Feb
04
2024

Beef and Dairy May Cause Cancer and MS

New cancer research suggests that chronic virus particles in beef and dairy may cause cancer and MS (multiple sclerosis). The Medical journal Medscape.com had a review article that summarized this line of research.

Papillomaviruses and cervical cancer

Harald zur Hausen, M.D., D.Sc., a German virologist, detected that papillomavirus causes cervical cancer. He was given the Nobel prize in Medicine in 2008 for “his discovery of human papillomaviruses causing cervical cancer”. In the meantime, we know that there are two strains, namely HPV-16 and HPV-18 that are carcinogenic. We also learnt that papillomavirus causes oropharyngeal cancer, anal cancer, penile cancer and vulvar cancer. Since then, HPV vaccines are commonly in use for cancer prevention.

Evidence for causation of colorectal cancer

Professor Harald zur Hausen and his wife, Professor Ethel-Michele de Villiers, continued work on looking for viral particles in many other cancers. This led them to state that colorectal cancer was due to a latent viral infection. He determined that, when women were breastfeeding their infants for prolonged periods of time (about 1 year), they transmitted oligosaccharides with the breast milk to their offspring, which gave lifelong prevention against colorectal cancer to their children. He also showed that colon cancer patients had round particles in their intestinal mucous membranes, which consisted of single-stranded DNA rings.

Persistent viruses

The researchers said that they came from viruses and they named them bovine meat and milk factors (BMMF). In the same areas in the intestine, they detected acid radicals from oxidative stress typical for chronic inflammation. They postulated that infants who are weaned from breast milk prematurely, and started on cow milk formulas ingest BMMF. This infects the lining of the gut where a chronic subclinical BMMF infection gets established. Decades later the patient comes down with colorectal cancer. They established that children who are breast fed for 1 year do not get BMMF particles in the lining of their guts or colorectal cancer. They also don’t get MS in adult life.

Criticism of two regulatory agencies in Germany

The above results of professor zur Hausen and his wife were published in February of 2019. This led to a lot of press releases questioning these results. In Germany the consumption of beef and milk products is popular. The DKFZ (Deutsches Krebsforschungszentrum) felt that an “all-clear signal” was necessary. The Bundesinstitut für Risikobewertung (BfR) stands for the German Federal Institute for Risk Assessment, situated in Berlin. It is a substructure of the German government responsible for food safety. The second agency is the Max Rubner Institute (MRI) in Karlsruhe, also known as Federal Research Institute of Nutrition and Food. Both agencies started to investigate the facts of Prof. zur Hausen’s research. At the end of November 2022 the BfR and MRI made a joint statement. They stated the following:

  • BMMF were not new viral agents, but variations of already known DNA sequences.
  • BMMF commonly occurred in a variety of animal- and plant-based foods.
  • BMMF were not capable of infecting human cells.
  • It was true that consumption of red and processed meat correlates with the incidence of intestinal tumors.
  • However, consumption of dairy products are linked to a reduced risk of intestinal tumors.
  • There is no evidence that breast cancer would be associated with the consumption of beef or dairy.
  • They stated that milk products and beef are valuable supplementary diet components for infants due to their micronutrients. They further stated that dairy and beef products are safe for people of all ages.

Evidence for causation of multiple sclerosis

Professor zur Hausen and his wife, Professor Ethel-Michele de Villiers both worked at the German Cancer Research Center in Heidelberg. They pursued research about MS. MS is usually attributed to IgG1 and IgG3 autoantibodies that destroy Schwann cells. The Hausen research team found the following perplexing facts:

  • MS was associated with the consumption of dairy products and beef products.
  • They isolated ring-shaped DNA molecules (BMMF) from dairy and cattle blood.
  • Epstein Barr virus (EBV) also plays a role in initiating MS. MS patients have higher antibody titers against EBV.
  • One research paper noticed that MS patients in Antarctica secreted EBV in their saliva in the winter month. However, vitamin D3 stopped the viral excretion. This is very interesting as vitamin D is an important immune response stimulator.

More evidence:

  • They isolated BMMF particles from lesions of MS patients.
  • They noticed the old fact that MS is more common further away from the equator. Vitamin D production from sun exposure reduced cases of MS.
  • Prolonged breast feeding up to one year prevents life threatening rotaviruses and noroviruses in the newborn. The reason is exposure to oligosaccharides in breast milk. The mother starts producing breast milk in the middle of her pregnancy. It protects mother from tumors (including breast cancer), from MS later in life as well as type 2 diabetes.
  • The researchers formulated the hypothesis that both EBV and BMMF are responsible in patients to form MS lesions in the brain when vitamin D levels are low. A good dose of vitamin D3 every day may be helping to keep EBV and BMMF in a dormant phase.

Discussion

At this point there is no consensus why an increased consumption of beef and processed meat causes more colorectal cancer. The question is whether BMMF particles cause colorectal cancer or whether meat consumption experiences metabolization into carcinogenic substances? Either way it would be desirable to cut down on your red meat consumption.

With respect to MS, we know that autoantibodies are destroying the Schwann cells. But the question is why the immune system produces autoantibodies. Could it be that persistent EBV viruses switch the immune system from a normal to an autoantibody mode? Would BMMF be an additional factor?

Beef and Dairy May Cause Cancer and MS

Beef and Dairy May Cause Cancer and MS

Conclusion

Professor zur Hausen, a virologist from Germany and his wife Professor Ethel-Michele de Villiers researched persistent viruses. Professor zur Hausen detected the connection of papilloma viruses to cervical cancer. He received the Nobel prize in medicine 2008. They proposed the theory that newborns in their first year of life have an immature immune system. If they are fed cow’s milk and/or beef during the first year they accumulate bovine meat and milk factors (BMMF), which can subsequently lead to colon cancer or to MS as an adult. Two top German institutes banded together to criticize Prof. zur Hausen’s research.

Criticism of Professor zur Hausen’s research

The Bundesinstitut für Risikobewertung (BfR) stands for the German Federal Institute for Risk Assessment, situated in Berlin. It is a substructure of the German government responsible for food safety. The second agency is the Max Rubner Institute (MRI) in Karlsruhe, also known as Federal Research Institute of Nutrition and Food. These research institutes concluded that not all of the findings of Professor zur Hausen were valid. I listed 7 of their concerns. On the other hand, they agreed that it was true that consumption of red and processed meat correlated with the incidence of intestinal tumors. Time will tell which parts of the research ultimately will be valid and which are not.

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Sep
09
2023

How the Immune System affects Parkinson’s Disease

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

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

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

The role of inflammation in Parkinson’s

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

Lifestyle factors that people can change to prevent PD

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

Changing diet can help postpone Parkinson’s disease

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

The gut connection to Parkinson’s disease

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

Can any diet fight gut dysbiosis?

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

Regular exercise to prevent Parkinson’s disease

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

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

How the Immune System affects Parkinson’s Disease

How the Immune System affects Parkinson’s Disease

Conclusion

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

Lifestyle changes help to postpone Parkinson’s disease

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

Dec
03
2022

The Bubonic Plague Still Affects some People today

Although the plague is of historic significance, it still is around and the Bubonic plague still affects some people today. In the Middle Ages the world population experienced a reduction from 475 million to 350–375 million between 1346 and 1353. This pandemic relied on fleas on ground rodents, which showed infection with the bacterium Yersinia pestis. Flea bites transmitted the plague bacteria to humans. Nowadays we have effective antibiotics against the plague. Doxycycline is the antibiotic of choice against this bacterium. But in the Middle Ages no antibiotic was available. Those who had a certain variant of the immune system survived, while others who did not have this perished.

Study from nature showing changes of the immune system due to the Bubonic plague

An international research article involving scientists from Canada, the US and France was published in the medical journal nature. Nature published this on Oct. 19, 2022. The title was:” Evolution of immune genes is associated with the Black Death “. The scientists worked with a hypothesis that the human immune genome underwent a shift after the plague in those who survived. They tested their hypothesis by doing DNA analyses in corpses from before, during and after the Black Death. Specifically, more than 300 skeletons came from London/England, where the plague hit hard. 198 samples came from 5 different locations in Denmark. Researchers extracted DNA from the roots of the teeth. They checked for the individual’s’ DNA and for the presence or absence of the bacterium Yersinia pestis. CNN summarized this here.

Results of the study

Hendrik Poinar is a professor of anthropology at McMaster University in Hamilton and coauthor of this study. He said: “It’s a long process, but in the end you have the sequence of those genes for those people from before, during and after the plague and you can ask: Do the genes one population carried look different than the ones another population carried?” There was one particular gene, ERAP2 that had a strong association with the plague. The London study showed that 40% of individuals had an ERAP2 variant protective of the plague prior to the plague. After the plague 50% of the individuals had this variant.

Denmark data

In Denmark prior to the plague 45% of the population carried the variant of ERAP2, while 70% of the population buried after the plague carried this variant. The researchers did in vitro experiments with cultured cells. They could show that macrophages, which are immune cells that initiate immune responses, kill Yersinia pestis bacteria better when the ERAP2 variants are present in comparison to when they are not.

The downside of immunity

The downside of the ERAP2 variant is that researchers linked it to a greater susceptibility to autoimmune disorders. Diseases like Crohn’s disease, rheumatoid arthritis and systemic lupus belong into this category. Luis Barreiro is a professor of genetic medicine at University of Chicago and a coauthor of the study. He said: “This suggests that populations that survived the Black Death paid a price, which is to have an immune system that increases our susceptibility to react against ourselves.” He mentioned further:” It is unlikely that Covid-19 outbreak would shape our immune system in a similar way — largely because the disease predominantly kills people after their reproductive age, meaning it’s unlikely genes that confer protection would be passed on to the next generation.”

The Bubonic Plague Still Affects some People today

The Bubonic Plague Still Affects some People today

Conclusion

A publication in October of 2022 examined 300 skeletons from London, England where the plague hit severely between 1346 and 1353. The study also examined skeletons from Denmark. In both locations the scientists timed the samples before, during and after the pandemic. They found a genetic variant of the immune system by the name of ERAP 2, which changed in the population before and after the plague. The London study showed that 40% of individuals had an ERAP2 variant protective of the plague prior to the plague. After the plague 50% of the individuals had this variant. In Denmark 45% of the population carried the variant of ERAP2, before the plague while 70% of the population buried after the plague carried this variant. In vitro studies showed that macrophages were more aggressive as a result of sensitization of the immune system from an increase of the ERAP2 variant.

Autoimmune diseases

The increase of the ERAP2 variants stimulates the immune system. The researchers determined with in vitro studies that the Yersinia pestis bacterium stimulate macrophages. The downside of the ERAP2 variant is that researchers linked it to a greater susceptibility to autoimmune disorders. Diseases like Crohn’s disease, rheumatoid arthritis and systemic lupus belong into this category. Professor Luis Barreiro from the University of Chicago said:” It is unlikely that Covid-19 outbreak would shape our immune system in a similar way — largely because the disease predominantly kills people after their reproductive age, meaning it’s unlikely genes that confer protection would be passed on to the next generation.”

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
19
2020

The Use of Biologics for Treatment of Autoimmune Diseases

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

Dupilumab (Dupixent)

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

Omalizumab (Xolair)

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

Rheumatoid arthritis

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

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

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

Crohn’s disease

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

There are three categories of treatment that are worth mentioning.

  • Anti-Tumor Necrosis Factor Agents

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

  • Integrin Receptor Antagonists

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

  • Interleukin-12 and -23 Antagonist

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

The Use of Biologics for Treatment of Autoimmune Diseases

The Use of Biologics for Treatment of Autoimmune Diseases

Conclusion

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

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

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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.

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.

May
09
2020

Vitamin D Is the Definitive Link

Vitamin D deficiency caused rickets in the past, but now we know that vitamin D is the definitive link for other health problems. The lack of it is the reason for numerous illnesses. A search in my website gives you more than 170 blogs where I am discussing the effect of vitamin D. These describe how vitamin D is the definitive link in a lot of different diseases. In a 2015 study from Brazil the authors noted that a critical vitamin D blood level was 12 ng/mL. All these critically ill patients received treatment in an ICU setting. In vitamin D blood levels of 12 ng/mL the mortality rate was 32.2%. A control group of ICU patients with more than 12 ng/mL had a mortality rate of only 13.2%. The authors concluded that a low vitamin D level on ICU admission was an independent risk factor for mortality in this critically ill patient group.

A few diseases where low vitamin D is the definitive link for a poor outcome

In patients, who have arthritis, cardiovascular disease, breast cancer, diabetes, osteoporosis, influenza and others, the laboratory tests that shows their 25-hydroxy vitamin D level, are usually below 15 ng/mL. This link has 269 peer reviewed references.

2015 Italian study showed that microvascular complications in diabetes patients were high, if the vitamin D3 blood levels were low. If patients had high levels of vitamin D, there were no complications such as retinopathy or nephropathy. But if levels were below 20 ng/mL, damages were significant in the capillaries of the eyes and kidneys.

Multiple sclerosis

It has been known for some time that in the northern hemisphere MS is more common because of the lack of sunshine, which in turn leads to less vitamin D3 production in the skin. Multiple sclerosis (MS) is an autoimmune disease where immune cells attack the lining of nerves. Both nerve cells and immune cells have vitamin D receptors. It appears that vitamin D calms down immune cells and remission of an MS relapse is more likely.

Dr. Fitzgerald and colleagues published a study in JAMA Neurology in 2015. Results of this study showed marked differences between MS patients with high and low vitamin D levels.

Multiple sclerosis rates with high and low vitamin D levels

Patients with the highest vitamin D blood levels (more than 40 ng/mL) had the lowest rates of new MS lesions. Previous studies found that a low blood level of vitamin D (less than 25 ng/mL) had an association with a higher risk of developing MS. Dr. Fitzgerald’s study showed that a 20 ng/mL (50.0-nmol/L) increase in serum vitamin D levels associated with a 31% lower rate of new MS lesions. Patients with the highest vitamin D level of more than 40 ng/mL (100 nmol/L) had the lowest amount of new MRI lesions (47% less than the patients with the lowest vitamin D levels).

Dementia and Alzheimer’s disease

A 2014 study showed that patients with a low vitamin D level had a connection with a high risk of dementia and Alzheimer’s disease.

Specifically, the researchers found the following observations.

  • Vitamin D level of less than 10 ng/mL: 122% increased risk of Alzheimer’s
  • A vitamin D level of 10 to 20 ng/mL: 51% increased risk of Alzheimer’s

Vitamin D is the definitive link for the immune system

In a publication of 2006 Dr. John Cannell and co-workers have reviewed why influenza has seasonal outbreaks. They found that the innate immune system was very dependent on vitamin D. Those who did not get enough sunlight in the northern hemisphere during January, February, March and April have an average 25-hydroxy vitamin D level of only 15 to 17 ng/mL. In contrast, from July to September the same volunteers had vitamin D levels of 24 to 29 ng/mL. The authors stressed that this was the reason why spring flus in the late winter/early spring season are common, but disappear in summer.

Vitamin D requirements for immune system is 2000 IU or more per day

Vitamin D is essential for the functioning of the innate and adaptive immune system. They also are the reason why children are not as affected by influenza viruses as adults are. Dr. Cannell said: “The innate immunity of the aged declined over the last 20 years due to medical and governmental warnings to avoid the sun. While the young usually ignore such advice, the elderly often follow it”. Had the older patients taken higher doses of vitamin D3 every day, their immunity would have been as strong as the children’s immunity. The publication cites another paper that found that 2000 IU per day or more will strengthen the immune system. Note that this is a higher dose than  treating rickets. Treatment of rickets responds to only 400 IU of vitamin D3 per day.

Mechanism of action of vitamin D in infectious diseases like influenza or Covid-19 coronavirus

Here is evidence from US researchers that states that higher doses of vitamin D3 will mitigate the course of influenza and of Covid-19 coronavirus. The researchers outlined that vitamin D has 3 effects:

  1. Maintaining tight epithelial junctions making it more difficult for the Covid-19 coronavirus to penetrate them.
  2. “Killing enveloped viruses through induction of cathelicidin and defensins.” These powerful antiviral polypeptides can kill viruses that have invaded the bloodstream within 1 to 2 days.
  3. “…And reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia.” People who get viral pneumonia are at a high risk of death. By bringing the vitamin D blood level up to the higher range of normal, between 50 and 80 ng/mL, patients that have encountered Covid-19 coronavirus are more likely to survive.

Criticism of high dose vitamin D treatment

A common criticism of treatment with higher doses of vitamin D is that people would develop high blood calcium levels and would get kidney stones. Three recent studies have demystified this. A 2012 study looked at patients who were in the higher range of calcium levels, but deficient in vitamin D. They were treated with vitamin D3 und closely supervised. The calcium levels did not change after 1 year of high doses of vitamin D.

This 2018 study observed that there is a small amount of kidney stone formers who will form kidney stone with or without vitamin D3 treatment.  However, the large majority of patients do not form kidney stones with vitamin D treatment and their blood calcium levels stay the same before and after vitamin D treatment.

Toxic vitamin D blood levels

Toxic levels of vitamin D blood levels are above150 ng/mL, or 375 nmol/L. The therapeutic levels discussed here are well below these toxic levels.

Placebo controlled New Zealand study fails to show kidney stones

A placebo-controlled study from New Zealand went on for 3.3 years. 100,000 IU of vitamin D3 monthly (3333 IU per day on average) in the experimental group were compared to a placebo group. There were no vitamin D induced kidney stones and also no changes in calcium levels.

In past studies regarding vitamin D toxicity were done. But with these investigations there were many confounding factors that led to false results.  The investigators at those times mistakenly thought that they were side-effects of vitamin D. Up to this day conventional medicine often warns of hypercalcemia and kidney stones with vitamin D treatment. While the patient is on higher vitamin D levels, the physician can do blood and urine tests to see whether or not there is any concern.

Polypeptides released by vitamin D

There are more than 100 polypeptide hormones that are controlled by vitamin D. The most important ones for control of bacterial and viral infections are the defensin family and the cathelicidin family of polypeptides. They are instrumental in preventing the cytokine storm with a Covid-19 coronavirus infection treated with high vitamin D doses.

Decades after the original description of vitamin D researchers found out that vitamin D actually is a hormone.

There are vitamin D hormone receptors on almost every cell of the body. Vitamin D integrates the body cells and they respond as one unit. It is only recently that researchers found out about the release of polypeptides, particularly defensin and cathelicidin. They are  vital in the defence against the Covid-19 Coronavirus and the various flu types.

Vitamin D Is the Definitive Link

Vitamin D Is the Definitive Link

Conclusion

The detection of vitamin D originally occurred when rickets was examined. But later researchers found that vitamin D has hormone qualities.

You can prevent several diseases, like arthritis, cardiovascular disease, breast cancer, diabetes, osteoporosis and influenza. But you must take adequate amounts of vitamin D to bring the vitamin D blood level up. 25-hydroxy vitamin D blood levels are now recognized as the standard test to measure whether you have enough vitamin D on board. When it comes to fighting infections the vitamin D blood level has to be above 30 ng/mL (above 75 nmol/L). At this level the immune system will release defensin and cathelicidin polypeptides. These are powerful antiviral and antibacterial substances that can even fight Covid-19 coronavirus.

High vitamin D therapy is safe

With careful monitoring of blood vitamin D levels side effects of high vitamin D dosages were not found. Conventional medicine keeps on repeating old studies with confounding errors. This scares people, and as a result they don’t want to take enough vitamin D for prevention. Hypercalcemia and kidney stones were NOT found in randomized newer studies. As long as the vitamin D level does not exceed 50-80 ng/mL (or 125-200 nmol/L) vitamin D therapy is perfectly safe.

Apr
18
2020

Changes of Metabolism by Inflammation

Dr. James LaValle gave a presentation about changes of metabolism by inflammation in Las Vegas. I listened to this lecture on Dec. 15, 2020. The 27th Annual World Congress on Anti-Aging Medicine in Las Vegas took place from Dec. 13 to 15th, 2019. His original title was: “Innovations in Metabolism and Metaflammation”. This talk was complex and as a result it may not be easy reading. But it shows how various factors can affect our metabolism and our life expectancy.

In the first place he understands “metabolism” as all of the chemical reactions together that make you feel the way you feel today. In the same way metabolism is the chemistry that drives you toward future health. It is equally important to note that disregulation of your metabolism occurs from global metabolic inflammatory signalling. As has been noted he called this “metaflammation” (inflammation affecting your metabolism).

Dr. LaValle said that understanding disruptors of your metabolism can lead to renew your health on a cellular level. The key to achieve this is to remove inflammatory signals.

Factors that accelerate aging and damage your metabolism

It is important to realize that several factors interfere with the normal aging process. Oxidative stress and inflammation are major factors. But hormone disbalance and increased blood sugar values and insulin resistance can also contribute to accelerated aging and damage your metabolism. Certainly, with a disturbance of the immune balance, autoimmune reactions can take place, which also does not help. In addition, pollutants from the environment derange the metabolism due to heavy metals that block important enzymatic reactions. In the minority there are also genetic factors that can interfere with a normal metabolism.

Many of the metabolic changes can lead to chronic inflammation. One source of inflammation can be lipopolysaccharides that stimulate the immune system to start an inflammatory process.

Many conditions are associated with inflammation such as diabetes, obesity, stress, the SAD diet (standard American diet), and liver or kidney damage.

How Metaflammation is developing

Metaflammation can start in the gut with microbiota alterations. The wrong types of bacteria can release lipopolysaccharides, and low grade endotoxemia develops. With obesity inflammatory kinins start circulating in the body. Stress can activate inflammatory substances in the brain and the rest of the body. Major contributors to inflammation in the body come from faulty diets. The Western diet contains too much sugar and refined carbs; it is too high in trans fats and saturated fats. It contains too many artificial additives, preservatives, salt, sweeteners and dyes. And it is too low in nutrients, complex carbs and fiber.

More problems with metaflammation

Kidney and liver illness can contribute to metaflammation. Several diseases come from chronic inflammation, like cardiovascular disease, type 2 diabetes, chronic kidney disease, depression, cancer, dementia, osteoporosis and anemia. Metaflammation alters the methylation patterns, which can slow down your metabolism. Increased blood lipids and chronic inflammation of the blood vessels lead to cardiovascular problems. The liver and kidneys are the major detoxification organs, and their disease leads to more metaflammation. Metaflammation also leads to hormone disbalances, sleep disorders and dysfunction of the immune system. The brain reacts to metaflammation with cognitive dysfunction and mood disorders. Muscle loss (sarcopenia) is another issue, so is osteoporosis. Finally, chronic metaflammation can cause cancer.

Major causes of metaflammation

The three major causes of metaflammation are changes of the gut microbiome, obesity and chronic stress. When the gut bacteria change because of a Western diet, the wrong bacteria release lipopolysaccharides that are absorbed into the blood. The gut barrier is breaking down and a low grade endotoxemia develops. With obesity adipokines, which are inflammatory substances secreted by the fatty tissue, circulate in the blood. Chronic stress activates inflammation in the brain and in the body.

Two major conditions are common with metaflammation: hyperlipidemia (high fat levels in the blood) and hyperglycemia. Both of these conditions change the metabolism and lead to cardiovascular disease (hyperlipidemia) or to type 2 diabetes (hyperglycemia). Both of these metabolic changes lead to one or more of the conditions mentioned above, accelerate the aging process and lead to premature deaths.

Interaction of various organ systems can cause metaflammation

Dr. LaValle stated that it is vital that your hormones stay balanced. With chronic stress cortisol production is high. This causes increased insulin production, reduced thyroid hormone and lowered serotonin and melatonin production in the brain. It also leads to autoimmune antibodies from the immune system and decreased DHEA production in the adrenal glands. In addition, growth hormone production and gonadotropin hormones are slowing down. We already heard that cortisol levels are up. The end result of these hormone changes is that the blood pressure is up and abdominal visceral obesity develops. The brain shows cognitive decline, with memory loss as a result. The bones show osteopenia, osteoporosis and fractures. The muscles shrink due to sarcopenia, frailty is very common. Heart attacks and strokes will develop after many years. The immune system is weak and infections may flare up rapidly. There are also higher death rates with flus.

Other mechanism for pathological changes with hormone disbalances

When Insulin is elevated, inflammatory markers are found in the bloodstream. This elevates the C-reactive protein and leads to damage of the lining of the blood vessels in the body. A combination of insulin resistance and enhanced atherosclerosis increases the danger for heart attacks or strokes significantly.

There is a triangle interaction between the thyroid, the pancreas and the adrenals. Normally the following occurs with normal function. The thyroid increases the metabolism, protein synthesis and the activity of the central nervous system. The pancreas through insulin converts glucose to glycogen in the liver. It also facilitates glucose uptake by body cells. The adrenal hormones are anti-inflammatory, regulate protein, carbohydrate and lipid metabolism and contribute to energy production.

Change of thyroid/pancreas/adrenals triangle when cortisol is elevated

When cortisol is elevated the balance of the thyroid/pancreas/adrenals’ triangle is severely disturbed. Cortisol is high, the T4 to T3 conversion is limited and, in the brain, there is hippocampus atrophy with memory loss and brain fog. The immune system will change with production of inflammatory kinins (IL-6 and TNF alpha). Insulin sensitivity is down, sugar craving up and weight gain develops (central obesity).

Change of thyroid/pancreas/adrenals triangle when the thyroid is depressed

The thyroid activity can be lower because of autoimmune antibodies (Hashimoto’s disease) or because of hypothyroidism developing in older age. This leads to decreased pregnenolone synthesis from cholesterol. As pregnenolone is the precursor for all the steroid hormones, the metabolism slows down profoundly. Mentally there is depressed cognition, memory and mood. The cardiovascular system shows reduced function. In the gut there is reduced gastric motility. The mitochondria, which are tiny energy packages in each cell, are reduced in number, which causes a loss of energy. There is increased oxidative stress, increased lactic acid production and decreased insulin sensitivity.

Cardiovascular disease not just a matter of high cholesterol

Dr. LaValle stressed that a heart attack or stroke is not just a matter of elevated cholesterol. Instead we are looking at a complicated interaction between hypothyroidism, diabetic constellation and inflammatory gut condition. The inflammatory leaky gut syndrome causes autoimmune macrophages and Hashimoto’s disease. The end result is hypothyroidism. The inflammatory kinins (TNF-alpha, IL-6) affect the lining of the blood vessels, which facilitates the development of strokes and heart attacks. You see from this that cardiovascular disease development is a multifactorial process.

Microbiome disruption from drugs

Drugs affecting the intestinal flora are antibiotics, corticosteroids, opioids, antipsychotics, statins, acid suppressing drugs like protein pump inhibitors (PPI’s) and H2-blockers. Other factors are: high sugar intake, pesticides in food, bactericidal chemicals in drinking water, metformin, heavy metals and alcohol overconsumption. Chronic stomach infection with H. pylori, stress and allergies can also interfere with the gut microbiome.

The microbiome disruption affects all facets of metabolism. This means that there can be inhibition of nutrient absorption and this may affect the gut/immune/brain axis. There are negative effects on blood glucose levels and insulin resistance. A disturbance of the sleep pattern may be present. A significant effect on the hormonal balance can occur (thyroid hormones, sex hormones and appetite related hormones). When liver and kidney functions slow down, there is interference of body detoxification.

Dr. LaValle talked more about details regarding the gut-brain-immune pathology. I will not comment on this any further.

Changes of Metabolism by Inflammation

Changes of Metabolism by Inflammation

Conclusion

Dr. LaValle gave an overview in a lecture regarding changes of metabolism by inflammation. This took place at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019.

This article is complex and contains a lot of detail, but there is one simple truth: oxidative stress and inflammation are major factors that influence our health on many parameters and lead to a list of illnesses. They lead to hormone disbalance and increased blood sugars and insulin resistance, which can also contribute to accelerated aging and damage of your metabolism. Dr. LaValle explained how high cortisol from chronic stress can lead to low thyroid hormones and in the brain, there is hippocampus atrophy with memory loss and brain fog. With alterations of the immune system there is production of inflammatory kinins (IL-6 and TNF alpha). Insulin sensitivity is down, sugar craving up and weight gain develops (central obesity). It does not stop there! We put our hope in medications, but the sad truth is that there are

Drugs that change the gut biome

Many drugs that are common also change the gut biome with resulting increased permeability of the gut wall (leaky gut syndrome). This overstimulates the immune system and leads to autoimmune diseases like Crohn’s disease and rheumatoid arthritis. Whenever there is an injury to the gut barrier, the blood brain barrier is following suit. This is how brain disease can develop as a result of a change in the gut biome. Impaired cognition, memory and mood can result from this. Alzheimer’s disease is one of the worst conditions that may be related to a combination of gut inflammation, chronic stress and inflammatory kinins.

Apr
04
2020

Side Effects of the Birth Control Pill

Dr. Jolene Brighten gave a lecture about side effects of the birth control pill. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. Her exact title was “Your Body on Birth Control- What Prescribers Should Know About the Effects of Birth Control on the Female Body”.

Most commonly the oral contraceptive pill is prescribed to prevent pregnancy. But the long-acting reversible contraceptives like the IUD and progestin implants are also popular. Depot Provera, the ring and the patch are the least popular ones.

Why women use the birth control pill

Women age 15 to 49 are often on some form of birth control method. 58% of women who use the birth control pill use it for reasons other than to prevent pregnancy. They use it to control symptoms of various conditions.

  • 31% use it for menstrual cramps
  • 28% want to regulate their periods
  • 14% hope to improve their acne
  • 4% use the pill for menstrual pains associated with endometriosis
  • 11% for other reasons

What the birth control pill does

The birth control pill exerts a negative influence on the hypothalamus and the pituitary gland. This is called “functional hypothalamic amenorrhea”. The birth control pill is not suitable to treat polycystic ovarian syndrome. Symptoms of bleeding may improve for 3 months, but after that the original symptoms return. Thyroid disease that may be present needs separate investigations.

The hormones that are part of the birth control pill are synthetic hormones. They do not quite fit the body’s hormone receptors. For instance, the progestins, artificial analogues of progesterone behave like estrogens, not progesterone. This causes clotting problems cancers of the uterus, breasts and cervix. It can also cause heart attacks and strokes.

List of side effects of the birth control pill 

From depression to liver health

The list of side effects of the birth control pill (BCP) is long. The BCP can worsen symptoms of depression and anxiety. The deeper the depression is, the higher is the risk for suicide. There is increased risk of hair loss. The BCP depletes nutrients in the body that the thyroid gland needs to produce thyroid hormones. This can result in hypothyroidism.

It also increases thyroid binding globulin, a protein in the blood that binds thyroid hormones. As a result, there are fewer thyroid hormones available to the body cells. Breasts may become tender and enlarged after the start of the BCP. In some women with fibrocystic disease of the breasts the BCP may improve her cyclical breast changes. The BCP changes the liver both structurally and genetically. As a result, there is a higher risk of developing benign liver tumors and liver cancer.

From gallstones to blood clots

Women with a history of gallstones may experience faster gallstone formation on the BCP. The pill also can elevate your blood pressure. You should have blood pressure checks from time to time to prevent a stroke. Weight gain is common on the BCP. However, some women experience weight loss. Usually the BCP is 99% effective for the prevention of pregnancy. Pain from heavy periods or menstrual cramps are often relieved by the BCP. There is an increased risk to develop diabetes, because insulin resistance is gets worse in patients on the BCP. In postmenopausal women on HRT there is an even higher risk of developing diabetes. Blot clots are a common side effect of the BCP. Being a smoker, having a heart or liver condition, a history of genetic risk of blood clots, having migraines with an aura or being overweight are all additional risk factors for developing blood clots.

From effects on the brain to cancer risks

The BCP can change brain function and structure. This may lead to a different mate selection and production of neurotoxins. Some women get relief from hormonal headaches; but others experience exacerbations of migraines and headaches. In some women acne improves on the BCP; in others acne gets worse. When it comes to stress, some women experience an altered hypothalamic-pituitary-adrenal gland response from the BCP. The BCP reduces some cancer risks, like the risk of ovarian, uterine and colorectal cancer. But the risk for breast cancer, brain cancer and liver cancer are higher. The BCP increases gut permeability, leads to leaky gut syndrome and the disruption of the microbiome. There is often overgrowth of yeast in the gut. In addition, people with a genetic predisposition for autoimmune disease of the gut can develop immune diseases. Multiple studies have shown malabsorption of vitamins, minerals and antioxidants when on the BCP.

From vaginal yeast infections to osteoporosis and autoimmune diseases

Many women develop vaginal yeast infections. Women on the BCP often complain about low or a lack of libido. There can be vaginal dryness and pain with sex.

Teenage women on the BCP often develop decreased bone density. Synthetic hormones lack the specificity to the natural hormone receptors, which leads to decreased bone density. On the other hand, bioidentical estrogen and bioidentical progesterone will indeed build up bone mass. In the past it was thought that hormones would be good for the bones and this is still true with the use of bioidentical hormones.

A number of autoimmune diseases have been identified to be directly related to the use of the BCP. These are Crohn’s disease, multiple sclerosis, lupus, interstitial cystitis and ulcerative colitis.

Synthetic hormones will always have side effects

The body is a complex organism with various hormone receptors built into its cells. In order to be able to cash in on patented modified hormones Big Pharma introduced progestins to replace natural progesterone and various synthetic estrogen products to replace natural estradiol. However, the Women’s Health Initiative has shown  in 2002  that these artificial hormones produced heart attacks, strokes, blood clots, colorectal and endometrial cancer and hip fractures. There was an increase of mortality of 15% over 5.2 years compared to controls who did not take artificial hormones within the same timeframe.

Bioidentical hormones have a perfect fit to the natural hormone receptors

In contrast, when bioidentical hormones are given in menopause, there is a 10 to 15 year extension of life expectancy and researchers did not see any of the above mentioned side effects that were noted with synthetic hormones. Many people in Europe have elected to stick to bioidentical hormones for decades; they did not use the synthetic hormones. As a result, there are good data going back to the 1960’s about the safety of bioidentical hormones. In this study several thousand postmenopausal women were followed for 9 years or more and showed no increase in the rate of heart attacks or any cancer. Their postmenopausal symptoms were optimally controlled. I conclude from this that bioidentical hormone replacement in menopause will protect the women from missing hormones safely. There are no side effects and for this reason the bioidentical hormone replacement should become the standard of care.

Side Effects of the Birth Control Pill

Side Effects of the Birth Control Pill

Conclusion

Synthetic hormones have a long list of devastating side effects. Yet, Big Pharma managed to influence general practitioners and gynecologist to prescribe them to postmenopausal women. The Women’s Health Initiative has changed everything. The promise was that synthetic hormones would show heart-protective effects, cancer protective effects and healing effects for osteoporosis. These have been empty promises! None of this occurred with synthetic hormones- to the contrary! Many physicians are now prescribing bioidentical hormone replacement for women in menopause.

No good alternative for teenage girls

However, for teenage girls there is no good alternative for the traditional birth control pill, even though the catalogue of side effects is of serious concern. One compromise is to limit prescribing the birth control pill for up to 5 years only and then switch to several years of a copper T or other intrauterine device (IUD). Suicide in teenage girls on the BCP is of real concern. Despite the list of side effects many doctors continue to prescribe synthetic hormones for decades to the same patients, who trust that it will benefit them. In time patients will know about the side effects, and unfortunately many will experience them. As a result, it is only a matter of time, till this will be exposed as malpractice!

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