Mortality Archives

Dec

2022

Certain Probiotics Are not as Harmless as Thought

By Ray Schilling | diet, Mortality, Nutrition

Recently a medical publication stated that certain probiotics are not as harmless as thought. Researchers presented their findings at the American College of Chest Physicians 2022 Annual Meeting. 23,533 ICU admissions to a number of hospitals in Colorado over a 5-year period were the data base for this study. There was a clear relationship between taking probiotic powder and the fact that some of these gut bacteria make their way into the blood stream. This condition has the name of bacteremia. Although bacteremia is uncommon (only 0.37%), the mortality rate for those who developed probiotic-related bacteremia was 25.6%. This is about twofold greater than the 13.5% mortality rate of controls who did not take probiotics. The risk ratio was 2.23-fold higher for ICU patients who ingested probiotics versus those who did not. What killed the patients who took probiotics were the gut bacteria that entered into their blood stream.

Discussion of “certain probiotics are not as harmless as thought”

Physicians often recommend probiotics as tools to improve the gut bacterial flora. Unfortunately, there is a lack of research in this area. There is no hard evidence that probiotics are beneficial for irritable bowel syndrome or ulcerative colitis. There is also no hard evidence that a previously deranged bowel flora would transition into a healthy bowel flora. On the other hand, we also know that fermented vegetable products like kimchi or sauerkraut also have beneficial bacteria in them that can support your bowel flora. One of the problems is the concentration of probiotic supplements. They come in 80 billion, 100 billion and higher bacteria counts per capsule. It is possible that some of these bacteria find their way through cracks in the lining of the bowel into the blood stream.

Patients outside the ICU setting

ICU patients are vulnerable and often have immune deficiencies. It may be that in regular patients outside the ICU probiotics may not be that problematical. But nobody knows for sure as there are no studies available that support this. The practice of recommending probiotics over sauerkraut and kimchi is simply based on hearsay.

Risk assessment necessary

Once probiotic bacteria are in the blood, they can freely travel through the circulatory system into the rest of the body. This is how septicemia develops. This is a dangerous condition, which does not always respond to antibiotics. It is because of this why there is such a high mortality rate as I mentioned above.

As mentioned, there is a lack of good evidence for the beneficial effects of probiotics. However, there is a risk of bacteremia in ICU patients. This warrants a risk assessment whether or not we should supplement our food intake with probiotic supplements or not. Fermented vegetable products like kimchi or sauerkraut are not as highly concentrated as probiotic capsules. Nevertheless, they are useful supplements that you can mix into salads or use as a side dish to your main meal. Until the time that more evidence is available about probiotics it is best to not take probiotics. Replace it with kimchi and sauerkraut.

Fermented foods versus probiotics

Fermented foods like sauerkraut and kimchi can help the gut balance its bacteria. But there are other fermented foods that can help your gut: yoghurt and kefir, which is a fermented probiotic milk drink. Other fermented foods are tempeh, miso, kombucha and pickles. The good bacteria outnumber the bad bacteria when you consume fermented foods regularly. Kimchi does not only provide healthy gut digestion, but it also prevents the formation of toxins from unhealthy gut bacteria. These toxins can damage the kidneys. So, kimchi prevents kidney damage.

Sauerkraut and kimchi are fermented foods that have been consumed for hundreds of years. They provide nutrients, vitamins and minerals along with plenty of fiber and probiotic bacteria to support the gut. I consider kimchi and sauerkraut the better probiotic than probiotic pills, which likely are too concentrated.

Certain Probiotics Are not as Harmless as Thought

Conclusion

Recently a publication reported about 23,533 ICU admissions to various hospitals in Colorado over a 5-year period. These patients took daily probiotics. There was a clear relationship between taking probiotic powder and the fact that some of these gut bacteria made their way into the blood stream. Unfortunately, there was a mortality risk of 25.6% for probiotic-related bacteremia. Controls not taking probiotics had a much lower mortality rate of 13.5%. The investigators concluded that a literature search failed to support beneficial effects of the probiotic powder. The evidence was rather weak and did not justify the risk of probiotic-bacteremia. In contrast, natural probiotics in the form of fermented foods like kimchi and sauerkraut have been around for centuries and are known to be safe. I see no reason why we should take a risk with probiotic pills when there are many alternative fermented foods.

Mar

2022

Adolescents’ Lifestyles Are Linked to Faster Aging in Adulthood

By Ray Schilling | diet, fasting mimicking diet, Mental Health, mitochondria, Mortality, Obesity, Smoking, Vitamins and supplements

A longitudinal study found that adolescents’ lifestyles are linked to faster aging in adulthood. The study started with a baseline examination in a group of adolescents around the age of 15. 30 years later doctors examined the same individuals again. The researchers found that smokers, obese people and people with untreated emotional problems were aging faster than controls who did not have these problems. CNN discussed this study as well. A fourth condition, asthma was also included in the study. Indeed, adolescents who suffered from asthma in their mid-teens were not more biologically aged at age 45 when compared to controls who never had asthma. The authors concluded that treated asthma did not prematurely age a person. However, lifestyle habits like smoking, excessive weight and untreated mental illness contributed to accelerated aging.

Does having a healthy lifestyle lower your risk of developing medical conditions and diseases?

It must be remembered that anti-aging medicine is watching out for new treatments that can prolong life. However, this is not just one “breakthrough”, but rather a number of factors that in combination lead to longevity.

Resveratrol

Resveratrol, the supplement from red grape skin can stimulate your mitochondria metabolism. Exercise more and regularly as this will also stimulate your mitochondria to multiply similar to the effects of PQQ, a supplement. I take 500 mg of resveratrol concentrate once daily.

Exercise regularly

The first thing to remember is that regular exercise will prevent about 50% of chronic diseases (diabetes, heart failure, arthritis). Consequently, this prolongs life: Lack of exercise is a major cause of chronic diseases.

Replacing missing hormones with bioidentical hormones

When you enter menopause or andropause replace missing hormones with bioidentical hormones. This will add 10–15 years of good life. This information comes from the anti-aging medicine circles and European studies of women on bioidentical hormone replacement. Here is a more conservative opinion from a US review: Counseling Postmenopausal Women about Bioidentical Hormones: Ten Discussion Points for Practicing Physicians.

Abandon sugar, starchy foods

Starchy foods (potatoes, pasta, rice, pastries and bread) and processed food accelerate aging. Avoid these foods for a healthier heart – Harvard Health. Many studies have confirmed that a Mediterranean diet is anti-inflammatory and prevents premature aging.

Are you deficient in human growth hormone?

Find out whether you are deficient in human growth hormone or not by taking an IGF-1 blood test. Dr. Hertoghe, an endocrinologist from Belgium said at various anti-aging conferences that HGH by itself prolongs life by about 15 to 20 years or more. I am deficient in HGH and I am injecting HGH myself regularly. My anti-aging physician orders my IGF-1 level three to four times per year to monitor the right dosage of HGH replacement. But it is crucial that the physician supervise the patient. This involves giving the patient only minimal amounts of HGH, which keeps IGF-1 levels in the high normal range. This is also re-emphasized in this review: Growth Hormone and Aging: Updated Review. When you overdose HGH, you lose all of the beneficial effects that HGH replacement brings.

Fasting mimicking diet (FMD)

Fasting for Longevity: 9 Questions for Dr. Valter D. Longo. When you consume only 500 to 600 calories daily for 5 days out of every month you are stimulating your telomeres (the caps on your chromosomes) to grow a little bit longer. Longer telomeres translate into longer life expectancy. In addition, your stem cells anywhere in your body also undergo stimulation. Here is more information: fasting mimicking diet for 5 days every month.

Lifestyle factors

It is best not to smoke. Keep your body mass index in the 21.0 to 22.0 range. Get enough sleep (7–8 hours every night). Use a form of relaxing exercise (yoga, self-hypnosis, meditation, Tai-Chi). This will keep the stress hormone cortisol under control; if it is constantly high from ongoing stress, it leads to premature deaths. The Science of STRESS – SLMA

Take key vitamins and minerals

When you take key vitamins and minerals every day you can add another 5 to 10 years of disease-free life to your life expectancy. Ray Schilling’s answer to Is taking vitamin supplements helpful or quackery?

All of these factors taken together help you to not age prematurely. A healthy lifestyle elongates your telomeres, which prolongs your life without diseases. It also prevents heart attacks and strokes, which again prolongs your life. And a healthy lifestyle prevents Alzheimer’s disease, so you can turn old and not have to worry about memory loss. I cannot overemphasize how important a healthy lifestyle is!

Conclusion

As summarized above, a recent study going on for about 30 years showed that premature biological aging occurs in adolescents who smoked, were obese or had untreated mental illness. On the other hand, treated asthmatics did not show this biological aging effect. I summarized what factors contribute to slowing down aging. It is a combination of proper diet, regular exercise, hormone replacement as you age and taking some supplements. One key to slower aging is to be aware of how important a healthy lifestyle is for you.

The section about having a healthy lifestyle was published previously here: Ray Schilling’s answer to What are the most exciting breakthroughs in longevity research?

Feb

2022

Stimulating the Immune System Leads to Better Cancer Survival

By Ray Schilling | immune system, Mortality, Nutrition, omega-3 fatty acids, Vitamins and supplements

Notably, conventional medicine has nothing to offer against advanced cancer, but stimulating the immune system leads to better cancer survival.

Dr. Hoffer’s survival experiment with incurable cancer patients

The following is a description of a 9-year follow-up of incurable cancer patients. They were given supplements known to stimulate the immune system and their survival rates were recorded. Ref. 1 describes the experiment by Dr. Hoffer, the father of orthomolecular medicine. It is important to realize that this is a branch of medicine that uses large doses of vitamins and minerals. This can rectify metabolic changes in various diseases. Dr. Hoffer treated 131 advanced cancer patients between 1976 and 1988 with a mixture of mega vitamins and minerals. There was a control group (not taking any supplements) and the experimental group.

Results regarding incurable cancer patients over 9 years

In fact, the results of this 9-year follow up study are depicted in the image below. The Y-axis represents the % of survival (at the zero point of time 100 % of each group were alive), the X-axis shows the time of survival in years. To clarify, the group of cancer patients taking meta vitamins is depicted with orange columns, the control group with blue columns. At 7 years of follow-up none of the controls survived. Explicitly, there was an 8-year survival advantage of the mega vitamin group versus the control group (control group 28% survival at year 1 of follow-up, mega vitamin group 34% survival at year 9 of follow-up).

List of supplements patients in the experimental group took daily

With this in mind, here is the detailed list of the supplements that Dr. Hoffer instructed his experimental group cancer patients to take daily.

Vitamin C, 10,000 to 40,000 mg orally daily; B3 vitamin (niacin or niacinamide) 300 to 3,000 mg; vitamin B6 (pyridoxine) 200 to 300 mg; folic acid 1 to 30 mg; vitamin E succinate 400 to 1,200 IU; Coenzyme Q10 300 to 600 mg; selenium 200 to 1,000 micrograms daily; zinc 25 to 100 mg; calcium and magnesium supplement (2:1 ratio); mixed carotenoids as carrot juice; multivitamins and minerals.

Ref. 1 (page 347) explains that in this case the Mayo Clinic did a study where they “duplicated” Dr. Hoffer’s study by using only high doses of vitamin C. It is important to realize that they failed to show any cancer fighting effect. However, they neglected to include all of the other cancer fighting supplements listed above. Vitamin C is an antioxidant that stimulates the immune system partially, but does not fight cancer by itself.

Strengthen your immune system by taking 14 supplements

In the following I like to share what I found when I investigated what supplements are necessary for optimal immune responses. The Linus Pauling Institute wrote a detailed review of the literature on the topic regarding “Immunity in depth”. It is published by the Oregon State University.

Essentially, there were 14 supplements that are listed below that were critical for the immune system to fully respond.

In the following I listed the 14 supplements, but, if they were present in Dr. Hoffer’s clinical cancer trial, I inserted them right after each item. 8 out of 14 supplements overlapped between Dr. Hoffer’s supplements and the supplements necessary to stimulate the immune system. There is a total overlap of 57%.

Vitamin A: mixed carotenoids as carrot juice
Vitamin B6: vitamin B6 (pyridoxine) 200 to 300 mg
B12 vitamin
Folic acid: folic acid 1 to 30 mg
Vitamin C: Vitamin C, 10,000 to 40,000 mg
D3 vitamin: Ray Schilling’s answer to Can vitamin D lower your risk of CoVID-19?
E vitamin: vitamin E succinate 400 to 1,200 IU
Iron
Copper
Selenium: selenium 200 to 1,000 micrograms daily
Magnesium: calcium and magnesium supplement (2:1 ratio)
Zinc: zinc 25 to 100 mg
Omega-3 fatty acids
Probiotics

Dr. Hoffer’s additional vitamins and minerals were: multivitamins and minerals; Coenzyme Q10 300 to 600 mg; and vitamin B3 (niacin or niacinamide) 300 to 3,000 mg. The 5 items that were missing in Dr. Hoffer’s clinical trial were vitamin B12, vitamin D3, iron, copper and probiotics.

Discussion

During the Covid epidemic the importance of the immune system for survival became very clear. One of the current mysteries regarding the immune system is why some people develop only very mild symptoms with Covid, while others get deadly sick. The other question has been around much longer: when it comes to cancer survival, why are there long-term survivors with some advanced cancers, but others perish. I believe that the key is how well the immune system is functioning. Dr. Hoffer’s end stage cancer survival trial achieved a 34% survival of cancer patients at year 9 of the clinical trial. At that time 100% of the control group were dead. Indeed, this is a remarkable finding.

Supplementation with vitamins and minerals prolonged cancer survival

The only difference was the supplementation with 57% of the Oregon University list of supplements necessary to stimulate the immune system. One of the more important supplements, namely vitamin D3 was not even included and yet there was a 34% survival in the experimental group after 9 years. Conventional medicine concentrates on surgery, radiotherapy and chemotherapy as the major therapeutic tools to fight cancer, but there is rarely if at all the mention of supplements. Ordinarily end stage cancer patients live on average 3 to 6 months.

Mayo Clinic’s attempt to jeopardize Dr. Hoffer’s cancer survival findings

When the Mayo Clinic got wind of Dr. Hoffer’s clinical trial they quickly attempted to “duplicate” the findings, but they left everything out except mega doses of vitamin C. Then they proclaimed that Dr. Hoffer’s data were flawed. In reality they failed to duplicate the findings, because they were poor copycats. Vitamin C is a powerful antioxidant, but it won’t be of help to cancer patients on its own. As the Oregon State University publication showed, there are 14 supplement that are necessary to work in symbiosis to stimulate to immune system to fight cancer.

It is significant that there was a 57% congruence between Dr. Hoffer’s list and the Oregon State University list of supplements to stimulate the immune system. Future cancer clinicians should revisit Dr. Hoffer’s clinical findings and finetune them to increase the long-term cancer survival times. For one, the supplement list should include vitamin D3, probiotics and omega-3 fatty acids.

Stimulating the Immune System Leads to Better Cancer Survival. (Image source).

Conclusion

Dr. Hoffer did a clinical trial that lasted 9 years between 1976 and 1988. Some patients were recruited earlier than others, but all were observed for a total of 9 years. He treated end-stage cancer patients with vitamin and mineral supplements. A control group that did not take any supplements was included in the trial. After 9 years the experimental mega vitamin group had a survival of 34%. None of the controls that did not take any supplements were still alive after 7 years. The literature by the Oregon University showed that 14 supplements are necessary to support the immune system. Dr. Hoffer’s clinical trial used 57% of these supplements. I am postulating that the good results of the mega vitamin group with respect to cancer survival likely comes from a strengthening of the immune system with the supplements.

The future of cancer treatments

Cancer treatments are entering a new phase where with the help of multiple treatment modalities combined (photodynamic therapy or PDT, immunostimulation, oxygen therapy and low-dose laser activated chemotherapy) it is now possible to cure many cancers that were untreatable in the past. The tunnel vision approach of conventional oncology with only a combination of surgery, chemotherapy and radiotherapy is obsolete for cases where cancer has metastasized. At this point the methods described here are promising, but have to be still considered experimental until larger clinical trials confirm Dr. Hoffer’s findings.

Reference

Ref. 1: Andrew W. Saul, PhD: “The Orthomolecular Treatment of Chronic disease”, Basic Health Publications Inc., Laguna Beach, CA 92651, 2014.

Dr. Hoffer’s cancer survivor experiment (part of the above) was previously published here.

Jan

2022

Booster Vaccinations Against Covid-19 Variants are Very Effective

By Ray Schilling | immune system, Infectious Disease, Mortality, vaccinations, Vitamins and supplements

This article will inform you that booster vaccinations against Covid-19 variants are very effective. Studies in patients from Israel who received a third vaccination (booster shot) showed much less omicron infections. Researchers compared the number of omicron infections in patients with only two shots and another group with three vaccinations (regular vaccination+booster shot). In patients who had booster shots infection rates were 10-fold lower.

Antibody titers matter

What seems to be happening is that antibody titers against Covid-19 rise after each vaccination providing more and more protection against the virus. Patients in this study had 90% less Covid-19 infections after a booster (=3 shots with the Pfizer vaccine) when compared to a double vaccinated group. Researchers compared nursing home residents who were previously sick with Covid-19 versus those who were not. They did PCR tests in April or June of 2020 to identify that there was a past history of Covid-19 infection with a subsequent recovery. Within 3 weeks after one dosage of an anti Covid-19 vaccine their antibody tests rose to above 40,000 arbitrary units (AU) per milliliter. The threshold was 50 AU to be positive.

The Israeli experience

An Israeli study was published on Nov. 5, 2021. Researcher determined the antibody titers in blood samples after anti-Covid-19 vaccinations. They investigated the antibody titers after two vaccinations and compared them to antibody titers after three vaccinations. The latter vaccination is often referred to as a booster shot. 97 study participants had blood tests taken after two vaccinations with an average antibody titer of 440 AU/mL. Any value above 50 was considered to be seropositive. However, 10 to 19 days following the booster shot the average antibody titer rose to 25,468 AU/mL, which is an enormous increase.

Older age patients and kidney transplant patients responding to booster shots

After two vaccinations there were lower antibody titers in older patients aged 67-74 compared to patients age 18-55. But after the booster shot this age difference was no longer present. On the sideline the researcher also followed a group of kidney transplant patients. These would be considered to be patients with a chronic disease. Initially, following the standard two vaccinations these patients were negative for an antibody response. But after the third vaccination (booster shot) 49% of the kidney transplant patients showed a positive antibody test.

Antibody titers in patients with past natural Covid-19 infection

Researchers also investigated the antibody response of patients against the spike protein of Covid-19. A publication showed after a natural Covid-19 infection plus one vaccination of the Pfizer/Moderna vaccine the antibody titer was 20,120 arbitrary units per milliliter. In contrast, the other group consisted of two vaccinations of the Pfizer/Moderna vaccine. They had antibody titers of 22,639 arbitrary units per milliliter. This was not significantly different from the first group. It also did not matter whether in the first group the prior natural Covid-19 infection was 1, 2, 3 or more months before the first vaccination with the Pfizer vaccine.

Discussion

New information emerged since the beginning of the Covid-19 pandemic. There was confusion about how often people would need a vaccination before they would be immune against Covid-19. After one vaccination with the Pfizer/Moderna vaccine the protection rate against Covid-19 is around 50%. After two vaccinations the protection rate is around 95%. Experience with the booster vaccination teaches us that the protection rate is almost 100%. There was no difference between the antibody response of the group with the age of 18-55 and the group with the age of 67-74 after the third shot (booster shot).

But there is a proviso: the immune system must be capable of full activation to produce enough antibodies by the B cells. B cells are the lymphocytes that traveled through the bone marrow after which they started producing antibodies against viruses. As the results with the kidney transplant patients showed, only 49% of them were able to produce positive antibody titers. The reason for this is that kidney transplant patients must take immune system suppressing drugs to avoid a rejection of the kidney transplant.

Other reason for poor antibody response

Other patients with chronic diseases (diabetics, autoimmune disease patients etc.) and patients older than 60 can also have a weaker immune system. Part of this can be when one or more of the 14 supplements is missing that are necessary for a full immune response. It is important before the Covid-19 vaccinations to take the 14 necessary supplements to get a good antibody response.

Booster Vaccinations Against Covid-19 Variants are Very Effective

Conclusion

Several studies showed that the antibody response after the anti-Covid-19 vaccine increases significantly. The measurements revealed that after two injections the antibody titer was 440 AU/mL. After the third (booster) injection the antibody titer increased significantly to 25,468 AU/mL. This explains why some people after one or two vaccinations still may be able to come down with Covid-19, but after the additional booster injection (3^rd vaccination) the immune response in terms of antibody production is 58-fold higher than after the second vaccination. This gives the immune system a full response. Some patients with chronic diseases (obesity, diabetes, autoimmune diseases etc.) will have certain immune deficiencies. This explains a higher infection rate among these people as well as a higher mortality rate. We all can take the booster vaccine against Covid-19. In addition, we can take the 14 immune supplements to stimulate our immune system.

Oct

2021

Acetaminophen Damages the Fetus

By Ray Schilling | Autism, Drugs, kidney disease, Mortality, neurological disease, toxins

Many women take acetaminophen when pregnant, but acetaminophen damages the fetus. It is important to realize that acetaminophen is a common over-the-counter pain reliever. In addition, it is also often combined with codeine as headache pills. Acetaminophen goes under these brand names: Tylenol, Tylenol Arthritis Pain, Tylenol Ext and Little Fevers Children’s Fever/Pain Reliever. The international name of acetaminophen is the name “paracetamol”.

An international group of 13 scientists are calling health care professionals to limit the use of acetaminophen in pregnant women. CNN reported about this under this link.

These scientists published an article in the medical journal Nature on the dangers of paracetamol use in pregnancy. Specifically, they said that acetaminophen can alter fetal development, which includes reproductive, neurodevelopmental and urogenital disorders.

History of acetaminophen

The chemical name for acetaminophen is N-acetyl-p-aminophenol. Acetaminophen is simply a shortened version of that chemical name. It was introduced in the US in 1955 as Tylenol® and in the United Kingdom in 1956 under the brand name Panadol®. In particular, acetaminophen was recommended to control fevers and to help with pain control.

In the 1960’s the Swiss watch industry provided workers who complained of headaches freely with acetaminophen. With this in mind, within a few years studies showed that many of these women who took a lot of this medication developed kidney problems. This led to an increase of the creatinine level in the blood. The kidney damage from acetaminophen was dubbed “phenacetin kidneys”. Outside of the US acetaminophen has the name phenacetin. Many of these patients subsequently had to receive dialysis and later kidney transplants.

Acetaminophen toxicity

The recommended dose of acetaminophen is 650 mg to 1000 mg 4-6 times daily, not to exceed 4 grams/day. The therapeutic window for this drug is very narrow, because 7.5 grams per day to 10 grams per day are already toxic. For children the dose is 15 mg/kg every 6 hours to a maximum of 60 mg/kg per day.

The other known toxicity concerns liver function. This article about Tylenol toxicity explains this in more detail.

Many people do not know about the limit for the over-the-counter acetaminophen and take too much for a fever or a painful condition. Just because a drug is available over the counter does not mean that it is harmless. If you don’t watch for toxic levels, you could end up dead or find yourself waiting for a liver transplant.

New evidence that acetaminophen damages the fetus

91 scientists from Australia, Brazil, Canada, Europe, Israel, Scotland, the UK and US have signed a declaration. In it they ask pregnant women not to take acetaminophen “unless its use is medically indicated”. Among the reasons for the declaration is that acetaminophen certainly can cause neural tube defects and cardiovascular disorders in fetuses. Pediatrician Dr. Leonardo Trasande, director of environmental pediatrics at NYU Langone Health, did not partake in this research. He has done safety studies on acetaminophen and pointed out the similarity in chemical structure between acetaminophen and phthalates. Like phthalates acetaminophen disrupts the reproductive development in animals and humans.

Evidence for neurodevelopmental disruption

Dr. Shanna Swan, a professor of environmental medicine at the Icahn School of Medicine at Mount Sinai in New York said: “There’s enough evidence to find increased risk of undescended testicles and a shortening of the anogenital distance, which is a predictive of later decreased sperm count and decreased fertility. We also see impaired ovarian function which has consequences for later fertility, although females have been less studied.”

The conditions that relate to acetaminophen toxicity were attention deficit hyperactivity disorder (ADHD), behavior abnormalities and autism spectrum disorders. In addition, language delays, conduct disorders and decreased IQ were due to neurodevelopment disruption from acetaminophen toxicity.

Mechanism of action of acetaminophen and side effects

Acetaminophen has been on the market for over 60 years. But scientists still don’t know exactly how it acts in the body to help control pain and reduce fever. There is a consensus that acetaminophen acts on the central nervous system inhibiting the synthesis of prostaglandins. These biological compounds have a leading role in causing fever, pain and inflammation. But the scientific proof for this consensus is still outstanding.

Side effects

There are a multitude of side effects that can occur with the use of acetaminophen. Common side effects are hives, itching, swelling of the mouth and throat and tingling in the mouth or throat. Other side effects are swelling in the face or hands, breathing difficulties or chest tightness. Acetaminophen can cause a loss of appetite, nausea and vomiting. Severe stomach pain can be another symptom of acetaminophen side effects. As you can see from the above link there are many more known side effects of acetaminophen.

Acetaminophen Damages the Fetus

Conclusion

Acetaminophen (=paracetamol, phenacetin) is a popular over-the-counter fever and pain remedy. But a narrow therapeutic width can cause serious overdoses where both the liver and the kidneys suffer irreparable damage. When people unknowingly take too much acetaminophen, they enter into the toxic range. This can cause disability and death. Kidney damage from acetaminophen became known as “phenacetin kidneys” already in the 1960’s in female workers of the watch industry in Switzerland. They developed headaches from constantly working with magnifying glasses and had free access to acetaminophen provided by the employer. Later, in North America liver disease developed when patients overdosed with over-the-counter acetaminophen for fever and pain control.

Interruption of fetal development from exposure of the fetus to acetaminophen

At the present time the focus is on newer findings of researchers. They noticed that exposure of pregnant women to acetaminophen damages the fetus. This results in undescended testicles and a shortening of the anogenital distance which is a predictive of later decreased sperm count and decreased fertility. These are findings for males. Findings in females are less studied at this point in time. Dr. Leonardo Trasande pointed out the similarity in chemical structure between acetaminophen and phthalates. Like phthalates acetaminophen disrupts the reproductive development in animals and humans. Patients should take acetaminophen only under supervision with doses that are safe. The old notion that acetaminophen would be safe in pregnancy is no longer true in light of the new medical findings. Any pregnant woman should discuss with her physician what she can safely take.

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Sep

2021

Effects of a Plant-centered Diet on Cardiovascular Disease in Midlife

By Ray Schilling | Cancer, Cardiovascular disease, cholesterol, diet, exercise, heart attack, Mortality, Nutrition, olive oil, omega-3 fatty acids, Processed food

A study followed younger patients for 32 years looking for the effects of a plant-centered diet on cardiovascular disease in midlife. The researchers determined the heart attack and stroke rates when the participants were in their 50’s to 60’s. When on a plant-based diet cardiovascular disease rates fell by 52% compared to a control group with a meat containing diet. One subgroup changed the diet from a regular diet to a plant-based diet over 13 years. This reduced the risk ratio by 61% for heart attacks and strokes when assessed later.

Details of this study

There were 4946 adults as participants of this 32-year study. They were recruited in 1985 and 1986, at which time none of them had cardiovascular disease. The study completed in 2018. The results were published on Aug. 4, 2021. The researchers assessed the plant-centered diet quality using a tool with the name “A Priori Diet Quality Score” (APDQS). The higher the score, the higher the quality of the food. This means the person consumed nutritionally rich plant foods, limited amounts of high-fat meat products and less healthy plant foods.

Although a plant-rich diet consisted primarily of nutritionally rich plant foods, small amounts of animal products were also allowed. This involved low-fat dairy products, non fried poultry and steamed or grilled fish. This made the diet tastier and ensured that people would stick to this diet for decades.

Improvements of heart attack rates with plant-centered diet

After 32 years 289 cases of cardiovascular disease developed. The researchers compared participants with the highest food quintile to participants with the lowest food quintile. As mentioned, the risk for participants on a plant-based diet was 52% lower to get a cardiovascular disease. Moreover, a subgroup changed from a higher risk (fatter meals, meat, less vegetables) diet to a lower risk diet (lean fat, lean poultry, vegetables). Physicians followed this subgroup for 13 years and the risk ratio for heart attacks and strokes fell by 61%.

Comparison to other diet studies

There are other studies that looked at the effect of diet changes on the risk of developing heart disease. One such study examined 86 cross-sectional studies and 10 prospective studies in a meta-analysis. Vegetarian diets reduced deaths from heart attacks by 25% and brought down the incidence of total cancer rates by 8%. A vegan diet reduced the risk of total cancer by 15%.

In a study from the United Kingdom dated March 2019 several clinical trials were analyzed regarding non-diabetic populations. The question came up, what the effect of a Mediterranean diet was on cardiovascular disease incidence and mortality. The authors reviewed 30 RCTs (49 papers) with 12,461 randomized participants and seven ongoing trials. In one study the observation time was 46 months. A Mediterranean diet reduced the cardiovascular disease mortality by 65%!

Another study from Spain

Another study from Spain published in 2019 examined 7356 older adults (average 67 years) and followed them for 6.8 years. The investigators kept track of the physical activity and put everybody except the controls on a Mediterranean diet. The group on the lightest leisure-time physical activity consuming a Mediterranean diet had the lowest mortality. The all-cause mortality of this group was 73% lower than the control group.

What is so healthy about the Mediterranean diet?

Despite a wide variation between all the 15 countries bordering the Mediterranean Sea, there are common characteristics: an abundance of vegetables and fruit, along with nuts and legumes. Cereal products are largely whole grain. Olive oil is the principal fat source, and people eat fish, seafoods and poultry in moderation. They consume red meat rarely. Cheese and yogurt can be part of the diet, depending on the region.

The first clinical evidence supporting the health benefits of the Mediterranean diet came from the Lyon Heart Study. The researchers placed patients who had a heart attack either on the diet designed by the American Heart Association or a Mediterranean style diet. After a follow-up of 27 months, the group eating the Mediterranean diet had a reduction of heart attacks by 73% and a decreased mortality by 70% compared to the other group.

More detail on the ingredients of the Mediterranean diet

An analysis of the various foods of the Mediterranean diet shows the reasons for the health benefits clearly. The fats that people on a Mediterranean diet eat are heart-healthy monounsaturated fats like olive oil or fats that contain omega-3 fatty acids. They come from fish (tuna, salmon, trout, sardines) or from plant sources (walnuts, other tree nuts and flax seed).

As there is an emphasis on natural foods, the diet is extremely low in trans fatty acids (hydrogenated fats), which otherwise increases the risk for cardiovascular disease. As people consume more than 300g of vegetables per capita daily, the contents of antioxidants and other beneficial plant chemicals is much higher in comparison to Western diets. There are many individual components of the Mediterranean diet that contribute to the reduction of disease. This is particularly true for heart disease. It also is apparent, that there is not one single food or nutrient that is responsible for the health benefits. What matters are the interactive effects of all the nutrients that lead to the health benefits.

No processed food means healthier living

The practical application does not mean deprivation and starvation, but a move away from processed fats (margarine), baked goods (donuts, muffins, pastries), and high saturated fat snacks and trans fats (chips, crackers, cookies, pies). Food choices move towards those of fresh fruit and vegetables, nuts, fish, and olive oil. Portions or servings have to be adequate to maintain a healthy weight.

Mediterranean food is not the heaping plate of pasta with an afterthought of vegetables. It also is not the super-size fast food pizza with pepperoni and cheese. Mediterranean food incorporates fresh food rather than fast food. It entails a shift from large portions of red meat to smaller portions of fish, a transition from highly processed foods to ample helpings of dark green vegetables with a dose of olive oil. Low amounts of alcohol, especially red wine can make a meal enjoyable, which means that the limit is one drink per day for women, and two drinks per day for men. After dinner go for a walk!

Olive oil is one of the reasons why the Mediterranean diet is so healthy

In the past it was thought that the monounsaturated fatty acids in olive oil would be the reason why it is protective of the heart. However, newer studies have shown that it is the polyphenols and among these in particular hydroxytyrosol that lower blood pressure and protect you from hardening of the arteries.

A 2012 study from Spain has found that mortality from heart attacks was 44% lower than that of a control group who did not incorporate olive oil in their diet.

How polyphenols in olive oil work for you

Only two tablespoons of extra virgin olive oil per day protect you from heart disease. It does so by reducing the total cholesterol level in the blood as well as the LDL cholesterol level. When there is more polyphenol in olive oil (such as in extra virgin olive oil), the body produces more HDL, which is essential to extract oxidized LDL from arterial plaque. On top of that polyphenol rich olive oil increases the size of the HDL particles (these larger particles have the name HDL2), which are more efficient in extracting oxidized LDL from arterial plaques. A Sept. 2014 study in humans showed that higher polyphenol olive oil as found in extra virgin olive oil caused an increase in the more effective HDL2 particles. This cleans out plaques from arteries more effectively than the regular, cheaper olive oil.

Effects of a Plant-centered Diet on Cardiovascular Disease in Midlife

Conclusion

Several large, well-controlled studies showed that there are pronounced effects of a plant-centered diet on cardiovascular disease in midlife. Heart attack rates and mortality rates were reduced by 25% to 73% on a Vegan diet or a Mediterranean diet. When people combine a plant-centered diet with regular physical exercise they also live longer. One of the ingredients of a Mediterranean diet is extra virgin olive oil. It contains polyphenols that lower total and LDL cholesterol. It also increases the larger particles of HDL cholesterol with the name HDL2. HDL2 is more efficient in extracting oxidized LDL cholesterol from arterial plaques.

What you can eat on a plant-centered diet

A plant-centered diet incorporates fresh food rather than fast food. It entails a shift from large portions of red meat to smaller portions of fish, a transition from highly processed foods to ample helpings of dark green vegetables with a dose of olive oil. Instead of large portions of beef and sausages shift to seafood (tuna, salmon, trout, sardines), walnuts, other tree nuts and flax seed. The statistics clearly showed the effects of a plant-centered diet on cardiovascular disease in midlife with a reduction of heart attacks and mortality.

Some of the text above was published previously here.

Jul

2021

Extreme Heat and Heat Related Deaths

By Ray Schilling | Health, heart attack, heat stroke, Mortality

Extreme heat and heat related deaths are closely linked. A record heat wave hit the North West of the US and British Columbia in late June/early July. Many people died from heat stroke and from cardiovascular problems. Here I like to review the medical literature regarding extreme heat and heat related deaths. Also, why is it important to cool down? Much of what I like to communicate was published in a review article by CNN. But I also reviewed many other websites and added links below.

How does global warming contribute to the summer heat?

There are a few explanations how global warming drives the heat in summer even higher. Essentially, what weather experts are saying is that the jet stream can get stuck in one place during a summer heat wave and the heat keeps getting more intense. Global warming is responsible for heat waves that are higher than in the past. Conversely, in winter global warming can produce cold waves that are colder than in previous years.

Why is extreme heat dangerous for us?

According to the CDC between 2004 and 2018 an average of about 700 Americans died from heat-related causes. The majority of deaths occurred between May and September. There are a number of observations that explain why more people die during a heat wave.

In 2006 there were widespread heat waves and as a result there was a peak in heat related deaths.

When people have pre-existing cardiovascular disease, this gets aggravated during a heat wave and the death rate from cardiovascular disease increases during a heat wave. About 25% of heat related deaths are due to an underlying cardiovascular disease.
Age by itself plays a big role in heat related deaths. People above the age of 65 are several times more likely to die from a heat related cardiovascular disease than the general population.

Under reporting of heat related deaths

Many times, it is not clear whether a death is due to a medical condition or due to exposure to heat. A death certificate that reports a heart attack as the cause of death during a heat wave will be missed when statisticians attempt to get a number for heat related deaths after a heat wave.

Medical causes why extreme heat and heat related deaths are linked

Our body is used to an inside temperature range between 97 to 99 degrees Fahrenheit (36.1 to 37.2 degrees Celsius). The body can compensate in two ways to counter a rise of the body temperature from heat exposure.

When the brain senses a rise in body temperature, the sweat glands open up and sweat is produced. The evaporating sweat cools down the body temperature.
The body has a second coping mechanism to cool you down. The body can dilate its blood vessels and increase the heart rate. This brings the blood more to the surface. This is when your forehead and the extremities give off heat and you lower your body temperature.
But with exposure to extreme high temperatures both of these mechanisms are not enough to decrease your core temperature.

Avoiding heat-related illness

The Mayo Clinic link explains that it is important to drink enough fluids to avoid dehydration. This helps with the second coping mechanism mentioned that cools you down (see above).
When the outside temperature rises beyond 86 degrees Fahrenheit (=30 degrees Celsius) it is wise to stay inside air-conditioned premises. This could be your house, if you have air-conditioning, an air-conditioned mall or a public building. A cool pool, bathtub, or cold cloths applied to your arms, legs and torso cool you down as well. Otherwise, intermittent cold showers or cold baths will do the same.

Health conditions that are a higher risk for heat related deaths

The population group at higher risk for developing heat-related illness and eventual deaths are infants and children up to age 4. In addition, anybody older than 65 years is also at risk. Pre-existing medical conditions like diabetes, heart disease and chronic lung disease (COPD) increase the risk of dying from excessive heat exposure. Being overweight or obese is also a risk factor. Heat exhaustion and heat stroke are conditions that require hospitalization.

Common heat-related symptoms

Symptoms of heat exhaustion are: profuse sweating, a pulse that is fast and weak, clammy skin, vomiting and nausea. In addition, there can be cramps in muscles, weakness, tiredness, dizziness, headaches and fainting.

Symptoms of heat stroke are: high fever of 104 degrees Fahrenheit (= 40 degrees Celsius) or higher. Take the temperature with a rectal thermometer to get the core temperature. Other symptoms of heat stroke are altered mental state (confusion, agitation, delirium and seizures). Further, the skin may turn red as the temperature increases, and there may be rapid and shallow breathing. The heartbeat races and the head may throb from a severe headache. Both patients with heat exhaustion and heat stroke need hospital care. Call an ambulance.

Extreme Heat and Heat Related Deaths

Conclusion

We have to take extreme heat and heat related deaths seriously. Only when we employ counter measures will the death toll from heat related deaths go down. Prevention is everything. But if a person develops heat exhaustion and heat stroke swift transportation to a hospital is a must. This can often save a life. We all need adopt an awareness what our risks are regarding heat and heat related deaths. We need to apply early countermeasures by getting into cooler areas and by drinking enough fluids to prevent dehydration. Prevention is everything regarding extreme heat and heat related deaths.

Jun

2021

Being A Morning Person Can Prevent Depression

By Ray Schilling | Anxiety, Cancer, Cardiovascular disease, Circadian rhythm, coffee, depression, Gastrointestinal Disease, heart attack, Insomnia, Lung Disease, Mortality, neurological disease, telomeres

A British study concluded that being a morning person can prevent depression. It was reviewed also in CNN. The study used sleep data from 85,000 UK participants in the Great Britain Biobank Study. They wore wrist activity monitors that provided sleep data. Researchers compared the sleep data with the self-reported mood changes. They found that if the sleep pattern is misaligned with the circadian rhythm, those who are night owls are at a higher risk of developing mood disorders. The controls were those who were morning persons. They were not affected by the misalignment effect.

Normal sleep pattern

Natural sleep habit or the circadian rhythm starts between 10 PM and 11 PM and continues for 7 to 8 hours. Your hormones are replenished during your sleep. This helps your body’s hormones and the immune system to restore itself overnight.

“The health problems associated with being a night owl are likely a result of being a night owl living in a morning person’s world, which leads to disruption in their body’s circadian rhythms”. This is what sleep specialist Kristen Knutson said. She is an associate professor of neurology and preventive medicine at Northwestern University Feinberg School of Medicine.

Reclaim your natural sleep habit

The key is to learn to live within your circadian rhythm pattern. Caffeine is a powerful stimulant and will stop you from falling asleep. For this reason, it is best to avoid caffeine-containing beverages. If you cannot live without your favourite cup of java, switch to the decaffeinated version. Stop using LED lights (from TV, computers, tablets or smartphones) 2 hours prior to your bedtime. Use dark curtains and enjoy a comfortable bed. Maybe read that thriller, earlier in the day instead of making it your bedtime story. And do yourself a favour: you do not need the eleven o’clock news on TV! They will probably stop you from falling asleep. Go to sleep between 10PM and 11PM.

Children can have problems with sleep disturbances and depression

Another study published March 22, 2021 in the Jama Network showed that depression had an association with sleep disturbances in youth and children.

A meta-analysis of 16 publications looked at depression and disturbed sleep. It showed that depression was 1.5-fold higher in sleep disturbed youths/children compared to controls with a normal sleep pattern.

Other studies re. being a morning person can prevent depression

Another study with Dr. Knutson as the lead author appeared in 2018. The authors found that various health conditions, mood disorders and mortality were on the increase the more the sleep rhythm deviated from the circadian rhythm. Morning persons were protected from this effect. But night shift workers and night owls were at a higher risk of disease. Specifically, they found the following associations for evening types.

Evening types compared to morning types had a 1.94-fold risk of psychological disorders
The risk of diabetes was 1.30-fold for evening types
Neurological disorders had a 1.25-fold risk in evening types
Gastrointestinal/abdominal disorders occurred 1.23-fold more often in evening types
respiratory disorders were 1.22-fold more common in evening types
Evening types had a 10% increased risk of all-cause mortality

The researchers concluded that externally imposed timing of work and social activities has potentially serious health consequences.

Circadian misalignment responsible for disease

Dr. Knutson also said: “Circadian misalignment could also lead to inadequate sleep duration and quality, which could also impair mood and exacerbate mood disorders.”

In other words, circadian misalignment to circadian rhythm problems. This can cause mood disturbances, but eventually lead to the diseases listed above.

Evidence of health risks in night shifts workers

The medical literature is full of examples that the health of night shift workers is significantly affected by circadian misalignment. Here are a few examples.

1.Here is a random selection to illustrate the health risks of night shifts workers. A study from 2015 examined the sleep patterns of 315 shift nurses and health care workers in Iranian teaching hospitals. They found that 83.2% suffered from poor sleep and half of them had moderate to excessive sleepiness when they were awake.

2.This South Korean study examined 244 male workers, aged 20 to 39 in a manufacturing plant. Researchers compared blood tests from daytime workers to blood tests from night shift workers. They also obtained inflammatory markers like the C-reactive protein and leukocyte counts. Night shift workers had significantly higher values. The investigators concluded that shift workers have increased inflammatory markers. This is a sign of a higher risk of developing cardiovascular disease in the future.

Higher mortality and higher cancer risk in nighttime workers

3. A Swedish study found that white-collar shift workers had a 2.6-fold higher mortality over a control group of daytime white-collar workers.

4. Another study compared night workers in the age group of 45 to 54 with daytime workers and found a 1.47-fold higher mortality rate in the night shift workers.

5.In a study from China 25,377 participants were part of a study that investigated cancer risk in males with more than 20 years of night shift work. They had a 2.03-fold increased risk to develop cancer compared to males working day shifts. Women with night shift work in this study showed no effect with regard to cancer development.

Healthy telomeres with healthy sleep pattern

It is true that you can suffer multiple health problems, as all of your hormones depend on the resetting during your deepest sleep between 2AM and 4AM triggered by the nighttime melatonin response. Even your telomeres, the caps of chromosomes in every cell get shortened from too much stress and too little sleep.

One example of such a study comes from Milan, Italy. https://oem.bmj.com/content/75/Suppl_2/A480.1

In this 2018 study researchers compared 46 nurses who had worked in night shifts with 51 nurses working day shifts. Among the night shift workers breast cancer was common, but not among day workers.

Shortened telomeres, hypomethylation of BRC1 gene and p53 gene

In the night shift nurses from Milan there was hypomethylation of the breast cancer gene BRC1. There was also hypomethylation of the general cancer gene p53. At the same time significant telomere shortening occurred in night shift nurses who had worked night shifts for more than 15 years. This likely all worked together in causing night nurses to develop breast cancer more frequently.

Shortened telomeres mean a shortened life span. The reason for this is that people with shortened telomeres develop heart attacks, strokes and cancer. This is what shortens the life span. How do we avoid this risk? Go back to healthy sleep habits. As mentioned above it is best to start going to sleep between 10PM and 11PM and sleep for 7 to 8 hours. Night owls delay going to sleep by 2 to 3 hours.

Being A Morning Person Can Prevent Depression (click image to enlarge)

Conclusion

A publication in Molecular Psychiatry demonstrated that evening person (night owls) are more likely to develop depression. This is in comparison to morning persons. As discussed, other researchers showed that evening persons also can develop diabetes and neurological disorders. In addition, respiratory disorders and gastrointestinal disorders are more common in night owls as well. When it comes to mortality, evening persons have a 10% increase of mortality over morning persons. There is a large body of literature regarding diseases of night shift workers. Night Shift work is perhaps the most extreme example of a circadian misalignment. It leads to poor sleep, inflammation in the body, increased cancer risk and higher mortality compared to day shift workers.

Prevent telomere shortening

Even the telomeres get shortened in night owls and night shift workers. We can prevent problems like these by going to bed in time and sleeping according to our circadian rhythm. If you had a poor night’s sleep, make up for it with the help of an afternoon nap. Do not sleep all afternoon though; half an hour or one hour will be enough. Even a short, restful nap after coming home from work can restore your feeling of wellness.

Feb

2021

Two Articles Showed that Fish Oil Reduces Cardiovascular Disease and Mortality

By Ray Schilling | Cardiovascular disease, fish oil, heart attack, High Blood Pressure, Mortality, omega-3 fatty acids

Recently two articles showed that fish oil reduces cardiovascular disease and mortality.

British study recording the effects of fish oil over 10 years

For one thing, the British Medical Journal published an article comparing people who supplemented with fish oil with people who did not. In this case, the ones who supplemented had a lower risk of mortality and had lower cardiovascular disease than the control group. In brief, 427,678 subjects were enrolled in this British study between 2006 and 2010. Questionnaires at the beginning of the study revealed how many capsules of fish oil the subjects consumed. Hospital records and death certificates provided information about cardiovascular disease mortality at the end of 2018. Altogether, 31% of the subjects said that they were taking fish oil supplements regularly.

In short, here are the results of the study showing what fish oil did.

7% lower cardiovascular events
16% lower risk of cardiovascular disease mortality
20% lower mortality risk from heart attacks
13% lower risk of death from any cause (when compared to people who did not use fish oil)

Discussion

Given these points, the authors stated that it was the omega-3 fatty acids in fish oil that caused all the beneficial effects. This included lowering of blood pressure, triglycerides and reducing the heart rate. Fish oil was also responsible for improvement of endothelial function, inflammation and blood clotting. In addition, fish oil protects against cardiac arrhythmias. They stated: “Fish oil supplementation could be an inexpensive, quick, safe way of increasing an individual’s omega-3 fatty acid intake”.

Mayo Clinic study of taking higher doses of omega-3 polyunsaturated fatty acids

A study dated Sept. 17, 2020 showed the cardiovascular benefits of higher doses of omega-3 fatty acids. This was the second of two articles that showed that fish oil reduces cardiovascular disease and mortality. It was published in Mayo Clinic Proceedings. This metaanalysis involved 40 interventional studies and 135,000 patients. Two types of omega-3 fatty acids, namely EPA and DHA were studied with regard to the prevention of cardiovascular disease. EPA and DHA supplementation had the following effects.

35% reduction of risk of a fatal heart attack
13% reduction of heart attacks in general
10% reduced risk of coronary heart disease occurrence
9% reduction of mortality from coronary heart disease

The researchers described that the higher the dose of omega-3 fatty acid supplementation, the greater the protection.

An extra dose of 1000 mg per day of EPA and DHA reduced the risk of cardiovascular disease as follows. There was a reduction of cardiovascular disease by 5.8% and of heart attacks by 9%. I take 1800 mg of EPA/DHA twice a day, a total of 3600 mg per day.

Two Articles Showed that Fish Oil Reduces Cardiovascular Disease and Mortality

Conclusion

Two independent studies of fish oil or omega-3 fatty acids came to similar conclusions. Heart attacks and strokes are significantly reduced. And mortality in the group that used fish oil supplementation was also significantly reduced. An extra dose of 1000 mg per day of EPA and DHA reduced the risk of cardiovascular disease as follows. There was a reduction of cardiovascular disease by 5.8% and of a heart attack by 9%. Based on these findings the researchers recommended that patients should use EPA/DHA supplementation to reduce cardiovascular risk. EPA/DHA supplementation lowers blood pressure, triglycerides and the heart rate. Fish oil was also responsible for improvement of endothelial function, also for the prevention of inflammation and blood clotting. In addition, fish oil protects against cardiac arrhythmias. The end result is that you live a healthier life.

Jan

2021

Review about Human Oncolytic Virus Research in 2020

By Ray Schilling | Cancer, immune system, Mortality

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

History of licencing of oncolytic viruses

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

Review of 20 years of human oncolytic virus research

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

*Oncolytic viruses derive from various types of viruses***

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

Stimulation of the immune system through GM-CSF

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

Types of cancer targeted with oncolytic viruses

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

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

Other drugs given along with oncolytic viruses

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

Side effects of treatment with oncolytic viruses

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

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

Antitumor activity in clinical trials with involvement of oncolytic viruses

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

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

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

Discussion

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

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

Conclusion

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