Medical Articles by Dr. Ray

Jan

2021

Melatonin Is More Than a Sleeping Aid

By Ray Schilling | 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.

Melatonin improves the sleeping pattern and increases the amount of REM sleep.
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.
Melatonin improves myelination of white matter in the brain. This prevents brain atrophy of old age.
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.
Chronic inflammation also increases with age, but melatonin deals with this condition in the brain.
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

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

2020

Hormones Play an Important Role in Survival from Covid-19

By Ray Schilling | andropause, Hormones, immune system, Infectious Disease, Menopause

I am describing here that hormones play an important role in survival from Covid-19. There are two publications that illustrate that point.

Estrogens protect women against Covid-19

A study from Dec. 4, 2020 covering 17 countries and involving nearly 70,000 women discovered these principal findings.

Women aged 20 to 50 have moderately higher Covid-19 infection rates than men
In all of the age groups men have higher mortality rates than women
Beyond the age of 50 the fatality rate from Covid-19 is 50% higher in men than that of women
Postmenopausal women above the age of 50 and on estradiol supplementation had 50% less mortality from Covid-19 than women without estradiol supplementation

The researchers said about the study: “In a nutshell, it’s likely that the apparently protective effects of 17β-estradiol, a naturally occurring, abundant female hormone, relate to a key property of this molecule: it attenuates the so-called “cytokine storm” that’s thought to underlie much of the cellular-scale and organ/tissue-level damage wrought by a SARS-CoV-2 infection, via dysregulation of a patient’s immune response.”

Men need enough testosterone to fight Covid-19

Another study from September 17, 2020 pointed out that males have much worse outcomes with Covid-19 than females. Men are affected by Covid-19 twice as often as females and they experience a much more severe course with a higher mortality. The authors also point out that there is a direct correlation between lower serum testosterone levels in men and inflammation severity by cytokines and poor clinical outcomes. The decline in total and free testosterone in aging men leads to serious pulmonary complications and the need to treat the patient in the ICU. The Covid-19 coronavirus utilizes Angiotensin-Converting Enzyme II (ACE2) for entry into the host cell. A male requires testosterone for ACE2 expression. Lower testosterone causes higher mortality in men. In contrast, if testosterone in a male is too high, blood clots can form in the circulatory system, which often lead to complications and deaths in patients with Covid-19.

Vitamin D levels and course of Covid-19

There are three major effects that vitamin D has.

A strengthening of the epithelial barrier not allowing the coronavirus to penetrate into the lung tissue as easily.
Release of defensins and cathelicidin, two crucial antiviral polypeptides, that eradicate the SARS-CoV-2 virus in the system.
Interruption of the “cytokine storm”, an overwhelming inflammation which is responsible for viral pneumonia to develop. Without the cytokine storm there is no damage to the lungs, and people do not need treatment in the ICU. This is particularly important for people above the age of 60 and for people with pre-existing diseases.

Similarly, with the stabilizing effect of vitamin D regarding the immune function more severe forms of Covid-19 can turn into less severe forms with a better outcome.

Discussion

Research showed that in women estrogen has a modifying effect on the course of Covid-19. In males it is testosterone that leads to an improved course of Covid-19. Both sexes require adequate doses of vitamin D, which helps to strengthen the epithelial barrier. In addition, enough vitamin D releases defensins and cathelicidin, two crucial antiviral polypeptides that eradicate any virus in the system. Vitamin D also interrupts the “cytokine storm”, an overwhelming inflammation, which is responsible for viral pneumonia to develop. All of these factors together modify the course of Covid-19 and improve the probability of survival from this otherwise serious viral illness.

Hormones Play an Important Role in Survival from Covid-19

Conclusion

Two lines of research showed that both women and men do better with Covid-19 when their hormone levels are either adequate or are substituted to normal levels. Women in menopause taking estradiol for postmenopausal symptoms had 50% less mortality from Covid-19. Men who were testosterone deficient and were put on testosterone supplementation do better with respect to Covid-19. In aging men total and free testosterone decline and serious pulmonary complications occur with a need to treat the patient in the ICU. On top of hormones both men and women benefit from high doses of vitamin D, which strengthens the epithelial barrier. Vitamin D also releases defensins and cathelicidin, two crucial antiviral polypeptides that fights the SARS-CoV-2 virus directly. In addition, vitamin D interrupts the “cytokine storm”, an overwhelming inflammation which causes the viral pneumonia. Taken together the hormones and vitamin D can improve the outcome of Covid-19 significantly.

This text includes part of this blog.

Dec

2020

The Use of Biologics for Treatment of Autoimmune Diseases

By Ray Schilling | 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

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.

Dec

2020

Mother’s Lifestyle Predicts Heart Attack Risk for Offsprings

By Ray Schilling | Cardiovascular disease, cholesterol, Diabetes, exercise, food, heart attack, High Blood Pressure, lifestyle, Nutrition, Smoking, Stroke

A European Society of Cardiology study found that mother’s lifestyle predicts heart attack risk for offsprings. This study was published in the Journal of Preventive Cardiology, a journal of the European Society of Cardiology. It was also summarized in Science Daily. The study author Dr. James Muchira of Vanderbilt University, Nashville said: “This maternal influence persists into the adulthood of their offspring.” What he meant is that the study found that lifestyles of mothers influence the choices of lifestyles of the offsprings, and with poor choices even determine when the next generation gets their heart attack or stroke.

In previous research the team established that both genetic factors as well as environmental and lifestyle factors are responsible for cardiovascular disease. Now the researchers wanted to determine the influence of each parent on the risk of cardiovascular disease of the offspring.

Set-up of the study

The study was done with offspring and the parents of the Framingham Heart Study. 1989 children from 1989 mothers and 1989 fathers were enrolled 1971 and followed for 46 years. The average age of the offspring at enrolment was 32 years. The study ended 2017. Dr. Muchira said: ”Crucially, the study followed children into most of their adult life when heart attacks and strokes actually occur.”

Risk factors for cardiovascular disease

The researchers rated the risks of fathers and mothers in the study according to 7 factors.

Smoking status (non-smoker preferred)
Diet (healthy or not)
Physical activity
Body mass index (normal or not)
If blood pressure is too high
Level of blood cholesterol
Blood sugar values

The researchers established three categories of cardiovascular health: poor (fulfilment of 0 to 2 factors); intermediate (fulfilment of 3 to 4 factors) and ideal (fulfilment of 5 to 7 factors). The researchers wanted to know how long the offspring were able to live without symptoms of cardiovascular disease.

Findings of the study

Here are the findings of the study.

Children of mothers with ideal cardiovascular health lived free of cardiovascular symptoms for 27 years; they were on average 32+27= 59 years when symptoms started.
Children of mothers with poor cardiovascular health lived free of cardiovascular symptoms for 18 years; they were 32+18= 50 years old when symptoms started; this is 9 years earlier than children from mothers with ideal cardiovascular health.
Father’s cardiovascular health did not influence the children’s onset of cardiovascular symptoms.

Cardiovascular risks of the children are due to a combination of things

A combination of the health status during the pregnancy and the environment in early life influenced the children.

Dr. Muchira said: “If mothers have diabetes or hypertension during pregnancy, those risk factors get imprinted in their children at a very early age. In addition, women are often the primary caregivers and the main role model for behaviors.” Sons were much more affected by their mother’s cardiovascular health status. Dr. Muchira explained: “This was because sons had more unfavourable lifestyle habits than daughters, making the situation even worse. It shows that individuals can take charge of their own health. People who inherit a high risk from their mother can reduce that risk by exercising and eating well. If they don’t, the risk will be multiplied.”

Discussion

We remember that the Framingham Heart Study long time ago established the above-mentioned risk factors for heart disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159698/ It is also important for the offspring to quit smoking as this is a high-risk factor for heart disease. Next eat a balanced diet, like the Mediterranean diet. With this you eat more vegetables, less meat, more fish and add olive oil. Engage in regular exercise, which will raise the protective HDL cholesterol. Keep your body mass index low (in the 21.0 to 22.0 range, but definitely below 25.0). Keep your blood pressure in the normal range (120/80 or less). Make sure that your blood cholesterol and blood sugar values are normal. This will give you the lowest risk to develop a heart attack or a stroke.

Mother’s Lifestyle Predicts Heart Attack Risk for Offsprings

Conclusion

We are normally concerned about our own cardiovascular health. But in a new study researchers examined children of participants in the Framingham Heart Study and their parents. This showed that the cardiovascular health status of the mother had a significant influence on the children’s cardiovascular health. The offspring had an average age of 32 years when the researchers started to follow them for 46 years. When the mother was in poor cardiovascular health, the offspring developed cardiovascular symptoms at age 50. But when the mother’s cardiovascular health was ideal, the children got symptoms of cardiovascular disease only at age 59. This delay of 9 years of disease onset was purely due to the mother’s cardiovascular health status.

Risk management of cardiovascular risks

The authors of the study say that the children can do a lot to minimize the cardiovascular risk. They need to work to reduce the known risk factors and also start a regular exercise program. The authors of the study mentioned that even people who inherited a risk for cardiovascular disease benefit significantly from cutting out risk factors for cardiovascular disease.

Nov

2020

Mental Illness and Covid-19

By Ray Schilling | alcohol, Anxiety, depression, Drugs, exercise, food, schizophrenia, Sleeep, stress, Stress management

A topic less discussed is mental illness and Covid-19. Covid-19 has been noticeably around us since March of 2020. With the various social distancing and quarantining methods people become more or less isolated emotionally. Social gatherings are outlawed depending on where you live. This helps to interrupt the spread of the virus, but it makes people feel more stressed as their relationships get interrupted.

Symptoms of stress

The CDC sums up that stress during a pandemic can cause the following:

Fear of your own health and the health of your loved ones
Loss of your job or financial support
Changes in eating habits
Changes in sleep pattern with lack in concentration
Increase in use of tobacco, alcohol or other substance consumption
Chronic health problems may deteriorate
Worsening of Mental health conditions

The more isolated we are, the more stress we feel. This undermines our stress coping mechanisms, makes us more anxious and more depressed.

Develop coping skills

Taking care of your family and friends may relieve your stress, but it needs to be balanced by taking care of yourself. Although you are physically isolated from others when you are in quarantine, you can stay in contact with others by phone or video chats. This makes you less lonely and isolated.

Take care of yourself. This includes eating well balanced meals, exercising regularly and getting enough sleep. Avoid the consumption of alcohol, tobacco and drugs. Share with a family member or friend how you feel. Maintain friendships through the phone, emails, social media and computer chats. This builds a strong support system for you.

Avoid too much exposure to news stories. Seeing negative stories about Covid-19 over and over again can be undermining, so take a break from the news media. Go for a walk. Take a nap.

Suicide

Sometimes depression can get out of control to the point of driving a person to the brink of suicide. In the US major depression is the leading cause of disability for ages 15-44. At any given year 16.1 million American adults (about 6.7% of the U.S. population age 18 and older) suffer from major depression. 10.3% of Americans have thought about suicide. If you feel that way, do not act on this impulse. Call 1-800-799-4889. That is the National Suicide Prevention Lifeline & Chat.

Medical literature about the psychological impact of Covid-19

In a July 2020 publication the authors pointed out that Covid-19 infection is a significant psychological stressor. There is the fear of getting the virus and uncertainty about the future. Pre-existing anxiety and depression disorders get accelerated from the stress. In addition, mental disorders like schizophrenia with psychosis may worsen. This may require more antipsychotic medication to control it.

A Kaiser Family Foundation poll found in March 2020 that the Covid-19 pandemic has caused a major impact on US citizens. 45% of respondents said that the pandemic has affected their mental wellbeing significantly. If you are scared, depressed or anxious, you are tense and you have problems falling asleep, you are not alone. You can seek and receive help!

Prevention of mental disease from Covid-19

Here is some practical advice from the World Health Organization.

Stay informed.
Have a daily routine. Get up and go to sleep at regular times. Eat healthy balanced meals. Exercise regularly. Have your work routine and also find time to rest. Do things that you enjoy.
Watch the news only to be informed, but limit news watching to a minimum. This will keep anxiety and depression in check.
Stay in contact with close friends by phone and computer technology.
Keep your alcohol consumption low. If you did not drink before at all, don’t start drinking in an attempt to deal with boredom, fear, anxiety or social isolation.
Take breaks from screen time. This reduces tension.
Video games: doing this may relax you for a short time. But longer video game activities can make you tense; you should balance this with the rest of your daily activities.
Social media. Use this for honest communication. Keep it brief. If you see misinformation, point out the truth.
Helping others: if you can, help others in the community with shopping or other chores.

Treatment for Mental disease from Covid-19

When you notice anxiety, depression or a flare-up of psychotic symptoms from schizophrenia, it is important to see your health professional right away. You may need some counselling. Others may need an antidepressant (for depression) or an adjustment to your antipsychotic medication. Some patients with milder depression or anxiety may benefit from cognitive/behavioral therapy. Most importantly, know that help is available! More info about cognitive therapy for suicide prevention.

Mental Illness and Covid-19

Conclusion

Mental illness and Covid-19 is a huge topic. People definitely have experienced more anxiety and depression since the Covid-19 epidemic. This is because our lifestyle is suddenly restricted. We may have to go through a 14-day quarantine. But we also cannot participate in large gatherings with more than 50 people. Often, we have to wear masks in stores. In areas with high cases of Covid-19 there is also a severe restriction regarding with whom you can visit, leading to feelings of isolation. All of this can lead to mental illness. Essentially there are two ways of coping with this. First, we need to get a routine that makes us more resistant to mental illness. Secondly, if this fails, seek the advice of a health professional right away.

Seek mental illness treatment right away

When you catch mental illness early, it is much easier to treat. Milder cases of depression or anxiety may benefit from cognitive/behavioral therapy. More severe cases often require medication. In this outline I have discussed mental illness during the Covid-19 epidemic. I have not discussed the cases where people came down with Covid-19 coronavirus and got affected in their brain function from the virus. These cases need treatment by a neurologist and psychiatrist, and they are much more complicated.

Nov

2020

Antibody Treatment for Rheumatoid Arthritis Was Superior

By Ray Schilling | 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

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

2020

Why We See More Food Allergies

By Ray Schilling | Allergies

A recent review in a BBC article explained why we see more food allergies. It is important to note that one of the more important food allergies are peanut allergies. Certainly, they have risen from 1 in 250 children in 1997 to 1 in 70 children in 2008.

By all means, allergies come in various degrees of severity; an anaphylactic reaction is the most severe form. Notably, in England there was a rise of hospital admissions for anaphylaxis from 1,015 in 2013 to 1746 in 2019. This is a 72% increase in 6 years!

Theories why there may be more food allergies now

There are a number of theories why food allergies have been on the rise. There is a consensus now that the right composition of the gut bacteria is important for normal immune reactions to take place.

Hygiene theory

David Strachan proposed the hygiene theory of allergies in 1989. Briefly, his observation was that children of larger families were less likely to develop allergies. He interpreted this to mean that infections among siblings stabilized the immune system. In the meantime, it has become obvious that the gut plays an important role for the immune system.

Graham Rook’s “old friends” theory

Graham Rook’s “old friends” theory came out in 2003. This theory states that friendly microbes in the environment are mixing with the gut flora. This trains the immune system to balance.

Gut bacteria theory

There is good evidence that the more a child is given antibiotics as a child, the more likely it is that the person develops a food allergy later. The mechanism seems to go via the gut flora. In a way this is the other coin of Graham Rook’s “old friends” theory. If you kill the “good friends” bacteria in the gut by antibiotics, the immune system strikes back with allergic reactions.

Dual-allergen exposure

By exposing the child at 4 to 11 months to peanuts or peanut butter, the immune system develops tolerance to the peanut protein (LEAP=learning early about peanut). A study showed that by doing this 80% of 5-year and older children and adults do not have a peanut allergy.

Prenatal vitamin D and food allergies

A German study found that prenatal exposure to higher amounts of vitamin D resulted in a higher risk of developing food allergies before the age of two.

Use antibiotics only when necessary

Gut biome studies showed that the use of antibiotics can have long lasting effects on the composition of the gut flora. A patient in sepsis may require antibiotics. But when the patient has recovered it is important that the bowel flora is restored with probiotics. This balances the immune system and avoids allergic reactions.

Immunotherapy for food allergies

Allergists have long used desensitisation techniques to deal with inhalant allergies. Allergy shots every two or three weeks can be very helpful to suppress immune reactions to inhalants. The same technique works also for many food allergies. The allergist tests the patient’s skin on the forearm to see what positive reactions occur. Based on these findings an allergy serum is composed. A small amount is injected in intervals. The smallest amount is given first and the concentration is gradually increased until the maintenance dose is reached. This causes the immune system to produce competing antibodies that reduce the antibody-mediated reaction to the food allergies.

Why We See More Food Allergies

Conclusion

Food allergies are increasing in frequency and severity. There are several theories why food allergies develop. The most likely one is that friendly bacteria in the environment become part of the gut environment in the newborn. If we have the right composition of gut bacteria our immune system reacts normally. Administering antibiotics frequently and overcleaning our kitchens with too many cleaning agents affects our bowel flora negatively. This disbalance can cause allergic reactions. On the other hand, exposing a newborn between the age of 4 and 11 months to a variety of adult foods including peanut products will desensitize the child to peanut protein and prevent future allergies. Those who are severely affected by food allergies can see an allergist for allergy testing and consider desensitisation through allergy injections.

Nov

2020

Removal of Senescent Cells Can Extend Life

By Ray Schilling | 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

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.

Oct

2020

Blood Type Has Some Bearing on the Severity of Covid-19 Coronavirus

By Ray Schilling | immune system, Infectious Disease, Inflammation

Two independent research publications concluded that blood type has some bearing on the severity of Covid-19 coronavirus infections. One was published in Denmark, the other one in Canada.

In the US the 4 common blood types occur with this frequency: group O: 45% (O positive 38%, O negative 7%); group A: 40% (A positive 34%, A negative 6%); group B: 11% (B positive 9%, B negative 2%) and group: AB 4% (AB positive 3%, AB negative 1%). Positive and negative stands for the Rh group (the rhesus factor, which is another type of blood group).

Two separate publications

Denmark study

Briefly, the Denmark study showed that when positive and negative tests for the SARS-CoV-2 virus were checked in relationship to blood groups, blood group O had 13% less coronavirus infections, group A had 9% more infections, group B had 6% more infections and group AB had 15% more infections than negative controls. This means that blood group O is relatively protected from the SARS-CoV-2 virus. The investigators were fast to add that this does not give people with a group O blood type a licence to go to the pub and celebrate.

Canadian study

The Canadian study looked at 125 critically ill people with positive SARS-CoV-2 virus tests. Of these 95 had ABO blood types available. All these patients were admitted to the ICU. Here are the significant findings: 32% of blood group A required intubation versus 84% of AB patients, 35% of O group patients and 61% of B patients required intubation. 12% of A patients and 32% of AB patients, but only 5% of blood group O patients and 9% of B patients required kidney support (continuous renal replacement therapy). In addition, group O and group B patients required a median ICU stay of only 9 days. In contrast, group A and AB had to stay in the ICU for 13.5 days.

Gene study to determine susceptibility for severe Covid-19 disease

In a European genetic study from Italy and Spain 835 patients and 1255 control participants had genetic studies done. It turned out that the genetic loci that determined the severity of Covid-19 followed the blood groups. Blood group A patients had a 45% higher risk of developing severe Covid-19 disease, while group O patients had a 35% lesser risk compared to other blood groups of developing severe Covid-19.

Discussion

Dr. Mypinder Sekhon, an intensive care physician at Vancouver General Hospital stated that people with a blood group O make less of a key clotting factor, which makes them less prone to clotting problems in the blood. Clotting is a major driver in complications of Covid-19. Other possible explanations are the blood group antigens and how they interact with antibodies from the infection with Covid-19 coronavirus. Finally, it could be related to the genes of the blood groups and how they interact with receptors of the immune system. It is interesting to also note that there are genetically different risks that go along the line of the blood groups with group A having much higher risk than group O to develop severe Covid-19 disease.

Blood Type Has Some Bearing on the Severity of Covid-19 Coronavirus

Conclusion

Both research in Denmark and in Canada confirmed that blood group O had less coronavirus infections. In the Denmark study there were 13% less severe Covid-19 cases in people with the blood group O than in negative controls. In the Canadian study of 95 patients with severe Covid-19 physicians had to admit them into the ICU. They noted that 84% of blood group AB patients in the ICU required intubation. In contrast, only 35% of O group patients required intubation. With regard to kidney support, 32% of AB patients, but only 5% of O patients required this during their ICU stay.

More research required to understand these findings

The researchers added that it is not clear why there are such differences among patients with different blood groups. They mentioned that more research is necessary. This will reveal why group O has a milder course. It will also show why group O patients require less intubation and shorter ICU stays. Separate genetic studies showed that severe Covid-19 disease develops with blood group A patients (45% higher risk). In contrast group O blood group patients have milder Covid-19 disease (35% less risk). It is with these investigations that we can now understand some of the peculiarities regarding the Covid-19 disease. It explains why some people develop severe Covid-19 disease while others develop only mild symptoms.

Oct

2020

Irregular Periods are Linked to Premature Deaths

By Ray Schilling | Hormones, irregular periods, Menopause, prostate cancer

A review in CNN describes that irregular periods are linked to premature deaths. This review is based on the original publication in the British Medical Journal published on September 30, 2020.

Essentially, the researchers followed 79,505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes for 24 years. The researchers recorded 1975 premature deaths. The definition for a premature death was someone dying before the age of 70. There were three age groups that the researchers followed separately for 24 years.

ages 14-17 years
18-22 years
29-46 years

The most common causes of death were 894 from cancer and deaths from 172 strokes and heart attacks.

Death rates after 24 years for the three subclasses just mentioned

The researchers noted that there were differences in survival for different age groups. But there were also differences in survival for irregular periods versus prolonged intervals between periods. Crude mortality rates for 1000 person years of follow-up for women with normal versus irregular periods were as follows.

Normal periods Irregular periods

14-17 age : 1.05 14-17 age: 1.0

18-22 age: 1.23 18-22 age: 1.37

29-46 age: 1.0 29-46 age: 1.68

Women with a cycle length of 40 days or more had a higher mortality rate. The researchers compared this to women with a normal cycle length (26-31 days). Here are the data in detail for two age groups at the outset of the study.

Women with a cycle length of 40 days or more

Age 18-22: 1.34

Age 29-46: 1.40

Heart attacks and strokes followed these death statistics closest.

Discussion

The researchers concluded that teenagers and women in their middle-age were at the highest risk. This risk was for premature mortality, if they had irregular periods or a cycle length of 40 days or more. There was also an association between irregular periods and a prolonged cycle length and type 2 diabetes, ovarian cancer and coronary heart disease. In addition, mental health problems were also related, the study said.

Dr. Adam Balen, a professor of reproductive Medicine at Leeds Teaching Hospitals in the UK said: “Young women with irregular periods need a thorough assessment not only of their hormones and metabolism, but also of their lifestyle so that they can be advised about steps that they can take which might enhance their overall health”.

Too much estradiol in women and men can cause cancer

In this context it is interesting that other studies have shown that unopposed estradiol may be the culprit for both irregular periods and larger intervals between periods. When estrogen is elevated in females, irregular periods can result. Unopposed estradiol can cause breast, uterine and ovarian cancer.

In males who also have a small amount of estrogen in their blood, it is important that a larger amount of testosterone balances the two hormones. Otherwise there is a risk of prostate cancer.

In addition, cardiovascular disease has been described as a side effect of standard hormone replacement therapy (HRT) in women with synthetic hormones.

The good news is that treatment with bioidentical hormones can treat these abnormal periods. This eliminates premature mortality and in many cases prolongs life.

Conclusion

Researchers followed 79,505 premenopausal women without a history of cardiovascular disease, cancer, or diabetes for 24 years. They found that there is a linkage between irregular periods and premature deaths. There were three age groups that the researchers followed. Some of them suffered from irregular periods and others had periods that were 40 days or longer apart. The researchers recorded the premature mortalities. At an age of 29-46 there was a 68% higher mortality in women with irregular periods. The scientists compared this to women who had regular periods. In addition, women aged 29-46 with a cycle length of 40 days or more had a 40% higher mortality.

Estrogen dominance could explain premature deaths

The researchers compared this to women with a normal cycle length. It is possible that women who died prematurely were having too much estrogen in their system, which can produce cardiovascular disease and cancer of the breast, uterus and ovary. Further studies need to clarify the mechanism behind irregular periods and why a cycle length of 40 days or more causes mortality.

Melatonin deficiency causing aging and various illnesses

The many clinical effects of melatonin

Melatonin’s actions against the aging process

More actions of melatonin

Prevention of cognitive decline

Conclusion

Estrogens protect women against Covid-19

Men need enough testosterone to fight Covid-19

Vitamin D levels and course of Covid-19

Discussion

Conclusion

Dupilumab (Dupixent)

Omalizumab (Xolair)

Rheumatoid arthritis

Crohn’s disease

Anti-Tumor Necrosis Factor Agents

Integrin Receptor Antagonists

Interleukin-12 and -23 Antagonist

Conclusion

Set-up of the study

Risk factors for cardiovascular disease

Findings of the study

Cardiovascular risks of the children are due to a combination of things

Discussion

Conclusion

Risk management of cardiovascular risks

Symptoms of stress

Develop coping skills

Suicide

Medical literature about the psychological impact of Covid-19

Prevention of mental disease from Covid-19

Treatment for Mental disease from Covid-19

Conclusion

Seek mental illness treatment right away

Details of mouse experiments

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

Inflammation from intraperitoneal injection of thioglycollate

Researchers used monoclonal F3 antibodies to treat mouse model of RA

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

Human experiments

Future therapy possibilities of rheumatoid arthritis with monoclonal antibodies

Conventional therapy for rheumatoid arthritis

Discussion

Conclusion

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

Theories why there may be more food allergies now

Hygiene theory

Graham Rook’s “old friends” theory

Gut bacteria theory

Dual-allergen exposure

Prenatal vitamin D and food allergies

Use antibiotics only when necessary

Immunotherapy for food allergies

Conclusion

Senescent cells causing premature aging

Senolytics

Details about animal experiments with senolytics

Details about human trials regarding senolytics

Alternative senolytics, so removal of senescent cells can extend life

Discussion

Conclusion

Two separate publications

Denmark study

Canadian study

Gene study to determine susceptibility for severe Covid-19 disease

Discussion

Conclusion

More research required to understand these findings

Death rates after 24 years for the three subclasses just mentioned

Normal periods Irregular periods

Women with a cycle length of 40 days or more

Discussion

Too much estradiol in women and men can cause cancer

Conclusion

Estrogen dominance could explain premature deaths

A Survivor’s Guide to Successful Aging

Prostate Cancer Unmasked

Healing Gone Wrong – Healing Done Right

Medical Question Answered

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