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 2011, which describes research from Poland and other countries 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.

Jun
06
2020

Adequate Vitamin D Level Strengthens the Immune System

The Covid-19 coronavirus crisis is teaching us that an adequate vitamin D level strengthens the immune system.

When we age, our resistance to infections weakens, but this may be because our immune system needs more vitamin D3. I have reviewed the super powers of vitamin D3 before in 2014. In the past the thought was that the human body would need only 400 IU of vitamin D3 every day to cure rickets. And these were the daily vitamin D3 recommendations from medical authorities for several decades. Gradually it became known that for cancer prevention, infection prevention, cardiovascular illness prevention and for diabetes prevention much higher doses of vitamin D3 were necessary. As pointed out in the previous link, almost 50% of the world population is deficient in vitamin D. This is due to a lack of exposure to sunlight and due to inadequate supplementation with vitamin D3.

History of vitamin D

Dr. Adolf Windaus received the Nobel prize for chemistry in 1928. It was to acknowledge “… his studies on the constitution of the sterols and their connection with vitamins”. His work involved the metabolism of vitamin D and the precursors of vitamin D.

Rickets

As the above link shows, rachitic children were treated since the mid 1800’s with cod liver oil and since the early 1900’s also with ultraviolet light. But we know now that 400 IU of vitamin D3 per day is just enough to cure rachitic children, but it is not enough to strengthen the immune system to fight influenza viruses or the Covid-19 coronavirus. I will discuss further below what vitamin D blood levels are important to achieve a healthy state of the immune system.

Adequate vitamin D level strengthens the immune system

The immune system is very complicated and consists of many cell types that interact with each other and the rest of the body. It is important to recognize that the innate immune system immediately inactivates intruding viruses. But the vitamin D blood concentration has to be high enough. The acquired immunity consists of antibodies that are produced by B cells. The antibodies were produced during prior infections that you have survived and you are now immune to. However, other antibodies that circulate in your blood may have originated from vaccines you received in the past (whooping cough, measles, tetanus, diphtheria etc.). With the Covid-19 coronavirus it is the innate immunity that plays the biggest role until a vaccine will be found in the future.

Vitamin D is a hormone

This 2013 paper explains that vitamin D is a hormone that stimulates its own vitamin D receptor. This is a nuclear receptor that has close relations to the cell DNA and can stimulate more than 900 polypeptides. They are messenger molecules that are involved in a variety of physiological functions. One of the key functions is the immune system. This link explains that T cells that have vitamin D receptors can develop into cytotoxic T cells (also known as “killer T cells”). They are important in fighting cancer, but also parasites.

The key is that the hormone vitamin D can release more than 100 polypeptides that have the power to fight virus attacks including the Covid-19 coronavirus.

Three mechanisms how vitamin D works against the virus

The researchers outlined 3 mechanisms of how vitamin D works:

  • Maintaining tight epithelial junctions making it more difficult for the Covid-19 coronavirus to penetrate.
  • “Killing enveloped viruses through induction of cathelicidin and defensins.” These powerful antiviral polypeptides can kill viruses that have invaded the blood stream within 1 to 2 days.
  • “…And reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia.” It is people who get the viral pneumonia that are at a high risk of death. By bringing the 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.

Two polypeptides, cathelicidin and defensins

Again, I like to emphasize that it is not vitamin D that has a direct effect on the virus. It is two polypeptides, cathelicidin and defensins, which are powerful antiviral polypeptides, that are released by vitamin D.

They can kill viruses that have invaded the blood stream and can eliminate the cytokine storm. This all happens very fast, within only 1 to 2 days. But you have to have an adequate vitamin blood level for this to occur (about 50-80 ng/mL).

Sources of vitamin D

First of all, vitamin D is readily absorbed from food. But there are not many foods that contain enough vitamin D for the immune system. The ones that contain vitamin D are as follows:

  • “Fatty fish, like tuna, mackerel, and salmon.
  • Foods fortified with vitamin D, like some dairy products, orange juice, soy milk, and cereals.
  • Beef liver.
  • Cheese
  • Egg yolks. “

Sun induced amount of vitamin D

Secondly, vitamin D can be synthesized in the skin from exposure to sunlight. But for this to happen all the necessary enzymes need to be present.  This link explains that many older people above the age of 65 have low vitamin D blood levels because of a lack of sun exposure and a lack of cutaneous synthesis because of enzyme issues.

Vitamin D supplements

The most reliable source of vitamin D are vitamin D3 supplements. When people supplement with the same dose of vitamin D3 there will be people who get higher vitamin D blood levels than others, as absorption in the gut is different for different people.  The ones who have relatively low vitamin D blood levels are often called “slow vitamin D absorbers”. But when the vitamin D3 dosage is increased even those people will reach the recommended high normal range (50-80 ng/mL).

Vitamin D blood level

The vitamin D blood test has the scientific name “25-hydroxy vitamin D level”. This is now the recognized gold standard for determining who is deficient or has normal levels with respect to vitamin D. The following 2013 publication has studied the vitamin D level of 1,470 healthy Swiss men and women, 60 years or older. Vitamin D levels were classified as severely deficient when the level was below 10 ng/mL. The vitamin D level was deficient between 10 and 20 ng/mL. The level was insufficient when between 21 and 29 ng/mL. A level above 30 ng/mL is normal.

8 % of the subjects were severely insufficient and 66% had insufficient vitamin D levels. Only 26.1% of the subjects had normal levels. Over 50% of healthy older Swiss (above the age of 70) had insufficient vitamin D levels.

Which vitamin D level is safe and which is not?

A peer-reviewed publication of the effects of vitamin D in health and disease contains 269 references.

What vitamin D level is optimal? This question was reviewed in this paper.

  • Below 15 ng/mL the immune system is paralyzed
  • With a level above 30 ng/mL the immune system is working
  • A level of 50-80 ng/mL has the immune system working optimally
  • Above 150 ng/mL toxic vitamin D levels start
  • With 300 ng/mL severe toxicity begins

Vitamin D toxicity

It is only with high levels of vitamin D (more than 150 ng/mL) that you have to worry about high calcium levels in the blood or kidney stones (toxic levels). But the key is to not exceed 80 ng/mL regarding the vitamin D blood level. This gives you a lot of flexibility before you reach toxic levels (above 150 ng/mL). For those who want more information, here is a thorough, peer reviewed publication about vitamin D toxicity with 59 references.

Vitamin D supplement compliance

The question is why not more people take adequate vitamin D3 supplements.  We know that vitamin D can prevent so many chronic diseases including serious viral infections. The answer is complex, but it includes a fear of the population of vitamin toxicity (kidney stone and high calcium levels). However, as pointed out before, this occurs only above a vitamin D level of 150 ng/mL. With proper vitamin D blood level monitoring you never reach toxic levels of vitamin D.

Denial

Denial likely is another major factor. People feel that if they have a balanced diet, they would be protected from vitamin D insufficiency. As pointed out before this is a grave error to think as our food does not contain sufficient vitamin D to strengthen our immune system.

False security with low doses of vitamin D

Finally, there are people who think that low doses of vitamin D, like 1000 IU of vitamin D daily, would be enough. But it is not enough. This is why testing vitamin D blood levels is so important. It is a reality check. The blood level must be in the high normal range (50-80 ng/mL). At this level the immune system functions optimally.

Compliance issues

In this context there was an interesting study done by LifeExtension, a company that publishes monthly health magazines. In this study the company examined the vitamin D blood levels of LifeExtension members. They are the ones who should be knowledgeable in how important it is to have good, preventative vitamin D blood levels. The study showed that 38% of the vitamin D test results were less than 30 ng/mL. In addition, 69% of the vitamin D tests were less than 40 ng/mL. Finally, 85% of the vitamin D test results were less than 50 ng/mL. What this means is that LifeExtension members were non-compliant when it came to taking regular adequate vitamin D3 doses. This resulted in levels that were too low for the majority to protect them from the Covid-19 coronavirus.

Covid-19 coronavirus infections and vitamin D blood level

There is a tight relationship between vitamin D blood levels and the strength of the immune system. Essentially, coronavirus mortality measures who is vitamin D deficient. Without enough vitamin D on board the virus penetrates into the blood stream and penetrates the lining of the respiratory tract. Next the cytokine storm develops, which leads to viral pneumonia. Higher doses of vitamin D3 will mitigate the course of Covid-19 coronavirus.

Adequate Vitamin D Level Strengthens the Immune System

Adequate Vitamin D Level Strengthens the Immune System

Conclusion

The Covid-19 coronavirus pandemic has taught us how important an intact immune system is to survive the virus when you get it. We do know for some time how closely related a good vitamin D level is with the functioning of the immune system. I have reviewed here what a desirable vitamin D level is and how we can achieve this with oral vitamin D3 supplements. The goal is to achieve a vitamin D level in the upper range of normal (50-80 ng/mL). With a level like this the virus cannot penetrate the mucous membranes of the respiratory tract and even if it did, it cannot produce a cytokine storm in the blood that would lead to the deadly viral pneumonia or to blood clots. When the virus invades the bloodstream, vitamin D releases powerful antiviral polypeptides that can kill viruses within 1 to 2 days.

Literature

Here are some peer-reviewed publications on vitamin D:

 

Apr
25
2020

Exosomes can Regenerate Your Stem Cells

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. In essence, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. His original topic was: “Placental MSC Exosomes for Longevity and Chronic Disease”. Notably, MSC stands for “mesenchymal stem cells”. Dr. Spiel recommended this website to look at applications of exosome therapy.

Essentially, what scientist found is that certain factors from stem cells can activate your own stem cells to regenerate tissues that grow old. These factors are messenger RNA (mRNA) and micro RNA (miRNA), which come as tiny particles of 40‐100 nm.

Advantages of administering exosomes

To emphasize, exosomes can be given systemically as infusion, and they can regenerate your stem cells, if they are in need of treatment. They cross the blood brain barrier, so it is possible to treat brain diseases. That is to say, there is no first-pass removal in the lungs as it is with mesenchymal stem cells (MSC). The potency is related to the age of the donor and his/her stem cells. Notably, exosomes are easy to store, freeze and administer.

Exosomes influence the growth of target cells and promote regeneration. In addition, exosomes stimulate immunomodulation and have anti-inflammatory and anti-fibrotic properties. To clarify, the only limitations are that the strength of the exosomes is related to the age of the blood donor. The exosome fraction comes from mesenchymal stem cells. That is to say, it circulates in the plasma portion of the blood, which is obtained by spinning blood cells down in a centrifuge. To emphasize, exosomes can regenerate your stem cells.

Applications of exosomes for various clinical conditions

Joint inflammation

Mesenchymal stem cells are useful to treat arthritis. But it is important to realize that exosomes from mesenchymal stem cells are doing the same by stimulating the body’s own stem cells situated in the joints. In fact, several target cells have been identified that are stimulated by exosomes. These are chondrocytes, chondrocyte progenitor cells, cartilage-derived stem cells and synovium‐resident multipotent progenitor cells. In addition, other target cells are osteoblasts and osteoclasts in resident MSC within the subchondral bone and chondrogenic cells in the knee joint.

Disc degeneration  

Degenerative intervertebral discs respond to exosome treatments. The IL1 beta cytokine is involved in intervertebral disc degeneration. Exosomes inactivate these cytokines and have antioxidant and anti-inflammatory effects. Exosomes are not all the same. Different sub-fractions were isolated that have anti-inflammatory, immune-stimulating, antioxidant and other effects on the body.

Aging research

Researchers were able to pinpoint aging to various factors that contribute to premature aging. To clarify, when there is a decrease of catabolic processes and an increase of anabolic processes, an older person can combat premature senescence. Another key point, aging is also linked to redox homeostasis. Simply put, oxygenation processes in the body need to be balanced by reduction processes. This keeps the body in a healthy state. ADP/NADH production can be stimulated by exosomes.

Longevity comes from good lifestyles

With the use of exosomes, the aging process slows down, as oxidative stress is neutralized, damaged mitochondria are removed and cellular debris as well. That is to say, this improves inflammation and premature aging.

As has been noted, in the past 200 years life expectancy has doubled in most countries. 4 areas where longevity is particularly common are: Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica and Loma Linda, USA. Only 7% of longevity stems from genetic factors, the rest is from lifestyles we adopt. In the final analysis, people who die prematurely followed a very poor lifestyle causing them to develop diseases, which ultimately killed them.

Clinical diseases from aging

Ultimately, advanced aging puts you at risk of getting cardiovascular disease (heart attacks and strokes), cancer and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease). From the third decade onwards, there is the risk of bone loss, which causes osteoporosis. As has been noted, loss of cartilage causes osteoarthritis. Loss of muscle strength and muscle mass is called sarcopenia. With aging there is often an accumulation of abdominal fat. Hormones are disbalanced. Blood pressure is often elevated and blood lipids as well. Insulin resistance can develop and the blood vessels become stiffer. This causes heart attacks and strokes.

The details of the aging process are much more complicated than originally thought of. There is a combination of aging of the DNA, mitochondrial aging, stem cell exhaustion and a change of intercellular communication due to dysregulated endocrine signalling. In addition, there is a decline of the immune system and epigenetic factors that can turn off longevity genes.

Oxidative stress as a cause of premature aging

Dr. Spiel pointed out that reactive oxidative species (also known as free radicals) cause damage to mitochondria and mitochondrial DNA. But we need the energy from the mitochondria for a comfortable life. In essence, antioxidants can neutralize free radicals. Age-related conditions due to oxidative stress are: cardiovascular disease, chronic kidney disease and type 2 diabetes, chronic obstructive pulmonary disease, cancer, neurodegenerative disease, frailty and sarcopenia. Surely, both reactive oxygen and reactive nitrogen are free radicals. They have one or more unpaired electrons and all aerobic body cells produce them. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development the diseases just mentioned.

Antioxidants help to prevent diseases

But antioxidants can contain these free radicals in various ways. The body has five built-in enzymatic ways to protect itself and five non-enzymatic ways (bilirubin, vitamin E, beta-carotene, albumin and uric acid). In addition, there are antioxidants that a person can take as supplements to inactivate RONS. These are: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine.

Without control of the oxidative stress RONS can lead to cellular senescence and chronic inflammation. This leads to a vicious cycle where chronic oxidative stress and inflammation feed on each other leading to premature diseases.

Causation of several diseases

As we age, the body reduces the inborn antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Before we can understand how to live longer, we need to be aware what happens in various health scenarios as follows.

  • The lack of inborn antioxidant enzymes leads to vascular endothelial dysfunction, high blood pressure and premature hardening of the arteries. This can become a precursor to heart attacks and strokes.
  • Elevated blood sugar in the case of type 2 diabetes leads to increased sugar concentration of body cells and formation of free radicals.
  • Oxidants from cigarette smoke activate macrophages and epithelial cells to produce inflammatory cytokines. Continued smoking releases proteases in the process that break down connective tissue and cause emphysema and COPD.

There are more diseases

  • Chronic kidney disease comes from oxidative stress affecting the filter units of the kidney, called glomeruli. With a lack of blood supply to the kidneys secondary high blood pressure develops and endothelial dysfunction. It also leads to chronic inflammation.
  • In the brain oxidative stress leads to cognitive impairment and dementia.
  • Oxidative stress and chronic inflammation are important ingredients for the development of cancer. RONS and cytokines release NF-kB, which activates cancer genes. RONS can also directly attack the DNA of cells and cause cancer through carcinogenesis.
  • Sarcopenia and frailty come from the action of RONS on the skeletal muscles. In old age there are less inborn antioxidants available. This leads to decreased muscle quantity or sarcopenia. Eventually frailty results with the risk of falls and fractures. 

Preventative measures for slowing the aging process

There is a number of steps that in combination help to slow the aging process.

  • A Mediterranean diet combined with a fasting mimicking diet or other calorie restricted diet
  • Regular physical activity
  • Cognitive training
  • Vitamin D3 supplementation
  • Reducing your risk to develop vascular disease
  • Certain drugs turn on the longevity gene (metformin, rifampin)
  • Spiel warned that due to limited compliance and variable response these steps alone may not be enough to prevent age-related problems

How to live longer

It is important to recognize the importance of antioxidants to counteract the development of these diseases. As already mentioned, the following counter the effect of free radicals: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine. Mesenchymal stem cells can also stop the action of free radicals. In addition, exosomes, which  are products of mesenchymal stem cells can do the same. Mitochondria, the power houses within the cells, create energy, but also release free radicals. In his clinic Dr. Spiel administers intravenous exosomes to counter the oxidative stress. Numerous studies linked mitochondrial dysfunction to various age-related diseases. There are markers in blood tests that the physician can order to analyze malfunctions in the body. Dr. Spiel showed 4 slides that contained a lot of medical information that is too technical. I omitted it for this review.

Intravenous infusions of exosomes

The important thing to remember is that epigenetics can be changed by exosome infusion and lifestyle changes mentioned above. Dr. Spiel said that generally he uses 15 ml of exosomes by intravenous infusion every 12 weeks for longevity and performance enhancement. This treats conditions like infertility, osteoporosis, osteopenia, heart, liver and kidney weaknesses. Here is the dosing for intravenous exosomes by weight:

20-50 lb: 5 ml; 50-90 lb: 10ml; more than 90 lb: 15 ml; more than 220 lb: 20 ml. Unfortunately, one exosome treatment costs between 500.00 and 922.00 USD, an amount that most people cannot afford.

Contraindication to the use of stem cells or exosome therapy

It is important to realize that a person who has cancer should not receive either mesenchymal stem cells or exosomes. Indeed, exosomes do not differentiate between cancer cells and healthy cells, but stimulate cell division. For the same reason people with myeloproliferative disease (sickle cell anemia, bone marrow dysplasia) should also not receive exosomes. To clarify, other conditions where the physician will not order exosomes are primary pulmonary hypertension, acute bacterial infection or an immune-compromised state. In addition, macular degeneration with neovascularization is also a condition where the health professional does not administer exosomes.

Exosomes can Regenerate Your Stem Cells

Exosomes can Regenerate Your Stem Cells

Conclusion

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. Specifically, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. Dr. Spiel explained how disease processes age our organs. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development of diseases. This involves the mitochondria in the cells as well. The good news is that a healthy lifestyle can counter these damaging processes to a certain extent. But it takes another step to re-establish the balance of our cells, exosome infusions. Exosomes are tiny particles that are shed by stem cells and that circulate in the blood. They can reenergize stem cells that are ailing to become functional again.

Expensive exosome infusions

He recommended an infusion with exosomes every 12 weeks for maintenance of good health and as a “fountain of youth”. Obviously, there are some limitations. As mentioned, it is not suitable for all patients, like cancer patients, patients with sickle cell anemia, acute bacterial infections or pulmonary hypertension. In addition, it is also not a treatment which many patients will seek out as the cost is prohibitive. One exosome treatment cost between 500.00 and 922.00 USD, an amount that most people cannot afford.

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.

Jan
18
2020

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Whoever treats a child’s cold must know that antibiotics in children can trigger allergies and asthma later in life. This is what a study released on Dec. 20, 2019 has shown. The researchers examined records of 798,426 children seen at the Department of Defense TRICARE health care program. They were born between 2001 and 2013. The physicians examined the children later again for allergies. The more antibiotics the children received in childhood, the more severe the youngster’s allergies were later in life.

More details about the study

The researchers found that different antibiotic types had different risks to cause allergic reactions later in life.

  • Penicillin: 1.3-fold risk
  • Penicillin with a β-lactamase inhibitor: 1.21-fold risk
  • Macrolides: 1.28-fold risk)
  • Cephalosporins: 1.19-fold risk
  • Sulfonamides: 1.06-fold risk

The type of allergies that the children developed later in life were food allergies, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis or contact dermatitis. The researchers stressed that their finding indicated an association between taking antibiotics and developing allergies later. It was not a causal relationship.

Food allergies in more detail

Anaphylaxis

This allergic condition is an emergency and requires immediate medical attention. It can occur when the body overreacts to peanuts or penicillin. It can occur with foods, and the reaction is sudden and severe. The symptoms may include wheezing, shortness of breath, a cough or tightness in the throat. The blood pressure may drop leading to light-headedness and passing out. The skin may show hives, swelling and a rash. The digestive symptoms may be nausea, vomiting and diarrhea. Other symptoms may involve itching eyes, headaches, anxiety and a feeling of impending doom.

Asthma

Airborne grass and tree pollens, mold spores and dust, but also peanuts and other strong allergens can trigger an asthma attack. The symptoms can be shortness of breath, wheezing, tightness in the chest, trouble falling asleep because of coughing and being short of breath.

Atopic dermatitis (eczema)

Often atopic dermatitis starts below the age of 5 and can last until late adolescence or adulthood. The symptoms can be dry skin, itching red patches of skin and thickened scaly skin. Allergic contact dermatitis is common in patients with atopic dermatitis.

Allergic rhinitis

People who suffer from allergic rhinitis are sensitized to particles in the air like grass and tree pollen, molds or cigarette fumes. They develop a stuffy nose, itching and watery eyes, sneezing and swelling around the eye lids. An allergist can do skin scratch tests to find out what the patient is allergic to. Subsequently, if the allergies are strong, the allergist may decide to start desensitization with allergy shots.

Allergic conjunctivitis

A person who is allergic to pollen and mold spores will react to this when in contact with it and often develop allergic conjunctivitis. An eye inflammation will develop within a few minutes leading to swelling of the conjunctiva around the eye ball. The eyes end up looking red, itching, burning and being watery.

Contact dermatitis

Contact dermatitis develops when your body brushes against a substance that your body has been previously sensitized to. One example is poison ivy contact dermatitis. But many other substances can cause similar reactions: solvents, shampoos, permanent wave solutions and rubbing alcohol. In addition, plants, bleach and detergents, fertilizers, pesticides and airborne substances (sawdust, dust from woollen materials) can also do the same.

The gut biome

Dr. Purvi Parikh is an allergist and immunologist at NYU Langone Health in New York. She was not involved in the study, but commented to it as follows: “One reason why there might be an association is because our microbiome, specifically in our gut, plays a large role in our immune systems. Antibiotics are known to not only kill the bacteria that are causing an infection, but also ‘good’ bacteria our immune system needs to protect us from developing allergic or autoimmune diseases.”

Treat bacterial infections with antibiotics when needed

She went on to say: “Overall, parents should know that this study shows an association but not necessarily cause and effect. So, if a child truly needs an antibiotic for a bacterial infection, they should not withhold it due to fear of allergic disease. However, on that same note, one should not over use antibiotics if not needed – for a virus or a cold – as there may be long-term consequences from over use.”

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Antibiotics In Children Can Trigger Allergies And Asthma Later In Life

Conclusion

A new study showed that antibiotics can cause allergies and asthma later in life. The reason seems to be that our gut bacteria react to the antibiotics and the gut dysbiosis (disbalance of the gut bacteria) persists, when the antibiotics have been discontinued. The immune system can then react in ways that are detrimental to the child and adolescent. Anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis or contact dermatitis are all different manifestations of allergies that can develop later in life. At this point we only know that there is an association between these allergic manifestations and the antibiotic use in childhood. More clinical trials will need to shed a light on what causes allergies in some children, but not in others.

Dec
07
2019

The Use Of Oncolytic Viruses For Cancer Treatment

In the first place, preliminary experiments indicate that the use of oncolytic viruses for cancer treatment may become a reality. There are several lines of research that point to the fact that oncolytic viruses can make a difference in treating incurable cancer patients.

Notably, Canadian researchers had reported in 2011 that oncolytic viruses created by genetically modifying smallpox vaccine viruses would enter tumor cells of patients, but not damage normal cells. Specifically, a high percentage of the end stage patients responded with tumor regression.

Shortly after Mayo Clinic physicians were desperate when two patients with end stage multiple myeloma, a vicious bone tumor, did not respond to chemotherapy. Significantly, they tried something unconventional: high doses of the measles vaccine in an attempt to stimulate the immune system. Here is an overview from 2014 that shows that many different cancers respond to various immunological approaches.

Study from Holland regarding end stage melanoma patients

Here is a small human study involving end-stage melanoma patients treated with the oncolytic virus T-VEC combined with pembrolizumab (Keytruda). It is important to realize that Keytruda helps to reactivate a T-cell response to the cancer cells. In this case the cancer cells absorb the oncolytic virus (T-VEC), but it leaves normal cells alone. Inside the cancer cells the oncolytic virus multiplies and destroys the cancer cells. In this 2017 study 21 patients with terminal, nonresectable melanoma received treatment with T-VEC and Keytruda. Specifically, 62% of the patients showed an objective response to the treatment. Moreover, 33% fulfilled the criteria of an immune-related response. In the past terminal patients like these had a 0% response to radiotherapy or chemotherapy.

History of research about oncolytic viruses

To begin with, in 1912 rabies virus treatment against cervical carcinoma was a first attempt to treat cancer. Researchers conducted many experiments between 1950 and 1970 with wild type or naturally attenuated viruses. This included, for example, hepatitis A and B viruses. In 1991 cancer researchers developed the concept of genetically engineered oncolytic viruses. Today cancer researchers know that the protection mechanisms in most cancer cells have deficiencies. This involves the interferon‐beta signal pathway. Having said this, there is an opportunity to let oncolytic viruses destroy cancer cells, while normal cells stay unaffected. An oncolytic virus that cancer experts use in human cancers is the genetically engineered herpes simplex virus type I (HSV‐1). Others that cancer researchers developed have strange names like T‐Vec, G47∆, JX594, CG0070 and Reolysin.

Various cancers that researchers treated with oncolytic viruses

Here are a few examples of cancers where researchers used oncolytic viruses to exert a significant therapeutic effect.

Glioblastoma

Glioblastoma is a deadly form of a brain tumor, which has a high rate of mortality. Researchers have investigated new avenues to treat this cancer. Researchers tested the genetically engineered dendritic vaccine. Initial clinical trials showed significant effectiveness compared to non-treated controls. In a large phase 3 clinical trial 331 patients with newly diagnosed glioblastoma received treatment at the time of neurosurgery with dendritic cell vaccine. 30.2% of the patients were still alive and doing well after 3 1/3 years. Without the added vaccination procedure all of these patients would have died in the past because of the aggressiveness of the glioblastoma.

Multiple myeloma

Researchers could cure multiple myeloma and other cancers by using the measles vaccine. Here is a report by the popular press about two women who had multiple myeloma. One woman got cured by high doses of a measles vaccine. The other women experienced some relief, but did not survive.

This publication explains that oncolytic viral therapy of cancer is a lot more complicated than originally thought.

Prostate cancer

Researchers found that vaccines against prostate cancer were effective with the combination of oncolytic virus therapy with regular anti-cancer treatments. But oncolytic virus therapy alone has a poorer prognosis than a combination of chemotherapy or radiotherapy with oncolytic virus therapy.

Cervical cancer

The high-risk HPV16 strain most often causes cervical cancer. The HPV (human papilloma virus) vaccine targets patients with previous exposure to HPV16. However, researchers have noticed that in some cases a phenomenon called the “HPV immune escape” has allowed in some vaccinated women to still develop cervical cancer. Now a group of researchers are investigating how the vaccine could be improved by finding out how the immune system is being tricked in these cases by the HPV virus to bypass the antibodies of the vaccine.

Pancreatic cancer

This cancer is very difficult to detect in the early stages, and as a result the outlook for chemotherapy or radiotherapy is extremely poor. Researchers have used several approaches as an alternative to conventional therapy. Immunotherapy is an option. Mayo clinic researchers have already announced that the measles vaccine approach will likely be applicable to pancreatic cancer treatment as well in the near future. However, other clinical trials are on the way to use alternative vaccination procedures.

Neuroblastoma, glioma and melanoma

This link shows that the FDA has accepted engineered oncolytic herpes virus (engineered to secrete GM-CSF) as a treatment against melanoma. Other approaches with engineered bacteria can affect neuroblastoma and glioma.

Survival data using oncolytic viruses for cancer treatment

Cancer researchers have completed a number of smaller clinical trials at this point. One of them describes end stage melanoma (stage III and IV) where the only treatment was with the oncolytic virus T‐Vec. The overall response rate compared to the control, which was only 5.7%, the experimental group with T-Vec was 26.4%. This is considered a good response rate given that we are dealing with end stage melanoma patients.

Mechanism of how oncolytic viruses stimulate the immune system to overcome various cancers

As mentioned above oncolytic viruses multiply in the cancer, once they have been incorporated. This leads to cancer cell death. It exposes the dead cancer tissue to the immune system. What helps in the process is that inhibitory proteins from the cancer cells that used to inhibit the immune system are no longer provided by the dead cancer cells. The end result is that the immune system mounts a formidable response against the cancer cells through killer T cells. This immune response also affects remote metastases of the same histological cancer type. This review article summarizes how oncolytic viruses work for cancer cell destruction and how this method can be combined with other treatment modalities.

The Use Of Oncolytic Viruses For Cancer Treatment

The Use Of Oncolytic Viruses For Cancer Treatment

Conclusion

Currently various cancer centers are involved with clinical trials in humans to test the power of oncolytic viruses. What cancer researchers have learnt is that oncolytic viruses are a useful tool to kill cancer cells. But the immune system of cancer patients is in a suppressed state. Pembrolizumab (Keytruda) is a medication that will stimulate the immune system by stimulating killer T cells to destroy cancer cells. The combined effect of killing cancer cells with oncolytic viruses and stimulating the immune system is the big news. This has been the breakthrough that cancer researchers have been waiting for. Now several clinical trials are on the way where survival rates for cancer patients given the new combination therapy are assessed.

Oncolytic virus therapy here to stay

It is a treatment which is no longer a thought model with animal experiments. Well known medical centers are using it in patients, and as the results become more obvious, it will very likely become a new treatment modality for cancer.

Mar
23
2019

Immune System Can Trigger chronic fatigue syndrome

A study from February 2019 stated that the immune system can trigger chronic fatigue syndrome. Specifically, researchers observed that interferon treatment in hepatitis C patients could lead to chronic fatigue syndrome in 33% of patients.

Interferon treated hepatitis C patients can develop chronic fatigue syndrome

In this cased 54 patients with hepatitis C received treatment with Interferon. 18 of them (33%) developed chronic fatigue syndrome, which persisted. 57 control did not develop it. With this in mind, patients were examined at baseline, during the 6 months to 1-year Interferon treatment and 6 months following the end of the treatment.

It was noted that baseline interleukin levels (IL-6 and IL-10) were higher in the fatigued patients. Interferon treatment worsened the interleukin levels, and the interleukin levels stayed high from then on. Moreover, symptoms of pain from chronic fatigue syndrome also stayed with the patients after the treatment had ended.

Patients with chronic fatigue syndrome have a viral illness in the beginning

The lead researcher, Carmine Pariante, professor of biological psychiatry at King’s College London, noted the following. Before patients come down with chronic fatigue syndrome they frequently have a major infection or a flu virus. This certainly mobilizes an interferon response from their immune system. Professor Pariante said that it is the overstimulation of the immune system that leads to an overproduction of interferon, which likely causes chronic fatigue syndrome.

In the US an estimated 836,000 to 2.5 million Americans present with chronic fatigue syndrome according to the CDC.

The observation described above confirms the theory that a chronic stimulation of the immune system likely underlies the development of chronic fatigue syndrome. It was the patients undergoing treatment for hepatitis C with interferon, persistently high IL-6 and IL-10 levels together with pain symptoms that caused chronic fatigue syndrome.

Example of a patient with chronic fatigue syndrome

A 19-year old patient with chronic fatigue syndrome (CFS) explained that her CFS kept her hostage inside. When she gets dressed it feels like there is a blackness going over her eyes. She cannot lead a conversation or speak as she has absolutely no energy. So, the only thing she can do is to lie down and exist. Her pain and fatigue is  debilitating. She feels that her body and brain are unable to recover from even the smallest effort. About 25% of CFS cases are severe cases. This means that they are house bound, bedridden and wheelchair dependent.

Immune System Can Trigger chronic fatigue syndrome

Immune System Can Trigger chronic fatigue syndrome

Conclusion

The cause of chronic fatigue syndrome (CFS) has been a mystery for a long time. But a new UK research study has shed some light on a hyperactive immune system that may cause CFS. The research team found that 33% of patients with hepatitis C who received treatment with interferon developed CFS. When lab tests analyzed their blood values, they had developed high interleukin levels (IL-6 and IL-10). This was a sign for an overstimulation of the immune system. Other patients who did not develop CFS normalized their interleukin levels. The control patients had no changes in interleukins.

Overactive immune system can trigger chronic fatigue syndrome

The researchers are of the opinion that an overactive immune system is responsible for the development of CFS. Chronic fatigue syndrome is a devastating multi-system chronic disease with pain and weakness. A significant number of patients suffer from permanent disability. The researchers hope that with more research they may be able to find a solution and treatment protocol. Presently no form of treatment is available.

Sep
29
2018

No Amount Of Alcohol Is Good

New research, more extensive than previous research has shown that no amount of alcohol is good.

This is completely against the widespread belief that moderate consumption of alcohol would prevent heart disease.

Specifically, previous research had shown the following: one glass of alcohol per day for women and 2 glasses of alcohol for men was reportedly make us live longer.

New research with larger population numbers

But a new study involving much larger population groups, all ages, and drinkers versus non-drinkers came to a different conclusion. It concluded that the previous recommendation was based on only heart attack rates, but excluded other causes of sudden death like heart failure, a rupture of the aorta (aneurysm), high blood pressure that kills (fatal hypertensive disease) and strokes. With the compilation of all these cardiovascular diseases, the statistics suddenly started to look different. Now even small amounts of alcohol killed. What is worse, there was clear evidence that binge drinkers have much worse survival statistics than moderate drinkers. When you drink according to the American Heart Association’s recommendation, you drink smaller amounts of alcohol daily.

Binge drinking

But many of us like to live it up on weekends or whenever there are friends over who also like a few drinks. This binge drinking habit lowers the life expectancy by an average of 10 years. It does so because the list of complications I mentioned above. In addition there are alcoholic liver cirrhosis, pancreatitis and various cancers that shorten your life.

Global health study

The funders of this global health study was the Bill and Melinda Gates Foundation, and it looked at the burden that alcohol puts on 195 countries. The original study appeared in the Lancet. The combined study population was 28 million individuals. There were 649,000 cases of various deaths due to alcohol. Here is a summary of the abbreviated outcome of the global health study. As you can see from this, there is no safe level of alcohol consumption as even small amounts of alcohol over a long period of time lead to significant damage in the body. You can prevent heart attacks to a certain extent. But instead people die from a ruptured aorta, from strokes or from heart failure. The leading cause of death for men and women age 15 to 49 worldwide was alcohol. It accounted for almost 1 in 10 deaths.

Some alcohol-related statistics

The following were the observations in the study.

  • Over 300 disabilities and diseases were directly related to alcohol consumption. The findings were collected in 195 countries, classified by age and sex. The data was gathered between 1990 and 2016.
  • Globally, 2.4 billion people drink alcohol. 25% are women who consume 0.73 drinks on average each day, 39% are men drinking 1.7 drinks a day.
  • Denmark, Norway and Germany drank the most alcohol globally.
  • For ages 50 and up the leading causes of death were: road injuries, suicides and tuberculosis.

More statistics

  • Most deaths caused by alcohol came from cardiovascular disease and cancer for all countries.
  • When you look only at drinkers, the standard recommendation of the American Heart Association regarding low alcohol consumption seems true. But the new study compared non-drinkers with drinkers. From this it is clear that even one drink a day has a risk of premature death.
  • At the age of 40 cutting down long-term alcohol use will add 1 to 2 years of life expectancy.
  • For all ages 2.8 million people die globally every year from alcohol related diseases.
  • Half of the world does not drink at all. This means that the ones, who drink, consume double as much as the statistics show.
  • Americans prefer beer. They drink about 27 gallons of beer, 2.6 gallons of wine and 2.2 gallons of spirits per adult/year.

Common clinical conditions from alcohol consumption

Binge drinking is the consumption of 5 drinks or more in an evening for men or 4 drinks for women. The CDC is concerned about binge drinking, because of its association with significant organ damages. There are 4 major concerns regarding these effects. Heart disease and cancer; diabetes; memory loss and appearance. In the following I will zero in on these alcohol-related conditions. 

Heart disease

As this article pointed out above, there is a very limited protective effect, but mostly in above 55-year-old women who drink in moderation (1 glass of alcohol; per day). They have some protection from developing heart attacks, because their LDL cholesterol gets lowered and their clotting system is influenced in positive ways. But 6% of breast cancer in women is due to the effect of alcohol consumption, which is a downfall. For both men and women binge drinking is what kills. Binge drinkers who drink more than 100 grams of alcohol per week (more than 7 drinks in the US) experience increased deaths. The causes are heart failure, strokes, fatal hypertensive disease and fatal aortic aneurysm, where the main artery bursts. Apart from that alcohol-related pancreatitis and liver cirrhosis can kill as well.

Cancer

A relatively new finding is that alcohol has a close relationship to causing various cancers. Alcohol weakens the immune system. Also, alcohol has a negative influence on the bacterial composition, the microbiome in our digestive tract. This can be a cause for colon cancer. Liver cancer, mouth cancer and breast cancer also has a direct relationship to increased alcohol consumption. Esophageal cancer and laryngeal cancer are also related to alcohol consumption.

Diabetes

Alcohol can stimulate the pancreas to release insulin, which may give you hypoglycemic attacks. As alcohol contains empty calories, over the course of several years alcohol consumption can add to your weight, causing obesity and type 2 diabetes. As diabetes has detrimental effects on the heart and blood vessels, this mixed with alcohol consumption, can worsen cardiovascular disease thus increasing the risk for heart attacks and strokes.

Memory loss

In the beginning of chronic alcohol consumption you may enjoy the relaxing effect of alcohol. This is merely the toxic effect of alcohol on brain cells. Alcohol has the effect of inhibiting brain cells, which makes you feel relaxed, super-sociable and even silly. In reality you are starting to loose control. After several years of this effect you are left with feelings of anxiety, depression and anger. This is when trouble starts to occur. People out of control are more likely to get into fights and get injured or killed. People can develop blackouts where they do not remember parts of the evening or an entire event. Memory loss is starting. The hippocampus is an important part of the brain that is involved in processing short- term memory into long-term memory. A form of dementia can occur that was brought on by chronic alcohol overconsumption.

Appearance

Alcohol dries out the skin cells and body cells. The face gets wrinkles. Your skin looks parched and gives you the appearance of a prematurely aged person. Alcohol can interfere with your sleep and when you have a lack of it you end up with dark circles around your eyes as well as puffy eyes. It does not make for a good picture, whether it happens inside the body or on your skin!

No Amount Of Alcohol Is Good

No Amount Of Alcohol Is Good

Conclusion

A new study that was larger and more comprehensive than any previous study has exposed the myth that one drink for women and two drinks for men would protect you from heart disease. It may protect you from heart attacks, but it definitely does nothing to protect you from other heart conditions. There is also sudden death from heart failure, a rupture of the aorta (aneurysm), high blood pressure that kills (fatal hypertensive disease) and stroke. When you factor all that in as well, even your low, moderate alcohol consumption has health risks. The global health study, funded by the Bill and Melinda Gates Foundation looked at the burden that alcohol puts on 195 countries. The combined study population was 28 million individuals.

Alcohol related deaths and diseases

649, 000 registered cases of various deaths occurred due to alcohol. This included deaths from traffic accidents, injuries, cancer, heart disease and suicide. This global study compared the life expectancy and disease frequencies of alcohol-consuming people with non-alcohol consuming people. It concluded that non-alcohol consuming people live on an average up to 10 years longer than their alcohol-consuming counterparts. No studies up to now have been that comprehensive. The results from twenty-eight million people speak for themselves, and the death statistics are clear. It is worthwhile to look at the details and draw your own conclusion.

Jul
27
2018

Modified Poliovirus Effective Against Brain Cancer

A clinical trial found modified poliovirus effective against brain cancer. 61 patients with glioblastoma, the most deadly brain cancer there is, have been enrolled in this trial since 2012.

Glioblastoma treatment with genetically modified poliovirus

Dr. Gromeier, one of the lead cancer researchers at Duke University, Durham, North Carolina has done animal experiments. Unlike poliovirus, he found that genetically modified poliovirus was harmless for the central nervous system and yet he found modified poliovirus effective against brain cancer. This genetically modified poliovirus was attacking glioblastoma cells in cell cultures and in human brains. Dr. Annick Desjardins, a co-author of the study explained that the researchers had to take a piece of RNA away from the poliovirus and replace it with a neutral piece of RNA. This way it is still attracted to the numerous poliovirus receptors, which are expressed on many human cancers. The genetic sequence that allows poliovirus to reproduce in normal cells was taken out with the genetic modification. An inert RNA piece from the rhinovirus, the cause of the common cold was replacing this.

Effect of the genetically modified poliovirus

This way the modified poliovirus is no longer destroying nervous tissue. But the virus can still multiply in the glioblastoma cells, release toxins and kill these cancer cells.

Dr. Bryan Choi is a fellow in the Cellular Immunotherapy Program at Massachusetts General Hospital Cancer Center. He also works at the Department of Neurosurgery at Harvard Medical School. Although he was not part of this study he stated that this study was a giant step forward. “Perhaps the most promising aspect is the ability for this genetically modified virus to not only directly kill brain cancer cells, but to release tumor antigens,” Choi said. Antigens are toxic substances that stimulate the immune system to mount an immune response against the cancer. This immunotherapeutic effect is an important aspect of this new treatment modality.

Some human statistics of the pilot study showing modified poliovirus effective against brain cancer

Here are the highlights.

  1. 21% of the poliovirus patients are still alive three years after treatment; this compares to just 4% of the control patients who only received chemotherapy.
  2. The average survival time for the 61 patients who have received the genetically modified poliovirus therapy was 12.5 months. This compares with 11.3 months for a control group of matched patients. These had received standard treatment (chemotherapy).
  3. Some patients were much better responders than others. A 20-year old man a 60-year-old man survived 69 months (nearly 6 years). They are still alive today. This was unthinkable of in the past for patients with glioblastoma.

Repeat modified poliovirus therapy for glioblastoma recurrence

Dr. Darell D. Bigner, a co-author of the study, a professor of pathology and emeritus director observed the following. Some patients experienced initial reduction of the glioblastoma, and when the cancer came back they received repeat modified poliovirus treatments. To the surprise of the investigators the tumors shrank again and again. This was never the case with conventional chemotherapy. Once a glioblastoma is chemotherapy-resistant, chemotherapy will not work again.

Experience with modified poliovirus therapy

  1. In this trial treatment for glioblastoma started with implanting a catheter right into the center of the glioblastoma. An infusion of the engineered poliovirus followed, a process that could take up to 6.5 hours. Removal of the catheter was next.
  2. In the beginning researchers used higher doses of the genetically engineered poliovirus. Some people developed severe inflammation causing seizures, which needed treatment. Confusion and language difficulties were also side effects. Others developed pronounced nausea. The researchers decided to lower the dosage of the genetically engineered poliovirus, and the patients still had good clinical results.
  3. “We are presently enrolling in a phase 2 trial combining the genetically modified poliovirus with one dose of chemotherapy,” Desjardins said. “We are also enrolling in a trial for pediatric brain tumor patients.” In addition studies using genetically engineered poliovirus against breast cancer and against skin cancer are also in the planning stage.
  4. There are other new approaches where there the doctor injects the photosensitizer indocyanine into breast cancer tissue. Next the doctor points a laser beam near the infrared frequency of light to the cancer area. You find details about this procedure here.
Modified Poliovirus Effective Against Brain Cancer

Modified Poliovirus Effective Against Brain Cancer

Conclusion

A new approach to treating glioblastoma, one of the deadliest brain cancers, has shown promising results. A genetically engineered poliovirus is no longer making the person sick with polio, but instead destroys glioblastoma cells and prolongs patients’ lives. Some patients lived up to 6 years while controls lived less than one year. The effect of this new treatment occurs from the release of toxins within the glioblastoma cancer. This leads to cancer cell death and the release of these toxins. The immune system receives stimulation to recognize and destroy the remaining glioblastoma cells. At this point the basic steps of this new therapy are in place.

Future direction of research

But the same method will one day likely be in use for other cancers. There are plans for new clinical trials to examine this further. The researchers also want to test cure rates of a combination of chemotherapy and genetically engineered poliovirus therapy. This will answer the question whether the combination treatment will be better than genetically engineered poliovirus therapy alone.