Jul
25
2020

The Immune System Changes With Age

When we are young, we do not think about our immune system, but the immune system changes with age. When we are older than age 60, we notice that we may be taking longer to recover from a flu.

How does the immune system work?

There are two parts to the immune system, the innate immune system and the adaptive immune system. The innate immune system works to protect us from bacteria, viruses, toxins and fungi from the time we are born. The adaptive immune system uses B lymphocytes from the bone marrow to produce antibodies against viruses. This provides often lifelong immunity against this specific virus, but takes 3 to 5 days to kick in. Vaccinations can also trigger antibody production to protect us from viruses in the future. Both the adaptive and the innate immune system work together closely.

What are the ingredients for a fully functioning immune system?

The immune system consists of various immune organs that are distributed throughout the body. The bone marrow produces lymphocytes, granulocytes, macrophages, eosinophils and basophils. The adenoids in the back of the nasal passages and the tonsils in the back of the throat contain a lot of lymphocytes that are ready to protect us from colds and flus. We have lymph nodes throughout the body and they are connected with lymphatic vessels. The lymph nodes filter the lymph fluid that travels in the lymphatic vessels.

Other sites of lymphocyte production

The small intestine contains the Peyer’s patches, a collection of lymphocytes that protect our gut from invading bacteria or viruses. The spleen is located in the left abdominal cavity under the diaphragm. It removes old red blood cells and provides lymphocytes for the immune system. The thymus gland is located between the breast bone and the trachea. It changes bone marrow derived lymphocytes (B cells) into T lymphocytes that can process antigens from viruses and pass them on to the adaptive immune system for a full antibody response.

Cellular interactions between various players of the immune system

Back in the 1970’s it was already known that there were bone marrow derived B lymphocytes and thymus processed T lymphocytes. We knew then that B cells were involved in antibody production (adaptive immunity). T lymphocytes were thought to turn into killer T lymphocytes to kill cancer cells. But some T cells were T helper cells to process antigen and present it to B lymphocytes for antibody production.

More research since then refined what we know about the cells of the immune system.

Natural killer cells (NK cells)

Natural killer cells (NK cells) are part of the innate immune system. They attack cancer cells and cells that are infected by viruses. It takes about 3 days for their full action to develop. NK cells utilize the cell surface histocompatibility complex to decide whether to destroy a cell or not. T cell lymphocytes do not have the ability to do that. In the Covid-19 coronavirus situation NK cells play an important role to combat the disease right away.

Monocytes

They are large white blood cells that can differentiate further into macrophages and dendritic cells. Monocytes are part of the innate immunity, but they have an antigen presenting capability, which makes them also part of the adaptive immunity.

Memory T cells

The immune system learns to adapt to viruses and bacteria that we have come in contact with. The reason for the memory of the immune cells are the memory T cells. They replicate like stem cells, which keeps a clone of T lymphocytes, T helper cells and cytotoxic T killer cells in the background. They circulate through the body including the lymph glands and the spleen.

Immunosenescence as we age

There are several factors that come together, which age our immune system. The term for this is “immunosenescence“. There are genetic differences and differences due to the sex hormones. Estrogens increase the response of the immune system. In contrast, progesterone and androgens (including testosterone) decrease the immune response. This may be the reason why women tend to live longer than men.

As we age there are more and more memory T cells (both cytotoxic T cells and T helper cells). This weakens the formation of the natural killer cells (NK cells) of the innate immune system. Even the initiation of the adaptive immune system can be slower when we age and also the response to the flu vaccine. In addition, this can pave the way to autoimmune diseases.

The immune system changes with age: Evidence of immunosenescence

The following 3 factors show whether a person has immunosenescence:

  • The immune system has difficulties to respond to new viruses/bacteria or to vaccines
  • Accumulation of memory T cells crowding out cells of the rest of the immune system
  • Low-grade inflammation that is chronic and persists (“inflamm-aging”)

The process of immunosenescence starts with the involution of the thymus gland around the time of puberty. At that time the sex hormone secretion is highest. At the same time a growth factor from the bone marrow and the thymus gland decreases. It has the name interleukin-7 (IL-7). The end result is a slow decrease of the innate immune system with age and a more substantial weakening of the adaptive immune system due to a lack of naïve T and B cells. 

Chronic viruses can weaken the immune system further

The varicella herpes zoster virus causes chickenpox. In some people the chickenpox virus can persist, but the immune system actively keeps it controlled. In the 60’s or 70’s when the immune system is weakened from aging, there can be a flare-up as shingles, a localized form of the chickenpox virus.

Another virus, the human cytomegalovirus can cause a chronic infection that often persists lifelong. In this case the immune system is chronically weakened because of a massive accumulation of T memory cells, which keeps the human cytomegalovirus infection at bay.

What we need when the immune system changes with age 

Vitamin A

Both the innate and adaptive immunity depend on vitamin A and its metabolites. The skin cells and mucosal cells function as a barrier, which is important for the innate immunity. The skin/mucosal lining of the eye, the respiratory tract, the gastrointestinal and genitourinary tracts help the innate immunity to keep viruses and bacteria out of the body. Vitamin A is important to support macrophages, neutrophils and natural killer (NK) cells. In addition, vitamin A supports the adaptive immune system, namely T and B lymphocytes, so that the body can produce specific antibodies against viruses.

I do not take vitamin A supplements as I eat diversified foods like spinach, vegetables, poultry, Brussels sprout, fish and dairy products that contain vitamin A and carotenoids.

Vitamin C

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

Vitamin D

The immune system is very dependent on vitamin D as the immune cells all contain vitamin D receptors. People who have less than 10 ng/mL of vitamin D in the blood are vitamin D deficient. They have much higher death rates when they get infected with the Covid-19 coronavirus.

Vitamin D regulates the expression of target genes. At the center is the vitamin D receptor, which is a nuclear transcription factor. Together with the retinoic X receptor (from vitamin A) the vitamin D receptor binds small sequences of DNA. They have the name “vitamin D response elements” and are capable of initiating a cascade of molecular interactions. The result is a modulation of specific genes. Researchers identified thousands of vitamin D response elements that regulate between 100 and 1250 genes.

You need enough vitamin D for your immune system

When enough vitamin D is present in the blood (more than 30 ng/mL) the immune system releases the peptides cathelicidins and defensins, which effectively destroy bacteria and viruses.

Vitamin D has mainly an inhibitory function regarding adaptive immunity. It inhibits antibody production from B cells and also dampens the effect of T cells. Researchers reported that vitamin D3 is useful in the treatment of autoimmune diseases.

I am a slow absorber of vitamin D3 as repeat blood vitamin D levels showed. I need 10,000 IU of vitamin D3 daily to get a blood level of 50-80 ng/mL (=125-200 nmol/L). This is the higher range of normal. Everybody is different. Ask your physician to check your blood level of vitamin D. Toxic vitamin D blood levels are only starting above 150 ng/mL (= 375 nmol/L).

Vitamin E

This is a vitamin that is fat soluble and helps the body to maintain its cell membranes. But researchers found that vitamin E also stimulates the T cell-mediated immune response. This is particularly important for the aging person to prevent respiratory tract infections. I take 125 mg of Annatto tocotrienols per day (this is the most potent form of vitamin E).

Vitamin B6

This vitamin is important for antibody production by B cells. Vitamin B6 regulates the metabolism of amino acids, which in turn form proteins. Antibodies and cytokines require vitamin B6. The T helper immune cells that initiate an adaptive immune response depend on vitamin B6 as well. I take a multi B complex vitamin (Mega B 50) twice per day, so I supplement with a total of 100 mg of vitamin B6 daily.

Folate

Folic acid is a coenzyme for the metabolism of nucleic acids and amino acids. Studies in humans and animals have shown that folate deficiency leads to increased susceptibility to infections. People with folate deficiency develop a megaloblastic anemia with immune weakness that leads to chronic infections. With my B complex supplement I get 2 mg of folic acid daily.

Vitamin B12

Methylation pathways depend on vitamin B12 as a coenzyme. Vitamin B12 is also involved as a coenzyme in the production of energy from fats and proteins. In addition, hemoglobin synthesis depends on vitamin B12. Patients with vitamin B12 deficiency develop pernicious anemia. These patients also have a weak immune system due to natural killer cell activity suppression and because circulating lymphocyte numbers are significantly decreased.

Treatment with cyanocobalamin reverses the immune weakness rapidly and treats pernicious anemia at the same time. I take 50 micrograms twice per day as part of the Mega-B50 multivitamin tablet. But I also inject 1000 micrograms of vitamin B12 every 6 months subcutaneously to be sure it is absorbed into the body. In older age the intrinsic factor from the stomach lining, which is required for absorption of vitamin B12 in the small intestine, can be missing, leading to vitamin B12 deficiency despite swallowing supplements.

Minerals required for a good immune response

Researchers identified five minerals that are essential for a strong immune system. They are zinc, iron, selenium, copper and magnesium.

Zinc

Zinc is important for a normal function of the innate and adaptive immune system. As zinc cannot be stored in the body, taking regular zinc supplements (30 to 50 mg daily) is important. I take 50 mg of amino acid chelated zinc daily.

Iron

Iron is important for cell oxygen transport and storage, DNA synthesis and for mounting an effective immune response. In particular it is the T cell differentiation and proliferation where iron is needed. Iron deficient people get a lot of infections because the immune system is paralyzed. I eat one spinach salad or steamed spinach daily, which gives me enough iron supply per day.

Selenium

Selenium is a trace mineral that is important for a normal immune response and for cancer prevention. When selenium is missing, both the adaptive and innate immune system are suffering. In this case viruses are more virulent. With selenium supplementation cell-mediated immunity is improved and the immune response to viruses is more potent. I take 200 micrograms of selenium per day.

Copper

Deficiency in copper results in a very low neutrophil blood count and causes susceptibility to infections. Copper is a trace mineral that participates in several enzymatic reactions. It is important for the innate immune response to bacterial infections. A well-balanced Mediterranean diet contains enough copper, which is why I do not supplement with extra copper.

Magnesium

An important cofactor for vitamin D in the body is magnesium. Magnesium participates in many enzymatic reactions. Between vitamin D and magnesium, the immune system is strengthened. I take 150 mg of magnesium citrate twice per day. By the way, magnesium also helps us to get a restful sleep, if we take it at bedtime.

Other dietary factors that strengthen the immune system

Polyunsaturated omega-3 fatty acids are essential for the body and help to modulate the immune system. I take 1800 mg of omega-3 (EPA/DHA) twice per day. I also like to eat fish and seafood at least 3 times per week.

Probiotics benefit both the innate and the adaptive immune system. They strengthen the epithelial gut barrier, which is an important innate immune defence. Probiotics also lower the risk for Clostridium difficile gut infections. I take one probiotic every morning.

The Immune System Changes With Age

The Immune System Changes With Age

Conclusion

The immune system consists of different organs like the bone marrow, the spleen, lymph glands, Peyer’s patches in the gut, the thymus gland and more. There is the innate immune system, which responds immediately to a virus like the Covid-19 coronavirus. The adaptive immune response involves antibody production against, for instance, the measle virus or the mumps virus. With the aging process the immune system slows down (immunosenescence). This involves an accumulation of memory T cells and a depletion of natural killer cells (NK cells). This means that the innate immunity is getting weaker as we age and chronic inflammation occurs more often. This is the reason why people above the age of 65 get more severe symptoms from the Covid-19 coronavirus. They are also more affected by influenza-type illnesses.

Take supplements to strengthen the immune system

I reviewed the cofactors of a healthy immune system in some detail. It is important that you pay attention to these, particularly the vitamin D3 intake. With a strong immune system, we can survive viral infections better, including the current Covid-19 coronavirus. Future research will likely detect how to reactivate a sluggish immune system in older people. This way vaccination responses following flu injections will become more reliable in seniors.

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Apr
18
2020

Changes of Metabolism by Inflammation

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

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

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

Factors that accelerate aging and damage your metabolism

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

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

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

How Metaflammation is developing

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

More problems with metaflammation

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

Major causes of metaflammation

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

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

Interaction of various organ systems can cause metaflammation

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

Other mechanism for pathological changes with hormone disbalances

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

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

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

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

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

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

Cardiovascular disease not just a matter of high cholesterol

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

Microbiome disruption from drugs

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

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

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

Changes of Metabolism by Inflammation

Changes of Metabolism by Inflammation

Conclusion

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

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

Drugs that change the gut biome

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

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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.

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.

Jul
22
2017

Relaxation Reduces Inflammation

Relaxation can calm your mind, but new research has shown that relaxation reduces inflammation as well.

This article is based on a research paper in Frontiers in Immunology in June of 2017.

It concentrated on the calming effect of meditation on the nuclear factor kappa B (NF-κB), which causes inflammation. We know that overstimulation of the sympathetic nervous system activates the inflammatory pathway by expressing the genes responsible for NF-κB. These authors showed that the reverse is true also, namely that  meditation suppresses inflammation.

This metaanalysis of 18 research papers included 846 participants.

Here are brief summary findings of these 18 studies. Note that diverse relaxation methods had very similar results on the genes expressing inflammatory markers.

1. Qigong practitioners

First of all, a group of Qigong practitioners had 132 downregulated genes and 118 upregulated genes when compared to non-meditating controls. Meditation strengthens the immune system and delays cell death.

2. Sudarshan Kriya yoga

Also, one form of yoga breathing is Sudarshan Kriya yoga. Subjects who practiced this form of breathing yoga for 1 hour per day did not have the stress-related response on white blood cells. In contrast, the controls who did not meditate this way showed no change in the white blood cell response to stress. Those practicing yoga had a strengthened immune system. The meditators also showed strengthening of genes that inhibit cell death.

3. Chronic lymphocytic leukemia

Furthermore, eight patients with chronic lymphocytic leukemia were practicing the “seven yoga breathing patterns”; the popular Indian yoga teacher, Swami Ramdev, developed these. Those patients practicing the breathing yoga technique activated 4,428 genes compared to controls. They showed an up to twofold upregulation, which strengthened their immune system.

4. Loneliness in older people

Another study noted that loneliness in older people causes inflammation, morbidity and mortality. 55-85 year old volunteers were taking a course of mindfulness-based stress reduction. The researchers wanted to find out whether it was due to increased inflammation that older people were more susceptible to disease. The physicians tested blood mononuclear cells for genome-wide transcriptional profiling. Those older persons who had reported loneliness had more transcription factors for nuclear factor kappa B (NF-κB) than controls without feelings of loneliness. After an 8-week course those who no longer felt loneliness had a reversal of proinflammatory gene expression. The genes that had changed expression were located on monocytes and B-lymphocytes; these are cells of the immune system.

5. Care workers for patients with mental health problems

Care workers who looked after patients with mental health problems or chronic physical problems often have stress-induced chronic inflammation markers in their blood. A study involving 23 caregivers used a practice of Kirtan Kriya Meditation (KKM) assisted by an audio recording every day for 8 weeks. The subjects filled in questionnaires for depression and mental health before and after the 8-week trial. Physicians also took blood samples for transcriptional profiling before and after the KKM trial.

Meditation effects genes and reduces inflammation

The KKM meditation group had significantly less depressive symptoms and showed improvements in mental health. There were down-regulations in 49 genes and up-regulations in 19 genes compared to the controls. The pro-inflammatory NF-κB expression showed a decrease; the anti-viral gene expression showed an increase. This was measured using the IRF-1 gene. This gene controls the expression of the interferon-regulatory factor 1 (IRF-1 gene), which controls the immune response to viral infections. The interesting observation here was that a time of only 8 weeks of meditation was able to reduce inflammatory substances in the blood and could activate the immune system to fight viruses better. Further tests showed that it was meditation that stimulated the B cells and the dendritic cells.

6. Younger breast cancer patients

Younger breast cancer patients taking a mindfulness meditation course: Another study involved younger stable breast cancer patients after treatment that also had insomnia. Patients with both breast cancer and insomnia often have a lot of inflammatory markers in the blood. In a study with 80 patients 40 underwent treatment with Tai-Chi exercises, the other group of 40 with cognitive-behavioral therapy. Tai-Chi exercises reduced IL-6 marginally and TNF (tumor necrosis factor) significantly. There was a 9% reduction with regard to the expression of 19 genes that were pro-inflammatory; there was also a 3.4% increase with regard to 34 genes involved in regulating the antiviral and anti-tumor activity in the Tai-Chi group when compared to the cognitive-behavioral therapy group.

Measurable results of mindfulness meditation course

While cognitive therapy has its benefits, the winner was the Tai-Chi group where there was down-regulation of 68 genes and up-regulation of 19 genes. As in the prior study there was a decrease of the pro-inflammatory NF-κB expression, which reduced the inflammatory response.

7.  Study with fatigued breast cancer patients

In another breast cancer study with fatigued breast cancer patients the patients practiced 3 months of Iyengar yoga. After 3 months of yoga 282 genes showed up-regulation and 153 genes showed down-regulation. There was significant lowering of the expression of NF-κB. This suggests a lowering of inflammation. At the same time questionnaires showed that the fatigue factors experienced a reduction 3 months after initiating yoga exercises.

8. Mindful meditation used in younger breast cancer patients

A group of 39 breast cancer patients diagnosed before the age of 50 received six weekly 2-hour sessions of mindful awareness practices (MAP). This program is very suitable for cancer survivors. In addition to the group sessions the patients also did daily exercises of between 5 minutes and 20 minutes by themselves. The control group consisted of patients on a wait list. The investigators used several psychological measure (depression and stress) and physical measures (fatigue, hot flashes and pain) to assess their progress. Gene expression in the genome and inflammatory proteins were measured at baseline and after the intervention.

Effects of mindful awareness practices

Mindful practices showed clear benefits: they reduced stress, and sleep disturbances, hot flashes and fatigue showed improvement. Depression also shoed a marginal reduction. There were 19 pro-inflammatory genes that were mad ineffective, but not in the control group that did not do mindful practices. Gene tests revealed that transcription factor NF-κB had significant down-regulation. Conversely the anti-inflammatory glucocorticoid receptor and the interferon regulatory factors showed higher values. Genes with down-regulation came from monocytes and dendritic cells while genes with up-regulation came from B lymphocytes.

9. Telomerase gene expression

Lifestyle modification changes telomerase gene expression: 48 patients with high blood pressure enrolled in an extensive lifestyle program teaching them about losing weight, eating less sodium, exercising, adopting a healthy diet and drinking less alcohol. The other choice was to use transcendental meditation (TM) combined with health education with weekly sessions for 4 months. It turned out that both programs led to an increased expression of telomerase genes. Both groups did not show telomerase changes, but the authors stated that the observation time was too short for that to occur. The extensive health education program turned out to be better for patients with high blood pressure as it decreased the diastolic blood pressure more and resulted in healthier lifestyles.

10. Older patients with insomnia

Mind-body interventions for older patients with insomnia: Examiners divided a sample of 120 older adults with insomnia into two groups. They treated one group with cognitive-behavioral therapy (CBT), the other group with Tai Chi. The control group consisted of a group of people participating in a sleep seminar. 4 months after the intervention the CBT group had a significantly reduced C-reactive protein (CRP). The pro-inflammatory markers were lower in both groups after 2 months and in the Tai Chi group this remained low until 16 months. Gene expression profiling showed that CBT downregulated 347 genes and upregulated 191 genes; the Tai Chi group had downregulated 202 genes and upregulated 52 genes. The downregulated genes were mostly inflammatory genes while the upregulated genes controlled mostly interferon and antibody responses.

11. Patients with bowel disease

19 patients with irritable bowel syndrome (IBS) and 29 patients with inflammatory bowel disease (IBD) were treated with a relaxation response-based mind-body intervention. This consisted of 9 weekly meetings, each lasting 1.5 hours and practices a home for 15-20 minutes. The participants were taught breathing exercises and cognitive skills designed to help manage stress. At the end of the mind-body intervention and at a follow-up visit 3 weeks later participants of both the IBS and IBD groups scored higher in quality of life and lower in the level of anxiety they had before. They had reduced symptoms of their conditions.

Results of relaxation response-based mind-body intervention on IBS patients

The IBS group showed an improvement in 1059 genes. These were mostly improvements in inflammatory responses, in cell growth, regarding proliferation, and also improvements in oxidative stress-related pathways. The IBD group showed improvements in 119 genes that were related to cell cycle regulation and DNA damages. Other genetic tests showed that NF-κB was a key molecule for both IBS and IBD. The main finding was that relaxation response-based mind-body intervention was able to down regulate inflammation in both IBD and IBS.

12. Caregivers for Alzheimer’s patients receiving a course of MBSR

25 caregivers participated in a course of mindfulness based stress reduction (MBSR). Using 194 differently expressed genes the investigators could predict who would be a poor, moderate or good responder to the MBSR intervention. These genes related to inflammation, depression and stress response. 91 genes could identify with an accuracy of 94.7% at baseline whether the person would receive psychological benefits from the MBSR program.

13. Higher state of consciousness in two experienced Buddha meditators

Genetic tests showed, similar to the description of other cases that genes affecting the immune system, cell death and the stress response experienced stimulation. EEG studies in both individuals during deep meditation were almost identical with an increase of theta and alpha frequency ranges.

14. Rapid gene expression in immune cells (lymphocytes) in the blood

One study used gentle yoga postures, meditation and breathing exercises. 10 participants recruited at a yoga camp had yoga experience between 1.5 months and 5 years. Their response resulted in 3-fold more gene changes than that of controls. Otherwise the findings were very similar to the other studies.

15. Genomic changes with the relaxation response

The relaxation response (RR) is the opposite of the stress response.  One study examined how various modes of entering into the relaxation response like yoga, Qi Gong, Tai Chi, breathing exercises, progressive muscle relaxation, meditation, and repetitive prayer would lead to beneficial gene effects. As in other studies inflammation was reduced and the immune system was stimulated from the relaxation response. This was verified with detailed gene studies. The authors noted that different genes were activated in people who had done long-term RR practice versus people who practiced RR only for a shorter time. There were distinctly different gene expressions.

16.  Energy metabolism and inflammation control

Relaxation responses beneficial for energy metabolism and inflammation control: Experts with experience in RR were compared with a group of novice RR practitioners. Experts and short-term practitioners expressed their genes differently at baseline. But after relaxation both experts and novices had gene changes in the area of energy metabolism, electron transport within the mitochondria, insulin secretion and cell aging. The upregulated genes are responsible for ATP synthase and insulin production. ATP synthase is responsible for energy production in the mitochondria and down regulates NF-κB pathway genes. Inflammation was reduced by these changes. All these beneficial gene changes were more prominent in expert RR practitioners. Other beneficial changes noted were telomere maintenance and nitric oxide production in both expert and novice RR practitioners.

17. Relaxation changes stress recovery and silences two inflammatory genes

Mindfulness meditation changes stress recovery and silences two inflammatory genes: Experienced meditators were tested after an intensive 8-h mindfulness meditation retreat workshop. Two inflammatory genes were silenced by mindfulness meditation compared to controls. Other genes that are involved in gene regulation were found to be downregulated as well. These experienced meditators had a faster cortisol recovery to social stress compared to controls.

18. Vacation and meditation effect on healing from disease

This last study investigated the effect of a 6-day holiday retreat. One group was offered a 4-day meditation course, one group was the control group just holidaying and the third group was an experienced meditation group who also took the retreat meditation course. Depression, stress, vitality, and mindfulness were measured with questionnaires. All groups were positively changed after the holiday and remained this way at 1 month after the retreat. 10 months after the retreat novice meditators were less depressed than the vacation control group. At the center of the experiment was the gene expression study.

Effects of holiday and meditation

390 genes had changed in all of the groups. The authors assumed that this was due to the relaxation experience of the retreat. The genes involved related to the stress response, wound healing, and injury. Other genes measured inflammation (control of tumor necrosis factor alpha). Another set of genes measured the control of protein synthesis of amyloid beta (Aβ) metabolism, which causes Alzheimer’s disease and dementia. All groups had markers that indicated less risk of dementia, depression and mortality, which was likely due to the relaxation from the retreat.

Relaxation Reduces Inflammation

Relaxation Reduces Inflammation

Conclusion

This study is a meta-analysis of 18 research papers. The authors found that very different approaches to relax the mind have fairly consistent universal effects on reducing inflammation. Most of this work was done with genetic markers. No matter what type of relaxation method you use, you will have beneficial effects from it. But the beneficial effect is not only strengthening the immune system, it also improves sleep, depression, anxiety and blood pressure. In addition it is improving your stress response, wound healing, risk of dementia and it reduces mortality. We don’t quite understand all of the details yet.

What is definitely documented is the effect of the mind-body interaction. It also points clearly to the relaxation response from meditation and similar relaxation methods. This has been proven beyond any doubt through genetic tests.

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Jul
01
2017

Advanced Glycation End Products (AGEs)

Advanced glycation end products (AGEs) form through cooking food at high temperatures. Sugar molecules react with proteins crosslinking them and changing how they function. It prevents proteins from doing their job. Glycation also causes inflammation, which damages mitochondria, the power packages inside cells that provide the body with energy. Overall AGEs lead to premature aging, which comes from the toxic protein reactions. Advanced glycation end products accumulate as glycated proteins in the tissues of the body. This leads to mitochondrial dysfunction.

Effect of advanced glycation end products (AGEs) on the body

The toxic effects of AGEs frequently occur in the following tissues.

  • The accumulation of AGEs can cause kidney disease and kidney failure (renal failure). In this case the kidneys no longer filter the blood to excrete waste. Hemodialysis may be necessary.
  • AGEs damager joint cartilage, so it can no longer handle stress and joint stiffness sets in. AGEs are now recognized as a major cause of osteoarthritis.
  • Cross-linked proteins from AGEs can cause Alzheimer’s and Parkinson’s disease. Damaged proteins accumulate in brain cells that disable and kill them eventually.
  • Glycation of LDL particles is an important cause of increasing the plaque formation in arteries by LDL. Glycated LDL is much more susceptible to oxidation than regular LDL. Oxidized LDL causes damage to the lining of the arteries and destroys endothelial nitric oxide synthase. This is a critical enzyme that maintains vasodilatation and blood flow. When glycation of LDL has set in, LDL receptors can no longer recognize it. This means that glycated LDL continues to circulate in the bloodstream where it contributes to the atherosclerotic process. It forms a plaque which becomes a reason for heart attacks and strokes. Glycation of LDL is particularly common in patients with diabetes.
  • Glycation of the skin sensitizes the skin to UV light damage. It triggers oxidative stress that increases the risk of skin cancer.
  • Glycation damages our eyes. It causes clouding of the lens (cataracts) and it damages the retina. Macular degeneration can ultimately cause blindness.
  • When glycation affects the discs in the spinal cord, this can cause disc protrusions and disc herniations. Injuries to the nearby spinal nerves can happen causing limping and leg or arm weakness.

Nutrients to counter AGEs

There are nutrients that can slow down the rate of glycation and as a result will halt the aging process.

Benfotiamine

Benfotiamine is a fat-soluble form of the water-soluble vitamin B1 (thiamine). It can reverse glycation in cell cultures and in humans.

As a result the damage to the cells that are lining arteries is reduced. Benfotiamine also counters diabetic neuropathy, retinopathy and nephropathy.

Pyridoxal 5’-phosphate

Pyridoxal 5’-phosphate is a metabolite of vitamin B6. It is similar to benfotiamine in that it counters glycation and dissolves deposited AGEs. It is particularly useful to stop fat and protein glycation. In diabetic patients lipid glycation is often a problem as these authors have shown. Pyridoxal 5’-phosphate traps glucose breakdown products before they become part of glycation reactions.

Carnosine

Carnosine is a dipeptide, made up of the amino acids histidine and beta-alanine. It is found in higher concentration in muscle and brain tissue. Carnosine scavenges for free radicals and prevents AGE formation. This prevents both lipid glycation and protein glycation. This publication states that carnosine can play a role in preventing Alzheimer’s disease. Carnosine prevents protein crosslinking. The result is that tangled protein clumps cannot accumulate and cause Alzheimer’s disease.

Carnosine also reduces blood lipid levels and stabilizes atherosclerotic plaques. This reduces the risk of plaque rupture, which can cause a heart attack or stroke.

Carnosine also has a mitochondria stabilizing function resisting the destructive effects of oxidative stresses.

Luteolin

Many plants contain luteolin, which is a bioflavonoid. It has anti-inflammatory effects and works by suppressing the master inflammatory complex, called NF-kB.  NF-kB triggers the production of multiple cytokines and is the cause of many cancers, chronic diseases, autoimmune diseases and septic shock. Kotanidou et al. did an experiment where they injected mice with Salmonella enteritis toxin, either with or without luteolin protection. Without luteolin only 4.1% of the mice survived on day 7. With luteolin protection 48% were alive on day 7.

Luteolin has been shown to be effective as an anti-inflammatory in the brain, the blood vessel lining, intestines, skin, lungs, bone and gums.

All these four supplements are available in the health food store. They work together and would be recommendable in diabetic patients where glycation is most prominent. But these supplements are also useful for older people who want to slow down the aging process in general.

Nutrients to slow down mitochondrial aging

Glycation causes mitochondrial deterioration and dysfunction. It accelerates aging in every aspect. AGEs (advanced glycation end products) crosslink proteins, lipids, but also damage enzymes and DNA. Glycation causes a slow down of mitochondrial energy production. The end result is a lack of energy and slower repair processes, which all depend on mitochondrial energy production. The following supplements have shown some merit in reversing this process.

Pyrroloquinoline quinone (PQQ)

PPQ is a supplement that is known to produce new mitochondria in cells. This helps the energy metabolism of aging cells to recover.

Taurine

Taurine is an amino acid that occurs abundantly in heart and skeletal muscles cells, brain cells and cells of the retina. These are areas in the body with high metabolic rates that can burn out mitochondria. Taurine regulates enzymes in mitochondria that harvest energy from food substances. In patients who experience accelerated aging, a lack of taurine can produce an energy crisis. But supplementation with taurine can rescue the cells by reducing oxidative stress and restoring the function of mitochondria in cells that are aging. Brain cells were putting out new shoots, called neurites when taurine was given as a supplement. This helps to improve brain connection, and preserves memory and cognition.

R-lipoic acid

R-lipoic acid helps to extract energy from foods and support mitochondrial function. When R-lipoic acid is given to aging animals, their metabolic function improves, the mitochondria become healthier and there are less oxidative stress-inducing byproducts. It protects their liver, heart and brain cells from oxidative stress in their mitochondria. It is becoming known as an energy-giving supplement.

Advanced Glycation End Products (AGEs)

Advanced Glycation End Products (AGEs)

Conclusion

Sugar overconsumption and overcooking food cause advanced glycation end products (AGEs) through lipid and proteins cross-linking. This leads to premature loss of organ function. The mitochondria are also slowed down. This creates premature aging. Fortunately there are a few supplements like benfotiamine, pyridoxal 5’-phosphate, carnosine and luteolin. They protect against glycation. Mitochondria can also be protected by PPQ, taurine and R-lipoic acid. Although we cannot stop the aging process, avoiding sugar and stopping to consume overcooked food, such as barbecued meats and deep fried food is a sensible step in prevention. Aging can slow down significantly with this approach and some supplements.

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Apr
01
2017

When Food Causes Inflammation

Dr. Hal Blatman gave a talk about when food causes inflammation. He gave his talk on Dec. 9 at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The original title was “Food, Pain and Dietary Effects of Inflammation”.

Dr. Blatman is the medical director of Blatman Health and Wellness Center, Cincinnati and Batman Medical Services, Manhattan.

General remarks about nutrition

Dr. Blatman pointed out that mistakes of nutrition are often behind chronic diseases and illnesses. The physician’s task is to explain to patients how they can change their food intake to improve inflammation in the body and to allow the body to heal itself.

Hippocrates said 400 BC “Let food be thy medicine and medicine be thy food”.

In this context Dr. Blatman stated that nutrition could exacerbate symptoms or relieve symptoms and there must be rules for good nutrition. If we do not take care of our nutrition, the gut flora composition changes and causes leaky gut syndrome. But if we consume healthy foods all of this improves.

Mathematical formula for when food causes inflammation

To make it easier to understand the impact of food on our health the speaker offered this formula:

G-B+R=P

G = stands for good, beneficial things you can put into your body.

B = bad, toxic things that affect your body negatively.

R = reserves that your body has since birth (minus the amounts you have used up)

P = pain and problems you are going to experience

It is P (pain and other medical problems) what brings the patient to see the doctor. G and B is what the patient can change. When done right, the P value in the formula reduces and the pain or medical problems go away.

Nutritional rules

Dr. Blatman said there are three rules about nutrition.

Rule #1 is to not eat fake or toxic foods

He listed NutraSweet, Splenda, Saccharin, margarine and olestra.

Aspartame

Aspartame experiments on rats showed that it can cause cancer: Dr. Blatman said that aspartame causes multiple myeloma and Hodgkin’s lymphoma in man. Aspartame worsens depression, 10% is metabolized in the liver into methanol, a nerve poison.

Splenda

Splenda (sucralose) originates from sugar. However, several chlorine atoms were inserted into the sugar molecule. It reduces beneficial microflora in the gut. It also interacts with liver enzymes, which interfere with the bioavailability of oral drugs.

Saccharin

Saccharin alters gut bacteria and increases glucose tolerance.

Hydrogenated fat and margarine

Insects don’t eat margarine, mold will not grow on it, and it will not support life. Merchants like it because food does not turn stale on shelves. Hydrogenated fats like margarine are like poisons. They raise the bad LDL cholesterol levels and reduce beneficial HDL cholesterol levels. The prostaglandin balance changes so that inflammation occurs. There is increased evidence of diabetes and the cell membrane composition changes. Proinflammatory cytokines can cause pain in the dorsal root ganglions. It follows from all of this that it is best to cut out all hydrogenated fat and margarines.

Partially hydrogenated vegetable oil

The cell membrane consists of two lipid layers at a specific ratio of omega-6 essential fatty acids and omega-3 essential fatty acids. It also contains triglycerides, phospholipids and protein. Cell membrane absorb nutrients to move into the cell and eliminate waste out of it. The cell membrane needs to remain flexible and within neurons needs to transmit electrical information. The membrane composition is critical for the cell membranes to perform optimally. It is here that the physician has to explain this to the patient. All the fats we eat are the raw material, which will make up our cell membranes. So what fat we eat that day travels into the cell wall that becomes part of it that day. The same process occurs with cell wall repair. If we eat hydrogenated fat that day, it travels into the cell wall.  A membrane with hydrogenated fat will:

  • Not transmit nutrients inside the cell
  • Will not transmit waste out
  • Causes the membrane to lose flexibility
  • In a nerve cell there will be abnormal neuron transmission

If we eat hydrogenated fat, we become like a “genuine GM truck fixed with inferior parts”, so Dr. Blatman. The interesting observation is that it takes 4 months after eliminating hydrogenated oil from the diet to get it out from red blood cells. Be aware that French fries increase pain for 4 months, so why eat them?

Olestra

Olestra, an artificial fat: This fat, Olestra has been developed as an artificial fat and is used in chips. It can cause diarrhea, abdominal cramps and weight gain with long-term use. Olestra belongs into the group of fake/toxic foods. Don’t eat Pringles or chips that are made with this.

Healthy oils

There are two types of essential fatty acids, omega-6 fatty acids and omega-3 fatty acids. Many processed foods contain only omega-6 fatty acids, because this is the cheapest way to produce them (they are based on vegetable oils). Instead you want to eat healthy fats like omega-3 fatty acids contained in nuts and fish. You can also add molecularly distilled, high potency omega-3 fatty acids (purified fish oil) as a supplement to help restore the balance between omega-6 and omega-3 in your food intake. Avoid omega-6 fatty acids from corn oil, safflower oil, grape seed oil, soybean oil, cottonseed oil, canola oil and peanut oil.

Metabolism of omega-6 fatty acids versus omega-3 fatty acids

Compare the metabolism of omega-6 fatty acids with that of omega-3 fatty acids.

The linoleic acid of omega-6 fatty acids gets metabolized into arachidonic acid, which causes pro-inflammatory mediators, PGE2 and LTB4. On the other hand with omega-3 fatty acids alpha-linolenic acid (ALA) is metabolized into EPA, DHA and the anti-inflammatory mediators PGE3 and LTB5.

It is easily understandable why a surplus of omega-6 fatty acids from processed foods will disbalance the omega-6 to omega-3 ratio. This ratio should be 1:1 to 3:1, but many Americans’ omega-6 to omega-3 ratio is 6:1 to 18:1. Omega-6-fatty acids cause arthritis, heart disease and strokes. Be particularly careful in avoiding soybean oil, which is the most popular oil in the last few decades to foul up the omega-6 to omega-3 ratio through processed foods.

Balance of omega-3 and omega-6 fatty acids

When it comes to balancing omega-3 and omega-6 fatty acids in your diet, be aware that nutritional balancing can help you restore the ideal omega-6 to omega-3 ratio of 1:1 to 3:1. An easy way is to cut out processed foods as much as possible. Supplement with molecularly distilled fish oil capsules to add more omega-3 fatty acids into your food intake. Dr. Blatman gave the example of rheumatoid arthritis patients that were put on omega-3 supplements. After 24 weeks their joint swelling and tenderness went down.

Rebalancing the omega-6 to omega-3 ratio was able to treat depression as this research showed. This makes you wonder how much depression may be caused by overconsumption of processed food.

Suggested doses of omega-3 fatty acid supplementation

Dr. Blatman suggested the following doses of omega-3 supplementation for various purposes:

  • 1 gram/day as supplementation for healthy adults with a good diet
  • 1-3 grams/day for people with cardiovascular disease
  • 5-10 grams/day for patients with an autoimmune disease, with chronic pain or with neuropsychiatric conditions

He mentioned that these doses are empirical, but in his opinion definitely help. Due to quality differences he suggested that you buy fish oil capsules in a health food store where the quality is best. Stay away from discount stores (the quality is the worst) and drug stores.

Other healthy oils are olive oil and coconut oil. They are also useful for cooking.

Rule #2 is not to eat inflammatory foods

Our body functions like a luxury car; it needs pure food to function. Anything less leads to inflammation, particularly when you eat sugar and processed foods.

Inflammatory foods are sugar, white flour, fruit juice and white/red potatoes. A medium potato=1/2 cup of sugar! Other problematic foods are wheat grain contained in breads, pasta, cereal and thickeners in soups and sauces.

What is the problem with these foods? They break down the zonulin proteins that are a bridge between the lining cells of the gut.

This leads to an increase of intestinal permeability, and leaky gut syndrome can develop. Inflammatory cytokines from visceral fat add to the gut inflammation, and cardiovascular disease and high blood pressure can develop.

Fried potatoes, in particular the consumption of French fries, have been identified as the cause of inflammatory bowel disorder (IBD). Countries with the highest consumption of French fries have the highest incidence of IBD.

A Mediterranean diet and the DASH diet are anti-inflammatory diets.

Rule #3 is to not disturb the bowel flora

A healthy bowel flora is symbiotic with the body. You achieve this by eating green leafy vegetables. A toxic flora from dysbiotic microbes comes from eating white flour, white sugar and red meat. Red meat leaves residues on which dysbiotic bacteria thrive.

Symbiotic gut bacteria produce vitamin K, cobalamin, pyridoxine, biotin, riboflavin, pantothenic acid and short fatty acids. They also degrade metabolic toxins, prevent pathogens from colonization and they stimulate the immune system to mature.

Dysbiosis occurs when the wrong diet consisting of sodas, white flour, sugar and red meat is over consumed. There are toxins that are produced by the dysbiotic microbes. These injure the bowel wall and make the immune system work harder. Immune system dysfunction, fatigue and fibromyalgia can follow.

Dr. Blatman stated that gut dysbiosis that causes leaky gut syndrome could also cause ulcer disease, diabetes, heart disease, fibromyalgia, chronic fatigue syndrome, chronic pain and even cancer.

When Food Causes Inflammation

When Food Causes Inflammation

Conclusion

This was a whirlwind tour through a talk given by Dr. Blatman during the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas. What food we eat determines what gut bacteria we harbor, symbiotic ones or toxic ones. This in turn determines which way our health develops. But the content of what we eat is also important. If we consume processed foods we end up consuming way too many omega-6 fatty acids, which cause inflammation, arthritis and heart disease. This is happening in front of our eyes, if we start seeing things the way they are. I was aware of this since the mid 1990’s. In a lecture I attended at a continuing education conference a cardiologist pointed out that inflammation was the determining factor of whether or not our patients would get a heart attack.

Cholesterol concept being replaced by inflammation concept

The lecturer mentioned then that the older cholesterol concept would be replaced by the newer inflammation concept. He was right, but it goes even further! There is the important omega-6 to omega-3 ratio, and fish oil supplementation helps. At the same time it is necessary cutting out processed foods. But there is the newer insight that our bowel flora and red meat consumption can culture toxic bacteria in our own gut. It is in our power to start eating more vegetables and cut out sugar and starchy food. It is time to see chips and French fries not as a “convenience” but a hazard to your health. Food does not have to cause inflammation; right food choices will help us to stay well and live longer.

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Jan
28
2017

Cardiovascular Disease And Inflammation

Dr. Mark Houston talked about cardiovascular disease and inflammation – “the evil twins”. He presented this lecture at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas. Dr. Houston is an associate clinical professor of medicine at the Vanderbilt University Medical School in Nashville, TN 37232.

New thinking about cardiovascular disease and inflammation

Dr. Houston pointed out that the old thinking about cardiovascular disease is defunct, needs replacing and, of course, that the new thinking needs to take its place. Specifically, here are a number of points regarding the new thinking.

  1. Coronary heart disease and congestive heart failure are diseases of inflammation. In the same fashion, oxidative stress, vascular immune dysfunction and dysfunction of the mitochondria are also part of them.
  2. Moreover, in the past it was difficult to reduce these cardiovascular diseases. In contrast, with the new thinking there are now new treatment approaches that help cure cardiovascular disease.
  3. On the whole, the development of heart disease has a long history. First, endothelial dysfunction predates coronary artery disease by many years. Second, the next step is vascular smooth muscle dysfunction. Finally, inflammation develops and structural changes occur in the small and larger blood vessels with atheromatous deposits (plaques) and final occlusion, at which point you get a heart attack.

New approach to the old problem of plugged coronary arteries

Canadian physician Sir William Osler has already stated more than 100 years ago “A man is as old as his blood vessels”. In the first place, the old thesis was that cholesterol would lead to deposits that close coronary blood vessels and cause heart attacks. Dr. Houston called this the “cholesterol-centric “ approach. In reality, the truth is that with conventional blood tests you are missing 50% of all the high-risk patients that are going to develop heart attacks. They are missing the ones that have chronic inflammation, but normal cholesterol levels.

Coronary artery damage from cholesterol elevation versus inflammation

What was not common knowledge in the past was that oxidative stress associated with normal aging can also lead to chronic low-grade inflammation. This oxidative stress leads to mitochondrial DNA changes. Associated with it are biochemical changes that cause chronic inflammation, which in turn will affect the lining of the arteries. The literature describes a metabolic change that known as metabolic syndrome. It leads to high blood pressure, hardening of the arteries and eventually heart attacks and strokes. Accordingly, the key today is to include in screening tests all parameters that will predict who is at risk to develop a heart attack or not.

Blood tests to screen for cardiovascular disease and inflammation

The physician should check blood tests and health history for dyslipidemia, high blood pressure (hypertension), hyperglycemia, smoking, diabetes, homocysteinemia, obesity etc. Also, patients with high GGTP (gamma-glutamyl transferase) levels in the blood are more at risk to develop diabetes. This in turn leads to inflammation of the arterial wall and heart attacks. There are 25 top risk factors that account for all causes of heart attacks.

Briefly, apart from the 7 factors already mentioned above the physician wants to check for high uric acid levels (hyperuricemia), kidney disease, high clotting factors (fibrinogen levels), elevated iron levels, trans fatty acid levels, omega-3 fatty acid levels and omega-6 to omega-3 ratio, low dietary potassium and magnesium intake with high sodium intake, increased high sensitivity C reactive protein level (hs CRP measuring inflammation).

Further high risk factors for coronary artery disease

The list to test for cardiovascular disease risk continues with blood tests for vascular immune dysfunction and increased oxidative stress, lack of sleep, lack of exercise, subclinical low thyroid levels, hormonal imbalances for both genders, chronic infections, low vitamin D and K levels, high heavy metals and environmental pollutants.

The speaker stated that he includes a hormone profile and vitamin D levels. He does biochemical tests to check for mitochondrial defects. Micronutrients are also checked as cardiovascular patients often have many nutritional deficiencies coupled with cardiovascular factors. Inflammation is monitored through testing the levels of C-reactive protein (CRP).

The Rasmussen score

In order to assess the risk of a patient Dr. Cohen, a cardiologist has developed the Rasmussen score, which is more accurate than the Framingham score.

The following tests are performed on the patient: computerized arterial pulse waveform analysis (medical imaging), blood pressure at rest and following exercise and left ventricular wall of the heart by echocardiography. Further tests include urine test for microalbuminuria, B-type natriuretic peptide (BNP, a measure of congestive heart failure), retinal score based on fundoscopy, intima-media thickness (IMT, measured by ultrasound on the carotid artery) and electrocardiogram recording (EKG).

Here is what the Rasmussen score means:

  • With a disease score of 0 to 2: likely no heart attack in the next 6 years
  • The disease score is 3 to 5: 5% likely cardiovascular events in the next 6 years
  • Disease score > 6: 15% likely cardiovascular events in the next 6 years

Non-intervention tests to measure cardiovascular health

1. The ENDOPAT test

With this test the brachial artery is occluded with a blood pressure cuff for 5 minutes. Endothelial dysfunction is measured as increased signal amplitude. A pre- and post occlusion index is calculated based on flow-mediated dilatation. The values are interpreted as follows: an index of 1.67 has a sensitivity of 82% and specificity of 77% to predict coronary endothelial dysfunction correctly. It also correlates to a future risk for coronary heart disease, congestive heart disease and high blood pressure.

2. The VC Profile

This test measures the elasticity of the arteries. There is a C1 index that measures the elasticity of the medium and smaller vessels and the C1 index, which measures elasticity of the larger arteries and the aorta. The smaller the numbers are, the less elastic the arterial walls.

3.The Corus CAD score

This is a genetically based blood test. The score can be between 0 and 40. If the score is 40, there is a risk of 68% that there is a major blockage in one or more coronary arteries.

4. Coronary artery calcification

The CAC score correlates very well with major event like a heart attack. There is a risk of between 6- and 35-fold depending how high the CAC score is. The key is not to wait until you have calcification in your coronary arteries, but work on prevention.

Treatment of cardiovascular disease and inflammation

When the doctor treats heart disease, all of the underlying problems require treatment as well. It starts with good nutrition like a DASH diet or the Mediterranean diet.

Next anti-inflammatory and other supplements are added: curcumin 500 mg to 1000 mg twice a day, pomegranate juice ¼ cup twice per day, chelated magnesium 500 mg twice per day, aged garlic 1200 mg once daily, taurine 3 grams twice per day, CoQ-10 300 mg twice per day and D-ribose 5 grams three times per day. This type of supplementation helps for chest pain associated with angina. On top of this metabolic cardiology program the regular cardiac medicines are also used.

Additional supplements used in the metabolic cardiology program may be resveratrol 500 mg twice per day, quercetin 500 mg twice per day, omega-3 fatty acid 5 grams per day, vitamin K2 (MK 7) 100-500 micrograms per day and MK4 1000 micrograms per day. In addition he gives 1000 mg of vitamin C twice per day. This program helps in plaque stabilization and reversal and reduction of coronary artery calcification.

Case study showing the effect of metabolic cardiology program

Here is a case study of a heart patient that was treated by Dr. Houston. He was a white male, first treated for congestive heart failure as a result of a heart attack in June 2005. Initially his ejection fraction was 15-20%. His medications were: digoxin 0.25 mg once daily, metoprolol 50 mg twice per day, ramipril 10 mg twice per day, spironolactone 25 mg twice per day and torsemide 20 mg once daily. These medications remained in place, but the patients followed the metabolic cardiology program in addition. Here are the results of his ejection fraction (EF) values after he was started on the metabolic program:

  • Initial measurement: EF15-20%. Marked shortness of breath on exertion.
  • 3 months: EF 20-25%. He reported improved symptoms.
  • 6 months: EF 25-30%. He said that he had now minimal symptoms.
  • 12 months: EF 40%. He had no more symptoms.
  • 24 months: EF 50%. He reported: “I feel normal and great”.
  • 5 years: EF 55%. He said” I feel the best in years”.

A normal value for an ejection fraction is 55% to 70%.

Cardiovascular Disease And Inflammation

Cardiovascular Disease And Inflammation

Conclusion

Testing for heart disease risk has become a lot more sophisticated than in the past, and the tests have opened up a window to early intervention. Metabolic cardiology is a new faculty of cardiology that assists in the reversal and stabilization of heart disease. It will help high blood pressure patients and stabilizes diabetes, which would otherwise have deleterious effects on heart disease. Metabolic cardiology improves angina patients. It also prevents restenosis of stented coronary arteries. As shown in one clinical example reduced ejection fractions with congestive heart failure will improve. The metabolic cardiology program achieved all of these improvements.

As usual, prevention is more powerful than conventional treatment later. To give your cardiac health a good start, don’t forget to cut out sugar, exercise regularly and follow a sensible diet.

Oct
17
2015

Depression Needs Treatment

Depression is common and depression needs treatment. 10% of all men and 20% of all women have a period of depression in their lives. In people with medical illnesses depression is more common: 20% to 40% (Ref.1).

First, the peak age for depression is usually the age of 25 to 44. There are special groups where depression is also common. In adolescents 5% are affected with depression and 13% of women tend to get depressed after delivery, a condition called postpartum depression.

Second, in any age group with depression there is a risk of suicide, but with adolescents this is particularly true.

Third, about 10% to 15% of people with general medical illness are developing depression, such as patients with Parkinson’s disease, stroke, Alzheimer’s disease, cardiac disease, HIV infection, end-stage renal failure and cancer.

Causes of depression

Officially it is not known what causes depression. That is what medical textbooks say. However, other books like Datis Kharrazian’s book “Why isn’t my brain working?” offers several scenarios that can cause depression and he has examples of cases that were cured of depression (Ref.2). He points out that deficiencies in two major brain transmitters can cause depression: serotonin and dopamine.

Serotonin

First of all, serotonin is produced in the midbrain from the amino acid tryptophan in two biochemical steps. These biochemical conversions require iron, vitamin B6, vitamin B12, niacin, folic acid and magnesium as co-factors. But you also need the “large neutral amino acid transporter” (LNAA) to transport tryptophan through the blood/brain barrier into the brain.

Dopamine

Furthermore, dopamine is a neurotransmitter that is produced in the frontal lobes of the brain. It is also necessary for learning. The brain synthesizes dopamine from tyrosine, which has to be manufactured in the liver from the amino acid phenylalanine. You need to have a healthy liver to produce tyrosine, which needs to be transported through the blood/brain barrier into the brain; similar to tryptophan this requires the “large neutral amino acid transporter” (LNAA). People with hepatitis, fatty liver, insulin resistance or diabetes may have problems with the LNAA transporter, which can cause dopamine deficiency (Ref.2). But they may also have low serotonin, if tryptophan did not enter the brain because of a transportation problem. This will happen with sugar overconsumption, as insulin resistance develops and affects the LNAA transporter resulting in both low serotonin and dopamine (Ref.2).

Inflammation

Finally, in the 1990’s researchers confirmed that inflammation is also a possible factor in the causation of neurological disease including depression. Ref. 2 points out that gut issues can become brain issues as inflammatory substances can leak trough a leaky gut into the blood stream and trough a leaky blood/brain barrier into the brain. Hypothyroidism can activate brain inflammation and lead to an imbalance of the neurotransmitters. Gluten sensitivity is also an important cause of depression through the inflammatory connection, but few physicians recognize the full impact of this.

Tests for depression

There are no laboratory tests that would define depression. However, every patient should receive a blood test to check for hypothyroidism, a common cause of depression. When the tests confirm hypothyroidism, the physician can easily treat this with thyroid hormone replacement.

Otherwise the physician diagnoses depression by doing a mental status examination, history and review of symptoms. A good start is to ask: “In the past 2 weeks how little interest or pleasure in doing things have you had?” and “Have you been feeling down, depressed, or hopeless in the past 2 weeks?” (Ref.3).

There are detailed psychometric questionnaires available such as the Beck Depression Inventory that can assist the physician to establish the diagnosis.

Myths of depression

One of the myths regarding depression is that it would be contagious. As a matter fo fact, a study on 2000 high school students showed that depression was not infective. The contrary was true: human interaction with friends who had a “healthy mood” improved depression. By the same token, when you constantly compare yourself with your Facebook friends, and you are not in the best mood, your mood may worsen and you could become depressed.

Treatment of depression

Despite advances in the treatment of depression the response rate with antidepressant therapy has a limit of 60% to 70%. According to Ref.4 inadequate dosing and misdiagnoses account for the fact that 30% to 40% of treated people with depression have treatment failures. Typically the first antidepressant involves a selective serotonin reuptake inhibitor (SSRI), but newer trials have shown that the older monoamine oxidase inhibitors (MAOIs) have a higher success rate when treating depression initially (Ref.4).

For example, a good antidepressant for mild to moderate depression is St. John’s wort, which is recommended by Ref. 5 as having less side-effects as other antidepressants.

In treating resistant depression the psychiatrist often employs other combinations of antidepressants. In addition the health professional recommends to add cognitive/behavioral therapy, which makes the overall treatment more successful. It goes without saying that complicated cases of depression belong into the hands of an experienced psychiatrist.

Suicides

Unfortunately a mental disease like depression still has a stigma attached to it. As a result many people are in deep denial about the fact that mental disease exists. Friends who do not understand depression may inadvertently say things that make the symptoms of the depressed person more severe and distance themselves at a time when they would need support from friends. The end result is that the patient feels lonely, misunderstood and that suicidal thoughts enter the mind. Men often resist seeking treatment for depression, women are better in seeking professional help and getting effective treatment.

Need for a psychiatrist to help prevent suicides

This is where a psychiatrist needs to intervene. If this does not happen, people start attempting suicide and finally commit suicide. In the US committed suicides have a gender ratio of male to female of 3:1 to 10:1. These situations become very difficult. The family needs to step in and talk to the patient. It is best to accompany the patient to the hospital for an assessment. You may want to go to the hospital in your private car or by ambulance. Don’t be shy to call 911 for an ambulance. Better to be cautious than have a major crisis that ends in completed suicide.

Alternative depression treatments

There are alternative treatments for depression.

  1. Magnetic therapy for depression: This therapy is also called transcranial magnetic stimulation (TMS) and was approved for Canada and in 2008 by the FDA. But it is not as powerful according to Ref. 3 as unitemporal electroconvulsive therapy.
  1. Bifrontal electroconvulsive therapy (ECT): Electroconvulsive therapy with two pedals applied to the front of the skull appears to have the best results in terms of treating depression.
  2. Omega-3 fatty acids (EPA and DHA) are powerful anti-inflammatory agents, which will take care of the inflammatory component of depression. Both fish oil and krill oil in combination give the optimal response as outlined here.

Vitamin D3 and light box therapy

  1. Vitamin D3 is also anti-inflammatory and will contribute to an improvement with existing depression, but it also helps prevent the development of depression when taken in regularly as a supplement.
  2. Light box therapy: The observation of seasonal affective disorder (SADS) can develop as a result of lack of light. This has led to the discovery that light boxes are helpful for treating depression and also for prevention of depression due to seasonal affective disorder.

The patients should use a light box for 30 minutes every morning during the fall and winter months. The box should emit at least 10,000 lux. Improvement can occur within 2 to 4 days of starting light therapy, but often it takes up to 4 weeks to reach its full benefit.

Avoid alcohol and too much sugar

  1. It is known for a long time that alcohol is a depressant; it can actually cause depression and in persons with bipolar disease it can trigger a flare-up of that disorder as well.
  2. Finally it matters what you eat: sugar and too much starchy foods (high glycemic index carbs) lead to insulin overproduction and insulin resistance. This causes inflammation, and this will cause depression. As mentioned earlier it also lowers the two key brain transmitters, dopamine and serotonin.

The solution is an anti-inflammatory diet, the Mediterranean diet without sugar and high glycemic index carbs; only low glycemic index carbs are part of this diet. This will normalize insulin production and eliminates inflammation.

B vitamins, electroacupuncture and exercise

  1. Vitamin supplements: Folate and vitamin B12: Up to 1/3 of depressed people have folate deficiency. Supplementation with 400 mcg to 1 mg of folic acid often helps. Vitamin B12 should also be taken to not mask a B12 deficiency (Ref.5). Folate and vitamin B12 are methyl donors for several brain neuropeptides.
  2. The symptoms of depression often improve with electro acupuncture, as shown in many studies. This treatment ameliorates the symptoms of depression and seems to work through the release of neurotransmitters in the brain (Ref.6).
  3. Exercise on a regular basis helps to equalize the mood and seems to exert a slight anti-depressant effect on the person who engages in regular physical activity.
Depression Needs Treatment

Depression Needs Treatment

Conclusion

I have attempted to show the complexity of depression and what we know about its causes and treatment. Very likely there are several causes for depression and further research will hopefully bring more clarity to this. Over the years psychiatrists have developed treatment modalities, both conventional and unconventional, by trial and error. The physician and patient need to use common sense: if a treatment is working, stick to it and use it. If it does not work, move on and try something else. More complex cases should be referred to a psychiatrist who has the most experience with patients that are difficult to treat. Do not neglect life-style factors and alternative depression treatments as they can often help to stabilize depression significantly. We all must be vigilant about suicide risks in depressed patients and act by calling 911, if necessary to intervene.

More info on depression: http://nethealthbook.com/mental-illness-mental-disorders/mood-disorders/depression/

References

1. Depression, Major: Fred F. Ferri M.D., F.A.C.P., Ferri’s Clinical Advisor 2016, by Elsevier, Inc.

2. Dr. Datis Kharrazian: “Why Isn’t My Brain Working?” © 2013, Elephant Press, Carlsbad, CA 92011

3. Goldman-Cecil Medicine “Major depressive disorder” 2016, by Saunders, an imprint of Elsevier Inc.

4. Massachusetts General Hospital Comprehensive Clinical Psychiatry, Second Edition: Theodore A. Stern MD, Maurizio Fava MD, Timothy E. Wilens MD and Jerrold F. Rosenbaum MD © 2016, Elsevier Inc.

5. Rakel: Integrative Medicine, 3rd ed. © 2012 Saunders.

6. George A. Ulett, M.D., Ph.D. and SongPing Han, B.M., Ph.D.: “The Biology of Acupuncture”, copyright 2002, Warren H. Green Inc., Saint Louis, Missouri, 63132 USA

Jan
22
2015

Life Expectancy Is Influenced By Lifestyle

The previous three blogs have dealt with telomeres, stem cells and lifestyle as a theme. In this blog you find summaries from three talks at the 22nd Annual World Congress on Anti-Aging Medicine In Las Vegas (Dec. 10-14, 2014) that dealt with telomere length and how nutrition can positively influence what our genes express, which ultimately determines how long we live. This is at the center of anti-aging medicine and this is why I dealt with it in some detail.

1) Dr. Theodore Piliszek: “Personalized Genetics: Applying Genomics to General Health, Nutrition, and Lifestyle Modification”

The individual’s metabolism is different from one person to the next. As a result of this, one needs to match the diet one recommends for a patient to that person’s genetic make-up.

The Mediterranean diet has 20% protein, 35% fat, 45% carbs; here is the composition of other diets:

Low carb diet: 30% protein, 30% fat, 40% carbs

Low fat diet: 20-25% protein, 20-25% fat, 50-55% carbs

Balanced diet: 20% protein, 25% fat, 55% carbs

Snack only on low caloric foods; otherwise leptins react and make you hungry. A sweet tooth predisposes you to develop diabetes. Lactose intolerance is more common than previously thought. 30% of type II diabetics presently will develop dementia and Alzheimer’s is now often referred to as type III diabetes. With sugar being present in so many processed foods, this figure will likely jump to 60% in the future!

Methylation is very important for your well being. Here is a quick link to explain methylation in simple terms without getting too much into biochemical nomenclature. Having said this, vitamin B2, B6, B12 are needed for this biochemical process, SAMe is also a supplement that supports methylation.

If you do not have a longevity gene, you need to watch that you stick to organic food, stay active, may be add methylated folate and vitamin B12. Each patient should get a supplement list that is customized.

The health practitioner should ask the patient to keep a food diary for 1 week, which gives the doctor the nutritional profile including what the patient consumes in the way of drinks. Check vitamin D3 blood levels! Adequate levels of vitamin D3 are necessary for the musculoskeletal system and the immune system. Endurance training is important up to age 45. Beyond that age emphasis should be on isometric exercises (weight lifting).

Dr. Piliszek stated that the life expectancy in the US is falling behind many other countries. I did a quick Google check regarding life expectancy around the world as follows: US: 78.7 years; Canada: 81.2 years; France: 82.7, Italy: 82.9; Spain: 82.3; Portugal 80.37; Sweden: 81.7; Denmark: 80.05; Norway: 81.45; Germany: 80.89; Poland 76.8; Russia: 70.56. Seeing that the conference took place in the US, there is a lot of room for the US to improve habits with regard to food intake.

Dr. Piliszek stated that the normal range for hemoglobin A1C is skewed in the medical literature and the recommendations are too high; it should be: 3.8 to 4.9 %. This is very important to know for diabetics and any caregiver who looks after diabetes patients, because if you are satisfied with a hemoglobin A1C of 6.0 as still being “normal”, the diabetic patient dies prematurely of a heart attack or a stroke. Contrary to the National Diabetes Information Clearinghouse (NDIC) recommendation it is important to take note: the new normal range for hemoglobin A1C is 3.8 to 4.9%! A patient whose hemoglobin A1C is 5.5 has diabetes and needs to be treated aggressively to prevent complications associated with diabetes.

2) George Rozakis, MD: “Nutrigenomics”

This talk focused on how one could use nutrition to heal when genetic errors are present in the metabolism. This field is called “nutrigenomics”. It deals with using diet modifications and nutrients to change gene expression. Another way to express this is that with proper epigenetic changes by using the right nutrients for a person with an inherited weakness, using the right nutrients for a person with an inherited weakness can extend life. At the same time you need to avoid nutrients that would harm a person with a certain genetic weakness.

We all have inherited some minor or not so minor genetic errors in the genetic code. We are made up of 50 trillion cells with 30,000 genes and 23 pairs of chromosomes, so there are bound to be a few minor genetic code errors that make us more or less susceptible to develop disease, particularly when our telomeres are shortening with age making self-repair of many of our aging cells difficult, if not impossible.

Genes program our cells to run biochemical reactions within the cells. Correct methylation pathways are important for normal cell function. However, if there is a methylation defect, abnormalities set in and homocysteine accumulates.

With various enzyme defects you need to use appropriate supplements to normalize the metabolic defect. Vitamin B2, B6 and B12 supplementation will often stabilize methylation defects and homocysteine levels return to normal. This is important as severe, familial cardiovascular disease can be postponed this way by several years or more.

In a similar vein Dr. Rozakis mentioned that 92% of migraine sufferers have a defective methylation pathway involving histamine overproduction and they can be helped with a histamine-restricted diet.

Autism, ADHD (hyperactivity) and learning disabilities are other diseases where methylation pathway defects are present. Every patient with autism should be checked for methylation pathway defects, and appropriate supplements and diet restrictions can help in normalizing the child’s metabolic defects. DAN physicians (“defeat autism now”) are well versed in this and should be consulted.

S-adenosylmethionine (SAMe) defects are another type of methylation defect, which is important in certain liver, colon and gastric cancers.

Dr. Rozakis went on to say that methylation defects lead to disbalances between T and B cells of the immune system and are important in autoimmune diseases like lupus or rheumatoid arthritis.

Methylation defects can also cause autoimmune thyroiditis and type 1 diabetes. They can also cause cardiac disease by raising homocysteine levels, which causes dysfunction of the lining of arteries and premature heart attacks.

Epigenetic factors through global methylation defects from vitamin B2, B6 and B12 deficiency cause many different cancers. Hypomethylation is the most common DNA defect of cancer cells.

Mental illness is another area where epigenetic factors play an important role. Depression that responds only partially or not at all to SSRI’s (antidepressants) often responds to L-methylfolate, a simple supplement from the health food store as a supplement. Similar epigenetic approaches can be used to treat psychosis, schizophrenia, bipolar disorder and Alzheimer’s disease.

With skin diseases it has come to light that atopic dermatitis, eczema, psoriasis, scleroderma and vitiligo are related to methylation.

When we age, certain hormones are gradually missing, which leads to menopause and andropause. This leads to impaired cell function, elevated cholesterol, arthritis, constipation, depression, low sex drive, elevated blood pressure, insomnia, irritable bowel syndrome and fatigue. Replace the missing hormones with bioidentical ones and symptoms normalize.

Life Expectancy Is Influenced By Lifestyle

Life Expectancy Is Influenced By Lifestyle

3) Dr. Al Sears: “Telo-Nutritioneering: The latest generation of telomere modulators”.

Shortened telomeres are causing cells to behave like old cells. In the lab we can lengthen telomeres. Telomerase activated animals regrew their brains!! In the human situation the goal is to find ways to preserve the length of our telomeres in all our key organs. Alternatively this can also be reached by inhibiting the breakdown of the enzyme telomerase, which will lead to a lengthening of telomeres. In his research Dr. Sears found at least 123 nutrients, vitamins and natural compounds that will elongate telomeres, often by stimulating telomerase.

Testing for critically short telomeres (HT Q-FISH method) is clinically more important than using average telomere length tests. Dr. Sears said when a patient has been shown to have short telomeres and this patient is started on telomerase stimulating supplements, telomere lengthening can be documented within one month of starting the supplementation. Acetyl-L-carnitine and resveratrol are two substances that reliably elongate telomeres.

Vitamin C will significantly delay shortening of telomeres, which translates into delayed aging. In addition vitamin C has recently been shown to stimulate telomerase activity in certain stem cells. There is an herb, called Silymarin extract, which was found to increase telomerase activity threefold. N-acetyl cysteine is a building block for glutathione, a powerful ant-oxidant. In addition it has been shown to turn on the human telomerase gene. Other telomerase stimulators are green tea extract, ginkgo biloba, gamma tocotrienol (one of the components of the vitamin E group), vitamin D3 and folic acid.

Dr. Sears suggested that we should take the following supplements and vitamins for “telo-nutritioneering” (alphabetically arranged) with recommended dosages:

Acetyl L-carnitine: 1,000 mg daily; alpha tocopherol: 400 IU daily; folic acid: 2 mg to 5 mg daily; gamma tocotrienol: 20 mg minimum daily; ginkgo biloba: 40 mg to 80 mg daily (cycle every 4 to 6 weeks); green tea (EGCG): 50 mg daily; L-arginine: 500 mg to 1,000 mg daily; N-acetyl cysteine: 1,800 mg to 2,400 mg daily; resveratrol: 10 mg to 20 mg daily; silymarin: 200mg twice daily; vitamin C: 540 mg minimum daily; and vitamin D3: 2,000 IU daily.

Even if you are only taking 5 or 6 of these twelve telomerase boosters daily, you are doing well, particularly if you are also watching your lifestyle (regular exercise, not smoking, cutting out excessive alcohol intake and avoiding sugar).

Conclusion

This is only the beginning of rethinking epigenetic treatment approaches. For too long organized medicine has used a “cookie-cutter” approach of diagnosing and treating diseases. Now we are realizing that changes in hormones and shortening of telomeres with aging can cause inflammation and premature deaths. The future of medicine, which has already started, uses nutritional changes, vitamins and supplements, bioidentical hormone replacements and exercise to stabilize cell metabolism and postpone age-related diseases.