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.

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.