Apr
03
2021

Pollen Allergies Make Covid-19 Infection Rates Worse

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
23
2021

Review about Human Oncolytic Virus Research in 2020

The British Medical Journal published a review about human oncolytic virus research in 2020. That is to say, the BMJ published this report in July 2020. On the negative side, the report is rather complex with many technical terms. With this in mind, I will keep it as simple as possible for this summary. Notably, oncolytic viruses are a new way of treating cancer. Adenovirus was the most common oncolytic virus in use by cancer research in the past 20 years. It must be remembered, researchers applied this to mainly melanoma and gastrointestinal cancers. In the past I discussed the use of oncolytic viruses in a related post.

History of licencing of oncolytic viruses

  1. The first oncolytic virus was licenced in 2004 in Latvia. This was an RNA virus derived from the native ECHO-7 strain of a picornavirus, called Rigvir. This oncolytic virus was approved for treating melanomas.
  2. Shortly after, in 2005, China approved a genetically modified adenovirus, H101 as an oncolytic virus. The approval was for the treatment of nasopharyngeal carcinoma combined with chemotherapy.
  3. In 2015, the U.S. the FDA approved T-VEC (Talimogene laherparepvec), an attenuated herpes simplex virus, type 1. This new oncovirus encodes granulocyte-macrophage colony-stimulating factor (GM-CSF). This is effective for the local treatment of inoperable, recurrent melanoma. It works for cutaneous, subcutaneous and nodal lesions in patients with recurrent melanoma after initial surgery.

Review of 20 years of human oncolytic virus research

The investigators reported about 97 clinical trials with oncolytic viruses performed between 2000 and 2020. That is to say, this involved 3233 patients with cancer. Most of these trials were phase I (50.5%) trials. There were an additional 6.2% studies, which were phase I/II. 11.3% were phase II clinical trials and only 2.1% were phase III clinical trials. 29.9 % of the literature did not specify what type of trial the investigations were about. However, they likely belonged into the phase I category as they reported on first trials of a therapy on man.

Oncolytic viruses derive from various types of viruses 

The number of studies that used a certain virus-derivative are included in brackets. It must be remembered that most of the studies dealt with six viruses: adenoviruses (30), herpes simplex virus (HSV-1) (23), reovirus (19), poxvirus (12), Newcastle disease virus (NDV) (5) and measles virus (3).

Stimulation of the immune system through GM-CSF

In 24 studies the researchers introduced GM-CSF transgene into an oncolytic virus. GM-CSF is a glycoprotein that is normally produced by granulocytes, a type of white blood cell. In this case, it stimulates dendritic cells, the precursors of T cells to produce killer T cells. Notably, this stimulates the immune system to better fight cancer.

Types of cancer targeted with oncolytic viruses

It is important to realize that the majority of the studies treated melanoma cases and gastrointestinal cancers. Namely, gastrointestinal cancers included esophageal cancer, gastric (stomach) cancer, colorectal cancer and pancreatic cancer. There were 30 studies involving melanomas with 1000 patients. There were 76 clinical trials regarding gastrointestinal cancers with 577 patients.

Moreover, other cancers where oncolytic viruses were studied were head and neck cancer (15 studies) breast and gynecological cancers (31 studies), genitourinary cancers (26 studies), and sarcomas (16 studies).

Other drugs given along with oncolytic viruses

It must be remembered that of the 97 total studies 62.9% were clinical trials where oncolytic viruses were the only therapy. In 37.1% of the studies physicians gave the oncolytic viruses along with cytotoxic chemotherapy, immunotherapy or radiotherapy.

Side effects of treatment with oncolytic viruses

The safety profile for treatment with oncolytic viruses appears to be tolerable. Fever was common, as were chills. Some patients reported nausea and vomiting, flu-like symptoms, fatigue and pain. But these symptoms disappeared within a few days.

Suppression of the bone marrow for a period of time was common, but more so when there was a combination of  oncolytic viruses with chemotherapy. None of the patients transmitted viruses to household contacts or the healthcare team.

Antitumor activity in clinical trials with involvement of oncolytic viruses

An analysis of clinical responses to oncolytic virus therapy showed the following:

  • 1% had disease control, which broke down as follows (items 2,3 and 4)
  • 4% complete control (=cure)
  • 7% partial control
  • 12% stable disease
  • 9% No response to treatment with oncolytic viruses

HSV-1 derived oncolytic viruses had the best response. The responses were not as good with adenovirus, reoviruses and with vaccinia viruses.

Discussion

Researchers of the BMJ publication analysed 97 clinical trials regarding oncolytic viruses over the past 20 years. This showed a number of points worth mentioning.

  1. The goal of oncolytic virus therapy is to induce tumor cell death. Physicians could achieve this indirectly by stimulating the immune system. Oncolytic viruses can stimulate both the innate immune system and the tumor-specific adaptive immune response.
  2. In the earlier years a lot of clinical trials investigated the safety of oncolytic viruses. But it became clear that oncolytic viruses were safe and fairly well tolerated.
  3. Many clinical trials involved oncogenic viruses with GM-CSF recombinant genes. This gene makes the oncolytic virus produce the GM-CSF protein, which stimulates dendritic cells. The end result is that the immune system produces more killer T cells that attack cancer cells, which results in higher cure rates.

More problems with oncolytic viruses

  1. There are still many questions about how oncolytic viruses stimulate the immune system. More basic research is necessary in this field. Despite 20 years of research the cure rate of 3.4% and achieving partial control and stable disease in another 17.7% is not acceptable. Perhaps combinations with other cancer treatment methods may improve the cancer cure rates. The reviewers suggested one such combination, namely immune checkpoint blockade with oncolytic virus therapy.
  2. There is no resolution about which route of administering oncolytic viruses is best. Intratumor application in melanoma cases seems the be optimal. But other solid tumors are difficult to reach. In these cases, intravenous applications were a choice. In this case oncolytic viruses experience dilution in the blood and do not have a high enough concentration when they arrive at the cancer.
Review about Human Oncolytic Virus Research in 2020

Review about Human Oncolytic Virus Research in 2020

Conclusion

In a review researchers discussed the use of oncolytic viruses in cancer therapy over 20 years . Oncolytic viruses are derivatives mostly from adenoviruses, herpes simplex virus (HSV-1), reovirus, poxvirus, Newcastle disease virus (NDV) and the measles virus. In various clinical trials researchers found that disease control was achieve in only 21.1% of treated cases. There was a cure rate of 3.4%, but another 17.7% had partial control of the cancer or stable disease. But 78.9% of treated patients showed no response to treatment with oncolytic viruses. Obviously more research is necessary to improve the cure rates in cancer patients treated with oncolytic viruses. Clinical trials with combinations of immune checkpoint blockade and oncolytic virus therapy would also be helpful. All in all, oncolytic therapy is at this point not yet an effective form of treatment for cancer.

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Jan
09
2021

Melatonin Is More Than a Sleeping Aid

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
26
2020

Hormones Play an Important Role in Survival from Covid-19

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.

  1. A strengthening of the epithelial barrier not allowing the coronavirus to penetrate into the lung tissue as easily.
  2. Release of defensins and cathelicidin, two crucial antiviral polypeptides, that eradicate the SARS-CoV-2 virus in the system.
  3. 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

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.

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Nov
21
2020

Antibody Treatment for Rheumatoid Arthritis Was Superior

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.

Oct
31
2020

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

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

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.

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Sep
05
2020

How to Manage Clot Formation with Covid-19

A publication in the Canadian Medical Association Journal describes how to manage clot formation with Covid-19. A significant amount of cases among Covid-19 patients come down with clotting problems. This means that an infection with SARS-CoV-2 (or Covid-19 coronavirus) may initially present with a fever and cough. But a few days later it can suddenly turn into a dangerous disease with severe clots, multiple organ failures and death.

Clot occurrence with Covid-19

It is important to realize that most patients with SARS-CoV-2 do not need hospitalization. But physicians admit 10 to 15% of patients to the hospital. Of these 20% end up with treatment in the Intensive Care Unit (ICU). Of all the hospitalized patients between 5% and 30% develop some form of thrombotic event. Notably, complications of clot formation can be a stroke, a heart attack, a pulmonary embolism or a deep vein thrombosis in the leg. In a recent study from the US 400 random hospitalized patients with Covid-19 144 patients were admitted to the ICU. 4.8% had radiologically confirmed deep vein thrombosis. Overall there were 9.5% with thrombotic events that developed during the hospital stay.

How does a coagulopathy develop with Covid-19?

Truly, SARS-CoV-2 enters the body cells through an interaction of its viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor. To explain, numerous organs and tissues express this receptor. This includes lung alveolar type 2 epithelial cells, endothelium, the brain, heart and kidneys. To emphasize, ACE2 leads to angiotensin II degradation. With the SARS-CoV-2 stimulation of the ACE2 receptor there may be an accumulation of angiotensin II, which causes a procoagulant state. Injury of the endothelium explains inflammation in the lining of the blood vessels in multiple organs. Commonly affected organs are lungs, heart, kidneys and intestines. The inflammatory reaction is what can lead to clot formation. When part of an organ has died off because of mini clots that destroyed part of the organ, this process can eventually lead to organ failure. Lung failure, heart failure and kidney failure can develop in these sick patients.

Adequate vitamin D blood levels are important for the immune system

By all means, vitamin D is very important for the integrity of the immune system. With vitamin D blood levels below 15 to 20 ng/mL (37.5–50 nmol/L) the immune system is paralyzed, and any viral or bacterial infection tends to overwhelm the body. Of course, this is the reason why the mortality due to Covid-19 coronavirus is highest in patients with these low vitamin D blood levels. People with secondary illnesses (diabetes, arthritis, autoimmune diseases, cancer) and patients above the age of 60 have the lowest vitamin D blood levels and have the highest mortality rates. This publication describes this in more detail.

Best vitamin D blood level is in the upper normal range (50-80 ng/mL)

Above a vitamin D blood level of 30 ng/mL (=75 nmol/L) a patient’s immune system is functioning normally. However, the immune system is strongest at a vitamin D blood level of 50–80 ng/mL (125–200 nmol/L), which is the upper range of the normal level for vitamin D in the blood.

Keep in mind that vitamin D toxicity occurs only above 150 ng/mL (375 nmol/L).

Specific effects of vitamin D on Covid-19

There are three major effects that vitamin D has.

  1. A strengthening of the epithelial barrier not allowing the coronavirus to penetrate into the lung tissue as easily.
  2. Release of defensins and cathelicidin, two crucial antiviral polypeptides that eradicate any virus in the system.
  3. 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.

In like manner, 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.

Treatment of patients with Covid-19 who have clotting problems

Patients need to be assessed with respect to their risk of developing clots. This publication describes that high risk patients have elevated D-dimer levels. When blood clots dissolve the body produces D-dimer, a protein fragment. Normally the D-dimer test is negative in a person that does not produce clots. But in sick patients with Covid-19 who form clots this blood test typically shows D-dimer >2500 ng/mL. In addition the tests show high platelet counts (more than 450 × 109/L), C-reactive protein (CRP) >100 mg/L and an erythrocyte sedimentation rate (ESR) >40 mm/h.

Indeed, with this constellation of blood tests in a severe Covid-19 case in the ICU setting, the physician uses heparin intravenously or subcutaneously to counter clot formation. However, this needs to be balanced against the risk of causing severe internal bleeding.

Separate from the anticoagulant effect, heparin seems to also suppress inflammatory cytokine levels. In addition, heparin suppresses neutrophil chemotaxis and migration. Physicians rescued many patients from death using heparin therapy.

Risk versus benefit clinical trials of heparin therapy are required

At this point there are only retrospective clinical trials available to describe risk versus benefit of heparin therapy. Some show no difference, others do. There are two international clinical trials on their way to shed more light on this situation. Until the results of these clinical trials are available, physicians need to treat patients to the best of their knowledge.

How to Manage Clot Formation with Covid-19

How to Manage Clot Formation with Covid-19

Conclusion

Clot formation in sick Covid-19 patients is responsible for many deaths in Covid-19 patients. The SARS-CoV-2 (or Covid-19 coronavirus) causes a cytokine storm with injury to the lining of the arteries. This can affect multiple vital organs and the condition may lead to organ failure. This activates the clotting system and causes clots all over the body. When this process occurs, patients get very sick and the death rate climbs. Physicians were able to rescue some patients with heparin therapy. Two international clinical trials are on the way. Hopefully  these trials answer questions about this newer treatment method. The downside of heparin therapy is the complication of massive bleeding, which causes deaths as well. When it comes to Covid-19, don’t rely on curative medicine. Strengthen your immune system by preventative therapy like vitamin D3 that can interrupt the cytokine storm.

And even with a “well-prepared” immune system it is extremely important to follow all the guidelines of distancing, disinfecting and wearing face masks. We need all the help we can get!

Aug
29
2020

Health Benefits from Vitamin C Supplements

Notably, there are health benefits from vitamin C supplements as I will explain below. A recent publication in the Journal of Intensive Care stated that vitamin C may lower ventilator time for sick patients in the ICU. In this case, researchers performed  a meta-regression analysis. It is important to realize that higher doses of vitamin C changed the need for ventilation. Vitamin C given intravenously or by mouth significantly reduced the need for ventilation in sick patients. To explain, the researchers pooled eight clinical trials and compared them to a control group who did not receive vitamin C treatment. In detail, the researchers noted that there was a 14% reduction with regard to ventilator use in the treatment group. To clarify, they had received vitamin C infusions while patients who did not receive vitamin C infusions served as controls.

Five of the clinical trials involved patients who received 10 hours or more ventilation treatment. Certainly, these patients were sicker than the average ICU patients. They experienced a 25% reduction of ventilator time after receiving between 1 and 6 grams of vitamin C. The physicians gave this intravenous or orally.

History of Mega doses of vitamin C

Indeed, in the 1940’s mega doses of vitamin C were given intravenously in an attempt to treat polio. Eventually, in the late 1960’s Linus Pauling called high doses of vitamin C the “healing factors for diseases”. But subsequent clinical investigations showed that vitamin C had limitations. The Oregon State University website reports that some of the claims about vitamin C in the past went overboard. Here are some points about vitamin C that we need to remember.

  • Vitamin C is an important cofactor in many enzymatic reactions, such as the biosynthesis of collagen, carnitine and neuropeptides. In addition, the regulation of gene expression requires vitamin C and vitamin C is an important antioxidant.
  • A prospective cohort study showed that higher vitamin C blood levels lowered the risk of high blood pressure, coronary heart disease and strokes.

More effects of vitamin C

  • Patients in need of a surgical procedure benefitted from vitamin C. Researchers showed that vitamin C was a valuable adjunct to conventional medicine in cardiovascular disease  Vitamin C reduced arrhythmia and myocardial injury following cardiac procedures.
  • There is insufficient evidence that regular vitamin C intake prevents cancer. Randomized controlled clinical trials reported no effect of vitamin C on cancer.
  • 10 grams per day of vitamin C has no association with toxic or adverse effects in most people. However, some adults are more sensitive to vitamin C and develop gastrointestinal disturbances and diarrhea with megadoses of vitamin C. For these people physicians recommend  taking up to 2 grams per day of vitamin C.

Vitamin C and disease prevention

Several clinical trials involving vitamin C supplements showed significant positive effects on patients. Below I am briefly reviewing these clinical trials.

Endothelial function

Endothelial function was improved with doses of above 500 mg of vitamin C. This likely is the reason that there is a reduction of cardiovascular disease in people who consume 1000 mg of vitamin C daily.

High blood pressure

Vitamin C at 500 mg daily lowers high blood pressure. A clinical trial found that 500 mg of vitamin C daily lowers the systolic blood pressure by 3.84 mm mercury and the diastolic blood pressure by 1.48 mm mercury. Over several years’ time this can prevent premature heart attacks and strokes.

Vitamin C and the immune system

Vitamin C is a powerful antioxidant. It can neutralize reactive oxygen species, which are produced when the immune cells fight viruses and bacteria. Neutrophils, lymphocytes and phagocytes are all supported by vitamin C. Vitamin C and E co-operate in their antioxidant functions. Vitamin C is essential for a strong antibody response with bacterial or viral infections. I take 1000 mg of vitamin C once daily.

Heart failure, strokes and heart attacks

Many studies showed some effects on reduction of heart attacks, strokes and congestive heart failure. With respect to strokes there was a 42% risk reduction over 9.5 years when the highest vitamin C plasma level was compared to the lowest level. But results regarding heart attack prevention and prevention of CHF were only marginal.

Cancer and vitamin C

Stomach cancer: there was a 45% reduction of stomach cancer when high vitamin C plasma level cases were compared to low plasma level cases.

Colon cancer: A pooled study based on 13 prospective cohort studies showed that vitamin C supplementation reduced colon cancer risk by 19%.

Large B cell lymphoma: After 11 years of follow-up the Women’s Health Initiative found that vitamin C supplementation reduced diffuse large B cell lymphoma by 31%.

Researchers could not show significant effects of vitamin C on other cancers.

Type 2 Diabetes (=adult onset diabetes)

A large European study going on for 12 years showed a strong inverse relationship between blood levels of vitamin C and the onset of diabetes. Patients with the highest vitamin C blood levels had a 62% lower risk of developing diabetes. Physicians compared this to low level vitamin C controls.

Mortality reduction with vitamin C supplementation

In the EPIC-Norfolk prospective study a clear inverse relationship was found with higher vitamin C blood levels and a reduction in risk of all-cause mortality.

Recommended dietary allowance for vitamin C

The official dietary recommendation for vitamin C in adults is 90 mg daily for males and 75 mg daily for females. However, in view of the above mentioned clinical trials I would recommend the following. Supplement with 500 mg to 1000 mg of vitamin C daily to have enough vitamin C reserves. The reason I say this is that the official dietary recommendation was based on preventing scurvy, the historic insufficiency disease of vitamin C. In addition, as mentioned before, vitamin C is safe to take up to 10 grams per day. Many physicians recommend taking a smaller amount of vitamin C found to prevent strokes, high blood pressure, type 2 diabetes, improve endothelial function and strengthen the immune system.

Health Benefits from Vitamin C Supplements

Health Benefits from Vitamin C Supplements

Conclusion

In my review I discussed health benefits from vitamin C supplements. Briefly, doctors noted that severely sick patients on respirators in the ICU setting were able to reduce the ventilator use.  This was significant after they received between 1 and 6 grams of intravenous or oral vitamin C. However, patients with the highest vitamin C supplementation had a 62% lower risk of developing diabetes than low level vitamin C controls. Vitamin C lowered high blood pressure moderately and prevented strokes by 42%. Vitamin C stimulates the immune system together with vitamin D, A, E and some trace minerals. There are many more health benefits from vitamin C supplements. The official dietary recommendation for vitamin C in adults is 90 mg daily for males and 75 mg daily for females. However, I take 1000 mg of vitamin C daily as the evidence shows that this is healthier.

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Jul
25
2020

The Immune System Changes With Age

When we are young, we do not think about our immune system, but the immune system changes with age. When we are older than age 60, we notice that we may be taking longer to recover from a flu.

How does the immune system work?

There are two parts to the immune system, the innate immune system and the adaptive immune system. The innate immune system works to protect us from bacteria, viruses, toxins and fungi from the time we are born. The adaptive immune system uses B lymphocytes from the bone marrow to produce antibodies against viruses. This provides often lifelong immunity against this specific virus, but takes 3 to 5 days to kick in. Vaccinations can also trigger antibody production to protect us from viruses in the future. Both the adaptive and the innate immune system work together closely.

What are the ingredients for a fully functioning immune system?

The immune system consists of various immune organs that are distributed throughout the body. The bone marrow produces lymphocytes, granulocytes, macrophages, eosinophils and basophils. The adenoids in the back of the nasal passages and the tonsils in the back of the throat contain a lot of lymphocytes that are ready to protect us from colds and flus. We have lymph nodes throughout the body and they are connected with lymphatic vessels. The lymph nodes filter the lymph fluid that travels in the lymphatic vessels.

Other sites of lymphocyte production

The small intestine contains the Peyer’s patches, a collection of lymphocytes that protect our gut from invading bacteria or viruses. The spleen is located in the left abdominal cavity under the diaphragm. It removes old red blood cells and provides lymphocytes for the immune system. The thymus gland is located between the breast bone and the trachea. It changes bone marrow derived lymphocytes (B cells) into T lymphocytes that can process antigens from viruses and pass them on to the adaptive immune system for a full antibody response.

Cellular interactions between various players of the immune system

Back in the 1970’s it was already known that there were bone marrow derived B lymphocytes and thymus processed T lymphocytes. We knew then that B cells were involved in antibody production (adaptive immunity). T lymphocytes were thought to turn into killer T lymphocytes to kill cancer cells. But some T cells were T helper cells to process antigen and present it to B lymphocytes for antibody production.

More research since then refined what we know about the cells of the immune system.

Natural killer cells (NK cells)

Natural killer cells (NK cells) are part of the innate immune system. They attack cancer cells and cells that are infected by viruses. It takes about 3 days for their full action to develop. NK cells utilize the cell surface histocompatibility complex to decide whether to destroy a cell or not. T cell lymphocytes do not have the ability to do that. In the Covid-19 coronavirus situation NK cells play an important role to combat the disease right away.

Monocytes

They are large white blood cells that can differentiate further into macrophages and dendritic cells. Monocytes are part of the innate immunity, but they have an antigen presenting capability, which makes them also part of the adaptive immunity.

Memory T cells

The immune system learns to adapt to viruses and bacteria that we have come in contact with. The reason for the memory of the immune cells are the memory T cells. They replicate like stem cells, which keeps a clone of T lymphocytes, T helper cells and cytotoxic T killer cells in the background. They circulate through the body including the lymph glands and the spleen.

Immunosenescence as we age

There are several factors that come together, which age our immune system. The term for this is “immunosenescence“. There are genetic differences and differences due to the sex hormones. Estrogens increase the response of the immune system. In contrast, progesterone and androgens (including testosterone) decrease the immune response. This may be the reason why women tend to live longer than men.

As we age there are more and more memory T cells (both cytotoxic T cells and T helper cells). This weakens the formation of the natural killer cells (NK cells) of the innate immune system. Even the initiation of the adaptive immune system can be slower when we age and also the response to the flu vaccine. In addition, this can pave the way to autoimmune diseases.

The immune system changes with age: Evidence of immunosenescence

The following 3 factors show whether a person has immunosenescence:

  • The immune system has difficulties to respond to new viruses/bacteria or to vaccines
  • Accumulation of memory T cells crowding out cells of the rest of the immune system
  • Low-grade inflammation that is chronic and persists (“inflamm-aging”)

The process of immunosenescence starts with the involution of the thymus gland around the time of puberty. At that time the sex hormone secretion is highest. At the same time a growth factor from the bone marrow and the thymus gland decreases. It has the name interleukin-7 (IL-7). The end result is a slow decrease of the innate immune system with age and a more substantial weakening of the adaptive immune system due to a lack of naïve T and B cells. 

Chronic viruses can weaken the immune system further

The varicella herpes zoster virus causes chickenpox. In some people the chickenpox virus can persist, but the immune system actively keeps it controlled. In the 60’s or 70’s when the immune system is weakened from aging, there can be a flare-up as shingles, a localized form of the chickenpox virus.

Another virus, the human cytomegalovirus can cause a chronic infection that often persists lifelong. In this case the immune system is chronically weakened because of a massive accumulation of T memory cells, which keeps the human cytomegalovirus infection at bay.

What we need when the immune system changes with age 

Vitamin A

Both the innate and adaptive immunity depend on vitamin A and its metabolites. The skin cells and mucosal cells function as a barrier, which is important for the innate immunity. The skin/mucosal lining of the eye, the respiratory tract, the gastrointestinal and genitourinary tracts help the innate immunity to keep viruses and bacteria out of the body. Vitamin A is important to support macrophages, neutrophils and natural killer (NK) cells. In addition, vitamin A supports the adaptive immune system, namely T and B lymphocytes, so that the body can produce specific antibodies against viruses.

I do not take vitamin A supplements as I eat diversified foods like spinach, vegetables, poultry, Brussels sprout, fish and dairy products that contain vitamin A and carotenoids.

Vitamin C

This vitamin is a powerful antioxidant. It can neutralize reactive oxygen species, which are produced when the immune cells fight viruses and bacteria. Neutrophils, lymphocytes and phagocytes are all supported by vitamin C. Vitamin C and E co-operate in their antioxidant functions. Vitamin C is essential for a strong antibody response with bacterial or viral infections. I take 1000 mg of vitamin C once daily.

Vitamin D

The immune system is very dependent on vitamin D as the immune cells all contain vitamin D receptors. People who have less than 10 ng/mL of vitamin D in the blood are vitamin D deficient. They have much higher death rates when they get infected with the Covid-19 coronavirus.

Vitamin D regulates the expression of target genes. At the center is the vitamin D receptor, which is a nuclear transcription factor. Together with the retinoic X receptor (from vitamin A) the vitamin D receptor binds small sequences of DNA. They have the name “vitamin D response elements” and are capable of initiating a cascade of molecular interactions. The result is a modulation of specific genes. Researchers identified thousands of vitamin D response elements that regulate between 100 and 1250 genes.

You need enough vitamin D for your immune system

When enough vitamin D is present in the blood (more than 30 ng/mL) the immune system releases the peptides cathelicidins and defensins, which effectively destroy bacteria and viruses.

Vitamin D has mainly an inhibitory function regarding adaptive immunity. It inhibits antibody production from B cells and also dampens the effect of T cells. Researchers reported that vitamin D3 is useful in the treatment of autoimmune diseases.

I am a slow absorber of vitamin D3 as repeat blood vitamin D levels showed. I need 10,000 IU of vitamin D3 daily to get a blood level of 50-80 ng/mL (=125-200 nmol/L). This is the higher range of normal. Everybody is different. Ask your physician to check your blood level of vitamin D. Toxic vitamin D blood levels are only starting above 150 ng/mL (= 375 nmol/L).

Vitamin E

This is a vitamin that is fat soluble and helps the body to maintain its cell membranes. But researchers found that vitamin E also stimulates the T cell-mediated immune response. This is particularly important for the aging person to prevent respiratory tract infections. I take 125 mg of Annatto tocotrienols per day (this is the most potent form of vitamin E).

Vitamin B6

This vitamin is important for antibody production by B cells. Vitamin B6 regulates the metabolism of amino acids, which in turn form proteins. Antibodies and cytokines require vitamin B6. The T helper immune cells that initiate an adaptive immune response depend on vitamin B6 as well. I take a multi B complex vitamin (Mega B 50) twice per day, so I supplement with a total of 100 mg of vitamin B6 daily.

Folate

Folic acid is a coenzyme for the metabolism of nucleic acids and amino acids. Studies in humans and animals have shown that folate deficiency leads to increased susceptibility to infections. People with folate deficiency develop a megaloblastic anemia with immune weakness that leads to chronic infections. With my B complex supplement I get 2 mg of folic acid daily.

Vitamin B12

Methylation pathways depend on vitamin B12 as a coenzyme. Vitamin B12 is also involved as a coenzyme in the production of energy from fats and proteins. In addition, hemoglobin synthesis depends on vitamin B12. Patients with vitamin B12 deficiency develop pernicious anemia. These patients also have a weak immune system due to natural killer cell activity suppression and because circulating lymphocyte numbers are significantly decreased.

Treatment with cyanocobalamin reverses the immune weakness rapidly and treats pernicious anemia at the same time. I take 50 micrograms twice per day as part of the Mega-B50 multivitamin tablet. But I also inject 1000 micrograms of vitamin B12 every 6 months subcutaneously to be sure it is absorbed into the body. In older age the intrinsic factor from the stomach lining, which is required for absorption of vitamin B12 in the small intestine, can be missing, leading to vitamin B12 deficiency despite swallowing supplements.

Minerals required for a good immune response

Researchers identified five minerals that are essential for a strong immune system. They are zinc, iron, selenium, copper and magnesium.

Zinc

Zinc is important for a normal function of the innate and adaptive immune system. As zinc cannot be stored in the body, taking regular zinc supplements (30 to 50 mg daily) is important. I take 50 mg of amino acid chelated zinc daily.

Iron

Iron is important for cell oxygen transport and storage, DNA synthesis and for mounting an effective immune response. In particular it is the T cell differentiation and proliferation where iron is needed. Iron deficient people get a lot of infections because the immune system is paralyzed. I eat one spinach salad or steamed spinach daily, which gives me enough iron supply per day.

Selenium

Selenium is a trace mineral that is important for a normal immune response and for cancer prevention. When selenium is missing, both the adaptive and innate immune system are suffering. In this case viruses are more virulent. With selenium supplementation cell-mediated immunity is improved and the immune response to viruses is more potent. I take 200 micrograms of selenium per day.

Copper

Deficiency in copper results in a very low neutrophil blood count and causes susceptibility to infections. Copper is a trace mineral that participates in several enzymatic reactions. It is important for the innate immune response to bacterial infections. A well-balanced Mediterranean diet contains enough copper, which is why I do not supplement with extra copper.

Magnesium

An important cofactor for vitamin D in the body is magnesium. Magnesium participates in many enzymatic reactions. Between vitamin D and magnesium, the immune system is strengthened. I take 150 mg of magnesium citrate twice per day. By the way, magnesium also helps us to get a restful sleep, if we take it at bedtime.

Other dietary factors that strengthen the immune system

Polyunsaturated omega-3 fatty acids

It is important to note that polyunsaturated omega-3 fatty acids are essential for the body and help to modulate the immune system. I take 1800 mg of omega-3 (EPA/DHA) twice per day. I also like to eat fish and seafood at least 3 times per week.

Probiotics

Prebiotics benefit both the innate and the adaptive immune system. They strengthen the epithelial gut barrier, which is an important innate immune defence. Probiotics also lower the risk for Clostridium difficile gut infections. I take one probiotic every morning.

The Immune System Changes With Age

The Immune System Changes With Age

Conclusion

The immune system consists of different organs like the bone marrow, the spleen, lymph glands, Peyer’s patches in the gut, the thymus gland and more. There is the innate immune system, which responds immediately to a virus like the Covid-19 coronavirus. The adaptive immune response involves antibody production against, for instance, the measle virus or the mumps virus. With the aging process the immune system slows down (immunosenescence). This involves an accumulation of memory T cells and a depletion of natural killer cells (NK cells). This means that the innate immunity is getting weaker as we age and chronic inflammation occurs more often. This is the reason why people above the age of 65 get more severe symptoms from the Covid-19 coronavirus. They are also more affected by influenza-type illnesses.

Take supplements to strengthen the immune system

I reviewed the cofactors of a healthy immune system in some detail. It is important that you pay attention to these, particularly the vitamin D3 intake. With a strong immune system, we can survive viral infections better, including the current Covid-19 coronavirus. Future research will likely detect how to reactivate a sluggish immune system in older people. This way vaccination responses following flu injections will become more reliable in seniors.

Jul
04
2020

Probiotics and a Phage Blend for Digestive Problems

In general, probiotics and a phage blend for digestive problems can help patients with irritable bowel syndrome (IBS). It is important to realize that about ¾ of Americans suffer from digestive problems. They develop symptoms of gas, bloating, diarrhea and stomach pains. To put it another way, about 1 in 7 Americans suffer from the condition, called chronic irritable bowel syndrome. That is to say, he underlying problem is an imbalance of gut bacteria where the bad ones outnumber the good ones. There are a number or reasons why bowel flora gets disrupted. We eat more processed foods, less fiber, and beef products from industry farms contain antibiotic residues. In feedlots for beef cattle antibiotics are fed to the animals as growth promoters. The residues in the meat kill the good bacteria in our guts and the bad ones proliferate. This causes digestive problems, but also weakens our immune system.

How probiotics work

Probiotics can restore our gut flora to a large extent. But some of the probiotic action gets lost in the stomach from the acidic milieu. A recent publication from a panel of gastroenterologists has not supported the wide use of probiotics. They came to the conclusion that probiotics have not shown enough benefit to a number of clinical conditions. The researchers mentioned Crohn’s disease, C. difficile infection, ulcerative colitis and irritable bowel syndrome (IBS) in particular of not responding to probiotics. But this may be because of inactivation of some of the power of the probiotics by stomach acid. In addition, by not using phages to potentiate the probiotic action probiotics may fail to permanently to improve the gut flora. I have previously discussed the importance of probiotics for the gut flora.

History and use of bacteriophages

Bacteriophages are now often just called phages. Dr. Frederick Twort, an Englishman detected phages in 1915 during World War I. Essentially a phage consists of either DNA or RNA and a protein envelope around this. Phages are very specific for certain bacterial strains. They attach to the bacteria and inject their own DNA or RNA into the bacteria. This stops the bacteria from multiplying, but makes the bacteria produce many more identical phages. Phages are useful to control the growth of problem bugs including antibiotic-resistant bacteria. However, the regulatory agencies were slow to approve phages despite a good safety record. Life Extension Magazine recently published a review article about this subject.

Phages helping to protect probiotic bacteria

Phages naturally play a role in keeping the gut flora stable. In this lengthy review, published in January 2020 phage actions are reviewed. It also mentions the connection between the gut flora and the immune system. The Life Extension Magazine article mentioned above describes experiments that show the action of phages. E. coli is the main bacterium in the large intestine. It is also the bacterium that can cause pneumonia, diarrhea and urinary tract infections.

Experiments with bacteria and phages in Petri dishes

According to the Life Extension Magazine article researchers did experiments with Bifidobacterium longum, one of the desirable gut bacteria. This was placed on a Petri dish along with E. coli bacteria. In a second Petri dish Bifidobacterium longum, E. coli and a phage mix were placed. After 5 hours there was hardly any growth of Bifidobacterium longum in the first petri dish, as it was crowded out by E. coli. The result in the second Petri dish was interesting: the Bifidobacterium longum colonies were 7000-times higher in number than in the other Petri dish without the phage mixture. The phages had selectively attacked the E. coli bacteria, which made room for the Bifidobacterium longum bacteria to multiply.

Animal experiments with bacteria and phages

The Life Extension Magazine review mentions animal experiments with phages next. One group of mice received B. longum and the disease-causing E. coli in their food. The other group had the same bacteria plus a mix of phages directed against E. coli. For the phage group the results within 24 hours were as follows.

  • The E. coli count in the small intestine was 10-fold lower, in the large intestine 100-fold lower and in the fecal matter 100-fold lower.
  • The phage group also had a 100-fold increase of the B. longum count in the small intestine. The large intestine also had a 100-fold increase of the B. longum count. And there was a 40-fold increase of B. longum in the fecal matter.

Control mice without the phage mix developed constipation and intestinal segments showed redness, swelling and leaks. In contrast, the phage mix group of mice showed no side effects and had improved digestive function.

Human studies using probiotics and a phage blend for digestive problems

Safety tests of phage therapy were next in 2005 involving 15 volunteers. There were no side effects using two different phage concentrations to diminish E. coli. Researchers had done other safety experiments in Russia and in Poland in the past. Patients with ulcerative colitis responded with improved symptoms and improved endoscopic findings to treatment with two probiotics. They received fermented milk products (Cultura) containing live lactobacilli (La-5) and bifidobacteria (Bb-12) for 4 weeks. There were 51 patients with ulcerative colitis and 10 patients with familial adenomatous polyposis. Abdominal cramps, Involuntary defecation, leakage and the need for napkins were significantly reduced in both groups. An endoscopic score of inflammation showed a significant decreased when the baseline exam was compared to the exam after the 4-week intervention.

Literature review about phages

Here is a thorough review in a publication dated 2004 from Poland describing the action of bacteriophages, now simply called phages. It lists many human experiments and shows that phages are safe to use in humans.

Irritable bowel syndrome

Irritable bowel syndrome (IBS) presents with a pathological intestinal function, which can be quite disabling. Another name for it is “spastic colon”, because many patients complain of significant bowel spasms. Some health providers still use this alternative term. This syndrome is more common among women and there is a theory that female hormones may have something to do with the pathophysiology of irritable bowel syndrome. Testosterone on the other hand may have a calming effect on the gastrointestinal tract.

Symptoms and treatment of IBS

Generally speaking, irritable bowel syndrome occurs first in the teens or early twenties, but then frequently tends to become chronic. The patient chiefly complains of abdominal bloating and distension. Bowel movements lead to a marked relief of pain. There is often mucous in the stools. After a bowel movement there is often a feeling that the rectum did not empty entirely, even though it did. Food intake or stress can bring on these symptoms and they always occur during the waking period. At nights most patients have no pain.

Among other measures taking probiotics alone or mixed with phages can normalize the bowel flora. In older men IBS symptoms may indicate a reduction in testosterone production. If the blood contains a low testosterone level, the physician may want to replace the missing testosterone with injections or bioidentical testosterone creams. This can improve IBS in older males.

A safe delivery system for probiotics and a phage blend for digestive problems

Life Extension has developed a dual capsule that brings the inner content safely through the stomach and protects the mix of probiotics and phages from stomach acid. The capsule only opens in the small intestine where it releases its content of probiotics and phages into the gut. This allows the good bacteria like B. longum to multiply and suppresses E. coli, which would otherwise interfere with the beneficial bacteria.

Probiotics and a Phage Blend for Digestive Problems

Probiotics and a Phage Blend for Digestive Problems

Conclusion

About ¾ of Americans suffer from digestive problems. Many have a disbalance of the gut flora. But it is not easy to replace poor gut flora with a healthy one. Recent research showed that a combination of 7 probiotic strains with a mix of 4 E. coli fighting phages can give tremendous relief from bloating, diarrhea and abdominal cramps to patients with irritable bowel syndrome (IBS). Life Extension has developed a special dual capsule that “sneaks” the capsule through the stomach. It will only open in the small intestine. This way the content of the inner capsule with the mix of probiotics/phages stays safe from the stomach acid. At the end many more beneficial bowel-bacteria are growing in the small and large intestine. This normalizes the symptoms of the patient and leads to better digestion of food. Probiotics and phages are the new players in the gut microbiome.