Feb
17
2024

Ashwagandha’s Benefits

Medical news today had an article in October 2023 that reviewed ashwagandha’s benefits. I thought it would be useful to discuss this topic in an abridged version. Often things get distorted on the Internet and a reality check helps to separate facts from fiction. Ashwagandha (botanical name: Withania somnifera) is a small shrub that grows in Southeast Asia, Africa and some areas of India. An alternative name is Indian ginseng.  Ashwagandha has been part of Ayurvedic medicine for more than 3000 years.

About ashwagandha’s effectiveness

Ashwagandha is part of natural medicines that go under the name of adaptogens. The effective substances of ashwagandha were isolated. Researchers named them withanolides. They are alkaloids and consist of polyoxygenated steroidal lactones with 28-carbon ergostane skeletons.

People are taking ashwagandha supplements to counter stress and fatigue. But it also increases testosterone, which increases muscle mass. In addition, there is an increase of libido in men as well as in women.

People with insomnia benefit from the relaxing and sleep-inducing effect of ashwagandha supplements. Ashwagandha stimulates the immune system. It also significantly counters the stress response, as it lowers cortisol levels.

The active chemical components of ashwagandha

Various researchers pinpointed the diverse actions of ashwagandha extracts to withanolides, which are the pharmacologically active ingredients. There are at least 25 different chemical structures of withanolides, which are depicted in this reference: This explains the diverse effects of ashwagandha extracts on the immune system, the stress hormone axis, the libido brain centers and testosterone production. One human study showed that within 96 hours of ashwagandha extract administration the immune system was activated; T cells and natural killer cells were measured and were significantly elevated in number in comparison to controls:

Specific clinical trials showing effects of ashwagandha

Effects on the brain

In a small clinical study oral intake of ashwagandha improved performance on cognitive tasks, executive function, attention, and reaction time.

Dr. Amala Soumyanath is a professor of neurology in the School of Medicine at Oregon Health & Science University. She stated: “These laboratory studies show that ashwagandha extracts can act on neurotransmitter pathways including those involving serotonin and Gamma-aminobutyric acid (GABA), and also affect systems like the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) axis.”

What does this mean? It means that ashwagandha contains a mix of withanolides that calm down the brain, particularly when it is stressed. At the same time, it increases serotonin and GABA, which has antidepressant and calming effects. Clinical trials have measured cortisol levels in volunteers and found that cortisol is lowered within a few weeks. This is the strongest evidence that ashwagandha in fact counteracts stress.

Libido and muscle strength

A small human study found that muscle strength was higher after exposure to oral ashwagandha in comparison to controls.

Ashwagandha showed a significant increase of maximum oxygen consumption (VO2max) in healthy adults and athletes, which is a direct measurement of exercise fitness. A clinical trial with 50 overweight males aged 40-70 years, showed that 16 weeks of oral ashwagandha increased their testosterone level by 14.7%. In addition, there were improvements in fatigue, vigor, and sexual and psychological well-being. There was also an increase of 18% of DHEA-S a precursor of testosterone. The authors felt that a larger study with a longer observation time would be beneficial to confirm this study. Overall, the objective effects of ashwagandha are in the mild to moderate category. The mild increase in testosterone affects libido only marginally. Some articles in social media are vastly exaggerating the objective findings.

Health risk of ashwagandha

There are downsides as well. Ashwagandha stimulates the immune system and in doing so may exacerbate autoimmune diseases. It also can increase thyroid hormones, which is important to know for people with hyperthyroidism or hypothyroidism. Men who have hormone sensitive prostate cancer should avoid ashwagandha, because it elevates testosterone.

Researchers pointed out that gastrointestinal upsets, such as diarrhea, nausea, and vomiting due to ashwagandha are common side effects. The higher the dosage and the longer the exposure is, the more likely it is that the patient experiences side effects. Researchers reported a few cases of reversible liver toxicity cases due to ashwagandha. At this point the effects of concomitant medications taken at the same time as ashwagandha is not known.

Ashwagandha’s Benefits

Ashwagandha’s Benefits

Conclusion

Lately social media is full of ashwagandha’s benefits. Rosy reports of increased libido, extra energy and boosts of confidence circulate on the Internet. Men are told that in order to build up muscle bulk with exercise they must take ashwagandha. This review checked the facts. There is a 14.7% rise in testosterone from taking ashwagandha and this may contribute to an increase of muscle mass with exercise, but this is not a huge effect. Also, the mild increase of libido due to the increase of testosterone is not as significant as reported in the social media. The active ingredients of ashwagandha are the withanolides, which researchers isolated. They do help to deal with stress-related problems like lack of energy and insomnia. In addition, they stimulate the immune system to give a stronger response.

Side effects of ashwagandha

But ashwagandha also has some side effects. It can make auto immune reactions worse. It can interfere with both hyperthyroidism and hypothyroidism. Men who have hormone sensitive prostate cancer must avoid ashwagandha because of the testosterone increase. Gastrointestinal upsets, such as diarrhea, nausea, and vomiting from ashwagandha supplementation are common side effects. So far scientific evidence is based on relatively small clinical trials. Scientists must conduct much bigger trials that are going on for several years to provide more in-depth information on the effects of ashwagandha.

Sep
09
2023

How the Immune System affects Parkinson’s Disease

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

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

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

The role of inflammation in Parkinson’s

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

Lifestyle factors that people can change to prevent PD

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

Changing diet can help postpone Parkinson’s disease

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

The gut connection to Parkinson’s disease

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

Can any diet fight gut dysbiosis?

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

Regular exercise to prevent Parkinson’s disease

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

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

How the Immune System affects Parkinson’s Disease

How the Immune System affects Parkinson’s Disease

Conclusion

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

Lifestyle changes help to postpone Parkinson’s disease

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

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Jan
14
2023

Cortisol is the Number 1 Longevity Hormone

At the 30th American Anti-Aging Academy Medicine Conference in Las Vegas one topic was that cortisol is the number 1 longevity hormone. Dr. Thierry Hertoghe, an endocrinologist from Brussels, Belgium gave a comprehensive lecture on Saturday, Dec.10, 2022. He explained that cortisol from our adrenal glands is vital to our health. Certainly, it is important for our quality of life and for health in general.  Indeed, cortisol keeps us alive when various circumstances challenge our health. Specifically, cortisol is on the bottom of the hormone cascade of corticotropin releasing hormone (CRH) from the hypothalamus/ Adrenocorticotropic hormone (ACTH) from the pituitary gland/and cortisol from the adrenal glands. It is important to realize that this is the hormone axis of the stress reaction that Dr. Selye first described.

Production of cortisol

Sedentary men produce 30 mg of cortisol per day, women 20 mg/day. Under stressful conditions ACTH production increases and causes an increase of cortisol production in the adrenal glands. To clarify, stressed men produce 40 to 60 mg per day and stressed women produce 30 to 40 mg/day. In addition, the older a person is, mononuclear leukocytes have less type 1 and type 2 glucocorticosteroid receptors.

Action of cortisol

Dr. Hertoghe pointed out that cortisol increases energy and stress resistance. It causes blood sugars to increase and also elevates blood pressure. The immune system gets stronger, allergies and inflammation decrease. Cortisol shapes our bodies: when there is cortisol deficiency the body is thin; with normal cortisol production the body has a normal configuration. Your body develops swelling and obesity with cortisol excess, but when cortisol is missing the body gets frail and thin.

Cortisol deficiency

Low cortisol production leads to low blood sugar and low blood pressure. This diminishes glycogen stores in the liver and muscle mass. A lack of circulating cortisol reduces gluconeogenesis in the liver, which is an alternative pathway of glucose production. One of the hallmark symptoms is mental fatigue, particularly in times of stress. With cortisol deficiency the person feels fatigue in the second part of the day.

Chronic fatigue syndrome

The peak age for chronic fatigue syndrome patients is 31 years. The mean duration of the illness lasts 7 years. 58% of patients have free serum cortisol levels at 20:00 hours, which is less than normal. In 40% of patients the total cortisol level is less than normal.

Burnout

With burnout the urinary free cortisol is diminished. Patients with cortisol deficiency have a hyper sensitivity to stress.

A lack of cortisol leads to feeling no energy and having no stress resistance. The person feels tense and has negative thinking. A person who has sufficient cortisol is full of energy, expresses emotions and handles stress well. With enough cortisol a person is relaxed, has positive feelings and finds solutions everywhere.

Adrenal crisis

Dr. Hertoghe explained that an adrenal crisis happens when there is not enough cortisol production in the adrenal glands to support the metabolism and the cardiovascular system. Gastrointestinal diseases, infectious diseases or stressful events like surgery, exposure to heat, strenuous physical activity, major pain or pregnancy can all trigger an adrenal crisis. When glucocorticoid therapy is withdrawn, this can also cause an adrenal crisis.

Addison’s disease

With Addison’s disease there is a lack of energy, muscle weakness, loss of appetite and unintentional weight loss. The reason for the symptoms is that the adrenal glands are not producing enough cortisol and aldosterone. There was a more than 2-fold increased risk of dying from Addison’s disease compared to a normal population in a Swedish study.

In another study the serum cortisol levels were determined in patients with heart attacks. The ones who had extremely low levels of cortisol were at almost a 9-fold risk of dying within 30 days compared to patients with a normal serum cortisol level. One of the famous patients with Addison’s disease was J.F. Kennedy. He collapsed in London, England and was finally diagnosed correctly in a British hospital after having suffered for several years without the correct diagnosis. This disease is not always easily diagnosed.

Cortisol therapy

With an adrenal crisis or Addison’s disease cortisol therapy can be life-saving. The physician uses physiological doses of glucocorticosteroid hormones (cortisol and others) and in emergency situations higher than normal doses. Dr. Hertoghe said that survival data were gathered with various severe disease conditions as follows.

Coronary heart disease survival

Dr. Hertoghe reported about a study that observed 1090 adults over 11 years. There was a 40% reduction of mortality when patients were treated with cortisol following a heart attack compared to controls who did not get cortisol treatments. The researchers also found that there was a 39% lower stroke risk when treatment with cortisol was instituted.

In a clinical trial with 39 patients who had heart attacks those patients treated with pharmacological doses of methylprednisolone (3 grams daily) experienced a significant reduction in infarction size.

In another study with 1118 patients Dr. Hertoghe reported a 28% reduction in mortality over 28 days compared with a placebo group. In this study medical researchers gave 2-3 grams of methylprednisolone early on into the heart attack. In the same study, after 6 months there was a 33% mortality reduction.

Stroke survival

Following a stroke, low cortisol levels (270 nmol/L) and high cortisol levels (550 nmol/L) both had an association with a poor long-term prognosis 1 year after follow-up.  However, the study also showed that patients with normal cortisol levels (between 270 nmol/L and 550 nmol/L) following a stroke had a very good long-term prognosis.

AIDS survival

AIDS patients belong into the group of chronic diseases that are associated with low cortisol levels in the blood. There are also clinical signs of low cortisol, namely dark circles around the eyes, hollow cheeks, brownish pale skin with pigment spots, hand creases that are pigmented and weight loss. Severely ill AIDS patients often have severe lung infections (Pneumocystis carinii pneumonia) due to their immune deficiency. A study involving 23 AIDS patients used methylprednisolone in the treatment group and no methylprednisolone in the placebo group. The clinicians administered 40 mg of methylprednisolone every 6 hours for 7 days in addition to antibiotic treatment for 3 weeks. They compared this to the placebo group without methylprednisolone. 75% of the treatment group survived until the hospital discharge compared to only 18% of the placebo group.

Sepsis and septic shock

Treatment of patients with septic shock with ACTH (the stress hormone) infusions showed that 88% had a cortisol response among survivors. The ultimate non-survivors only had a 27% cortisol response of their adrenal glands when stimulated by intravenous ACTH. Dr. Hertoghe pointed out that this suggests that some patients with septic shock may have relative adrenocortical insufficiency. This would explain why the adrenal glands of septic shock patients can be non-responsive to ACTH. In these cases, it is important that the physician treat with either intravenous cortisol or with synthetic glucocorticoids.

Treating septic shock with intravenous hydro-cortisol

One study showed that treating septic shock with intravenous hydro-cortisol gave the following results compared to placebo:

  • 7- fold higher septic shock resolution when compared to the placebo group
  • 8 – fold survival in the intensive care unit
  • 2 – fold higher hospital survival
  • 2 – fold better septic shock reversal in 7 days
  • 8 – fold better survival in the next 28 days.

Overall, this study clearly revealed that septic shock recovery is much better with intravenous hydro-cortisol treatment.

Cancer survival

A study found that breast cancer patients with metastases had flat saliva cortisol curves when compared to patients without breast cancer. If left alone breast cancer patients with a flat cortisol curve die earlier than those who used cortisol supplementation.  The researchers found out that the natural killer cells (NK cells) in these patients were missing. These are special lymphocytes that can kill cancer cells with their enzyme vesicles.

Glucocorticoid treatment

Dr. Hertoghe talked about short-term high-dosed glucocorticoid therapy and the difference between synthetic cortisol equivalents (Dexamethasone etc.) and the natural cortisol. He also talked about adding small amounts of these hormones: DHEA, fludrocortisone (0.1 mg daily orally), and bioidentical vasopressin to optimize cortisol replacement.

Cortisol is the Number 1 Longevity Hormone

Cortisol is the Number 1 Longevity Hormone

Conclusion

One of the vital hormones in our bodies is cortisol, the stress hormone. There is a hormone cascade starting with CRH in the hypothalamus, which stimulates ACTH release from the pituitary gland. This in turn releases cortisol from the adrenal glands. The end product, cortisol is the number 1 longevity hormone. It helps us to survive any stressful event. It gives us energy, stimulates the immune system and helps us to overcome dangerous illnesses. Dr. Hertoghe, an endocrinologist from Belgium gave a detailed lecture at the 30th American Anti-Aging Academy Medicine Conference in Las Vegas on Dec. 10, 2022. Dr. Hertoghe discussed how to survive a heart attack or stroke, sepsis, AIDS or Addison’s disease (=adrenal gland insufficiency) by adding appropriate cortisol doses or equivalent synthetic glucocorticosteroids. One thing is clear: we all need cortisol until the end of our lives.

Dec
03
2022

The Bubonic Plague Still Affects some People today

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

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

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

Results of the study

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

Denmark data

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

The downside of immunity

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

The Bubonic Plague Still Affects some People today

The Bubonic Plague Still Affects some People today

Conclusion

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

Autoimmune diseases

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

Nov
19
2022

Lack of Sleep Harms the Immune System and Causes Inflammation

A research group from Boston, MA and New York, NY found that a lack of sleep harms the immune system and causes inflammation. This was summarized in this CNN article.

Specifically, they first conducted experiments with a mouse model. They studied the effects of sleep disruption and sleep deprivation and could later confirm identical changes in man. The observation was that a lack of sleep caused the hematopoietic cells in the bone marrow to proliferate, but the cell diversity was less than in people with normal sleep patterns. The same pattern of bone marrow proliferation was present in mice. This research was published Sept. 21, 2022 in the Journal of Experimental Medicine.

Chronic sleep deficit

A chronic sleep deficit caused chronic inflammation and eventually autoimmune diseases. Again, this was a pattern present in both the mouse model and in humans. Next the researchers observed what happened with sleep recovery. In the past it was assumed that with sleep recovery all of the physical changes from sleep deprivation would disappear. However, the opposite was true: both in mice and in humans the bone marrow stimulation and the lack of cell diversity persisted.

In the mouse model the researchers could show that there were permanent epigenetic changes, which were caused by sleep deprivation. The same is true with humans, but this is more difficult to show than in the mouse model. The researchers came to the conclusion that sleep deprivation stimulates bone marrow maturation, but restricts the clonal differentiation. In doing so the body initiates inflammation, which becomes chronic even with sleep restoration.

Human sleep studies

There were 14 volunteers that were the test subjects. One group was the normal sleep control. The other group underwent chronic sleep deprivation. Each group did this for 6 weeks. There was a 4-to-6-week washout period. Following this the previous normal sleep group started a 6-week sleep deprivation program. On the other hand, the prior sleep-deprived group switched to 6 weeks of normal sleep. All of the participants had daily late afternoon blood tests.

There are many sleep disruptions, which cause a sleep deficit

In modern life sleep gets disrupted in many ways. There can be sleep fragmentation, sleep restriction, jet lag, obstructive sleep apnea (OSA), and insomnia.

People with these conditions often oscillate between these various types. They may have a few days of normal sleep, but then have sleep deprivation again for a few days. Every time they have sleep deprivation the bone marrow enhances hematopoietic activity. Normally there is a high leukocyte number in the blood at the end of the day and in the morning a lower leukocyte count. But with sleep deprivation there is a high monocyte count in the blood that stays high even when subjects switch back to a normal sleep pattern.

Epigenetic effect of sleep deprivation on bone marrow cells

The authors found that sleep deprivation affects the genetic control of hematopoietic cells in the bone marrow. They called this the epigenetic effect of sleep deprivation. This is responsible for the evening leukocyte response, the monocytosis and the tendency for autoimmune diseases. They summed this up by saying: “Our findings support the hypothesis that periods of poor sleep, even if followed by sleep recovery, have sustained consequences on immunological health.”

Lack of sleep harms the immune system and causes inflammation says the literature

There is ample evidence that a lack of sleep causes cardiovascular disease, diabetes, depression and more frequent infections. Healthy sleep is important when you want to age well without complications. But enough sleep is also necessary to prevent obesity, diabetes and cardiovascular disease. Experts consider getting enough high-quality sleep as essential as a balanced diet and regular exercise.

Lack of Sleep Harms Immune System and Causes Inflammation

Lack of Sleep Harms Immune System and Causes Inflammation

Conclusion

So far, most researchers believed that when you miss some sleep for a few nights that a afternoon nap or a few nights of longer sleep would compensate for the sleep deficit with no sequelae. Think again, because new research from a group in Boston, MA and New York, NY found that lack of sleep harms the immune system and causes inflammation permanently. Sleep deprivation stimulates the bone marrow cells to multiply and causing proliferation of monocytes, called monocytosis as well. Despite afternoon naps and recovery sleep this condition remains  and can lead to autoimmune diseases. All this was unknown up to now. Our bone marrow cells need regular sleep hours to stay diversified and to optimally fight infections in the body. This prevents autoimmune diseases and keeps our defenses against viral diseases strong.

Feb
20
2022

Stimulating the Immune System Leads to Better Cancer Survival

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

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
22
2022

Booster Vaccinations Against Covid-19 Variants are Very Effective

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

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 (3rd 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.

Nov
14
2020

Why We See More Food Allergies

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

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

Theories why there may be more food allergies now

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

Hygiene theory

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

Graham Rook’s “old friends” theory

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

Gut bacteria theory

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

Dual-allergen exposure

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

Prenatal vitamin D and food allergies

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

Use antibiotics only when necessary

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

Immunotherapy for food allergies

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

Why We See More Food Allergies

Why We See More Food Allergies

Conclusion

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

Aug
29
2020

Health Benefits from Vitamin C Supplements

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

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

History of Mega doses of vitamin C

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

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

More effects of vitamin C

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

Vitamin C and disease prevention

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

Endothelial function

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

High blood pressure

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

Vitamin C and the immune system

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

Heart failure, strokes and heart attacks

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

Cancer and vitamin C

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

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

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

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

Type 2 Diabetes (=adult onset diabetes)

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

Mortality reduction with vitamin C supplementation

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

Recommended dietary allowance for vitamin C

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

Health Benefits from Vitamin C Supplements

Health Benefits from Vitamin C Supplements

Conclusion

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

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.