Feb
15
2020

Rheumatoid Arthritis Treatment by Regenerative Medicine

By | Arthritis, autoimmune disease, fasting mimicking diet, Nutrition, stem cells

Dr. David Lans gave a talk at a conference in Las Vegas about rheumatoid arthritis treatment by regenerative medicine. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. The full title of his presentation was “Rheumatoid Arthritis, A Regenerative Medicine Approach”.

Dr. Lans is a rheumatologist and Assistant Clinical Professor of Medicine at the New York Presbyterian Lawrence Hospital, Bronxville, NY.

Introduction

Rheumatoid arthritis is a worldwide immune disorder. About 1% of the general population suffer of this illness with a female to male ratio of 3:1. Typically it can affect  the synovial membranes of all joints. To clarify, the presentation is usually symmetrical, but in 40% of all cases this systemic inflammatory disease can also involve other tissues and organs. 70% of cases have a positive rheumatoid factor (RF) in blood tests. However, a newer, more specific blood test for rheumatoid arthritis is anti-cyclic citrullinated peptide (anti-CCP). Symptoms of rheumatoid arthritis are anemia, fatigue, malaise, joint pain and joint stiffness. Inflammatory blood markers are positive.

Causes of rheumatoid arthritis

Genetic causes play an important role in the causation of rheumatoid arthritis. Over 100 genes  can increase due to genetics. Twin studies showed that the concordance rate to develop RA is only 15-20%. Certainly, this means that in order to develop RA you need a double hit: the genetic vulnerability for RA and also an environmental triggering factor. Meanwhile, here is a list of environmental risk factors:

  • Smoking
  • Gum disease (chronic gingivitis)
  • Any chronic infection
  • Dysbiosis in the gut
  • Environmental toxins
  • Heavy metal toxicity
  • Poor diet and nutrition

In other words, the common denominator to all of these environmental risk factors is the disruption of the mucosal integrity. In fact, this starts the process of chronic inflammation and autoantibodies (like RF and anti-CCP) resulting in chronic synovitis.

How inflammation travels from mucosal surfaces to the synovium of joints

Inflammation in gums, lungs or gut can travel via the blood and the lymphatic system into periarticular bone. This leads to bone and cartilage damage. Consequently, the bone destruction leads to chronic synovitis. To emphasize, Dr. Lans said that no patient with rheumatoid arthritis will develop symptoms of RA unless the autoantibodies have developed. In the same vein, there is a distinct preclinical period of RA with positive blood tests for RA, but absent clinical symptoms.

Prevention of synovitis through a preventative program

It is important to realize that because of this time relationship there is room for a preventative program where patients are taught the importance of dental hygiene. Another key point is that good health habits and nutrition are also important for prevention. When patients develop early-onset RA, the following measures often help to alleviate the development of symptoms: anti-inflammatory diet, stress management, intermittent fasting, a gut healing program, nutraceuticals like vitamin D3 and fish oil. Herbal therapies are also important like curcumin, Boswellia serrata, devil’s claw, ginger, Ashwagandha and others.

Conventional medicine approach versus the regenerative medical approach

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfosalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients.

Regenerative medical treatments for RA patients

Significantly, platelet rich plasma (PRP), peptides, stem cell therapy and exosomes are some of the modalities that show promise. (I’ll explain the meaning of exosomes later.) In addition, red light therapy and low-level laser therapy can help joint synovitis.

PRP provides growth factors to repair damaged tissues and is anti-inflammatory. Peptides consist of short chains of amino acids that have anti-inflammatory effects and promote healing of damaged tissues. Thymosin-alpha 1, Thymosin-beta 4, BPC-157, Melanotan II and FOXO4-DRI are examples of peptides used in patients. Special blood tests are used to monitor whether the treatment of RA is successful. These tests are: C-reactive protein, sedimentation rate (ESR) and Vectra. Vectra measures 12 protein markers that are important in RA.

More info about peptide therapy

Researchers noticed that peptides are very safe, but they are also very effective. HAP-1 seems to bind to synovial surfaces. RDG peptides work closely together with integrin-binding proteins. Together they have an anti-inflammatory effect in rheumatoid arthritis. They are capable of blocking both the inflammatory and autoimmune components of rheumatoid arthritis. Thymosin-alpha 1 is a peptide with powerful effects as an immune and inflammation modulator. Thymosin-beta 4 is promoting tissue healing. BPC-157 is a peptide with 15 amino acids. It helps with the regeneration of tissue after damage.

Melanotan II is a synthetic peptide derived from melanocortin, a pituitary hormone. It helps to suppress cytokine-meditated inflammation.

FOXO4-DRI is a peptide that stimulates the removal of senescent cells. Because of this it is called a senolytic. Researchers are still investigating FOXO4-DRI in humans and for the tissue repair effect in rheumatoid arthritis patients.

The use of stem cells in RA therapy

Another biological remedy for treating RA patients is the use of mesenchymal stem cells. In 2013 rheumatoid patients received umbilical cord stem cells to study the effect of stem cells. The clinical trial consisted of 172 patients. In the trial disease modifying anti-rheumatic drugs plus placebo were compared to disease modifying anti-rheumatic drugs plus umbilical cord stem cells (treatment group). In the treatment group inflammatory cytokines were reduced and regulatory T cells were increased. Improvement was assessed with objective clinical measures and blood tests. The improvement lasted between 3 and 6 months.

Exosome therapy from mesenchymal stem cells 

Many of the effects of stem cells are explainable by so-called exosomes. They are cell particles shed by stem cells. They contain signalling proteins (integrins), messenger RNA and many other healing substances. The bioactive effects are very diverse. Exosomes are bactericidal, antifungal, stimulate angiogenesis and stimulate tissue regeneration. They are also anti-apoptosis, anti-tumoral, anti-fibrosis, stimulate immunomodulation and cause chemoattraction.

What does that mean clinically? Exosomes suppress the release of inflammatory cytokines. Anti-inflammatory cytokines (like transforming growth factor beta or TGF-beta) are increased. Exosomes reduce the Th17 cells (T helper cells that produce the inflammatory cytokine IL-17). They also promote osteochondral regeneration, which is important for joint healing in the treatment of RA patients.

Treatment of RA using the integrative and regenerative medicine approach

  1. The physician assesses all affected joints and orders blood tests to check the inflammatory status.
  2. Identify the triggers that perpetuate the RA disease. Typically there are gut dysbiosis issues that need treatment. Sleep hygiene and stress issues require modification.
  3. Assess the need for disease modifying anti-rheumatic drugs (DMARDs); these are drugs like methotrexate, sulfosalazine and others.
  4. Peptide protocol: BPC-157: 300 micrograms once or twice daily IV; Thymosin alpha: 300 micrograms once or twice daily IV; Thymosin beta: 100 to 300 micrograms once daily IV, limit to 3-month cycle.
  5. Mesenchymal stem cell therapy and exosomes.
Rheumatoid Arthritis Treatment by Regenerative Medicine

Rheumatoid Arthritis Treatment by Regenerative Medicine

Conclusion

Rheumatoid arthritis is a common autoimmune disease, which leaves the patient disabled, if she receives no treatment for it. Conventional rheumatologist protocols treat the inflammation with various drugs, but they cause a lot of side effects.

There is an emergence of regenerative therapies that may be able to help treat the inflammation of the rheumatoid arthritis patient with less side effects. At the same time these treatments can also help to repair the damaged tissues. There is a great need for more clinical studies. Current human data are limited. Safe options to treat RA patients are mesenchymal stem cell therapy, exosome treatment and peptide therapies. The approach of the physician depends on the clinical stage the patient is in. It is common sense that early diagnosis and treatment will have better results. Also, an integrative approach has the best chance to help the patient with the least side-effects.

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Jan
04
2020

Preserving Youthful Power

By | exercise, fasting mimicking diet, Fitness, Health

Dr. Christopher W. Shade (PH.D.) presented a lecture in Las Vegas on Dec.13, 2019 talking about preserving youthful power. The presentation was at the 27th Annual World Congress on Anti-Aging Medicine and his title was “Building Youthful NAD+ Power with Precursors, Sirtuin-Activating Compounds, and Methylation support”.

In the first place, nicotinamide adenine dinucleotide (NAD+) is a signalling molecule between the DNA of the nucleus of cells and the energy producing mitochondria that reside in the cells. The exact nature of the interaction is described in this review article. It describes how stress leads to a depletion of NAD+ and sirtuins, and causes accelerated aging. On the other hand, calorie restriction and exercise lead to increased production of NAD+, activation of sirtuins and longevity.

Details about low NAD+ activity

It is important to realize that when NAD+ is below a critical level the following disease states can develop. First, in the brain it is Alzheimer’s disease and neurodegenerative disease. Second, in the eyes macular degeneration and keratoconjunctivitis sicca can develop. Third, severe plaque-type psoriasis can occur in the skin. Fourth, the pancreas develops hyperinsulinemia and metabolic syndrome. Fifth, type 2 diabetes can make your muscles weak. Sixth, sarcopenia with loss of muscle mass and cardiovascular disease in the heart can also develop. Seventh, the liver reacts to the metabolic syndrome by causing hepatic steatosis. Metabolic syndrome causes inflammatory cytokines in the fatty tissue. Eighth, the lungs react by developing chronic obstructive pulmonary disease. Ninth, your blood can get endotoxin-induced inflammation and sepsis from bacteria. A lack of NAD+ causes all of these negative changes simultaneously in the body.

In fact, when a person exercises regularly, uses intermittent fasting as a tool of calorie restriction and takes supplements of NAD+ all of these negative processes stop and sirtuins are activated restoring the body to a more youthful condition.

Summary about the effects of NAD+

In other words, NAD+ is important for cardiometabolic health, energy balance, liver health, immune health and cognitive health. NAD+ is also involved in maintaining the membrane polarity of cell walls. The blood /brain barrier and the gut/blood barrier are also kept intact by NAD+. In addition, NAD+ is involved in detoxification and control of the action of free radicals. It also is important to control Inflammation. For these reasons, it is not a surprise that people with normal NAD+ function will be healthier than those who have a problem with this.

Sugar reduces NAD+ to NADH

It is important to note that scientists could show in animal models and in humans that sugar overconsumption leads to the reduction of NAD+ to NADH. All of the negative effects described above for low NAD+ are then coming true. NADH is a reduced and disabled form of the oxidized NAD+. In essence, this substance has no biological action.

Energy metabolism

Biochemists have determined with regard to the energy metabolism of mitochondria that there are three occasions where enzymes are dependent on NAD+. Without NAD+ the energy-providing oxidative metabolism in mitochondria would not take place. As NAD+ is lower in older age, this explains why an aging population has less energy. In addition, as we age, the number of mitochondria per cell is decreasing. That is to say that an aging population has less energy than youthful people.

Other factors that are important in preserving youthful power

The AMPK signalling pathway

AMPK stands for 5′ AMP-activated protein kinase. This is an enzyme that consists of three protein portions. In humans it is expressed in liver, brain and muscle tissue. It provides energy in the liver by fatty acid oxidation. In muscles it stimulates glucose uptake and fatty acid oxidation. AMPK also inhibits cholesterol synthesis, lipogenesis and triglyceride synthesis. Fasting and exercise can stimulate AMPK production, which in turn will stimulate SIR1 genes and NAD+ production. This is especially happening in muscle tissue. To put it another way, there are a close-linked metabolic reactions between NAD+, AMPK and sirtuins.

Balance between AMPK, NAD+ and methylation

Given the right circumstances this can lead to detoxification, longevity and energy. This is what intermittent fasting and exercise can do for you. AMPK needs high NAD+ levels to give you all of the benefits. But NAD+ must be balanced with methylation. This is a somewhat difficult subject to explain, but the link explains it in somewhat technical terms. In other words, with a balance of the body’s biochemistry the person is healthy. When there is a disbalance, you get sick.

Practical application how to supplement for preserving youthful power

Dr. Shade asked the rhetorical question: how can we achieve a balance between NAD+ and methylation?

His answer is to supplement with the following supplements.

  • Trimethylglycine (Betaine) 2‐5g/day
  • Vitamin B2: 10‐30mg/day
  • SAMe or methylcobalamin 1000‐3000mcg/day
  • Measure Homocysteine as marker of methylation; if it is low, the methylation pathway is normal and there is balance.

Next: how to we raise NAD+? The answer is by cardio-metabolic blending.

  • Berberine and quercetin (they are respiratory chain modulators)
  • Resveratrol, silymarin and lipoic acid (they are liver kinase B1 activators)
  • Resveratrol or pterostilbene and quercetin (they are sirtuin activators)
  • Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) 200- 400 mg per day
  • Trimethylglycine (Betaine) 2-5 grams per day and methylcobalamin, B2, and others (methylation support)
Preserving Youthful Power

Preserving Youthful Power

Conclusion

It is difficult to describe energy flow in biochemical terms. Dr. Christopher W. Shade did exactly that in a lecture he gave at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec.13, 2019. The key for preserving youthful power is to balance the metabolism that occurs in the nucleus of the body cells with the metabolism taking place in the mitochondria. The mitochondria are the energy producers, but the steering of this occurs through the metabolic products from the cell nucleus. NAD+ plays a key role in our energy metabolism. But there is an interplay with AMPK, which stands for 5′ AMP-activated protein kinase. Sirtuin genes interact with these messenger molecules as well and this is where longevity comes in.

Longevity through sirtuin stimulation

Sirtuins are longevity genes that help us get more energy for a longer period of time. Regular exercise stimulates this complex biochemistry giving us extra NAD+ for energy. Intermittent fasting also stimulates sirtuins, which adds to the extra energy and gives us longevity. This is not a bad deal when you look at it from a distance. We can achieve a lot preserving our energy through an active life style. Supplements can be an auxiliary measure, but they are not effective enough without positive lifestyle choices.

Aug
10
2019

Fasting Mimicking Diet For 5 Days Every Month

By | Anti-aging medicine, autoimmune disease, Cancer, Cardiovascular disease, cholesterol, Diabetes, diet, fasting mimicking diet, food, heart attack, High Blood Pressure, Multiple sclerosis, Nutrition, Obesity, Pain, Prevention, stem cells, Stroke, telomeres

In December 2017 I heard Dr. Longo speak at a medical conference in Las Vegas. He suggested the use of the fasting mimicking diet for 5 days every month. I am getting into the age group where a little help from nature would not harm (I am 74 years old). I started immediately in December 2017 to do a fasting mimicking diet (FMD) for 5 days.

Effects of fasting mimicking diet

In the beginning you just notice that you are not as hungry as you thought you would be, because you do take in three mini meals of about 200 calories each, which curbs your appetite. It is also important to consume enough liquids. Please note: liquids! Not liquor! Wine, beer or any alcoholic drinks are not part of the diet. You can drink water, but, this may get boring, and you can take water with lemon, herbal teas, black tea and coffee, as long as you stay away from sugar-laced drinks.

How the FMD works

Your total calorie intake will amount to no more than 600 calories per day for the 5 days where you do the fasting mimicking diet. Your body mass index (BMI) decreases between 0.1 and 0.4 per day to a total of 0.5 to 0.9 for the 5 days. This does not seem much, but if it is accumulating every month, a person who is obese now could have a normal weight within one year. The first day of this fast may present some challenges. I found that in the afternoon I felt hungry. What helped was a hot drink( tea, coffee, clear broth). Day two was better, and from day three it has become a routine. There are  no ferocious hunger pangs, no headaches or feelings of weakness or tiredness. I am always surprised that my energy level is improving when I do the fasting mimicking diet for 5 days every month.Dr. Longo suggests not to exercise during the fast. It is obvious that this time is not suitable for half- marathons or taxing hikes, but I found that thirty minutes of aerobics and thirty minutes of weight training felt good. Listen to your body! If you feel lightheaded at any time, stop! The emphasis is on “moderate”.

Dr. Longo noticed the following findings in a mouse model as well as on humans. I summarized this before in a previous blog:

Specific results when on the fasting mimicking diet for 5 days every month

  • Obesity diminishes, because of the weight loss effect due to missing calories.
  • Diabetes: insulin resistance becomes lower and blood sugar levels drop.
  • High blood pressure reduced: many patients were able to reduce their medications or discontinue them
  • Pain conditions improve as all kinds of pain disappears, an effect for which there is no explanation at this point
  • Autoimmune diseases like MS and rheumatoid arthritis improve, likely because of the effect of increased stem cell circulation
  • Prevention of heart attacks and strokes because of reduction of LDL, triglycerides and CRP
  • Cancer cure rates improve by protecting normal cells, the bone marrow and stimulating the immune cells
  • Longevity improved in mice with a 3-fold increase of their life span. Telomere length in humans was increased. Increased stem cells will find defective areas that need repair. This effect leads to less disease in older age.

Meal samples of fasting mimicking diet

Dr. Longo developed a kit containing all pre-packaged foods for 5 days under the name “ProLon Fasting Mimicking Diet”. The package is not larger than a shoebox, and the diet is plant-based, has some nutrition bars, drinks as well as freeze-dried soups. You can argue about the nutritional value, as it has an average rating of 3.5 out of 5. It also comes in at a hefty price of 300.00 USD. In reality it is a matter of calorie-math to consume very little food. There are plenty of tables available on the Internet that tell you the nutritional value of foods, and it does not take much effort to compose your own menu.

Here is a fairly typical list of foods

Breakfast: A typical breakfast consists of 2 slices of rye crisp bread (Wasa or Ryvita) with a bit of almond butter on it, a cup of coffee and either black or with stevia and milk.

Lunch: 8 oz. of tomato soup and coffee or tea.

Dinner: A tossed salad with organic bell peppers, ½ tomato, and two thin slices of avocado, vinegar and 1 tablespoon of olive oil.

Here is an alternative meal sample:

Breakfast: Eat a nutrition bar that is based on nuts. It should not be more than 250 calories. Alternatively make your own! Have tea or coffee.

Lunch: 8 oz. of homemade vegetable soup without the addition of pasta or beans.

Dinner: Miso soup and 4 rice crackers, alternatively a small tossed salad with olive oil and vinegar.

Results of fasting mimicking diet for 5 days every month

Here are typical results that I found over several months. I am using body composition scales every day to measure my weight, body fat percentage, visceral fat percentage, muscle percentage, calories burnt and the BMI.

One month the BMI went from 21.9 to 21.1 during a 5-day FMD. Another month the BMI experienced a reduction from 21.7 to 21. 2. Here is a list of the some of the 5-day losses of my BMI on a couple of occasions: 0.8, 0.4, 0.9, 0.7, 0.6, 0.5, 0.7 and so on.

It is important that you are not going on an eating binge after those five days. The FMD conditioned your body to be content with very small amounts of food. Enjoy your food, but stick to moderate portions.

Discussion of fasting mimicking diet for 5 days every month

An intermittent fasting mimicking diet was shown to have a diversified positive health effect in both animal models and humans. For instance, inflammatory bowel disease improves on FMD by improving the bowel microbiota and by promoting the intestinal regeneration.

Intermittent fasting, as this article shows, can prevent age-associated diseases.

This article suggests that T-killer cells that attack cancers are promoted by the intermittent fasting mimicking diet.

A FMD in type 1 diabetic patients has been shown to restore insulin generation in islets of the pancreas of these patients. The result was an improvement of their type 1 diabetes.

More research data on fasting mimicking diet

A clinical trial with 100 subjects was undertaken by Dr. Longo and his research team. He measured markers after 3 cycles of a fasting mimicking diet for 5 days every month. They found that the FMD reduced aging markers, improved diabetes and reduced susceptibility for cancer and cardiovascular disease. In another publication Dr. Longo and co-authors describe how autoimmune diseases can be improved by the use the fasting mimicking diet for 5 days every month.

Another publication by Dr. Longo describes that “age-related disorders including diabetes, cardiovascular disease, cancers and neurological disorders such as Alzheimer’s disease, Parkinson’s disease and stroke” can be prevented by fasting mimicking diet for 5 days every month.

Even cancer prevention and cancer treatment can be helped by the fasting mimicking diet.  The FMD makes chemotherapy more tolerable.

Fasting Mimicking Diet For 5 Days Every Month

Fasting Mimicking Diet For 5 Days Every Month

Conclusion

I have shown that with the fasting mimicking diet (FMD) done for 5 days in every month you can lower your body mass index (BMI) by 0.4 to 0.9 units. On the long-term this helps you to keep your BMI stable and in the 21.0 to 22.0 range. Dr. Longo has researched the effect of the FMD in both mice and humans. He found that you age better with less age-related diseases. In addition, inflammatory bowel disease, autoimmune diseases like MS, rheumatoid arthritis and type-1 diabetes improve. Cancer patients who need chemotherapy tolerate it better. Their immune system also produces more killer T cells that destroy cancer cells. The FMD prevents heart attacks, strokes and cancer. Dr. Longo also has shown that there is stimulation of stem cell production and telomeres are increasing in length. Telomeres are important for longevity, which allows you to age healthier with less disease.