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 (products of mesenchymal stem cells) 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 the 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.

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Apr
11
2020

Our Immune System Needs Vitamin D3

When we age, our resistance to infections weakens, but this may be because our immune system needs more vitamin D3. I have reviewed the super powers of vitamin D3 before in 2014. In the past it was thought that the human body would need only 400 IU of vitamin D3 every day to cure rickets. And this was the daily recommendation for vitamin D3 for several decades. Gradually it became known that for cancer prevention, infection prevention, cardiovascular illness prevention and for diabetes prevention much higher doses of vitamin D3 were needed. As this link points out, almost 50% of the world population is deficient in vitamin D. This is due to a lack of exposure to sunlight and due to inadequate supplementation with vitamin D3.

25-hydroxy vitamin D level

For several years now the 25-hydroxy vitamin D level in serum is accepted as the best tool to assess the vitamin D status of a person.  In the following you find data from this link.

Various 25-hydroxy vitamin D levels

Vitamin D deficiency (leading to rickets in infants or osteomalacia in adults): less than 12 ng/mL (less than 30 nmol/L)

 Inadequate vitamin D levels in healthy individuals (inadequate for bone or general health): 12 ng/mL to less than 20 ng/mL (30 to less than 50 nmol/L)

 Considered adequate for bone and overall health: 20 or more ng/mL (50 or more nmol/L)

 “Emerging evidence links potential adverse effects to such high levels”: >50 ng/mL(particularly >60 ng/mL); or >125 (particularly >150 nmol/L)

Vitamin D requirement in diseases other than rickets

We see from this that in terms of rickets there is a clear dose-response curve, where low vitamin D serum levels give a child rickets and higher levels prevent rickets. This is historically how vitamin D was detected as a vitamin. In the meantime, researchers have found vitamin receptors on many cells, so that endocrinologists consider vitamin D3 a hormone and signalling molecule.

The above link said that a vitamin D level of 20 to 50 ng/mL is normal. This link says that 20 and 40 ng/mL would be normal. But it adds that others recommend a level between 30 and 50 ng/mL.

Mortality of ICU patients is higher when vitamin D is low

A study from 2015 examined the mortality of 135 ICU patients. The researchers correlated Vitamin D blood levels with mortality rates of the patients. When vitamin D levels were below 12 ng/mL, there was a mortality rate of 32.2%. Patients with higher levels of vitamin D had a mortality rate of 13.2%. The authors concluded that low vitamin D blood levels were an independent risk factor for mortality. Patients less than 12 ng/ml had a 2.4-fold higher risk of dying than patients with normal vitamin D levels.

Stroke patients with low vitamin D worse off

Studies have shown that patients with the lowest level of vitamin D have the poorest functional outcomes following a stroke. When the vitamin D level was below 30 ng/mL the area of dead brain tissue was about two times larger than in those who had adequate vitamin D levels. Moreover, for every 10 ng/mL decrease in vitamin D levels the odds of a healthy recovery 3 months after the stroke fell by about half. This was independent of age and the initial stroke severity.

Seasonal vitamin D3 deficiency from January through April contributes to influenza

In a publication of 2006 Dr. John Cannell and co-workers have reviewed why influenza has seasonal outbreaks. They found that the innate immune system was very dependent on vitamin D3. Those who did not get enough sunlight in the northern hemisphere during January, February, March and April have an average 25-hydroxy vitamin D level of only 15 to 17 ng/mL. In contrast, from July to September the same volunteers had vitamin D levels of 24 to 29 ng/mL. The authors stressed that this was the reason why in the late winter/early spring flu seasons come and go every year while in summer they disappear.

Vitamin D requirements for immune system is 2000 IU or more per day

Vitamin D is essential for the functioning of the innate and adaptive immune system. They also had a reason why children are not as affected by influenza viruses as adults are: “The innate immunity of the aged declined over the last 20 years due to medical and governmental warnings to avoid the sun. While the young usually ignore such advice, the elderly often follow it”. Had the older patients taken higher doses of vitamin D3 every day their immunity would have been as strong as the children’s immunity. The publication cites another publication that found that 2000 IU per day or more will strengthen the immune system. Note that this is a higher dose than for rickets that responds to only 400 IU of vitamin D3.

Patients with many diseases lack vitamin D, but improve with vitamin D3

Many diseases showed an association with an underlying lack of vitamin D. When doctors examine patients’ blood who have arthritis, cardiovascular disease, breast cancer, diabetes, osteoporosis, influenza and others, their 25-hydroxy vitamin D level is usually below 15 ng/mL. This means that these patients have a very weak immune system. Vitamin D3 can restore their immune system and also restore more than 100 polypeptides that contribute to the healing process.

Here is evidence from US researchers that states that higher doses of vitamin D3 will mitigate the course of influenza and of Covid-19 coronavirus. The researchers outlined vitamin D has 3 effects:

  1. Maintaining tight epithelial junctions making it more difficult for the Covid-19 coronavirus to penetrate.
  2. “Killing enveloped viruses through induction of cathelicidin and defensins.” These powerful antiviral polypeptides can kill viruses that have invaded the blood stream within 1 to 2 days.
  3. “…And reducing production of proinflammatory cytokines by the innate immune system, thereby reducing the risk of a cytokine storm leading to pneumonia.” It is people who get the viral pneumonia that are at a high risk of being killed. By bringing the blood level up to the higher range of normal, between 50 and 80 ng/mL, patients that have encountered Covid-19 coronavirus are more likely to survive.

Higher doses of vitamin D3 for various diseases

Dr. Norman Shealy has summarized here what Dr. Joe Prendergast, an endocrinologist and diabetologist did for various patients. This link also contains many references regarding the use of high doses of vitamin D3.

During 30 years of clinical practice Dr. Prendergast treated some conditions where the vitamin D level was extremely low and where patients had a profound weakness of the immune system.

He treated these patients with 50,000 IU of vitamin D3 daily for various times. The diseases that responded to vitamin D3 therapy follow.

Conditions responding to vitamin D3 therapy

  • Reversal of advanced coronary disease
  • Reversal of advanced lung disease, avoiding a lung transplant!
  • Cure of multiple sclerosis
  • Cure of amyotrophic lateral sclerosis
  • Regression of rheumatoid arthritis
  • Improvement in allergies
  • Control of many cancers including prostate, breast, colon, brain tumors, leukemia, myeloma, etc.
  • Reversal of osteoporosis
  • Prevention of influenza
  • Cure of depression and many other mental disorders
  • Hashimoto’s hyperthyroidism

No toxicity with higher doses of vitamin D3

LinkedIn summarizes Dr. Prendergast’s career as follows:

“J. Joseph Prendergast has been a practicing physician for over 30 years. He is Board Certified in Internal Medicine as well as Endocrinology and Metabolism. A graduate of Wayne State University in Detroit, Michigan he completed a fellowship in Endocrinology and Metabolism at Henry Ford Hospital Detroit, MI and his residency at the University of California, San Francisco. Dr. Prendergast has published over 40 medical articles in well-known publications such as the Journal of the American Medical Association, The New England Journal of Medicine and Diabetes Care.”

Do not take calcium supplements when on higher doses of vitamin D3

Dr. Prendergast had no complications in patients with these high doses of vitamin D3, but he stressed that the patient is instructed not to take calcium supplements to prevent high calcium levels. He checks vitamin D blood levels and aims at levels of 80 to 150 ng/mL.

The dosage suggested on this audiotape is 50,000 IU per day for one week, then a maintenance dose of 50,000 IU once per week (=7143 IU per day). But it is also important to change your nutrition to a well-balanced diet. He stated that there is no toxicity with this treatment schedule as long as you do not take additional calcium supplements. On the other hand, dairy products are OK to take.

Our Immune System Needs Vitamin D3

Our Immune System Needs Vitamin D3

Conclusion

Many patients with diseases like osteoporosis, high blood pressure, cardiovascular disease, influenza, multiple sclerosis, allergies and other disease listed above have very low vitamin D blood levels. Vitamin D is necessary to produce more than 100 polypeptides. The body requires these for normal cell function. Rickets was first cured by supplements of only 400 IU of vitamin D3 per day. In the meantime, it is recognized that a vitamin D level of less than 15 ng/mL constitutes a vitamin D deficiency. To cure other diseases requires much higher vitamin D levels in the blood, in the order of 50 to 80 ng/mL.

Dr. Prendergast uses higher vitamin D levels with better results

Dr. Prendergast states that patients with pre-existing diseases have to take much higher levels of vitamin D3. This rebalances their metabolism and cell function. In time this will gradually cure their disease. He suggests 50,000 IU of vitamin D3 daily for 7 days. This is then followed by 50,000 IU per week (7143 IU per day) for maintenance. He said that this will lead to a vitamin D level of between 80 and 150 ng/mL. In 30 years of practice he has not seen a single case of vitamin D3 toxicity, provided the patient refrains from taking calcium supplements. This is the exact opposite of what the Mayo Clinic or Harvard University websites say. It also shows that there are always some pioneering forces in the generally ultra-conservative medical society.

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Mar
28
2020

Fasting Can Prevent Cardiovascular Diseases

Dr. Joel Kahn gave a lecture in Las Vegas in which he explained that fasting can prevent cardiovascular diseases. Dr. Kahn is a Clinical Professor of Medicine at Wayne State University School of Medicine. He spoke at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas. The conference took place from Dec. 13 to 15th, 2019.

According to the CDC cardiovascular diseases like heart attacks and strokes are hitting the middle age adults in large numbers. Part of the problem is obesity and diabetes, both of which cause an increase of cardiovascular diseases. Heart attacks, strokes, heart failure and other related cardiovascular conditions caused 2.2 million hospitalizations in the US in 2016. This resulted in 415,000 deaths and a health care cost of $32.7 billion.

Fasting can improve the risk for cardiovascular disease

Dr. Kahn asked whether fasting can reduce the aging pathways, build up resilience and protect the heart from aging and heart disease. In a few words: eat less, live more! He showed with slides that fasting can indeed do that. One heart catheterization study showed that a fasting group had only 64% coronary artery disease compared to a non-fasting control group with 76%.

Another study showed that fasting patients had only 10.3% diabetes compared to controls with 22.0%. With heart catheterization 63.2% of fasting patients had cardiovascular disease while 75.0% of non-fasting control patients did have lesions in their coronary arteries.

Animal experiments confirmed that fasting had beneficial effects on heart health as well. In rats, researchers showed that fasting reduced infarct size and inflammation. It also preserved left ventricular function. With mice fasting produced less inflammatory response and less tissue damage.

Alternate day fasting shows benefit in clinical human trial

A 2019 publication reported about a 4-week randomized clinical trial on 60 healthy non-obese human subjects. The effect of alternate day fasting was compared to controls. On average there was a 37% calorie reduction in the alternate fasting group. The fasting group had improved fat mass, improved fat-to-lean ratio and cardiovascular markers. There was a reduction of age-associated inflammatory markers and low-density lipoprotein.

Fasting mimicking diet

A newer form of fasting is the fasting mimicking diet (FMD), which was invented and researched in depth by Dr. Valter Longo. Both animal experiments as well as human trials have shown that the FMD is safe and effective. It can be followed 5 days out of every month and will lead to some weight loss, an increase of telomeres, stem cells and lowered inflammatory markers.

My own experience with the fasting mimicking diet

My wife and I heard about the FMD from Dr. Longo when he spoke about it at the 2017 Anti-Aging Conference in Las Vegas. We immediately started the FMD in December of 2017 and have done it every month for 5 days since. But we never ordered the expensive meal kit. Instead, we calculated calories and use regular food to do the calorie-restricted diet. We eat 600 to 700 calories every day during the FMD days. In between we have unrestricted calories, but we noticed that we are more careful about our meal choices. I find that the result of the FMD is more energy, an improved sleep pattern and an easier way to keep my body-mass index in the 21.0 to 22.0 range. Here is a description of the effects of the FMD.

Use of FMD in high-risk patients

Dr. Khan said that the FMD is an ideal diet that the high-risk population of the US should use. 34% of the US population has a compromised metabolic condition. They are obese and at a high risk to develop diabetes. But on the FMD they gradually lose abdominal obesity, lower their cholesterol and triglycerides levels, which otherwise causes a high risk for heart attacks and strokes. The fasting blood sugar is lowering reducing the risk to get diabetes. The systolic and diastolic blood pressure comes down. And the C-reactive protein, which is a general inflammatory marker, becomes lower.

In non-obese patients the main effect of the FMD is a stimulation of stem cell release and telomere elongation. This postpones the aging process and with it delays the onset of cardiovascular diseases.

Fasting Can Prevent Cardiovascular Diseases

Fasting Can Prevent Cardiovascular Diseases

Conclusion

Dr. Joel Kahn gave a lecture at a Las Vegas conference that fasting can prevent cardiovascular diseases. He compared alternate day fasting with the fasting mimicking diet (FMD). The FMD was more effective in reducing danger markers, abdominal girth measurements and blood markers of cardiovascular diseases. Ultimately, he said, it was easier to follow an FMD where you only reduce your calorie intake to 600 to 700 calories per day for 5 days in one month. In those who are wanting to do this just for good health, the FMD increases stem cells and elongates telomeres. This postpones the aging process and keeps a person younger for longer. At the same time, it delays the onset of cardiovascular diseases.

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Mar
14
2020

Telomeres are Important

In the first place, Dr. Joseph Raphaele reviewed why telomeres are important at a Conference in Las Vegas in December 2019. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15, 2019. The actual title of his lecture was: “Telomeres in 2019; clinical developments and cutting-edge applications”.

Notably, Dr. Raphaele reviewed how various animals have quite different life expectancies. First, the Aldabra giant tortoises, for instance can live up to 152 years. Second, the house mouse can at the most live up to 6 years, but its predator, the cat lives up to 38 years. Finally, humans can live up to 122.5 years.That is to say, the average mortality rate doubling curve of man is 8 years. Dr. Raphaele introduced the terms “lifespan” and “health-span”.

Lifespan versus health-span

The first thing to remember is that our lifespan is defined by the number of years we live. On the contrary, the health-span is defined by the number of years you do not have any disease and your physical and mental health are good. Dr. Raphaele explained that for the most part the body’s organs have a limit of functioning after 80. For this reason the kidneys, the maximum heart rate, the maximum breathing capacity and the maximum work rate (oxygen uptake) all decline after the age of 80. It is important to realize that in 1961 Dr. Leonard Hayflick showed that there is a limit of how often cells can divide. After 60 doublings cells in tissue culture either die or just stop dividing. The built-in molecular clock resides in the telomeres. The telomeres are the caps at the end of the chromosomes in the cell’s nucleus.

Telomeres and their function in aging

In a word, what is the function of telomeres? In essence, the telomeres protect the integrity of our genes. For the most part, they protect the chromosomes from deteriorating, prevent DNA fusion and massive instability of the genes. In addition, the telomeres allow the cells to divide in an orderly fashion, but only up to the Hayflick limits. In short, the bottom line is that telomeres prevent cells from mutations of the DNA, from senescence and from death.

Shortening of telomere length with age

Dr. Raphaele said that one of the important findings was that telomere length is shortening with age. Notably, he showed a slide similar to this. To clarify, this graph shows telomere length as a function of the lifespan in years. The telomere length is obtained by a blood test. This determines the length of the telomeres in white blood cells. At a young age it has a length of between 8 and 10 kb. kb stands for kilobase. A kilobase consists of 1,000 pairs of nucleic acid sequences. So, 10 kb means 10,000 pairs of nucleic acid sequences. Around the age of 80 people have much shorter telomeres, only 4 to 6 kb. There is an enzyme, called telomerase that can elongate telomeres by approximately 10%. But this may not be desirable as too much telomerase activation can also stimulate cancer growth.

Age changes telomere length

Dr. Raphaele explained further that a telomere loses about 100 base pairs per cell division. But there are other factors that shorten telomeres. Smoking, sedentary lifestyle, high blood pressure, stress and a low antioxidant status all can shorten telomeres. Certain congenital conditions can shorten telomeres by 28%. Dyskeratosis congenita is such a condition where 80% patients die by the age of 30 due to aplastic anemia. This is associated with bone marrow failure. 10% of these patients die from cancer. Apart from age, which shortens telomeres slowly, lifestyle factors are very important. A good lifestyle where you exercise regularly, you don’t smoke and you eat a healthy diet will slow down the shortening of your telomeres. Controlling your stress, sleeping enough hours per night and taking supplements also delays telomere shortening. Certain medications that control diabetes, high blood pressure or thyroid medication that treats hypothyroidism also delay telomere shortening.

Telomeres and shortened lifespan

Researchers could show that good lifestyle practices work by increasing telomerase to a certain degree. This results in lengthening of telomeres and translates into up to 10 years of increased life span. Jerry Shay, PhD said in 2011: “While the aging process is complex and certainly cannot be explained solely on the basis of telomere biology, there is a growing consensus that in some situations telomere biology and telomere tests may have important utility similar to cholesterol assays or blood pressure monitoring measurements.”

Telomeres are not just a biological clock inside our cells. They have a great influence on the function of mitochondria and on how many mitochondria multiply inside cells. This latter process is called mitochondrial biogenesis. In addition, telomeres regulate gene expression.

Chronic diseases associated with shortened telomeres

Here is a list of chronic diseases where all the patients have shortened telomeres.

  • High blood pressure
  • Hardening of the arteries (atherosclerosis)
  • Cancer
  • Chronic obstructive pulmonary disease (COPD)
  • Alzheimer’s disease
  • Diabetes and obesity
  • Chronic stress
  • Metabolic syndrome

Telomeres in cardiovascular disease

Telomere length was found to be shortened in those who developed a heart attack. Researchers compared the telomere length in coronary artery disease (CAD) patients to people with no history of heart attacks. In comparison to this normal group the heart attack victims had telomeres typical for people who are chronologically 11.3 years older than the healthy controls. The researchers calculated that people with telomere shortening had a 3-fold higher risk of coming down with a heart attack.

Telomere length enhancers

  1. Lifestyle changes can have positive effects on telomere length. Examples are smoking cessation, weight loss and stress reduction.
  2. Dietary changes: we know that fish oil (omega-3 fatty acids) supplements elongate telomeres as does a low-fat diet.
  3. Supplements like vitamin D3, antioxidants (vitamin C and E) and astragalus (TA-65) elongate telomeres as well. The astragalus supplement, TA-65 showed a significant elongation of telomeres after 12 months while controls lost telomere length.
  4. Exercise: in a 24-week experiment of care workers regular aerobic exercise increased the telomeres by 67.3 base pairs.
  5. Bioidentical hormone replacement in aging people: when hormones are missing after andropause and menopause, the natural hormones need replacing, or the telomeres are shortening.
  6. High cortisol levels cause telomere shortening.
  7. Human growth hormone elongates telomeres via telomerase activation.
  8. The fasting mimicking diet (FMD) was shown to extend life and telomeres as well.

Therapeutic rationale for telomere lengthening in CAD and AD

Patients with coronary artery disease (CAD) are at risk for developing heart attacks and other cardiovascular diseases. Here is an overview of many clinical trials that have been done in humans with CAD. It shows shortening of telomeres in these high-risk patients. But the review also shows that telomeres can lengthen by changing the risk factors of cardiovascular disease. Researchers were increasing the enzyme telomerase that indirectly lengthens telomeres. Both approaches prevent serious cardiovascular disease and increase life expectancy significantly. In severe cases of telomere shortening the physician can consider TERT gene therapy.

Alzheimer’s disease (AD) also is a condition where telomeres are shortened compared to normal controls. Time will tell whether TERT gene therapy is possible to prevent Alzheimer’s disease.

Telomeres are Important

Telomeres are Important

Conclusion

Telomeres are the caps of the chromosomes in our cells. In the past the word “telomere” appeared obscure and only scientists discussed this among themselves. Now we know that telomere shortening is often the reason for chronic illnesses like high blood pressure, hardening of the arteries (atherosclerosis), cancer, chronic obstructive pulmonary disease (COPD), Alzheimer’s disease, diabetes and obesity. Patients who have these conditions often have shortened telomeres in their white blood cells. Over the years we have learnt that lifestyle changes can have positive effects on telomere length. Smoking cessation, exercise, weight loss and stress reduction are elongating telomeres.

Additional factors elongating telomeres

In addition, supplements like antioxidants (vitamin C and E), vitamin D3 and astragalus root (TA-65) elongate telomeres as well. By elongating telomeres, a person can add 10 to 11 years of disease-free life to the normal life expectancy. Researchers showed that telomerase activation by human growth hormone increased telomere length without causing cancer. Dr. Thierry Hertoghe, an endocrinologist from Belgium spoke about HGH replacement in aging people on other occasions. He said that cautiously treating patients with low doses of HGH when blood tests showed deficiency, adds about two decades of life-expectancy to these patients’ lives.

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Feb
22
2020

Clinical Applications of the Fasting Mimicking Diet

Dr. Kurt Hong, professor of clinical medicine spoke about clinical applications of the fasting mimicking diet in Las Vegas. This was at the 27th Annual World Congress on Anti-Aging Medicine on Dec. 14, 2019. Although he spoke on various forms of fasting, he concluded that the fasting mimicking diet had the best results and was most consumer-friendly.

How we age

Dr. Hong reviewed the processes of aging. We age, because our cells experience oxidative damage and our telomeres (the end caps of our chromosomes) get shorter in time. We also age, because there are genetic mutations in our cells’ DNA and our mitochondria are aging as well. The mitochondria are the small energy packages inside the cells that give us energy. When people age, they have lost mitochondria, there is less energy that the body makes out of food and we feel chronically tired.

Above the age of 65 we are also likely to develop diseases of various organs:

  • Heart disease: 31%
  • Cancer: 24%
  • Chronic lung disease (lower respiratory disease): 21%
  • Alzheimer’s disease: 13%
  • Diabetes: 11%

Women are generally healthier than men and their life expectation is 4 to 5 years longer than that of men.

Cellular and molecular aging

Longevity researchers have done mouse experiments and human clinical trials for decades. Dr. Hong asked the question: how much longer could humans live, if we could cure cancer, heart disease, stroke and diabetes? The answer is: 13 years. But if we transfer the animal data to humans it should be 30 years of longer life. Why is there such a discrepancy? The answer is that it is easy to force good lifestyles onto animals, but humans are resistant to changes. Humans have their habits; they like to continue to smoke and eat fast food instead of switching to a healthier Mediterranean diet. Humans also resist a regular exercise program. And they do not want to hear that they should replace missing hormones with bioidentical ones. The result is that we humans will prolong our lives only by less than 50% of what we could achieve.

The concept of intermittent fasting

Dr. Hong stated, that ten thousand years ago, people did not always have enough food to eat. They were forced to intermittently fast. That did not mean that they had long life expectancies, as there was no cure for any disease. But one fact was true: the body learnt to rejuvenate itself during periods of fasting. And these longevity genes are still present in our genes. But they will only help us when we actually fast for some periods of time.

Dr. Hong reviewed what kind of fasting methods are available.

Prolonged fasting and juice fasting are not among the options. With prolonged fasting electrolyte disturbances become an issue. Juice fasting does not remove enough calories and nutrients. This, however is needed to allow the body to stimulate the longevity genes.

How fasting diets work

Dr. Hong explained that there are essentially 5 fasting diets that are effective in regulating the key nutrient sensitive pathways of IGF-1, TOR and PKA. This increases cellular protection and maintenance. It also increases activation of stress resistance pathways and removes and replaces damaged and dysfunctional cells. Finally, a fasting diet also reduces inflammation, which is often the start of disease.

A review of the 5 fasting diets

Time-restricted eating (TRE)

With TRE the person fasts for 12 to 16 hours every day. The person restricts the daily food consumption to a 4- to 12-hour window. The disadvantage is that this fast is done every day. The period of fasting may not be long enough to change the metabolism, where the above-mentioned effects take place.

Alternate-day fasting  

This is a 24-hour fast every other day with a 1:1 day eating-fasting cycle. This does not appear to be physiological and is disruptive with regard to social activities.

5:2 intermittent fasting

With this fast you fast for 2 days every week. With this 2:5 eating-fasting cycle the person fasts for 2 days every week; the other 5 days you eat as much as you desire.

Although this is effective, it can be quite disruptive to your lifestyle.

Periodic fasting

You fast for 48 to 72 hours every couple of months. This fast is socially more acceptable. It is not that often, just a couple of times in a year. The question remains whether it is effective in changing the metabolism to trigger the effects mentioned above.

Fasting-mimicking diet (FMD)

The original suggestion by Dr. Longo, the inventor of the FMD was that you should fast for 5 days once every month. Since then he has modified it and said that you can achieve similar metabolic changes, if you only fast for 3 days and do this a couple of times per year. I have done the FMD since December 2017 and I adhere to the original schedule of doing the FMD monthly for 5 days. This has provided me with more energy. It is easier to keep my body mass index in the 21.0 to 22.0 range. Dr. Hong explained that the FMD allows you to eat, but it tricks the body into acting like you are fasting. Because you are eating 500 to 600 calories per day, you are getting some fluid and nutrients, so the hunger pangs are tolerable.

More details about the FMD

Here is Dr. Hong’s summary about the FMD: “The stomach sees food, while the cells see fasting”. Dr. Hong said that the FMD is the most user-friendly method of fasting. It also has had the most scientific studies to validate that it is indeed working. Poorly functioning mitochondria and misfolded proteins are removed by a process of phagocytosis. The FMD reduces heart disease, cancer, and neurodegenerative disorders. Stem cell production also gets a boost. This promotes cell regeneration and reduces risk factors of premature aging.

Publication on the effectiveness of the FMD

A publication came out in 2017 reporting about the findings of a clinical trial regarding the FMD.

Researchers followed markers of aging, diabetes, cancer and cardiovascular disease in 100 volunteers. They underwent a FMD for 5 days on 3 consecutive months. The results were astounding. The body mass index, the fasting blood sugar level, triglycerides, total and LDL cholesterol and the CRP were all lower. CRP stands for C-reactive protein, which measures the degree of inflammation in the body. The blood pressure was also lower. Overall the 5-day FMD was a safe method with no side effects. The FMD reduced markers and risk factors of aging and age-related diseases. In doing so it prolongs life by reducing the likelihood of coming down with disease.

Who should abstain from fasting?

Dr. Hong mentioned that the FMD is not for everybody. Pregnant women should refrain from going on it, also type 1 and type 2 insulin dependent diabetics. Anybody who has a sign of an active infection (coughing, having a fever or diarrhea) should be excluded. Other exclusions are people who are underweight (BMI less than 18.5) or are malnourished (protein deficiency). Patients with heart failure and advanced kidney or liver disease should not take part in a fasting program.

Autoimmune diseases and FMD

The myelin sheath around the axon of nerve cells in the central nervous system are supported by oligodendrocytes. In multiple sclerosis (MS) patients T lymphocytes activate macrophages and B cells to produce autoantibodies. They destroy oligodendrocytes breaking down the insulating barrier of the myelin sheath. In MS patients the broken-down myelin sheath suppresses the electrical impulses transmitted through the nerve fibers. The FMD led to clinical improvements.

In a pilot study intermittent fasting changed the gut flora into a healthier flora.

This triggered the immune system in the gut to make less inflammatory T cells producing the IL-17 cytokines. There was also an increase in regulatory T helper cells.

Inflammatory bowel disease (IBM) can be improved with several courses of FMD. As the authors showed, intestinal inflammation improved with FMD. The intestinal gut flora improved with the FMD and it promoted intestinal regeneration.

Reversal of physical and functional decline

The fasting mimicking diet (FMD) has a variety of effects on the human body. Dr. Hong showed a slide where we could see that ketone bodies, cortisol and ghrelin levels are increased in the blood. At the same time glucose, insulin, leptin and IGF-1 levels are reduced. In addition, triglycerides and LDL levels are getting lower. Inflammatory markers including the C-reactive protein (CRP) are reduced as well.

Effects of the FMD on various organs in the body

A look at all of the organs shows that in the liver the ketone body production and insulin sensitivity are up. Glycogen production in the liver as well as the liver size are down.

The intestines produce ketone bodies. In the skeletal muscles the insulin sensitivity is increased, while the muscle structure and function are improved. In the brain the hunger feeling increases the release of neurotropic factors including the neuropeptide Y. Cognitive function and stress resistance increase with the FMD. The FMD reduces inflammation and oxidative stress in the brain. With respect to the cardiovascular system the heart rate drops down and blood pressure gets lower. The insulin production in the pancreas is reduced.

Fatty tissue

In fatty tissue lipolysis is up and also the production of adiponectin. This is a protein hormone involved in glucose and fatty acid metabolism. Insulin sensitivity with the FMD is also increased. On the other hand, the FMD reduces fat mass, leptin production and inflammation.

The FMD is the solution to preventing disease and prolonging your life

All of these effects lead to a reversal of physiologic and functional declines. Age-related metabolic diseases like type 2 diabetes are postponed or eliminated. The FMD prevents neuro-cognitive decline like Alzheimer’s disease. In addition, the risk of developing cancer is getting lower. In summary, the FMD improves the health-span, quality of life and can prepare you for a long life.

Clinical Applications of the Fasting Mimicking Diet

Clinical Applications of the Fasting Mimicking Diet

Conclusion

Dr. Kurt Hong is a professor of clinical medicine at UCLA. He gave a talk at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec. 14, 2019. He discussed what we could do to help patients with various autoimmune diseases like multiple sclerosis, rheumatoid arthritis and inflammatory bowel disease. It turns out that the fasting mimicking diet (FMD) is the best solution to reduce inflammation and modify  the autoimmune response from aggressive T lymphocytes. With the FMD you consume only 500 to 600 calories per day for 5 days every month. The rest of the days of the month you eat a healthy Mediterranean-type diet.

Fasting mimicking diet, the best way to treat autoimmune diseases

Dr. Hong explained in detail what cellular mechanisms are at work to achieve the modification of the immune system in autoimmune diseases. The FMD is also the solution to slow down aging in healthy people. Dr. Hong discussed clinical applications of the fasting mimicking diet fort autoimmune diseases. It is easier to prevent disease than it is to cure an illness. The FMD is an easier way, because you don’t fast completely, you only reduce your food intake to the bare minimum, but your body “thinks” that you are fasting.

Ultimately, this approach does take some effort, and it does take time to familiarize yourself with it. If patients do it for the first time, they will experience some hunger, the first and second day tend to be a hurdle! Once you make it part of a health routine on a regular basis, it is a lot easier.

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Jan
11
2020

Centenarians Are Positive Thinkers

Dr. Thierry Hertoghe gave a presentation in Las Vegas on Dec. 14, 2019 where he stated that centenarians are positive thinkers. This was at the 27th Annual World Congress on Anti-Aging Medicine. The topic of his talk was “Positive Psychological Attitudes of Centenarians “.

Dr. Hertoghe is an endocrinologist in Belgium. Dr. Hertoghe took an interest in people above the age of 100. He felt that these people are special people with a very optimistic outlook on life. He went on to study the literature about this topic in detail and this is what this talk was about.

The oldest man, Gustav Gerneth died at 114 years 7 days in Germany (Oct. 22, 2019). The oldest female is Japan’s Kane Tanaka at 117 years (birthday Jan. 2,1903).

So, what is their secret to age that well? Here is what Dr. Hertoghe found out about centenarians.

Attributes of centenarians

Centenarians have a will to live. They adapt to changes; they have a sense of purpose, and they stay active. Other psychological features show that they have is a positive mood and they avoid stress and anxiety. Another important attribute is self-determination. They are very sociable, have close family ties, love their relationships and often have a strong religious faith. There is a connection between their basic values and beliefs and their spirituality. Centenarians insist on their freedom and they have a feeling of youth. Centenarians have their own centenarian spirit where they can feel young or old.

In the following I am reviewing the details that Dr. Hertoghe gave. He covered 13 subtopics regarding causes of longevity in centenarians.

The will to live

It takes courage to grow old and all centenarians have this. They say “Life is worth living”. They have a certain resiliency in a world that has an obsession about youth. Despite negative experiences they had to overcome they do not give up and they enjoy life as much as they can. A Finnish study examined 400 individuals aged 75-90 and followed them for 10 years. Group 1 who wished to live less than 5 years had a mortality rate of 68%. Group 2 wished to live for 5-10 years. They had a mortality of 45.6%. The last group, group 3 wanted to live more than 10 years. Their mortality was only 33.3%. Be careful what you wish for!

Adaptability

This describes the capacity to overcome adversity and your ability to adjust. In a study of 7400 Chinese centenarians’ resilience to changes was measured with psychometric psychological tests. The majority of subjects did not qualify for being resilient. Only 9% of male centenarians and 6% of female centenarians had the resiliency where they qualified for high adaptability. This high resilience group was associated with 2%-4% lower mortality risk. They had a 36%-55% higher odds of not developing cognitive impairment and they rated themselves as being in good health and having a “good life” satisfaction. These resilient centenarians had a 7%-12% higher probability of not developing a physical disability. Short-term health decline was not associated with these high resilient centenarians.

A sense of purpose

Centenarians can still contribute to society. Tao Porchon-Lynch turned 100 in 2014. She opened the Westchester Institute of Yoga in 1982 and is still practicing yoga. There are many ways how centenarians express a sense of purpose. Males often work in their old job, but only part-time. They may help with babysitting the great-grandchildren. Others do volunteer service. Still others may enrol in a university and study what they always wanted to do.

In a 2016 publication people older than 65 were followed between February 2011 and November 2014. Those who had neither hobbies or a purpose in life did not fare well. They had a risk of mortality of 2.08-fold compared to those with a sense of purpose. Dr. Hertoghe provided 9 more references regarding studies that showed the same finding.

Remaining active

If a centenarian remains active and moves about several hours per day, the body functions are preserved. Anna Mary Robertson Moses who was known by her nickname “Grandma Moses” took up painting at age 78. She died at age 101 in 1961.

Positive emotions

One study of 54 Ashkenazi Jewish older adults (aged 98-107) compared those with positive emotions to those with negative emotions. The researchers noted that a positive attitude about life allowed centenarians to live longer.

A study involving 2282 Mexican Americans aged 65 to 99 showed that positive affect scores were a predictor for the following. Subjects with a high positive affect had a 52% lower probability of becoming physically disabled. They were 36% less likely than the negative controls to lose their walking speed. In addition, they were 47% less likely to die during the two-year observation period than their negative controls.

Nurses’ Health Study and Veterans Affairs Normative Aging Study

Two studies, the Nurses’ Health Study (NHS) and men from the Veterans Affairs Normative Aging Study measured optimism. The researchers found that those with the highest optimism scores had a 1.5-fold higher probability in women and 1.7-fold in men to survive to age 85. This was compared to a control with the lowest optimism scores. Dr. Hertoghe provided 19 more studies that showed the effects of positive emotions regarding long term survival. For brevity reasons I will not dwell on them here.

Better stress management

Centenarians avoid excessive stress and attempt to relax instead.  It has been known since the ground-breaking work by Dr. Hans Selye that stress undermines longevity. By using relaxation methods intermittently one can reduce the stress response, which normalizes the excessive ACTH production in the pituitary gland and the concomitant cortisol production in the adrenal glands.

Self-determination

Long-living people have a strong willpower and are determined to succeed with what they want. They have a sense of self-worth and self-esteem. Centenarians have concerns for others, but they also have a healthy regard for themselves. Dr. Hertoghe provided 4 references to illustrate this, but for brevity reasons I will omit them here.

Social involvement

Centenarians have an active social life. They are involved with their family, with the community including often church communities. Sociability has a 2.3-fold higher probability of survival (mortality reduced by 57% due to sociability).

Practicing religion

Those who are centenarians were often raised in religious families. They developed a strong faith in God. A common theme among centenarians is that they trust in God and believe it is His will that they lived a long life. They also believe that eventually God will call them “home” when He is ready for them. Centenarians who practice religion have a strong belief in an afterlife, which sustains them to live and they accept death when it comes. In a 2017 study 18,370 participants aged 50 and older were interviewed in 2004 and followed for all-cause mortality to 2014. Regular church attendants had a mortality that was 40% less than those who did not attend. Dr. Hertoghe provided 20 more references that showed similar findings.

Spiritual involvement

Attributes of spiritual involvement are high ethical principles, resilience and hope that everything will turn out OK. Dr. Hertoghe cited from 7 different references that the average effect of spirituality leads to a 2- to 4-fold greater survival over 17 years.

A feeling of freedom

This makes centenarians less concerned what other people think of them. Dr. Helen Langner, a psychiatrist, still does a part-time psychiatric practice at age 100. She says about a feeling of freedom: “In old age, there’s often a sense of personal freedom because there is less pressure of a career or the responsibilities of work or raising a

family. It can and should be a time for people to do the things that are important to them and a time to enjoy. “

A feeling of youth

Many centenarians are young at heart. Even though they may look physically old, they don’t feel old in their heart.

What is the centenarian spirit?

When people are older than 100 years, they often have a mix of humor and eccentricity; they express emotions openly and they are happy people. They accept the death of spouses, siblings and significant others.

By the way, humor has a strong predictive survivor value. In a study that researchers conducted over 15 years, there was a clear positive effect of humor regarding mortality. A sense of humor reduced the all-cause mortality by 48%. In women humor lowered mortality regarding cardiovascular disease by 73%. Humor reduced death due to infections in women by 83%. Men had a non-significant reduction of all‐cause mortality by 12% and a significant lower mortality due to infections by 74%.

Dr. Hertoghe cited three more publications that showed the power of humor in reducing disease and disability.

Jeanne Louise Calment 

As an illustration for humor Dr. Hertoghe introduced Jeanne Louise Calment to the audience. She was a French woman who broke the record for being the oldest centenarian in the world.  Jeanne Calment died on August 4, 1997 at the age of 122 years and 164 days. She was asked by someone: “Why do you live so long?” She replied: “Because God has forgotten me…” Next question: “How do you consider your future life?” “Very, very short”. Last question:” What do you think of your wrinkles?” “The only wrinkle I have is the one I am sitting on”.

Centenarians Are Positive Thinkers

Centenarians Are Positive Thinkers

Conclusion

Centenarians have certain attributes that make them more resilient than others who die earlier. They have a will to live, an ability to adjust, a sense of purpose and they stay active. Their psychological make-up is such that they have a positive mood and they tend to avoid stress and anxiety. They have a sense of self-determination. They are very sociable, have close family ties, love relationships with people around them, and often have a strong religious faith. Their spirituality has a connection to their basic values and beliefs. Centenarians insist on their freedom and they have a feeling of youth. They have their own centenarian spirit where they can feel young or old. But they also have humor as documented above with the oldest woman that lived. She was 122 years and 164 days old when she died in 1997.

Nov
30
2019

Ketogenic Diet With Ketone Supplementation

There is a newer way to shed some pounds using a ketogenic diet with ketone supplementation. Ketosis with a ketogenic diet is difficult to achieve because it requires a lot of fat consumption and at the same time extremely low carb intake to trigger the ketogenic response. The October 2019 issue of LifeExtension magazine contained an article about a ketogenic diet with ketone supplementation. There are dip sticks with which you can test your urine for ketone bodies to verify that your metabolism has switched to ketosis. But you can also take some ketone supplements including beta-hydroxybutyrate. By adding this supplement it is easier to achieve ketosis.

Why do people think of starting a ketogenic diet?

Calorie restriction can mimic the effects of fasting. It leads to ketone production and improved energy metabolism. Your blood sugar goes down, you lose weight and diabetes becomes easier to manage. In an animal experiment with worms with the pretty name “C. elegans” researchers fed beta-hydroxybutyrate to these roundworms. They extended their lifespan by 20%.

Many who are motivated to go on a ketogenic diet hope to lose weight and others may hope to live longer. One large US study from the Brigham and Women’s Hospital, Boston, MA showed that mortality over a period of 25 years was lowest when carbohydrates were in the 50 to 55% range. In the same study when carbohydrates were replaced in ketogenic diets with animal-derived protein and fat sources, mortality increased by 18%. Meat and fat were from sources such as lamb, beef, pork, and chicken.

Problems with ketogenic diets

Physicians have had the concern that their patients on ketogenic diets tend to eat cheap fats and meats that contain trans fats. These unhealthy fats lead to premature death from accelerated hardening of the arteries resulting in heart attacks and strokes.

The alternative: a ketogenic diet with ketone supplementation

A new approach to anti-aging is taking ketone bodies like beta-hydroxybutyrate as a supplement. A publication from 2017 stated that oral ketone bodies could mimic the life extending properties of caloric restriction. The authors stated: “An exogenous ketone ester provides a new tool for mimicking the effects of caloric restriction that can be used in future research. The ability to power mitochondria in aged individuals that have limited ability to oxidize glucose metabolites due to pyruvate dehydrogenase inhibition suggests new lines of research for preventative measures and treatments for aging and aging-related disorders.”

Another publication from 2017 describes how ketones can be used as alternatives to glucose for energy. Brain cells and muscle cells in particular are very capable to utilize ketone bodies for energy. Two principal ketones are significant: acetoacetate and beta-hydroxybutyrate. The liver is involved when fatty acids are broken down and ketones are manufactured.

Ketone metabolism

Ketones provide energy without raising blood sugar levels or stimulating insulin secretion. The body requires less processing of ketones to release energy. This means that less NAD+ is used to metabolize ketones. The end result is that more NAD+ circulates in the body, which is used to repair damaged DNA and helps slow down the aging process. Ketones mimic many of the effects of caloric restriction and intermittent fasting dieting. Ketone metabolism reduces risk factors for diabetes and heart disease.

Human experiments

A 2018 study took 20 individuals aged between 18 and 35 years and tested them with an oral glucose tolerance test. Half of the subjects received a ketogenic hydroxybutyrate monoester, the other half just water (placebo group). The ketogenic group had 16% lower blood glucose levels. Their insulin sensitivity was 11% lower. The authors concluded: “These results suggest that ketone monoester supplements could have therapeutic potential in the management and prevention of metabolic diseases.”

Longevity in humans 

There has been a lot of research in the last few years indicating that sirtuins (SIR1 and SIR3) are important anti-aging genes. NAD+ needs to activate sirtuins first to make them effective. Unfortunately with the aging process less NAD+ is available, which leaves the sirtuins genes inactivated.

In rat experiments feeding of a ketogenic diet resulted in increased levels of NAD+. The researchers measured an oxidative DNA damage marker in the hippocampus of the brain. This showed much less DNA damage in rats fed a ketogenic diet when compared to controls on a regular diet.

Study of humans with Alzheimer’s disease

Another human study examined the blood of Alzheimer patients, patients with mild cognitive impairment and normal controls.  Alzheimer patients had low ketone levels in the blood as well as low 2-hydroxybutyric acid. Overall this showed that there is a change in metabolism in Alzheimer’s patients that leads to low ketone bodies in the blood on one hand and beta amyloid deposits on the other hand leading to memory loss.

A further experiment with Alzheimer’s patients showed that cognitive function improved after elevation of ketone blood levels following ingestion of beta-hydroxybutyrate.

A healthy way to raise ketones

Investigators in this human study determined whether various ketone-drinks were elevating blood ketone bodies reliably. 15 volunteers received ketone esters or ketone salts as a drink. There was a reduction of blood pH by 0.1 units using ketone esters. The ketone salts elevated the urinary pH from 5.7 to 8.5. An experiment with 16 volunteers measured the effect of having a meal before taking ketone esters. The ketone blood level showed a reduction of 33% after the volunteers consumed a meal and they took the ketone supplement afterwards. Ketone supplements lowered blood glucose, lowered free fatty acid and also lowered triglyceride concentrations. On the other hand, there was no change of the electrolyte levels. The authors said: “We conclude that exogenous ketone drinks are a practical, efficacious way to achieve ketosis.”

Ketogenic Diet With Ketone Supplementation

Ketogenic Diet With Ketone Supplementation

Conclusion

The liver produces ketones when a person is fasting or is on a ketogenic diet. However the high fat content of a ketogenic diet can lead to atherosclerotic plaques in the arteries with the subsequent developments of strokes and heart attacks. A much safer way of raising ketone bodies in the blood is by taking ketogenic supplements by mouth. Animal experiments and clinical trials have shown that oral ingestion of ketogenic substances appear in the blood stream within 30 minutes and remain there for 3 to 4 hours. The body tolerates ketogenic supplements well with no side effects.

Prevention of Alzheimer’s disease, achieving weight loss and longevity

They likely will play a larger role in the prevention of Alzheimer’s disease in the future. Ketogenic supplements may be an adjunct to weight loss diets. In addition, fatty acids metabolize into ketones, which turn into energy in brain cells and muscles. Oral ketones stimulate the formation of NAD+, which activate longevity genes (sirtuins). Older people have a hard time to metabolize glucose because of certain enzyme deficiencies. But the brain and the muscle tissue can metabolize ketones rapidly, even in older age. Unfortunately the price of such supplementation is forbidding at the present time.

Aug
10
2019

Fasting Mimicking Diet For 5 Days Every Month

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.

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Dec
16
2018

Can Longevity Research Make Us Age Slower?

Longevity research has done a lot of experiments, but can longevity research make us age slower?

This year an 800-page summary was published of all the longevity research that has been going on. A review of this research is in this abbreviated article. In the following I like to address some of the problems of anti-aging or longevity research.

Telomere lengthening

We know that people with longer telomeres live longer than people with short telomeres. When telomeres are longer, the cells can continue to divide and function normally. When telomeres shorten there comes a point when no more cell division is possible.  At this point the cell will normally be dissolved. When it persists, there is the danger that it undergoes a malignant transformation. This can cause premature deaths. On the other hand, if enough shortened telomeres accumulate in various organs, organ failure ensues. This will also result in premature deaths.

Research in humans has shown that increased physical activity elongate telomeres. So do vitamin C, E, vitamin D3 supplementation and resveratrol. A Mediterranean diet and marine omega-3 fatty acid supplementation elongate telomeres as well. In addition higher fiber intake, bioidentical estrogen in women and testosterone replacement in men can be effective in elongating telomeres. Finally, relaxation techniques like yoga and meditation are also elongating telomeres.

Antioxidants

Many processes lead to free radicals. Free radicals are unstable atoms that may damage cells and can cause illness and premature aging. Inflammation, the metabolism of our mitochondria, radiation exposure, industrial solvents and ozone are just some examples of what can cause free radicals in our system. If we have enough antioxidants on board, there is a balance between free radicals and antioxidants. No damage would occur then. In humans the two major antioxidants present are vitamin C and glutathione. Vitamin C comes from our food. Glutathione is produced by the liver and circulates in the blood. These two antioxidants are keeping free radicals in balance.

 

Anti-inflammatories

This Harvard site explains that even food can cause inflammation in us. For instance sugar, French fries, red meat and margarine cause free radicals. Anti-inflammatory foods are tomatoes, green leafy vegetables, olive oil, nuts, fatty fish, berries and fruit. A Mediterranean diet has anti-inflammatory qualities. There are 6 anti-inflammatory supplements that are useful to know about: ginger, fish oil, alpha-lipoic acid, curcumin, resveratrol and spirulina. In addition to the above, vitamin D3 also has anti-inflammatory effects in higher doses.

Chronic inflammation can cause cancer down the road, so it is important to prevent this by eating sufficient amounts of anti-inflammatory foods and supplements.

Genetic repairs

Spontaneous mutations of DNA, mutations of suppressor genes, oncogene activation and insufficient DNA damage response can all lead to cancer. In the past there was the hope of using chemotherapy and radiation therapy as a means to influence the outcome of cancer treatment. A reinvestigation of this concept is ongoing.

More specific treatment modalities are under investigation. When more cancer can be prevented and when it is possible to cure more cancers longevity in the population will increase. Cancer has been one of the major killers over the years.

Metformin research

Metformin has been in use for decades to prevent and treat diabetes. But beyond this it also has anti-cancer activity, it prevents Alzheimer’s, prevents cardiovascular disease and may be the first anti-aging drug. A trial to this effect is ongoing.

It makes sense that a drug that treats and prevents diabetes would be a longevity drug at the same time. The fact that it also helps to prevent cardiovascular disease and Alzheimer’s disease also makes sense. Anytime you remove a chronic disease, life expectancy improves. As a result metformin will likely receive approval as a longevity drug soon.

Mitochondrial repair

The mitochondria are small organelles in each cell. The purpose of this structure is to provide energy. In normal cells there are hundred of these organelles in each cell. In heart muscle cells, brain cells and liver cells there are thousands of mitochondria in each cell to provide energy. Muscles, nerve cells and liver cells require more energy to function properly.

Two supplements have been in use for some time to support mitochondria function.

  1. Co-Q10. This supplement supports mitochondrial function. It prevents heart disease, together with vit. K2 and vitamin D3 and it keeps blood vessels open.
  2. Pyrroloquinoline Quinone (PQQ). This supplement can increase the number of mitochondria in a cell. It can also improve their functioning. With aging we know that we are slowly losing mitochondria. It is important to know that there is a supplement that can counter the aging effect and prevent further mitochondrial loss.
Can Longevity Research Make Us Age Slower?

Can Longevity Research Make Us Age Slower?

Conclusion

For centuries people were hoping to live longer. Nowadays this dream seems to become a reality. But it does not happen with one magic pill. The aging process involves multiple targets that need attention. The telomere length is one factor. I listed a number of items that will elongate telomeres, like regular exercise and a Mediterranean diet. Antioxidants and anti-inflammatories are prolonging life as well. You want to preserve the function of your genes. Research is concentrating on improving gene repair.

Metformin has been found to prolong life. This molecule might be the first longevity drug. It has been in use to prevent and treat diabetes, but it also helps to prevent cardiovascular disease and Alzheimer’s disease. Two supplements help with mitochondrial repair, namely Co-Q10 and PQQ. Because life is all about energy, it is important to have well functioning mitochondria in all of your cells. When mitochondria are functioning, your body functions at its best, and you feel well.

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Nov
26
2018

Gut Bacteria Crucial To Healthy Aging

New research presented at the London Microbiome Meeting asked the question “are gut bacteria crucial to healthy aging?” Marina Ezcurra, is a Ph.D. is a researcher working at the Queen Mary University of London in the United Kingdom. She uses a nematode (round worm) model to investigate various aspects of aging. Nematodes like C. elegans provide a useful model not only for genetic work, but also for the human gut flora as well. Moreover, it allows making observations about the connection between bacterial genes and aging. Coupled with the fact that the worm has such a short lifespan, the researchers can test bacterial genes, the aging of the worm and get meaningful results in short order.

It seems like one of the research objectives was changing the nematode’s gut flora and observing life expectancy and age-related diseases.

Pathological versus healthy gut bacteria composition

Dr. Ezcurra did a couple of experiments with the nematode C. elegans as a model. She could show that the worm’s gut bacteria composition mattered. First of all, if there was a pathological composition of the gut flora, the worm did not turn as old and there were various age-related diseases that developed. Secondly, they were very comparable to human age-related degenerative diseases like Alzheimer’s disease.

Another senior author researched how genes of gut bacteria influence life expectancy

Meet Dr. Meng Wang, associate professor of molecular and human genetics, Baylor College of Medicine in Houston, TX. He did extensive genetic research on C. elegans. He used this model, because C. elegance lives only 2 to 3 weeks. This animal model is easy to manipulate. For instance, he studied the gut bacteria composition. This link explains that he tested about 4000 E.coli bacteria with various gene defects. 29 E.coli strains when deleted, increased the worms’ lifespan.12 bacterial mutants among those prevented cancer and amyloid-beta, found in Alzheimer’s disease. Some mutant bacteria caused longevity by acting on processes linked to aging.

Colanic acid is an important anti-aging factor in C.elegans

Dr. Wang joined Dr. Christophe Herman, associate professor of molecular and human genetics at Baylor, for further research. It turned out that one of the keys to longevity of the nematodes were the mutant bacteria in the gut over-producing the polysaccharide colanic acid. This allowed the nematodes to live much longer. The researchers could show further that fission and fusion processes with regard to mitochondria are important. Mitochondria are the energy packages in cells and these processes are regulated by the presence of colanic acid. As a result, if your gut has good bacteria you can grow old and escape Alzheimer’s disease and cancer.

Dr. Meng Wang said: “Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms’ lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimer’s disease in humans.” 

Creating longevity with metformin, a diabetic drug

Physicians have known for some time that metformin stimulates longevity genes. This is the reason why diabetics on metformin live longer than diabetics on insulin. Dr. Ezcurra mentioned on 24 October, 2018 in her talk at the London microbiome Meeting that she had done experiments with C. elegans and metformin. Metformin reduces the risk of cancer and increases longevity in C. elegans as well as in mice (other experiments). Currently there is a clinical trial going on that investigates anti-aging under the influence of metformin in older people.

Effects of metformin on anti-aging

Metformin has the potential to target diabetes, cancer and Alzheimer’s pathologies all at once.

The anti-aging effect in humans with metformin involves the gut bacteria. Dr. Ezcurra says that this is the reason why diabetics on metformin live longer than diabetics on insulin. Metformin influences the folate bacterial metabolism of the gut flora. Other research has shown that the Akkermansia bacteria in the gut, which are good, desirable bacteria, will increase from 3-5% to 12.44% of the gut flora under the influence of metformin. Here is the discussion in detail in the following link.

Effect of gut bacteria on psychiatric diseases, obesity and diabetes

Dr. Ezcurra said that there are many studies showing that dysbiosis of the gut can lead to psychiatric diseases, Parkinson’s disease, obesity and diabetes etc.

We need to know more about whether a healthy gut flora will let us age without causing age-related diseases. Dr. Ezcurra stated: “By better understanding the links between nutrition, microbiome, and health, we can understand how the elderly can maintain their microbiome, and also help them directly by using pre- and probiotic strategies. This would help us age in a better way, maintaining health and quality of life in old age without drugs or surgery.”

Gut Bacteria Crucial To Healthy Aging

Gut Bacteria Crucial To Healthy Aging

Conclusion

The composition of the gut microbiome appears to determine whether we age gracefully or not and whether we get sick as we age or not. Everything depends on the diversity of the gut flora. There are bacteria in the gut that are good for us and also bacteria that are bad for us. Metformin has been shown to stimulate the good gut bacteria to multiply. Dr. Ezcurra is continuing her research into this. She clearly stated that it should be possible for us to age in a better way and maintain health and quality of life in old age without drugs or surgery.