Sleep, Vitamins Sleep, Vitamins and and

Cardiovascular Cardiovascular DiseaseDiseaseDr. Stasha GominakDr. Stasha Gominak

ETMC Neurologic Institute, 700 Olympic Plaza, 912ETMC Neurologic Institute, 700 Olympic Plaza, 912Tyler, TX (903) 596-3808Tyler, TX (903) 596-3808

www.drgominak.comwww.drgominak.com1/14/20111/14/2011

Why don’t we doctors know much about Sleep?

We all do it. We spend 1/3 of each 24 hours doing it, why?

We all know we feel terrible the next day when we don’t sleep well. What if we felt that way every day?

How important is it to our patients? Why don’t we learn about it in residency? Dr. Perkins has just shown you why it’s

particularly important to the field of Cardiology.

Sleep and HeadacheSleep and Headache I became interested in sleep when one of my I became interested in sleep when one of my

daily headache patients had sleep apnea.daily headache patients had sleep apnea. She did not have significant drops in oxygen. She did not have significant drops in oxygen.

She was not fat but she did have obstructive She was not fat but she did have obstructive sleep apnea.sleep apnea.

Two years of trying medications had failed, 3 Two years of trying medications had failed, 3 weeks of of wearing a CPAP mask cured her weeks of of wearing a CPAP mask cured her headaches.headaches.

Why would that be? Could other daily Why would that be? Could other daily headache sufferers also have sleep disorders?headache sufferers also have sleep disorders?

Is something happening in the brain during Is something happening in the brain during sleep to make chemicals that are like the sleep to make chemicals that are like the daily headache preventative medicines we daily headache preventative medicines we use; Ca++ channel blockers or Na+ channel use; Ca++ channel blockers or Na+ channel blockers?blockers?

6 years of sleep studies: 9/10 daily 6 years of sleep studies: 9/10 daily headache sufferers have abnormal headache sufferers have abnormal

sleepsleep Obstructive sleep apnea is just one of the Obstructive sleep apnea is just one of the

sleep disorders seen in my young, healthy sleep disorders seen in my young, healthy patients with daily headache. patients with daily headache.

Others have multiple unexplained Others have multiple unexplained awakenings, no REM sleep, no slow wave awakenings, no REM sleep, no slow wave sleep, or REM related apnea. They do not sleep, or REM related apnea. They do not have large oxygen drops.have large oxygen drops.

Some also kick their legs in sleep; Periodic Some also kick their legs in sleep; Periodic Limb Movements of Sleep (PLMS). Why?Limb Movements of Sleep (PLMS). Why?

Are these many different disorders or are they Are these many different disorders or are they several ways of manifesting a malfunction of a several ways of manifesting a malfunction of a certain area?certain area?

Normal Sleep is a highly Normal Sleep is a highly organized processorganized process

what follows are my ideas of what we are doing what follows are my ideas of what we are doing in sleep and whyin sleep and why

What is Light Sleep?What is Light Sleep? Light Sleep: We begin Light Sleep: We begin

Stage I move to Stage II. Stage I move to Stage II. We are asleep but are We are asleep but are easily awakened. easily awakened.

I think I think we are waiting to we are waiting to be sure we’re in a safe be sure we’re in a safe place to get paralyzedplace to get paralyzed..

I believe that in light sleep I believe that in light sleep we are asleep but we are asleep but not not doing the work of sleep.doing the work of sleep.

Deep Sleep: Slow Wave Deep Sleep: Slow Wave SleepSleep

As soon as our brain is sure that As soon as our brain is sure that we’re in a safe place to get we’re in a safe place to get paralyzed (lying down) we enter paralyzed (lying down) we enter Stage III sleep. (Stage III sleep. (Stage III and what Stage III and what was Stage IV are now grouped together was Stage IV are now grouped together as just Stage IIIas just Stage III) )

Stage III is called “Slow Wave Stage III is called “Slow Wave Sleep” (SWS) because the brain Sleep” (SWS) because the brain wave pattern becomes slow and wave pattern becomes slow and synchronized. synchronized.

During Stage III sleep our During Stage III sleep our body body becomes paralyzed.becomes paralyzed.

Growth hormone (GH) is Growth hormone (GH) is released from the brain in a released from the brain in a pulsatile fashion in SWS , if pulsatile fashion in SWS , if you don’t get and stay in you don’t get and stay in SWS you don’t get this GH.SWS you don’t get this GH.

Growth Hormone in Slow Growth Hormone in Slow Wave Sleep may help us Wave Sleep may help us

healheal Growth Hormone (GH) is the same Growth Hormone (GH) is the same

hormone that makes kids grow hormone that makes kids grow during sleep. during sleep. In childrenIn children it is a it is a sustained release during SWS, sustained release during SWS, they they grow while paralyzedgrow while paralyzed..

I believe that nightly GH in adults I believe that nightly GH in adults may act analogously, as a repair may act analogously, as a repair hormone; the “boss hormone” that hormone; the “boss hormone” that calls out all of the individual muscle, calls out all of the individual muscle, bone, tendon, artery, nerve, repair bone, tendon, artery, nerve, repair factors. factors. In adults paralysis for In adults paralysis for repair.repair.

People with PLMS often wake in the People with PLMS often wake in the morning with leg or back pain.morning with leg or back pain.

This may suggest that if your SWS is This may suggest that if your SWS is frequently interrupted or shortened frequently interrupted or shortened by apnea or PLMS, your repair phase by apnea or PLMS, your repair phase doesn’t happen normally and you doesn’t happen normally and you may wake up with pain in the may wake up with pain in the morning.morning.

Deep Sleep: REM SleepDeep Sleep: REM Sleep After SWS we enter REM After SWS we enter REM

(Rapid Eye Movement) sleep. (Rapid Eye Movement) sleep. In REM sleep In REM sleep we’re the we’re the

most paralyzed of all (so most paralyzed of all (so we don’t act out our we don’t act out our dreams)dreams). So milder sleep . So milder sleep apnea may present as just apnea may present as just “REM related apnea”.“REM related apnea”.

Most of my daily headache Most of my daily headache sufferers have REM related sufferers have REM related apneaapnea. They also have mood . They also have mood and memory problems, and and memory problems, and REM is also where we do REM is also where we do memory and mood.memory and mood.

9/10 daily headache sufferers in 9/10 daily headache sufferers in my practice have abnormal sleepmy practice have abnormal sleep

CPAP is great! When it works miraculous things CPAP is great! When it works miraculous things do do happen. happen. BP better, headaches gone, tremor gone, diabetes gone.BP better, headaches gone, tremor gone, diabetes gone.

But what should I do to treat the others?But what should I do to treat the others? Multiple awakenings to light sleep.Multiple awakenings to light sleep. No REM sleep, no SW sleep. No REM sleep, no SW sleep. REM related apnea. REM related apnea. Periodic Limb Movements of Sleep (PLMS).Periodic Limb Movements of Sleep (PLMS).

Why aren’t there any medicines that give back normal Why aren’t there any medicines that give back normal sleep?sleep?

Are these many different disorders or are they several ways Are these many different disorders or are they several ways of manifesting a malfunction of a certain area? Where does of manifesting a malfunction of a certain area? Where does this happen? Why does it happen? this happen? Why does it happen?

If we could fix this we could dump the CPAP device!!!!If we could fix this we could dump the CPAP device!!!! Because I’m thinking about headache all the time Because I’m thinking about headache all the time I’m I’m

focused on the posterior brainstem. focused on the posterior brainstem. Why is that area Why is that area important?important?

The Migraine “Brainstem Generator”

is in the same area of the brainstem where we do timing and paralysis of

sleep

Posterior brainstem Posterior brainstem Periaquiductal Gray plays a large Periaquiductal Gray plays a large role in sleep and sleep paralysisrole in sleep and sleep paralysis

There are There are pacemakers pacemakers in in the periaquiductal grey the periaquiductal grey that switch sleep on and that switch sleep on and off. They are theoff. They are the brain brain clock.clock.

The paralysis switch is The paralysis switch is here also.here also.

They are heavily They are heavily intertwined so we only intertwined so we only get paralyzed while we get paralyzed while we are deeply asleep.are deeply asleep.

We must all get We must all get paralyzed in deep sleep paralyzed in deep sleep to complete the work of to complete the work of sleepsleep

Features of my patients’ sleep disorders:

(They don’t have fat necks!) Young, healthy headache sufferers. Some of them get too paralyzed; apnea

results. Some are not paralyzed enough; their legs or arms or jaw moves.

Usually both features are present to some degree.

Do they have two separate sleep disorders? Why would young, healthy people have

not one, but two sleep disorders? Could it be one problem producing both features?

How could we model a paralysis switch that when it malfunctions causes both findings?

The Wobbly Paralysis The Wobbly Paralysis SwitchSwitch

The bulbar muscles have to be The bulbar muscles have to be perfectly paralyzed for an hour or perfectly paralyzed for an hour or more: If you can’t swallow you’ll more: If you can’t swallow you’ll drown, too paralyzed, airway drown, too paralyzed, airway collapses, not paralyzed enough collapses, not paralyzed enough you talk or chew. you talk or chew.

What if we model the brainstem What if we model the brainstem paralysis switch as more of a paralysis switch as more of a speedometer needle, cruise control speedometer needle, cruise control 65 mph perfectly paralyzed?65 mph perfectly paralyzed?

This paralysis switch is run by This paralysis switch is run by dopaminergic pacemaker cells that dopaminergic pacemaker cells that are firing at a certain rate with a are firing at a certain rate with a certain amount of “jitter” in beat to certain amount of “jitter” in beat to beat frequency in the posterior beat frequency in the posterior brainstem.brainstem.

I think these patients have a I think these patients have a paralysis switch that wobbles from paralysis switch that wobbles from “too paralyzed” causing apnea, “too paralyzed” causing apnea, back to “not paralyzed enough” back to “not paralyzed enough” causing leg kicks, talking, chewing.causing leg kicks, talking, chewing.

Not Paralyzed Enough

Too Paralyzed

Not Paralyzed Enough

All the abnormal sleep studies have 2 common

features: We could view all of the abnormal sleep

studies as having one or both of : problems with the timing of sleep, (falling into appropriate stages)– or--the paralysis of sleep.

Both of these features are controlled by the posterior brainstem nuclei and are heavily intertwined.

All of the sleep disorders can be viewed as different facets of these two “switches” not operating correctly.

If headache improves how If headache improves how about other pain?about other pain?

Some of the daily headache sufferers Some of the daily headache sufferers said their back pain got better on CPAP. said their back pain got better on CPAP.

So I started sending many of my chronic So I started sending many of my chronic pain patients for sleep studies.pain patients for sleep studies.

Then the patients who had back pain Then the patients who had back pain and abnormal sleep studies got better and abnormal sleep studies got better on CPAP. Why? on CPAP. Why?

Why does every one of my patients seem Why does every one of my patients seem to have an abnormal sleep study?to have an abnormal sleep study?

Why does everyone Why does everyone and his brother and his brother

seem to have Sleep seem to have Sleep Apnea?Apnea?Did we make it up?Did we make it up?

Has it always been there or is it Has it always been there or is it new?new?

What’s causing it?What’s causing it?Why is it more in “developed Why is it more in “developed

countries”?countries”?

All over the world 9/10 sleep All over the world 9/10 sleep studies are abnormal. With sleep studies are abnormal. With sleep

apnea comes:apnea comes: High blood pressureHigh blood pressure Heart attack, heart arrhythmia (atrial fibrillation)Heart attack, heart arrhythmia (atrial fibrillation) DiabetesDiabetes StrokeStroke ObesityObesity Daytime sleepinessDaytime sleepiness Memory problemsMemory problems DepressionDepression Daily headacheDaily headache Unexplained body pain (“Fibromyalgia”)Unexplained body pain (“Fibromyalgia”) FatigueFatigue

I thought Sleep I thought Sleep Apnea only Apnea only

happened to fat happened to fat peoplepeople

Does obesity cause Does obesity cause sleep apnea or sleep apnea or

does sleep apnea does sleep apnea cause obesity?cause obesity?

Obesity and Sleep ApneaObesity and Sleep Apnea In patients with sleep apnea orexin In patients with sleep apnea orexin

(hypocreatin) ghrelin and leptin levels are (hypocreatin) ghrelin and leptin levels are deranged causing increased appetite and deranged causing increased appetite and increase in fat deposition per calorie increase in fat deposition per calorie consumed.consumed.

Obesity comes with the Sleep Apnea and Obesity comes with the Sleep Apnea and not the reverse.not the reverse.

Losing weight is not the whole story of Losing weight is not the whole story of making Sleep Apnea go away.making Sleep Apnea go away.

Lap band or gastric bypass may help Lap band or gastric bypass may help temporarily but it does not fix the original temporarily but it does not fix the original cause of sleep apnea. They may snore less cause of sleep apnea. They may snore less but still not have restorative sleep.but still not have restorative sleep.

Why is the CPAP experience Why is the CPAP experience important?important?

I just spent the last 5 years trying to help patients I just spent the last 5 years trying to help patients “tolerate” their CPAP mask. “tolerate” their CPAP mask.

It is very hard to do, therefore has very little It is very hard to do, therefore has very little placebo effect in my opinion and it’s not a drug.placebo effect in my opinion and it’s not a drug.

Despite being hard to do, miraculous things Despite being hard to do, miraculous things dodo happen when it’s successful:happen when it’s successful:

Pain goes away, blood pressure goes down, Pain goes away, blood pressure goes down, diabetes gets better, headaches better, mood diabetes gets better, headaches better, mood better, tremor, walking disorders, seizures better.better, tremor, walking disorders, seizures better.

But in many patients, over years, we have to But in many patients, over years, we have to increase the CPAP pressure. increase the CPAP pressure. Whatever is causing Whatever is causing this is still getting worse in the background. this is still getting worse in the background.

In my patients it’sIn my patients it’s not the oxygen!not the oxygen!

Our genetic diseases start to Our genetic diseases start to show up when our repair show up when our repair

phase begins to failphase begins to fail We are all dealt a genetic “deck” the day we

are born. That means every person who sees me with

daily headache has had that genetic tendency since day 1. Why does it start in one person at 15 and another family member at 72?

While we sleep we strengthen or “shore up” every one of our existing genetic weaknesses. When this sleep process fails we can only manifest the “diseases” we have genes for.

But that also means the brain/body still knows what to do but it hasn’t had the time in sleep to make the proper nightly repairs.

Using Sleep as Therapy There are some genetic disorders, like

cerebellar ataxia, where we know the gene mutation but we have no treatment.

I learned that if I could treat the sleep the symptoms improved.

This may mean that neurologic “degenerative” diseases are only inexorably degenerative if the sleep remains non restorative. It may also explain why some people get better and we don’t know why.

These same concepts apply to the heart, the blood vessels, and the autonomic nervous system.

What’s happening here that’s What’s happening here that’s goofing up my patients’ sleep?goofing up my patients’ sleep?

Periaquiductal gray

Why don’t we fix the sleep Why don’t we fix the sleep instead of blowing air up instead of blowing air up

the nose?the nose? In July 2009 one of my 18 y/o patients with daily In July 2009 one of my 18 y/o patients with daily

headache and a sleep study showing headache and a sleep study showing 35 35 unexplained awakenings/hourunexplained awakenings/hour turned out to turned out to have B12 deficiency. have B12 deficiency.

Adding back a Adding back a vitaminvitamin to fix the sleep? to fix the sleep? The brain still remembers what to do, but it is The brain still remembers what to do, but it is

lacking an essential element that it needs? lacking an essential element that it needs? The next month one of my patients mentioned her The next month one of my patients mentioned her

doctor gave her vitamin D and it made her pain doctor gave her vitamin D and it made her pain better.better.

All of a sudden everyone in my practice gets a All of a sudden everyone in my practice gets a B12 and a D level drawn. They all have abnormal B12 and a D level drawn. They all have abnormal sleep studies.sleep studies.

Vitamins and SleepVitamins and Sleep From 8/09 to 12/09 I measured B12 and Vitamin From 8/09 to 12/09 I measured B12 and Vitamin

D levels on every single patient who had a bad D levels on every single patient who had a bad sleep study.sleep study.

A few of the sickest ones, with the worst sleep, A few of the sickest ones, with the worst sleep, had B12 deficiency but every single D was low. had B12 deficiency but every single D was low. (<30 ng/ml)(<30 ng/ml)

In December 2009 two of my headache patients, In December 2009 two of my headache patients, who had been wearing CPAP without who had been wearing CPAP without improvement, came back and said “after three improvement, came back and said “after three weeks that vitamin D made my sleep better and weeks that vitamin D made my sleep better and my headaches went away.” my headaches went away.”

What?What?

Vitamin D and Sleep What is vitamin D and what could it have to What is vitamin D and what could it have to

do with sleep?do with sleep? I thought D was all about bones and calcium.I thought D was all about bones and calcium. Are there vitamin D receptors in the brain? Are there vitamin D receptors in the brain?

Why would there be vitamin D receptors in Why would there be vitamin D receptors in the brain?the brain?

It turns out that there It turns out that there areare vitamin D vitamin D receptors in the brain and they’re receptors in the brain and they’re concentrated in that posterior brainstem concentrated in that posterior brainstem stripe I’ve been looking at for the last 6 stripe I’ve been looking at for the last 6 years.years.

Vitamin D receptors concentrate in 3 Vitamin D receptors concentrate in 3 brain areas; brain areas; periaquiductal grey, lateral periaquiductal grey, lateral

ventricles and pituitary/hypothalamusventricles and pituitary/hypothalamus

What is Vitamin D What is Vitamin D anyway?anyway?

IT’S NOT A VITAMIN!!!IT’S NOT A VITAMIN!!! It’s a HORMONEIt’s a HORMONE that we make, like thyroid, that we make, like thyroid,

cortisol, estrogen, testosterone.cortisol, estrogen, testosterone. We make it on our skin from cholesterolWe make it on our skin from cholesterol.. UVB light hits the skin and changes 7 UVB light hits the skin and changes 7

dehydrocholesterol to D hormone; cholecalciferol.dehydrocholesterol to D hormone; cholecalciferol. Every animal on the planet; hamsters, birds, reptiles, Every animal on the planet; hamsters, birds, reptiles,

fish and insects make this chemical, on their skin, fish and insects make this chemical, on their skin, from UVB light.from UVB light.

This implies that it is very, very old.This implies that it is very, very old. Probably the dinosaurs made Hormone D. If it’s found Probably the dinosaurs made Hormone D. If it’s found

in fish it’s there from way before we all crawled out of in fish it’s there from way before we all crawled out of the water.the water.

What’s it for?What’s it for? Would it have anything to do with sleep?Would it have anything to do with sleep?

In the 1970’s- 80’s Dr. In the 1970’s- 80’s Dr. Walter Stumpf “explained” Walter Stumpf “explained”

what D hormone doeswhat D hormone does

Dr. Walter Stumpf and D Dr. Walter Stumpf and D hormonehormone

Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HF. Stumpf WE, Sar M, Reid FA, Tanaka Y, DeLuca HF. Target cells for 1,25-dihydroxyvitamin D3 in intestinal tract, stomach, kidney, skin, pituitary, and parathyroid. Science. 1979 Dec 7;206(4423):1188-90.. Science. 1979 Dec 7;206(4423):1188-90.

Stumpf, WE and O'Brien, LP. Stumpf, WE and O'Brien, LP. 1,25 (OH)2 Vitamin D3 sites of action in the brain: an autoradiographic study. Histochem.87:393-406, 1987.. Histochem.87:393-406, 1987.

Stumpf, WE, Clark, SA, O'Brien, LP and Reid, FA. Stumpf, WE, Clark, SA, O'Brien, LP and Reid, FA. 1,25 (OH)2 vitamin D3 sites of action in spinal cord and sensory ganglion. Anat. Embriol. 177:307-310, 1988.. Anat. Embriol. 177:307-310, 1988.

Stumpf WE, Denny MEStumpf WE, Denny ME. Vitamin D (soltriol), light, and reproduction. Am J Obstet Gynecol. 1989 Am J Obstet Gynecol. 1989 Nov;161(5):1375-84. Nov;161(5):1375-84.

Stumpf WE, Privette TH. Stumpf WE, Privette TH. Light, vitamin D and psychiatry. Role Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder and other mental processes. seasonal affective disorder and other mental processes. Psychopharmacology (Berl). 1989;97(3):285-94 Psychopharmacology (Berl). 1989;97(3):285-94

Bidmon HJ, Gutkowska J, Murakami R, Stumpf WE. Bidmon HJ, Gutkowska J, Murakami R, Stumpf WE. Vitamin D receptors in heart: effects on atrial natriuretic factor. . Experientia. 1991 Sep 15;47(9):958-62. Experientia. 1991 Sep 15;47(9):958-62.

(This is a small sample of many, many articles.)(This is a small sample of many, many articles.)

Why would we have a hormone Why would we have a hormone made by UVB that bosses the made by UVB that bosses the pituitary and hypothalamus?pituitary and hypothalamus?

UVB is the only wavelength UVB is the only wavelength present in summer present in summer not in winter.not in winter.

D hormone adjusts metabolism to the two, very D hormone adjusts metabolism to the two, very different, states of weather and food availability.different, states of weather and food availability.

In the summer we eat lots of perishable food, In the summer we eat lots of perishable food, plow the soil, gather food, build things, sleep plow the soil, gather food, build things, sleep little.little.

In the winter In the winter there is no foodthere is no food. . We hibernate, we sleep more, channel more of We hibernate, we sleep more, channel more of

the calories we eat into fat.the calories we eat into fat. Any animal that can eat very little and still put Any animal that can eat very little and still put

on a little fat in the winter has a survival on a little fat in the winter has a survival advantage.advantage.

Where are the D Receptors? Where are the D Receptors? (Where they are may suggest what (Where they are may suggest what

they do.)they do.) GI tract:GI tract: Teeth, salivary glands, tongue, Teeth, salivary glands, tongue,

esophageal sphincter, esophageal sphincter, Stomach cells that make acidStomach cells that make acid Liver cells that make bileLiver cells that make bile Pancreatic islet cells that make Pancreatic islet cells that make

insulininsulin

Summer: High D message Summer: High D message (70-85)(70-85)

Eat 10,000 calories per day, digest it all easily.Eat 10,000 calories per day, digest it all easily. Put all of those calories into building the body.Put all of those calories into building the body. Sleep fewer hours ( deep, paralyzed, work sleep Sleep fewer hours ( deep, paralyzed, work sleep

done in 6-8 hours).done in 6-8 hours). There are D receptors in ovaries, fallopian tubes, There are D receptors in ovaries, fallopian tubes,

testes;testes; The estrogen and testosterone follow the D. The estrogen and testosterone follow the D.

September is harvest time, the D is at its highest, September is harvest time, the D is at its highest, it’s time to mate and make a baby.it’s time to mate and make a baby.

Make a baby in Sept. it’s born in June, baby’s in Make a baby in Sept. it’s born in June, baby’s in the sun to make D hormone on his skin.the sun to make D hormone on his skin.

Thyroid follows the D also. All cellular energy Thyroid follows the D also. All cellular energy increases.increases.

Winter: Lower D message Winter: Lower D message (50-70)(50-70)

Because there is only UVB in the summer, Because there is only UVB in the summer, after September we start to depend on our D after September we start to depend on our D hormone stores. hormone stores.

Sleep longer, paralyzed phases much less Sleep longer, paralyzed phases much less consolidated.consolidated.

Eat less, but put half of everything we eat Eat less, but put half of everything we eat into fat. Remember those hormones that into fat. Remember those hormones that make you hungry and tell your body to store make you hungry and tell your body to store more fat? (Orexin, ghrelin, leptin.)more fat? (Orexin, ghrelin, leptin.)

Very low D may lead to very goofed up sleep. Very low D may lead to very goofed up sleep. Could this be the cause of sleep apnea?Could this be the cause of sleep apnea?

D Hormone and SleepD Hormone and Sleep This implies there may be a natural This implies there may be a natural reasonreason and and curecure

for the recent epidemic of obstructive sleep apneafor the recent epidemic of obstructive sleep apnea There is no proof of this yet, it is only my There is no proof of this yet, it is only my

hypothesis, but the timing and the populations hypothesis, but the timing and the populations affected make it very likely.affected make it very likely.

Early 1980’s: Begin the epidemics of OSA, Early 1980’s: Begin the epidemics of OSA, fibromyalgia, chronic fatigue and pain specialists.fibromyalgia, chronic fatigue and pain specialists.

Late 70’s early 80’s; sunscreen, air conditioning, Late 70’s early 80’s; sunscreen, air conditioning, television, and computers.television, and computers.

Sleep apnea and associated disorders are epidemic Sleep apnea and associated disorders are epidemic in “developed” countries. in “developed” countries.

Once the electricity arrives so does the air Once the electricity arrives so does the air conditioning. Humans aren’t stupid, now when it’s conditioning. Humans aren’t stupid, now when it’s hot we go inside or buy an air conditioned tractor.hot we go inside or buy an air conditioned tractor.

D Hormone not Vitamin D

The sleep connection is the only new observation, everything else was described 30 years ago but you didn’t learn about it in medical school. Why is that?

When the word “vitamin” was applied to this chemical it became overlooked by Medicine and has not been taught to those of us who should be conveying this to our patients.

Over the last 30 years all of the basic science observations to support Dr. Stumpf’s theories have been published. Why don’t we know about these articles?

They’re in the Nutrition Journals, the European Endocrine Journals, and just the last 5 years, our medical journals.

Epidemiologically related to Epidemiologically related to D deficiency- (same list as D deficiency- (same list as

sleep apnea)sleep apnea) High blood pressureHigh blood pressure High cholesterol High cholesterol Heart attack, atherosclerosisHeart attack, atherosclerosis Heart arrhythmia ( Atrial fibrillation)Heart arrhythmia ( Atrial fibrillation) StrokeStroke ObesityObesity Memory problemsMemory problems DepressionDepression Daily headacheDaily headache Unexplained body pain (“Fibromyalgia”)Unexplained body pain (“Fibromyalgia”)

Disorders of GI tract Disorders of GI tract epidemiologically related to D epidemiologically related to D

deficiencydeficiency Gastric refluxGastric reflux B 12 deficiency is usually a secondary deficiency B 12 deficiency is usually a secondary deficiency

caused by D deficiency. (Not enough stomach acid, caused by D deficiency. (Not enough stomach acid, can’t break the B12 off the meat. Iron deficiency the can’t break the B12 off the meat. Iron deficiency the same.)same.)

Poor stomach motilityPoor stomach motility Gallstones, (D and cholesterol are liquid component Gallstones, (D and cholesterol are liquid component

of bile)of bile) Diabetes (islet cells have D receptors)Diabetes (islet cells have D receptors) Decreased “good” colonic bacteria with bloating etc.Decreased “good” colonic bacteria with bloating etc. ConstipationConstipation Esophageal cancerEsophageal cancer Colon cancerColon cancer

Cholesterol and D Cholesterol and D HormoneHormone

If we make vitamin D on our skin from If we make vitamin D on our skin from cholesterol does that mean that everyone in my cholesterol does that mean that everyone in my practice with high cholesterol has a low D? practice with high cholesterol has a low D?

There is conflicting literature concerning this. There is conflicting literature concerning this. Are there really two ways to treat this high Are there really two ways to treat this high

cholesterol? cholesterol? Give the natural D hormone that’s lacking or give Give the natural D hormone that’s lacking or give

a statin?a statin?

7 dehydrocholesterol Pre vitamin D

Cholesterol and D Cholesterol and D HormoneHormone

When the statin lowers the cholesterol does that mean When the statin lowers the cholesterol does that mean that 7 dehydrocholesterol, the raw material that that 7 dehydrocholesterol, the raw material that makes vitamin D, is lower on the skin too? If so does makes vitamin D, is lower on the skin too? If so does that imply that I won’t be able to make vitamin D now that imply that I won’t be able to make vitamin D now when I go out in the sun? when I go out in the sun?

There is conflicting literature on this as well.There is conflicting literature on this as well. Might this also mean that my sun exposed areas are Might this also mean that my sun exposed areas are

now exposed without the protective effects of vitamin now exposed without the protective effects of vitamin D producing more wrinkling, color changes, and D producing more wrinkling, color changes, and bruising?bruising?

We have the enzyme that makes active D 1,25 OH on We have the enzyme that makes active D 1,25 OH on our skin, it keeps the skin cells in line, keeps them our skin, it keeps the skin cells in line, keeps them from turning cancerous or reproducing from turning cancerous or reproducing inappropriately. Keeps the fibroblasts healthy repairing inappropriately. Keeps the fibroblasts healthy repairing our skin.our skin.

Vitamin D inflammatory Vitamin D inflammatory connectionconnection

There are D receptors all over the WBC’s. There are D receptors all over the WBC’s. Low D appears to increase proinflamatory actions, Low D appears to increase proinflamatory actions,

leading to joint inflammation that in combination leading to joint inflammation that in combination with lack of repair in sleep leads to with lack of repair in sleep leads to Knee replacementKnee replacement Hip arthritis, replacementHip arthritis, replacement Rotator cuff surgeriesRotator cuff surgeries ? Vascular damage leading to aneurysms and ? Vascular damage leading to aneurysms and

atherosclerosisatherosclerosis D is needed not only for bone health but also for D is needed not only for bone health but also for

fibroblast, skin and blood vessel health.fibroblast, skin and blood vessel health. All blood cells have vitamin D receptors, even All blood cells have vitamin D receptors, even

platelets and red cells.platelets and red cells. Probably the Probably the time that we do most of the time that we do most of the

maintenance using this hormone is during maintenance using this hormone is during sleepsleep, so the effect of it’s absence is doubled or , so the effect of it’s absence is doubled or tripled by the disrupted sleep.tripled by the disrupted sleep.

Autoimmune Diseases Autoimmune Diseases Epidemiologically linked to D Epidemiologically linked to D

deficiencydeficiency Rheumatoid arthritisRheumatoid arthritis LupusLupus Ulcerative ColitisUlcerative Colitis PsoriasisPsoriasis Celiac DiseaseCeliac Disease AsthmaAsthma AllergiesAllergies Multiple SclerosisMultiple Sclerosis ?Inflammatory aspects of cardiovascular ?Inflammatory aspects of cardiovascular

diseasedisease

Why did they call it a vitamin if it’s not one?

Why the “D2” and “D3” numbers ? The original rickets model was established by narrowing

down a rat’s diet until their bones got osteoporotic. Oops, rats are nocturnal animals, they don’t go out in the

sun. In order to become nocturnal they had to evolve a D receptor that could use the D found in food. (Vampires apparently use our D.)

The first chemicals found that corrected the rat’s bone disorder were from fungus on grain. They were named vitamin D1 and D2. They appeared to be vitamins, they were, in fact, in the food.

Unfortunately what we make on our skin is D3, a different chemical. That chemical may have different effects at different D receptor subtypes within the body. Every non nocturnal animal on this planet including man makes and uses D3, and it’s not in the food anywhere. It is not a vitamin.

D2 may have variable effects in different species and different individuals. In my patients it seems to worsen the sleep. It may act as a partial agonist at some sites, partial antagonist at others.

What does this D have to do with what I do in

Cardiology?

Vitamin D and Cardiovascular Dz

25 hydroxyvitamin D, IGF-1 and metabolic syndrome at 45 years of age: a cross sectional study in the 1958 British Birth Cohort. Diabetes 2008 Feb 57(2) 298-305. Serum 25 (OH) D is inversely associated with metabolic syndrome. Metabolic syndrome prevalence is lowest when both 25(OH) D and IGF-1 are high.

25 Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis. 2009 205 (1) 255-260. Strong independent relationship of 25 (OH) deficiency with prevalence CVD in a large sample.

Vitamin D, race and cardiovascular mortality: findings from a national US sample. Ann Fam Med 2010 Jan-Feb 8(1) 11-18. Black white differences in 25(OH) D levels may contribute to excess cardiovascular mortality in blacks.

Vitamin D and Cardiovascular Dz Adiposity, cardiometabolic risk, and vitamin D status: the

Framingham Heart Study. Diabetes. 2010 Jan 59 (1) 242-248. Vitamin D status is strongly associated with variation in subcutaneous and especially visceral adiposity.

Vitamin D status and Cardiometabolic Risk Factors in the United State Adolescent Population. Pediatrics 2009 Aug 3. Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia and metabolic syndrome independent of adiposity.

Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population. Eur J Endocrinol 2009 160(6) 965-71. In non obese young subjects we observe new relationships between 25 (OH) D and several metabolic risk factors and adiponectin.

Vitamin D and Cardiovascular Dz

Association of leptin, 25 hydroxyvitamin D and parthyroid hormone in women. Nutr Cancer 2009 61(2) 225-31. Leptin was highly correlated with the BMI/25 OH Vit D ratio consistent with a model in which BMI and 25 (OH) Vit D are the primary determinants of circulating leptin and PTH levels.

Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endo Metab 2009 Oct 94(10) 4023-30. 25 (OH) D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Hypoviaminosis D associated endothelial dysfunction may predisopose to higher rates of cardiovascular disease.

Vitamin D and Atrial Naturetic Factor

Vitamin D receptors in heart: Effects on atrial naturetic factor. Experimentia 1991 47 958-962. In rats vitamin D receptors concentrated in the right atrium, colocalizing with atrial naturetic peptide. Changes in ANF tissue and blood levels under dietary deficiency and treatment with 1,25 D3 suggest direct genomic action of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion.

Vitamin D and lipid/cholesterol

Simvastatin does not affect vitamin D status, but low vitamin D levels are associated with dyslipidemia: Results form a randomised controlled trial. Int J End 2010 Article ID 957174 6 pgs. These findings do not support a pharmacologic effect of statins on vitamin D status, but do suggest that vitamin D may influence plasma lipid profile and thus be of importance to cardiovascular health.

My personal feeling is that we’ve developed statins over the last 30 years to treat an epidemic of high cholesterol that has arisen due to the pandemic of vitamin D deficiency.

I do not have enough proof to suggest that you should use D to bring the cholesterol to normal, however I do want to suggest that you watch for this possibility.

Epidemiology is fine. What about treatment trials?

OK so they’re seen together. Lets see the vitamin D cure the disease.

VITAMIN What’s the right dose? HORMONE What’s the right level? What’s the dose to get to the right

level? This is the hard part. Why is the sleep observation so

pivotal?

Sleep is the cure for Cardiovascular Risk Factors Dr. Perkins just showed you how correcting the sleep has

profound effects on the multiple cardiovascular risk factors. The cure is the sleep, not the D. CPAP is one way, D perhaps

another. And if it’s a deficiency state why not try Rx that first?

The curative effect is not D, it’s a perfect D level producing restorative sleep every night. Too high D makes the sleep disorder return 60-80 appears to be the normal range.

Normal sleep, night after night, is what cures the body.

Presumably people who live outside get to 80 in November and fall by 10 pts a month during the winter to 50 in March or April.

Lower than 50 appears to bring on the sleep disorder.

How to replace the D to fix the How to replace the D to fix the sleep and why all the sleep and why all the

controversy about dosing?controversy about dosing? From 8/2010 - 12/2010 I had given everyone 1000 IU of From 8/2010 - 12/2010 I had given everyone 1000 IU of

vitamin D3 because that is what the FDA recommends. vitamin D3 because that is what the FDA recommends. (Contrary to popular rumor I am not (Contrary to popular rumor I am not reallyreally a vitamin nut.) a vitamin nut.)

The two guys wearing the CPAP were the only ones who The two guys wearing the CPAP were the only ones who got better probably because their D levels were higher, in got better probably because their D levels were higher, in the 40’s, before supplementing and CPAP definitely helps the 40’s, before supplementing and CPAP definitely helps so it probably gave the boost they needed to normalize so it probably gave the boost they needed to normalize their sleep.their sleep.

In January 2010, after learning about D, I came back In January 2010, after learning about D, I came back expecting all my headache patients to be cured, but none expecting all my headache patients to be cured, but none were better, they still couldn’t sleep and had a headache were better, they still couldn’t sleep and had a headache every day.So I checked their levels again. every day.So I checked their levels again.

On 1000 IU/day their D levels were all 10 points On 1000 IU/day their D levels were all 10 points lowerlower. After 4 months of winter, taking FDA . After 4 months of winter, taking FDA recommended dose, they were 28 in August, 18 in January. recommended dose, they were 28 in August, 18 in January. So 1000 IU per day is just fine if you start with a level of So 1000 IU per day is just fine if you start with a level of 80 in August, but it won’t get you normal sleep in the 80 in August, but it won’t get you normal sleep in the winter if you’re starting below 30..winter if you’re starting below 30..

What is the right level ?What is the right level ? By February I was giving 2,000 IU/day. By February I was giving 2,000 IU/day.

“Call me back about your sleep.”“Call me back about your sleep.” And what is a “normal D”? (30-100) If all of And what is a “normal D”? (30-100) If all of

my patients with a level of 28 have lousy my patients with a level of 28 have lousy sleep and a headache, is 30-35 really sleep and a headache, is 30-35 really “normal”?“normal”?

www.vitamindcouncil.orgwww.vitamindcouncil.org believes the believes the level should be 80 ng/ml in September and level should be 80 ng/ml in September and no lower than 50 at the end of winter and no lower than 50 at the end of winter and it takes 10,000 IU/day to STAY THE SAME. it takes 10,000 IU/day to STAY THE SAME.

What is the right level to achieve normal What is the right level to achieve normal sleep? sleep?

What’s the right dose? We make 20,000 IU on our skin in 1-6

hours in the sun, middle of the summer, middle of the day based on skin color.

If we’re not out there every day in summer 1,000 IU/day is probably not going to replace this.

Is it 10,000 IU to “stay the same” both in winter and summer?

What’s the level of a thriving human on no pills with normal sleep and no pain?

Probably 60-80 ng/ml

The right daily dose is different The right daily dose is different for every person, it’s the level to for every person, it’s the level to be achieved that is the same, just be achieved that is the same, just

like thyroid or estrogen.like thyroid or estrogen. The right dose is the dose that allows you and your The right dose is the dose that allows you and your patients to sleep normally and wake up rested without a patients to sleep normally and wake up rested without a sleeping pill or a pain pill or a reflux pill, etc.sleeping pill or a pain pill or a reflux pill, etc.

The The one time dose to replete D storesone time dose to replete D stores is much higher is much higher than what is being tried in most clinical trials. And than what is being tried in most clinical trials. And is is not the same concept as a daily maintenance dosenot the same concept as a daily maintenance dose in a patient who’s level is now 60-80.in a patient who’s level is now 60-80.

Also for normal sleep, Also for normal sleep, dosing once a week, or a dosing once a week, or a month, does not appear to be the same as daily month, does not appear to be the same as daily dosingdosing. But it’s still the level, not the dose that’s . But it’s still the level, not the dose that’s important.important.

The proper treatment trials aren’t out yet because it’s The proper treatment trials aren’t out yet because it’s not clear to many of the researchers that this is a not clear to many of the researchers that this is a hormone,hormone, it’s not the dose it’s the level. it’s not the dose it’s the level.

And they don’t know that it’s the sleep that cures the And they don’t know that it’s the sleep that cures the disease, whether that’s stroke, heart attack or metabolic disease, whether that’s stroke, heart attack or metabolic syndrome.syndrome.

Vitamin D Toxicity and why the FDA’s not crazy

All of the “toxicity” refers to hyper calcemia but most of my patients had “toxicity” symptoms way before the calcium went up.

In most patients the symptoms of fatigue, pain and poor sleep start to return above a level of 90-95. The movements in sleep come back leading to pain on awakening again.

THE SLEEP DISORDER COMES BACK with a too high D just like too low D.

As with every hormone: go too high things go wrong, go too low things go wrong.

Vitamin D Toxicity and why the FDA’s not crazy

This is not only a hormone, it is a hormone with a narrow band of normal and it changes in each person from month to month and year to year based on sun exposure and skin type.

How could the FDA possibly recommend a single dose for all Americans living from Florida to Alaska with very divergent skin colors and lifestyles without screwing everyone up?

They wisely chose to recommend a tiny, tiny dose, i.e., not enough to screw anyone up.

This chemical should never be supplemented by the government, it’s as odd as putting testosterone or estrogen in the milk.

It should never have been over the counter so that we’re not sure how much is in the non regulated pills we’re taking.

And And THE FDA RECOMMENDED DOSE HAS ABSOLUTELY THE FDA RECOMMENDED DOSE HAS ABSOLUTELY NOTHING TO DO WITH THE LEVEL THAT NEEDS TO NOTHING TO DO WITH THE LEVEL THAT NEEDS TO BE ACHIEVED IN A CLINICAL TRIALBE ACHIEVED IN A CLINICAL TRIAL to produce normal to produce normal sleep and normal physiologic effect.sleep and normal physiologic effect.

D Hormone and D D Hormone and D receptors: multilayered receptors: multilayered

complexitycomplexity ““Vitamin D” will turn out to be a multi layered endocrine Vitamin D” will turn out to be a multi layered endocrine

system with at least 3, maybe more, separate, active system with at least 3, maybe more, separate, active forms. In certain situations D25OH and D1,25OH may forms. In certain situations D25OH and D1,25OH may both bind to D receptors and produce a heterodimer of 2 D both bind to D receptors and produce a heterodimer of 2 D receptors that has a different effect than D 1,25 OH by receptors that has a different effect than D 1,25 OH by itself. D 24, 25 OH may have other responsibilities.itself. D 24, 25 OH may have other responsibilities.

There are different receptor subtypes in different organs of There are different receptor subtypes in different organs of the body and species differences in receptor subtypes as the body and species differences in receptor subtypes as well. Observations in nocturnal animals such as rats (or well. Observations in nocturnal animals such as rats (or vampires) cannot always be generalized to humans.vampires) cannot always be generalized to humans.

Different organs in the body make their active D at the Different organs in the body make their active D at the rate they need it and D 1,25 OH probably does not rate they need it and D 1,25 OH probably does not penetrate into the brain. (Which is after all the only penetrate into the brain. (Which is after all the only important organ in the body.)important organ in the body.)

D 1,25 OH is D 1,25 OH is notnot the only active chemical and D25 OH is the only active chemical and D25 OH is notnot just a storage chemical. In higher “summer” doses just a storage chemical. In higher “summer” doses D25OH is probably active on mood and sleep the day it is D25OH is probably active on mood and sleep the day it is given.given.

The D is not the only sleep chemical, dopamine runs

the sleep The single group that has terrible sleep studies

but deny being tired in the morning are the Parkinsons patients.

Many, many of your cardiology patients in their 60-80’s with A fib are these patients. They all have low vitamin D’s.

They also have a dopamine deficiency that magnifies their sleep disorder because dopamine runs the sleep.

If you find a B12 <400 likely the D is low causing this. Always replace both. The daily B12 pills are better.

If they’re not better when their D and B12 are normal send them to me to fix the dopamine.

Other common presentations linked to D

hormone deficiency Young women who have just had a few babies and come

in to the ER with chest pain and rapid heart beat and you can’t find a cause; Check the vitamin D (and B12) level.

The babies suck up mom’s vitamin D and it never gets replaced because prenatal vitamins have 400 IU of vitamin D.

They see me for headache but many of them have also seen you for what was called “panic attack” and is really something going on in the heart. Atrial D receptors? A PFO that is opening?

Young people with unexplained valvular disease or cardiomyopathy may have vitamin D deficiency always look for it and treat it first.

This D has something to do with high CPK’s from statins. There are vitamin D receptors in the anterior horn cells and the complaint of “weakness” is often in the background in D deficiency.

Other supporting factors D hormone has other cofactors that are

necessary for its action so I usually give a multivitamin also.

B12 helps the sleep and should be >500. If it’s below 500 I supplement with 1000 mcg per day as well.

Iron is a cofactor to make dopamine and should be supplemented if low also.

With higher D doses if leg cramps occur or headaches worsen give sunflower or pumpkin seeds as a magnesium source daily. OK, so that does sound a bit like a vitamin wacko, sorry, (Dr. Fanous taught me this.)

My Basic Sleep ConceptsMy Basic Sleep Concepts

Our patients are unconscious and can’t report what Our patients are unconscious and can’t report what happened in sleep. That does not mean it’s not happened in sleep. That does not mean it’s not important.important.

We blame people who can’t sleep. We tell them We blame people who can’t sleep. We tell them they’re “doing it wrong”. But sleep is involuntary, they’re “doing it wrong”. But sleep is involuntary, you can’t really “do it wrong”.you can’t really “do it wrong”.

Normal healthy humans all fall asleep around 9-10 Normal healthy humans all fall asleep around 9-10 pm, all do the same things at about the same time in pm, all do the same things at about the same time in sleep and wake up about 6-7am. sleep and wake up about 6-7am.

DrowsinessDrowsiness is a specific state that warns us that we is a specific state that warns us that we are going to fall asleep. We assume that it’s always are going to fall asleep. We assume that it’s always going to be there before we fall asleep. Some of your going to be there before we fall asleep. Some of your patients with unexplained loss of consciousness are patients with unexplained loss of consciousness are falling asleep abruptly without drowsiness because falling asleep abruptly without drowsiness because their sleep mechanism is so severely abnormal that their sleep mechanism is so severely abnormal that the warning is not there any more.the warning is not there any more.

Now what do I do? The right test is D25OH. Don’t test D1, 25 OH it does not reflect The right test is D25OH. Don’t test D1, 25 OH it does not reflect

the D stores. the D stores. Medicare pays for it 4 times per year ICD 9: 268.9.Medicare pays for it 4 times per year ICD 9: 268.9. If the patient has been on D2 your measurement has to test D3 If the patient has been on D2 your measurement has to test D3

25OH separately from D2 25OH. Look at the D3 25 OH level.25OH separately from D2 25OH. Look at the D3 25 OH level. D2 and D3 are D2 and D3 are not not really the samereally the same. Our arrogance continues to . Our arrogance continues to

limit us. We really do not know everything, err on the side of the limit us. We really do not know everything, err on the side of the natural chemical, it’s free!natural chemical, it’s free!

Start yourself and your patients on whatever dose you feel Start yourself and your patients on whatever dose you feel comfortable with daily, then measure a level again in 2-3 comfortable with daily, then measure a level again in 2-3 months. months.

Get the level to 60-80 ng/ml. Sleep does not get better until Get the level to 60-80 ng/ml. Sleep does not get better until then. then.

Even though you’re not used to seeing a level in this range it Even though you’re not used to seeing a level in this range it really is the really is the normalnormal range. If the recognized “normal” is 30-100 range. If the recognized “normal” is 30-100 it can’t hurt to get the level to 60-80. See how you and your it can’t hurt to get the level to 60-80. See how you and your patients feel there instead of 15-20.patients feel there instead of 15-20.

Our healthy vitamin D Our healthy vitamin D futurefuture