Nov
19
2022

Lack of Sleep Harms the Immune System and Causes Inflammation

A research group from Boston, MA and New York, NY found that a lack of sleep harms the immune system and causes inflammation. This was summarized in this CNN article.

Specifically, they first conducted experiments with a mouse model. They studied the effects of sleep disruption and sleep deprivation and could later confirm identical changes in man. The observation was that a lack of sleep caused the hematopoietic cells in the bone marrow to proliferate, but the cell diversity was less than in people with normal sleep patterns. The same pattern of bone marrow proliferation was present in mice. This research was published Sept. 21, 2022 in the Journal of Experimental Medicine.

Chronic sleep deficit

A chronic sleep deficit caused chronic inflammation and eventually autoimmune diseases. Again, this was a pattern present in both the mouse model and in humans. Next the researchers observed what happened with sleep recovery. In the past it was assumed that with sleep recovery all of the physical changes from sleep deprivation would disappear. However, the opposite was true: both in mice and in humans the bone marrow stimulation and the lack of cell diversity persisted.

In the mouse model the researchers could show that there were permanent epigenetic changes, which were caused by sleep deprivation. The same is true with humans, but this is more difficult to show than in the mouse model. The researchers came to the conclusion that sleep deprivation stimulates bone marrow maturation, but restricts the clonal differentiation. In doing so the body initiates inflammation, which becomes chronic even with sleep restoration.

Human sleep studies

There were 14 volunteers that were the test subjects. One group was the normal sleep control. The other group underwent chronic sleep deprivation. Each group did this for 6 weeks. There was a 4-to-6-week washout period. Following this the previous normal sleep group started a 6-week sleep deprivation program. On the other hand, the prior sleep-deprived group switched to 6 weeks of normal sleep. All of the participants had daily late afternoon blood tests.

There are many sleep disruptions, which cause a sleep deficit

In modern life sleep gets disrupted in many ways. There can be sleep fragmentation, sleep restriction, jet lag, obstructive sleep apnea (OSA), and insomnia.

People with these conditions often oscillate between these various types. They may have a few days of normal sleep, but then have sleep deprivation again for a few days. Every time they have sleep deprivation the bone marrow enhances hematopoietic activity. Normally there is a high leukocyte number in the blood at the end of the day and in the morning a lower leukocyte count. But with sleep deprivation there is a high monocyte count in the blood that stays high even when subjects switch back to a normal sleep pattern.

Epigenetic effect of sleep deprivation on bone marrow cells

The authors found that sleep deprivation affects the genetic control of hematopoietic cells in the bone marrow. They called this the epigenetic effect of sleep deprivation. This is responsible for the evening leukocyte response, the monocytosis and the tendency for autoimmune diseases. They summed this up by saying: “Our findings support the hypothesis that periods of poor sleep, even if followed by sleep recovery, have sustained consequences on immunological health.”

Lack of sleep harms the immune system and causes inflammation says the literature

There is ample evidence that a lack of sleep causes cardiovascular disease, diabetes, depression and more frequent infections. Healthy sleep is important when you want to age well without complications. But enough sleep is also necessary to prevent obesity, diabetes and cardiovascular disease. Experts consider getting enough high-quality sleep as essential as a balanced diet and regular exercise.

Lack of Sleep Harms Immune System and Causes Inflammation

Lack of Sleep Harms Immune System and Causes Inflammation

Conclusion

So far, most researchers believed that when you miss some sleep for a few nights that a afternoon nap or a few nights of longer sleep would compensate for the sleep deficit with no sequelae. Think again, because new research from a group in Boston, MA and New York, NY found that lack of sleep harms the immune system and causes inflammation permanently. Sleep deprivation stimulates the bone marrow cells to multiply and causing proliferation of monocytes, called monocytosis as well. Despite afternoon naps and recovery sleep this condition remains  and can lead to autoimmune diseases. All this was unknown up to now. Our bone marrow cells need regular sleep hours to stay diversified and to optimally fight infections in the body. This prevents autoimmune diseases and keeps our defenses against viral diseases strong.

Dec
19
2020

The Use of Biologics for Treatment of Autoimmune Diseases

Notably, the use of biologics for treatment of autoimmune diseases is one of the newer achievements of medicine. In particular, a recent review summarized the use of biologics. For instance, chronic inflammatory conditions like skin eczema and asthma are some of the diseases where physicians use biologics.

Dupilumab (Dupixent)

It is important to realize that biologics are newer medications. They are mostly monoclonal antibodies developed in the lab and directed against various receptors. In particular, one of these is an interleukin-4 receptor. Specifically, this blocks inflammatory mediators such as interleukin-4 and interleukin-13. Dupilumab (Dupixent) is a monoclonal antibody. It must be remembered that it is a useful tool to treat atopic dermatitis (eczema), asthma and nasal polyps from chronic allergic rhinitis. For one thing, the common denominator for all these conditions is chronic inflammation. Here is more background information about Dupilumab. Specifically, this drug blocks certain proteins from attacking your own body. Besides, side effects of the drug are pink eye like inflammation of the eyes. Another side effect were mild skin rashes at the injection site.

Omalizumab (Xolair)

This drug is a monoclonal antibody also. It is given by injection into the skin every 2 to 4 weeks by a doctor or nurse. Originally it was developed for control of moderate to severe asthma. However, subsequently physicians treated moderate to severe atopic dermatitis cases also. Biologics are very expensive. It depends on your insurance carrier whether or not it is affordable for you.

Rheumatoid arthritis

Another disease that is autoimmune is rheumatoid arthritis. This can lead to crippling deformities in the hands and feet. Two of the earlier biologics for RA were etanercept (Enbrel) and adalimumab (Humira). But there are a host of other biologics that are effective as well.  Generally speaking, the physician will start with conventional medicine, like Methotrexate. If Methotrexate does not sufficiently control the symptoms of rheumatoid arthritis, the physician usually adds biologics. Often patients need a combination of Methotrexate and biologics.

Different biologics affect different aspects of the autoimmune response. The first biologic for RA was a tumor necrosis factor (TNF)-antagonist, etanercept (Enbrel). Other TNF antagonists are infliximab (Remicade) and adalimumab (Humira). A different approach is an interleukin (IL)-1 inhibitor, called anakinra (Kineret). This biologic interrupts the inflammatory pathway of RA. Another biologic interrupts the T-cells or killer cells; it is called a T cell co-stimulation blocker, abatacept (Orencia). A different mechanism of action is the B-cell depleting agent, rituximab (Rituxan and Mabthera). This suppresses the formation of RA-autoantibodies from B cells.

The rheumatologist has a wide range of biologics from which to choose. The key is that the specialist individualizes the treatment protocol according to the response of each patient.

Crohn’s disease

Crohn’s disease and ulcerative colitis belong to the inflammatory bowel diseases (IBD). They are also autoimmune diseases where biologics can be useful.

There are three categories of treatment that are worth mentioning.

  • Anti-Tumor Necrosis Factor Agents

Adalimumab (Humira) was one of the first anti-tumor necrosis factor agents. The physician uses Humira in moderate to severe cases of Crohn’s disease and ulcerative colitis. It will calm down the symptoms of Crohn’s/ulcerative colitis and will maintain the disease in this symptom-free state. There are 8 other anti-tumor necrosis factor agents on the market.

  • Integrin Receptor Antagonists

These medications block a protein that coats the inflammatory cells. This arrests the cells, so they don’t move out into blood vessels and to tissues where they could cause tissue destruction. Examples are vedolizumab (Entyvio) and natalizumab (Tysabri). Unfortunately, natalizumab can have a serious side effect, a brain condition called progressive multifocal leukoencephalopathy (PML), This is caused by John Cunningham (JC) virus, which is a virus that 60% of the population carry. Natalizumab suppresses the immune system, which allows the JC virus to flare up and cause PML in the brain. Vedolizumab (Entyvio) is an alternative drug among the integrin receptor antagonists. Contrary to natalizumab it does not enter the brain. In a large clinical trial, it did not cause PML. This drug is infused over 30 minutes initially, then after 2 weeks, 6 weeks and every 8 weeks for maintenance.

  • Interleukin-12 and -23 Antagonist

Two inflammatory kinins, interleukin-12 and interleukin-23 are involved in causing inflammation in Crohn’s disease. They are proteins and the interleukin-12 and -23 antagonist helps to suppress the inflammation. The FDA approved ustekinumab (Stelara) for moderately or severe Crohn’s disease cases where conventional treatment did not show adequate responses. The physician administers the first treatment intravenously. The follow-up treatment occurs subcutaneously every 8 weeks by a nurse. Alternatively, the patient trains to self-inject the drug subcutaneously and administers the drug every 8 weeks.

The Use of Biologics for Treatment of Autoimmune Diseases

The Use of Biologics for Treatment of Autoimmune Diseases

Conclusion

Biologics have entered the treatment world of autoimmune diseases. Biologics can be monoclonal antibodies that inactivate part of an inflammatory cause, such as interleukins. Others may counter certain hyperactive immune cells. One of the side effects can be that the immune system is weakened. This allows latent viruses such as the John Cunningham (JC) virus to suddenly flare up. This is the case with progressive multifocal leukoencephalopathy (PML) following natalizumab (Tysabri) treatment for Crohn’s disease. Due to the development of new medications, this treatment is no longer the best option. Vedolizumab (Entyvio) is an alternative drug among the integrin receptor antagonists where PML does not develop.

Such varied conditions like rheumatoid arthritis, atopic dermatitis (eczema), Crohn’s disease and ulcerative colitis respond to biologics. In addition, nasal polyps from chronic allergic rhinitis and asthma also respond to these drugs. The physician has to carefully match the treatment option to the condition of the patient. The more specific the targets of biologics are the less immunosuppressive side effects they have.

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Feb
22
2020

Clinical Applications of the Fasting Mimicking Diet

Dr. Kurt Hong, professor of clinical medicine spoke about clinical applications of the fasting mimicking diet in Las Vegas. This was at the 27th Annual World Congress on Anti-Aging Medicine on Dec. 14, 2019. Although he spoke on various forms of fasting, he concluded that the fasting mimicking diet had the best results and was most consumer-friendly.

How we age

Dr. Hong reviewed the processes of aging. We age, because our cells experience oxidative damage and our telomeres (the end caps of our chromosomes) get shorter in time. We also age, because there are genetic mutations in our cells’ DNA and our mitochondria are aging as well. The mitochondria are the small energy packages inside the cells that give us energy. When people age, they have lost mitochondria, there is less energy that the body makes out of food and we feel chronically tired.

Above the age of 65 we are also likely to develop diseases of various organs:

  • Heart disease: 31%
  • Cancer: 24%
  • Chronic lung disease (lower respiratory disease): 21%
  • Alzheimer’s disease: 13%
  • Diabetes: 11%

Women are generally healthier than men and their life expectation is 4 to 5 years longer than that of men.

Cellular and molecular aging

Longevity researchers have done mouse experiments and human clinical trials for decades. Dr. Hong asked the question: how much longer could humans live, if we could cure cancer, heart disease, stroke and diabetes? The answer is: 13 years. But if we transfer the animal data to humans it should be 30 years of longer life. Why is there such a discrepancy? The answer is that it is easy to force good lifestyles onto animals, but humans are resistant to changes. Humans have their habits; they like to continue to smoke and eat fast food instead of switching to a healthier Mediterranean diet. Humans also resist a regular exercise program. And they do not want to hear that they should replace missing hormones with bioidentical ones. The result is that we humans will prolong our lives only by less than 50% of what we could achieve.

The concept of intermittent fasting

Dr. Hong stated, that ten thousand years ago, people did not always have enough food to eat. They were forced to intermittently fast. That did not mean that they had long life expectancies, as there was no cure for any disease. But one fact was true: the body learnt to rejuvenate itself during periods of fasting. And these longevity genes are still present in our genes. But they will only help us when we actually fast for some periods of time.

Dr. Hong reviewed what kind of fasting methods are available.

Prolonged fasting and juice fasting are not among the options. With prolonged fasting electrolyte disturbances become an issue. Juice fasting does not remove enough calories and nutrients. This, however is needed to allow the body to stimulate the longevity genes.

How fasting diets work

Dr. Hong explained that there are essentially 5 fasting diets that are effective in regulating the key nutrient sensitive pathways of IGF-1, TOR and PKA. This increases cellular protection and maintenance. It also increases activation of stress resistance pathways and removes and replaces damaged and dysfunctional cells. Finally, a fasting diet also reduces inflammation, which is often the start of disease.

A review of the 5 fasting diets

Time-restricted eating (TRE)

With TRE the person fasts for 12 to 16 hours every day. The person restricts the daily food consumption to a 4- to 12-hour window. The disadvantage is that this fast is done every day. The period of fasting may not be long enough to change the metabolism, where the above-mentioned effects take place.

Alternate-day fasting  

This is a 24-hour fast every other day with a 1:1 day eating-fasting cycle. This does not appear to be physiological and is disruptive with regard to social activities.

5:2 intermittent fasting

With this fast you fast for 2 days every week. With this 2:5 eating-fasting cycle the person fasts for 2 days every week; the other 5 days you eat as much as you desire.

Although this is effective, it can be quite disruptive to your lifestyle.

Periodic fasting

You fast for 48 to 72 hours every couple of months. This fast is socially more acceptable. It is not that often, just a couple of times in a year. The question remains whether it is effective in changing the metabolism to trigger the effects mentioned above.

Fasting-mimicking diet (FMD)

The original suggestion by Dr. Longo, the inventor of the FMD was that you should fast for 5 days once every month. Since then he has modified it and said that you can achieve similar metabolic changes, if you only fast for 3 days and do this a couple of times per year. I have done the FMD since December 2017 and I adhere to the original schedule of doing the FMD monthly for 5 days. This has provided me with more energy. It is easier to keep my body mass index in the 21.0 to 22.0 range. Dr. Hong explained that the FMD allows you to eat, but it tricks the body into acting like you are fasting. Because you are eating 500 to 600 calories per day, you are getting some fluid and nutrients, so the hunger pangs are tolerable.

More details about the FMD

Here is Dr. Hong’s summary about the FMD: “The stomach sees food, while the cells see fasting”. Dr. Hong said that the FMD is the most user-friendly method of fasting. It also has had the most scientific studies to validate that it is indeed working. Poorly functioning mitochondria and misfolded proteins are removed by a process of phagocytosis. The FMD reduces heart disease, cancer, and neurodegenerative disorders. Stem cell production also gets a boost. This promotes cell regeneration and reduces risk factors of premature aging.

Publication on the effectiveness of the FMD

A publication came out in 2017 reporting about the findings of a clinical trial regarding the FMD.

Researchers followed markers of aging, diabetes, cancer and cardiovascular disease in 100 volunteers. They underwent a FMD for 5 days on 3 consecutive months. The results were astounding. The body mass index, the fasting blood sugar level, triglycerides, total and LDL cholesterol and the CRP were all lower. CRP stands for C-reactive protein, which measures the degree of inflammation in the body. The blood pressure was also lower. Overall the 5-day FMD was a safe method with no side effects. The FMD reduced markers and risk factors of aging and age-related diseases. In doing so it prolongs life by reducing the likelihood of coming down with disease.

Who should abstain from fasting?

Dr. Hong mentioned that the FMD is not for everybody. Pregnant women should refrain from going on it, also type 1 and type 2 insulin dependent diabetics. Anybody who has a sign of an active infection (coughing, having a fever or diarrhea) should be excluded. Other exclusions are people who are underweight (BMI less than 18.5) or are malnourished (protein deficiency). Patients with heart failure and advanced kidney or liver disease should not take part in a fasting program.

Autoimmune diseases and FMD

The myelin sheath around the axon of nerve cells in the central nervous system are supported by oligodendrocytes. In multiple sclerosis (MS) patients T lymphocytes activate macrophages and B cells to produce autoantibodies. They destroy oligodendrocytes breaking down the insulating barrier of the myelin sheath. In MS patients the broken-down myelin sheath suppresses the electrical impulses transmitted through the nerve fibers. The FMD led to clinical improvements.

In a pilot study intermittent fasting changed the gut flora into a healthier flora.

This triggered the immune system in the gut to make less inflammatory T cells producing the IL-17 cytokines. There was also an increase in regulatory T helper cells.

Inflammatory bowel disease (IBM) can be improved with several courses of FMD. As the authors showed, intestinal inflammation improved with FMD. The intestinal gut flora improved with the FMD and it promoted intestinal regeneration.

Reversal of physical and functional decline

The fasting mimicking diet (FMD) has a variety of effects on the human body. Dr. Hong showed a slide where we could see that ketone bodies, cortisol and ghrelin levels are increased in the blood. At the same time glucose, insulin, leptin and IGF-1 levels are reduced. In addition, triglycerides and LDL levels are getting lower. Inflammatory markers including the C-reactive protein (CRP) are reduced as well.

Effects of the FMD on various organs in the body

A look at all of the organs shows that in the liver the ketone body production and insulin sensitivity are up. Glycogen production in the liver as well as the liver size are down.

The intestines produce ketone bodies. In the skeletal muscles the insulin sensitivity is increased, while the muscle structure and function are improved. In the brain the hunger feeling increases the release of neurotropic factors including the neuropeptide Y. Cognitive function and stress resistance increase with the FMD. The FMD reduces inflammation and oxidative stress in the brain. With respect to the cardiovascular system the heart rate drops down and blood pressure gets lower. The insulin production in the pancreas is reduced.

Fatty tissue

In fatty tissue lipolysis is up and also the production of adiponectin. This is a protein hormone involved in glucose and fatty acid metabolism. Insulin sensitivity with the FMD is also increased. On the other hand, the FMD reduces fat mass, leptin production and inflammation.

The FMD is the solution to preventing disease and prolonging your life

All of these effects lead to a reversal of physiologic and functional declines. Age-related metabolic diseases like type 2 diabetes are postponed or eliminated. The FMD prevents neuro-cognitive decline like Alzheimer’s disease. In addition, the risk of developing cancer is getting lower. In summary, the FMD improves the health-span, quality of life and can prepare you for a long life.

Clinical Applications of the Fasting Mimicking Diet

Clinical Applications of the Fasting Mimicking Diet

Conclusion

Dr. Kurt Hong is a professor of clinical medicine at UCLA. He gave a talk at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec. 14, 2019. He discussed what we could do to help patients with various autoimmune diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease. It turns out that the fasting mimicking diet (FMD) is the best solution to reduce inflammation and modify  the autoimmune response from aggressive T lymphocytes. With the FMD you consume only 500 to 600 calories per day for 5 days every month. The rest of the days of the month you eat a healthy Mediterranean-type diet.

Fasting mimicking diet, the best way to treat autoimmune diseases

Dr. Hong explained in detail what cellular mechanisms are at work to achieve the modification of the immune system in autoimmune diseases. The FMD is also the solution to slow down aging in healthy people. Dr. Hong discussed clinical applications of the fasting mimicking diet fort autoimmune diseases. It is easier to prevent disease than it is to cure an illness. The FMD is an easier way, because you don’t fast completely, you only reduce your food intake to the bare minimum, but your body “thinks” that you are fasting.

Ultimately, this approach does take some effort, and it does take time to familiarize yourself with it. If patients do it for the first time, they will experience some hunger, the first and second day tend to be a hurdle! Once you make it part of a health routine on a regular basis, it is a lot easier.

Aug
10
2019

Fasting Mimicking Diet For 5 Days Every Month

In December 2017 I heard Dr. Longo speak at a medical conference in Las Vegas. He suggested the use of the fasting mimicking diet for 5 days every month. I am getting into the age group where a little help from nature would not harm (I am 74 years old). I started immediately in December 2017 to do a fasting mimicking diet (FMD) for 5 days.

Effects of fasting mimicking diet

In the beginning you just notice that you are not as hungry as you thought you would be, because you do take in three mini meals of about 200 calories each, which curbs your appetite. It is also important to consume enough liquids. Please note: liquids! Not liquor! Wine, beer or any alcoholic drinks are not part of the diet. You can drink water, but, this may get boring, and you can take water with lemon, herbal teas, black tea and coffee, as long as you stay away from sugar-laced drinks.

How the FMD works

Your total calorie intake will amount to no more than 600 calories per day for the 5 days where you do the fasting mimicking diet. Your body mass index (BMI) decreases between 0.1 and 0.4 per day to a total of 0.5 to 0.9 for the 5 days. This does not seem much, but if it is accumulating every month, a person who is obese now could have a normal weight within one year. The first day of this fast may present some challenges. I found that in the afternoon I felt hungry. What helped was a hot drink( tea, coffee, clear broth). Day two was better, and from day three it has become a routine. There are  no ferocious hunger pangs, no headaches or feelings of weakness or tiredness. I am always surprised that my energy level is improving when I do the fasting mimicking diet for 5 days every month.Dr. Longo suggests not to exercise during the fast. It is obvious that this time is not suitable for half- marathons or taxing hikes, but I found that thirty minutes of aerobics and thirty minutes of weight training felt good. Listen to your body! If you feel lightheaded at any time, stop! The emphasis is on “moderate”.

Dr. Longo noticed the following findings in a mouse model as well as on humans. I summarized this before in a previous blog:

Specific results when on the fasting mimicking diet for 5 days every month

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells, the bone marrow and stimulating the immune cells
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect leads to less disease in older age.

Meal samples of fasting mimicking diet

Dr. Longo developed a kit containing all pre-packaged foods for 5 days under the name “ProLon Fasting Mimicking Diet”. The package is not larger than a shoebox, and the diet is plant-based, has some nutrition bars, drinks as well as freeze-dried soups. You can argue about the nutritional value, as it has an average rating of 3.5 out of 5. It also comes in at a hefty price of 300.00 USD. In reality it is a matter of calorie-math to consume very little food. There are plenty of tables available on the Internet that tell you the nutritional value of foods, and it does not take much effort to compose your own menu.

Here is a fairly typical list of foods

Breakfast: A typical breakfast consists of 2 slices of rye crisp bread (Wasa or Ryvita) with a bit of almond butter on it, a cup of coffee and either black or with stevia and milk.

Lunch: 8 oz. of tomato soup and coffee or tea.

Dinner: A tossed salad with organic bell peppers, ½ tomato, and two thin slices of avocado, vinegar and 1 tablespoon of olive oil.

Here is an alternative meal sample:

Breakfast: Eat a nutrition bar that is based on nuts. It should not be more than 250 calories. Alternatively make your own! Have tea or coffee.

Lunch: 8 oz. of homemade vegetable soup without the addition of pasta or beans.

Dinner: Miso soup and 4 rice crackers, alternatively a small tossed salad with olive oil and vinegar.

Results of fasting mimicking diet for 5 days every month

Here are typical results that I found over several months. I am using body composition scales every day to measure my weight, body fat percentage, visceral fat percentage, muscle percentage, calories burnt and the BMI.

One month the BMI went from 21.9 to 21.1 during a 5-day FMD. Another month the BMI experienced a reduction from 21.7 to 21. 2. Here is a list of the some of the 5-day losses of my BMI on a couple of occasions: 0.8, 0.4, 0.9, 0.7, 0.6, 0.5, 0.7 and so on.

It is important that you are not going on an eating binge after those five days. The FMD conditioned your body to be content with very small amounts of food. Enjoy your food, but stick to moderate portions.

Discussion of fasting mimicking diet for 5 days every month

An intermittent fasting mimicking diet was shown to have a diversified positive health effect in both animal models and humans. For instance, inflammatory bowel disease improves on FMD by improving the bowel microbiota and by promoting the intestinal regeneration.

Intermittent fasting, as this article shows, can prevent age-associated diseases.

This article suggests that T-killer cells that attack cancers are promoted by the intermittent fasting mimicking diet.

A FMD in type 1 diabetic patients has been shown to restore insulin generation in islets of the pancreas of these patients. The result was an improvement of their type 1 diabetes.

More research data on fasting mimicking diet

A clinical trial with 100 subjects was undertaken by Dr. Longo and his research team. He measured markers after 3 cycles of a fasting mimicking diet for 5 days every month. They found that the FMD reduced aging markers, improved diabetes and reduced susceptibility for cancer and cardiovascular disease. In another publication Dr. Longo and co-authors describe how autoimmune diseases can be improved by the use the fasting mimicking diet for 5 days every month.

Another publication by Dr. Longo describes that “age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease, Parkinson’s disease and stroke” can be prevented by fasting mimicking diet for 5 days every month.

Even cancer prevention and cancer treatment can be helped by the fasting mimicking diet.  The FMD makes chemotherapy more tolerable.

Fasting Mimicking Diet For 5 Days Every Month

Fasting Mimicking Diet For 5 Days Every Month

Conclusion

I have shown that with the fasting mimicking diet (FMD) done for 5 days in every month you can lower your body mass index (BMI) by 0.4 to 0.9 units. On the long-term this helps you to keep your BMI stable and in the 21.0 to 22.0 range. Dr. Longo has researched the effect of the FMD in both mice and humans. He found that you age better with less age-related diseases. In addition, inflammatory bowel disease, autoimmune diseases like MS, rheumatoid arthritis and type-1 diabetes improve. Cancer patients who need chemotherapy tolerate it better. Their immune system also produces more killer T cells that destroy cancer cells. The FMD prevents heart attacks, strokes and cancer. Dr. Longo also has shown that there is stimulation of stem cell production and telomeres are increasing in length. Telomeres are important for longevity, which allows you to age healthier with less disease.

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Dec
29
2018

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Several speakers in Las Vegas said that the fasting mimicking diet is very relevant for health and longevity. This happened on day 1 of the 26th Annual A4M World Congress 2018 in Las Vegas.

What were the findings that are relevant?

Dr. Longo has done a lot of animal experiments with intermittent fasting and studying longevity. He repeated what he has learnt over the years from animal experiments and from research on humans. Here are the results that he shared already at last year’s Anti-aging Conference in Las Vegas.

Effects of fasting mimicking diet

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells and the bone marrow
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect leads to less disease in older age.

Increased life span, less heart attack and cancer rates

We know from these animal experiments that mice have a threefold increase in life span. But when heart attack rates and stroke rates improve in humans, cancer cure rates improve and telomere length in humans increase, there is strong evidence that it increases human life expectancy as well. It may take another 10 to 20 years before we have better statistics about the real survival advantage on this diet versus the Standard American diet. But what we know now is a significant start.

Patients on chemotherapy and FMD have much better healing rates than controls

The lecture by Dr. Longo on Dec. 13, 2018 did provide more human data. Patients undergoing chemotherapy tolerate and survive chemotherapy much better when combined with the fasting mimicking diet (FMD). The human data is very similar to the previous mouse model data. This human research was done at the Charité Hospital in Berlin, Germany. Dr. Longo is starting to engage in clinical trials by partnering with physicians, but the publication of this will take several years. In the meantime the FMD is an effective way to rejuvenate on an ongoing basis. Since last year I underwent 12 courses of 5-day FMD every month. Dr. Longo says that even 3 to 4 courses of FMD per year would have a lasting rejuvenating effect.

About the right food intake and getting enough sleep

Dr. La Valle gave a talk in the afternoon of the first conference day where he pointed out several important things. He started his talk by saying that North Americans eat the wrong foods, they eat too much of it and they often eat it at the wrong time (in the middle of the night when the body wants to rest). This can interfere with our diurnal hormone rhythm, which in turn will eventually lead to inflammation in the body. Fasting overnight rests our hormone receptors so they are fully active the following day.

Preventing Alzheimer’s disease

Dr. La Valle praised the FMD as being able to elevate brain derived neurotropic factor. Newer research is pointing at the importance of this factor for preventing Alzheimer’s disease and Parkinson’s disease. He pointed out that the FMD is a good start to change other things in a patient’s life. Such things like exercise, bioidentical hormone replacement and taking vitamins and supplements. All of these all in combination will build up a patient’s health.

More human data about anti-aging

The internist, Dr. Kurt Hong said that he is seeing 200 patients every week. He has done clinical studies on various forms of fasting. The FMD, he said he liked best as it is easy to do (5 days out of one month 500 calories on each of the FMD days). Dr. Hong has seen amazing improvements in patients with MS, Hashimoto’s disease and Crohn’s disease. His talk concentrated on how fasting improved the metabolic syndrome, improved inflammation in the body and improved immune diseases. The FOXO pathway involves transcription factors that are important to regulate cell death (apoptosis). A variant of FOXO3 is responsible for longevity in humans and has been found in centenarians.

Dr. Hong pointed out that self-cleaning (autophagy) is an important rejuvenation process in the body. The FMD stimulates this process. In a 2017 study Dr. Longo and Dr. Hong compared 100 regular patients with 100 patients on the FMD. Only the patients on the FMD showed that the body weight came down. In addition the blood pressure came down as well and the pluripotent stem cells in the blood were up. So, the FMD has a positive effect on various organ systems without any medication. The strongest effect of the FMD would be in the age group of 20 to 40 for anti-aging purposes as it stimulates stem cell production and elongates telomeres.

Fasting and women’s health

Dr. Felice Gersh gave a talk about the effects of fasting on women’s health. She pointed out how important estrogen is in a woman for every organ system. All of the major organ systems including the skin have estrogen receptors. Estrogen stimulates the metabolism. It stimulates the immune system by stimulating macrophages that also have estrogen receptors. In menopause less estrogen production leads to a lack of energy, because the mitochondria are no longer stimulated as they were before. Estrogen also stimulates sirtuins, which is important for anti-aging. Studies with the FMD have shown that estrogen production is re-stimulated in women.

Dr. Joel Kahn was another speaker in the afternoon. He talked about how important the FMD is for cardiovascular health. He does not think that coronary artery surgeries and stents will suddenly get abandoned, but he thinks that the FMD is a powerful tool to delay arteriosclerosis in the arteries. This will delay coronary artery lesions from developing and will add life. In his opinion 40 to 60 year old patients should start using the FMD to prevent cardiovascular disease.

Aging drives chronic disease

Sebastian Brandhorst, PhD pointed out that if we stay active and eat healthy, we will age well. The US is the only country on earth where the life expectancy goes down after there was an initial health gain in the past.

Yeast, worms, flies and mammals follow a nutrient-sensing pathway. That means when food is not around, starvation increases resistance to a variety of toxins. One important aspect of the FMD is the observation that it protects the body against the toxic effects from chemotherapy. FMD and chemotherapy combined almost completely blocked progression of breast cancer in mice. Further studies showed that cytotoxic T cells were responsible for stopping cancer growth. When antibodies against T cells were administered, the beneficial cytotoxic T cell effects against cancer were wiped out. In humans the same protective effect of the FMD was observed. The FMD combined with chemotherapy gave the best survival data in cancer patients.

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Fasting Mimicking Diet Is Very Relevant For Health And Longevity

Conclusion

The fasting mimicking diet (FMD) was ranking very prominently among last year’s anti-aging conference in Las Vegas. Several speakers of this year’s anti-aging conference pointed to the health supporting effect of the FMD. It is now evident that the previous findings in animal research are also true in humans. Missing at this time are prolonged clinical trials that analyze the mechanisms of why the FMD works so well. In the meantime everybody can safely use FMD 5 days out of every month, which will rejuvenate your system by gradually prolonging pluripotent stem cell activation and telomere lengthening. It is just a matter of time when the missing links will be filled in.

More info: intermittent fasting may benefit health.

Jan
31
2016

The Gut and Brain Connection

There is a lot of talk about the gut and brain connection. At the 23rd Annual World Congress on Anti-Aging Medicine (Dec. 11-13, 2015) in Las Vegas there were several lectures pointing out the importance of the gut flora for proper brain function. As a matter of fact, if you have the wrong gut flora, you can get a number of diseases like diabetes, fibromyalgia, rheumatoid arthritis, multiple sclerosis, muscular dystrophy, some cancers and even obesity. Martin P. Gallagher, MD, DC talked about this in his talk entitled “Gut on Fire, Brain on Fire!”

Function of the microbiome

The microbiome is the sum of all microbial organisms inhabiting the human body, which colonize mainly the colon, but also to a lesser degree the small intestine. Dr. Gallagher stated that the microbiome weighs only 7.1 oz., although in the past some have estimated its weight to be as high as 3 pounds. The purpose of the microbiome is to help form a gut/blood barrier. It forms a 30-micron thick layer in the GI tract, protects the intestinal lining and metabolizes food remnants, especially from carbohydrates. In addition, it also communicates with the immune system. There is a cross talk between the lining of the gut and the and the body’s immune system. The gut bacteria help the body to create stability; as a result the good bacteria also decrease intestinal permeability.

Leaky gut syndrome develops

When inflammation occurs in the gut, the thickness of the biofilm is less than 30 microns. Intestinal permeability increases and becomes “leaky gut syndrome”. This can be the cause of autoimmune diseases and possibly other diseases.

The enteric nervous system

The gut can produce as many neurotransmitters as the brain and spinal cord can synthesize. The enteric nervous system communicates with the brain through the vagal nerve. Serotonin is an important neurotransmitter that regulates motility of the gut. The control system of the gut can work on its own and override the concerns of the central nervous system.

Parkinson’s disease is a disorder of the enteric nervous system as well as the brain. With Alzheimer’s disease the characteristic brain lesions are also present in the enteric nervous system!

A mouse experiment showed the following. The Lactobacillus strain is  normally part of the microbiome of the gut.  Re-introduction of Lactobacillus into the gut flora resulted in healing certain parts of the brains of these animals, which researchers associate with anxiety and depression. But when the researchers severed the vagal nerve of these animals, none of these healing changes occurred.

The gut-brain-axis

For this reason the researchers suggested that the gut bacteria are able to communicate with the brain via the vagal nerve. Researchers have coined this connection the “gut-brain axis”. These protective gut bacteria have the ability to protect humans from gastric acidity, from bile acid toxicity, they adhere to the lining of the gut and they persist to reside within the gastrointestinal tract. Probiotics help the immune system to maintain the immunologic memory and to secrete antibodies, called immunoglobulins.

Two strains with benefit to humans are Lactobacillus rhamnosus GG and Saccharomyces boulardii. Probiotics often help against diarrhea. The natural food for gut bacteria in the colon comes from starches of chicory, asparagus, inulin and onions that are indigestible in the stomach and small intestine, but are fermented in the colon to provide food for the bacteria residing there.

Small Intestinal Bacterial Overgrowth (SIBO)

Overgrowth of the small intestine with bacteria that produce endotoxins appears to have significance in both animal models and human disease. Chlamydia species as well as Borrelia burgdorferi (Lyme) can produce toxins that cause hypersensitivity to pain in soft tissues in fibromyalgia and animal models of fibromyalgia. Moreover, SIBO – small intestinal bacterial overgrowth – in experimental animals caused the same hypersensitivity of the soft tissues and also leaky gut syndrome.

Risk factors for SIBO

What causes SIBO is too little stomach acid production, treatment with proton pump inhibitors (powerful anti acid medications) and antibiotics. To summarize, Dr.Gallagher said that SIBO also occurs in post-surgical patients, in patients with diabetes, is brought on by alcohol, nicotine, drugs and GMO foods.

Neurogenic inflammation

Normally the blood brain barrier keeps immune cells from the body out of the brain. Only glucose, proteins and lipids are allowed into the brain, but not lipophilic neurotoxins. In contrast, neurogenic triggers, when admitted to the brain, will compromise the function of the immune cells of the CNS, called microglia. In essence, this can result in memory loss, Alzheimer’s, dementia, seizures, migraines, Parkinson’s Disease, multiple sclerosis, cancer, weakness, numbness, etc.

What triggers inflammation?

Here is a long list of different items that cause inflammation: aging, hormone deficiencies, obesity, diabetes mellitus, cardiovascular disease, fungal infection, the Standard American diet (SAD), pain, trauma and mechanical stress, heavy metals, food allergies, toxins, gut dysbiosis, small intestinal bacterial overgrowth, mal-digestion/absorption, prescription drugs, over-the-counter drugs, recreational drugs and alcohol, lack of exercise and lack of sleep.

Neurotoxic insults start the chain of reactions  like heavy metals, nutritional deficiencies, viruses/fungus/bacteria, inflammatory diet, MSG, solvents, pesticides, herbicides, etc.. One or more of these factors destabilize the tight junctions of the blood brain barrier, which leads to neurogenic inflammation.

Result of neurogenic inflammation

The result is Parkinson’s disease, MS, dementia, chronic pain, behavioral and personality changes, Alzheimer’s disease, ALS and Lyme disease. What seems to be happening a lot is that there is overgrowth of abnormal bacteria in the small bowel, which produce toxins. These in turn lead to leaky gut syndrome, which allows neurogenic triggers to attack the blood brain barrier. It seems like from here it is a short step to neurotoxic insults of the brain overstimulating the microglia, which will produce the diseases listed above.

Healing of brain inflammation

First of all, treatment starts with the Mediterranean diet, which has been shown to have anti-inflammatory properties. Second, people who are gluten sensitive need to eliminate gluten entirely from their food. Third, casein sensitive people need to eliminate dairy products. Furthermore, a triple strength, molecularly distilled fish oil product is taken as a supplement every day with 4 grams or more of DHA/EPA. This helps the anti-inflammatory response.

Glutathione

One of the most powerful antioxidants and anti-inflammatories is intravenous glutathione. This is given as intravenous chelation therapy, which removes heavy metals. Other chelation agents such as EDTA intravenously may be given alternatively. Dr.Gallagher said that glutathione serves as primary cellular defense against free radicals, is a powerful antioxidant and serves as detoxifying agent against xenobiotics. Xenobiotics are remnants of artificial fertilizers, pesticides and pollutants that are contained in crops we eat.

Dr. Gallagher gives 600mg of glutathione twice per day intravenously for 30 days. Uniquely, in Parkinson’s disease patients whose mid brain is often poisoned by mercury this leads to 42% decline of disabilities and the effect lasts for 2 to 4 months after this treatment has been stopped. Coupled with this the treatment also protects telomeres, the caps on the ends of cellular DNA as well as mitochondrial DNA. In addition, glutathione is protective of neurons and nerves.

Curcumin

This common Indian spice, found in turmeric is a potent anti-inflammatory. It is a safe natural agent and has also anti-viral and anti-tumor activities. It binds to the vitamin D receptor and works synergistically together with vitamin D3. Solid lipid curcumin particle technology makes curcumin 65-fold more bioavailable; free curcumin is allowed to pass the blood brain barrier. Lower doses achieve the same effect than regular curcumin.

According to a publication using lipidated curcumin the following observations were made: improved vascular function; equally important, inflammatory markers reduced by 14%; in like manner, triglycerides lowered by 14%; by the same token, oxidative stress reduced; not to mention, catalase increased and finally total antioxidant status improved. Here is another paper about lipidated curcumin.

Omega-3 fatty acids

Omega-3 fatty acids are anti-inflammatory by countering the arachidonic acid pathway that leads to inflammation. Physicians recommend it as triple strength, molecularly distilled fish oil. DHA/EPA are the active ingredients. Chronic inflammation requires 2 to 12 grams daily; irritable bowel syndrome 6 to 12 grams daily; depression, anxiety and insomnia require 2 to 4 grams per day; autoimmune disease, back pain and degenerative joint disease 4 to 12 grams per day.

Gut/brain dysbiosis

For gut/brain dysbiosis Dr. Gallagher recommended to start with a 10-day fruit/vegetable detox program. Milk thistle, glutathione and pancreatic enzymes in combination lead to improvement. Lipidated curcumin is also useful. The physician also gives glutamine, prebiotics and probiotics for gut support. He also tells the patient to take molecularly distilled fish oil (DHA/EPA) and vitamin D3 as anti-inflammatories. Doctors also administer oral and intravenous glutathione to detoxify. Many doctors use natural as a combination of glutathione, oregano, olive leaf and silver salts.

The Gut and Brain Connection

The Gut and Brain Connection

Conclusion

Inflammation can start in the gut, lead to leaky gut syndrome and break down the blood/brain barrier. The end result is that inflammation develops in the brain and Alzheimer’s disease and dementia can occur. The sooner the physician starts with treatment, the faster the recovery is. When the patient has reached the end stage, it is difficult to turn the inflammatory process around. Fortunately there are effective ways to get the inflammation under control with intravenous glutathione in the beginning and subsequent treatment with lipidated curcumin, omega-3 fatty acid and vitamin D3. A permanent switch to a Mediterranean diet is important as well to keep inflammation under control.

Lifestyle and nutrition choices are important for prevention

A few years back this mainstream medicine considered this type of approach as “quackery”; now it is the latest information from research into the brain/gut connection. The right lifestyle and nutrition choices can do a lot on a preventative basis. Once disease has taken root, treatment may still be possible, but once it is at a later stage a full cure is unlikely.

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Sep
28
2013

Sleepless Nights

Sleeping problems (insomnia) are very common. About 10% of the population suffers from chronic insomnia; 30% of the population suffers from occasional sleep problems. In a large outpatient population of a clinic consisting of 3500 patients who had at least one major clinical condition, 50% complained of insomnia, 16% had severe symptoms, 34% had mild symptoms (Ref.1). Insomnia is more common among women, and older people as well as in people with medical or psychiatric illnesses. Long-term studies have shown that the same insomnia problems persist throughout many years. It is not possible to offer a simple remedy for insomnia, because insomnia is a complex problem. Here I will discuss some of the causes of insomnia and also discuss some of the treatment options.

Symptoms of insomnia

The person who suffers from insomnia will usually state that they have problems falling asleep. Worries of the day suddenly circulate through their thoughts and they toss and turn nervously looking at the clock from time to time and getting more and more anxious that they cannot sleep. Others fall asleep OK, but in the middle of the night they wake up perhaps to visit the restroom, but then they cannot go back to sleep. Others wake up 2 hours before their normal alarm clock time and they feel their stomach rumbling making it impossible to fall back to sleep. Older people with chronic diseases and general poor health suffer more from insomnia. In this setting insomnia may be more related to the underlying disease rather than old age. Psychiatric disorders also are associated with more insomnia. Treat the underlying psychiatric illness, and the insomnia disappears.

Although insomnia is a sleep disturbance during the nighttime, people who are affected with this complain of daytime fatigue, of overstimulation, yet they catch themselves making frequent mistakes, and their inability to pay attention gets them involved in accidents and falls. Longitudinal studies have shown (Ref. 1) that people with chronic insomnia are more likely to develop psychiatric disease, such as major depression,  anxiety disorder and alcohol and substance abuse. Unfortunately these disorders can by themselves again cause insomnia, which reinforces chronic insomnia. Insomnia leads to poorer social and physical functioning, affects emotions, leads to a lack of vitality and physical endurance, contributes to worsening of pain and can affect general and mental health.

Research about insomnia

Much has been learnt from sleep studies using polysomnography monitoring during a full night’s sleep. These studies have been used mainly as a research tool. In such studies eye movements, brain wave activity, muscle activity, chest movements, airflow, heart beats, oxygen saturation and snoring (with a microphone) are all simultaneously recorded. This way restless leg syndrome, sleep apnea, snoring, seizure disorders, deep depression etc. that can all lead to insomnia can be diagnosed and separated from insomnia. The stages of sleep (wakefulness, stage 1 to 3 sleep and the REM sleep stage) can also be readily measured using polysomnography (Ref.2). According to this reference the majority of insomnia cases do not need this complex procedure done.

Sleepless Nights

Sleepless Nights

Causes of insomnia

Traditionally insomnia cases are classified into primary insomnia and secondary insomnia. Secondary insomnia is caused by all of the factors discussed below. When they are dealt with, we are left with cases of primary insomnia.

The following medical conditions can cause insomnia: heart disease, pulmonary diseases like asthma and chronic obstructive pulmonary disease (COPD); gastrointestinal disease like liver cirrhosis, pancreatitis, irritable bowel syndrome, ulcers, colitis, Crohn’s disease; chronic kidney disease; musculoskeletal disease like arthritis, fractures, osteoporosis; neurodegenerative disease like MS, Parkinson’s disease, Alzheimer’s disease; endocrine disease like diabetes, hyper- or hypothyroidism, adrenal gland fatigue and insufficiency; and chronic pain conditions. Also, psychiatric conditions like major depression, schizophrenia and anxiety disorders can cause insomnia.

This list in not complete, but it gives you an idea of how complex the topic of insomnia is.
The physician who is seeing a patient with insomnia needs to rule out any of these other causes of insomnia to be certain that the only condition that is left to treat in the patient is insomnia itself. The other diagnoses have to be dealt with separately or else treatment of insomnia will fail.

Ref. 1 points to a useful model of how to think about causation of insomnia: there are three points to consider, namely predisposing, precipitating, and perpetuating factors. Let’s briefly discuss some of these.

Predisposing factors

We are all different in our personal make-up. If you are well grounded, chances are you are not susceptible to insomnia. Anxious persons or persons who have been through a lot of negative experiences in life will have personality traits that make them more prone to insomnia. Lifestyle choices such as late nights out, drinking with the buddies in a bar (extreme circadian phase tendencies) will have an impact on whether or not you develop insomnia.

Precipitating factors

A situational crisis like a job change or the death of a loved one can initiate insomnia.  However, there could be a medical illness such as a heart attack, a stroke or the new diagnosis of a psychiatric illness that has become a precipitating factor. Sleep apnea and restless leg syndrome belong into this group as well as would the stimulating effect of coffee and caffeine containing drinks. Jet lag and nighttime shift work can also be precipitating factors.

Perpetuating factors

Daytime napping to make up for lost sleep the night before can undermine sleep initiation the following night, which can lead to a vicious cycle. Similarly, the use of bedtime alcoholic drinks leads to sleep disruption later that night and can become a perpetuating factor, if this habit is maintained. Even the psychological conditioning of being anxious about whether or not you will fall asleep easily or not the next night can become a perpetuating factor.

I will return to this classification and the factor model of causation of insomnia when we address treatment options.

Drugs that can cause insomnia

One major possible cause for insomnia  can be side effects from medications that patients are on (would belong to the ‘perpetuating factors’ among causes). Physicians call this “iatrogenic insomnia”. The antidepressants, called selective serotonin reuptake inhibitors (SSRI’s) like Prozac are particularly troublesome with regard to causing insomnia as a side effect. Other antidepressants like trazodone (Desyrel) are used in small doses to help patients with insomnia to fall asleep. Some asthmatics and people with autoimmune diseases may be on prednisone, a corticosteroid drug. This can cause insomnia, particularly in higher doses; so can decongestants you may use for allergies; beta-blockers used for heart disease and hypertension treatment; theophylline, an asthma medication and diuretics. Central nervous stimulants like caffeine or illicit drugs can also cause insomnia. Hormone disbalance in general and hyperthyroidism specifically as well as Cushing’s disease, where cortisol levels are high will cause insomnia.

Treatment of insomnia

So, how should the physician approach a patient with insomnia? First it has to be established whether there is secondary insomnia present due to one of the predisposing, precipitating or perpetuating factors. In other words, is there secondary insomnia due to other underlying illnesses? If so, these are being addressed first. Lifestyle choices (staying up late every night) would have to be changed; alcohol and drug abuse and overindulging in coffee or caffeine containing drinks needs to be dealt with. Cognitive therapy may be beneficial when mild depression or anxiety is a contributing factor to insomnia.

The remaining insomnia (also medically termed “primary insomnia”) is now being treated.

The following general points are useful to get into the sleeping mode (modified from Ref. 3):

  1. Ensure your bedroom is dark, soundproof, and comfortable with the room temperature being not too warm, and you develop a “sleep hygiene”. This means you get to sleep around the same time each night, have some down time 1 hour or so before going to bed and get up after your average fill of sleep (for most people between 7 to 9 hours). Do not sleep in, but use an alarm clock to help you get into your sleep routine.
  2. Avoid caffeine drinks, alcohol, nicotine and recreational drugs. If you must smoke, don’t smoke later than 7PM.
  3. Get into a regular exercise program, either at home or at a gym.
  4. Avoid a heavy meal late at night. A light snack including some warm milk would be OK.
  5. Do not use your bedroom as an office, reading place or media center. This would condition you to be awake.  Reserve your bedroom use only for intimacy and sleeping.
  6. If you wake up at night and you are wide awake, leave the bedroom and sit in the living room doing something until you feel tired and then return to bed.
  7. A self-hypnosis recording is a useful adjunct to a sleep routine. Listen to it when you go to bed to give you something to focus on (low volume) and you will find it easier to stop thinking.

Drugs and supplements for insomnia

1. In the past benzodiazepines, such as diazepam (Valium), lorazepam (Ativan), fluorazepam (Dalmane), temazepam (Restoril), triazolam (Halcion) and others were and still are used as sleeping pills. However, it was noted that there are significant side effects with this group of drugs. Notably, there is amnesia (memory loss), which can be quite distressing to people such as not remembering that someone phoned while under the influence of the drug, you promised certain things, but you cannot remember the following morning what it was. Another problem is the development of addiction to the drugs with worse insomnia when the drugs are discontinued. Many physicians have stopped prescribing benzodiazepines.

2. There are non-benzodiazepines drugs that are used as sleeping pills (hypnotics), such as Zaleplon (Sonata), Zolpidem (Ambien) and Eszopiclone (Lunesta).  They seem to be better tolerated.

3. Ramelteon, a melatonin agonist, is available by prescription in the US. It probably is the best-tolerated mild sleeping pill and works similar to melatonin, but is more expensive. Chances are that your physician likely would prescribe one of the non-benzodiazepines drugs or Ramelteon for you as they do not seem to be addicting.

4. However, there is an alternative: Many patients with insomnia tolerate a low dose of trazodone (Desyrel), which is an antidepressant with sleep restoring properties. A low dose of 25 to 50 mg at bedtime is usually enough for insomnia. This allows the patient to fall asleep within about 30 minutes of taking it, and sleep lasts through most of the night without a hangover in the morning. Many specialists who run sleep laboratories recommend trazodone when primary insomnia is diagnosed. However, this is still a drug with potential side effects as mentioned in the trazodone link, but 50 mg is only ¼ of the full dose, so the side effects will also be less or negligible.

5. I prefer the use of melatonin, which is the natural brain hormone designed to put us to sleep. Between 1 mg and 6 mg are sufficient for most people. We know from other literature that up to 20 mg of melatonin has been used in humans as an immune stimulant in patients with metastatic melanoma with no untoward side effects other than nightmares and some tiredness in the morning. A review from the Vanderbilt University, Holland found melatonin to be very safe as a sleeping aid. There are several melatonin receptors in the body of vertebrates (including humans), which are stimulated by melatonin.

6. Other natural methods are the use of L-Tryptophan at a dose of 500 mg at bedtime, which can be combined with melatonin. It is the amino acid contained in turkey meat, which makes you tired after a Thanksgiving meal. GABA is another supplement, which is the relaxing hormone of your brain, but with this supplement tolerance develops after about 4 to 5 days, so it is only suitable for very short term use. Herbal sleep aids are hops, valerian extract and passionflower extract. They are available in health food stores.

Conclusion

A lack of sleep (insomnia) is almost a given in our fast paced lives.

When it comes to treatment, all of the other causes of secondary insomnia need to be treated or else treatment attempts would fail. What is left is primary insomnia. This is treated as follows:

We need to review our sleeping habits, lifestyles and substance abuse. Remove what is detrimental to your sleep. Start with the least invasive treatment modalities such as self-hypnosis tapes, melatonin, L-Tryptophan or herbal extracts. Should this not quite do the trick, asks your doctor for advice. The non-benzodiazepines drugs or Ramelteon would be the next level up. It may be that an alternative such as low dose trazodone would be of help. Only, if all this fails would I recommend to go to the more potent sleeping pills (keep in mind the potential for addiction to them).

References

1. David N. Neubauer, MD (John Hopkins University, Baltimore, MD): Insomnia. Primary Care: Clinics in Office Practice – Volume 32, Issue 2 (June 2005)  © 2005, W. B. Saunders Company

2: Behrouz Jafari, MD and Vahid Mohsenin, MD (Yale Center for Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA): Polysomnography. Clinics in Chest Medicine – Volume 31, Issue 2 (June 2010), © 2010 W. B. Saunders Company

3. Jean Gray, editor: “Therapeutic choices”, 5th edition, Chapter 8 by Jonathan A.E. Fleming, MB, FRCPC: Insomnia, © 2008, Canadian Pharmacists Association.

Last edited Sept. 28, 2014

Jul
20
2013

Our Endangered Food

This is about our endangered food. Our grandparents ate foods that were healthier and more pure than today’s mass produced food. Beef came from grass-fed cattle; milk came from cows that grazed on pastures; bread was baked from the old Emmer wheat or Einkorn wheat. Geneticists were not around yet, so their food was safe from adulteration.

The adulterated modern wheat

Fast forward to the late 1990’s. Now farmers around the world are growing 19 different Clearfield wheat varieties. Researchers produced them by hybridization from exposure to toxic chemicals in the 1960’s and 1970’s. At that time  GMO (genetically modified organisms) regulations were not around yet.  Hybridization with grasses using exposure to a toxic substance like sodium azide produced modern wheat. Technically this forced chemical hybridization is different from genetic engineering although in both cases there are significant genetic changes of the chromosomes in the plant. The end result with regard to wheat hybridizations were wheat varieties that grow under adverse conditions and that have much faster growing rates, higher yields and are easier to harvest because they grow only to a about 2 feet height instead of 4 feet.

Chromosomal changes of the new wheat

When compared to the older Emmer and Einkorn types of wheat there have been significant chromosomal changes. Einkorn (Triticum monoccocum) has 14 chromosomes; Emmer (Triticum diccocum) has 28 chromosomes. Modern wheat, the Clearfield variety has 42 chromosomes, like spelt. The hybridization process for Clearfield wheat by BASF is summarized in this link. Here is a discussion with Dr. Davis, the author of the book “Wheat Belly” (Ref.1), which reviews the history of modern wheat

Modern wheat has much more gliadin content

The point of mentioning all this here is that modern wheat with many more chromosomes than the original Einkorn wheat has also much more gliadin content, which is the protein that makes celiac disease sufferers sick when they eat wheat. However, despite the significant chromosomal changes of modern wheat, which his grown in 99% of the world today no safety test were done to show that it is harmless to your health. There were no animal experiments and no human exposure trials with proper controls to show that exposure to the modern wheat varieties is safe on the long-term.

The manufacturer mixes wheat  into processed foods

It turns out now in hindsight that it is not only the person with celiac disease that has to fear modern wheat. The increased concentration of gliadin in modern wheat is the protein that splits the sealant between gut cells and sensitizes your body to produce autoantibodies. The food processing plants mix wheat into soups, baby food, lip stick, sauces and a host of other foods. This increases the gliadin concentration that your system has to cope with, if you do not read labels and eliminate it. You have to be a detective in the supermarket and constantly read labels to look for wheat and avoid it, at least I do.

Modern wheat can cause antibodies against gliadin

The reason is that even low doses of wheat over a long period of time cause leaky gut syndrome and cause antibodies against gliadin. Soon after the formation of autoimmune antibodies against your own tissues form that attack your gut cells (causing irritable bowel syndrome, celiac disease and ulcerative colitis); joint cells (causing rheumatoid arthritis), thyroid cells (causing Hashimoto disease) and it can even cause colon cancer.

Remember, there have never been any clinical trials to show that modern wheat is safe.

Our Endangered Food

Our Endangered Food

Alternatives to wheat

Oats used to be thought safe to eat for celiac disease patients, provided they are not contaminated with rye, wheat or barley.

As this publication shows there can still be prolamins in oats, which are different from gliadin, but may be toxic for celiac patients. Another paper showed that there are different levels of gliadin- and glutenin-like avenins in different varieties of oats. These are subunits of prolamin. It depends on what type of avenins or prolamins are in the content of an oat variety. A label on an oat package may proclaim that it is entirely gluten free. But the question remains whether the manufacturer tested the oats before they reached the shelves of the grocery store.

Are “gluten free oats” safe to eat for celiac patients?

For a celiac patient it would not be safe to eat these types of oats as labeling requirements for avenins or prolamins do not yet exist. So, the label “gluten free oats” may be misleading as oats containing prolamins or avenins still could make celiac patients sick.

So, what are safe gluten substitutes? Rice, corn, soy, chickpeas, sweet potatoes and nuts. A helpful reference can be found through this link.

As we will discover below, unfortunately in the US most rice, corn and soy is now GMO food and celiac patients will likely react much more to these as they are more sensitive and will likely produce autoantibodies easier. So stick to organic rice, organic corn and organic soy (often the package will mention” free of GMO”).

GMO foods to avoid

It is interesting that the US and Canada did not pass a law that GMO foods should be labeled. This is changing rapidly as people realize that in Europe many countries have required all GMO foods to be labeled as such. Here is a publication that shows that the GMO labeling campaign is gaining momentum.

Genetically modified corn and soy contains the Bt toxin; it has been found in babies as mentioned in this article. Bt toxin damages the small bowel (the ileum) through Cry1Ab (the protein produced in genetically modified corn and soy), which disables the absorption of vitamin B12. This in turn will cause anemia (historically the cause of pernicious anemia was found to be due to a lack of vitamin B12 absorption).

Cytochrome P450 (CYP) detoxification enzymes

Drs. Anthony Samsel and Stephanie Seneff  stated about the effects of Roundup in a publication dated April 2013  that glyphosate’s inhibition of cytochrome P450 (CYP) enzymes, which is a crucial detoxification enzyme complex in the liver has been overlooked when studies were done regarding toxicity in mammals. The CYP enzymes in the liver is important to metabolize and eliminate estrogens and also helps to detoxify xenobiotics, which are estrogen-like substances as residues from insecticides and other chemicals. Thus, glyphosate (=”Roundup” produced by Monsanto) amplifies the damaging effect of environmental toxins and chemical residues from non-organic food that we eat. The build-up of estrogens and xenoestrogens has been shown to be responsible for many cancers (atypical Hodgkin’s lymphoma, breast cancer, prostate cancer, colon cancer etc.).

The ten most common GMO foods in the US

Here is a summary of the 10 most common GM foods in the US : Sugar beets, cotton seed oil, corn, canola oil, milk, aspartame (from genetically modified bacteria), zucchini, yellow squash, soybeans, papaya. You see that genetic engineering invaded almost all of our food.

Why is that of any concern?

The problem is that it is extremely difficult to conduct safety studies for human consumption. It likely takes three generations of feeding GMO food before diseases develop. In the case of humans the reproductive cycle is 30 years. This would mean that it could take up to 90 years to obtain meaningful human safety study results. From a commercial point of view researchers perceived that 90 years was too long. Instead they opted for the standard rat or mouse model of 90 day testing. Researchers used this test model instead as a “test for toxicity for mammals”.  However, typically this does not show any change between GMO food compared to regular food as it is too short an observation time. I have described this earlier in this blog. In this recent publication pigs fed GM crops were found to have severe stomach inflammation and the female GMO fed pigs developed a 25% larger uterus than the non-GMO-fed controls.

The approval process for GMO foods is flawed

The 20-year approval process for GMO foods is flawed according to this review. Belgium researchers found virus particles in GMO foods that they did not expect to be there. Farmers feed this in feedlots to milk producing animals and beef cows. There is transmission of these particles into milk and beef. But the FDA, USDA and other official food safety agencies continue to state that GMO foods are safe. A significant proportion of the US public disagrees about the safety testing process regarding  GMO foods.  The public wants clear labeling of all GMO, so they have a choice of what they buy. We should have a choice whether we get organic food with no chemicals, no antibiotics and no GMO. Or whether we buy the cheaper regular food.

Remember, you are what you eat.

Conclusion

Originally researchers modified wheat by hybridization to “save” the world from hunger. The production worldwide has improved tremendously so that this objective has been reached. However, since then genetic engineers have worked on adulterating the rest of our foods. The purpose was mostly with the aim to make farming on a large scale easier. In both instances researchers never performed safety testing on animals and humans. It is only now that it is becoming apparent that there are flaws with regard to food safety testing. This is true for both wheat and GMO foods.

Leaky gut syndrome and autoimmunity

With wheat it is the higher concentration of gluten and gluten-like substances that are the problem. This causes a leaky gut, a breakdown of the gut/blood barrier. It also causes autoimmunity and colon cancer. GMO foods may transmit viral particles and Bt toxin. This can cause autoimmune diseases and fertility problems. But it also can interfere with the liver’s detoxification system. This in turn can cause cancers. The full health impact is not clear at this point. It may take another 70 years for wheat show the full ramifications. And it likely will take another 80 years for GMO foods to find out all the consequences. Some people have decided not to be part of this mass experiment and rather buy organic foods. I belong to this group.

More information on genetically modified food: http://nethealthbook.com/health-nutrition-and-fitness/nutrition/genetically-engineered-foods/

Reference

1. William Davis, MD: “Wheat belly. Lose the wheat, lose the weight, and find your path back to health.” HarperCollins Publishers Ltd., 2011.

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May
01
2008

Early Use of Immunosuppressive Drugs for Early Crohn’s Patients

So far the strategy of treating patients, who were newly diagnosed with Crohn’s disease, was the use of corticosteroids to control abdominal pain and bloody diarrhea. The conventional mode of treatment consisted of a “step-up” treatment: after corticosteroids the use of immunosuppressants and finally antibody treatment would follow to curb the inflammatory response. International data which were published in the Lancet (February 23 issue) points to a safer and more effective treatment protocol. It consists of a “top-down” approach rather than of the conventional “step-up” approach. Patients receive immunosuppression early in the form of azathioprine and also the antibody infliximab, known as Remicade. Another study examined patients who were on maintenance therapy with adalimumab (Humira). They experienced sustained improvements in the symptoms that are associated with Crohn’s disease. After 4 weeks of induction therapy with the medication patients with mild and severe depression had improved to such an extent that they returned to the normal range. They were also assessed regarding fatigue and after treatment they showed a significant improvement in their daily functioning. The two treatment protocols were compared in a trial involving 129 patients with Crohn’s disease who had no previous treatment. At the end of the trial the researcher found that 65% of the group that had received the “top-down” treatment was symptom free after 26 weeks of treatment. Contrary to this only 36% of the “step-up” patients went into remission during the same time.

Early Use of Immunosuppressive Drugs for Early Crohn's Patient

Crohn’s before and after immunosuppressive drugs

When the patients were examined after 1 year, 62% of the “top-down” group was still symptom free, but only 42% of the “step-up” group had no symptoms. Dr. Brian Feagan of the University of Western Ontario coordinated this trial involving international sites in Belgium, Holland and Germany. He points out that the newly diagnosed Crohn’s disease patient that has the worst prognostic signs will benefit from this form of treatment. The top-down modality also is safer, as it protects the patient from high exposure to steroids. Similar results were demonstrated in patients with rheumatoid arthritis. The results of these trials and Dr. Feagan’s research suggest that the top-down treatment option could also give the best chance to patients with other chronic autoimmune diseases such as ulcerative colitis.

More information about Crohn’s disease: http://nethealthbook.com/digestive-system-and-gastrointestinal-disorders/crohns-disease-crohns-disease/

Reference: The Medical Post, March 4, 2008, page 2; April 1, 2008, page 17

Last edited November 3, 2014

Sep
01
2007

MS Vaccine Breakthrough

One of the great hopes associated with genetic research is the goal to combat disease. With the human genome project completed it is now possible to look at new therapies. The work remains large and seems to be overwhelming, but a new vaccine for MS represents a major triumph. MS has been an illness that has devastated individuals and their families. It also has vexed and frustrated researchers and health professionals. Immunomodulating therapy with interferon has been able to make a difference in the quality of life for many patients, but so far it has been a seemingly impossible dream to find a vaccine that is safe and effective.

Montreal research, which has been published in August, confirms that the vaccine works by reducing the numbers of the immune system cells attacking the nerve fiber sheath. MS belongs to the groups of autoimmune diseases, meaning that cells of the own immune system turn against other body cells and destroy them. The challenge has been to stop these cells. So far immunomodulators have been looked at as an answer to this problem. This breakthrough represents a first in the history of medicine where a DNA vaccine will be used in the treatment of an autoimmune disease, which is MS.

MS Vaccine Breakthrough

MS Vaccine Breakthrough

Other autoimmune diseases are lupus or rheumatoid arthritis. No vaccine is available for these diseases, but the first DNA vaccine represents hope for many, that more therapies will become available.

As this review shows, the DNA vaccine experiment against MS failed, because in clinical trials it did not stop MS lesions from growing: http://multiple-sclerosis-research.blogspot.com/2012/01/research-myelin-dna-vaccination-and.html

More information about MS: http://nethealthbook.com/neurology-neurological-disease/multiple-sclerosis/

Reference: National Review of Medicine, August 30, 2007, page 10

Last edited November 3, 2014