eaters.  They found that in night eaters compared with controls, the CRH-induced cortisol response was significantly decreased. In conclusion, disturbances in the hypothalamic-pituitary-adrenal axis with an attenuated ACTH and cortisol response to CRH were found in subjects with night-eating syndrome.

Lesions on the SCN abolish glucocorticoid and feeding rhythms.   In “clock mutant” mice, the feeding schedule is distorted in a way that almost doubles calorie intake.  Mice typically eat 75 percent of their calories in the nighttime, yet when they become Mutant Clocks they end up consuming the same volume of food also in the day time.   These mice also experience diurnal variation in glucose and triglyceride levels.  Their gluconeogenesis is almost entirely suppressed.  Why this happens is not known, though it is clear that the signalling from the SCN clock must be received and interpreted in the liver in order for gluconeogenesis to function properly.  This is especially interesting because we see that feeding-stimulating (orexic) and feeding-inhibiting (anorexigenic) genes in these mice are both decreased as a result of the clock mutation.  We would think, then, that these two decreases would balance each other out.  And maybe they do.  What seems to be the real problem with night eating syndrome is the dysregulation in the communication between the SCN and the digestive organs.

Throwing off glucose metabolism in this way begets leptin problems as well.  And how does leptin dysregulation contribute to the development of night eating syndrome?    It’s a slow but insidious process.  Sleep curtailment inhibits the leptin response. Decreased leptin levels leads to an increased need to eat–particularly of carbohydrates.  This is likely due to a whole host of types of neurons that respond to starvation signalling (ie, low leptin levels or poor leptin sensitivity) with drives toward carbohydrate refueling, particularly Neuropeptide Y and hypocretin neurons.  When sleep-curtailed individuals wake up in the morning, they have impaired glucose tolerance and crave carbohydrates right away.  Throughout the day, blood sugar swings and inhibited leptin signalling and responsiveness lead to incessant snacking.   Additionally, an altered cortisol profile from the disturbed sleep disrupts the liver and stomach clocks.  These several phenomena result in an increased need for food and for calories late in the day.  Leptin levels have dipped, glucose and insulin functioning has been impaired, cortisol has been on the rise, and the brain has been told it’s starving.  Thenso late in the day, the individual eats because he is hungry.   His leptin levels will rise, particularly in response to a high carbohydrate, high insulin meal.  This can help him sleep, via calming hypocretin neurons, as well as sooth his cravings.   But it’s not over.  With other timers off in the stomach and the liver, the brain will get appetite and waking signals (again, partly facilitated by hypocretins) strong enough to rouse the individual from sleep.   If hypocretin neurons are significantly stimulated, the organism will always rise.  Continually then throughout the night hypocretin neurons respond to all of the hormones coming out of the liver and the stomach and get the organism up to feed.

This all results in a vicious cycle.   What needs to be done about it is not exactly known.  Patients can supplement with 5 HTP and tyrosine in order to raise brain neurotransmitter levels, which can curb appetite.  Patients can do light therapy in order to strengthen the power of the suprachiasmatic signalling.  And patients can perhaps take melatonin or valerian, or any other sleep aid, in order to try and get a full night’s rest and a full night’s recovery of leptin signalling capabilities.   Mealtimes can be gradually shifted and snacking reduced such that the individual can still fall asleep and sleep well at the appropriate times.  Finally, reducing stress is also–as always–one of the most helpful factors.

 

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Hypocretin Neurons: The Link Between Fasting, Stress, and Arousal, or, Why Fasting Breeds Insomniacs

Posted by on Apr 30, 2012 in Blog, Fasting, HPA axis, Neurobiology of Eating, Sleep | 16 comments

Hypocretin Neurons: The Link Between Fasting, Stress, and Arousal, or, Why Fasting Breeds Insomniacs

There is a hell of a dichotomy occurring in the Paleo blogosphere this month.   99 percent of the time I am pleased as Pooh stuck up a honey tree, nestled in my esoteric corner of paleo-feminist rage, but every once in a while I wish more people could hear what I have to say.  Today is one of those days.

The split I am talking about is not all that nefarious.  In most cases, it’s benign and can be ignored.   But in general I would like to draw attention to it, because I think there’s a lot going on beneath the surface (and here, the depths are not just Nemo and Dory but are instead people’s lives), and that depth requires speaking to.  Immediately.

Mark’s Daily Apple has recently done a beautiful series on the benefits of fasting.   I loved it.  I learned plenty, as I always do on MDA.  The series was well-written and -organized, and in fact I ended up directing people who are unfamiliar with fasting to the site in hopes of swaying their opinions.   (So let it be clear: I am not against fasting per se.) Yet Chris Kresser has also done an April “Best your Stress” challenge.   Serendipitously enough, it concludes today.  And it is exactly what it sounds like: an endeavor to spend 30 days taking practical steps to counteract stress.  Chris’s idea was that people often spend 30 days trying to get their diets in line.  But what about their stress, and their lives?  I couldn’t agree more.   This man is a gale of fresh, important ideas.

The reason I say these two Big Themes are at odds is because they are.  Fasting is a stressor.  Period.  Mark Sisson would agree.  All people who advocate fasting would agree.  But all they ever do is put an asterisk at the end of their posts: *people who are stressed should probably not fast, they say.   But why?  Who is affected, and how?   What can fasting and other forms of restriction do to our brains, and to our lives?

What I want to draw attention to today are little loci that sit on the border of the hypothalamus called Hypocretin Neurons.    Hypocretin neurons (also called Orexins–and note that the word “orexin” means “appetite increasing”) were discovered just 14 years ago in 1998, but they have radically altered the landscape of eating neurobiology since then.   No, they are not the sole molecules responsible for sleep and waking.  Mice that have had these neurons removed still sleep and wake in roughly normal patterns.  But they never feel alert, and they never suffer insomnia.  And when the neurons are activated, the mice leap into action.  Hypocretin neurons wake animals up.  This much is certain.

The lack of Hypocretin Neuron signalling is the cause of narcolepsy, while elevated Hypocretin levels induce arousal, elevate food intake, and elevate adiposity.  Hypocretin Neurons  upregulate the production of molecules down several other pathways, too: these include noradrenergic, histaminergic, cholinergic, dopamine, and serotonergic.

The anatomy of Hypocretin Neurons is also coming into greater light.   When are the neurons active?  What signals do they receive, and what signals do they produce?     Research is beginning to show that Hypocretin Neurons are excited by excitatory synaptic currents and asymmetric synapses with minimum inhibitory input.   The fact of asymmetry is important.  It means that Hypocretin Neurons are instead always acted upon by mostly uniform – excitatory - signals they receive.    Hypocretin Neurons only ever up-regulate and relax.  They do not down-regulate.   Excitatory signals outnumber inhibitory signals 10:1.

One notable source of excitation is corticotrophin releasing hormone, which suggests that stress activates the activity of Hypocretin Neurons.    GABA neurons also create a bridge between Neuropeptite Y, which is the molecule that arguably has the strongest appetite-stimulating effect on the brain, and Hypocretin Neurons (more on Neuropeptide Y later this week).  From there, Hypocretin Neurons project to all regions of the brain, including the hypothalamus, cerebral cortex, brain stem, and spinal cord.   It seems as though Hypocretin Neurons may act as a nexus of signal input for the appropriate synchronization of various autonomic, endocrine, and metabolic processes.

Food restriction further augments recruitment of excitatory inputs onto Hypocretin cells.   This explains the relationship between insomnia and adiposity: because of the easy excitability of Hypocretin Neurons, any signal that triggers their activity, regardless of homeostatic needs, will elevate the need to feed in brain circuits such as the locus coeruleus and the melanocortin system while also promoting wakefulness through activation of noradrenaline-stimulating neurons.  Anything that promotes the release of corticotrophin releasing hormone (CRH) such as reduced sleep will further trigger Hyocretin Neuron firing and Appetite.   This is a vicious cycle.  Hypocretin Neurons play the role both of trigger and of accelerator, taking states of wakefulness, insomnia, stress, and obesity into continual positive feedback loops.

So how does leptin factor in?  Hypocretin Neurons express leptin receptors.   Moreover, some recent complicated neurobiological work done on mice has shown that injecting them with leptin decreases the activity of their Hypocretin Neurons.   What this means is that Hypocretin Neuron activity is stimulated in part by decreasing levels of leptin in the blood, and that increased leptin levels reduce the level of excitation running through Hypocretin Neurons.   This is coupled by ghrelin activity, which is also detected by Hypocretin Neurons.   Ghrelin, which originates in the gut and is known to stimulate appetite, also excites Hypocretin Neurons.   What does feeding do, then, for Hypocretin Neuron excitation?   Experiments on mice show that re-feeding restores normal Hypocretin activity, to an extent.  Repeated abuse takes longer to recover from, but the simple presence of leptin in the blood normalizes the brains of mice.

Hooray!  This is good for fasting, right?  So long as one re-feeds appropriately, everything should be fine?  Well, yes.  In a healthfully functioning individual.  But not in a) someone who is both stressed and leptin resistant, since increased leptin levels from the re-feed might not be powerful enough to offset other excitatory pathways b) someone who is currently emerging from yo-yo dieting or caloric restriction c) someone who is dealing with an over-stimulated appetite, d) someone experiencing stress, e) someone who has had a history of insomnia, f) someone who is underweight, since they have low leptin levels, g) anyone who has ever had an eating disorder, particularly bulimia or binge eating disorder or h) anyone with HPA axis or endocrine dysregulation, particularly women, including overt stress, hypogonadism, hypothalamic amenorrhea, hypercortisolism, or hypocortisolism (adrenal fatigue.)  I am sure the list is incomplete.

In animals, Hypocretin Neurons serve an important evolutionary function.  Arousal is a vital behavior in all species.    And normally, Hypocretin Neurons respond quickly to changes in input.  But in situations of chronic metabolic or endocrine stress, or of recovering from a stressor, they can lead to hyper-activity and hyper-feeding.

Researchers have long known about the link between leptin, sleep, and obesity.  The less someone sleeps, the lower her leptin levels, so the more she eats, and the heavier she gets.  Hypocretin Neurons may serve as one of the answers to the question of exactly how that phenomenon comes about.  Or at least it plays a role.  Because 1) Hypocretins simultaneously stimulate appetite and wakefulness, particularly through orexigenic output of the melanocortin system, and subsequent release of CRH, which activates the stress response, and 2) while Hypocretin Neurons wake us up, they also need to be quiet enough for people to go to sleep.

Finally, I raise the questions: how many disordered eaters have trouble sleeping?  How many anorexics, binge eaters, calorie restrictors, exercise-addicts, stressed-out individuals, and very low-carb dieters have trouble sleeping?   How many people try intermittent fasting and find that it disrupts their sleep or circadian rhythms?  How many people wake up in the middle of the night or early in the morning, even though they still need sleep, but for the life of them feel so awake?  Part of that answer lies in blood sugar metabolism, for sure.  And in other places.  Sleep is a hell of a complex phenomenon.  But here– Hypocretin Neurons can become overburdened by excitatory signals.  They get hyped up in the face of both decreasing leptin levels and leptin insensitivity.   They are upset by restriction, and they are upset by fasting.  Hypocretin Neurons demonstrate why so many people have difficulty with their appetite and their sleep.  If you find that fasting disturbs your sleep, or that you are suffering disordered circadian rhythms along with stress or appetite problems, do you best to relax your system.  Don’t fast.  Relax.  Exercise less.  Reduce stress.  Eat more.  Put on weight.  Eat more carbohydrates.  Don’t graze.  Increase your leptin sensitivity.  And listen to your body.

Coming up next: nighttime eating syndrome, and how it’s all related.

 

 

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Leptin, Sleep, and Obesity: Is Reduced Sleep Making America Fat?

Posted by on Apr 30, 2012 in Blog, HPA axis, Neurobiology of Eating, Sleep | 0 comments

Leptin, Sleep, and Obesity: Is Reduced Sleep Making America Fat?

The literature on sleep and obesity is becoming dense.  Lots of things happen to people when they sleep.   One of them has to do with appetite regulation, so many researchers are coming to believe that sleep plays a dominant role in today’s vast American Overfeed.

This hunch is supported by striking correlations.

In 1960, a survey of over 1 million people found a modal sleep duration of 8-9 hours. In 2002, polls conducted by the National Sleep Foundation indicated that the average duration of sleep for Americans had fallen to 6.9-7 hours.  Recent data indicate that a higher percentage of adult Americans report sleeping 6 hours or less. In 2005, in the US, more than 30% of adult men and women between the ages of 30 and 64 years reported sleeping on average less than 6 hours each night.   This decrease in sleep duration has occurred over the same time as the increase in the prevalence of obesity and diabetes.

Leptin has a distinct diurnal and circadian rhythm.  It has minimum values during daytime and a nocturnal rise with maximum values during early to mid sleep.  The amplitude of the circadian variation averages approximately thirty per cent.    Leptin levels rise during the night to suppress appetite while sleeping.   Moreover, the reduction of leptin at night spells bad news for the rest of the day: it sets the individual up not just with lower leptin levels in general but also decreased glucose tolerance and an increased craving for carbohydrates.

In order to test the effects of sleep deprivation on leptin production, a number of studies have been conducted.  They’re all fascinating, so I have provided a quick review of some of the more revealing studies.

1)   Many studies are conducted on people with sleep apnea.   Epidemiological studies show that they are heavier than the rest of the population.  They have greater rates of diabetes and metabolic syndrome.  Yet when their sleep apnea is corrected, these people lose weight naturally, and their metabolisms normalize.  This probably has to do both with decreased appetite as well as improved metabolic functioning.

2) In one study at the University of Chicago, doctors measured levels of leptin and ghrelin in 12 healthy men. They also noted their hunger and appetite levels. Soon after, the men were subjected to two days of sleep deprivation followed by two days of extended sleep. During this time doctors continued to monitor hormone levels, appetite, and activity.  The end result: When sleep was restricted, leptin levels went down and ghrelin levels went up. Not surprisingly, the men’s appetite also increased proportionally. Their desire for high carbohydrate, calorie-dense foods increased by a whopping 45%.

3) In another study at the University of Chicago, a similar protocol was conducted but men were asked to return a year later for a comparison. For six days they got four hours of sleep — their week of sleep deprivation.  The men’s food and activity levels were strictly regulated and hormone levels were taken during the day and while they slept.   One year later, the men returned for a six-day study with an 8-hour sleep period, so they served as their own comparison group.  The results: After their six-day sleep deprivation period, volunteers had a leptin decrease ranging from 19-26 percent.

4) In another study — a joint project between Stanford and the University of Wisconsin — about 1,000 volunteers reported the number of hours they slept each night. Doctors then measured their levels of ghrelin and leptin, as well as adiponectin, insulin, glucose, a lipid profile, and they also charted their weight.  The result: Those who slept less than eight hours a night not only had lower levels of leptin and higher levels of ghrelin, but they also had a higher level of body fat. What’s more, that level of body fat seemed to correlate with their sleep patterns. Specifically, those who slept the fewest hours per night weighed the most.

5)   In the final study, young, healthy subjects who were studied after 6 days of sleep restriction where they were allowed four hours in bed. After full sleep recovery, their levels of blood glucose after breakfast were higher in the state of sleep debt despite normal or even slightly elevated insulin responses. The difference in peak glucose levels in response to breakfast averaged was large enough to suggest a clinically significant impairment of glucose tolerance. These findings were confirmed by the results of intravenous glucose tolerance testing. Indeed, the rate of disappearance of glucose post injection was nearly 40 per cent slower in the sleep-debt condition than after recovery, and the acute insulin response to glucose was reduced by 30 per cent.

How fast do leptin levels recover from sleep deprivation?

Leptin levels recover almost as soon as regular sleep is resumed, at least in controlled studies.  In the first night.  However, these studies occur over a week or two at most.  If the sleep deprivation is chronic, it seems to have the same effect as fasting does on leptin.  Levels remain low–at least for some time–despite resumption of “normal” sleep or eating.  It takes time for the system to re-equilibrate after chronic stressors.

How does stress act on this system?

Stress activates cortisol secretion, but it also stimulates sympathetic nervous system activity.  This gets adrenaline running in the system, increases heart rate, and increases blood pressure.  These two things increase during both partial and acute sleep deprivation.  It is well kown that andrenergic (adrenal-related) receptor activation is suppressive of leptin production, and that leptin is reduced in response to adrenaline infusions.  For this reason, whatever dampening that stress puts on sleep negatively affects appetite activity.

There are other downstream effects of sleep deprivation.   I’ll cover some of them briefly here, then hopefully return to them each on their own.

1)  More cortisol dysregulation.  One effect of sleep deprivation is a decrease early evening cortisol levels.   Normally at that time of day, cortisol concentrations are rapidly decreasing in order to attain minimal levels shortly before habitual bedtime.  Yet in one study the rate of decrease of cortisol concentrations in the early evening was approximately 6-fold slower in subjects who had undergone 6 days of sleep restriction than in subjects who were fully rested. This means, basically, that it takes longer for people who have lost sleep to ramp down from that stress and be able to go to sleep again.

2)  Thyroid reduction.  In one study, after 6 days of 4-hour sleep time, people experienced a striking decrease in the normal nocturnal TSH rise, and the overall mean TSH levels were reduced by more than 30%. A normal pattern of TSH release reappeared when the subjects had fully recovered. T4 was higher in the sleep-restricted condition than the normal condition, indicating that decreased sleep decreases the body’s rate of conversion from T4 to T3.

3)  Growth hormone reduction.  The temporal organization of Growth Hormone secretion is also altered by chronic partial sleep loss. The normal single GH pulse occurring shortly after people fall asleep splits into 2 smaller pulses, 1 before sleep and 1 after sleep.  With decreased sleep, peripheral tissues are exposed to high GH levels for an extended period of time.  GH has anti-insulin-like effects, so an increased overnight exposure to GH negatively impacts insulin sensitivity and glucose tolerance.

 

 

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