Scientists Want to Align Your Internal Clock Because Timing Is Everything


internal clock

In life, timing is everything.

Your body’s internal clock — the circadian rhythm — regulates an enormous variety of processes: when you sleep and wake, when you’re hungry, when you’re most productive. Given its palpable effect on so much of our lives, it’s not surprising that it has an enormous impact on our health as well. Researchers have linked circadian health to the risk of diabetes, cardiovascular disease, and neurodegeneration. It’s also known that the timing of meals and medicines can influence how they’re metabolized.

The ability to measure one’s internal clock is vital to improving health and personalizing medicine. It could be used to predict who is at risk for disease and track recovery from injuries. It can also be used to time the delivery of chemotherapy and blood pressure and other drugs so that they have the optimum effect at lower doses, minimizing the risk of side effects.

However, reading one’s internal clock precisely enough remains a major challenge in sleep and circadian health. The current approach requires taking hourly samples of blood melatonin — the hormone that controls sleep — during day and night, which is expensive and extremely burdensome for the patient. This makes it impossible to incorporate into routine clinical evaluations.

My colleagues and I wanted to obtain precise measurements of internal time without the need for burdensome serial sampling. I’m a computational biologist with a passion for using mathematical and computational algorithms to make sense of complex data. My collaborators, Phyllis Zee and Ravi Allada, are world-renowned experts in sleep medicine and circadian biology. Working together, we designed a simple blood test to read a person’s internal clock.

Listening to the Music of Cells

The circadian rhythm is present in every single cell of your body, guided by the central clock that resides in the suprachiasmatic nucleus region of the brain. Like the secondary clocks in an old factory, these so-called “peripheral” clocks are synchronized to the master clock in your brain, but also tick forward on their owneven in petri dishes!

Your cells keep time through a network of core clock genes that interact in a feedback loop: When one gene turns on, its activity causes another molecule to turn it back down, and this competition results in an ebb and flow of gene activation within a 24-hour cycle. These genes in turn regulate the activity of other genes, which also oscillate over the course of the day. This mechanism of periodic gene activation orchestrates biological processes across cells and tissues, allowing them to take place in synchrony at specific times of day.

The circadian rhythm orchestrates many biological processes, including digestion, immune function, and blood pressure, all of which rise and fall at specific times of the day. Misregulation of the circadian rhythm can have adverse effects on metabolism, cognitive function, and cardiovascular health.
The circadian rhythm orchestrates many biological processes, including digestion, immune function, and blood pressure, all of which rise and fall at specific times of the day. Misregulation of the circadian rhythm can have adverse effects on metabolism, cognitive function, and cardiovascular health.

The discovery of the core clock genes is so fundamental to our understanding of how biological functions are orchestrated that it was recognized by the Nobel Committee last year. Jeffrey C. Hall, Michael Rosbash, and Michael W. Young together won the 2017 Nobel Prize in Physiology or Medicine “for their discoveries of molecular mechanisms controlling the circadian rhythm.” Other researchers have noted that as many as 40 percent of all other genes respond to the circadian rhythm, changing their activity over the course of the day as well.

This gave us an idea: Perhaps we could use the activity levels of a set of genes in the blood to deduce a person’s internal time — the time your body thinks it is, regardless of what the clock on the wall says. Many of us have had the experience of feeling “out of sync” with our environments — of feeling like it’s 5:00 a.m. even though our alarm insists it’s already 7:00 a.m. That can be a result of our activities being out of sync with our internal clock — the clock on the wall isn’t always a good indication of what time it is for you personally. Knowing what a profound impact one’s internal clock can have on biology and health, we were inspired to try to gauge gene activity to measure the precise internal time in an individual’s body. We developed TimeSignature: a sophisticated computational algorithm that could measure a person’s internal clock from gene expression using two simple blood draws.

Designing a Robust Test

To achieve our goals, TimeSignature had to be easy (measuring a minimal number of genes in just a couple blood draws), highly accurate, and — most importantly — robust. That is, it should provide just as accurate a measure of your intrinsic physiological time regardless of whether you’d gotten a good night’s sleep, recently returned from an overseas vacation, or were up all night with a new baby. And it needed to work not just in our labs but in labs across the country and around the world.

A mismatch between our internal time and our daily activities may raise the risk of disease.
A mismatch between our internal time and our daily activities may raise the risk of disease.

To develop the gene signature biomarker, we collected tens of thousands of measurements every two hours from a group of healthy adult volunteers. These measurements indicated how active each gene was in the blood of each person during the course of the day. We also used published data from three other studies that had collected similar measurements. We then developed a new machine learning algorithm, called TimeSignature, that could computationally search through this data to pull out a small set of biomarkers that would reveal the time of day. A set of 41 genes was identified as being the best markers.

Surprisingly, not all the TimeSignature genes are part of the known “core clock” circuit — many of them are genes for other biological functions, such as your immune system, that are driven by the clock to fluctuate over the day. This underscores how important circadian control is — its effect on other biological processes is so strong that we can use those processes to monitor the clock!

Using data from a small subset of the patients from one of the public studies, we trained the TimeSignature machine to predict the time of day based on the activity of those 41 genes. (Data from the other patients was kept separate for testing our method.) Based on the training data, TimeSignature was able to “learn” how different patterns of gene activity correlate with different times of day. Having learned those patterns, TimeSignature can then analyze the activity of these genes in combination to work out the time that your body thinks it is. For example, although it might be 7 a.m. outside, the gene activity in your blood might correspond to the 5 a.m. pattern, indicating that it’s still 5 a.m. in your body.

Many genes peak in activity at different times of day. This set of 41 genes, each shown as a different color, shows a robust wave of circadian expression. By monitoring the level of each gene relative to the others, the TimeSignature algorithm learns to ‘read’ your body’s internal clock.
Many genes peak in activity at different times of day. This set of 41 genes, each shown as a different color, shows a robust wave of circadian expression. By monitoring the level of each gene relative to the others, the TimeSignature algorithm learns to ‘read’ your body’s internal clock. 

We then tested our TimeSignature algorithm by applying it to the remaining data, and demonstrated that it was highly accurate: We were able to deduce a person’s internal time to within 1.5 hours. We also demonstrated our algorithm works on data collected in different labs around the world, suggesting it could be easily adopted. We were also able to demonstrate that our TimeSignature test could detect a person’s intrinsic circadian rhythm with high accuracy, even if they were sleep-deprived or jet-lagged.

Harmonizing Health With TimeSignature

By making circadian rhythms easy to measure, TimeSignature opens up a wide range of possibilities for integrating time into personalized medicine. Although the importance of circadian rhythms to health has been noted, we have really only scratched the surface when it comes to understanding how they work. With TimeSignature, researchers can now easily include highly accurate measures of internal time in their studies, incorporating this vital measurement using just two simple blood draws. TimeSignature enables scientists to investigate how the physiological clock impacts the risk of various diseases, the efficacy of new drugs, the best times to study or exercise, and more.

Of course, there’s still a lot of work to be done. While we know that circadian misalignment is a risk factor for disease, we don’t yet know how much misalignment is bad for you. TimeSignature enables further research to quantify the precise relationships between circadian rhythms and disease. By comparing the TimeSignatures of people with and without disease, we can investigate how a disrupted clock correlates with disease and predict who is at risk.

Down the road, we envision that TimeSignature will make its way into your doctor’s office, where your circadian health could be monitored just as quickly, easily, and accurately as a cholesterol test. Many drugs, for example, have optimal times for dosing, but the best time for you to take your blood pressure medicine or chemotherapy may differ from somebody else.

Previously, there was no clinically feasible way to measure this, but TimeSignature makes it possible for your doctor to do a simple blood test, analyze the activity of 41 genes, and recommend the time that would give you the most effective benefits. We also know that circadian misalignment — when your body’s clock is out of sync with the external time — is a treatable risk factor for cognitive decline; with TimeSignature, we could predict who is at risk, and potentially intervene to align their clocks.

Dancing to the circadian rhythm: NHLBI researcher finds new genes for body’s internal clock


Might lead to better understanding of sleep disorders, heart disease, and more

If you feel energized or tired around the same time each day, or routinely get up early or stay up late—the familiar ‘early riser’ or ‘night owl’ syndrome—you are witnessing, in real time, your circadian rhythm at work. That’s the 24-hour internal body clock which controls your sleep/wake cycle.

Circadian rhythms have long fascinated researchers—decades ago three of them marked a critical milestone when they discovered the molecular components behind that mysterious timing cycle. For this game-changing finding, the trio recently was awarded the 2017 Nobel Prize in Physiology or Medicine. Since their discovery researchers have come to know that the circadian clock affects not just sleep, but hormone production, eating habits, body temperature, heart rate, and other biological functions.

Yet, for all these advances, scientists still know relatively little about the clock’s genetic underpinnings. Now a team of NHLBI researchers is working to change that with the discovery of scores of new genes they say have a profound impact on the circadian rhythm. These researchers say these genes could hold the key to a new understanding of a wide range of health conditions, from insomnia to heart disease, and perhaps pave the way for new treatments for them.

Dr. Susan Harbison holding a sleep monitor
NHLBI researcher Dr. Susan Harbison displays a device used to record sleep and activity in fruit flies.

“We all ‘dance’ to the circadian rhythm,” said Susan Harbison, Ph.D., an investigator in the NHLBI’s Laboratory of Systems Genetics, who is among an elite cadre of scientists studying the complex genetics of the biological clock. “Quietly, this clock influences our body and our health in ways that are just now being understood.”For sure, the studies are slowly unfolding. For example, long-term night shift work has been associated with an increased risk of high blood pressure, obesity, and heart disease. Some studies have shown a link between circadian rhythm changes and cancer.  And a recent study by researchers in France found that heart surgery is safer in the afternoon than in the morning, a phenomenon they attribute to the body’s circadian clock having a better repair mechanism in the afternoon than in the morning.

Now, thanks to Harbison and her research team, new insights into why some people experience longer or shorter periods of wakefulness or sleepiness than others—and what it might mean for a host of health conditions—could be on the horizon.

To explore this line of research more deeply, Harbison is working with a favorite laboratory model of sleep researchers: Drosophila melanogaster, the common fruit fly.  While this little fly may seem like an unlikely choice, it turns out to be an appropriate stand-in for humans.

“The clock mechanisms regulating circadian rhythm in humans and fruit flies are remarkably similar,” Harbison said. “They both have biological rhythms of about 24 hours. In fact, the genes involved in mammalian circadian rhythms were first identified in flies.”

Previous studies by other researchers had identified approximately 126 genes for circadian rhythms in fruit flies.  In recent studies using a natural population of flies, Harbison’s group estimates that there are more than 250 new genes associated with the circadian clock, among the largest number identified to date.  Many of the genes appear to be associated with nerve cell development—not surprising, she said, given the wide-ranging impact of circadian rhythms on biological processes.

In addition to finding this treasure trove of clock-related genes, Harbison’s group also found that the circadian patterns among the flies were highly variable, and that some of the genes code for variability in the circadian clock. Some flies had unusually long circadian periods—up to 31 hours—while others had extremely short circadian periods of 15 hours.  In other words: Just like people, there were ‘early risers’ and ‘night owls’ and long sleepers and short sleepers among the fruit flies.

“Before we did our studies, there was little attention paid to the genes responsible for variability in the circadian period,” noted Harbison, who is also looking at environmental factors that might influence these genes, such as drugs like alcohol and caffeine. “We now have new details about this variability, and that opens up a whole new avenue of research in understanding what these genes do and how they influence the circadian clock.”

See description
This graph shows rest and activity patterns for two different fruit flies. The graph on the left shows the rest and activity of a fly with a normal circadian period (about 24 hours). Vertical blue bars show the fly's activity during the day (yellow horizontal bars) and night (black horizontal bars). The graph on the right shows the rest and activity of a fly with an abnormal circadian period (about 31 hours). The abnormal pattern is similar to an individual with a circadian rhythm disorder. Graphic courtesy of Susan Harbison, NHLBI.

Harbison says that for most people, disruptions to the circadian clock have a temporary effect, as occurs with daylight saving time or jet lag from overseas travel, when a person may experience short-term fatigue as they adjust to a time change or new time zone. But for some, disruptions to the clock are associated with chronic health effects, as occurs with night shift workers. Others who suffer from certain circadian rhythm disorders— such as delayed sleep phase disorder—may find it extremely difficult to fall asleep at a desired time.

“The clock architecture is not set in stone and is not a ‘one size fits all’ device,” she noted. “What we’re finding is that the effect of disrupting the circadian clock differs depending on the genetic makeup of the individual. Just as human height and other traits are variable, the same is true of circadian traits among different individuals.”

In the future, Harbison hopes that these newly identified genes might ultimately be linked to specific disease processes in humans. Her findings could lead to the discovery of new biomarkers for diagnosing circadian disorders and lay the groundwork for new treatments for sleep and circadian disorders in humans.

7 science-backed reasons ‘early to bed, early to rise’ really works


You’re probably familiar with Ben Franklin’s old saying “Early to bed, and early to rise makes a man healthy, wealthy and wise.”

It’s actually true.

I know. I’m not a morning person either, but I’ve found that by going to bed earlier, I actually can wake up first thing in the A.M. That has made me more productive, and dare I say more successful. But, that’s not just me.

Here’s the science to back up the words of advice from Ben Franklin.

dawn texting early morning

 1. Sleep helps you better deal with negativity.

Unhappily, a study in 2014 determined that people who go to bed later are more likely to be overwhelmed with repetitive negative thoughts. As an entrepreneur, I can vouch for that statement. I can’t count how many nights of sleep I’ve lost worrying about a team member, problem-solving how to secure more funding or wondering if maybe it’s time to close-up shop.

But while sleep disruption leads to more pessimistic thoughts, a good night’s rest helps you deal with problems and improves problem-solving. Developing a pattern that allows you to sleep a full 6-9 hours each night helps you handle any negativity that’s being thrown your way.

 

2. Sleep enhances your chances of success.

According to Christopher Randler, a biology professor at the University of Education in Heidelberg, Germany, “When it comes to business success, morning people hold the important cards. My earlier research showed that they tend to get better grades in school, which get them into better colleges, which then lead to better job opportunities. Morning people also anticipate problems and try to minimize them.”

Randler added, “They’re proactive. Many studies have linked this trait, proactivity, with better job performance, greater career success, and higher wages.”

“Though evening people do have some advantages — other studies reveal they tend to be smarter and more creative than morning types, have a better sense of humor, and are more outgoing — they’re out of sync with the typical corporate schedule.”

Furthermore, a good night’s rest can make you more productive since it assists with improving your concentration, memory, and solving complex problems.

3. Morning people are more persistent, cooperative, agreeable, conscientious, and proactive.

Randler’s work listed above already determined that larks are more active than night owls, but his research also discovered that early-risers tended to be more persistent, cooperative, agreeable, and conscientious. These are all positive traits that leaders and successful possess since they make them more likable, disciplined, appreciative, and eager to learn.


4. Sleep keeps you healthy.

If you’re a freelancer, small business owner and a parent, like so many of us are, you can’t afford to get sick. Luckily, that’s something that getting enough shuteye and waking up early can help you with.

For starters, research has found that getting plenty of sleep strengthens your immune system — which is an excellent preventive against whatever nasty bugs are going around.

Secondly, getting enough rest keeps you energized enough so that you can exercise — besides waking up earlier gives you the time to squeeze in a workout before you get distracted. And, when you sleep-in, you tend to skip breakfast, which means when you do get hungry you’re going to crave unhealthier options.

 

5. Sleep reduces stress and makes you happier.

Here’s two scenarios.

You have to be out of the door by 8 a.m., and you sleep-in until 7:30 a.m. You’re rushing to take a shower, brush your teeth, grab something to eat and make sure that you have everything you need for the rest of the day.

If you woke up at 6 a.m. that gives you two hours to not only get ready, but also catch up on emails, the news, or work on a pet project. Most importantly, it makes your mornings less stressful, which in turn, will make your days less stressful.

The first hour or so of your morning sets the tone for the rest of your day. A study conducted by Dr. Joerg Huber of Roehampton University in London found that “Morning people tend to be healthier and happier as well as having lower body mass indexes.”

 

6. You procrastinate less.

A 2008 study found that early risers didn’t procrastinate as much as people who stayed up later. This statement shouldn’t come as a surprise, since they’re proactive and have more quiet time in the morning to complete tasks. When you aren’t waiting until the last minute, you reduce your stress and can fall asleep worry-free.

7. Sleep makes you look better.

There was an interesting study from the University of Stockholm that found that those who appeared tired are also more likely to be perceived as unhealthy and less attractive. That’s not necessarily the end of the world, but when you’re trying to make a solid first impression on the opposite sex, potential client, or prospective investor, you want to look as good as you possibly can.

You can make the switch to morning person.

If you’re not a morning person or you are having a difficult time trying or staying to fall asleep, here are a couple of pointers to help you sleep better at night:

Take baby steps. Start slowly by waking up earlier than you normally do, like 15 minutes for the first week, 20 minutes the following week, and so forth until you reach your goal time.

Create and stick to a sleep schedule. Even if you don’t fall asleep right away, at least make it a habit to start getting into bed at a set time every night, such as by 9 p.m.

Stay away from bright lights. Electronics, such as your TV and smartphone, produce light that stimulates your brain. Instead of watching Netflix, read for an hour.

Follow the circadian rhythm. This is your body’s clock telling you when to sleep and when to wake-up. Since it’s a part of nature, try camping for a couple of days to get back on-track.

Set the mood. The ideal sleeping condition is pitch black and a temperature between 60 and 67 degrees.

Avoid alcohol and eating before bed. Both of these prevent you from getting a good night’s sleep.

Exercise. This makes you tired enough so that you’ll sleep straight through the night.

E-Readers Foil Good Night’s Sleep


Light-emitting electronic devices keep readers awake longer than old-fashioned print.

Use of a light-emitting electronic book (LE-eBook) in the hours before bedtime can adversely impact overall health, alertness and the circadian clock, which synchronizes the daily rhythm of sleep to external environmental time cues, according to Harvard Medical School researchers at Brigham and Women’s Hospital. These findings of the study that compared the biological effects of reading an LE-eBook to a printed book are published in the Proceedings of the National Academy of Sciences on December 22, 2014.

iStock

“We found the body’s natural circadian rhythms were interrupted by the short-wavelength enriched light, otherwise known as blue light, from these electronic devices,” said Anne-Marie Chang, corresponding author and associate neuroscientist at Brigham and Women’s Division of Sleep and Circadian Disorders. “Participants reading an LE-eBook took longer to fall asleep and had reduced evening sleepiness, reduced melatonin secretion, later timing of their circadian clock and reduced next-morning alertness than when reading a printed book.”

Previous research has shown that blue light suppresses melatonin, impacts the circadian clock and increases alertness, but little was known about the effects of this popular technology on sleep. The use of light-emitting devices immediately before bedtime is a concern because of the extremely powerful effect that light has on the body’s natural sleep/wake pattern and how that may play a role in perpetuating sleep deficiency.

During the two-week inpatient study, twelve participants read digital books on an iPad for four hours before bedtime each night for five consecutive nights. This was repeated with printed books. The order was randomized with some reading on the iPad first and others reading the printed book first. Participants reading on the iPad took longer to fall asleep, were less sleepy in the evening and spent less time in REM sleep. They had reduced secretion of melatonin, a hormone that normally rises in the evening and plays a role in inducing sleepiness. Additionally, iPad readers had a delayed circadian rhythm, indicated by melatonin levels, of more than an hour. Participants who read on the iPad were less sleepy before bedtime but were sleepier and less alert the following morning after eight hours of sleep. Although iPads were used in this study, researchers also measured other devices that emit blue light, including eReaders, laptops, cell phones and LED monitors.

“In the past 50 years, there has been a decline in average sleep duration and quality,” said Charles Czeisler, the HMS Frank Baldino, Jr., Ph.D. Professor of Sleep Medicine and chief of the Brigham and Women’s Division of Sleep and Circadian Disorders. “Since more people are choosing electronic devices for reading, communication and entertainment, particularly children and adolescents who already experience significant sleep loss, epidemiological research evaluating the long-term consequences of these devices on health and safety is urgently needed.”

Researchers emphasize the importance of these findings, given recent evidence linking chronic suppression of melatonin secretion by nocturnal light exposure with the increased risk of breast cancer, colorectal cancer and prostate cancer.

Altering the circadian rhythm: an interview with Dr. Doug Kojetin.


Please can you give a brief overview of the circadian rhythm?

The human circadian rhythm is an internal “clock” that controls numerous physiological processes in the body.

The circadian rhythm is affected by many different stimuli—such as sleep and light, which are the most broadly appreciated ways—but also eating— all of which can modulate, or change, important processes in our bodies such as temperature, production of hormones or other signalling small molecules, cellular regeneration, and others.

How much is currently known about the physiological processes that underlie the circadian rhythm in humans?

It has become clear that the circadian rhythm is an important physiological control mechanism in our bodies, not only in terms of regulating entire organs, such as the brain, but studies have also shown that the circadian rhythm persists in (and can be controlled to affect) individual cells within our body.

And more recently there have been significant advances in identifying proteins and receptors that are involved in regulating the human circadian rhythm. Some of the proteins, such as the REV-ERB receptors, appear to be druggable, indicating we may be able to design drugs to alter the circadian rhythm.

What potential benefits would the ability to alter the circadian rhythm have?

There are likely many benefits that could arise from designing a drug to alter the circadian rhythm. It is possible such drugs could cure sleeping disorders, for example, or to extend wakefulness in cases where it may be appropriate or necessary to do so.

In addition, dysfunction in the circadian rhythm is implicated in numerous diseases. As one example, people who work the night shift have increased risk for a number of diseases, including substance abuse, depression, obesity, cardiovascular issues, cancer, as well as family/home problems. Drugs targeting the circadian rhythm may help to treat these types of issues and others.

It was recently announced that you had discovered a pair of compounds that could potentially alter the circadian rhythm. What are these compounds and how did you discover them?

These are compounds that bind to and affect the function of a class of receptors called the REV-ERBs. These compounds are similar to a natural porphyrin ligand found in the body, heme.

Heme, which contains an iron metal center, is the natural ligand for the REV-ERB receptors. We were curious to know if REV-ERBs could bind to a heme-like molecule with a different metal center that is not normally found in the body.

In our study published in the Journal of Biological Chemistry, we show that two additional porphyrin analogs of heme, which contain cobalt or zinc instead of iron, can bind to REV-ERBs similar to heme—but interestingly they have different functional effects on REV-ERB activity.

How are REV-ERBs normally regulated and why do cobalt protoporphyrin IX (CoPP) and zinc protoporphyrin IX (ZnPP) have a different effect on REV-ERBs?

Our study indeed found that changing the metal center of the porphyrin scaffold of heme—called protoporphyrin IX—from iron to either cobalt (CoPP) or zinc (ZnPP) inhibited the function of REV-ERB.

To determine why CoPP and ZnPP inhibits REV-ERB function, we studied how the compounds bind to REV-ERB on the atomic level. Interestingly, or perhaps unfortunately, the results were in fact quite similar to other published studies on heme-bound REV-ERB. This indicates to us that there are likely more complex functional mechanisms at play here as opposed to the compound simply binding to REV-ERB.

In fact, other studies have shown that REV-ERB function can be affected by small molecule gases in our body—such as molecular oxygen (O2), carbon monoxide (CO) and nitric oxide (NO)—binding to the heme/REV-ERB complex. Our data on CoPP and ZnPP indicate that changing the metal center might affect the ability of these small molecule gases to bind to REV-ERB.

How could the compounds you discovered be used to uncover new therapeutics for diabetes and obesity?

There is great interest in designing “synthetic” compounds that can alter the circadian rhythm and optimizing them for use as therapeutics in humans. Unfortunately, many compounds that are developed synthetically through medicinal chemistry approaches can be toxic in the body.

Once nice feature about CoPP and ZnPP is that they are derived from a natural product commonly found in the body, heme—which is a natural ligand for the REV-ERBs. In fact, prior studies have demonstrated that CoPP has functional effects “in vivo” (in mice), including anti-obesity activity.

What impact do you think your results will have and what are the next steps in your research?

In other studies, we have designed “synthetic” REV-ERB compounds that do alter the circadian rhythm. However, all of these “synthetic” compounds are REV-ERB agonists (or activators). Thus these new compounds, CoPP and ZnPP, which are REV-ERB antagonists (inhibitors), may provide a unique tool to determine how different classes of potential, future REV-ERB drugs (activators vs. inhibitors) can alter the circadian rhythm.

In addition to working with other scientists to determine their functional effects in vivo, we are also working to study the molecular details of why changing the metal center of the natural ligand heme can cause an opposite effect on REV-ERB activity.

How far do you think we will be able to alter the circadian rhythm in the future? What will be the main limiting factors?

Although we have come a long way in understanding how the circadian rhythm is controlled, there is still a lot we do not know. Certainly a dysfunctional circadian rhythm can cause disease, and drugs may be a viable treatment, but there are always risks to using a drug to treat any disorder.

In addition, the major challenge for any drug development project is optimizing the drugs for use in humans. Although a compound may show beneficial effects in controlled laboratory settings or in animal models, one cannot easily predict if the same compound can be tolerated in humans and it can take years to work around this bottleneck.

Where can readers find more information?

Our study was published in the Journal of Biological Chemistry. The text can be found at the journal website:

http://www.jbc.org/content/early/2014/05/28/jbc.M113.545111.abstract

And at the US National Library of Medicine “PubMed” website:

http://www.ncbi.nlm.nih.gov/pubmed/24872411

Hospital Room Lighting May Worsen Your Mood and Pain.


Story at-a-glance

  • Hospital patients are exposed to insufficient levels of light, disrupting both their circadian rhythms and sleep cycles
  • Light-deprived patients had fragmented and low levels of sleep, and those with the lowest exposures to light during the day reported more depressed mood and fatigue
  • Inadequate bright-light exposure has a far-reaching impact on your most critical bodily functions, including your ability to heal
  • Exposure to night-time light may also hinder the production of the hormone melatonin, which is very important for immune health
  • If you or a loved one is confined to a hospital room, move to areas with brighter natural light as much as possible, or bring in some full-spectrum light bulbs, and wear an eye mask at night to block night-time artificial light exposures

Hopefully you have never spent much time in a hospital, but if you have you likely experienced frequent disruptions to your sleep.

Aside from the beeping machines and nightly checks from hospital staff, your room was probably dimly lit with artificial light both day and night — a major impediment to proper sleep and well-being.

As a new study in the Journal of Advanced Nursing1 revealed, the lighting in many hospital rooms may be so bad that it actually worsens patients’ sleep, mood and pain levels.

Hospital-Room Lighting May Lead to Disrupted Sleep Cycles, Increased Pain and Fatigue

The study found that, on average, hospital patients in the study were exposed to about 105 lux (a measure of light emission) daily. This is a very low level of light; for comparison, an office would generally provide about 500 lux and being outdoors on a sunny day could provide 100,000 lux.2

The rooms were so dimly lit that many hospital patients had trouble sleeping. Your body requires a minimum of 1,500 lux for 15 minutes a day just to maintain a normal sleep-wake cycle, but ideally it should be closer to 4,000 for healthful sleep.3

Not surprisingly, the researchers found that the patients’ sleep time was “fragmented and low,” with most averaging just four hours of sleep a night.

Those with the lowest exposures to light during the day also reported more depressed mood and fatigue than those exposed to more light. The researchers noted:4 “Low light exposure significantly predicted fatigue and total mood disturbance.”

Why You Need Exposure to Bright Light During the Day

When full-spectrum light enters your eyes, it not only goes to your visual centers enabling you to see, it also goes to your brain’s hypothalamus where it affects your entire body.

Your hypothalamus controls body temperature, hunger and thirst, water balance and blood pressure. Additionally, it controls your body’s master gland, the pituitary, which secretes many essential hormones, including those that influence your mood.

Exposure to full-spectrum lighting is actually one effective therapy used for treating depression, infection, and much more – so it’s not surprising that hospital patients deprived of such exposures had poorer moods and fatigue.

Studies have also shown that poor lighting in the workplace triggers headaches, stress, fatigue and strained watery eyes, not to mention inferior work production.

Conversely, companies that have switched to full-spectrum lights report improved employee morale, greater productivity, reduced errors and decreased absenteeism. Some experts even believe that “malillumination” is to light what malnutrition is to food.

In a hospital setting, this has serious ramifications, as patients are already under profound stress due to illness and may be further stressed by a lack of natural bright light.

Your ‘body clock’ is also housed in tiny centers located in your hypothalamus, controlling your body’s circadian rhythm. This light-sensitive rhythm is dependent on Mother Nature, with its natural cycles of light and darkness, to function optimally.

Consequently, anything that disrupts these rhythms, like inadequate sunlight exposure to your body (including your eyes), has a far-reaching impact on your body’s ability to function and, certainly, also on its ability to heal.

Nighttime Light Exposure is Also Detrimental

While the featured study didn’t focus specifically on hospital patients’ nighttime light exposures, they’re likely to be significant. Most hospital room doors remain ajar all night, allowing artificial light from the hall to flood the room. There are also lights on medical equipment and monitors, and if your room is not private you may also be exposed to light from a roommates’ television or bathroom trips.

This is important because just as your body requires bright-light exposure during the day, it requires pitch-blackness at night to function optimally – which is all the more critical in the case of a hospital stay when bodily self-healing is most needed.

When you turn on a light at night, you immediately send your brain misinformation about the light-dark cycle. The only thing your brain interprets light to be is day. Believing daytime has arrived, your biological clock instructs your pineal gland to immediately cease its production of the hormone melatonin – a significant blow to your health, especially if you’re ill, as melatonin produces a number of health benefits in terms of your immune system. It’s a powerful antioxidant and free radical scavenger that helps combat inflammation.

In fact, melatonin is so integral to your immune system that a lack of it causes your thymus gland, a critically important part of your immune system, to atrophy.5 In addition, melatonin helps you fall asleep and bestows a feeling of overall comfort and well being, and it has proven to have an impressive array of anti-cancer benefits.6 So unnaturally suppressing this essential hormone is the last thing that a recovering hospital patient needs.

If a Loved One is In the Hospital, Let the Daylight Shine In

The best way to get exposure to healthy full-spectrum light is to do it the way nature intended, by going out in the sun with your bare skin – and ‘bare’ eyes — exposed on a regular basis. If you or a loved one is confined to a hospital room, however, the next best option is to move to areas with brighter natural light as much as possible, or alternatively bring in some full-spectrum light bulbs.

At night, the opposite holds true. You should turn off lights as much as possible, keep the door closed and close the blinds on the window. Wearing an eye mask is another simple trick that can help to keep unwanted light exposures to a minimum if you’re spending the night in a hospital. Taken together, these are simple ways to boost mood and improve sleep and fatigue levels among hospitalized patients.

The Other Major Risk of Spending Time in a Hospital

No matter how important it is, poor lighting may be the least of your worries if you find yourself hospitalized, as once you’re hospitalized you’re immediately at risk for medical errors, which is actually a leading cause of death in the US. According to the most recent research7 into the cost of medical mistakes in terms of lives lost, 210,000 Americans are killed by preventable hospital errors each year.

When deaths related to diagnostic errors, errors of omission, and failure to follow guidelines are included, the number skyrockets to an estimated 440,000 preventable hospital deaths each year!

One of the best safeguards is to have someone there with you. Dr. Andrew Saul has written an entire book on the issue of safeguarding your health while hospitalized. Frequently, you’re going to be relatively debilitated, especially post-op when you’re under the influence of anesthesia, and you won’t have the opportunity to see clearly the types of processes that are going on.

For every medication given in the hospital, ask, “What is this medication? What is it for? What’s the dose?” Take notes. Ask questions. Building a relationship with the nurses can go a long way. Also, when they realize they’re going to be questioned, they’re more likely to go through that extra step of due diligence to make sure they’re getting it right—that’s human nature. Of course, knowing how to prevent disease so you can avoid hospitals in the first place is clearly your best bet. One of the best strategies on that end is to optimize your diet. You can get up to speed on that by reviewing my comprehensive Nutrition Plan.

It’s Important for Virtually Everyone to Optimize Light Exposure: 5 Top Tips

Getting back to the issue of lighting, this isn’t only an issue for hospital patients. Virtually everyone requires exposure to bright light during the day and darkness at night for optimal health. Toward that end, here are my top tips to optimize your light exposure on a daily (and nightly) basis:

1.    Get some sun in the morning, if possible. Your circadian system needs bright light to reset itself. Ten to 15 minutes of morning sunlight will send a strong message to your internal clock that day has arrived, making it less likely to be confused by weaker light signals during the night. More sunlight exposure is required as you age.

2.    Make sure you get BRIGHT sun exposure regularly. Remember, your pineal gland produces melatonin roughly in approximation to the contrast of bright sun exposure in the day and complete darkness at night. If you work indoors, make a point to get outdoors during your breaks.

3.    Avoid watching TV or using your computer in the evening, at least an hour or so before going to bed.These devices emit blue light, which tricks your brain into thinking it’s still daytime. Normally your brain starts secreting melatonin between 9 and 10 pm, and these devices emit light that may stifle that process.

4.    Sleep in complete darkness, or as close to it as possible. Even the slightest bit of light in your bedroom can disrupt your biological clock and your pineal gland’s melatonin production. This means that even the tiny glow from your clock radio could be interfering with your sleep, so cover your alarm clock up at night or get rid of it altogether. You may want to cover your windows with drapes or blackout shades, or wear an eye mask while you sleep.

5.    Install a low-wattage yellow, orange or red light bulb if you need a source of light for navigation at night.Light in these bandwidths does not shut down melatonin production in the way that white and blue bandwidth light does. Salt lamps are handy for this purpose.

 

 

 

 

To Sleep, Perchance to Clean.


Study reveals brain ‘takes out the trash’ while we sleep.

In findings that give fresh meaning to the old adage that a good night’s sleep clears the mind, a new study shows that a recently discovered system that flushes waste from the brain is primarily active during sleep. This revelation could transform scientists’ understanding of the biological purpose of sleep and point to new ways to treat neurological disorders.

“This study shows that the brain has different functional states when asleep and when awake,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center (URMC) Center for Translational Neuromedicine and lead author of the article. “In fact, the restorative nature of sleep appears to be the result of the active clearance of the by-products of neural activity that accumulate during wakefulness.”

The study, which was published today in the journal Science, reveals that the brain’s unique method of waste removal – dubbed the glymphatic system – is highly active during sleep, clearing away toxins responsible for Alzheimer’s disease and other neurological disorders. Furthermore, the researchers found that during sleep the brain’s cells reduce in size, allowing waste to be removed more effectively.

Image shows cerebral spinal fluid (in blue) entering the brain via a “plumbing system” that piggybacks on the brain’s blood vessels.

The purpose of sleep is a question that has captivated both philosophers and scientists since the time of the ancient Greeks. When considered from a practical standpoint, sleep is a puzzling biological state. Practically every species of animal from the fruit fly to the right whale is known to sleep in some fashion. But this period of dormancy has significant drawbacks, particularly when predators lurk about. This has led to the observation that if sleep does not perform a vital biological function then it is perhaps one of evolution’s biggest mistakes.

While recent findings have shown that sleep can help store and consolidate memories, these benefits do not appear to outweigh the accompanying vulnerability, leading scientists to speculate that there must be a more essential function to the sleep-wake cycle.

The new findings hinge on the discovery last year by Nedergaard and her colleagues of a previously unknown system of waste removal that is unique to the brain. The system responsible for disposing cellular waste in the rest of the body, the lymphatic system, does not extend to the brain. This is because the brain maintains its own closed “ecosystem” and is protected by a complex system molecular gateways – called the blood-brain barrier – that tightly control what enters and exits the brain.

The brain’s process of clearing waste had long eluded scientists for the simple fact that it could only be observed in the living brain, something that was not possible before the advent of new imaging technologies, namely two-photon microscopy. Using these techniques, researchers were able to observe in mice – whose brains are remarkably similar to humans – what amounts to a plumbing system that piggybacks on the brain’s blood vessels and pumps cerebral spinal fluid (CSF) through the brain’s tissue, flushing waste back into the circulatory system where it eventually makes its way to the general blood circulation system and, ultimately, the liver.

The timely removal of waste from the brain is essential where the unchecked accumulation of toxic proteins such as amyloid-beta can lead to Alzheimer’s disease. In fact, almost every neurodegenerative disease is associated with the accumulation of cellular waste products.

One of the clues hinting that the glymphatic system may be more active during sleep was the fact that the amount of energy consumed by the brain does not decrease dramatically while we sleep. Because pumping CSF demands a great deal of energy, researchers speculated that the process of cleaning may not be compatible with the functions the brain must perform when we are awake and actively processing information.

Through a series of experiments in mice, the researchers observed that the glymphatic system was almost 10-fold more active during sleep and that the sleeping brain removed significantly more amyloid-beta.

“The brain only has limited energy at its disposal and it appears that it must choice between two different functional states – awake and aware or asleep and cleaning up,” said Nedergaard. “You can think of it like having a house party. You can either entertain the guests or clean up the house, but you can’t really do both at the same time.”

Another startling finding was that the cells in the brain “shrink” by 60 percent during sleep. This contraction creates more space between the cells and allows CSF to wash more freely through the brain tissue. In contrast, when awake the brain’s cells are closer together, restricting the flow of CSF.

The researchers observed that a hormone called noradrenaline is less active in sleep. This neurotransmitter is known to be released in bursts when brain needs to become alert, typically in response to fear or other external stimulus. The researchers speculate that noradrenaline may serve as a “master regulator” controlling the contraction and expansion of the brain’s cells during sleep-wake cycles.

“These findings have significant implications for treating ‘dirty brain’ disease like Alzheimer’s,” said Nedergaard. “Understanding precisely how and when the brain activates the glymphatic system and clears waste is a critical first step in efforts to potentially modulate this system and make it work more efficiently.”

Study reveals why the body clock is slow to adjust to time changes.


New research in mice reveals why the body is so slow to recover from jet-lag and identifies a target for the development of drugs that could help us to adjust faster to changes in time zone.

With funding from the Wellcome Trust and F. Hoffmann La Roche, researchers at the University of Oxford, University of Notre Dame and F. Hoffmann La Roche have identified a mechanism that limits the ability of the body clock to adjust to changes in patterns of light and dark. And the team show that if you block the activity of this gene in mice, they recover faster from disturbances in their daily light/dark cycle that were designed to simulate jet-lag.

plane

Nearly all life on Earth has an internal circadian body clock that keeps us ticking on a 24-hour cycle, synchronising a variety of bodily functions such as sleeping and eating with the cycle of light and dark in a solar day. When we travel to a different time zone our body clock eventually adjusts to the local time. However this can take up to one day for every hour the clock is shifted, resulting in several days of fatigue and discombobulation.

In mammals, the circadian clock is controlled by an area of the brain called the suprachiasmatic nuclei (SCN) which pulls every cell in the body into the same biological rhythm. It receives information from a specialised system in the eyes, separate from the mechanisms we use to ‘see’, which senses the time of day by detecting environmental light, synchronising the clock to local time. Until now, little was known about the molecular mechanisms of how light affects activity in the SCN to ‘tune’ the clock and why it takes so long to adjust when the light cycle changes.

To investigate this, the Oxford University team led by Dr Stuart Peirson and Professor Russell Foster, used mice to examine the patterns of gene expression in the SCN following a pulse of light during the hours of darkness. They identified around 100 genes that were switched on in response to light, revealing a sequence of events that act to retune the circadian clock. Amongst these, they identified one molecule, SIK1, that terminates this response, acting as a brake to limit the effects of light on the clock. When they blocked the activity of SIK1, the mice adjusted faster to changes in light cycle.

Dr Peirson explains: “We’ve identified a system that actively prevents the body clock from re-adjusting. If you think about, it makes sense to have a buffering mechanism in place to provide some stability to the clock. The clock needs to be sure that it is getting a reliable signal, and if the signal occurs at the same time over several days it probably has biological relevance. But it is this same buffering mechanism that slows down our ability to adjust to a new time zone and causes jet lag.”

Disruptions in the circadian system have been linked to chronic diseases including cancer, diabetes, and heart disease, as well as weakened immunity to infections and impaired cognition. More recently, researchers are uncovering that circadian disturbances are a common feature of several mental illnesses, including schizophrenia and bipolar disorder.

Russell Foster, Director of the recently established Oxford University Sleep and Circadian Neuroscience Institute supported by the Wellcome Trust, said: “We’re still several years away from a cure for jet-lag but understanding the mechanisms that generate and regulate our circadian clock gives us targets to develop drugs to help bring our bodies in tune with the solar cycle.Such drugs could potentially have broader therapeutic value for people with mental health issues.”

Source: Cell.

 

 

Tips for Resetting Your Internal Clock and Sleeping Better.


Story at-a-glance

  • Factors contributing to poor sleep include vitamin and mineral deficiencies
  • Magnesium deficiency can cause insomnia; lack of potassium can lead to difficulty staying asleep; and vitamin D deficiency has been linked to excessive daytime sleepiness
  • Melatonin is one of the most important nutrients to help you optimize your sleep, as it plays a crucial role in your circadian rhythm or internal clock
  • Camping could help you reset an internal clock gone haywire from modern living, as the sun adjusts your clock to its natural state, undoing the influence of light bulbs
  • To promote good sleep, make sure you’re exposed to full natural light during the day, and avoid artificial lighting once the sun goes down, especially as bedtime draws near.
  • vitamins-sleep

Good sleep is one of the cornerstones of health, without which optimal health will remain elusive. Impaired sleep can increase your risk of a wide variety of diseases and disorders, including:

Numerous factors can contribute to poor sleep, including vitamin and mineral deficiencies. The featured article by LiveScience1 highlights three nutrients tied to three common sleep problems. To this, I would add melatonin, which is both a hormone and an antioxidant:

  • Magnesium deficiency can cause insomnia
  • Lack of potassium can lead to difficulty staying asleep throughout the night
  • Vitamin D deficiency has been linked to excessive daytime sleepiness

The Importance of Melatonin

I personally believe that melatonin is one of the most important nutrients to help you optimize your sleep, as it plays a crucial role in your circadian rhythm or internal clock.

Melatonin is produced by a pea-sized gland in the middle of your brain called the pineal gland. When your circadian rhythms are disrupted, your body produces less melatonin, which reduces your ability to fight cancer.

Melatonin actually helps suppress free radicals that can lead to cancer. (This is why tumors grow faster when you sleep poorly.) It also produces a number of health benefits related to your immune system.

For most people, the pineal gland is totally inactive during the day. But, at night, when  you are exposed to darkness, your pineal gland   begins producing melatonin to be released into your blood.

Melatonin makes you feel sleepy, and in a normal night’s sleep, your melatonin levels stay elevated for about 12 hours (usually between 9 pm and 9 am). Then, as the sun rises and your day begins, your pineal gland reduces your production of melatonin.

The levels in your blood decrease until they’re hardly measurable at all. This rise and fall of your melatonin levels are part and parcel of your internal clock that dictates when you’re sleepy and when you feel fully awake.

How to Optimize Your Melatonin and Reset Your Circadian Rhythm

In related news, research2 suggests camping could help you reset an internal clock gone haywire from modern living. As reported by the Christian Science Monitor3:

“Scientists at the University of Colorado Boulder found that if you live by the sun’s schedule, you are more likely to go to bed at least an hour earlier, wake up an hour earlier, and be less groggy, because your internal clock and external reality are more in sync. The sun adjusts your clock to what may be its natural state, undoing the influence of light bulbs. “

Since humans evolved in the glow of firelight, the yellow, orange and red wavelengths don’t suppress melatonin production the way white and blue wavelengths do. If you want to protect your melatonin cycle, when the sun goes down you would shift to a low wattage bulb with yellow, orange, or red light.

One good option is using a salt lamp illuminated by a 5-watt bulb. It’s important to realize that turning on a light in the middle of the night, even for a short moment, such as when you get up to go to the bathroom, will disrupt yourmelatonin production and interfere with your sleep.

Ideally it is best to increase melatonin levels naturally with exposure to bright sunlight in the daytime (along with full spectrum fluorescent bulbs in the winter) and absolute complete darkness at night. If that isn’t possible, you may want to consider a melatonin supplement.

In scientific studies, melatonin has been shown to help people fall asleep faster and stay asleep, experience less restlessness, and prevent daytime fatigue. Keep in mind that only a very small dose is required — typically 0.25mg or 0.5mg to start with, and you can adjust it up from there.

Taking higher doses, such as 3 mg, can sometimes make you more wakeful instead of sleepier, so adjust your dose carefully. While melatonin is most commonly used in tablet or spray form, certain foods also contain it. Cherries, for instance, are a natural source of melatonin, and drinking tart cherry juice has been found to be beneficial in improving sleep duration and quality4.

Up to 80 Percent of Americans are Magnesium-Deficient

Lack of magnesium may play a role in insomnia, and dietary surveys suggest that the majority of Americans are simply not getting enough magnesium from their diet alone5. Other factors that can make you more prone to magnesium deficiency include:

An unhealthy digestive system, which impairs your body’s ability to absorb magnesium (Crohn’s disease, leaky gut, etc.) Diabetes, especially if it’s poorly controlled, leading to increased magnesium loss in urine Age — older adults are more likely to be magnesium deficient because absorption decreases with age and the elderly are more likely to take medications that can interfere with absorption
Unhealthy kidneys, which contribute to excessive loss of magnesium in urine Alcoholism — up to 60 percent of alcoholics have low blood levels of magnesium6 Certain medications — diuretics, antibiotics and medications used to treat cancer can all result in magnesium deficiency

 

To avoid magnesium deficiency, make sure you’re eating a varied, whole-food diet like the one described in my nutrition plan. Green leafy vegetables like spinach and Swiss chard are excellent sources of magnesium, as are some beans, nuts and seeds, like almonds, pumpkin seeds, sunflower- and sesame seeds. Avocados are also a good source. Juicing your greens is an excellent way to optimize your nutrition. This is my personal strategy. I typically drink one pint to one quart of fresh green vegetable juice every day, and it is one of my primary sources of magnesium.

If you decide to use a supplement, magnesium threonate is likely one of the best sources of magnesium as it seems to penetrate cell membranes, including the mitochondria, which results in higher energy levels. Additionally it also penetrates the blood-brain barrier and seems to do wonders to treat and prevent dementia and improve memory.

Balance Your Magnesium with Calcium, Vitamin K2 and D

One of the major benefits of getting your nutrients from a varied whole food diet is that you’re far less likely to end up with too much of one nutrient at the expense of others. Foods in general contain all the cofactors and needed co-nutrients in the proper amounts for optimal health, which takes out the guess work. When you’re using supplements, you need to become a bit more savvy about how nutrients influence and synergistically affect each other.

For example, it’s important to maintain the proper balance between magnesium, calcium, vitamin K2, and vitamin D. These all work together synergistically, and lack of balance between these nutrients is why calcium supplements have become associated with increased risk of heart attacks and stroke, and why some people experience vitamin D toxicity. To learn more about this, please see this previous article that delves into this at some depth.

Do You Need More Potassium in Your Diet?

Potassium is an essential mineral “salt” that is sometimes referred to as the “good salt.” It’s most commonly known for its role in blood pressure regulation, and it works synergistically with magnesium to improve sleep, among other things. This combination may be of particular benefit if muscle cramps are keeping you awake.

As an electrolyte, potassium is a positive charged ion that must maintain a certain concentration7 in order to carry out its functions, which includes interacting with sodium to help control nerve impulse transmission, muscle contraction and heart function. In fact, maintaining the proper ratio of potassium to sodium is an important factor for optimal health. It’s generally recommended that you take in five times more potassium than sodium8, but because most Americans’ diets are so rich in high-sodium processed foods, most people get double the amount of sodium compared to potassium from their diet.

If you have high blood pressure, it could be a sign that you’re lacking in this vital mineral or that your ratio of potassium to sodium is upside-down from an improper diet. Signs of severe potassium deficiency include fatigue, muscle weakness, abdominal pain and cramps, and in severe cases abnormal heart rhythms and muscular paralysis. The ideal way to increase your potassium is to obtain it from vegetables, such as:

Swiss chard (960 mg of potassium per 1 cup) Spinach (838 mg per cup) Broccoli (505 mg per cup) Celery (344 mg per cup)
Avocado (874 mg per cup) Crimini mushrooms (635 mg in 5 ounces) Brussels sprouts (494 mg per cup) Romaine lettuce (324 mg per 2 cups)

Vitamin D Deficiency May Be the Cause of Excessive Sleepiness

A growing body of research clearly shows the absolute necessity of vitamin D for good health and disease prevention, and it may even play an important role in sleep. According to research presented at last year’s Associated Professional Sleep Societies meeting, people with daytime sleepiness and musculoskeletal pain, which can easily sabotage sleep, are likely to have vitamin D insufficiency or deficiency. According to a writeup by Mother Nature Network9:

“[T]he team decided to test the vitamin D levels of patients who had complained of chronic pain as part of the workup that was done for other sleep disturbances. McCarty and colleagues performed research and reviews of 153 patients at a sleep clinic. Eighty-four percent of patients had either vitamin D insufficiency (30 percent) or deficiency (54 percent).

They discovered that some patients who exhibited low levels of vitamin D experienced complete resolution of daytime sleepiness symptoms after treatment for vitamin D deficiency. McCarty and colleagues concluded that it is biologically plausible that low vitamin D could contribute to sleepiness because of its role in systemic inflammation.”

Vitamin D3 is an oil-soluble steroid hormone (the term “vitamin” is a misnomer) that forms when your skin is exposed to UVB radiation from the sun or a safe tanning bed. When UVB strikes the surface of your skin, your skin converts a cholesterol derivative into vitamin D3, and this is, by far, the best way to optimize your vitamin D levels.

If you opt for a vitamin D supplement, you also need to boost your intake of vitamin K2 through food and/or a supplement. How do you know if your vitamin D level is in the right range? The most important factor is having your vitamin D serum leveltested every six months, as people vary widely in their response to ultraviolet exposure or oral D3 supplementation. Your goal is to reach a clinically relevant serum level of 50-70 ng/ml. As a general guideline, research by GrassrootsHealth suggests that adults need about 8,000 IU’s per day to achieve a serum level of 40 ng/ml.

Tips to Help You Sleep Better

Besides nutritional deficiencies, there are many other variables that can impact how well you sleep. I suggest you read through my full set of 33 healthy sleep guidelines for all of the details, but to start, making some adjustments to your sleeping area can go a long way to ensure uninterrupted, restful sleep.

  1. Cover your windows with blackout shades or drapes to ensure complete darkness. Even the tiniest bit of light in the room can disrupt your pineal gland’s production of melatonin and the melatonin precursor serotonin, thereby disrupting your sleep cycle.

So close your bedroom door, get rid of night-lights, and refrain from turning on any light during the night, even when getting up to go to the bathroom. If you have to use a light, install so-called “low blue” light bulbs in your bedroom and bathroom. These emit amber light that will not suppress melatonin production.

  1. Keep the temperature in your bedroom at or below 70 degrees F (21 degrees Celsius). Many people keep their homes and particularly their upstairs bedrooms too warm. Studies show that the optimal room temperature for sleep is quite cool, between 60 to 68 degrees F (15.5 to 20 C). Keeping your room cooler or hotter can lead to restless sleep.
  2. Check your bedroom for electro-magnetic fields (EMFs). These can also disrupt your pineal gland’s production of melatonin and serotonin, and may have other negative effects as well. To do this, you need a gauss meter. You can find various models online, starting around $50 to $200. Some experts even recommend pulling your circuit breaker before bed to kill all power in your house.
  3. Move alarm clocks and other electrical devices away from your head. If these devices must be used, keep them as far away from your bed as possible, preferably at least three feet.
  4. Reduce use of light-emitting technology, such as your TV, iPad, and computer, before going to bed. These emit the type of light that will suppress melatonin production, which in turn will hamper your ability to fall asleep, as well as increase your cancer risk (melatonin helps to suppress harmful free radicals in your body and slows the production of estrogen, which can contribute to cancer). Ideally, you’ll want to turn all such light-emitting gadgets off at least one hour prior to bedtime.

As previously discussed by Dr. Rubin Naiman, a leader in integrative medicine approaches to sleep and dreams, sleep is the outcome of an interaction between two variables, namely sleepiness and what he refers to as “noise.” This is any kind of stimulation that inhibits or disrupts sleep. In order to get a good night’s sleep, you want your sleepiness level to be high, and the “noise” level to be low. Under normal conditions, your sleepiness should gradually increase throughout the day and evening, peaking just before you go to bed at night. However, if noise is conceptually greater than your level of sleepiness, you will not be able to fall asleep.

Improving Your Nutrition May Help You Sleep Better

If you aren’t sleeping well, it is just a matter of time before it will adversely affect your health, even if you’re doing everything else right. Fortunately, there are many simple solutions to address poor sleep, starting with your diet and lifestyle. Certain nutrients, such as melatonin, magnesium, potassium and vitamin D can play an important role. It’s also crucial to pay attention to your use of artificial lighting. To promote good sleep, make sure you’re exposed to full natural light during the day, and avoid artificial lighting once the sun goes down, especially as bedtime draws near.

To make your bedroom into a suitable sleep sanctuary, begin by making sure it’s pitch-black, cool, and quiet. Remember, even the tiniest bit of light can disrupt your pineal gland’s production of melatonin and serotonin. For this reason, I highly recommend adding room-darkening blinds or drapes to your bedroom, or if this is not possible wearing an eye mask to block out any stray light.

For even more helpful guidance on how to improve your sleep, please review my 33 Secrets to a Good Night’s Sleep. If you’re even slightly sleep deprived I encourage you to implement some of these tips tonight, as high-quality sleep is one of the most important factors in your health and quality of life.

Source: mercola.com

 

5 Tips for Recovering from Emotional Pain

  1. If you allow yourself to feel helpless after a failure, or blame it on your lack of ability or bad luck, it’s likely to lower your self-esteem. Blaming a failure on specific factors within your control, such as planning and execution, is likely to be less damaging, but even better is focusing on ways you can improve and be better informed so you can succeed next time.
    1. Emotional pain often exacts a greater toll on your quality of life than physical pain. The stress and negative emotions associated with any trying event can even lead to physical pain and disease.
    2. In fact, emotional stress is linked to health problems including chronic inflammation, lowered immune function, increased blood pressure, altered brain chemistry, increased tumor growth and more.
    3. Of course, emotional pain can be so severe that it interferes with your ability to enjoy life and, in extreme cases, may even make you question whether your life is worth living.
    4. As the featured article reported, Guy Winch, author of Emotional First Aid: Practical Strategies for Treating Failure, Rejection, Guilt and Other Everyday Psychological Injuries, recently shared five tips for healing your emotional pain.
    5. 1. Let Go of Rejection
    6. Rejection actually activates the same pathways in your brain as physical pain, which is one reason why it hurts so much. The feeling of rejection toys with your innate need to belong, and is so distressing that it interferes with your ability to think, recall memories and make decisions. The sooner you let go of painful rejections, the better off your mental health will be.
    7. 2. Avoid Ruminating
    8. When you ruminate, or brood, over a past hurt, the memories you replay in your mind only become increasingly distressing and cause more anger – without providing any new insights. In other words, while reflecting on a painful event can help you to reach an understanding or closure about it, ruminating simply increases your stress levels, and can actually be addictive.
    9. Ruminating on a stressful incident can also increase your levels of C-reactive protein, a marker of inflammation in your body linked to cardiovascular disease.1
    10. 3. Turn Failure Into Something Positive
    11. If you allow yourself to feel helpless after a failure, or blame it on your lack of ability or bad luck, it’s likely to lower your self-esteem. Blaming a failure on specific factors within your control, such as planning and execution, is likely to be less damaging, but even better is focusing on ways you can improve and be better informed or prepared so you can succeed next time (and try again, so there is a next time).
    12. 4. Make Sure Guilt Remains a Useful Emotion
    13. Guilt can be beneficial in that it can stop you from doing something that may harm another person (making it a strong ‘relationship protector). But guilt that lingers or is excessive can impair your ability to focus and enjoy life.
    14. If you still feel guilty after apologizing for a wrongdoing, be sure you have expressed empathy toward them and conveyed that you understand how your actions impacted them. This will likely lead to authentic forgiveness and relief of your guilty feelings.
    15. 5. Use Self-Affirmations if You Have Low Self-Esteem
    16. While positive affirmations are excellent tools for emotional health, if they fall outside the boundaries of your beliefs they may be ineffective. This may be the case for people with low self-esteem, for whom self-affirmations may be more useful. Self-affirmations, such as “I have a great work ethic” can help to reinforce positive qualities you believe you have, as can making a list of your best qualities.
    17. Many, if not most, people carry emotional scars — traumas that can adversely affect your health and quality of life. Using techniques like energy psychology, you can correct the emotional short-circuiting that contributes to your chronic emotional pain. My favorite technique for this is the Emotional Freedom Technique (EFT), which is the most comprehensive and most popular version of energy psychology. EFT is a form of psychological acupressure based on the same energy meridians used in traditional acupuncture to treat physical and emotional ailments for over 5,000 years, but without the invasiveness of needles.
    18. Instead, simple tapping with the fingertips is used to transfer kinetic energy onto specific meridians on your head and chest while you think about your specific problem — whether it is a traumatic event, an addiction, pain, anxiety, etc. — and voice positive affirmations.
    19. This combination of tapping the energy meridians and voicing positive affirmation works to clear the “short-circuit”—the emotional block—from your body’s bioenergy system, thus restoring your mind and body’s balance, which is essential for optimal health and the healing of physical disease. The beauty about EFT is that it can reprogram your body’s reactions to the unavoidable stressors of everyday life, thereby providing a more lasting effect.
    20. More than any traditional or alternative method I have used or researched, EFT has the most potential to literally work magic. Clinical trials have shown that EFT is able to rapidly reduce the emotional impact of memories and incidents that trigger emotional distress. Once the distress is reduced or removed, your body can often rebalance itself, and accelerate healing.
    21. For a demonstration of how to perform EFT, please see the video below featuring EFT practitioner Julie Schiffman. The first video is a general demonstration, which can be tailored to just about any problem, and the second demonstrates how to tap for depression. While this technique is particularly effective for relieving emotional or mental stress and anxiety, it can be used for all manner of physical pain relief as well.

5.    5 Tips for Healing Emotional Pain

19.  My Most Highly Recommended Tool for Emotional Healing

Emotional Health Takes Ongoing Care: 9 More Tips for Well-Being

Just as eating healthy, exercising and getting a good night’s sleep are habits that must be held to in the long run to be effective, your emotional health requires ongoing care as well. And, just like your physical body, your mind can only take so much stress before it breaks down. Yet many neglect to tend to their emotional health with the same devotion they give to their physical well-being. This is a mistake, but one that’s easily remedied with the following tips for emotional nurturing.2

1. Be an Optimist

Looking on the bright side increases your ability to experience happiness in your day-to-day life while helping you cope more effectively with stress.

2. Have Hope

Having hope allows you to see the light at the end of the tunnel, helping you push through even dark, challenging times. Accomplishing goals, even small ones, can help you to build your level of hope.

3. Accept Yourself

Self-deprecating remarks and thoughts will shroud your mind with negativity and foster increased levels of stress. Seek out and embrace the positive traits of yourself and your life, and avoid measuring your own worth by comparing yourself to those around you.

4. Stay Connected

Having loving and supportive relationships helps you feel connected and accepted, and promote a more positive mood. Intimate relationships help meet your emotional needs, so make it a point to reach out to others to develop and nurture these relationships in your life.

5. Express Gratitude

People who are thankful for what they have are better able to cope with stress, have more positive emotions, and are better able to reach their goals. The best way to harness the positive power of gratitude is to keep a gratitude journal or list, where you actively write down exactly what you’re grateful for each day. Doing so has been linked to happier moods, greater optimism and even better physical health.

6. Find Your Purpose and Meaning

When you have a purpose or goal that you’re striving for, your life will take on a new meaning that supports your mental well-being. If you’re not sure what your purpose is, explore your natural talents and interests to help find it, and also consider your role in intimate relationships and ability to grow spiritually.

7. Master Your Environment

When you have mastery over your environment, you’ve learned how to best modify your unique circumstances for the most emotional balance, which leads to feelings of pride and success. Mastery entails using skills such as time management and prioritization along with believing in your ability to handle whatever life throws your way.

8. Exercise Regularly

Exercise boosts levels of health-promoting neurochemicals like serotonin, dopamine, and norepinephrine, which may help buffer some of the effects of stress and also relieve some symptoms of depression. Rather than viewing exercise as a medical tool to lose weight, prevent disease, and live longer – all benefits that occur in the future – try viewing exercise as a daily tool to immediately enhance your frame of mind, reduce stress and feel happier.

9. Practice Mindfulness

Practicing “mindfulness” means that you’re actively paying attention to the moment you’re in right now. Rather than letting your mind wander, when you’re mindful you’re living in the moment and letting distracting or negative thoughts pass through your mind without getting caught up in their emotional implications. Mindfulness can help you reduce stress for increased well-being as well as achieve undistracted focus.

Physical Health Also Supports Emotional Health and Healing

It’s a mistake to view your emotional health as a separate entity from your physical health, as the two are intricately connected. You’ll have an easier time bouncing back from emotional setbacks when you’re physically well, and healthy habits will also help keep your mood elevated naturally in the midst of stress. Happy people tend to be healthy people, and vice versa, so in addition to the tips above, the following lifestyle strategies can also help to support emotional wellness and healing:

  • Eat well: What you eat directly impacts your mood and energy levels in both the short and long term. Whereas eating right can prime your body and brain to be in a focused, happy state, eating processed junk foods will leave you sluggish and prone to chronic disease. My free nutrition plan is an excellent tool to help you choose the best foods for both physical and emotional wellness.
  • Proper sleep: Sleep deprivation is linked to psychiatric disorders such as anxiety and bipolar depression, while getting the right amount of sleep has been linked to positive personality characteristics such as optimism and greater self-esteem, as well as a greater ability to solve difficult problems.3
  • Animal-based omega-3 fats: Low concentrations of the omega-3 fats EPA and DHA are known to increase your risk for mood swings and mood disorders. Those suffering from depression have been found to have lower levels of omega-3 in their blood, compared to non-depressed individuals. Krill oil is my preferred source of omega-3 fats.
  • Regular sun exposure: This is essential for vitamin D production, low levels of which are linked to depression. But even beyond vitamin D, regular safe sun exposure is known to enhance mood and energy through the release of endorphins.

Source: mercola.com

 

Interlinks between sleep and metabolism.


sleep

Lack of sleep is increasingly associated with weight gain and metabolic problems. Interfaces between the pathways that regulate circadian timing and metabolism might underlie these adverse health effects. Jill Jouret reports.

Getting a good night’s sleep is a basic, but often eluded, prescription for good health. Modern lifestyles provide opportunities for 24 h activity, and minimising sleep is often thought to be a harmless, efficient, or merely necessary means to accommodate schedules. However, feeling tired at night is more than an instruction to rest. Behaviour and physiology are intricately linked to light and dark cycles, and an internal timing mechanism has evolved to ensure that physiological processes occur at optimum times in a 24 h cycle. Maintaining the synchrony of this endogenous circadian clock seems to have wide-ranging health implications.

Although the mechanisms are not fully clear, evidence is mounting that insufficient sleep and disruption in circadian rhythms contribute to pathogenesis of metabolic disorders, cardiovascular disease, and cancer. Worldwide, metabolic syndrome is on the rise, as is the introduction of artificial light and activity into night-time hours. Epidemiological and clinical studies have shown that short-duration and poor-quality sleep predict development of type 2 diabetes and obesity, suggesting that sleep, circadian rhythms, and metabolic systems are interconnected.

In mammals, circadian rhythms are generated centrally by the suprachiasmatic nuclei in the anterior hypothalamus. Light perception by the retina synchronises these single-celled oscillators, generating rhythmic outputs that regulate sleep and wakefulness, feeding and energy expenditure, and glucose homoeostasis. This central clock also sends signals via direct innervation and humoral factors to clock components in peripheral tissues, thus maintaining the circadian timing of an array of physiological processes. Transcription—translation feedback loops implicating specific clock genes lead to a roughly 24 h cycle.

Molecular links between circadian and metabolic pathways have been identified and many hormones implicated in metabolism and energy balance exhibit circadian oscillation—eg, expression and secretion of leptin, a hormone that signals satiety, peaks at night. The complex signalling systems that govern glucose homoeostasis and metabolism of fatty acids, cholesterol, bile acids, and toxins receive inputs from the local and central circadian clocks, allowing cells to anticipate metabolic reactions in a 24 h period. In-vitro studies show that metabolic cues can be transmitted to core components of the circadian clock. Such crosstalk suggests a mechanism by which eating (and possibly sleeping) patterns could shift innate circadian timing.

study published in March, 2013, by a group at the University of Surrey (Guildford, UK) highlighted the interconnection between sleep, circadian rhythmicity, and metabolism. Whole-blood RNA samples were taken from participants after a week of restricted nightly sleep (5·7 h) and also after a week of adequate sleep (8·5 h). Transcriptome analysis showed that 711 genes were upregulated or downregulated by insufficient sleep, including genes associated with circadian rhythms and metabolism.

Sleep restriction also reduced the total number of genes with circadian expression profiles, implying that even a week of poor sleep can disrupt the body’s intricate physiological timing.

Melatonin, a key regulator of sleep, could be an important link connecting circadian timing and insulin signalling. Melatonin production is suppressed by light, and peaks around 3—5 h after sleep onset; it regulates the sleep—wake cycle by lowering body temperature and causing drowsiness, and also inhibits insulin secretion by pancreatic β cells. A 2013 case-control studywithin the Nurses’ Health Study cohort showed that, compared with women in the highest category of melatonin secretion, women in the lowest category had about a twice the risk of developing type 2 diabetes (after controlling for demographic, lifestyle, and other risk factors). Previous studies have shown that single nucleotide polymorphisms of the melatonin receptor are also associated with an increased risk of type 2 diabetes.

More clinical research is needed to characterise this association between sleep, melatonin concentrations, and type 2 diabetes, and to elucidate, for example, whether melatonin supplementation has a role in treatment. Irregular and extended working hours are a reality for many industries, and epidemiological studies have shown lower melatonin concentrations in night-shift workers than in day-shift workers and an increasing risk of type 2 diabetes with number of years of shift work. For this substantial proportion of the workforce, more solutions are needed to prevent people from falling into economically driven health traps.

Insufficient sleep is a risk factor for weight gain and obesity, in addition to type 2 diabetes, and understanding the underlying mechanisms could help to guide novel weight-loss strategies. A study published on April 2, 2013, showed that eating behaviours, particularly night-time eating, contributed to weight gain during sleep loss. Whole-room calorimetry measured daily energy expenditure in adults undergoing 5-day cycles of inadequate (5 h) or adequate (9 h) nightly sleep. Energy expenditure was about 5% higher with insufficient sleep, but increased food intake more than compensated for this energetic cost. In the sleep-loss condition, participants ate a smaller breakfast but consumed 42% more calories as after-dinner snacks, leading to weight gain. The study investigators suggested that participants’ eating patterns during sleep loss resulted from a delayed circadian phase—ie, a later onset of melatonin secretion at night, assessed by hourly blood samples from an intravenous catheter—which might have led to a circadian drive for more food intake. Furthermore, the time between waking and melatonin offset was longer in the 5 h sleep condition; thus, participants awoke during an earlier circadian phase (while still in biological night) and might have been less hungry for breakfast. Previous studies have suggested that disrupted signalling of satiety and hunger hormones leads to the overeating associated with insufficient sleep; however, in both the 5 h and 9 h conditions, excessive food intake was accompanied by appropriate increases in the satiety hormones leptin and peptide YY and decreases in ghrelin, which stimulates hunger.

Future studies should examine how sleep deprivation leads to delays in circadian phase and how circadian timing of meals affects energy metabolism. For the millions of people whose working week necessitates a disrupted sleep schedule, a physiological drive for more food intake, the availability of high-calorie foods, and exhaustion leading to less physical activity overall could be a potent formula for weight gain.

Whether for work, play, or travel, voluntary sleep curtailment has become endemic; however, restricted sleep seems to interfere with the crosstalk between complex physiological and circadian networks that have evolved to couple our bodily functions with the Earth’s 24 h rotation. Many more issues deserve investigation, such as the differential effects on health of acute versus chronic sleep deprivation, and how light exposure mediates the effects of sleep loss. As more evidence emerges of the circadian orchestration of metabolism, perhaps the time has come for sleep to figure more prominently in treatment and public health guidelines.

Source: Lancet

 

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