Apr
25
2020

Exosomes can Regenerate Your Stem Cells

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

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

Advantages of administering exosomes

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

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

Applications of exosomes for various clinical conditions

Joint inflammation

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

Disc degeneration  

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

Aging research

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

Longevity comes from good lifestyles

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

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

Clinical diseases from aging

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

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

Oxidative stress as a cause of premature aging

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

Antioxidants help to prevent diseases

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

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

Causation of several diseases

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

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

There are more diseases

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

Preventative measures for slowing the aging process

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

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

How to live longer

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

Intravenous infusions of exosomes

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

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

Contraindication to the use of stem cells or exosome therapy

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

Exosomes can Regenerate Your Stem Cells

Exosomes can Regenerate Your Stem Cells

Conclusion

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

Expensive exosome infusions

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

Apr
18
2020

Changes of Metabolism by Inflammation

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

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

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

Factors that accelerate aging and damage your metabolism

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

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

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

How Metaflammation is developing

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

More problems with metaflammation

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

Major causes of metaflammation

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

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

Interaction of various organ systems can cause metaflammation

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

Other mechanism for pathological changes with hormone disbalances

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

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

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

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

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

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

Cardiovascular disease not just a matter of high cholesterol

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

Microbiome disruption from drugs

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

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

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

Changes of Metabolism by Inflammation

Changes of Metabolism by Inflammation

Conclusion

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

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

Drugs that change the gut biome

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

Feb
29
2020

Celiac Disease in Various Disguises

Dr. Tom O’Bryan gave a lecture in Las Vegas on Dec. 13, 2019 about celiac disease in various disguises. This was at the 27th Annual World Congress on Anti-Aging Medicine. The title of his talk: “An Ounce of Prevention Is Worth a Pound of Protocols: Halting Our Brains Slow Deterioration”.

Case # 1: 44-year old male with an assumed diagnosis of ALS

In the first place a 44-year old male had a history of a right leg weakness that developed over the last 6 months. He had intermittent spasms in his right quadriceps muscle. In addition, over the last few months he noticed a weakness develop in his right arm with difficulties writing. Significantly, his family history revealed that a maternal aunt had celiac disease. Moreover, a sister had Crohn’s disease and his maternal grandmother had multiple sclerosis. Electromyographic studies showed widespread acute denervation. An MRI scan of the spine showed hyperintensity in the corticospinal tracts. A diagnosis of amyotrophic lateral sclerosis (ALS) followed as a result based on the MRI scan findings.

Further tests

At the same time blood tests revealed that his anti-endomysial antibodies were elevated.  Duodenal biopsy demonstrated villous atrophy, crypt-hyperplasia and increased intraepithelial lymphocytes consistent with gluten-sensitive enteropathy (celiac disease). An MRI scan of the brain also showed some hyperintense lesion in the left-brain hemisphere.

Gluten free diet instituted

It was clear with these test results that the initial diagnosis was a misdiagnosis. The real diagnosis was celiac disease. 7 months after the onset of his symptoms he started on a gluten free diet. He received no medications. Notably, his right arm function returned to normal after 9 month of the gluten free diet. Although there was some improvement in his right leg function, he still had some muscle wasting and spasticity in his right leg. However, he could now walk without any aid. His hand-writing was back to normal, and he could button his shirts again. Repeat MRI scans followed 2 months and 9 months after the start of the gluten free diet. At two months after initiation of the gluten free diet the brain lesion in the left brain was somewhat larger than before, but at 9 months it was half the original size.

Case #2: Autism in children, youth depression and Alzheimer’s patients

The autism spectrum disorder (ASD) has significantly increased from 1 in 166 in 2004 to 1 in 40 in 2018. In addition, Dr. O’Bryan also mentioned that in 2017 statistics showed that 13.3% among youth aged 12 to 17 in the US suffered major depressive episodes. 1 in every 12 youth suffer from severe behavioral and emotional problems. According to the CDC since 1994 the number of children on psycho-stimulants increased 5-fold. In the same time children under 18 with bipolar disorder have increased 40-fold. There has been a 6-fold increase of prescriptions for antipsychotic medications for children in the same time frame.

Other effects on adolescents

However, I like to point out that there are other powerful factors that can explain increased depression and emotional problems in adolescence. The Canadian Medical Association published an article about social media and smart phones and the effects they have on adolescence.

On the other end of the life cycle 1 in 3 seniors die with Alzheimer’s disease or dementia. Between 2000 and 2015 death from Alzheimer’s disease has increased by 213%.

Breakdown of the blood brain barrier

According to Dr. O’Bryan autism in children, behavioral and emotional problems in teenagers and dementia from Alzheimer’s disease are all related to the same process, namely a breakdown of the gut barrier, often called leaky gut syndrome. It is important to realize that this leads to a secondary breakdown of the blood brain barrier. The end result is a compromise of the brain, where antibodies attack the brain protein. In young children this causes lower adaptive and cognitive function and behaviors typical for autism. Teenagers are more likely to present with depression or schizophrenia. In older people the breakdown of the blood brain barrier can result in Alzheimer’s disease and other forms of dementia.

25 to 30% of protein in wheat are non-gluten. Antibodies can be directed against gluten, but also against non-gluten protein.

IgG antibodies against gluten cross placenta

In the later stages of pregnancy IgG antibodies cross the placenta easily. They provide passive immunity from various viral infections. Unfortunately, antibodies against gluten also cross through the placenta, which can lead to a breakdown of the fetal gut lining, in the sense of leaky gut syndrome. In this study 211 children were found to have a risk of 1.7-fold to develop psychosis later in life. The mothers were positive for anti-gliadin IgG antibodies in the last 4 weeks of pregnancy. Anti-casein antibodies did not have this psychosis effect (risk only 0.8-fold). The investigators felt that an allergy to wheat in the mother set up general inflammation. Psychosis in the offspring only develops when inflammatory mediators reached the brain of the fetus. It was the brain inflammation, which caused the subsequent psychosis later in the child.

Blood brain barrier and healthy gut barrier

Another key point is that the barrier both in the gut and in the blood brain barrier consists of a single epithelial layer. The cells are held together by zonulin and occludin proteins. Autistic children were exposed already in the uterus to mother’s wheat induced anti-gliadin antibodies. This led to a break-down of the children’s blood brain barrier and the symptoms of the autism spectrum disorder. These children have a lot of brain inflammation and in addition often have impaired gut barrier integrity. It must be remembered that they require a comprehensive program to improve the gut flora, build up the gut barrier integrity and re-establish the blood brain barrier.

Effects of phthalates on young children

A 2014 study measured urinary metabolites of phthalates and related this to the children when they were 7 years old.

The investigators did several cognitive tests and measured the IQ (Wechsler Intelligence Scale). Children of mothers with the highest quartile of phthalates had an IQ, which was on average 7.0 points lower than the control group of the lowest quartile of phthalates. Dr. O’Bryan showed a slide taken from this study.

With this in mind, it points out that a pregnant woman has an intact blood brain barrier, which prevents antibodies from entering. However, the immature brain of the fetus has not developed an efficient blood brain barrier yet. This allows maternal gliadin antibodies from wheat intolerance to enter the fetal brain and cause autism spectrum disorder (ASD).

PCB’s disrupt the blood brain barrier

In mouse experiments the effects of PCB’s were investigated. By the same token, researchers found that the blood brain barrier was broken down by PCB’s that are known to have carcinogenic and neurotoxic properties on the brain. The researchers injected melanoma cells into the animals and found that the PCB pretreated mice sustained brain metastases. However, the control animals that did not have PCB pre-treatment did not develop brain metastases. They concluded from this that PCB’s are breaking down the blood brain barrier.

Maternal brain antibodies causing autism in children

This publication examined antibodies to two different brain proteins. The researchers found that 86% of the children from mothers with two different fetal brain antibodies were diagnosed with autistic regression. According to this publication there are at least 50 different epitopes of gluten peptides that exert cytotoxic, gut permeating and immunomodulatory activities.

DNA microarray technology can now detect many subtypes of food disorders and gluten sensitivities. The tests for celiac disease have a sensitivity of 97% for IgG and 99% for IgA. With regard to specificity the test is now 98% accurate for IgG and 100% for IgA.

Case #3: 34-year old female vegan patient with depression and mild cognitive decline

A 34-year old woman has followed a Vegan lifestyle for 10 years. She has been working long hours and had a lot of stress. In addition, her thyroid was borderline low with high TPO antibodies. A blood test for vitamin D showed vitamin D deficiency. For the past year her energy level was low and she had developed chronic depression. Her physician did a genetic test that found she carried the gene that converts GABA into glutamate. She thinks that she has small intestinal bacterial overgrowth (SIBO). A review of her dietary habits revealed that she ate more cooked foods and less raw food. Her memory is slightly off, her speech not as fluid and she has some cognitive decline.

Her blood tests showed anti-immunity to RAGE peptides. To put it another way, RAGE stands for “receptor for advanced glycation end products”. When you eat too much overcooked foods you ingest advanced glycation end products. This can have adverse effects on your body, particularly the brain.

More tests regarding this woman

Another specific test revealed a blood brain barrier disruption with the presence of anti-brain antibodies. A stool sample was obtained. It showed low Akkermansia, low Faecali bacterium, low Bifido longum and low Bifido adolescentis bacteria. A chemical analysis revealed low butyrate, propionate and acetate. The treating physician concluded that she had a gut dysbiosis and a dysfunctional gut barrier. This has also affected her blood brain barrier. The constellation of symptoms and blood tests explain her clinical condition. She has developed autoantibodies that affect her thyroid gland and her brain because of the antibodies against her RAGE peptides. People can develop Alzheimer’s disease given enough time with exposure to these antibodies. The leaky gut has led to a break-down of her blood brain barrier and exposed her brain to autoimmune antibodies directed against brain cells.

Treatment of gut dysbiosis

This patient started a gluten free diet (GFD). But one of the problems of the GFD is that wheat is removed that normally provides 69% inulin and 71% oligofructose, both important prebiotics that are necessary for probiotics to work with. Inulin is contained in beets, leeks, asparagus, onions, garlic and bananas. Oligofructose is contained in chicory root, bananas, onion, and garlic.

When people consume a typical Western diet, they get between 1 and 4 grams of inulin daily. But others who eat balanced diets get up to 25 to 100 grams of inulin per day. Dr. O’Bryan explained that going on a GFD leads to an altered microbiome.

Experiment with volunteers to measure the effects of a gluten free diet

He discussed an experiment on 10 healthy volunteers who were fed a GFD for 1 month.

The researchers ordere stool samples in the beginning and at the end of the experiment. There was less of the good bacteria and more of the the bad bacteria. This led to a less protective and more inflammatory environment. The remedy for that is to eat 1 root vegetable and 2 other prebiotics per day. The patient on a GFD must supplement with prebiotic-rich foods to prevent this from happening.

Non-digestible oligosaccharide supplement

Inulin and oligosaccharides support the intestinal microbiota.  Dr. O’Brien suggested to add a supplement, called Precision Prebiotic™, non-digestible oligosaccharides that can increase microbial diversity. This supplement supports the growth of the healthy bacteria. These are keystone bacteria like Akkermansia muciniphila, Faecal bacterium prausnitzii, and Bifidobacteria.

Other supportive measures for the gut

  • 1 tablespoon of fermented vegetables like sauerkraut once per day
  • The ingestion of fermented foods increases the beneficial gut bacteria by a factor of 10,000-fold!
  • A 100% spore-based probiotic supplement increases diversity of the gut flora and helps to maintain the gut barrier
  • Sodium butyrate, which comes from fermented food is an important modulator of the central nervous system
  • In addition, sodium butyrate also inhibits pathological gut bacteria and maintains the gastrointestinal balance
  • In neurodegenerative disorders sodium butyrate provides anti-inflammatory and neuroprotective effects
  • Sodium butyrate restores the blood brain barrier
  • Following heart attacks or strokes sodium butyrate promotes tissue repair and recovery through cell survival
Celiac Disease in Various Disguises

Celiac Disease in Various Disguises

Conclusion

Dr. Tom O’Bryan delivered a lecture at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec.13, 2019. Wheat allergies have increased in the last decades. Researchers have found that in many people there is a deterioration of the gut flora and a breakdown of the gut barrier. This leads to antibody formation against gluten or gliadin (wheat proteins). This exposes the body to many proteins from the gut. The body reacts by producing antibodies to them. These are also affecting cells in the body as they cross react with body proteins. The inflammation from the autoantibodies cause the blood brain barrier to break down. Now the immune system can produce antibodies against brain tissue. In the past  with an intact blood brain barrier this was not possible.

Autoantibodies in various life epochs

At a young age autism can develop because of antibodies against gliadin from wheat. In our youth schizophrenia and depression can occur from gut dysbiosis and a subsequent break down of our blood brain barrier. In old age Alzheimer’s disease develops in 1 out of 3 people due to gut dysbiosis and a breakdown of the blood brain barrier with anti-brain antibodies. Dr. O’Bryan explained how a person can turn this negative spiral around and start a new life without these problems. You can avoid a lot of these diseases by eliminating wheat and processed food from your diet.

Apr
23
2016

Healing Powers Of Green Tea

Powerful catechins that are a special form of bioflavonoids provide the healing powers of green tea. Researchers have proven that these catechins are only in green tea, not so much in black tea. The most effective of several catechins contained in green tea is EGCG, which stands for EpiGalloCatechin-3-Gallate. It crosses the blood/brain barrier and is very important for the protection of the brain from Alzheimer’s disease. But green tea or green tea extract has a diversified pharmacological action. Researchers said that green tea protects you from cardiovascular disease, from obesity, from diabetes, from autoimmune disorders, from cancer, from Alzheimer’s and dementia.

In the following I like to comment on how green tea or its extract can protect from all of these diseases.

Alzheimer’s disease

Although there are 5 or 6 approved anti-Alzheimer’s drugs, none of them work for very long. They may at best postpone the deteriorating memory for 6 months, but then the effect of the drug wears off. The reason is that the drugs do not stop the production of the deadly beta-amyloid. It is the beta-amyloid that damages nerve cells that you want to preserve so you can think and memorize. In contrast a simple phytochemical, the catechin EGCG has been shown in animal experiments and in human trials to stop beta-amyloid production and increase solubility of beta-amyloid fragments in the brain. The end result is better memory and no further deterioration.

Two studies showing less strokes and better working memory processing with green tea

In a study of 13,988 elderly Japanese observed over 3 years the group that consumed 3 to 4 cups of green tea daily had 33% less strokes, cognitive impairment and osteoporosis.

Researchers at the University of Basel, Switzerland enrolled 12 healthy volunteers aged 21 to 28 and fed them extracts of green tea or placebo fluid via feeding tubes. They did this to rule out taste as a factor. The patients underwent functional MRI scans and they also received memory-stimulating tasks. Only the green tea extract was boosting activity in the frontal brain of the subjects. This was located in a specific area, called dorsolateral prefrontal cortex. This area has a connection with language comprehension, reasoning and learning. It also switches short-term memory into long-term memory, called working memory processing.

Healing powers of green tea through new nerve cell development

Researchers showed with animal experiments that green tea extract protects nerve cells from the toxic effect of beta-amyloid. At the same time green tea extract triggers the production of new brain nerve cells (neurons). This is really good news for Alzheimer’s disease patients and their families: green tea extract delays further memory deterioration and stimulates the development of new nerve cells in the brain!

Cardiovascular disease

In a 2006 Japanese study 40,530 Japanese adults aged 40 to 79 years without history of stroke, coronary heart disease, or cancer at baseline were observed for 7 years. Diaries were kept about how many cups of green tea each person was drinking per day. The prevention of heart attacks and strokes was the the biggest effect of green tea extracts.

Men had a mortality reduction of 12% for heart attacks when they drank 5 cups or more of green tea; in women the corresponding mortality reduction for heart attack was 31%, a bigger effect. Overall mortality from strokes was lower than from heart attacks. This made the effect of green tea consumption even more beneficial with respect to stroke prevention. This study did not show any cancer prevention effect for green tea.

Obesity

It appears that green tea increases heat production and burns fat in the process. There was a small effect in terms of weight loss and a beneficial effect increasing the protective HDL cholesterol in this 2012 Polish study on obese patients. The authors compared either 379 mg of green tea extract, or a placebo, daily for 3 months. They concluded: “The results of this study confirm the beneficial effects of green tea extract supplementation on body mass index, lipid profile, and total antioxidant status in patients with obesity.”

Diabetes

Although there are claims in some studies that green tea would prevent diabetes, this question was thoroughly investigated in this Chinese 2014 study.

Researchers did not see any effects on fasting blood sugars or on hemoglobin A1C values. Hemoglobin A1C is a very sensitive indicator for the presence or absence of diabetes. All these lab tests showed no change following consumption of green tea or green tea extract. Forget using green tea for diabetes prevention; cut out sugar and starchy foods instead.

Autoimmune disorders

Sjogren’s syndrome and lupus are both autoimmune diseases. Green tea extract has shown in humans that symptom severity can improve; green tea polyphenols (GTPs) possess anti-inflammatory properties that benefit patients with autoimmune diseases.

In an animal model arthritis researchers determined that T helper cells are weakened and bone resorption is inhibited by EGCG from green tea extract.

Researchers at Harvard Medical School, Boston, MA have noted that green tea extract is useful in calming down the immune response in autoimmune diseases. They concluded: “Altogether, these studies identify and support the use of EGCG as a potential therapeutic agent in preventing and ameliorating T cell-mediated autoimmune diseases.”

Cancer

Many researchers found that EGCG from green tea extract has immune modulatory effects. Furthermore, they saw a positive effect when patients received EGCG in combination with chemotherapy. A combination of cisplatin therapy with green tea extract has been found to have more effects on colorectal cancer and ovarian cancer than each one on its own. Similarly chemotherapy of breast cancer had better results in humans when EGCG from green tea extract was added as an immune modulation. More research, particularly in humans is needed to fully understand the mechanism of action of EGCG.

Toxicity of green tea extract

Animal experiments showed that higher doses of green tea extract could cause toxicity in the liver and in the nose of rats and mice. I was not able to find objective evidence for green tea toxicity in the PubMed system with respect to humans.

Healing Powers Of Green Tea

Healing Powers Of Green Tea

Conclusion

Perhaps the most important discovery regarding green tea extract is as follows. It crosses easily through the blood/brain barrier into the brain. This can postpone Alzheimer’s disease and can even lead to new neuron formation. The beneficial cardiovascular effects are also useful and combine well with exercise and good nutrition for prevention. Particularly stroke prevention is a useful property of EGCG from green tea extract. The effect on obesity is marginal whereas there was no effect of green tea on prevention of diabetes. The immune modulatory effect of green tea extract is useful in the treatment of autoimmune diseases and of cancer. Existing treatments for these conditions are becoming more effective by adding green tea extract.

Jan
31
2016

The Gut and Brain Connection

There is a lot of talk about the gut and brain connection. At the 23rd Annual World Congress on Anti-Aging Medicine (Dec. 11-13, 2015) in Las Vegas there were several lectures pointing out the importance of the gut flora for proper brain function. As a matter of fact, if you have the wrong gut flora, you can get a number of diseases like diabetes, fibromyalgia, rheumatoid arthritis, multiple sclerosis, muscular dystrophy, some cancers and even obesity. Martin P. Gallagher, MD, DC talked about this in his talk entitled “Gut on Fire, Brain on Fire!”

Function of the microbiome

The microbiome is the sum of all microbial organisms inhabiting the human body, which colonize mainly the colon, but also to a lesser degree the small intestine. Dr. Gallagher stated that the microbiome weighs only 7.1 oz., although in the past some have estimated its weight to be as high as 3 pounds. The purpose of the microbiome is to help form a gut/blood barrier. It forms a 30-micron thick layer in the GI tract, protects the intestinal lining and metabolizes food remnants, especially from carbohydrates. In addition, it also communicates with the immune system. There is a cross talk between the lining of the gut and the and the body’s immune system. The gut bacteria help the body to create stability; as a result the good bacteria also decrease intestinal permeability.

Leaky gut syndrome develops

When inflammation occurs in the gut, the thickness of the biofilm is less than 30 microns. Intestinal permeability increases and becomes “leaky gut syndrome”. This can be the cause of autoimmune diseases and possibly other diseases.

The enteric nervous system

The gut can produce as many neurotransmitters as the brain and spinal cord can synthesize. The enteric nervous system communicates with the brain through the vagal nerve. Serotonin is an important neurotransmitter that regulates motility of the gut. The control system of the gut can work on its own and override the concerns of the central nervous system.

Parkinson’s disease is a disorder of the enteric nervous system as well as the brain. With Alzheimer’s disease the characteristic brain lesions are also present in the enteric nervous system!

A mouse experiment showed the following. The Lactobacillus strain is  normally part of the microbiome of the gut.  Re-introduction of Lactobacillus into the gut flora resulted in healing certain parts of the brains of these animals, which researchers associate with anxiety and depression. But when the researchers severed the vagal nerve of these animals, none of these healing changes occurred.

The gut-brain-axis

For this reason the researchers suggested that the gut bacteria are able to communicate with the brain via the vagal nerve. Researchers have coined this connection the “gut-brain axis”. These protective gut bacteria have the ability to protect humans from gastric acidity, from bile acid toxicity, they adhere to the lining of the gut and they persist to reside within the gastrointestinal tract. Probiotics help the immune system to maintain the immunologic memory and to secrete antibodies, called immunoglobulins.

Two strains with benefit to humans are Lactobacillus rhamnosus GG and Saccharomyces boulardii. Probiotics often help against diarrhea. The natural food for gut bacteria in the colon comes from starches of chicory, asparagus, inulin and onions that are indigestible in the stomach and small intestine, but are fermented in the colon to provide food for the bacteria residing there.

Small Intestinal Bacterial Overgrowth (SIBO)

Overgrowth of the small intestine with bacteria that produce endotoxins appears to have significance in both animal models and human disease. Chlamydia species as well as Borrelia burgdorferi (Lyme) can produce toxins that cause hypersensitivity to pain in soft tissues in fibromyalgia and animal models of fibromyalgia. Moreover, SIBO – small intestinal bacterial overgrowth – in experimental animals caused the same hypersensitivity of the soft tissues and also leaky gut syndrome.

Risk factors for SIBO

What causes SIBO is too little stomach acid production, treatment with proton pump inhibitors (powerful anti acid medications) and antibiotics. To summarize, Dr.Gallagher said that SIBO also occurs in post-surgical patients, in patients with diabetes, is brought on by alcohol, nicotine, drugs and GMO foods.

Neurogenic inflammation

Normally the blood brain barrier keeps immune cells from the body out of the brain. Only glucose, proteins and lipids are allowed into the brain, but not lipophilic neurotoxins. In contrast, neurogenic triggers, when admitted to the brain, will compromise the function of the immune cells of the CNS, called microglia. In essence, this can result in memory loss, Alzheimer’s, dementia, seizures, migraines, Parkinson’s Disease, multiple sclerosis, cancer, weakness, numbness, etc.

What triggers inflammation?

Here is a long list of different items that cause inflammation: aging, hormone deficiencies, obesity, diabetes mellitus, cardiovascular disease, fungal infection, the Standard American diet (SAD), pain, trauma and mechanical stress, heavy metals, food allergies, toxins, gut dysbiosis, small intestinal bacterial overgrowth, mal-digestion/absorption, prescription drugs, over-the-counter drugs, recreational drugs and alcohol, lack of exercise and lack of sleep.

Neurotoxic insults start the chain of reactions  like heavy metals, nutritional deficiencies, viruses/fungus/bacteria, inflammatory diet, MSG, solvents, pesticides, herbicides, etc.. One or more of these factors destabilize the tight junctions of the blood brain barrier, which leads to neurogenic inflammation.

Result of neurogenic inflammation

The result is Parkinson’s disease, MS, dementia, chronic pain, behavioral and personality changes, Alzheimer’s disease, ALS and Lyme disease. What seems to be happening a lot is that there is overgrowth of abnormal bacteria in the small bowel, which produce toxins. These in turn lead to leaky gut syndrome, which allows neurogenic triggers to attack the blood brain barrier. It seems like from here it is a short step to neurotoxic insults of the brain overstimulating the microglia, which will produce the diseases listed above.

Healing of brain inflammation

First of all, treatment starts with the Mediterranean diet, which has been shown to have anti-inflammatory properties. Second, people who are gluten sensitive need to eliminate gluten entirely from their food. Third, casein sensitive people need to eliminate dairy products. Furthermore, a triple strength, molecularly distilled fish oil product is taken as a supplement every day with 4 grams or more of DHA/EPA. This helps the anti-inflammatory response.

Glutathione

One of the most powerful antioxidants and anti-inflammatories is intravenous glutathione. This is given as intravenous chelation therapy, which removes heavy metals. Other chelation agents such as EDTA intravenously may be given alternatively. Dr.Gallagher said that glutathione serves as primary cellular defense against free radicals, is a powerful antioxidant and serves as detoxifying agent against xenobiotics. Xenobiotics are remnants of artificial fertilizers, pesticides and pollutants that are contained in crops we eat.

Dr. Gallagher gives 600mg of glutathione twice per day intravenously for 30 days. Uniquely, in Parkinson’s disease patients whose mid brain is often poisoned by mercury this leads to 42% decline of disabilities and the effect lasts for 2 to 4 months after this treatment has been stopped. Coupled with this the treatment also protects telomeres, the caps on the ends of cellular DNA as well as mitochondrial DNA. In addition, glutathione is protective of neurons and nerves.

Curcumin

This common Indian spice, found in turmeric is a potent anti-inflammatory. It is a safe natural agent and has also anti-viral and anti-tumor activities. It binds to the vitamin D receptor and works synergistically together with vitamin D3. Solid lipid curcumin particle technology makes curcumin 65-fold more bioavailable; free curcumin is allowed to pass the blood brain barrier. Lower doses achieve the same effect than regular curcumin.

According to a publication using lipidated curcumin the following observations were made: improved vascular function; equally important, inflammatory markers reduced by 14%; in like manner, triglycerides lowered by 14%; by the same token, oxidative stress reduced; not to mention, catalase increased and finally total antioxidant status improved. Here is another paper about lipidated curcumin.

Omega-3 fatty acids

Omega-3 fatty acids are anti-inflammatory by countering the arachidonic acid pathway that leads to inflammation. Physicians recommend it as triple strength, molecularly distilled fish oil. DHA/EPA are the active ingredients. Chronic inflammation requires 2 to 12 grams daily; irritable bowel syndrome 6 to 12 grams daily; depression, anxiety and insomnia require 2 to 4 grams per day; autoimmune disease, back pain and degenerative joint disease 4 to 12 grams per day.

Gut/brain dysbiosis

For gut/brain dysbiosis Dr. Gallagher recommended to start with a 10-day fruit/vegetable detox program. Milk thistle, glutathione and pancreatic enzymes in combination lead to improvement. Lipidated curcumin is also useful. The physician also gives glutamine, prebiotics and probiotics for gut support. He also tells the patient to take molecularly distilled fish oil (DHA/EPA) and vitamin D3 as anti-inflammatories. Doctors also administer oral and intravenous glutathione to detoxify. Many doctors use natural as a combination of glutathione, oregano, olive leaf and silver salts.

The Gut and Brain Connection

The Gut and Brain Connection

Conclusion

Inflammation can start in the gut, lead to leaky gut syndrome and break down the blood/brain barrier. The end result is that inflammation develops in the brain and Alzheimer’s disease and dementia can occur. The sooner the physician starts with treatment, the faster the recovery is. When the patient has reached the end stage, it is difficult to turn the inflammatory process around. Fortunately there are effective ways to get the inflammation under control with intravenous glutathione in the beginning and subsequent treatment with lipidated curcumin, omega-3 fatty acid and vitamin D3. A permanent switch to a Mediterranean diet is important as well to keep inflammation under control.

Lifestyle and nutrition choices are important for prevention

A few years back this mainstream medicine considered this type of approach as “quackery”; now it is the latest information from research into the brain/gut connection. The right lifestyle and nutrition choices can do a lot on a preventative basis. Once disease has taken root, treatment may still be possible, but once it is at a later stage a full cure is unlikely.

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