Missing sleep can lead to Alzheimers

By Dr. Mercola

Poor sleep may be an “early warning beacon” or a “distress call” alerting to the beginnings of Alzheimer’s disease, according to new research. While sleep problems are common in Alzheimer’s patients, poor sleep may also be contributing to the disease by driving the buildup of amyloid plaques in the brain, a hallmark of Alzheimer’s disease.

Study author Bryce Mander, a postdoctoral fellow at the University of California, Berkeley, told Medicine Net:1

“Sleep appears to be a missing piece in the Alzheimer’s puzzle, and enhancing sleep may lessen the cognitive burden that Alzheimer’s disease imparts.”

Disrupted Deep Sleep May Lead to Memory Impairment

Researchers measured the brain waves of 26 cognitively normal older adults during sleep and found those with disrupted deep sleep patterns had higher amounts of amyloid plaques in their brain.2

In addition, both disrupted sleep and the higher levels of amyloid plaque were associated with worse performance on memory tests conducted before and after sleep. The study participants were not followed to see if anyone developed mild cognitive impairment, which is often a precursor to Alzheimer’s, or Alzheimer’s disease in the years to come.

However, the study did show interrupted deep sleep contributes to a buildup of amyloid, which in turn is linked to impaired performance on memory tests. What this suggests is that poor sleep may be an indicator of amyloid buildup, which could be causing very subtle brain changes, long before disease develops.

It’s unclear at this time if remedying sleep problems could slow this progression specifically, but it is known that sleep is absolutely crucial for brain health. And past research has also linked lack of sleep to Alzheimer’s…

Sleep Loss Damages Your Brain

Sleep is necessary for maintaining metabolic homeostasis in your brain. Wakefulness is associated with mitochondrial stress, and without sufficient sleep, neuron degeneration sets in.

In one animal study, inconsistent, intermittent sleep (similar to what might be experienced by shift workers) resulted in remarkably considerable, and irreversible, brain damage—the mice actually lost 25 percent of the neurons located in their locus coeruleus, a nucleus in the brainstem associated with arousal, wakefulness, and certain cognitive processes.3 As reported by Timemagazine:4

“The scientists believe that when the mice slept inconsistently, their newer cells would create more sirtuin type 3, a protein meant to energize and protect the mice. But after several days of missing sleep, as a shift worker might, the protein creation fell off and cells began to die off at a faster pace.”

Further, according to research published in the journal Neurology, lack of sleep may affect the size of your brain.5 A total of 147 adult volunteers underwent MRI scans to assess the link between sleep and brain volume.

As it turns out, sleep problems like insomnia can have a distinct impact on your brain over time, causing it to shrink—and shrink more rapidly, compared to those who sleep well. This effect was particularly significant in those over 60.

Your Brain Needs Sleep to Detoxify

In your body, the lymphatic system is the system responsible for eliminating cellular waste products. However, the lymphatic system does not include your brain. The reason for this is that your brain is a closed system, protected by the blood-brain barrier, which controls what can go through and what cannot.

Your brain has a unique method of removing toxic waste through what’s been dubbed the glymphatic system. The “g” in glymphatic is a nod to “glial cells”—the brain cells that manage this system.

By pumping cerebral spinal fluid through your brain’s tissues, the glymphatic system flushes the waste, from your brain, back into your body’s circulatory system. From there, the waste eventually reaches your liver, where it’s ultimately eliminated.

This system ramps up its activity during sleep, thereby allowing your brain to clear out toxins, including harmful proteins linked to Alzheimer’s disease, for example. During sleep, the glymphatic system becomes 10 times more active than during wakefulness.

What’s more, they discovered that your brain cells actually shrink by about 60 percent during sleep, which allows for more efficient waste removal.6 Amyloid-beta, for example, is removed in significantly greater quantities during sleep. According to lead author Maiken Nedergaard, M.D., D.M.Sc.:7

“The brain only has limited energy at its disposal and it appears that it must choose between two different functional states — awake and aware or asleep and cleaning up. 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.

…These findings have significant implications for treating ‘dirty brain’ disease like Alzheimer’s. 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.”

Poor Sleep May Accelerate the Onset of Alzheimer’s

Adding to the sizeable quantity of research linking poor sleep with brain damage and Alzheimer’s, another study used mice bred to develop Alzheimer’s and exposed one group of mice to 12 hours of light and 12 hours of darkness, while another group was exposed to 20 hours of light and only four hours of darkness.8 This lack of darkness significantly reduced the amount of time the mice slept.

At the end of the eight-week study, the mice that slept less were found to have significantly poorer memory. Their ability to learn new things was also impaired—despite the fact that the two groups of mice had about the same amount of amyloid plaque in their brains.

According to lead author Domenico Praticò, professor of pharmacology and microbiology/immunology in the university’s School of Medicine:9

“[W]e did observe that the sleep disturbance group had a significant increase in the amount of tau protein that became phosphorylated and formed the tangles inside the brain’s neuronal cells…

Because of the tau’s abnormal phosphorylation, the sleep-deprived mice had a huge disruption of this synaptic connection. This disruption will eventually impair the brain’s ability for learning, forming new memory and other cognitive functions, and contributes to Alzheimer’s disease.”

Since both groups of mice were bred to develop Alzheimer’s but the sleep deprived group developed these dementia-related problems sooner than the others, the researchers believe poor sleep acts as a trigger of pathological processes that accelerate the disease.

The researchers concluded, “Chronic sleep disturbance is an environmental risk factor for Alzheimer’s disease.” As UC Berkeley neuroscience professor Matthew Walker, who worked on the featured study, told CBS News:10

“Sleep is helping wash away toxic proteins at night, preventing them from building up and from potentially destroying brain cells… It’s providing a power cleanse for the brain.”

Sleep Disturbances Are Widespread in the US

Sleep disturbances are endemic in the US, where nearly 40 percent of adults reported unintentionally falling asleep during the day in the past month, and five percent reported nodding off while driving.11 Forty-five percent of teens also don’t get enough sleep on school nights and 25 percent report falling asleep in class at least once a week.

While many are struggling with actual sleep disorders, others lack sleep because they simply stay up too late. If you go to bed at 10 pm and get out of bed at 7 am, you might say you’ve slept for nine hours. In reality, you probably spent at least 15-30 minutes falling asleep and may have woken during the night one or more times.

With the advent of fitness-tracking wristbands such as Jawbone’s UP, however, you can access actual sleep data (and more), which is quite useful on a personal level. Newer devices, like Jawbone’s UP3, can even tell you what activities led to your best sleep and what factors resulted in poor sleep. You may be surprised at how little sleep you’re actually getting. When I first started using a fitness tracker, I was striving to get 8 hours of sleep, but my Jawbone UP typically recorded me at 7.5 to 7.75.

I have since increased my sleep time, not just time in bed, but total sleep time to over 8 hours per day, and the fitness tracker helped me realize that unless I am asleep, not just in bed, but asleep by 10 pm I won’t get my 8 hours. Gradually I have been able to get this down to 9:30 pm. So even if you go to bed at a reasonable hour, you might still be lacking in sleep. Aside from using a fitness tracker, how can you tell if you’re getting enough? And how much do you actually need?

How Much Sleep Should You Be Getting?

Dr. Rubin Naiman — a clinical psychologist, author, teacher, and the leader in integrative medicine approaches to sleep and dreams – recommends you simply sleep “enough hours so that your energy is sustained through the day without artificial stimulation, with the exception of a daytime nap,” which he believes you are biologically programmed for. I agree with this functional description rather than trying to come up with a specific numeric range. I would add to that guideline, however, the suggestion to watch out for physical or biological symptoms.

For example, when I push myself and don’t get high-quality sleep or enough sleep, I’m predisposed to postprandial hypoglycemia. In other words, I have low insulin resistance so when I sleep poorly, it doesn’t take much sugar or carbs for it to be easily metabolized and drop my blood sugar—which also makes me really sleepy. When I get enough sleep, I’m far less susceptible to it. Pay attention to clues your body may be giving you.

For instance, if you need an alarm clock to wake up and you wake up feeling tired and groggy, you probably need to go to sleep earlier (or get more restful sleep). It’s also said that if you fall asleep within a few minutes of your head hitting the pillow, you’re probably sleep deprived. A well-rested person will take about 10-15 minutes to fall asleep at night.12 If you’re tired during the day, there’s a good chance you need to get more sleep, too. Even if you think can ‘get by’ on five or six hours a night, you’re not fooling your body.

It’s Not Only Your Brain That’s Harmed by Lack of Sleep

Sleep deprivation has the same effect on your immune system as physical stress or illness,13 which may help explain why lack of sleep is tied to an increased risk of numerous chronic diseases. Sleeping less than six hours per night more than triples your risk of high blood pressure, and women who get less than four hours of shut-eye per night double their chances of dying from heart disease.14 According to research from Great Britain, poor or insufficient sleep is actually the strongestpredictor for pain in adults over 50.15 Besides making you more susceptible to physical aches and pains, interrupted or impaired sleep can also:

  • Increase your risk of cancer
  • Harm your brain by halting new neuron production. Sleep deprivation can increase levels of corticosterone (a stress hormone), resulting in fewer new brain cells being created in your hippocampus
  • Contribute to a pre-diabetic state, making you feel hungry even if you’ve already eaten, which can lead to weight gain
  • Contribute to premature aging by interfering with your growth hormone production, normally released by your pituitary gland during deep sleep (and during certain types of exercise, such as high-intensity interval training)
  • Increase your risk of dying from any cause

Researchers find genetic variant that could improve drug dosing in African Americans

By John Easton

A multi-institutional team of researchers has identified a common genetic variation that can help physicians estimate the correct dose of the widely used blood-thinning drug warfarin, the first genome-wide association study to focus on warfarin dose requirement in African Americans.

The discovery, reported online first in The Lancet, suggests that people of African ancestry who carry this variant—more than 40 percent of the patients enrolled in this study—need significantly less warfarin to obtain optimal benefits compared to those who lack this variant.

Adding this genetic marker to standard dosing algorithms could improve the predictability of warfarin dosing by 21 percent in these individuals, increasing the safety and effectiveness of this notoriously hard to administer drug,” said Julie Johnson, a distinguished professor of pharmacy and medicine at the University of Florida and a leader of the International Warfarin Pharmacogenetics Consortium.

Warfarin, used to prevent blood clots after a heart attack, stroke or major surgery, is one of the world’s most widely prescribed drugs, accounting for more than 33 million prescriptions in the United States in 2012. It is also a drug for which correct dosing is notoriously difficult.

“It’s very important to get warfarin dosing right,” said the study’s lead author, Minoli Perera, assistant professor of medicine at the University of Chicago. “People take this drug because they’ve had a clotting problem. If you give them too little, they could form another clot, possibly causing a stroke or pulmonary embolism. If you give too much, they could bleed.”

But dose requirements vary widely, making it difficult to get the quantity right. “Some people need a few milligrams per day, and some need 20,” Perera said. The average dose for African Americans generally has been about 30 percent higher than that for Caucasians.

As a consequence, warfarin contributes to a third of hospitalizations for adverse drug reactions in people older than 65 years in the United States. “It is one of the most litigated of drugs,” Perera said.

Earlier studies found that variations of two genes, VKORC1 and CYP2C9, can predict about 30 percent of the difference in warfarin response in people of European or Asian ancestry. These genetic markers have proved less useful in determining the proper dose in African Americans.

To identify additional genetic factors that control warfarin dose requirements in African Americans, Perera, Johnson and colleagues analyzed health information and DNA samples from 533 African American adults on stable doses of warfarin from several sites. The majority of patients came from the University of Chicago, the University of Illinois at Chicago, and the University of Alabama at Birmingham.

The researchers found a strong association between one gene variant known as rs12777823 on chromosome 10 and warfarin dose. This finding was corroborated in a second independent cohort of 432 additional African American patients.

The genome study showed that African Americans who possess one copy of this genetic variant need to reduce their dose by about 6 milligrams per week. Those with two copies of this variant may need to reduce their dose by as much as 9 milligrams per week.

By factoring genetic information into the standard formula for estimating the dose, physicians could improve their starting point for determining the optimal warfarin dose by 21 percent.

“We still don’t know every genetic or environmental factor that plays a role in determining the ideal dose,” Perera said. “But this improves our starting point. Working from that baseline, we can adjust doses until we have it right. This finding can help us get to the therapeutic dose quicker.”

In an accompanying editorial in the journal, stroke specialist Mark Alberts, professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Dallas, notes that there has long been a need to identify “additional genetic factors that play a role in determining warfarin metabolism … so that the accuracy of various dosing algorithms can be optimized.”

“This is particularly true for African American patients,” he wrote, “since prior studies have not enrolled such patients in large numbers, and current genetic markers appear to be less predictive of dosing regimens in this population.”

This study is also a triumph for a growing effort to focus more attention on genomic studies of health issues among African Americans.

“There have been several studies like this one that relied almost entirely on Caucasian populations, and they came up dry,” Perera said. “They kept finding the same genes over and over again. It’s reassuring to replicate previous studies, but only when we shifted the focus to African Americans did we find something new and different.”

“The need for more studies such as this in the African American population is critical,” she added. “Not only do they help to make personalized medicine available to everyone, but as our study demonstrates, they can provide clinically important results that could never have been found by looking for them only in Caucasians.”

Funding for the study came from the National Institutes of Health, American Heart Association, Wellcome Trust, Wisconsin Network for Health Research and the Howard Hughes Medical Institute.

The International Warfarin Pharmacogenetics Consortium includes 42 researchers from 17 institutions. In addition to Johnson and Perera, study authors include Eric Gamazon, Anuar Konkashbaev, Anna Pluzhnikov, Nancy Cox and Yusuke Nakamura from the University of Chicago; Larisa Cavallari, Edith Nutescu and Shitalben Patel from the University of Illinois at Chicago; Nita Limdi, Jelai Wang and Nianjun Liu from the University of Alabama at Birmingham; Roxana Daneshjou, Nicholas Tatonetti, Hersh Sagreiya, Russ Altman and Teri Klein from Stanford University; Dana Crawford, Yukiko Bradford, Matthew Oetjens and Dan Roden from Vanderbilt University; Stephane Bourgeois and Panos Deloukas from the Wellcome Trust Sanger Institute; Harumi Takahashi from Meiji Pharmaceutical University, Tokyo; Benjamin Burkley, Taimour Langaee and Mohamed Shahin from the University of Florida, Gainsville; Robert Desnick, Stuart Scott and Jonathan L Halperin from Mount Sinai School of Medicine; Sherief Khalifa from Qatar University; Steven Lubitz from Massachusetts General Hospital; Matthew Tector from Aurora St. Luke’s Medical Center, Milwaukee; Karen Weck and Michael Wagner from the University of North Carolina; Mark Rieder from the University of Washington; Alan Wu from the University of California at San Francisco; James Burmester from the Marshfield Clinic Research Foundation, Wisconsin; Mia Wadelius from Uppsala University, Sweden; Taisei Mushiroda and Michiaki Kubo from RIKEN Center for Genomic Medicine, Yokohama, Japan.

– See more at: http://news.uchicago.edu/article/2013/06/05/researchers-find-genetic-variant-could-improve-drug-dosing-african-americans#sthash.oN4jBNHo.dpuf

2015 Dietary Guidelines for Americans Makes Strides Toward Better Nutrition, But Fallacies Remain

By Dr. Mercola

Every five years, the US Departments of Agriculture (USDA) and Health and Human Services (HHS) convene a 15-member panel to update the nation’s dietary guidelines.

The panel’s stated mission is to identify foods and beverages that help you achieve and maintain a healthy weight, promote health, and prevent disease. These guidelines also serve as the foundation for national nutrition policies, such as school lunch programs and feeding programs for the elderly.

The 2015 dietary guidelines1,2,3 include a number of positive modifications, although I still do not agree with all of its recommendations. Public comments on the report were only accepted through April 8, 2015.4

Cholesterol Limit Removed from 2015 Dietary Guidelines

On the up-side, the advisory panel has decided to eliminate warnings about dietary cholesterol, which for decades has been wrongfully blamed for causing heart disease.

The latest guidelines accurately state that there is no such link. According to the report, “cholesterol is not a nutrient of concern for overconsumption.”

Until now, the guidelines have recommended limiting dietary cholesterol to 300 milligrams (mg) per day, which amounts to about two eggs. As noted by Steven Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic:

“Many of us for a long time have believed the dietary guidelines were pointing in the wrong direction. It is long overdue.”

Saturated Fat Myth Remains…

Unfortunately, while high-cholesterol foods like eggs are off the hook, they still insist that saturated fat causes high cholesterol in your blood, thereby promoting heart disease…

The panel recommends limiting both trans fats (which are indeed harmful) and saturated fat (which is not) to less than 10 percent of daily calories. This is still way off base, so while there’s cause for celebration that eggs have been vindicated, there’s still work to be done to correct people’s fear of saturated fat.

Saturated fats are actually important for optimal health, and most people likely need anywhere from 50 to 80 percent of their daily calories from healthy fat—far more than the upper limit of 10 percent suggested by federal guidelines.

For weight loss, they also recommend sticking to low- and non-fat dairy, which I believe is a mistake. Low-fat recommendations are likely to do more harm than good across the board, but it may be particularly counterproductive if you’re trying to lose weight.

In fact, mounting evidence clearly shows that a high-fat, low-carb diet can be exceptionally effective for weight loss—provided you’re eating the right kinds of fats. Saturated fats are not only essential for proper cellular and hormonal function, they also provide a concentrated source of energy in your diet.

The high-fat, low-carb combination is therefore ideal because when you cut down on carbs, you generally need to replace that lost energy by increasing your fat consumption. Sources of healthy fats that you’ll want to add to your diet include:

Olives and olive oil(for cold dishes) Coconuts andcoconut oil (for all types of cooking and baking) Butter made from raw grass-fed organic milk
Raw nuts, such as macadamias and pecans Organic pastured egg yolks Avocados
Grass-fed meats Palm oil Unheated organic nut oils

Another healthy fat is the omega-3 fat docosahexaenoic acid (DHA). Approximately 60 percent of your brain is composed of fats—25 percent of which is DHA. Omega-3 fats such as DHA are considered essential because your body cannot produce it, and must get it from your daily diet.

I recommend taking an animal-based omega-3 fat such as krill oil on a regular basis, while simultaneously limiting damaged omega-6 fats found in abundance in vegetable oils and processed foods.

Trans Fat and Sugar Are the Dietary Culprits That Cause Heart Disease

To learn more about the flawed science that led us this far afield, I highly recommend taking the time to watch Dr. Maryanne Demasi’s report on thesaturated fat myth, which aired on ABC News in Australia about two years ago.

Dr. Fred Kummerow, author of Cholesterol Is Not the Culprit, has also detailed exactly where we went off the track. Dr. Kummerow, now nearly 100 years old, was the first researcher to identify trans fat as the real culprit behind clogged arteries, all the way back in 1957!

His research has also demonstrated that neither dietary cholesterol nor saturated fat promote arterial plaque, and are being wrongfully shunned… As initially postulated by Dr. Yudkin in the 1960s, sugar is another major dietary culprit in the development of heart disease.

To break it down into simple terms, to protect your heart health you need to address your insulin and leptin resistance, which is the result of eating a diet too high in sugars and grains. To safely and effectively reverse insulin and leptin resistance, thereby lowering your heart disease risk, you need to:

  • Avoid processed foods and other sources of refined sugar and processed fructose, as well as refined grains. Whole grains are also best avoided if you’re insulin and leptin resistant
  • Focus your diet on whole foods, ideally organic, and replace the grain carbs with:
    • Large amounts of vegetables
    • Low-to-moderate amount of high-quality protein (think organically raised, pastured animals)
    • As much high quality healthy fat as you want (saturated and monosaturated from animal and tropical oil sources)

Other Notable Changes in the 2015 Dietary Guidelines

Despite continuing the saturated fat myth for another five years, overall, the 2015 guidelines5,6,7 are probably better than they’ve been in decades. Among the most notable changes is a partial turnaround on artificial sweeteners. While they say artificial sweeteners such as aspartame are probably okay in moderation, they should not be promoted for weight loss.

I believe artificial sweeteners should be removed from the market altogether due to their numerous health risks, but at least this recommendation reflects the voluminous evidence showing that artificial sweeteners do NOT promote weight loss. On the contrary, they tend to promote weight gain, and have been shown to worsen insulin resistance and metabolic disorders to a greater degree than refined sugar.

The 2015 guidelines also reflect the shift away from focusing on specific nutrients such as fat, carbs or protein—which in the past has led to an ever-growing plethora of processed “functional” foods—toward a general focus on eating more whole foods. My only objection there is that they still do not consider the hazards of eating too many whole grains, which can exacerbate insulin and leptin resistance. That said, the panel does recommend limiting refined grains.

As for the panel’s review of research into foods that help combat disease, vegetables and fruits are the only dietary elements found to be consistently helpful against every disease included in the review. One can only hope that this will sink in and eventually lead to much needed changes in agricultural subsidies, which are currently geared entirely toward the manufacturing of disease-promoting processed foods that are high in added sugars.

The 2015 guidelines also break new ground by commenting on the environmental impact of our food choices. The panel notes that switching to a healthier diet higher in veggies, fruits, nuts, and legumes, and lower in animal products, could reduce greenhouse gas emissions and use up less resources such as water and energy.

Take Control of Your Health

There’s little doubt that simplifying nutritional guidelines to focus on whole foods is a giant step in the right direction. That alone can automatically eliminate most of the added sugars and unhealthy fats from your diet. The rest is just a matter of tweaking the ratios of fat, carbs, and protein to suit your individual situation. So, if processed food still make up the bulk of your meals, you’d be wise to reconsider your eating habits. This is particularly important if you have kids. Not only are processed foods the primary culprit in obesity and related diseases, including insulin resistance and type 2 diabetes, processed foods can also affect the IQ of young children.

One British study8 revealed that kids who ate a predominantly processed food diet at age three had lower IQ scores at age 8.5. For each measured increase in processed foods, participants had a 1.67-point decrease in IQ. Another study published in the journal Clinical Pediatrics9,10,11 also warns that frequent fast food consumption may stunt your child’s academic performance. Parents would certainly be well advised to pay heed as you do not need to be a rocket scientist to realize that poor nutrition will ultimately have an adverse effect on performance—both physical and mental.

To optimize nutrition, focus your diet on whole, ideally organic, unprocessed or minimally processed foods. Another key is to trade refined sugar and processed fructose for healthy fat, as discussed earlier. This will optimize insulin and leptin levels, which is key for maintaining a healthy weight and optimal health. Healthy fat is particularly important for optimal brain function and memory. This is true throughout life, but especially during childhood. For more detailed guidance, please see my optimalnutrition plan. It’s a step-by-step guide to feeding your family right, and I encourage you to read through it. I’ve also created my own “food pyramid,” based on nutritional science, which you can print out and share.

Where to Find Healthy Foods

Your best bet for finding healthy food is to connect with a local farmer that raises crops and animals according to organic standards. In the case of eggs, what you’re looking for is eggs from pastured, free-range hens. In the US, the following organizations can help you locate farm-fresh foods:

Weston Price Foundation12 has local chapters in most states, and many of them are connected with buying clubs in which you can easily purchase organic foods, including grass fed raw dairy products like milk and butter.
Local Harvest — This Web site will help you find farmers’ markets, family farms, and other sources of sustainably grown food in your area where you can buy produce, grass-fed meats, and many other goodies.
Farmers’ Markets — A national listing of farmers’ markets.
Eat Well Guide: Wholesome Food from Healthy Animals — The Eat Well Guide is a free online directory of sustainably raised meat, poultry, dairy, and eggs from farms, stores, restaurants, inns, and hotels, and online outlets in the United States and Canada.
Community Involved in Sustaining Agriculture (CISA) — CISA is dedicated to sustaining agriculture and promoting the products of small farms.
FoodRoutes — The FoodRoutes “Find Good Food” map can help you connect with local farmers to find the freshest, tastiest food possible. On their interactive map, you can find a listing for local farmers, CSAs, and markets near you.