Mar
10
2018

Dementia From Excessive Alcohol Abuse

A new study from France documented dementia from excessive alcohol abuse. One million patients who needed admission to hospitals in France for early dementia took part in that study. This was based on this publication. Dementia is a clinical syndrome, where the cognitive ability deteriorates progressively.

The study from France regarding dementia from excessive alcohol abuse

According to the French National Hospital Discharge database it was especially relevant that alcohol use disorders were present in 16.5% of the men and 4% of the women with dementia. Those who did not have the diagnosis of dementia had only half the amount of alcohol abuse disorders in both sexes.

There are other diseases that can lead to dementia like Parkinson’s disease and Huntington’s disease. These cases were not part of this study.

The association with alcohol abuse was particularly evident in early dementia cases at an age below 65.

Furthermore, alcoholics also have a shorter life expectancy.

Several mechanisms responsible for dementia development

Alcohol can cause dementia in several ways.

  • First of all, alcohol and the metabolic by-product acetaldehyde have toxic effects on the brain. They cause long-term toxic effects and functional brain damage is the result.
  • Furthermore, heavy alcohol abuse leads to liver damage with resulting changes in metabolism. Ammonia production from the cirrhotic liver causes brain damage in a condition called hepatic encephalopathy.
  • In addition, heavy drinking is a strong vascular risk factor. This leads to diabetes, high blood pressure, heart attacks and strokes.
  • Often it is the population group that is uneducated, people who smoke and people with depression who suffer from the effects of alcohol abuse.
  • Finally, heavy drinking is more frequent in men than in women. In men the dementia risk was 4.7-fold, in women 4.3-fold.
  • Obesity, smoking and high blood pressure are also risk factors for dementia. If these cases were not part of the study, heavy alcohol abuse caused an increase in dementia in both sexes by a factor of 3-fold.

Possible biases of the study

Dr. Kostas Lyketsos, a neuropsychiatry professor and director of the John Hopkins Memory and Alzheimer’s Treatment Center did not take part in the study and its investigation. A non- biased observer, Dr. Kostas Lyketsos stated that there is a problem with precision of the data the larger the study population is. In this case there were more than 1 million participants, so a number of biases can influence the outcome of the study. For instance, one problem is that these patients with mild cognitive impairment were inpatients in a hospital. Normally such patients would not be in a hospital. Another fact was that none of the participants had received questionnaires of the amount of alcoholic drinks they consumed, and as a result it is difficult to knows exactly how high the amount of alcohol was that caused the damage to the brain.

Country bias

The large sample size was from only one country, France. This means that we do not know whether there would be ethnic differences between countries. Nevertheless the findings of this study are important. In a 2014 review by the WHO the average person in France consumed 12.2 liters of pure alcohol per year. In contrast the average person in the US consumed only 9.2 liters of pure alcohol in this year. Apart from these concerns it is important to realize that alcohol has toxic effects on the brain. This can also result in dementia.

Other studies regarding alcohol abuse and dementia

The media has praised alcohol for preventing heart attacks. On the other hand, there are other articles in which we hear about alcoholic hepatitis and liver cirrhosis, both of which can be killer diseases. To get some clarification, let us examine the various facts.

Dr. Finnel mentioned that 7.9% of all emergency room visits in the US are due conditions which have an association to alcohol(Ref.1). When the causes of deaths  that are a consequence to alcohol are listed, they are: cancer of the mouth and pharynx, alcohol abuse disorders, coronary heart disease causing heart attacks, cirrhosis of the liver, traffic accidents, poisonings, falls and intentional injuries. You don’t get that from the news. Instead you read about the one glass of red wine per day that is good for women and up to two glasses of red wine that is good for men to prevent heart attacks and strokes.

Bioflavonoids

It is the bioflavonoids and among those in particular resveratrol, that are the active ingredient responsible for heart health.

Resveratrol is a powerful antioxidant that protects against ischemia-reperfusion injuries.  It is responsible for the cardio protective properties of red wine known as the “French paradox” (Ref.2). According to this reference resveratrol contributes to at least 3 processes that stabilize the metabolism.

Toxicity of alcohol

According to the WHO 5.9% of all deaths worldwide is a consequence of alcohol overconsumption.  In 2012 the WHO recorded that 7.6% of deaths in males, but only 4% of female deaths were due to alcohol. Toxicity comes from the breakdown product acetaldehyde, which all cells can convert from alcohol. Liver cells are especially able to do that. According to Ref. 3 alcohol diffuses easily through all of the cell membranes and reaches every organ in the body. The toxicity of acetaldehyde is shutting down the mitochondria, which affects the energy metabolism and causes cell death. The immune system reacts with inflammation, when it attempts to repair the damage.

So, what are the major damages which alcohol can cause? First there is fat accumulation (steatosis), next chronic inflammation followed by necrosis (dying of cells) and finally fibrosis. An example of fibrosis is liver cirrhosis, where non-functioning connective tissue replaces liver cells.

Different tissue sensitivity to alcohol

Certain tissues are more susceptible to alcohol toxicity than others. As the concentration of alcohol is highest in tissues that are in direct contact with alcoholic drinks, cancers related to alcohol consumption develop in the oral cavity, pharynx, larynx, esophagus, and in the colon and rectum. The pancreas is particularly vulnerable to inflammation and fibrotic changes with degeneration into cancer of the pancreas. The heart tissue and the arteries are very sensitive to alcohol.  Hypertension, heart attacks, stroke, cardiomyopathy and myocarditis as well as irregular heart beats (arrhythmias) can develop. The brain is very sensitive to toxic effects of alcohol as well. This causes major depression, personality changes with violent behavior, car accidents and injuries.

Other toxic effects of alcohol on organs

Kidney disease (alcoholic nephropathy) is another illness due to too much alcohol. Five percent  of breast cancers in northern Europe and North America are a direct consequence to the toxic effects of alcohol (Ref.3). Finally, the liver being so active in detoxifying alcohol, will be not functioning and finally develops liver cirrhosis, as described before. This accounts for a lot of premature deaths at a relatively young age (typically in the mid to late 50’s).

Ref. 3 goes on to say that literature exists which claims that 1 to 2 drinks per day would be useful for prevention of heart disease. But the observation of the authors is that people will not discipline themselves to stick to these limits and very quickly enter into the zone of alcohol toxicity. The authors further noted that with regard to causing any kind of cancer there is no safe lower limit; the risk is directly proportional to the amount of alcohol consumed and the risk starts right above the zero point.

The pathologist has the last word

When I studied medicine at the University of Tübingen, Germany I attended lectures in the pathology department where Professor A. Bohle, M.D. demonstrated pathology findings of deceased patients. Dr. Bohle had a special interest in Mallory bodies. These are alcohol inclusion cysts within liver cells that can be stained with a bright red dye.

Histological documentation of toxic effects in livers of corpses

I will never forget when Prof. Bohle pointed out that the livers of this most diverse population, whose bodies we had the privilege as medical students to study, had a rate of 25% positive Mallory bodies. He wanted to impress on us as medical students to watch out for the alcoholics that are usually missed in general practice. Obviously 25% of the pathology population was affected by the consumption of alcohol. It was Prof. Bohle’s hope that we could perhaps interfere on the primary care level before things went out of control. Many of these corpses were the sad results of traffic accidents that could have been prevented. (In 2018 things have changed: seat belts and alcohol limits are standard, in 1968 in Germany they were not).

Alcohol as an aging substance

Consistent use of alcohol on a regular basis will slow down cell metabolism and hormone production significantly. The major effect of alcohol leads to poisoning of the mitochondria in multiple organs, which translates into faster aging and a shortened life expectancy. This in turn results in a change of appearance. An older person who has abused alcohol for a number of years may look 5 to 10 years older than their chronological age.

50% of people above the age of 65 drink daily (Ref.4). Some more statistics: alcohol abuse in elderly men is 4-times higher than in elderly women. 5% to 10% of all dementia cases are related to alcohol abuse. About 15% of older adults are experiencing health risks from abusing alcohol. And about 90% of older adults are using medications. Close to 100% of medications can adversely interact with alcohol (Ref.4).

Social pressure

These are the scientific facts, and then there is social pressure, when you are invited to a party.

When you are young and believe that you are invincible, do you care what the science says? You want to have a “good time” and not worry about consequences. The data about long-term exposure and a slowly increasing cancer risk is there. The wine industry will remind you that 1 drink for women and two drinks for men will protect you from heart attacks. They will withhold the cancer information from you, as they don’t really want to hear about that (yes, it’s bad for their business!).

Resisting social pressure and doing what is good for you

Can you have a good time at a party without drinking alcohol? Yes, you can. You can talk and you can listen; you are probably more with it than those who had too much to drink. I like mineral water and hold on to a glass of that.

I explained in a blog before how I was convinced by three speakers at an A4M conference to join those who abstain from alcohol.

Socializing without alcohol is doable. You may at times miss it, but you can warm up even to a crowd that had a few drinks too much. It is about choice: we can choose what we want out of life.

 

Dementia From Excessive Alcohol Abuse

Dementia From Excessive Alcohol Abuse

Conclusion

Alcohol is a cell and nerve poison. The medical need for “one glass of wine for women and two glasses of wine for men to prevent heart attacks and strokes” has been vastly exaggerated. Fact is that resveratrol and other antioxidants like vitamin C and vitamin E can also prevent cardiovascular disease. They are alcohol-free! The risk of dementia development as a long-term result of alcohol exposure is something that is only now getting attention by the medical profession. We live longer these days, and this makes alcohol exposure over the decades a real threat to our mental wellbeing. Consumption of alcohol needs to be re-evaluated by every one of us. What risks are we willing to take? Is the stress-relieving effect of alcohol worth the risk of losing our mind to Alzheimer’s disease? If we care about our future the answer should be clear!

References

Ref. 1: John T. Finnell: “: Alcohol-Related Disease“ Rosen’s Emergency Medicine, Chapter 185, 2378-2394. Saunders 2014.

Ref. 2: “Hurst’s The Heart”, 13th edition, The McGraw-Hill Companies, Inc., 2011. Chapter 54. Coronary Blood Flow and Myocardial Ischemia.

Ref. 3: Ivan Rusyn and Ramon Bataller: “Alcohol and toxicity”, 2013-08-01Z, Volume 59, Issue 2, Pages 387-388; copyright 2013 European Association for the Study of the Liver.

Ref. 4: Tom J. Wachtel and Marsha D. Fretwell: Practical Guide to the Care of the Geriatric Patient, Third Edition, Copyright 2007 by Mosby.

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Feb
24
2018

What Causes Premature Aging?

Some people look 10 years older than their stated age, and we often wonder: what causes premature aging? Accelerated or premature aging can have a multitude of underlying causes. I will list a few here:

1. Weakening hormones

Men go through andropause at around the age of 60 to 65 and women go through menopause around the age of 55 to 65. In both males and females it is the sex hormones that are missing around that age. If hormones replacement follows fairly quickly with bioidentical hormones, this will not affect the visual appearance that much. In contrast, if bioidentical hormones are not the therapeutic choice for  hormone replacement, but synthetic ones, the hormones are not in balance, as synthetic hormones do not restore the hormonal balance. Nothing is gained, as the person will still age prematurely.

Synthetic versus bioidentical hormone replacement

In addition the synthetic hormones will cause heart attacks, strokes, clots, and cancer. Prescriptions for synthetic hormones are often the cause that the aging patient population gets these serious complications. Frequently physicians insist on using synthetic hormones from a “reputable” drug company to replace missing hormones. The reason this does not work is that a male has testosterone receptors. They need to be stimulated by bioidentical testosterone to restore all of his missing functions. Also, the same is true in menopausal females who need stimulation of their estrogen receptors and progesterone receptors. Consequently, only bioidentical hormones will return a postmenopausal woman back to normal. There is a perfect fit between the bioidentical replacement hormones and her hormone receptors. Using synthetic hormones is like trying to unlock a door with a key that does not have a perfect fit: you damage the lock!

2. Missing human growth hormone (HGH) and thyroid hormones

These hormones have a special place in aging.

Human growth hormone deficiency

First, HGH production is running out in many people at age 60. A person with HGH deficiency will have lower muscle mass and strength. Other symptoms are dry and thin skin, particularly at the back of the hands. Men are balding, and they loose interest in sex. There are difficulties concentrating and they may have “senior moments”, which are memory lapses. Often they are prone to depression and anxiety. A blood test will frequently show elevated triglycerides. A blood test (IGF-1) and a urine test exist which make it possible to look for HGH metabolites to assess whether a 40, 50 or 60 year-old person is producing enough HGH. Many may need replacement of HGH. This is administered by injection through a tiny needle into the skin, similar to a diabetic injecting insulin. This will bring back what was missing due to HGH deficiency.

Thyroid hormone deficiency

Thyroid hormones (T3 and T4) are other important factors that could make you look older prematurely. Your hair is getting thinner; your skin turns dry and pale. The nails may be getting brittle. When the outside half of the eyebrows is very thin or missing, this can be a sign of hypothyroidism. In a similar vein the skin in the face may be puffed up due to swelling of the layers under the skin (myxedema). It is important to diagnose hypothyroidism, which is common in the aging population. The physician needs to order a blood tests (TSH, T3 and T4). If TSH is above the upper limit, your physician needs to replace both T3 and T4 by tablets (I prefer Armour as the T3 and T4 is balanced).

3. Smoking

The lining of the airways absorb cigarette smoke. The chemicals circulate around in the blood and lead to aging of the skin. Chronic cigarette smoke exposure also melts away the subcutaneous tissue. The end result is a haggard look. The natural glow disappears from the skin and because of carbon monoxide binding to hemoglobin the skin color looks more greyish. In addition the blood vessels are narrowing or clogging. This means that the body cannot absorb nutrients as well, and cells are starving. There is only one remedy for this: quit smoking!

4. Overexposure to ultraviolet light

The radiation of UV light can penetrate deep into and under the skin. This makes the subcutaneous fat melt away. The largest UV exposure is in the facial area. As a result we see aging there. The end result is a sagging appearance of the face. This link has an image of a woman before and after a non-surgical facelift with stem cells and fatty tissue: Stem Cell Treatments That Are Currently Available – Medical Articles by Dr. Ray

In a surgical procedure the physician harvests mesenchymal stem cells from fatty tissue by liposuction. A cell separator separates the mesenchymal stem cells, the connective tissue and the fat cells. The connective tissue is discarded. Mesenchymal stem cells and fat cells are mixed and injected into the thinned subcutaneous fatty tissue until the person’s younger facial contour is back to normal. Typically this will last for 10 years or more.

5. Drugs and alcohol abuse

Both can lead to malnutrition with weight loss and loss of subcutaneous fatty tissue, which causes sagging breasts in women. In men “beer tits” are common. The reason for this is estrogen accumulation, as alcohol interferes with the elimination of estrogen in the liver. Alcohol is a general cell poison. It causes all of the cells to age prematurely. The more alcohol you drink, the faster you age. The skin develops wrinkles, loss of elasticity and collagen, redness and puffiness. In other words chronic alcohol abuse ages you prematurely. The only remedy for this is to quit drinking. Some of your skin vitality may come back. Our body has an amazing capability to heal itself!

6. Medical illnesses

Many medical illnesses like diabetes, mental illness (depression and schizophrenia), multiple sclerosis, inflammatory bowel disease; cancer and others make you look a lot older very fast.

I will briefly explain the reasons for this.

  • Diabetes

With diabetes type 2 the pancreas releases too much insulin after a meal with starches and sugar; think about a sweet muffin or a toast with jam. The extra insulin causes inflammation. This stimulates enzymes that break down elastin and collagen, leading to wrinkles and sagging skin.

  • Mental illness like depression and schizophrenia

We know from studies that depression leads to shortening of telomeres. This in turn causes cell death in the most rapidly dividing cells like in the skin and hair follicles. The end result is prematurely aged hair and skin. Schizophrenia also leads to premature shortening of the telomeres, which causes premature aging, mitochondrial dysfunction, inflammation and oxidative stress. The end result is that the person looks older than what their chronological age is.

  • Multiple sclerosis

It is sometimes difficult to discern in patients with MS what is normal aging and what is aging from the disease. This link gives some background on this. Many MS patients are anxious, and anxiety and stress by itself also leads to premature aging.

  • Inflammatory bowel disease

The chronic inflammation of either ulcerative colitis or Crohn’s disease can lead to premature aging. High doses of vitamin D3 and molecularly distilled fish oil can be useful to help treat the inflammation. Probiotics are also important to restore the bowel flora.

  • Cancer

Cancer leads to cachexia (excessive weight loss). There is also excessive inflammation, which leads to accelerated aging. The inflammation causes increased oxidative stress. This leads to tissue damage and DNA damage, which makes all cells more vulnerable to develop other cancers. Oxidative stress can substantially accelerate telomere shortening. As a result skin can become saggy, wrinkles develop and the person looks prematurely aged.

7. A chronic lack of physical activity

People who never exercise tend to get overweight and eventually obese. This leads to premature aging. Exercise would elongate telomeres, but inactivity shortens them. Obesity leads to increased oxidative stress and to DNA damage. Obesity also shortens telomeres. All of this leads to premature aging.

What Causes Premature Aging?

What Causes Premature Aging?

Conclusion

These are only a few examples of causes of accelerated aging. The key is to stick to a healthy, balanced diet (like the Mediterranean diet) and exercise regularly. Stop smoking (if you do), don’t take street drugs, and make sure you get enough sleep. Getting enough sleep helps your hormones regenerate overnight. The sympathetic overdrive from your daily activities is counterbalanced by the parasympathetic activities during sleep that causes relaxation. For hormone replacement you may have to see an anti-aging physician, a naturopath or integrative medicine physician. This may be your only chance to address any hormonal deficiencies. Conventional medicine does a very poor job of HRT (hormone replacement therapy) with synthetic hormones. Conventional practitioners want to treat you with synthetic hormones that will make you sick. Hormones for replacement have to be bioidentical! This way you will live 10 to 15 years longer, look younger and stay healthy.

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Jan
27
2018

Bacterial Toxins Threatening The Brain

Dr. Robert G. Silverman gave a talk about bacterial toxins threatening the brain. He spoke at the 25th Annual World Congress on Anti-Aging Medicine in Las Vegas on Dec. 15, 2017. First of all, he pointed out how changes in the gut flora can affect the integrity of the gut wall. In addition this can eventually this lead to a leaky gut syndrome. But it does not end here. As a result the toxins enter the blood stream and affect the blood/brain barrier. Consequently in the end various neurological diseases can develop from this.

Here I am giving a brief overview of the talk by Dr. Silverman. But he was not the only one speaking to this subject. Several other speakers also brought up this subject throughout the conference. They stressed the importance of rectifying any gut dysbiosis to stop leaky gut syndrome and a leaking blood/brain barrier.

Leaky gut syndrome

When the gut flora changes there are often enteropathogenic E. coli strains, Shigella and Salmonella that invade the lining of the gut causing leaky gut syndrome. When toxins enter the blood stream, the body is starting to form antibodies against various proteins. Antibodies are acting against various targets: bacterial cytotoxins, cytoskeletal proteins, tight junction proteins and food antigens. Lipopolysaccharides (LPS) from toxins of gram-negative gut bacteria can also leak into the blood. This affects key organs like the liver, the heart, lungs, the joints, the immune system and the thyroid. When this process has gone on for some time, the blood/brain barrier is breaking down next. The intestinal inflammation causes the release of inflammatory cytokines that circulate in the blood stream. The cytokines cross the blood/brain barrier and activate the support cells in the brain, called microglia. This in turn causes inflammatory degenerative changes in the brain.

Blood/brain barrier

LPS circulating in the blood from gut bacteria endotoxins increase the permeability of the blood/brain barrier. This is bad news for the brain as it becomes vulnerable to attacks from the antibodies mentioned and from food particles. Dr. Silverman cited papers showing that circulating antibodies that cause inflammation in the brain can be the starting point for early Parkinson’s disease. Autoimmune antibodies can cause even depression.

Intestinal permeability can be assessed by various antibody constellations. For instance IgA antibodies point to an ongoing issue/early leaky gut syndrome. IgM antibodies indicate early onset and IgG antibodies chronic issues of leaky gut syndrome. If you add various antigens like LPS, zonulin and actomyosin you can pinpoint which structure of the gut wall is affected by leaky gut syndrome, and the antibody type adds more information about the timing of the onset of leaky gut syndrome.

Bacterial toxins threatening the brain when BBB damaged

As I already mentioned the blood/brain barrier (BBB) is often simultaneously affected when there has been leaky gut syndrome. There may be a delay, but eventually the BBB breaks down also, and the brain will be in jeopardy. Dr. Silverman gave an example of how depression can develop as result of a breakdown of the BBB. Chronic intestinal inflammation can suppress the sensitive hippocampus cells from regenerating. Physicians call that impairment of hippocampal neurogenesis. Inflammatory cytokines damage the neuronal cell progenitors. As a result patients with inflammatory bowel disease can have mood disorders and cognitive impairment. Sophisticated BBB blood tests can pinpoint whether the BBB is intact or establish whether there is impairment. The important thing to remember: there is a gut brain connection.

Fixing the gut to stop bacterial toxins threatening the brain

In order to fix the BBB, you must first concentrate on fixing leaky gut syndrome.

  • Avoid gluten, as gluten is causing inflammation of the gut wall.
  • Start taking probiotics that contain more than 30 Billion lactobacillus plantarum, lactobacillus acidophilus and Bifidobacterium lactis per daily dose.
  • Do a heavy metal detox involving phytonutrients, hops, turmeric, Andrographis, zinc, polyphenols, omega-3 fatty acids, and watercress plant extract. Andrographis, also known as the “King of Bitters”, is an Ayurvedic medicine used to promote digestion and stimulate appetite.

Nutrients to fix the blood/brain barrier

Dr. Silverman uses the following nutrients to repair the blood brain barrier.

  • Acetyl L-Carnitine: this helps to protect the mitochondria from oxidative damage
  • Berberine: reduces inflammation in brain injuries
  • Alpha-lipoic acid: preserves the integrity of the BBB by controlling oxidative stress
  • Curcumin: decreases brain swelling, preserves the BBB and increases tight junction protein in brain cells
  • Vitamin D3 (5000 IU or more): protects the BBB by various mechanisms
  • Omega-3 fatty acids: they increase cell membrane fluidity and protect the BBB
  • Resveratrol: reduces inflammation and restores the BBB

Neuroplasticity

In order for the brain to adapt to changes, it must be flexible, which means on a cellular level that nerve cells form new synapses, neurological pathways etc. This is what neuroplasticity means. Here are the factors that Dr. Silverman listed as facilitating neuroplasticity.

  • Regular exercise
  • DHA from fish oil capsule supplements
  • Turmeric
  • Whole coffee extract
  • Alpha-lipoic acid
  • Lactobacillus brevis and Bifidobacterium longum
  • Bifidobacterium animalis Lactis 420 (B420)
  • Probiotics: they feed the healthy gut bacteria (e.g. apple cider vinegar)
  • Elevate magnesium in the brain through L-threonate
Bacterial Toxins Threatening The Brain

Bacterial Toxins Threatening The Brain

Conclusion

In the last few years it has become abundantly clear that leaky gut syndrome is not an isolated matter. It is invariably connected to a breakdown of the blood/brain barrier (BBB). Leaky gut syndrome alone is bad enough as it can lead to a number of autoimmune diseases, like Hashimoto thyroiditis and others. But when the BBB is affected, antibodies can now affect nerve cells, can cause Parkinson’s disease, depression, and even Alzheimer’s disease. There is no reliable database for what can happen to the brain when the BBB breaks down.

Because of these connections it is important to sanitize the gut, re-establish a healthy gut flora and overcome leaky gut syndrome. This will at the same time repair the broken down BBB. It will also prevent further possible damage to the brain in the future. Your gut health is your brain health. Take care of both your gut as well as your brain!

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Jan
06
2018

Lyme Disease The Great Imitator

Dr. Pamela Smith talked about Lyme disease the great imitator when she gave a presentation. This was at the 25th Congress of the American Academy of Anti-Aging Medicine, Dec. 14-17, 2017, which I attended. Dr. Smith gave a talk about how to approach a complex patient when multiple systems are affected. Part of that talk dealt with Lyme disease, which I will review below in some detail.

Transmission of Lyme disease

Lyme disease is one of the fastest growing infectious diseases in the US. As a result about 200,000 new cases of Lyme disease occur in the US every year.

The transmission occurs through ticks that that carry a spirochete, called Borrelia burgdorferi.

This bacterium, much as syphilis, which also is caused by a spirochete, produces imitator disease patterns. Clinically it can be a challenge to diagnose Lyme disease.

The common way of transmission to humans is by infected ticks that bite the skin. But Dr. Smith said that transmission of the spirochete can also occur by breastfeeding, blood transfusions, in vitro fertilization and finally by sex. Although originally Lyme disease infected ticks were found on deer, other species can also be carriers. Ticks from mice, foxes, raccoons, songbirds, chipmunks, and squirrels can also transmit Lyme disease.

Clinical presentation of Lyme disease

Only 30 – 40% of adults with Lyme disease have the characteristic rash of the “bull’s-eye lesion” (erythema migrans). With children this presentation is even less common (only 10% have erythema migrans). If there is a bull’s-eye lesion, this will last from one week to several months. A laboratory test using an enzyme-linked immunosorbent assay (ELISA test) can confirm the diagnosis of the disease.

Disseminated early or late Lyme disease

Fatigue, headaches and weakness can be non-specific symptoms of Lyme disease. Furthermore, other non-specific symptoms like back pain, muscle and joint pains as well as chills can detract the physician from diagnosing Lyme disease. In addition irregular heartbeats, nausea, vomiting, swollen lymph glands, memory loss, gait problems, bladder and kidney problems are other symptoms. Finally, liver problems, sore throat, fever, seizures, depression, dementia, hallucinations, mood swings and arthritis can be other symptoms.Even eating disorders, verbal aggression, schizophrenia and suicide can be symptoms of Lyme disease.

Common symptoms that have a link to Lyme disease

Common symptoms of Lyme disease include headaches, fatigue, joint pain and swelling of joints, stiffness of the neck or back. There can be difficulties with concentration, speech or writing. Further symptoms are sleep disturbances, numbness or tingling of arms or feet and forgetfulness. 

Lyme disease development

Borrelia burgdorferi can be found inside body cells and outside of cells as biofilms. This form makes them resistant as it allows Borrelia burgdorferi to exchange DNA and makes them resistant to antibiotics. There are also two major forms of Borrelia burgdorferi, namely cell-wall forms and cystic forms. Once the patient has been bitten by the infected tick Borrelia can quickly change shape into the more difficult to treat cystic form. Within 24 hours Lyme disease can spread to other parts of the body. Common such areas are the eyes, brain tissue and glial cells, heart, collagen, synovial fluid of joints and skeletal muscle fibers.

Lyme disease can also complicate many other diseases. These are ALS, Alzheimer’s disease, fibromyalgia, MS, bipolar disorder, neurological disease, heart disease (Lyme carditis) and autism.

Treatment of Lyme disease

  1. Dr. Smith said that Lyme disease is often complicated by dysfunctional gut flora. She prefers to start patients on a sugar-free and gluten-free diet. The patient also has to take probiotics.
  2. 75% of Lyme disease patients show a cure after three weeks of Doxycycline 100 mg twice per day. Alternatively cefuroxime 500 mg twice per day is a medication of choice.
  3. Cefuroxime only treats the cell‐wall forms. Doxycycline treats the intracellular forms. Metronidazole or tinidazole will help to eradicate the cystic forms of Lyme disease.
  4. Grapefruit seed extract is another treatment modality if the patient is allergic to Metronidazole. It eradicates the cystic form of Lyme disease.
  5. Serrapeptase from whole leaf stevia extract will also help to eradicate Borrelia biofilms and persisters.
  6. Monolaurin, a coconut oil extract is effective in treating all three morphological forms of Borrelia burgdorferi.

Patients with neurological symptoms

Patients with neck stiffness, headaches or neuropathy need treatment for a longer period of time. These patients also need monitoring for recurrent Lyme disease at the end of the treatment.

Case presentation of a patient with Lyme disease

Dr. Smith presented one of her patients with Lyme disease in detail. She was a 45-year old executive. She suffered from extreme fatigue. It took quite a few tests to find out that her antibody titers against Lyme disease were very high.

Here is her long list of symptoms: hair loss, four urinary tract infections in quick succession, brain fog, extreme fatigue, systemic pain, musculoskeletal pain, anxiety and depression, eczema, psoriasis, itching, stomach ache, trouble eating, weight loss of 12 pounds, flu, strep presented like meningitis.

Comprehensive treatment of patient with Lyme disease

Dr. Pamela Smith instituted a comprehensive treatment protocol. It turned out that she had developed gastritis, which was the reason for her weight loss. This needed conventional treatment. After the treatment with antibiotics, her energy picked up, and her appetite came back. She also engaged in yoga and other self-awareness programs. She deliberately slowed down her lifestyle activities. Her symptoms were mostly gone or significantly diminished. She was able to function. She experienced energy, joy, and could focus again. The only symptoms left were some mild pain, some bladder problems, some limitations with her diet and mild brain fog.

Husband had Lyme disease

Part of the work-up was to test her husband for Lyme disease. He tested positive. He was also treated although he was entirely asymptomatic. When his treatment was finished, the doctor tested him for a specific antibody and this came back as negative. This meant that he now was free of Borrelia burgdorferi and would no longer be able to infect her. The doctor thought that it was most likely through sex that she had contracted Lyme disease. The problem is that some people are completely asymptomatic, but nevertheless they can be carriers of Lyme disease.

Lyme Disease The Great Imitator

Lyme Disease The Great Imitator

Conclusion

Lyme disease, the great imitator, has become a more common disease in the US and around the world. Years back Lyme disease was often overlooked. But lately physicians have diagnosed Lyme disease earlier as diagnostic tests have improved. With earlier treatment a lot of suffering of the patient can be prevented. But in many cases symptoms are confusing as Lyme disease involves several organ systems. This makes the diagnosis more difficult. By diagnosing Lyme disease earlier, treatment can start at an earlier stage, and the patient will soon return to a state of wellness.

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Oct
14
2017

A New Genetic Marker For Alzheimer’s

“A new genetic marker for Alzheimer’s”; so reported a study dated August 11, 2017. Most of all, they found that a genetic marker, TOMM40 was stronger than the established genetic marker APOE4. It seems like the older studies overlooked the importance of the new TOMM40 genetic marker. This new marker may have been present at the same time as APOE4.

Details of study regarding a new genetic marker for Alzheimer’s

The APOE4 is especially relevant for the formation of lipoproteins. APOE4 showed a strong association with the formation of amyloid plaque. This is located in the brain areas where Alzheimer’s disease developed. Therefore the thinking in the past was that APOE4 would be the culprit behind memory loss and Alzheimer’s disease. In contrast, the new study shows evidence that the TOMM40 genetic marker is the gene that actually orchestrates the development of Alzheimer’s disease. Thalida Em Arpawong is a postdoctoral fellow at the University of Southern California (USC) Dornsife College. She conducted research about the TOMM40 marker. Her supervisor was senior investigator Carol A. Prescott, who is a professor of psychology at the USC Dornsife College. She co-published the paper.

More info about the study involving a new genetic marker for Alzheimer’s

Professor Prescott used two verbal memory test results. They were the United States Health and Retirement Survey (HRS) and the English Longitudinal Study of Ageing (ELSA). In these tests immediate recall was compared to delayed recall 5 minutes later. Alzheimer’s patients have problems with short term memory recall.  In total the study examined 20,650 HRS participants and 11,391 ELSA participants. Their age was 50 years and above since this is the typical age for the onset of Alzheimer’s disease. Genetic data was part of the examination in 7,486 HRS participants and 6,898 ELSA participants. The scientists looked at 1.2 million genetic variations of the human genome to fit the memory loss. In conclusion, only one gene area, TOMM40 showed a strong association with decline in immediate and delayed memory recall.

Hence professor Carol A. Prescott summarized the findings: “The results from this study…raise the question of how many findings in other studies show an association with APOE4 that may in fact be due to TOMM40 or a combination of TOMM40 and APOE4.”

Possible future clues from a trial using TOMM40 marker

A review paper points out the start of a new trial, called TOMMOROW. The review paper points out that the location of APOE and TOMM40 are on chromosome 19 in very close proximity. Pioglitazone is a drug that controls diabetes. Patients tolerate it well. It is used in the TOMMORROW trial. As this review paper states the TOMM40 gene is responsible for the outer mitochondrion membrane. Consequently the paper states: the “outer mitochondrial membrane channel through which peptides and proteins travel into mitochondria to support mitochondrial function and biogenesis” is the key for understanding Alzheimer’s disease. Because pioglitazone is a drug that induces mitochondrial doubling the researchers hope that it will help Alzheimer’s patients.  It will probably be interesting to follow the phase 3 trial TOMMORROW, where research will observe the delay in onset of minimal cognitive impairment.

A New Genetic Marker For Alzheimer’s

A New Genetic Marker For Alzheimer’s

Conclusion

Research has found a new genetic marker for Alzheimer’s, TOMM40 that identifies a higher risk of getting Alzheimer’s disease. Its location is close to the marker APOE on chromosome 19. It appears that TOMM40 may be more reliable in identifying patients at risk for Alzheimer’s disease than the older APOE marker. As a result research has started a new phase 3 trial, called TOMMORROW. This will tell whether or not Pioglitazone, a diabetic drug maybe useful in delaying Alzheimer’s disease in high-risk patients.

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Sep
09
2017

Young Heart Stem Cells Can Cure Old Hearts

Young heart stem cells can cure old hearts in rats. This is what research at the Cedars-Sinai Heart Institute in Los Angeles found. You may not be that impressed, because this talks about rats and not humans. But this is a brand-new concept, so of course research of animal experiments is first.

The heart experiment

Dr. Eduardo Marbán, MD, PhD, is the research director of the Cedars-Sinai Heart Institute. His idea was to take cardiac stem cells (called cardiosphere-derived cells) from hearts of newborn rats. He injected them into 22 months old rats. The human equivalent for 22 months old rats are older people with older hearts. Within one months of the stem cells’ injections the older rats had normal functioning hearts. Their telomeres were also normal. Telomeres are the caps of the chromosomes of the heart cells. The researchers were astonished to find that the previously short telomeres had become longer. This happened within only one month of the stem cell injections. To Marbán’s surprise the older rats also grew hair faster and gained 20% of their previous exercise tolerance limit. In other words, the injection of heart stem cells had rejuvenated the old rats.

Dr. Marbán has previously shown that exosomes play an important role with stem cell regeneration of old heart cells. These particles from the stem cell donor contain RNA and other growth factors.

Overview of how stem cells can reverse heart failure

Cardiovascular disease includes high blood pressure, coronary artery disease, stroke and congestive heart failure. About 2600 Americans die from cardiovascular disease each day in the US. This is roughly one death every 34 seconds. With old age, if a heart attack does not kill you, congestive heart failure will. With heart failure your heart ceases to pump enough blood through your system. Nutrients and oxygen need to reach all of our cells or it means death for the patient. With the knowledge of this serious background, stem cells have come into the focus in an attempt to combat congestive heart failure.

Animal experiments with stem cells in mice, rats and pigs have shown some progress in restoring better heart function. Researchers used different sources of stem cells, like cardiac stem cells that reside in the heart muscle itself. They also used other stem cell sources. Among these were myoblasts (from muscle), mesenchymal stem cells (from fat tissue) and bone marrow stem cells. Several smaller human trials showed that improvement of heart function was possible following a heart attack. In the procedure the surgeon opened coronary arteries and injected stem cells into the affected damaged heart muscle. How can we assess the result of a successful stem cell treatment? By measuring the left ventricular ejection fraction. This means that the heart can deliver a larger volume of blood every minute. The heart pumps more blood from the left ventricle with each heartbeat than before the treatment.

Other experiments that rejuvenate tissues of older animals

Another line of experiments in this paper shows that certain growth factors are necessary to activate stem cells.

  1. One experiment from the 1950’s describes the stitching together of the skin on their flanks joined an old and a young rat. After this procedure the blood vessels grew and joined the two animals circulatory systems. The older animals knee cartilage damage was no longer there, as the cells from the young animals’ blood had healed the damage.
  2. Research had no knowledge of this fact at that time. But another research group in the 2000’s repeated the experiment and could prove that the stem cells of the young animals activated the growth factors in the old animals.
  3. In 2004 Dr. Rando noted that muscle cells of aging mice were aging because of a lack of stimulation of the local skeletal muscle stem cells. These are satellite cells. Experiments similar to the rat experiment showed that there were factors in the blood of young mice that could re-activate stem cells in the muscles of old mice. Agility and movement of the older mice improved. The improvement in the older mice with knee arthritis disappearing and liver cells rejuvenating was astounding.

More evidence that rejuvenation of heart cells is possible

  1. Amy J. Wagers, a former colleague of Dr. Rando carried on experiments with respect to rejuvenation of hearts in mice. She and her colleagues found what stimulated the hearts of old mice. It was a protein called GDF11 (from young mice).  This 2016 publication describes the action of GDF11.
  2. A 2014 paper describes that GDF11 was able to restore aging muscles to a youthful state. But the researchers were also able to rejuvenate stem cell function in general with GDF11.
  3. Another paper describes that blood from young mice stimulates the brain of older animals to achieve rejuvenation. It is the protein of the young stem cells (called GDF11) and possibly other growth factors to bring about this rejuvenation. It works not only on heart cells, but also on hippocampus tissue in dementia models. This may be important in humans for treatment of Alzheimer’s disease.

“We can turn back the clock instead of slowing the clock down.” Dr. Toren Finkel said. He is the director of the Center for Molecular Medicine at the National Heart, Lung and Blood Institute. He went on to say: “That’s a nice thought, if it pans out.” But others who caution that overstimulation of stem cells could cause cancers say: “It is quite possible that it will dramatically increase the incidence of cancer,” Dr. Irina M. Conboy said, a professor of bioengineering at the University of California, Berkeley. “You have to be careful about overselling it.”

Degenerative changes in humans responding to stem cells

Many degenerative changes in humans respond to stem cell treatments. Are there stem cells present in degenerative tissue in humans similar to the animal experiments described above? Are the stem cells merely providing growth factors so the dormant stem cells jump into action and regenerate? Could it be that in future therapists could give a certain growth factor mix  intravenously to a patient, and the same effect as stem cell injections would be posssible? These are all unanswered questions, but research in the next decade should answer at least some of those questions.

Growth hormone improving heart function in heart failure patients

In 2008 a metaanalysis of human studies of congestive heart failure and treatment with human growth hormone (HGH) injections was a research topic. It showed an average increase of the ejection fraction by 4.3%. There were also increased cardiac output, decreased systemic vascular resistance and improved hemodynamic effects. The question is whether the effect is a direct effect on the heart muscle cells by HGH or whether HGH was recruiting dormant heart muscle stem cells. This is not clear at this point.

Young Heart Stem Cells Can Cure Old Hearts

Young Heart Stem Cells Can Cure Old Hearts

Conclusion

We have entered an exciting period of medical research. Although there is only a record of many animal experiments, there is overwhelming evidence that the same principles are true in humans. Many stem cell protocols for humans have already seen use for various applications. But stem cell treatments for heart disease are still in their early stages. As it becomes obvious from my review of this topic, some patients who were part of clinical trials have already experienced positive results. Congestive heart failure or poor pump performance following a heart attack have improved following various stem cell procedures. In the next few years there likely will be a proliferation of treatment options for patients. Although some critics have pointed out a possibility of cancer developing as a side effect of stem cell treatment, no evidence is noticeable at this point.

Sep
02
2017

Resveratrol Effective In Humans

Resveratrol is a powerful antioxidant; but is resveratrol effective in humans?

  1. Quack watch says: don’t buy into the hype that resveratrol is effective in humans.
  2. WebMD claims that there would not be enough medical evidence to say that the average person should supplement with resveratrol to receive benefits.

Despite these recommendations the following evidence supports that resveratrol is indeed effective in humans.

Resveratrol effective in humans: high blood pressure patients

First of all, a 2017 study of high blood pressure patients examined resveratrol supplementation with two groups, 46 stage 1 hypertension patients and 51 stage 2 hypertension patients. Stage 1 hypertension had a systolic blood pressure of 140–159 mmHg and a diastolic blood pressure of 90–99 mmHg. Stage 2 hypertension had a systolic blood pressure of 160–179 mmHg and a diastolic blood pressure of 100–109 mmHg. Analysts divided both stage 1 and 2 subgroups into two groups, one receiving regular antihypertensive medication, and the other group receiving regular antihypertensive medication plus Evelor. Evelor is a micronized formulation of resveratrol. The trial lasted two years.

Blood pressure lowering effect of resveratrol

The purpose of the trial was to determine the effect of resveratrol.  added to the regular antihypertensive medication (or not) to see whether it had blood pressure lowering effects. The interesting result showed that the resveratrol addition was sufficient to bring the blood pressure down to normal levels with only one antihypertensive drug. The control group without resveratrol needed two or three drugs to get the blood pressure under control. In addition, liver function tests showed that resveratrol normalized negative side effects of the antihypertensive drug on the liver. Both liver enzymes, glutamate-pyruvate transaminase (SGPT) and gammaglutamyl transferase (Gamma-GT) were normal in the resveratrol group.

Resveratrol effective in humans: diabetes patients

Diabetes patients can get help with resveratrol. Resveratrol, the bioflavonoid from red  wine is a powerful anti-inflammatory. This antioxidant has several other effects, which make it challenging to measure each effect by itself. Another group of investigators managed to simultaneously measure these effects. They found that resveratrol lowered the C-reactive protein by 26% and tumor necrosis factor-alpha by 19.8%. Resveratrol also decreased fasting blood sugar and insulin; in addition it reduced hemoglobin A1C and insulin resistance. The recommended daily dose of resveratrol was 1000 to 5000 mg.

Resveratrol effective in humans: improves bone density

Furthermore, resveratrol improves bone density in men: 66 middle-aged obese men with an average age of 49.3 years and a mean body mass index of 33.7 were recruited for this randomized, double blind, placebo-controlled trial. The purpose was to study whether there would be changes in bone turnover markers (LDH, an enzyme involved in bone turnover), but also whether bone mineral density (BMD) would increase. The researchers gave resveratrol to a high group (1000 mg per day), a low group (150 mg) and the third group received a placebo (fake pills). The end point was an elevation of the bone alkaline phosphatase (BAP). The investigators measured this in the beginning of the study and at 4, 8 and 16 weeks.

Difference between high and low dose resveratrol

The high group of resveratrol had a 16% increase of the BAP throughout the study and a 2.6% in lumbar spine bone density (measured by a trabecular volumetric method). The low resveratrol group showed no bone restoring effect. MJ Ornstrup, MD, the lead investigator said that this was the first time that a clinical team has proven that resveratrol can serve as an anti-osteoporosis drug in humans. She added that resveratrol appears to stimulate bone-forming cells within the body.

Resveratrol effective in humans: anti-aging effects

Finally, the Nurses’ Health Study showed that both a Mediterranean diet and resveratrol can elongate telomeres.

The fact that you can have a longer life with a Mediterranean diet is common knowledge for some time. But now a study has shown that the reason for a longer life is the fact that telomeres get elongated from the Mediterranean diet. Telomeres are the caps at the end of chromosomes, and they get shorter with each cell division. This is the normal aging process.

Important information from the Nurses’ Health Study 

The finding of elongated telomeres comes from the ongoing Nurses’ Health Study that started enrolling subjects in 1976. At that time 121 700 nurses from 11 states enrolled in the study. In 1980 participants filled in diet sheets to determine who was adhering to a Mediterranean diet. The researchers accepted 4676 middle-aged participants in this study. This diet consists of a combination of vegetables, legumes, fruits, nuts, grains and olive oil. They also consumed fish and lean meats. The control group followed a regular diet. Between 1989 and 1990 blood tests were obtained to measure telomere length in white blood cells. It is known that smoking, stress and inflammation shortens telomeres.

Slowed telomere shortening

The lead author Marta Crous-Bou stated that overall healthy eating was responsible for longer telomeres in comparison to the control group. But the strongest association was in women eating a Mediterranean diet in comparison to the controls. For the best diet adherence score there was a 4.5 year longer life expectancy due to slowed telomere shortening.

Resveratrol lengthens telomeres

Longer telomeres associated with the lowest risk to develop chronic diseases and the highest probability of an increase of the life span. I have reviewed the importance of lifestyle factors in this blog where I pointed out that Dr. Chang found a whole host of factors that can elongate telomeres by stimulating telomerase. Research in humans supports the notion that an increase in physical activity elongates telomeres. So did vitamin C, E and vitamin D3 supplementation, resveratrol, a Mediterranean diet and marine omega-3 fatty acid supplementation. In addition higher fiber intake, bioidentical estrogen and progesterone replacement in aging women and testosterone in aging men, as well as relaxation techniques like yoga and meditation are also elongating telomeres.

Aging is due to shortening of telomeres. Elongation of telomeres by resveratrol leads to prolonged life (or anti-aging).

Resveratrol effective in humans: resveratrol and cancer

In addition, this overview shows, it seems that several mechanisms of action give resveratrol the power to be an anticancer agent. Resveratrol is anti-proliferative and has anti-angiogenesis mechanisms. In addition resveratrol stimulates apoptosis, which is programmed cell death. All these actions together help resveratrol to have anticancer properties. Resveratrol is also useful in combination with other cancer treatments, which improves survival figures. As the link above explains, there is a need for more cancer clinical trials with a variety of cancers and larger patient numbers. Many smaller clinical trials have already been very successful showing efficacy of resveratrol as a chemotherapeutic agent.

Resveratrol is anti-inflammatory

Also, in this 2015 publication about malignancies and resveratrol an overview is given about the use of resveratrol and cancer treatment. It summarizes that the development of cancer is a multifactorial process that involves the 3 stages of initiation, promotion and progression. One of the cancer promoting factors is chronic inflammation. Resveratrol has anti-inflammatory qualities. At this point it is not clear how the animal experiments will translate into the human situation. More clinical observations are necessary.

Resveratrol effective in humans: cardiovascular disease

Resveratrol has beneficial effects on preventing hardening of the arteries, diabetes, various cancers and inflammatory conditions like Crohn’s disease and arthritis. Furthermore,  as this link explains resveratrol also stimulates the antiaging gene SIRT1 by 13-fold. This confirms the anti-aging effect of resveratrol. This 2012 study confirmed that it is resveratrol from red wine that is responsible for the “French paradox” (longer life expectancy despite high saturated fat intake).

Resveratrol effective in humans: polycystic ovarian syndrome 

Similarly, polycystic ovarian syndrome could be significantly healed with resveratrol in a randomized, double blind, placebo-controlled trial. It involved 30 subjects who completed the trial. Each of the subjects received 1500 mg of resveratrol or placebo daily for 3 months. Measurements showed a decrease of serum total testosterone by 23.1% at the end of 3 months in the experimental group versus the placebo group. There was also a decrease of dehydroepiandrosterone sulfate of 22.2%.There was a reduction of the fasting insulin level by 31.8%. At the same time there was an increase of the insulin sensitivity by 66.3%. The authors concluded that resveratrol had significantly reduced ovarian and adrenal gland male hormones (androgens). This may be in part from the drop in insulin levels and the increase of insulin sensitivity.

Resveratrol effective in humans: anti-arteriosclerotic effects in diabetics

Most noteworthy, a double blind, randomized, placebo-controlled study was done on 50 diabetics. Arterial stiffness was determined by the cardio-ankle vascular index (CAVI). The purpose of this study was to determine the effect of resveratrol on the stiffness of arteries in a group of diabetics and compare this to a placebo. Diabetics have premature hardening of the arteries (arteriosclerotic changes). After 12 weeks of taking 100 mg of resveratrol per day there was a significant reduction in arterial stiffness in the experimental group, but not in the placebo group. Blood pressure also decreased by 5 mm mercury (systolic) in the experimental group.

Resveratrol effective in humans: ulcerative colitis patients

Finally, 56 patients with mild to moderate ulcerative colitis received 500 mg of resveratrol or placebo and were observed for 6 weeks. This was a randomized, double blind, placebo-controlled pilot study. The researchers used bowel disease questionnaires to assess the bowel disease activity before and after the treatment. The resveratrol group decreased the disease activity significantly, but it also increased their quality of life. Blood tests showed that this improvement occurred as a result of reducing oxidative stress by resveratrol.

Resveratrol effective in humans: Alzheimer’s disease prevention

Here is a study where 52 Alzheimer’s patients were divided into two groups; one group received 200 mg of resveratrol for a number of weeks, the other group placebo pills. There was a significant improvement in memory tests in the resveratrol group and functional MRI scans showed better functional connectivity in the hippocampi of the subjects. The hippocampus is the seat for short-term memory, which is not functioning normally in Alzheimer’s patients.

Resveratrol Effective In Humans

Resveratrol Effective In Humans

Conclusion

Resveratrol has a long history of showing evidence of improving health. It does so by countering oxidation of LDL cholesterol, which lessens hardening of arteries. This prevents heart attacks and strokes. Resveratrol is also a powerful anti-inflammatory, which helps patients with diabetes, with Crohn’s disease and arthritis. There is even a cancer preventing effect of resveratrol because of anti-proliferative and anti-angiogenesis effects as well as stimulating apoptosis. These combined anticancer properties make resveratrol a chemotherapeutic agent. It is also effective in combination with conventional anticancer drugs.

Resveratrol helps prevent hardening of arteries and cancer

There are enough randomized, double blind, placebo-controlled trials in humans to show that resveratrol is effective in preventing and treating several disease conditions. The medical establishment claims that there would not be enough medical evidence to say that the average person should supplement with resveratrol to receive health benefits. After my review outlined above I come to the opposite conclusion. It is quite clear that resveratrol has several important healing properties. It can improve diabetes; prevent hardening of arteries, lower blood pressure, attack osteoporosis and prevent Alzheimer’s disease. I have been taking 500 mg of resveratrol daily for years. It has not harmed me.

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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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Jun
10
2017

Dementia And Strokes From Diet Drinks

,You can get dementia and strokes from diet drinks. This is what a recent study published on April 20, 2017 in the American Heart Association Journals has shown. Because of the bad press around sugary drinks more and more people have switched to diet drinks. But the authors of this study have found a correlation of consuming diet soft drinks (with artificial sweeteners), dementia and ischemic strokes.

How was the study done?

The community-based Framingham Heart Study followed patients on diet soft drinks for 10 years. There were two age groups: mean age of 62 and mean age of 69. There were 2888 participants in the younger age group and 1484 participants in the older age group. Researchers observed the younger age group for strokes, the older for dementia. During the observation time there were 97 cases of stroke (82 of them ischemic) and 81 cases of dementia (63 due to Alzheimer’s disease). In comparison to the controls with no consumption of diet drinks, there was an increase of 296% of ischemic stroke and 289% increase of Alzheimer’s disease. This was the data consuming diet soft drinks for 10 years. Another control group had consumed sugar-sweetened beverages. They did not develop strokes or dementia (observation time too short). As can be seen under this link the popular press also reviewed the study.

What do we know about artificial sweeteners?

Here is a brief review of the most common sweeteners.

1. Saccharin

This sweetener’s history goes back to 1879 when the Russian chemist Constantin Fahlberg first noted experimenting with coal tar compounds that one of the end products, benzoic sulfanide, tasted sweet. In fact it was between 200 and 700 times sweeter than granulated sugar! But there were political struggles that accompanied this saccharin throughout the years. There were rumours that in rats saccharin could cause bladder cancer. The health authorities became concerned. This led to Congress passing the Pure Food and Drug Act in June of 1906, to protect the public from “adulterated or misbranded or poisonous or deleterious foods, drugs or medicines.”

The origin of the FDA

This was the precursor of the FDA that would examine all of the medical evidence and consider the pros and cons of sweeteners as well. President Roosevelt took saccharin for weight control to replace sugar. In 1908 Roosevelt felt he had to stop the actions of overzealous Dr. Harvey Wiley, chief of the U.S. Department of Agriculture’s chemical division who was of the opinion that saccharin should disappear from market. Dr. Wiley did not give up his fight and finally the FDA decided to ban saccharin in processed foods, but to continue to allow private sales of saccharin.

2. Cyclamate 

Cyclamate first appeared in 1937. The company marketed the sweetener initially to achieve better control of blood sugars in diabetes. Because of the reduction in sugar consumption it allowed diabetic patients to cut the amount of insulin required to control diabetes. Cyclamate did not have a bitter aftertaste, so in a marketing move the company mixed cyclamate with saccharine. The ratio was 10 parts of cyclamate to 1 part of saccharin , which resulted in the creation of “Sweet ‘N Low. In 1958 the FDA gave cyclamate the GRAS designation: “generally recognized as safe”. The good fortunes of cyclamate did not last long: in 1969 damaging animal experiments showed that cyclamate/saccharin had caused chromosomal breaks in sperm of rats. Another study from 1970 showed bladder tumors in rats. Other studies showed lung, stomach and reproductive tumors in animal experiments with cyclamates/saccharin.

History of Sweet N’ Low sweetener

The FDA wanted to shut down the sale of the Sweet N’ Low sweetener, but public pressure and the food processing industry forced the issue to be brought up in front of Congress. The compromise was to use a warning label: “Use of this product may be hazardous to your health. This product contains saccharin which has been determined to cause cancer in laboratory animals.” In the year 2000 and beyond researchers did several animal experiments. The data from Denmark, Britain, Canada and the United States on humans showed no signs of bladder cancer from exposure to Sweet N’ Low. In 2000 Congress removed the warning labels.

3. Aspartame 

The detection of aspartame occurred in 1965. James M. Schlatter, a chemist, was looking for anti-ulcer drugs, but noticed the intensely sweet flavor when he licked his fingers. This led to the newest sweetener by 1973. We know it by the trade names Equal, NutraSweet or Sugar Twin. As this sweetener consists two amino acids, phenylalanine and aspartic acid. The body metabolizes it except people with phenylketonuria, with certain rare liver disorders or pregnant women. High levels of phenylalanine occur in their blood, because they cannot metabolize aspartame properly. Any food made with aspartame has to carry that restriction on the label, a requirement by the FDA.

Problems with Aspartame

In 1996 W. Olney and his associates presented research that implied that Aspartame would have caused brain tumors in rats. But later these experiments were disproven and studies from children with brain tumors showed “little biological or experimental evidence that aspartame is likely to act as a human brain carcinogen.”

4. Sucralose

The history of sucralose goes back to 1976 when insecticide researchers looked for new types of insecticides. They found that chlorinated sugar worked as an insecticide. One of the researchers tasted sucralose and to his surprise it was very sweet. If you Google “Splenda and insecticide”, you have a hard time finding references regarding the history of sucralose, but 20 years ago I found a detailed description that explained how one of the chemists doing insecticide research accidentally tasted one of the research products, and it was about 600-times sweeter than table sugar.

Sucralose kills ants

Here is one of the few references that explains that sucralose was discovered while looking for new insecticides. I have repeated the insecticide experiment myself in Hawaii where small ants are ubiquitous. Out of curiosity I took a package of Splenda from a coffee shop and sprinkled the contents in the path of ants. In the beginning the ants were reluctant to eat it, but after a short time they came and took it in. They slowed down, and finally they were all dead. A few hours later the only thing visible were dead ants that were only 1/3 of their original size. This was proof enough for me that Splenda, which originates from insecticide research, is not suitable for human consumption.

Side effects of sucralose in humans

In the meantime Dr. Axe in the above references lists the side effects in humans: “Migraines, agitation, numbness, dizziness, diarrhea, swelling, muscle aches, stomach and intestinal cramps and bladder problems.” In the Splenda marketing scheme they decided to first introduce Splenda gradually into diabetic foods as a sweetener, then later sell it to the public at large. Don’t fall for it! It was a side product of insecticide research, and insecticides have the undesirable quality of being xenoestrogens, which block estrogen receptors in women. As a result estrogen can no longer access the body cells, including the heart. The final consequence for a woman is a higher risk for cardiovascular disease. This can cause heart attacks, strokes and cancer. In men estrogen-blocking xenoestrogens can cause breast growth and erectile dysfunction. Taken everything together Splenda seems to be too risky for its sweetness.

5. Other sweeteners

Other sweeteners researchers have not stopped looking for newer, better sweeteners. There is a number of sugar alcohols with less calories than sugar such as erythritol. Another common sugar alcohol is xylitol, used in chewing gum. The advantage is that these are natural sweet alcohols that exist in nature. Xylitol originated from birch wood and the general opinion was that it was useful to fight tooth decay. Manufacturers of chewing gum mixed xylitol into some of their products. Karl Clauss and Harald Jensen in Frankfurt, Germany detected another sweetener, acesulfame potassium, also known by the names acesulfame K, Ace-K, or ACK in 1967 when they experimented with various chemicals. This is known under the brand name “Sweet One”, but is often disguised in processed foods together with other artificial sweeteners to mimic the taste of sugar.

6. Stevia 

Stevia has been used for over 400 years, particularly in South America. It grows like a small bushy herb with leaves that can be taken to sweeten foods.  With modern, reliable extracting procedures (Sephadex column) it is possible to separate the bitter component of stevia and discard it leaving stevia behind without any bitter aftertaste. Stevia occupies 40% of the sweetener market in Japan. In Europe and North America there is a lot of competition with the above-mentioned sweeteners, mainly because of clever marketing techniques. The FDA gave stevia GRAS status  in 2008.

What does sugar in soft drinks do?

Sugar is an emotional topic that can get people caught up in heated discussions. The sugar industry and the sugar substitute industry have also powerful lobby groups that provide the Internet and the popular press with conflicting stories to convince you to buy their product. There is good data to show that sugary drinks cause heart attacks, strokes and diabetes. Let’s not forget the metabolism behind the various sugars and starchy foods leading to fat deposits, high triglycerides and high LDL cholesterol.

Cut out sweets, cut out artificial sweeteners, but you can use stevia

Forget the emotions of severing yourself from your favorite fix.  Instead replace the familiar sweet taste you are used to from childhood on with stevia. At least this is what I do. The only alternative would be to take the plunge and cut out any sweet substance altogether, which I am not prepared to do. If you can do it, by all means go ahead. For more details regarding the effects of sugar and starchy foods read the blog under this link.

Dementia And Strokes From Diet Drinks

Dementia And Strokes From Diet Drinks

Conclusion

Diet soft drinks have become very popular. The reason is that studies in the past showed that sugary drinks can cause heart attacks and strokes. Now a new study revealed that diet soft drink consumption is associated with dementia and strokes. These drinks contained saccharin, cyclamate, aspartame or sucralose. They did not contain stevia, a natural sweetener because it is a natural, not a patented sweetener. It seems that companies’ profits are higher with chemical, patented sweeteners.

The problem with manufacturers and the FDA regulatory body

Looking back in time it seems perfectly legal that a company produces a chemical, patents it and sneaks it through the FDA channels for approval. The company then markets diet soft drinks turn out later to produce dementia and ischemic strokes in much larger studies. The FDA originally based their judgement on much smaller experiments for the initial approval. I have noticed that companies are now quietly introducing stevia, a natural sweetener to avoid potential legal problems down the road. Perhaps it is time to follow the Japanese lead where stevia is already occupying 40% of the sweetener market.

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May
20
2017

Prevention Of Telomere Shortening

Dr. Mark Rosenberg gave a talk on prevention of telomere shortening. This was presented at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The detailed title was: “The Clinical Value of Telomere Testing”.

What are telomeres?

Telomeres are the caps at the end of chromosomes. They are very important in the aging process. Prematurely shortened telomeres are linked closely to all major diseases like cardiovascular disease, cancer, diabetes and more. Telomeres are also a measure of the aging process. Aging occurs due to a decrease of the number of cells in organs and/or because of a lack of functioning of these organs. Telomeres get shortened every time a cell divides. But when the telomeres are used up, there comes a time when cells can no longer divide. These cells become senescent cells or they enter apoptosis (programmed cell death).

The senescent cells can become a problem when they get transformed into cancer cells and their telomeres lengthen again. These cancer cells divide rapidly and this can become the reason why cancer patients to die.

What is the significance of telomeres?

Telomere dysfunction is the first sign that the telomeres are getting shorter in a person compared to the average telomere length in a comparable age group. This is not only important for aging, but also has clinical implications. The shorter telomeres are, the higher the risk for cardiovascular disease. Telomere length also provides prognostic information about the mortality risk (risk of dying) with type 2 diabetes and for many cancers. Many physicians incorporate a telomere blood test into periodic health checks, if the patient can afford it.

Interventions that help telomere length

Here are a number of things we can do to lengthen our telomeres.

  1. Rosenberg mentioned that the strongest effect on telomere lengthening comes from caloric restriction and weight loss. 80 years ago they showed at the Cornell University that rats put on calorie restriction had a 30% increase in their mean and maximum lifespan. Many research papers have confirmed that the same is true in man and that the common denominator is telomere lengthening.
  2. Next are regular physical activity, meditation, reduction of alcohol consumption and stopping to smoke.
  3. Taking antioxidants and omega-3 fatty acids regularly will also lengthen telomeres.
  4. Improving one’s dietary pattern by adopting a Mediterranean type diet that contains cold-pressed, virgin olive oil.
  5. Telomerase activators. Here is some background on the TA-65 telomerase activator, which is based on Chinese medicine. A one year trial was completed with 250 units and 1000 units of TA-65 per day. The lower dose (250 units) showed effective telomere lengthening, while the placebo dose did not. The 1000 unit dose did not show statistical significance.

Should you wish to take TA-65, only take 250 units per day, not more.

Cancer and telomeres

There is a strong correlation between cancer and telomere shortening. When cells are at the brink of dying toward the end of their life cycle the telomeres get shorter and shorter. This is the point where the cells can turn malignant. Certain genetic abnormalities help the malignant transformation, like 11q or 17q deletions or a p53-dependent apoptosis response. Once cancer cells have established themselves they activate telomerase in 85% of cases. In the remaining 15% of cancer cases telomeres are activated through telomerase-independent mechanisms. Here are a few examples.

CLL

CLL stands for chronic lymphocytic leukemia. It is a disease of the aging population. At age 90 people’s bone marrow cells have a telomere length of only 50% of the length at birth. This is the reason that in older age CLL is more common. Researchers observed a population segment and found that the shorter telomeres were, the poorer the overall prognosis and overall survival for CLL was.

Lung cancer

Researchers examined the telomerase activity in patients with non-small cell lung cancer. When telomerase activity was present, the 5-year survival was only 55%. When telomerase activity was absent, the prognosis was 90% survival after 5 years.

Prostate cancer

  1. Prostate cancer risk correlated with telomere shortening in stromal cells. Men with shorter telomere length in stromal cells had a 266% higher risk of death compared to men with normal telomere length.
  2. Another study took blood samples and determined the telomere length in lymphocytes (the immune cells). Those men who came down with prostate cancer within a year after they had their blood sample, had short telomeres. The risk for prostate cancer in these patients was 355% higher than in the prostate cancer negative controls.

Yet another study looked at surgical tissue samples from 596 men that

Underwent surgery for clinically localized prostate cancer. Patients whose samples showed variable telomere lengths in prostate cancer cells and shorter telomeres compared to prostate samples with less variable telomere length and longer telomeres had a much poorer prognosis. They had 8-times the risk to progress to lethal prostate cancer. And they had 14-times the risk of dying from their prostate cancer.

Breast cancer

Breast cancer is diverse and consists of cases whose origins are genetic (BRCA1 and BRCA2), but there are also cases where the cancer is local or has a higher stage. In families with mutated BRCA1 and BRCA2 telomeres are significantly shorter than in spontaneous breast cancer. Increased telomerase activity in breast cancer cases is directly related to how invasive and aggressive the breast cancer is.

  1. In one study researchers analyzed blood leukocytes in 52 patients with breast cancer for telomere length  versus 47 control patients. Average telomere length was significantly shorter in patients with a more advanced stage of breast cancer than in early breast cancer. Mutated HER patients had the shortest telomeres. It follows from this that checking for the HER status and blood telomere testing adds to the knowledge of potential cancer development and prognosis.
  2. In patients with with larger breast tumors, more lymph node metastases and more vascular invasion the researchers found short telomere length of the cancer cells.
  3. More aggressive breast cancer cells have higher telomerase activity. More than 90% of triple negative breast cancers have short telomeres.

CNS disorders and telomeres

Dr. Rosenberg presented evidence for a correlation between shorter telomeres and the development of dementia. But dementias with Lewy bodies and Alzheimer’s disease are also linked to short leukocyte telomeres. The length of blood telomeres predicts how well stroke patients will do and how people with depression will respond to antidepressants.

Cardiovascular disease and telomeres

The renin-angiotensin-aldosterone system controls our blood pressure and keeps it constant. When this system is not stable, our blood pressure shoots up and causes cardiovascular disease. This is tough for the heart, as it has to pump harder against a higher-pressure gradient. A study of 1203 individuals was examining the connection between leukocyte telomere length and renin, aldosterone and angiotensin II activity. It concluded that oxidative stress and inflammatory responses affect the telomere length of leukocytes and that the more stress there is in the renin-angiotensin-aldosterone system, the more cardiovascular disease develops. The conclusion of the study was that the overall cardiovascular stress leads to shortening of leukocyte telomeres.

Prevention Of Telomere Shortening

Prevention Of Telomere Shortening

Conclusion

Telomere length testing from a simple blood test will become a more important test in the future as hopefully the cost comes down (currently about 300$). It can predict the general aging status by comparing a single case to the general telomere length of the public. But it can also predict the cancer risk, risk for mental disease and cognitive deficits (Alzheimer’s disease). In addition your cardiovascular status correlated globally with this test. What are the options for the patient, if the test comes back with short telomeres?

It allows you to change your lifestyle and adopt a healthy diet. You can exercise regularly, take antioxidants and meditate. There are even telomerase activators that are gradually becoming more known. They lengthen the telomeres. The cost of telomerase activators will likely still be a problem for some time. All in all telomere length tests are here to stay, but healthy lifestyle choices are the only tool for effective intervention at this point. This is good news: healthy lifestyle choices like non-smoking, exercise and avoiding non-processed foods are either free or have a reasonable price tag. Telomerase activators are big business and at this point not really affordable!

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