Sep
09
2023

How the Immune System affects Parkinson’s Disease

By | autoimmune disease, diet, Fitness, immune system, Inflammation, Parkinson’s disease

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This article explains how the immune system affects Parkinson’s disease (PD). Notably, in the past physicians thought that Parkinson’s disease was due to a degenerative change of the substantia nigra. This explained why balancing was a problem, why shaking of the hands occurred and why falls happened often. It it important to realize that nobody thought about the immune system.  And no-one knew that an autoimmune process could be behind Parkinson’s disease.

T cells that react to a damaged protein called alpha-synuclein

There are specific changes in the immune system approximately 10 years before Parkinson’s disease symptoms occur in patients who come down with the disease. Researchers from the La Jolla Institute for Immunology showed that T cells play a key role in causing PD. They react to a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells. Laboratory physicians can assay this through a simple blood test, which becomes a screening tool for early Parkinson’s disease. The reactive T cells stay around for about 10 years, then fade away. There seem to be other immune factors that weaken the initial aggressive phase of the T cells.

The role of inflammation in Parkinson’s

When the immune system malfunctions chronic inflammation can develop. In farmers exposed to pesticides the later development of Parkinson’s disease was observed. The researchers thought that the pesticides caused an irritation of the immune system leading to chronic inflammation. There is evidence that the gut bacteria are different in Parkinson’s disease patients when compared to normal controls. The gut absorbs the metabolites of the abnormal gut bacteria and causes chronic inflammation. In an attempt to stop the inflammatory process, the immune system can develop autoimmune antibodies, which can cross react with cells of the substantia nigra. This in turn can cause Parkinson’s disease.

Lifestyle factors that people can change to prevent PD

Dr. Rebecca Gilbert, vice-president and chief scientific officer for the American Parkinson Disease Association (APDA) commented on the importance of lifestyle changes. She said: “It makes intuitive sense that instituting lifestyle modifications that potentially decrease inflammation may decrease the risk of Parkinson’s disease. Exercise, for example, has been shown to reduce inflammation and is probably one of the many reasons that exercise reduces the risk of Parkinson’s disease and also improves established Parkinson’s disease.” She commented further: “Also, we should avoid things like excessive alcohol and nicotine that we know have negative effects on the immune system,” she added. “And managing our stress as best as possible can slow and help maximize outcomes of many diseases.”

Changing diet can help postpone Parkinson’s disease

With regard to the best diet that will help Parkinson’s disease patients she said: “The MIND diet emphasizes whole grains, vegetables, nuts, legumes, and berries. Fish is the preferred protein and olive oil is the preferred fat. Recently a study showed that adherence to the MIND diet and the Mediterranean diet had an association with later onset of Parkinson’s disease.”

The gut connection to Parkinson’s disease

According to the WHO the global prevalence of Parkinson’s disease has doubled in the last 25 years. At this point we do not know why this is so. But many investigations have shown that there is a significant difference in the gut bacteria composition of healthy controls and Parkinson’s disease patients. There is a 30% difference between the bacterial composition of healthy controls and patients with Parkinson’s disease. This has led to Braak’s Hypothesis of Parkinson’s Disease. This hypothesis says that an unknown pathogen enters through the nose, the person swallows it and it ends up in the gut. Absorption gets it into the gut wall and it migrates through the vagus nerve into the central nervous system where it leads to accumulation off alpha-synuclein in the substantia nigra. This destroys the dopamine producing cells in that region causing the symptoms of PD.

Can any diet fight gut dysbiosis?

  • In 2022 study they found that flavonoids, the pigments of fruit were associated with a lower mortality of patients with Parkinson’s disease.
  • In an earlier study of 2018 researchers determined that a protein from fish with the name parvalbumin helped Parkinson’s patients to stop producing alpha-synuclein. PD patients suffer from clumping of alpha-synuclein, which causes their symptoms.
  • Restriction of refined carbohydrates “especially diets with a low glycemic index, rich of vitamins and polyphenols, a Mediterranean diet for example, can be recommended”.

Regular exercise to prevent Parkinson’s disease

Regular physical exercise maintains body function and muscle strength. Dr. Emer MacSweeney said: “Being physically active is one of the best things you can do for your body. Exercise helps protect against many diseases and keeps the heart, muscles, bones, and brain in optimum condition. Exercise promotes the oxygenation of the brain and stimulation of multiple neurochemicals.”

Several studies showed that patients with PD deteriorate slower, if they exercise regularly. Part of that response is due to the release of endorphins and serotonin, but we do not know all of the positive mechanisms of exercise at this time.

How the Immune System affects Parkinson’s Disease

How the Immune System affects Parkinson’s Disease

Conclusion

Recent research changed what we know about Parkinson’s disease (PD). Braak’s Hypothesis of Parkinson’s Disease states that an unknown pathogen enters through the nose, gets swallowed and ends up in the gut. From there it gets taken up into the gut wall and migrates through the vagus nerve into the central nervous system. There it leads to accumulation of alpha-synuclein in the substantia nigra. This destroys the dopamine producing cells in that region causing the symptoms of PD. But we also know that chronic inflammation can aggravate the symptoms of PD patients. When the composition of the gut bacteria deteriorates, this too will make PD patients worse.

Lifestyle changes help to postpone Parkinson’s disease

A healthy diet, like the MIND diet, DASH diet or the Mediterranean diet have beneficial effects on PD patients. Many studies also found that regular physical exercise is a stabilizing factor in PD patients. There are still many gaps in what we know about the causation of PD. But the above summarized factors are a good start.

Apr
23
2023

Help with Menopausal Symptoms

By | blood test, Diabetes, diet, Inflammation, Insomnia, irregular periods, Menopause, Nutrition, sleep

At the 30th A4M Conference mid-December Dr. Anna Cabeca lectured about “Help with menopausal symptoms”. A4M stands for “Conference of the American Academy of Anti-Aging Medicine”. It is a yearly event at the Sand Conference Center of the Venetian Palace in Las Vegas. The following is a summary of the very detailed lecture by Dr. Anna Cabeca.

Definition of postmenopausal symptoms

Dr. Cabeca’s detailed title for her lecture was: “Menopause: Hot flashes, brain fog and vaginal dryness; 3 symptoms women don’t have to experience.”  The first thing to remember is this detailed list of symptoms of menopause:

  • Hormones are disbalanced
  • Unusual behaviors and moodiness
  • Gaining weight (accumulating fat)
  • Tiredness
  • Loss of willpower
  • Sleep disturbance: can’t sleep or sleeps all the time
  • Brain fog and memory problems
  • Lost your “edge”
  • No sex drive
  • Aging rapidly
  • Hair loss
  • Thyroid problems
  • Hysterectomy (to remedy excessive periods)

Hormone changes with menopause

To clarify, there are major hormone changes with menopause as follows. To explain, at the age of 35 progesterone suddenly experiences a major reduction, which completes by the age of 45. In contrast, estrogen levels remain high until the age of 40 when it, too is reduced to background activity by the age of 50. In fact, at this point estrogen production is still more than progesterone synthesis. This is the basis of what is called estrogen dominance.

In general, symptoms of estrogen dominance are: PMS, hot flashes, night sweats, mood swings, weight gain, vaginal dryness, brain fog, irregular periods, less libido, missing or increased periods, bone loss and sleep disturbance.

To emphasize, the production of male hormones, DHEA and testosterone, slows down around the age of 30 and reaches a low plateau around the age of 45. This explains, for example, the lack of sex drive mentioned above. In addition, it is also partially responsible for brain fog, tiredness, hair loss and unusual behaviors and moodiness.

Perimenopause and menopause increase risk for diabetes

By all means, there is a clear relationship between age and the risk of developing diabetes in both males and females. But it must be remembered that the hormone weaknesses in combination with weight increases can also trigger diabetes.

Head-to-toe patient work-up

There are two parts to a patient’s work-up, a thorough assessment and a patient’s education.

The patient’s assessment includes:

  • Energy, mind, spirit
  • Hormone balance
  • Inflammation
  • Assessment of diet and nutritional intervention
  • Gastrointestinal health and digestion
  • Detoxification
  • Structural investigation

Surely, another key point is that patient education is important to be successful in the multiple step intervention to normalize the metabolism, shed excessive weight and help the patient to refocus.

Comments to the patient’s assessment

Indeed, the display of energy in a patient is closely related to hormone balance. Notably, when hormones are measured and they are out of balance, this usually explains the multiple symptoms. It is important to realize that inflammation is measured with the high-sensitivity CRP blood test. This test measures the level of inflammation. Initially, the level may be 30, but with weight loss it often normalizes with values of 2 or 3. At the same time weight loss stabilizes blood sugar (indicated by an initially high, but later normalizing hemoglobin A1C) and diabetes can completely disappear. Frequently, an analysis of the diet often shows that the patient is eating too much sugar and starchy foods.

Faulty nutrition, heavy metals and osteoporosis

In addition, many patients also eat too much meat and processed meat products, which leads to elevated cholesterol and triglycerides. Also, introducing more vegetables and fruit reduces lipids in the blood. Certainly, patients’ blood tests often show high levels of heavy metals like mercury, lead and cadmium. This can be chelated out with intravenous EDTA. Often 6 treatments at weekly intervals will rid the body of these toxins from pollution and the consumption of fish that has high mercury content.

Structural investigation of the bone with bone density measurements can diagnose osteoporosis. An initial remedy for this is supplementation with 5000 IU of vitamin D3 and vitamin K2 200 micrograms daily.

Low carb diet can help rebalance body metabolism

People who are overweight or obese get metabolic changes in their blood that physicians call metabolic syndrome. It raises blood pressure, often leads to elevation of cholesterol, triglycerides and blood sugars and also causes inflammation. A diet like the Mediterranean diet can help stabilize the metabolism. Dr. Anna Cabeca recommended a ketogenic diet, but from my reading a Mediterranean diet will achieve the same. In addition, a ketogenic diet carries a higher risk of heart attacks and strokes. For this reason I cannot recommend a ketogenic diet. The end result is an improvement of organ function, improvement of blood tests and less reliance on medications. Our body simply performs and functions better.

Fasting improves mitochondrial health

Mitochondria are small particles inside the plasma of all the body cells. Their functioning is essential for our energy and for cell metabolism in all of our organs. The energy, which is produced by the mitochondria is stored in a small molecule, called adenosine triphosphate or ATP.  I discussed earlier that heavy metals must be removed from the body by chelation therapy. One known effect of heavy metals is the poisoning of mitochondria. A person who has high blood levels of heavy metals in the body complaints of low energy and brain fog. After several intravenous chelation treatments, the energy returns and the brain fog disappears.

The fasting mimicking diet of Dr. Valter Longo is another tool to reactivate mitochondria.

Bioidentical hormone replacement

Many postmenopausal women require some help with regard to their hormonal balance. There are doctors who specialize in this area. They order a baseline panel of hormones. If there is a lack of progesterone, they order bioidentical hormone replacement, a hormone cream that the patient applies herself to the forearm or abdomen. Hormone saliva tests must show a ratio between progesterone and estrogen of 200 to 1 or higher. Many women have too much estrogen in their system relative to progesterone. By balancing this hormone ratio, the risk of getting cancer from estrogen that is not in balance experiences a significant reduction. The patient will also feel more energy and sleep better.

Help with Menopausal Symptoms

Help with Menopausal Symptoms

Conclusion

Menopause does not have to be the dreaded time in a woman’s life, when her periods stop. With a bit of attention to her nutrition, her hormone balance and other symptoms the physician can help her experience none of the symptoms. It will require some hormone and other blood tests. It may also require some detoxification with intravenous EDTA infusions. At the end that postmenopausal patient will feel energy again, clear up her foggy brain and sleep better. In addition, the woman will regain her sex drive and feel more energy. The physician treats estrogen dominance by adding progesterone cream supplementation. This also assist with regard to sleeping better.

It does take the effort to have all the necessary blood tests and saliva tests to establish deficiencies. A physician who has experience in anti-aging medicine will be of important help to bring a menopausal patient back on the road to wellness.

Dec
17
2022

Mast Cell Activation Syndrome

By | alcohol, Allergies, anaphylactic reaction, diet, immune system, Inflammation

Mast cell activation syndrome (MCAS) also goes by the name of systemic macrocytosis. That is to say it is a syndrome where mast cells are multiplying abundantly and secreting the inflammatory substances histamine, leukotrienes and cytokines. Certainly, people who suffer from MCAS can get severe anaphylactic reactions, but an epinephrine injection can often stop this.  Indeed, the physician must look for potential triggering factors like alcohol, spicy foods, exercise, insect stings, possible heavy metal accumulation or certain medications. In some cases heavy metal accumulation could also be a factor that triggers mast cells to release histamine.  In these cases a series of 20 chelation therapy sessions would be stabilizing.

Symptoms of mast cell activation syndrome

  • When there is skin involvement in patients with mast cell activation syndrome, they get flushing, itching and skin rashes.
  • With gastrointestinal involvement patients experience nausea and vomiting, bloating, abdominal pain, diarrhea and reflux (GERD).
  • Patients with neurological symptoms develop brain fog, headaches, cognitive problems, tremors and anxiety/depression.
  • When MCAS affects your endocrine glands, you may develop bone pain, bone lesions or weak bones.
  • Patients where the heart is affected may be fainting, their blood pressure may fluctuate between with high or low readings and they may experience heart palpitations.
  • When your respiratory system is affected, your lungs may be wheezing and you may develop nasal congestion.
  • More symptoms
  • The most dangerous symptom is anaphylaxis. This is a life-threatening allergic reaction where your air way entry could close off.
  • Any of these symptoms can get triggered by heat, cold or temperature changes. Stress, friction, insect bites or stings can also trigger a reaction. Additional factors can be environmental odors or perfumes, certain foods or medicine, alcohol and contrast dyes.

Diagnosis of mast cell activation syndrome

The most appropriate specialist to see is an allergist or immunologist. Other specialists could be a dermatologist, gastroenterologist, hematologist or endocrinologist. You will need blood tests like a serum tryptase level, which is a marker for mast cell burden. It is best to get a baseline tryptase level and also get a tryptase level after a mast cell reaction. In addition, you need a 24-hour urine collection for a number of mast cell activators. Depending on where your mast cell activation syndrome is located you need a skin or bone marrow biopsy.

More possible tests

The physician may decide to do an endoscopy or colonoscopy of the gastrointestinal tract. The pathologist can do several staining procedures with biopsy material to specifically look at mast cells. If there is a strong family history of mast cell activation syndrome the physician may decide to do genetic tests. In order to assess mast cell damage, your doctor may order a bone density test and bone scans including CT scans of the abdomen and chest.

Treatment of mast cell activation syndrome

The treatment of mast cell activation syndrome consists of a combination of multiple steps. First, if there is a life-threatening anaphylactic reaction, the patient applies an epinephrine injection. The physician taught the patient earlier how to do an epinephrine injection. This stops the sudden, rapid release of mediators from mast cells. After the epinephrine injection the patient needs transport to the nearest ER of a hospital for follow-up care. It is important that any patient with this syndrome should carry injectable epinephrine( an Epi-Pen) at all times.The purpose of treatment against mast cell activation syndrome is to block reactivity of mast cells or to stop the effects of mast cell mediators.

A number of medications are available to do this.

You can lower your risk of getting mast cell activation syndrome by watching your diet. Here is a list of the foods that will protect you:

Mast Cell Activation Syndrome

Mast Cell Activation Syndrome

Conclusion

Mast cell activation syndrome is a complex disease entity. Often there are several factors that contribute to this. Conventional medicine still cannot offer a treatment modality that will cure this condition, the only possibility is to control it. The physician must therefore use a combination of treatment modalities in order to help the patient with this condition. In cases of heavy metal accumulation several treatments with chelation therapy are beneficial. With an acute anaphylactic reaction, the

Mast Cell Activation Syndrome applies an epinephrine injection, which will stabilize the condition. But the patient should now follow this up with a series of blood tests in the emergency department of a hospital.

Treating mast cell hyperactivity

The purpose of treating mast cell activation syndrome is to block reactivity of mast cells or to stop the effects of mast cell mediators. H1 and H2 antihistamines help for gastrointestinal hyperactivity. Cromolyn sodium and ketotifen are mast cell stabilizers. Leukotriene inhibitors such as montelukast help to stabilize the mast cells to not secrete cytokines, which cause inflammation. Aggressive mast cell disease may require chemotherapy treatment, similar to what is needed to treat cancer.

The purpose of treatment is to help the patient control the mast cell hyperactivity. At this time medical science does not have all the answers. Unfortunately, at this point conventional medicine has no cure for this syndrome, but it can be managed with a lot of attention to the symptoms.

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Nov
19
2022

Lack of Sleep Harms the Immune System and Causes Inflammation

By | Cardiovascular disease, depression, Diabetes, Heart Disease, Inflammation, Insomnia, sleep, Sleep apnea

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.

Feb
13
2022

How healthy are Carbohydrates?

By | diet, fasting mimicking diet, heart attack, Inflammation, lifestyle, Nutrition, Processed food, Stroke

A recent review article asked: how healthy are carbohydrates? The three food components that occur in natural food are carbohydrates, fats and protein. Among the carbohydrates it is important to distinguish between simple carbohydrates (such as sugar) and complex carbohydrates. Simple carbohydrates are readily absorbed into the blood, which causes an insulin peak. After a few hours the peak is gone, and there is a “crash”. You will know the feeling of feeling hungry just a few hours after eating doughnuts! Complex carbs like peas, beans, fruit and vegetables take longer to get digested. The final breakdown product of the digestive process is sugar as well. But this process takes longer meaning that the concentration of sugar in the blood is much lower. There is also no “crash”. The result is that complex carbs cause less insulin secretion into the blood.

Long-term effect of eating too much sugar

Integrated over several decades of life, this means that a person who constantly consumes beverages with sugar and snacks containing sugar is at a higher risk of developing type 2 diabetes. In contrast, a person who eats well balanced meals where the insulin secretion is low, will not develop diabetes and have much less hardening of the arteries. This translates into a lower risk to develop heart attacks and strokes.

The types of carbohydrates

Before I discuss the health effects of various carbohydrates, we need to look at the types of carbohydrates.

Simple carbohydrates

Table sugar is a disaccharide, which consists of one molecule of glucose and one molecule of fructose.

The enzyme amylase very quickly breaks down the chemical bond between fructose and glucose and creates these monosaccharides in the small intestine from which they are rapidly absorbed. Milk sugar is a disaccharide, which consists of a molecule of glucose bound to a molecule of galactose. Milk contains 2 to 8% of milk sugar. We have to watch these simple carbs, because they trigger insulin production and lead to accelerated hardening of the arteries, heart attacks and strokes.

Complex carbohydrates

In contrast, complex carbs are healthy, because they take some time to be digested in the digestive tract. They consist of polysaccharides, long chains of sugar molecules. Both starches and dietary fiber consist of complex carbohydrates. They often are present in vegetables and many fruit. Complex carbs slow down the absorption of their breakdown products and minimize the insulin response. Dietary fiber is the indigestible part of fruit and vegetables. It contributes to good gut health as the beneficial gut bacteria can multiply on the fibre particles.

Healthy carbs

When simple carbohydrates dominate in our food intake, we are in trouble because they are loaded with calories. Overconsumption of them leads to weight gain and obesity, to diabetes, heart attacks, strokes and even cancer. On the other hand, consumption of complex carbohydrates is healthy. We get them from eating apples, bananas, berries, vegetables like spinach, tomatoes and carrots. Other healthy complex carbs are whole grain flour, quinoa and brown rice. Black beans, lentils, peas and garbanzo beans are also healthy complex carbs. Dairy products like low fat milk, yogurt and ricotta cheese are healthy as well.

Mediterranean diet as an example of a healthy, balanced diet

In 2019 a study was published where women with polycystic ovary syndrome (PCOS) were either put on a Mediterranean diet or not. This study showed that a Mediterranean diet was anti-inflammatory, reduced insulin resistance and reduced testosterone levels in PCOS patients.  But the same is true in a general population. The Mediterranean diet is one example of a healthy, balanced diet with complex carbohydrates. It prevents insulin resistance, inflammation and hormone disbalance. Other diets have similar effects like the DASH diet, the Zone diet and the Pritikin diet.

Quantity and quality of your food intake matters

A 2018 study from India showed that it matters how many carbohydrates we consume.  On average Indians eat a diet with 65-75 percent of calories coming from carbohydrates. Many of these carbs are the unhealthy simple carbohydrates. How healthy are  carbohydrates? The authors recommended to reduce complex carbohydrates to 50-55% and to add 20-25% protein, mostly from vegetable sources and add 20-30% from fat. The fat consumption needs to include monounsaturated fats (e.g., olive oil, nuts and seeds). Among the carbs a lot of green leafy vegetables help to balance the diet. This prevents the development of type 2 diabetes, heart attacks and strokes.

The above addresses the issue of quality of food. But it is also important what quantity of food we are eating. This is where counting or estimating calories comes in. If we overeat, we will very quickly gain weight and eventually can develop obesity.

The glycemic index and glycemic load

In order to help you with the choice of right carbohydrates the glycemic index was developed.

Here is another reference about the glycemic index/glycemic load.

In table 1 towards the end of the last link you find a column designated “GI” for glycemic index. All the foods that have a value less than 55 are foods that you can eat freely.

Problematical carbohydrate foods

Baked russet potatoes and boiled potatoes are very high on the GI index list. Puffed rice cakes, doughnuts, jelly beans and corn flakes measure high on the glycemic index list. But water melons, dried dates, white bread and white rice are also items to be avoided.

You best avoid anything with a glycemic index above 55. The column to the right of GI shows you a serving size and the last column on the right the glycemic load. The lower the glycemic load per serving, the better it is for your health. The glycemic index and the glycemic load are useful concepts of helping you to sort out your diet items.

My wife and I used this in 2001 to shed weight. We both lost 50 pounds (=22.72 kilograms) each in a period of 3 months.

Fasting mimicking diet (FMD)

According to Dr. Longo intermittent fasting stimulates the stem cells of the bone marrow. This leads to new clones of lymphocytes (B cells and T cells), which are part of the immune system. Your immune system becomes stronger from this.

Dr. Longo has done detailed mouse experiments, which inspired him to develop a new diet plan. Patients would receive a fasting mimicking diet (FMD) on 5 consecutive days per month. The rest of the month consists of a normal, balanced diet. 5 days of the month the person consumes a low 600-800-calorie diet. This reduced calorie intake is enough to ensure adherence to the diet, but low enough to lead to enormous positive metabolic changes including youth-preserving stem cell stimulation.

I am following the FMD

I have followed a FMD since December 2017. It helps me to keep my weight (BMI) in the 21 to 22 range. I feel more energetic and have managed to stay in good health.

The above chapter on the FMD was previously published here.

How healthy are Carbohydrates?

How healthy are Carbohydrates?

Conclusion

Healthy eating consists of 50-55% calories from complex carbohydrates; add to this 20-25% protein, mostly from vegetable sources and add 20-30% of total calories from fat. The fat consumption needs to include monounsaturated fats (e.g., olive oil, nuts and seeds). Unfortunately, most “convenience foods” (=processed foods) are incompatible with a healthy lifestyle. They contain too much simple carbs (sugar). Many people live on 65-75 percent of calories coming from simple carbohydrates, which are too many carbs. It should be complex carbs that digest slower and that do not induce insulin resistance. The glycemic index and glycemic load are useful concepts to help you chose the right foods that keep you healthy. The fasting mimicking diet can help you to take the last few pounds off that may be difficult to shed. Weight loss and weight maintenance are possible when you choose the right foods.

Apr
03
2021

Pollen Allergies Make Covid-19 Infection Rates Worse

By | Allergies, Asthma, immune system, Infectious Disease, Inflammation, Prevention

A recent study showed that pollen allergies make Covid-19 infection rates worse. This was published in the Proceedings of the National Academy of Sciences (PNAS) in March 2021.

The study determined that airborne pollen exposure enhances susceptibility to respiratory viral infections. Specifically, this includes SARS-CoV-2 infections as well. There were 130 test sites in 31 countries across 5 continents where measurements were made. Pollen concentration, air humidity and temperature, population density and lockdown effects on Covid-19 figures were measured. In countries with high pollen counts, high humidity and higher temperatures the Covid-19 rates were up to 44% higher than in countries with low pollen counts and colder climates.

PNAS study in more detail

In the following I am discussing the PNAS study in more detail. The SARS-CoV virus from the SARS epidemic in 2002 and the present SARS-CoV-2 virus are both capable to suppress the body’s interferon response to either virus. Additionally, there are intracellular proteins with the name “inflammasomes”, which the SARS-CoV-2 virus activates. With excessive activation this causes a cytokine storm, where inflammation spreads through the whole body. In the blood this leads to disseminated coagulopathy with multi organ failures. In the lungs severe acute respiratory syndrome occurs with severe viral pneumonia. On average mortality is 3.4%.

Tree and weed pollen can weaken the immune response

A study from South Korea examined what happens with exposure in asthmatic and allergic school-aged children to tree and weed pollen. https://www.sciencedirect.com/science/article/pii/S0091674919311856.

Allergic reactions make allergic children more prone to rhinovirus infections by reducing interferon in the blood. In addition, allergic reactions stimulate inflammasomes. When the SARS-CoV-2 virus affects an allergic child, both interferon depletion and excessive inflammasome activation make Covid-19 much more severe than in a child without allergies.

Warm spell in the Northern Hemisphere

On March 12, 2020 the WHO announced the Covid-19 pandemic when over 33% of the world’s countries were affected by the SARS-CoV-2 virus. However, at the same time there was a large-scale warm spell across the Northern Hemisphere with tree pollens being distributed across the same regions. This resulted in an exponential increase of Covid-19 cases. The researchers determined that the rates of Covid-19 infections were highest in areas where there was a high tree pollen count, crowding of people and high humidity/temperatures. The researchers used data from 248 airborne pollen monitoring sites in 31 countries. The highest exponential growth rates of Covid-19 occurred in the countries with the highest pollen counts. 6 out of 8 countries studied with regard to high pollen counts showed a significant correlation with regard to Covid-19 infections in excess to just person-to person virus transmission.

Population density and lockdown affecting daily SARS-CoV-2 virus rate

Some countries had a complete lockdown when rates of infection were high. This reduced transmission of the SARS-CoV-2 virus by 50%. Those countries with only a partial lockdown still experienced a significant reduction of infection rates. Rural areas had significantly less daily SARS-CoV-2 virus rates compared to very densely populated cities.

The researchers observed the following:

  • There was a lag effect of 4 days between the increase of pollen concentration in the air and infection increase with the SARS-CoV-2 virus
  • Pollens in the air caused infection rates of SARS-CoV-2 to rise by 10 to 30%, but in some high pollen areas even up to 44%.
  • Lockdowns reduced infection rates of SARS-CoV-2 by 50%
  • Higher environmental temperatures and higher humidity of the air also increased infection rates of SARS-CoV-2, although this may have occurred indirectly by increasing the pollen count in the air

Discussion

  1. The authors added a thorough discussion of the multiple factors regarding the increase of the infection rate of Covid-19 in 2020. They pointed out that climatic factors, air pollutants, or pollen, often exert their effects at the same time. They quantitated the contribution of the pollen count in the air easily. In contrast, pollution and climatic factors were not predictable in their effects.
  2. The infection rate of the SARS-CoV-2 virus always lagged behind the increase in pollen count by 4 days. The researchers observed this in all those countries where increasing pollen counts were a significant factor.
  3. The epithelial lining of the nasal cavity is the target of inhaled pollen. The researchers cited several publications regarding reduced interferon production as a result of exposure to pollens in the nasal mucous membranes. This leaves the immune system with a weakness, which the SARS-CoV-2 virus exploits. Recently specialists discussed the use of intravenous interferon to interrupt the cytokine storm caused by the SARS-CoV-2 virus.
Pollen Allergies Make Covid-19 Infection Rates Worse

Pollen Allergies Make Covid-19 Infection Rates Worse

Conclusion

In a recent publication researchers showed that pollen allergies make Covid-19 infection rates worse. The investigators had 130 test sites in 31 countries across 5 continents where they took measurements. They measured pollen concentration, air humidity, temperature, population density and lockdown effects on Covid-19 figures. In March of 2020 there was a warming trend in the Northern Hemisphere. This caused pollen counts to significantly rise in many countries. The result was that the mucous membranes in the nasal cavity weakened. This made it easier for the SARS-CoV-2 virus to multiply and invade. A lag period of 4 days occurred between the rise of the pollen count and the start of SARS-CoV-2 infection. The authors recommend that those who react to pollens in the air should wear pollen filtering masks in the spring season. This minimizes the danger of getting viral infections including SARS-CoV-2 infections following pollen exposure.

Jan
09
2021

Melatonin Is More Than a Sleeping Aid

By | Alzheimer’s disease, Anti-aging medicine, Autism, autoimmune disease, Cancer, Cardiovascular disease, Circadian rhythm, Dementia, Diabetes, Health, heart attack, Heart Disease, Hormones, immune system, Inflammation, Insomnia, melatonin, Menopause, mitochondria, Multiple sclerosis, neurological disease, Osteoporosis, Parkinson’s disease, sleep, Stroke

Notably, the January 2021 issue of the Life Extension magazine informs you that melatonin is more than a sleeping aid. It contains an interview between Dr. Roman Rozencwaig and a Life Extension (LE) magazine reporter. It must be remembered that Dr. Rozencwaig dedicated much of his career to the healing effects of melatonin. Another keypoint is that in 1987 Dr. Rozencwaig published a paper together with two other researchers. Specifically, it showed that melatonin production by the pineal gland declines in older age. Markedly, they stated that this is the reason why people age and why diseases of aging develop. Another key point is that Dr. Rozencwaig also stated that taking oral melatonin can promote a healthier life.

Melatonin deficiency causing aging and various illnesses

With the aging process the pineal gland calcifies and melatonin production is steadily declining. Surely, along with this is a deterioration of the circadian hormone rhythm. Meanwhile, the neuroendocrine system in the brain gets disorganized. Accordingly, this causes various diseases to occur. To emphasize, Dr. Rozencwaig says that a proper balance between melatonin and neurotransmitters is what we need to maintain health and longevity. As a result, a daily intake of melatonin supports healthy aging and longevity.

The many clinical effects of melatonin

Oral melatonin tablets help you to fall asleep easier, particularly the population that is older than 60 years.

But besides that, melatonin has many other clinical effects.

  • Melatonin improves immunity, which improves resistance against infections. It helps also in cancer prevention
  • Melatonin maintains the circadian hormone rhythm by synchronizing pituitary and hypothalamic hormone production
  • It protects the brain and may prevent Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, autism, and others
  • Melatonin modulates anti-inflammatory cytokinins in different diseases

Dr. Rozencwaig mentioned that melatonin slows down the aging process. There are multiple intertwining reasons for this. 

Melatonin’s actions against the aging process 

  • Melatonin regulates gene expression. This means that some signs and symptoms of aging can be reversed through genetic switches
  • Because melatonin regulates the immune response, the body is more protected against viral, bacterial and parasitic infections
  • Melatonin helps to overcome chronic inflammation that produces cytokines
  • Melatonin is also liver-protective through stimulation of an enzyme (AMPK). This enzyme regulates cellular metabolism.
  • There are other processes that melatonin is involved in: energy metabolism by protection and restoration of mitochondria.
  • Melatonin protects against osteoporosis by balancing and regulating bone formation versus bone loss.

More actions of melatonin

  • An important function of melatonin is the stimulation of antioxidant enzymes like glutathione peroxidase and superoxide dismutase (SOD)
  • Melatonin regulates sirtuins, which are proteins that maintain cellular health. They protect you from obesity, type 2 diabetes, cancer, heart attacks and strokes, dementia and more
  • As already mentioned, melatonin is a neuroprotective agent and may prevent Alzheimer’s and dementia
  • Melatonin stimulates apoptosis of cancer cells.
  • Oral health and melatonin are related. Melatonin suppresses herpes infections and periodontal disease. Melatonin prevents oral cancers to a certain degree. In addition, dental implants survive better when melatonin is present in saliva.

Prevention of cognitive decline

Dr. Rozencwaig mentioned that melatonin stops much of the cognitive decline of aging. To achieve this the following processes take place.

  1. Melatonin improves the sleeping pattern and increases the amount of REM sleep.
  2. During sleep melatonin removes toxic amyloid and tau proteins. We know that with Alzheimer’s disease these are the proteins that accumulate in the brain.
  3. Melatonin improves myelination of white matter in the brain. This prevents brain atrophy of old age.
  4. The brain is metabolically very active and produces toxic free radicals. But melatonin is a strong antioxidant dealing with free radicals. Melatonin can cross the blood brain barrier and stimulates enzyme production to eliminate toxic reactive oxygen species.
  5. Chronic inflammation also increases with age, but melatonin deals with this condition in the brain.
  6. Here are 3 subtypes of melatonin receptors. The body integrates the multitude of actions of melatonin with the help of these receptors.
Melatonin Is More Than a Sleeping Aid

Melatonin Is More Than a Sleeping Aid

Conclusion

Melatonin is a powerful antioxidant that has many other useful protective qualities as explained. The body integrates various functions like anti-aging, anti-free radical activity, neuroprotection in the brain and more. Melatonin even synchronizes pituitary and hypothalamic hormone production. This helps to integrate the effect of melatonin, which benefits the body in many ways. Melatonin prevents Parkinson’s and Alzheimer’s disease, multiple sclerosis, autism, obesity, type 2 diabetes, cancer, heart attacks, strokes and dementia. Melatonin production deteriorates from the age of about 60 onwards. It is important to supplement with melatonin at nighttime from that age on. Usually, you only need small amounts of melatonin, between 1mg and 3 mg at bedtime. This prevents most of the serious diseases of old age, stimulates your immune system and lets you age gracefully.

Dec
19
2020

The Use of Biologics for Treatment of Autoimmune Diseases

By | autoimmune disease, Inflammation

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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Nov
21
2020

Antibody Treatment for Rheumatoid Arthritis Was Superior

By | autoimmune disease, fasting mimicking diet, immune system, Inflammation, psoriasis

Researchers found that antibody treatment for rheumatoid arthritis was superior to conventional therapy. In particular, rheumatoid arthritis is an autoimmune disease where autoantibodies attack the synovial lining of joints. In this case, subsequently macrophages are activated, which attack joint surfaces. As an illustration, this process leads to crippling joint deformities.

The original study was published in June, 2019, but this is difficult to understand. The magazine Sciworthy published a review article on August 24, 2020 with more understandable language.

To emphasize, in mouse experiments the researchers found that only a small subfraction of activated macrophages caused symptoms of rheumatoid arthritis. They were folate receptor beta (FR-β) positive macrophages. It is important to realize that the researchers found them both in mice with rheumatoid arthritis and in man. The evidence in humans were the same findings in human tissue samples of people with autoimmune diseases.

Details of mouse experiments

Folate receptor beta (FR-β) positive macrophages are key in mouse model of RA

Explicitly, the researchers started experiments with a mouse model of rheumatoid arthritis, because it is easier to do than human research. They found that the key to developing rheumatoid arthritis was the presence of folate receptor beta (FR-β) positive macrophages. Chiefly, macrophages remove cell debris, bacteria or viruses from the blood. However, once they are activated and they carry FR-β receptors on their surface, they destroy joints. Certainly, in the mouse model monoclonal F3 antibodies were developed that kill activated macrophages. On the contrary, the human equivalent for the F3 antibodies is monoclonal antibodies with the name m909. They are directed at the FR-β receptors on the surface of activated macrophages. But first to the mouse experiments.

Inflammation from intraperitoneal injection of thioglycollate

In the first place, the researchers created an inflammatory condition by injecting thioglycollate into their peritoneal cavity. They could demonstrate that inflammation did occur. With this in mind they found macrophages in the peritoneal fluid. There were a lot of activated macrophages in it. Histological slides were analyzed with the help of F3 antibodies. In this case they visualized the activated macrophages. Subsequently the researchers treated mice with varying concentrations of monoclonal F3 antibodies. They found that the higher concentrations cured intraabdominal inflammation of the mice.

Researchers used monoclonal F3 antibodies to treat mouse model of RA

The researchers treated collagen-induced arthritis next in a number of experiments. Several concentrations of monoclonal F3 antibodies were given to these mice. Other experiments showed that monoclonal F3 antibodies specifically attacked only the activated macrophages and killed them. The killing of the activated macrophages in the mouse model of rheumatoid arthritis cured the arthritis. Fig. 5 shows this.

Mice treated with maximum concentrations of monoclonal F3 antibodies showed decrease in bone density

Next the researchers treated rheumatoid arthritis mice with maximum concentrations of monoclonal F3 antibodies to treat the arthritis. The swelling of their paws went down completely. CT scans of the bone in the paws showed decrease in bone density, while untreated controls showed significant loss of bone density. Monoclonal F3 antibodies were indeed a cure for RA in mice (Fig. 6).

Human experiments

Researchers confined human experiments to tissue samples from patients with various autoimmune diseases. Skin biopsies from patients with psoriasis, scleroderma, and sarcoidosis showed the distribution of FR-β-positive macrophages by special staining. This staining technique used human monoclonal antibodies (m909) against human FR-β receptors on activated macrophages. The publication depicts images that show abundant activity in all three autoimmune diseases (Fig. 1).

Researchers examined tissue samples from other autoimmune diseases with monoclonal antibodies (m909) against human FR-β receptors. The activated macrophages including rheumatoid arthritis, Crohn’s disease, ulcerative colitis and idiopathic pulmonary fibrosis lit up on fluorescence microscopy. In addition, nonspecific interstitial pneumonia, chronic obstructive pulmonary disease, systemic lupus erythematosus, psoriasis, and scleroderma tested positive as well.

Future therapy possibilities of rheumatoid arthritis with monoclonal antibodies

A series of experiments showed that two mechanisms can eliminate FR-β-positive macrophages: complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity. It means that there is a strong possibility that autoimmune diseases may be treatable with monoclonal antibodies. Fig. 2 summarizes these experiments.

Conventional therapy for rheumatoid arthritis

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfasalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients. Research described here proved that antibody treatment for rheumatoid arthritis was superior to conventional therapy in a mouse model.

Discussion

Monoclonal antibodies (m909) against human FR-β receptors targeting activated macrophages opened up a new therapy method against rheumatoid arthritis. The equivalent F3 antibodies in mice were a useful tool to expedite research in this field. The publication that I reviewed here was able to combine mouse experiments and work on human tissue samples essentially showing the same results . Monoclonal antibodies (m909) against human FR-β receptors work potentially like a broad-spectrum anti-inflammatory drug. The monoclonal antibodies reduce the accumulation of inflammatory immune cells, which treats the cause of rheumatoid arthritis. This will likely be the future cure of rheumatoid arthritis and other autoimmune diseases. We urgently need clinical trials to prove in humans that the findings from a mouse model and human tissue samples are correct.

Antibody Treatment for Rheumatoid Arthritis Was Superior

Antibody Treatment for Rheumatoid Arthritis Was Superior

Conclusion

Researchers recently showed in a mouse model that a small portion of activated macrophages cause rheumatoid arthritis (RA). But they also examined many biopsies from patients with autoimmune diseases. The findings in human tissue samples were identical to the findings in a mouse model. Activated macrophages are sensitised to attack the linings of joints as is the case with rheumatoid arthritis. These macrophages develop special receptors, called folate receptor beta (FR-β), and the macrophages release cytokinins. The cytokinins (TNFα, IL-1, IL-6, IL-12 and others) cause inflammation and make the RA worse. They also recruit more neutral macrophages and convert them into activated macrophages. The research group found that monoclonal antibodies against human or mouse FR-β receptors killed the activated macrophages. This alleviated the arthritic symptoms and after enough antibody treatments cured the RA. There were no negative effects on the rest of the immune system.

Physicians will cure human autoimmune diseases with monoclonal antibodies in the future

Researchers demonstrated this mostly in a mouse model. But the authors have manufactured human monoclonal antibodies against the FR-β receptors of activated macrophages. This has set the stage for curing human autoimmune diseases with monoclonal antibodies as well. At this point there is a need for clinical trials with various autoimmune diseases including rheumatoid arthritis with monoclonal antibodies against activated macrophages.

Nov
07
2020

Removal of Senescent Cells Can Extend Life

By | Inflammation, Mortality, telomeres

Several animal and human studies by the Mayo Clinic showed that removal of senescent cells can extend life. Researchers Xu et al. showed in 2018 that senescent cells weaken the body. Senescent cells are damaged cells that are still living. They can cause the release of inflammatory cytokines. The researchers showed in mouse experiments that intermittent senolytics increased life expectancy by 36%. Senolytics are drugs that dissolve senescent cells; the senolytic cocktail consisted of dasatinib plus quercetin.

In these mouse experiments their risk of dying was reduced by 65% compared to control mice that did not take senolytics.

Senescent cells causing premature aging

In the past 5 years research on aging and on chronic diseases made a lot of progress. Researchers realized that the accumulation of senescent cells is what causes both. All this happens because the process of apoptosis, the removal of dead cells, is impaired in the aging person. It appears that in older age there is a problem with dying cells and their removal. Instead they linger on and start producing cytokines, which cause inflammation. This can damage other cells and lead to organ failures. All this explains why older people often get chronic diseases and do not reach their normal lifespan. The accumulation of senescent cells also blocks regenerative factors that improve one’s health.

Senolytics

Dasatinib is a kinase inhibitor that was developed to treat acute myelogenous leukemia in adults and children. Researchers did animal experiments with a combination of dasatinib and quercetin for several years. They also have started smaller pilot clinical trials in humans. It appears that the human findings are very similar to the animal findings. But more research is needed to answer questions about side-effects and effects of removal of senescent cells.

Details about animal experiments with senolytics

The Mayo Clinic research showed that old mice treated with senolytics (dasatinib and quercetin) live 36% longer than controls that did not receive senolytics. Another part of this series of experiments showed that senescent cells are indeed what kills prematurely. They took senescent cells from old mice and transplanted them into young mice. Soon the young animals showed deterioration health wise and they died prematurely. Another control group were older mice that received senescent cells from old mice. They too died prematurely. Treatment with senolytics (dasatinib and quercetin) improved physical functioning and also survival.

Details about human trials regarding senolytics

For three days 11 participants received senolytics (dasatinib and quercetin). The effect of the drugs was evident for 11 days. The subjects took 100 mg of dasatinib daily and 500 mg of quercetin twice per day for 3 consecutive days. This dose was repeated twice more on a weekly basis for a total of 3 weeks. These patients had idiopathic pulmonary fibrosis. This is an incurable disease where senescent cells accumulate. These patients showed significantly improved gait speed, walking endurance, chair rise test performance and scores of other physical performances. All this occurred on day 5 after the initial dose of senolytics.

Alternative senolytics, so removal of senescent cells can extend life

Dasatinib as a senolytic has significant side effects.

For this reason, researchers looked for alternatives. Theaflavins, isolated from black tea fits this bill. It is non-toxic, but it is also effective as a senolytic. Researchers from Life Extension have developed a senolytic product containing theaflavins and quercetin. Instead of regular quercetin they included quercetin phytosome, which has 50-times more potent bioavailability. One capsule contains 74 mg of quercetin phytosome (the equivalent of 1250 mg of regular quercetin) and 275 mg of theaflavins.

Discussion

Future research needs to show whether or not the Life Extension senolytic indeed does what it promises. It claims that only one capsule per week stimulates apoptosis, reduces cytokines and increases longevity. I would like to see a clinical study that examines all these parameters. One measure of longevity is to determine the length of leukocyte telomeres. All the other laboratory tests are readily available. Research in this field will certainly continue and scientists will likely develop other senolytics.

Removal of Senescent Cells Can Extend Life

Removal of Senescent Cells Can Extend Life

Conclusion

The accumulation of senescent cells causes both aging and chronic diseases. Research showed that in older age the process of apoptosis, the removal of dying cells, is incomplete. As a result dying cells accumulate. They produce inflammatory cytokines, can damage other healthy cells and lead to chronic organ failure. In addition, cancer cells can develop and the patients can die prematurely. Senolytics are substances that clear out senescent cells. In mouse experiments they have already led to improved survival and health. Clinicians performed a clinical trial on patients with idiopathic pulmonary fibrosis, which is an incurable disease where senescent cells accumulate. They showed significantly improved gait speed, walking endurance, chair rise test performance and scores of other physical performances. One pill once per week with dasatinib and quercetin can achieve this. More research in this area can clarify why senolytics work and what the side effects are.