Oct
21
2017

Bioidentical Hormone Replacement

Recently Medical News Today published an article on bioidentical hormone replacement in the Sept. 19, 2017 edition.

Although it was partially informative, I felt that there was an underlying bias against the use of bioidentical hormone replacement. The article made it sound as if hormone replacement therapy would not be safe. But the opposite is true with bioidentical hormone replacement.

Why are many women afraid of bioidentical hormone replacement?

At the time when there was a lot of confusion about hormone replacement therapy (HRT) the results of the Women’s Health Initiative (WHI) made it even more confusing. After all there was one trial to show once and for all that HRT would be beneficial. The expectation was that HRT prevents osteoporosis, heart attacks and breast cancer. But the results were quite different. Instead the study found a 41% increase in strokes, 29% increase in heart attacks, 26% increase in breast cancer, 22% increase in total cardiovascular disease and a doubling in the risk for blood clots.

Missing information about synthetic hormones

What the authors of the study did not explain was the fact that it was the properties of the synthetic hormones, progestin and Premarin were responsible for the negative effects. Had research insisted to perform the study with bioidentical hormones, the results would have been quite the opposite! With bioidentical hormone replacement we see the prevention of heart attacks and clots; cancer rates are lower than controls, and the prevention of osteoporosis is another benefit. The end result is a reduction in mortality rates. But the horrifying results that are due to the use of synthetic hormones and that the WHI warned about linger on in the minds of many women.

The use of bioidentical hormone replacement

Dr. John Lee pointed out in several of his books that the physician should only replace hormone loss with bioidentical hormones. He also pointed out that physicians should only replace those hormones that are at low levels or missing. This means that the woman should have confirmatory blood tests like FSH, LH, blood estrogen and salivary progesterone. If estrogen and progesterone are missing, the physician usually starts the woman on progesterone cream first. After two months, when laboratory tests show a saturation with progesterone , the addition of estrogen can follow, typically as the Bi-Est cream. This is a mix of estriol and estradiol.

Caution to balance against estrogen dominance

Progesterone is started first to balance against the potential cancer-inducing effect of estradiol. With the addition of progesterone a balance is the result, and estrogen will not cause breast cancer. This is also why Bi-Est is used: it is a mix of estriol and estradiol. Estriol is neutral with regard to causing breast cancer. Estradiol is the main natural estrogen in a woman, so some of it is necessary to make the woman feel normal. This is how the body receptors are functioning. But estradiol alone, when not in balance with progesterone, can cause breast cancer and uterine cancer.

The key is that only women who need bioidentical hormones should receive it. There are some women whose blood tests do not show a lack of estrogen, but only a lack of progesterone. These women should receive replacement with bioidentical progesterone to re-establish the hormone balance between estradiol and progesterone.

Safety of bioidentical hormone replacement products

As I have mentioned before, the Women’s Health Initiative in 2002 showed that on Premarin and progestin, two synthetic hormone products women came down with breast cancer, heart attacks, stroke, and thromboembolic events. They were using the synthetic drugs, namely conjugated equine estrogen and medroxyprogesterone acetate. The reason these women had to suffer these side effects was because their physicians insisted in using “pure hormones that a drug company had manufactured”. But these synthetic hormones were not pure hormones; they were adulterated with side chains so that pharmaceutical companies could patent them. These side chains made the synthetic hormones not fit the body’s hormone receptors. And this is the reason why the synthetic hormones created chaos in form of breast cancer, strokes and heart attacks.

Women’s Health Initiative authors whitewashed study results

Instead of admitting their mistakes, the full truth never became public. Instead the authors of the WHI study stated that it would be necessary to limit hormone replacement in menopause to the minimum amount of synthetic hormones to control symptoms, and their use should not exceed more than 5 years. These authors never distinguished between bioidentical hormones that fit the body’s hormone receptors and the synthetic hormones that irritated or blocked the body’s hormone receptors. There are thousands of women in Europe who have been on bioidentical hormones for decades, and they are doing just fine!

Bioidentical hormones in balance have no side effects

The truth is that bioidentical hormones –as long as they are kept in balance-do not have any side effects. Bioidentical hormones are the same that a woman produces in her ovaries before menopause sets in. The production of her bioidentical hormones kept her healthy. But the treating physician needs to carefully watch the balance of the hormones in the woman who is replaced with bioidentical estrogen and progesterone. This means that she needs to get enough progesterone to counterbalance estrogen stimulation. Hormones are constantly changing and if you don’t measure them, you don’t know what you are dealing with.

Dr. Lee said to measure hormone levels

John Lee showed a long time ago that you should measure hormones and identify those women who are truly hormone deficient. These are the ones who need hormone replacement. However, physicians should use only bioidentical hormones to replace what is missing. And they should also replace only as much as necessary to normalize the levels. This is also the level where postmenopausal symptoms disappear. Dr. Lee noted: “A 10-year French study of HRT using a low-dose estradiol patch plus oral progesterone shows no increased risk of breast cancer, strokes or heart attacks”.

How is bioidentical hormone replacement done?

The best method is usually a bioidentical hormone cream application to the forearms or to the chest wall once per day. This avoids the first-pass metabolism where the hormones, if absorbed from a pill in the gut have to pass through the liver. Part of the hormones can get metabolized and some of the hormone effect may disappear. By applying bioidentical Bi-Est cream and progesterone cream to the skin, the hormones get directly absorbed into the blood stream and can do their job without interference. The treating physician can prescribe different amounts of the bioidentical hormones depending on saliva tests or blood tests. 1 or 2 months later repeat blood or saliva tests can follow to verify that the amounts of the replacement hormones and their absorption are adequate for the patient’s need.

What are the side effects of bioidentical hormone replacement?

Normally, when estrogen and progesterone are in balance, there should be no side effect. However, in the beginning of replacement therapy sometimes one of the hormones gets too high. If this happens with estrogen replacement, the woman becomes estrogen-dominant. She would experience symptoms of bloating, fatigue, weight gain, depression, headaches, loss of sex drive. She can also develop uterine fibroids, endometriosis and hypothyroidism. It was Dr. John Lee who first described this (Ref.1). There can also be mood swings, craving for sweets, irritability, and sluggishness in the morning. The key is to cut back on the estrogen dosage; alternatively, if progesterone is low in saliva tests, this hormone may need an increase, which would rebalance estrogen. At the end of fine-tuning of bioidentical hormone replacement the woman will feel normal and have no negative side effects, but the process of fine-tuning may take several months.

Difficulties to measure progesterone levels

Dr. David Zava, PhD gave a talk on breast cancer risks. This was a presentation at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. Dr. Zava, who runs the ZRT laboratory spent some time to explain how to measure progesterone in a physiological way.

Blood (serum) progesterone levels do not adequately reflect what the hormone tissue level is like in a woman’s breasts. On the other hand saliva hormone levels are giving an accurate account of what breast tissue levels are like.

Progesterone blood levels versus progesterone tissues levels

Dr. Zava gave an example of a woman who received an application of 30 mg of topical progesterone. Next, laboratory tests observed hourly progesterone levels in the serum and in the saliva. The serum progesterone levels remained at around 2 ng/ml, while the saliva progesterone levels peaked 3 to 5 hours after the application. It reached 16 ng/ml in saliva, which also represents the breast tissue progesterone level. Dr. Zava said that the important lesson to learn from this is not to trust blood progesterone levels. Too many physicians fall into this trap and order too much progesterone cream based on a misleading blood test. This leads to overdosing progesterone. With salivary progesterone levels you see the physiological tissue levels, with blood tests you don’t. Dr. Zava emphasized that testing blood or urine as progesterone hormone tests will underestimate bio-potency and lead to overdosing the patient.

Bioidentical Hormone Replacement

Bioidentical Hormone Replacement

Conclusion

Bioidentical hormone replacement, properly done, does not cause cancer, does not cause blood clots and prevents heart attacks and strokes. It also prevents osteoporosis and the associated fractures in older women. The key is that the natural hormones fit the body’s own hormone receptors. The reason why menopausal symptoms appear is that natural hormones (estrogen and progesterone) are missing. Physicians treated patients with synthetic hormones during the Women’s Health Initiative. In contrast, hormone replacement for missing hormones in a menopausal woman with bioidentical hormones  has no side effect. Contrary to the Women’s Health Initiative in 2002 there are no breast cancers, no heart attacks and no strokes with bioidentical hormone replacement. What is even better is that these women will live without all the postmenopausal problems, and their life expectancy will be about 10 years longer than without bioidentical hormone replacement.

References

Ref. 1. Dr. John R. Lee: “What your doctor may not tell you about menopause: the breakthrough book on natural hormone balance”. Sept. 2004.

Sep
23
2017

Close Diabetes Control Prolongs Life

 

A 20-year study showed that close diabetes control prolongs life. A study divided 160 people with diabetes into two groups. The one group continued to get standard care. Yet the other group received a multi targeted, aggressive treatment protocol. As a result after 20 years the group with the intensive treatment protocol lived 7.9 years longer than the group with the standard treatment.

Dr. Oluf Pederson was the senior investigator of the physician team that followed the diabetes group. He said that they concentrated on a number of known adverse factors and treated them aggressively. These factors were first of all high blood glucose values and clotting risks, also high blood pressure and high triglycerides and in addition cholesterol values. Behavior modification was the therapeutic method to get people with risk factors to exercise more, adopt a healthy diet and stop smoking. Medication in select cases also played a role.

More details about the study

The intervention of intensive treatment lasted 8 years. After that the patients were still in a follow-up study for 13 years. At the beginning of the study patients were on average 55 years old and were borderline obese.

The investigation team screened for complications of diabetes. This included screening for kidney disease, heart disease and blindness. Dr. Joel Zonszein, the director of the New York Clinical Diabetes Center at Montefiore Medical Center said: ”These results are impressive and most patients do not receive the correct treatment, according to national surveys.”

Other studies about diabetes  

Foreign studies

Study from Croatia
  • Another study from Croatia involved 200 patients. It concentrated on patients who did not respond to metformin. Physicians used alternative treatment modalities, and they observed and measured blood sugars and hemoglobin A1C in the following 6 months. The study concluded that those patients who received aggressive treatment of their condition did better than those who did not receive the same vigorous approach.
Study from Japan
  • This Japanese study documented that female patients with type-2 diabetes developed kidney damage earlier than their male counterparts.  Consequently, the investigators pointed out how important it is to treat diabetes aggressively to avoid kidney damage.
Study from Singapore
  • This 2016 study from Singapore analyzed retroactively the impact of diabetes on the long-term survival after coronary bypass grafting (CABG).  5720 consecutive patients had their isolated first CABG surgery between 1982 and 1999. The mean follow-up was 13 years. 34.6% of the patients had diabetes, 51% had high blood pressure and 46.6% had elevated blood lipids. The initial mortality after the CABG surgery was 2.4% in the diabetic group and 1.8% in the non-diabetic group. 20-year survival rates following CABG surgery were 30.9% in diabetics and 49.2% in the non-diabetics, an 18.3% difference. The 20-year freedom from cardiac mortality rates was 56% in diabetics and 68.4% in non-diabetics. Other risk factors that led to cardiac mortality were the following: female gender (1.43-fold risk), diabetes (1.51-fold risk), previous heart attack (1.54-fold risk) and a low left ventricular ejection fraction of less than 35% (2.6-fold risk). The conclusion from this study was that long-term survival in diabetics following CABG surgery was much lower than that of non-diabetic controls. Hence the key to improving long-term survival for diabetics is to treat comorbidities like high blood pressure and elevated lipids aggressively as well as getting blood sugars and hemoglobin A1C values under control.

US studies

  • In this US study 558 youth (age less than 21) between February 2012 to July 2015 received follow-up. Between 40% and 50% of these diabetics needed insulin to improve their diabetes. Unfortunately their diabetes showed poor control, as their high hemoglobin A1C values indicated. Median HbA1C was 6.7%, 8.5%, 9.6%, and 9.7% in those with disease duration less than 1 year, 1-2 years, 2-3 years and less than 4  In other words, the longer the young patients had diabetes, the less seriously they took their treatment. Only 33% treated their high blood pressure and only 11% their elevated blood lipids. Microalbuminuria, an indicator of diabetic kidney disease, and non-alcoholic fatty liver disease were present in 5% to 6% of these young diabetic patients. The authors came to the conclusion that there were serious gaps in treating these young diabetics. Further follow-up data of the same group of patients in the coming years will provide further data. In conclusion, the new hemoglobin A1C ranges of 3.8% to 4.9% as the new normal range explains why these youths who do not treat their diabetes properly are at high risk to develop complications from their poorly controlled diabetes.
Heart attacks and erectile dysfunction
  • Heart attacks are more common among patients with uncontrolled diabetes. This US study classified diabetics according to the tightness of their diabetes control. Researchers found examining 606 men and 606 women with diabetes that they could reduce their risk of a heart attack, if they controlled smoking, glycated hemoglobin (hemoglobin A1C), systolic blood pressure, and total and high-density lipoprotein cholesterol. The control of all these risk factors could contribute to the prevention of heart attacks. 35% of men and 45% of women could prevent having a heart attack. A laxer control still would prevent 36% of heart attacks in men and 38% in women. A very aggressive diabetes control could prevent 51% of heart attacks in men and 61% in women. Most noteworthy: close diabetes control prolongs life.
  • Erectile dysfunction (ED) is a big problem among diabetic men. This study from Seattle shows the investigation of 136, 306 men with erectile dysfunction. 19, 236 of these men had diabetes prior to their ED problem. Over a two-year observation period diabetic men had much worse ED problems. As a result they needed to receive secondary line treatments  like penile suppositories or injectables. Others needed tertiary treatments like penile prostheses. In those whose diabetes control was good, oral agents as first-line therapies were usually sufficient.
More studies about risks and benefits of lifestyle
  • Middle-aged women with diabetes have a 4- to 5-fold higher risk for developing heart attacks while men do not show such a higher risk. It is probably particularly important for women to control diabetes when they are diagnosed with it to reduce the risk of coming down with a heart attack.
  • In 2011 Taylor from Newcastle University showed in a group of diabetes patients that he could cure diabetes permanently with an extremely low calorie diet. The trial was simple: he took overweight or obese patients with diabetes and put them on a starvation diet of 600-700 calories per day for 8 weeks. Consequently 43% of diabetic patients received a permanent cure of their diabetes. More info: http://nethealthbook.com/news/cure-diabetes-permanently/

 

Close Diabetes Control Prolongs Life

Close Diabetes Control Prolongs Life

Conclusion

The new hemoglobin A1C ranges that are desirable are between 3.8% to 4.9%. When diabetics bring their hemoglobin A1C level into this range, they do not get complications from their previously poorly controlled diabetes. Close diabetes control prolongs life. But as can be seen from a brief review of the literature physicians tend to be lax, patients are lax, and diabetes is often not well controlled. This leads to erectile dysfunction in males, to heart attacks and kidney failure in both sexes. Blindness and painful diabetic neuropathy are also common complications of poorly controlled diabetes. Amputations from clogged arteries are also among the complications. “Close diabetes control prolongs life” is the new mantra that everybody with diabetes needs to follow.

Lifestyle changes control diabetes and prolong life

As stated above Dr. Taylor from Great Britain has shown that a brief 600 to 700 calorie diet can cure 43% of diabetic patients permanently. Quit smoking, bring the glycated hemoglobin (hemoglobin A1C) into the normal range, control your systolic blood pressure as well as your total and high-density lipoprotein cholesterol. Do all these things, exercise regularly, and your diabetes will be well controlled. Remember: close diabetes control prolongs life!

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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Aug
12
2017

Curcumin And Cancer

Many clinicians give their attention to curcumin and cancer. Physicians may use curcumin not as a primary treatment, but may add it as an adjunct to other cancer treatments. Curcumin is the effective ingredient of the old Indian spice, turmeric. The question is how effective curcumin is against cancer? Is it safe to use? What is the evidence?

Frequency of cancer

According to the American Cancer Society there will be 1,688,780 new cancer cases in 2017 and 600,920 cancer deaths will occur in the US.

Causes of cancer

There are many different causes for cancer. Hidden in the many causes may be the possible solution to new cures.

Lack of exercise

A lack of exercise may contribute to the development of cancer because of a lack of tissue circulation. And exercise will help to support your normal cell metabolism (explained below). Wrong foods may or may not have a contributory role regarding cancer development (a high sugar and starch diet causing insulin response, which changes the metabolism). The Mediterranean diet is an anti-inflammatory diet and has been credited to prevent a lot of cancers.

Carcinogens

Chemicals, called carcinogens can cause cancer. But oncoviruses can also cause it. Genetic mutations can also cause cancer. That’s why it tends to run more often in certain cancer prone families. But Warburg has researched the metabolism of cancer almost 100 years ago, even got the Nobel price for it in 1931 and yet the elusive cancer cure has not materialized yet.

DNA mutations, tumor suppressor genes metabolic difference between cancer cells and normal cells

Following Warburg’s research Watson/Crick detected DNA in our cells. Ever since geneticists found this fascinating by it. They also found that a cancer suppressive gene, regulated by the p53 gene could develop mutations and then cancer would occur: tumor suppressor genes. For decades this was the “in” thing. But in the last 5 to 10 years there is a revitalization of the original Warburg idea that one should concentrate on the metabolic differences between cancer cells and normal cells. This is starting to show some timid results. Cancer cells are more acidic from lactic acid and burn glucose for energy without requiring oxygen (anaerobic pathway), while normal cells burn glucose in the aerobic pathway in the mitochondria. This difference is important. Certain manipulations are more likely to kill cancer cells.

Cryoablation therapy for prostate cancer

Take cryoablation therapy for prostate cancer. Cryosurgery for prostate cancer. A local deep freeze method like cryoablation therapy kills the more vulnerable cancer cells preferentially leaving  the normal cells intact. Another example is photodynamic therapy for cancer that has been used for lung cancer and esophageal cancer.  This method may be a lot more universally applicable than believed so far. The physician injects a photosensitized dye, which is normal cells eliminate, but cancer cells retain.  Next the physician uses a laser beam that kills the cancer cells preferentially by absorbing the specific laser wavelength that is specific for the dye.

Consumer driven cancer therapies

Nobody knows which way cancer research is going. But I think that consumers will drive this: consumers want better cures. When new methods have better cure rates, consumers will demand treatments with these. Less effective methods will become history. I think that researchers will revitalize Warburg’s ideas and develop new therapies from this as I indicated.

Curcumin and cancer: malignant conversion

There are three development stages for any cancer to develop.

Originally cancer researchers used skin cancers a model. Later they could confirm that initiation, promotion and progression also were present with the development of cervical cancer. The name for this is “malignant conversion”. This needs to happen before a normal cell transforms into a cancer cell. Here are the three stages.

  • Initiation
  • Promotion
  • Progression

This is important to know in the context of curcumin. Basic research has shown that curcumin interferes with all of these stages of tumor development, both in terms of prevention as well as in terms of being curative. Here is a link that points out the complex multiple steps of cancer growth that curcumin interferes with.

Multiple actions of curcumin

As can be seen from it, curcumin interferes with the initiation of multiple cancers, reduces inflammation, and interferes with angiogenesis and this reduces the amount of metastases that can form. But curcumin further interferes with proliferation of cancer cells, reduces invasion, prevents resistance and improves survival. The underlying molecular and genetic reasons for curcumin’s actions are all contained in that link.

Curcumin and cancer: research in tissue culture and animal experiments

When it comes to cancer research, you usually hear about in vitro culture experiments and animal experiments. This type of research is used to establish that there is an anti-cancer effect, that it is reproducible and non-toxic. The September issue of the 2016 Life Extension Magazine reviewed this in detail. It was entitled “How Curcumin Targets Cancer”.

But as a former clinician I am more interested in seeing cancer patients cured. This has to be verified by clinical trials first. When I looked through PubMed.com for objective evidence of the effects of curcumin in cancer patients, this type of information was more difficult to find. But in the following there are a number of examples that I did find.

Curcumin and cancer: clinical trials

1. Reduction of tumor necrosis factor-alpha

A 2016 meta-analysis of eight randomized studies investigated the effect of curcumin in patients with various inflammatory diseases including cancer. They found that curcumin consistently reduced tumor necrosis factor-alpha. In cancer patients this inflammatory substance is responsible for further cancer growth and developments of metastases.

2. Poor bioavailability of curcumin

A study with increasing amounts of curcumin showed poor absorption of curcumin into the blood. In this study researchers were giving dosages between 500 mg up to 12,000 mg per day of curcumin. 500 mg to 8000 mg of curcumin did not result in any positive serum level of curcumin. Only the higher dosages, 10,000 and 12,000 mg of curcumin, caused positive curcumin levels in the blood.  Patients have to take higher amounts of curcumin to have a clinical response. Toxicity studies were done when using higher amounts of curcumin. The results showed taht it was safe and patients tolerated high dose curcumin fairly well.

3. Precancerous colonic polyps reduced in number and size

A smaller study consisted of 5 subjects with familial adenomatous polyposis (FAP). This is an autosomal-dominant disorder where hundreds of colorectal adenomas develop in the lining of the colon. From these colorectal cancer can arise. Five patients received 480 mg of curcumin and 20 mg quercetin orally three times per day. After 6 months the number of polyps and the size had reduced by 60.4%.

4. Premalignant colonic lesions suppressed by curcumin

44 eligible smoker subjects received a baseline colonoscopy where aberrant crypt foci (ACF) were determined. ACI are the very first focal areas in the colon that lead to colon cancer. Smokers have more of these lesions, which was the reason that researchers chose smoker subjects for this trial. The patients received either a supplement of 2000 mg of curcumin or 4000 mg of curcumin for 30 days. These are fairly high doses. They were used to overcome the poor absorption of curcumin. Colonoscopies were done again after one month of curcumin supplementation. 41 subjects completed the study. In the 4000 mg curcumin group the ACF numbers were reduced significantly by 40% compared to the 2000 mg group, which showed no reduction. The 4000 mg group showed a 5-fold increase of curcumin blood levels compared to baseline. The 2000 mg group had no change in blood levels.

5. Reduction of radiation dermatitis with radiation therapy in breast cancer patients

30 breast cancer patients were divided into an experimental group and a placebo group. All of them had a mastectomy first and subsequently radiation therapy. The experimental group received 6 grams (2 grams three times per day) of curcumin during the time of radiotherapy following mastectomy. The experimental group had  significantly reduced radiation dermatitis following radiotherapy when compared to the placebo group. Only 28.6% had significant radiation dermatitis in the curcumin group versus 87.5% in the placebo group.

6. Chronic multiple myeloma patients

An Australian study involving chronic multiple myeloma patients found that curcumin at 4 Grams per day and even more so at 8 Grams per day stabilized the disease and improved kidney function.

7. Descriptive studies

Descriptive studies investigating the effect of various doses of curcumin have been done regarding breast cancer,  and advanced pancreatic cancer. But these clinical trials were all rather small.

8. Chemoprevention of cancer

A phase II trial enrolled 21 patients with end-stage pancreatic cancer patients. The only FDA approved treatments for this are gemcitabine and erlotinib, but this would normally only lead to clinical responses in less than10% of patients. In this study the investigators used curcumin to enhance the anti-tumor response of either gemcitabine or erlotinib. The study summary stated: “Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.” 2 of the 21 patients had stable disease for more than 18 months; one of the 21 patients had a brief tumor regression of 78%, but then relapsed and died.

9. Chemoprevention of prostate cancer

Chemoprevention of prostate cancer is discussed in this publication: There was specific reference made to prevention of prostate cancer and the opinion of the researchers was: “At present, there is no convincing clinical proof or evidence that the cited phytochemicals might be used in an attempt to cure cancer of the prostate.”

Curcumin And Cancer

Curcumin And Cancer

Conclusion

For years there have been reports to indicate that curcumin was a promising natural supplement that can improve cancer survival. Many clinical trials regarding the effects of curcumin on colorectal cancer, pancreas cancer, prostate cancer, breast cancer, ovarian cancer and others had a poor design. But on closer look the hype seems to come mostly from in vitro studies (tissue culture experiments) or from animal studies. Clinicians, however, demand well-constructed randomized clinical trials with clear research objectives before they can accept a new agent like curcumin to be effective. These clinical trials are missing! Instead there are many in-between trials of questionable quality as listed above.

Problems with bioavailability of curcumin

There have been problems of bioavailability due to poor absorption of curcumin. Pushing the dosage to 6000 to 8000 mg per day succeeded in overcoming this limitation to a certain extent. But a significant percentage of people (around 30%) suffered from abdominal cramps and nausea and had to discontinue these high doses of curcumin. Researchers have developed newer curcumin compounds, but at this point it is unknown what the bioequivalent dosage is of these newer curcumin agents in comparison to the original curcumin dosages.

It is quite possible that researchers will one day design clinical trials  that will bring better news on survival rates of various cancer patients involving curcumin therapy. But in my opinion right now it is not yet prime time for curcumin!

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Aug
05
2017

Death From Heartburn Drugs

A study was recently published showing that death from heartburn drugs can come early, when compared to controls. The study was published in June 2017 in the online British Medical Journal Open. The researchers were located at the Washington University School of Medicine, Saint Louis, Missouri, USA.

They compared 349, 312 US veterans on proton pump inhibitors (PPI) to an equal amount of veterans on conventional H2 blockers. Over a follow-up period of 5.71 years there was an increased risk of death of 25% when patients took PPI drugs. No matter to what the researchers compared the PPI group to, there were always more deaths in the PPI group versus other control groups.

Causes of death

According to the senior author, Dr. Ziyad Al-Aly many deaths were due to kidney disease, dementia, fractures, pneumonia, Clostridium difficile infections and cardiovascular disease. Out of 500 patients who took the PPI drug there was one death within one year. But over the years the deaths increased. Dr. Al-Aly thinks that the PPI drug is interfering in some way with the genetic expression of some genes and suppressing others. These genetic differences may explain the early deaths.

As this was a retrospective study, it can only show an association of PPI drugs with earlier deaths, but this does not prove causation. It would require a prospective random study to prove causation.

Other studies regarding the risk of PPI drugs

An Icelandic study from May 2017 showed that there was a 30% increased risk of fractures in males and females following PPI drugs when observed over 10 years. Opiates had a risk of almost 50%, sedatives a 40% risk of increased fractures. Control groups of NSAIDs, statins and beta-blockers showed no increased fracture risk, nor did histamine H2-antagonists.

Side effects of PPI’s

An article from March 2017 is a critical review of the safety of PPI drugs. It notices that with long-term use there are adverse effects like fractures of the long bones, enteric infections and hypomagnesemia. PPI’s can increase the risk for heart attacks and can cause kidney disease and dementia. One of the problems is that gastroesophageal reflux usually dictates the long term use of anti acid drugs like PPI’s, but the longer patients are taking these drugs, the higher the death rate and side-effect rate. The physician should only use PPI drugs initially and after a few weeks switch to the less potent histamine H2-antagonists (like ranitidine).

Listeriosis as side effect of PPI’s

A Danish study from April 2017 noted an increased risk for listeriosis in patients who were on PPI drugs. Over 5 years there was a 2.81-fold higher risk of developing listeriosis in patients on PPI’s compared to a control group. If patients were on corticosteroids and a PPI the risk was even higher, namely 4.61-fold increase to develop listeriosis. In contrast, using histamine H2-antagonists had a risk of only 1.82-fold of developing listeriosis.

Poor prescribing habits for PPI’s

Dec. 2016 study from Dublin, Ireland with patients older than 65 examined their PPI drug use. The comparison of data occurred between 1997 and for 2012. The researchers noted that the maximal PPI dose for long-term use was 0.8% of individuals in 1997 and 23.6% in 2012. The risk of prescribing high dose PPI drugs in 2012 was 6.3-fold in comparison to the risk in 1997. Examination of the health records showed that the indication for prescribing PPI drugs had no correlation with significant gastrointestinal bleeding risk factors. The study concluded that there was definitely room for improving prescribing habits.

Triple therapy

This January 2016 paper describes the standard treatment of H. pylori and gastric and duodenal ulcer treatment, which involves the triple therapy consisting of a PPI and two antibiotics. It pointed out that this treatment protocol “improves healing and prevents complications and recurrences”.

PPI’s causing risk for fractures

A paper from Leipzig, Germany dated July 2016 reviews the usage of PPIs. It mentions that there has been a significant increase of prescriptions in the past 25 years. Patients on PPI’ are at a greater risk for fractures. There is also a risk of low B12 levels from malabsorption of B12. The physician should check this from time to time, and if necessary give B12 injections.

Clostridium difficile infections

A Canadian study from May 2015 found that Clostridium difficile infections (CDI) were linked to chronic antibiotic use or to prolonged use of high doses of PPI drugs. There was a 1.5-fold risk of recurrent CDI in patients older than 75 years who were taking PPI drugs continuously. There was a 1.3-fold recurrence of CDI after antibiotic re-exposure.

Alternative remedies for heartburn

  • Dr. Weil recommends the use of deglycyrrhizinated licorice (DGL) for heartburn or early ulcers.
  • Here is a clinical study with 56 patients with duodenal and gastric ulcers that was published in 1968. Both radiographic evidence as well as clinical findings showed that the ulcers healed and that stomach spasms subsided with DGL treatment. Nobody knew at that time that DGL had antibacterial effects and that often chronic heartburn, stomach and duodenal ulcers can be due to H. pylori infections that are simultaneously present.
  • A December 2016 study showed that probiotics could be a valuable adjunct in triple therapy for H. pylori infection. The study also points out that H. pylori is present in about 50% of the world’s population.

Antibacterial effects of DGL

  • A paper of December of 2012 shows that an important tooth decay bacterium responds to DGL.
  • In a 1989 study 20 patients with aphthous mouth ulcers were followed. DGL mouthwash led to a 50 to 75% improvement in 15 patients within one day of treatment and by the 3rd day there was complete resolution.
  • Here is a suggestion of a four-step approach against H. pylori.
  • DGL has been shown to be useful in gut regeneration in patients with Clostridium difficile infection.

Discussion

I started with a review of a recent paper that pointed out the side effects of PPI drugs. PPI’s are common medications for acid reflux disease, stomach and duodenal ulcers, either alone or as part of the triple therapy. Chronic infection of H. pylori is often the cause of these problems. I reviewed the literature surrounding deglycyrrhizinated licorice (DGL), a natural antacid remedy. It turns out that DGL can be quite useful either as a parallel treatment or instead of the triple therapy.

The problem over the past 25 years is that physicians have been treating acid problems with higher and higher doses of PPI’s. They are also using ASA prophylaxis against heart attacks and strokes more often. This has caused gastric erosions that are bleeding, which in turn caused physicians to prescribe more PPI’s. The side effects of PPI’s belongs to the iatrogenic (doctor- induced) diseases. This is an artificial disease that occurs from the side effects of overprescribed medicine. PPI’s are a very useful short-term anti-acid medication. However, do not use this medication for more than 4 to 8 weeks. But as patients receive years and years of this medication, serious problems like heart attacks, fractures, kidney disease, dementia, and pneumonia as well as Clostridium difficile infections become the consequence. Overall there was an increase of the death rate of 25%.

It sounds quite reasonable that doctors should return to a more conservative approach as the FDA has suggested. This includes alternative natural methods including DGL and probiotics.

Death From Heartburn Drugs

Death From Heartburn Drugs

Conclusion

A recent study from the online British Medical Journal Open has pointed out a high death rate among long-term proton pump inhibitor (PPI) drug users. The se drugs are used to suppress acid formation in the stomach. They are helpful, if there are significant gastrointestinal bleeding risk factors present. But prolonged use of PPIs causes severe side effects as described, including a chronic persistent Clostridium difficile infection (CDI) of the gut that can become resistant to antibiotic therapy. In cases of recurrent CDI one important step is to discontinue PPIs. The physician should consider switching to one of the conventional histamine H2-antagonist drugs (like ranitidine). Overusing PPIs in an older population is not responsible, as this leads to disease that is caused by a physician! There is no need for this to happen.

Avoiding toxic drug levels of PPI’s

The prescribing physician has to exercise caution and restraint and the patients, and their loved ones need to be aware of multidrug interactions. PPIs belong to the drugs that are eliminated in the liver through the cytochrome P450 enzyme system (CYP2C19). But this enzyme system interfering with the drug elimination process may also eliminate other drugs taken by the patient. The end results can be toxic drug levels of PPIs. It can potentiate the side effects and become responsible for the 25% increased risk of death when the patient takes PPI drugs chronically. Even though PPIs are the newer medication, newer does not always mean better.

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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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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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Apr
15
2017

What Foods Lower Insulin Resistance?

When people get diabetes or prediabetes, what foods lower insulin resistance? You may have heard that eating too many carbs and gaining weight can cause high insulin values. This causes the body’s insulin receptors to become sluggish, a condition called insulin resistance. Continuing to eat too many refined carbs leads to a critical point. You can suddenly run out of enough insulin and would develop type 2 diabetes at this time.

So, what foods lower insulin resistance?

Low glycemic food

Insulin resistance and type 2 diabetes occur because people do not pay attention to the glycemic load of the food they choose. Many people eat bread, pasta and starchy vegetables like potatoes. They also eat excessive sugary sweets, such as cupcakes, ice cream, or chocolate bars. All the pancreas can do is keeping blood sugar stable by overproducing insulin. But you can assist your pancreas to not overwork itself.

Leave the high glycemic index foods alone. Instead eat low glycemic foods like non-starchy vegetables (peppers, broccoli), lean meats, fish and nuts. Add high-fiber foods like beans and some whole grains. Eat foods rich in omega-3 fatty acids like salmon. Have a dessert with berries that are rich in antioxidants. Blueberries, strawberries, raspberries and black berries are all low glycemic foods, rich in vitamin C and antioxidants. They are “nature’s candy”.

Research on insulin resistance

In a study from Singapore differences of insulin sensitivity were found between lean Asian Indians and Chinese and Malays, living in Singapore. The Asian Indians had less insulin sensitivity, which means they had higher insulin resistance. This occurs because of a genetic variant of insulin sensitivity.

Another lengthy publication investigated the connection between metabolic syndrome and insulin resistance. In addition it examined the connection of heart attacks and strokes to wrong diets. The researchers pointed out that the percentage of diabetes and cardiovascular disease will reduce significantly on a sensible diet. How is this achievable? By adopting a healthy diet that also leads to weight loss.

Diets in the US and in the Western world have major shortfalls, due to the fact that people consume not enough vegetables, fruit and whole grains. Instead we see a higher intake of red and processed meat. In addition there was higher intake of sugar-sweetened foods and beverages. Refined grains and flour products are another unhealthy food source. In the US and other westernized countries we see an overconsumption of sodium and saturated fat.The key to a healthy diet was adopting a Mediterranean diet. A study exists where a group of patients with metabolic syndrome consumed mostly whole grains, vegetables, fruits, nuts, and olive oil. The control group simply followed a “prudent” diet.

What foods lower insulin resistance? The Mediterranean diet does!

Two years later the group on the Mediterranean diet showed the following results: they had a higher intake of monounsaturated fat (olive oil) and polyunsaturated fat (fish oil) and fiber. Their omega-6 to omega-3 ratio had decreased. The high-sensitivity C-reactive protein, a general measure for inflammation, had decreased. Other inflammatory kinins like interleukins had also decreased. The insulin sensitivity endothelial function score showed improvement. The important part overall was that the Mediterranean diet prevented the metabolic syndrome compared to the “prudent” control diet.

In 2018 a study from Spain was looking for positive effects when supplementing with olive oil or nuts. A Mediterranean diet with extra olive oil or extra nuts reduced the risk of heart attacks in a high-risk group compared to controls. The study included 7447 persons and these were the results after 4.8 years: the Mediterranean diet group that used more olive oil had 28% fewer cardiovascular events compared to the control group. The Mediterranean diet group with nuts had 31% less events. Heart attacks, strokes or death from cardiovascular disease were these “events”!

What foods are unhealthy?

In order to be able to avoid unhealthy foods it is important to identify what harms us. Foods to avoid are listed in this link. Sweetened beverages, fountain drinks, sodas and fruit juices contain loads of sugar. They will cause an insulin response and on the long-term insulin resistance. Avoid starchy vegetables, such as potatoes, pumpkin, corn, and yams. Also avoid processed snacks and boxed foods. Starchy foods break down into sugar, which also stimulates insulin release. Your no-food list continues with excessive sugary sweets, such as cupcakes, ice cream and chocolate bars. White bread, rice, pasta, and flour are also starchy, and the body breaks down starch into sugar and stimulates insulin production.

Some saturated fats are acceptable, but hydrogenated fat must be avoided altogether.

Epigenetic factors regarding insulin resistance

A recent publication on March 14, 2017 investigated the effect of exercise on insulin sensitivity in a mouse model where the mother mouse was obese.

Pregnant, obese mice were insulin resistant and the offspring came down with diabetes. But when the pregnant mice exercised, the insulin sensitivity came back to normal. In addition the offspring were not diabetic. This effect was not due to genetic factors. Instead the authors believe it was due to epigenetic factors, in this case treating insulin resistance with exercise. When the pregnant mother turns insulin sensitive, the offspring is programmed to regulate their blood sugar metabolism normally.

An April 2017 study from Korea investigated the effects of healthy nutrition on patients with metabolic syndrome and insulin resistance. They noted that avoiding unhealthy foods could normalize markers of disease.

The authors discuss how nutritional factors can contribute to inheritance of epigenetic markers in the next generation. They also showed how dietary bioactive compounds could modify epigenetic factors. Taking dietary components that regulate epigenetic factors contribute significantly to health. The authors concluded that a healthy diet could prevent pathological processes that otherwise would cause metabolic disease.

What Foods Lower Insulin Resistance?

What Foods Lower Insulin Resistance?

Conclusion

It is interesting to note that insulin resistance can be reversed into insulin sensitivity by eating healthy foods. Research papers are now describing how a healthy diet of the mother can affect her offspring positively. These effects are due to epigenetic factors, as genetic factors have not changed.

We are already hearing that diseases like heart attacks, high blood pressure, strokes, diabetes and others can largely be prevented by a proper diet. The key is to avoid high glycemic foods and eat low glycemic foods instead. It is not complicated. Eat non-starchy vegetables (leafy greens, peppers, broccoli), lean meats, fish and nuts. Add high-fiber foods like beans and some whole grains. Eat foods rich in omega-3 fatty acids like salmon. The end result is that insulin resistance disappears and metabolic processes return to normal. This was what Hippocrates had in mind when he stated “Let food be thy medicine and medicine be thy food.”

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Mar
04
2017

Weight Loss Surgery Is Unnecessary

Dr. Flavio A. Cadegiani gave a talk saying that weight loss surgery is unnecessary. Dr. Cadegiani is the director of a weight loss clinic with the name Corpometria Institute in Brasilia, Brazil. He is board certified in endocrinology and metabolism and in internal medicine. He presented his talk at the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended.

Here are the main topics that he presented.

Weight measurements are wrong when based on the BMI

Dr. Cadegiani stated that we do not understand obesity, because we look at it from the wrong angle. Current dietary approaches have failed. But obesity research is still proceeding in the wrong way. If all else fails, weight loss surgery is finally the last resort. But this is wrong.

The problem with body mass index (BMI) is that people would consider an athletic body type “obese”, because the BMI exceeds 30.0. However in a very muscular person the reason for the elevated BMI is an increased muscles mass, not fat. Body composition scales reveal that, but a simple weight measurement does not.

Dr. Cadegiani recommended measuring waist circumference with <94 cm (37 inches) for men and <88 cm (34.65 inches) for women being normal.

10 reasons why we are misled by the BMI

  1. The inventor of the BMI was a mathematician. He explicitly stated that the BMI would not predict the level of fatness of an individual. The other factors are bone mass and muscle mass.
  2. Because the BMI ignores the waist size, it is scientifically invalid.
  3. There are physiological reasons why it is wrong: studies did not factor in the relative proportion of the bone, muscle and fat content.
  4. The BMI gets the logic wrong: the CDC site claims that the BMI “is a reliable indicator of body fatness for people”. This is simply not true!
  5. The BMI is based on bad mathematics: the formula assumes low muscle mass and high fat content.
  6. The BMI is lying by scientific authority: Dr. Cadegiani said it has an “air of scientific authority, but it is mathematical snake oil.”
  7. The BMI suggests that there are distinct categories of underweight, ideal, overweight and obese. It assumes sharp boundaries that hinge on a decimal place. All of this is nonsense.
  8. Cynical people could suspect that medical insurance companies lobby for the continued use of the BMI as it keeps their profits high. Sometimes insurance companies charge higher fees for people with an elevated BMI.
  9. Doctors can contribute to the continued use of the BMI, if they don’t feel the need to use another way of assessing their obese patients.
  10. It is embarrassing that we still base the assessment of obesity on a 200-year-old mathematical formula when we know of  more reliable measures.

Bariatric surgery done too easily

Dr. Cadegiani noted that publications on bariatric surgery (=weight loss surgery)

underreport surgical complications and deaths. The bariatric industry is rich, and 90% of the booths during obesity conferences belong to bariatric-related companies. Long-term follow-up studies are lacking. Those who do follow-ups report an increase of pancreatic tumors after 10 years following bariatric surgery.

Long-term follow-ups also describe a 70% increase of psychiatric disorders including depression and alcoholism. Those who had bariatric surgery experience a 200% increase in suicides.

Overcoming weight centered approach

Here is how to avoid the weight-centered approach that would lead the clinician to wrong conclusions.

There are four factors that need consideration:

  1. The assessment includes metabolic blood markers
  2. The assessment incorporates body composition scales
  3. The patient participates by measuring waist circumference and body weight
  4. The clinician incorporates clinical signs and symptoms

Classic metabolic markers are liver enzymes and hormone levels like testosterone, Thyroid (T3) LH and IGF-1. Apo B and triglyceride levels have to come into consideration  for a lipid metabolism assessment. The physician monitors inflammation through a combination of uric acid levels, ferritin and C-reactive protein (CRP). An oral glucose tolerance test and fasting insulin level can predict diabetes 5 to 10 years before it will occur clinically. Other metabolic markers are homocysteine and metalloproteinases. There are newer tests to measure insulin resistance.

Oxidized LDLc is the only marker that is linked to diabetic retinopathy. Another marker, resistin is an independent marker for obesity-related cancer, cardiovascular disease and overall mortality. A triglyceride-waist circumference index has been found to be the best predictor for future development of diabetes.

Body composition analysis

The patient measures his/her own waist circumference and body weight on body composition scales. This gives additional information about fat and muscle composition. Dr. Cadegiani’s team likes to understand what is really going on in terms of what triggers fat excess.

Questions are: what is the level of emotional overeating? How much anxiety is there in the patient’s life that leads to overeating? What is the social and cultural environment? What were previous weight loss attempts? And what is the family history in term of excessive weight?

Other important factors are to check for binge eating disorders or night eating syndrome. In addition any patient planning to go for weight loss therapy should be checked for depression, mood disorders and suicide potential.

Otherwise body composition scales by electrical bioimpedance were found to be very useful in assessing fat and muscle percentage as well as visceral fat percentage.

Aggressive clinical approach improves metabolism

Dr. Cadegiani and his group have published their own research paper in February 2017 showing that an aggressive clinical approach can prevent the need for bariatric surgery.  This publication describes that in a group of 43 subjects who were thought to be bariatric surgery candidates only 3 patients (7%) went on to have the procedure done. 93% of the subjects were able to shed pounds with the method offered and avoided bariatric surgery.

They documented that clinical parameters and blood tests all improved on their program. The researchers focused on triggers that caused obesity in their patients. The measured markers were oxidized LDL cholesterol, triglycerides, the liver enzymes ALT and μGT, fasting glucose, Hemoglobin A1C, uric acid and CRP. All of these parameters improved with the modification in food intake. 81.2% of the weight loss was from the reduction of fat mass. 46.5% of patients had a normal waist circumference measurement at the end of the trial. They also achieved normal body fat and visceral fat percentages. As already stated 93% of all the patients in this trial avoided weight loss surgery, called bariatric surgery.

Dr. Cadegiani suggested that obesity should be approached with a scientifically based and responsible method. This will change the way we manage obesity.

Weight Loss Surgery Is Unnecessary

Weight Loss Surgery Is Unnecessary

Conclusion

Attention to detail of the patient with weight problems will allow the patient to reduce fat percentage. Waist measurements should be regularly performed as well as body composition scales measurements. This way the physician can follow the fat and muscle percentages. Key to success is to reduce the refined carb contents of food intake (sugar and starchy foods) and have a calorie deficit diet. Exercise is also an important component. An aggressive clinical approach to obesity can improve the clinical outcome and can prevent bariatric surgery.

Feb
25
2017

Heart Health Improves With Hormone Replacement

Dr. Pamela Smith gave a lecture in December 2016 showing that heart health improves with hormone replacement. Her talk was part of the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9 to Dec. 11, 2016) in Las Vegas, which I attended. The title of the talk was: “Heart health: The Importance of Hormonal Balance for Men and Women”. Her keynote lecture contained 255 slides. I am only presenting a factual summary of the pertinent points here.

1. Estrogen

First of all, estrogens are the main female hormones in women that protects them from heart attacks.

Observations regarding risk of heart attacks

  1. Women have a lower risk of heart attacks before menopause compared to men of the same age.
  2. Heart attack rates go up significantly after menopause.
  3. Estrogen replacement therapy may reduce the risk of heart attacks by 50% for postmenopausal women.

Lipid profile after menopause

There is an elevation of LDL cholesterol, total cholesterol and triglycerides as well as lower HDL cholesterol levels. All of this causes a higher risk of heart attacks for postmenopausal women. Estrogen replacement therapy increases the large VLDL particles, decreases LDL levels and raises HDL-2. Postmenopausal women who do estrogen replacement therapy (ERT) are helping to reduce their heart attack rates.

Difference between oral and transdermal estrogen replacement

The liver metabolizes estrogen taken by mouth. This reduces the protective effect on the cardiovascular system. In contrast, transdermal estrogen (from commercial estrogen patches or from bioidentical estrogen creams) has a higher cardioprotective effect. The liver does not metabolize transdermal estrogen. Dr. Smith explained using many slides how estrogen prevents heart attacks. Apart from lipid lowering effects there are protective effects to the lining of the arteries. In addition there are metabolic processes in heart cells and mitochondria that benefit from estrogens. The end result is that postmenopausal women who replace estrogen will outlive men by about 10 years. The production of Premarin involved pregnant mares. In other words, it is not human estrogen and it does not fit the human estrogen receptors. Also the liver metabolizes estrogen taken as tablet form, which loses a lot of the beneficial effects that you get from transdermal estrogen. 

How can you document the beneficial effects of estrogen replacement?

  1. Carotid intima measurements in postmenopausal women on ERT show a consistent reduction in thickness compared to controls.
  2. Postmenopausal women on ERT reduce their physical and emotional stress response compared to postmenopausal women without ERT.
  3. Hormone replacement therapy in postmenopausal women reduces blood pressure. Measurements showed this effect to be due to a reduction of angiotensin converting enzyme (ACE) by 20%. This is the equivalent of treating a woman with an ACE inhibitor without the side effects of these pills.
  4. Coronary calcification scores were lower in postmenopausal women on ERT than a control group without ERT. These calcification scores correlate with the risk for heart attacks.
  5. Oral estrogen replacement leads to proinflammatory metabolites from the liver metabolism of estrogen. No proinflammatory metabolites occur in the blood of women using transdermal estrogen. The anti-inflammatory effect of transdermal estrogen is another mechanism that prevents heart attacks.
  6. Postmenopausal women on ERT had no increased risk of heart attacks or venous thromboembolism (clots in veins). Menopausal women without ERT have a risk of 40% of dying from a heart attack. Their risk of developing breast cancer is 5.5%, the risk of dying from breast cancer is about 1%. There was an increase of venous thromboembolism in women who took oral estrogen.
  7. Estrogen has antiarrhythmic effects stabilizing the heart rhythm. Dr. Smith said that in the future intravenous estrogen might be used to prevent serious arrhythmias following heart attacks.

Estrogen levels in males

Males require a small amount of estrogens to maintain their memory, for bone maturation and regulation of bone resorption. But they also need small amounts of estrogen for their normal lipid metabolism.

However, if the estrogen levels are too high as is the case in an obese, elderly man, there is an increased risk of heart disease. Factors that lead to increased estrogen levels in an older man are: increased aromatase activity in fatty tissue, overuse of alcohol and a change in liver metabolism, zinc deficiency, ingestion of estrogen-containing foods and environmental estrogens (also called xenoestrogens).

2. Progesterone

Furthermore, progesterone is the second most important female hormone, the importance of which has been neglected in the past. Progesterone is significantly different from the progestin medroxyprogesterone (MPA). MPA was the oral progestin that was responsible for heart attacks and blood clots in the Women’s Health Initiative. MPA increases smooth muscle cell proliferation. This in turn causes hardening of the coronary arteries. In contrast, progesterone inhibits smooth muscle cell proliferation, which prevents heart attacks. Progesterone also lowers blood pressure and elevates HDL cholesterol, but MPA does not.

Progesterone in males

In a small study Depo-Provera was given to males for 17 days. Blood tests showed a lowering of triglycerides, LDL cholesterol and Apo A-1.

3. Testosterone

Finally, testosterone is the third sex hormone that is present in women. In men it is the main hormone, but women benefit from just a small amounts of it for libido, clarity of thought and muscle endurance.

Testosterone replacement in women

Testosterone in women does not only increase their sex drive, but also relaxes the coronary arteries in women who were testosterone deficient. This allows more blood flow to the heart. In postmenopausal women testosterone replacement lowered lipoprotein (a) levels up to 65%. The physician replaces first with bioidentical estrogen; only then does he consider replacing missing testosterone in women. Otherwise testosterone alone can cause heart attacks in women.

Elevated testosterone in women with PCOS

Women with polycystic ovary syndrome (PCOS) can have increased testosterone levels when they go through premenopause or menopause.

Women with PCOS are at a higher risk to develop diabetes, heart disease and high blood pressure. 50% of women with PCOS have insulin resistance. 70% of women with PCOS in the US have lipid abnormalities in their blood.

Elevated testosterone levels in the blood can lower the protective HDL cholesterol and increase homocysteine levels. Both can cause heart attacks.

Women with PCOS have a 4-fold risk of developing high blood pressure.

Testosterone replacement in males

A 2010 study showed that low testosterone levels in males were predictive of higher mortality due to heart attacks and cancer. Low testosterone ca cause high blood pressure, heart failure and increased risk of cardiovascular deaths. There was a higher incidence of deaths from heart attacks when testosterone levels were low compared to men with normal testosterone levels.

Low testosterone can cause diabetes and metabolic syndrome, which in turn can cause heart attacks.

It is important that men with low testosterone get testosterone replacement therapy.

DHT (Dihydrotestosterone)

DHT is much more potent than testosterone. Conversion of testosterone leads to DHT via the enzyme 5-alpha-reductase. While testosterone can be aromatized into estrogen, DHT cannot. Some men have elevated levels of DHT. This leads to a risk of heart attacks, prostate enlargement and hair loss of the scalp.

Andropause treatment

Only about 5% of men in andropause with low testosterone levels receive testosterone replacement in the US. This may be due to rumors that testosterone may cause prostate cancer or liver cancer. The patient or the physician may be reluctant to treat with testosterone. Researchers sh0wed that bioidentical testosterone does not cause any harm. It is safe to use testosterone cream transdermally. It does not cause prostate cancer or benign prostatic hypertrophy.

An increase of 6-nmol/L-serum testosterone was associated with a 19% drop in all-cause mortality.

Testosterone helps build up new blood vessels after a heart attack. Testosterone replacement increases coronary blood flow in patients with coronary artery disease. Another effect of testosterone is the decrease of inflammation. Inflammation is an important component of cardiovascular disease.

Testosterone replacement improves exercise capacity, insulin resistance and muscle performance (including the heart muscle).

Apart from the beneficial effect of testosterone on the heart it is also beneficial for the brain. Testosterone treatment prevents Alzheimer’s disease in older men by preventing beta amyloid precursor protein production.

4. DHEA

The adrenal glands produce the hormone dehydroepiandrosterone (DHEA). It is a precursor for male and female sex hormones, but has actions on its own. It supports muscle strength. Postmenopausal women had a higher mortality from heart disease when their DHEA blood levels were low.

Similar studies in men showed the same results. Congestive heart failure patients of both sexes had more severe disease the lower the DHEA levels were. Other studies have used DHEA supplementation in heart patients, congestive heart failure patients and patients with diabetes to show that clinical symptoms improved.

5. Melatonin

Low levels of melatonin have been demonstrated in patients with heart disease. Melatonin inhibits platelet aggregation and suppresses nighttime sympathetic activity (epinephrine and norepinephrine). Sympathetic activity damages the lining of coronary arteries. Melatonin reduces hypoxia in patients with ischemic stroke or ischemic heart disease. Lower nocturnal melatonin levels are associated with higher adverse effects following a heart attack. Among these are recurrent heart attacks, congestive heart failure or death. Melatonin widens blood vessels, is a free radical scavenger and inhibits oxidation of LDL cholesterol. Melatonin reduces inflammation following a heart attack. This can be measured using the C-reactive protein.

In patients who had angioplasties done for blocked coronary arteries intravenous melatonin decreased CRP, reduced tissue damage, decreased various irregular heart beat patterns and allowed damaged heart tissue to recover.

6. Thyroid hormones

It has been known for more than 100 years that dysfunction of the thyroid leads to heart disease. Hypothyroidism can cause heart attacks, hardening of the coronary arteries and congestive heart failure. Lesser-known connections to hypothyroidism are congestive heart failure, depression, fibromyalgia, ankylosing spondylitis and insulin resistance. Some cases of attention deficit hyperactivity disorder (ADHD) with low thyroid levels may successfully respond to thyroid replacement.

Thyroid hormones improve lipids in the blood, improve arterial stiffness and improve cardiac remodeling following a heart attack. Thyroid hormones help with the repair of the injured heart muscle. They also work directly on the heart muscle helping it to contract more efficiently. Lower thyroid stimulating hormone (TSH) values and higher T3 and T4 thyroid hormone levels lead to improved insulin sensitivity, higher HDL values (= protective cholesterol) and overall better functioning of the lining of the arteries.

Dr. Smith said that thyroid replacement should achieve that

  • TSH is below 2.0, but above the lower limit of normal
  • Free T3 should be dead center of normal or slightly above
  • Free T4 should be dead center of normal or slightly above

Most patients with hypothyroidism require replacement of both T3 and T4 (like with the use of Armour thyroid pills).

7. Cortisol

Cortisol is the only human hormone that increases with age. All other hormones drop off to lower values with age. The adrenal glands manufacture cortisol. With stress cortisol is rising, but when stress is over, it is supposed to come down to normal levels. Many people today are constantly overstressed, so their adrenal glands are often chronically over stimulated. This can lead to a lack of progesterone. It also causes a lack of functional thyroid hormones as they get bound and are less active. When women have decreased estradiol in menopause there is a decline in norepinephrine production, production of serotonin, dopamine and acetylcholine. Women with this experience depression, lack of drive and slower thought processes.

Heart Health Improves With Hormone Replacement

Heart Health Improves With Hormone Replacement

Conclusion

Seven major hormones have been reviewed here that all have a bearing on the risk of developing a heart attack. It is important that these hormones are balanced, so they can work with each other. Hormones can be compared to a team that works together and is responsible for our health. If one or several of the team players are ineffective, our health will suffer. For this reason hormone replacement is crucial.

Hormone effects on heart muscle

Hormones have effects on mitochondria of the heart muscles cells. They stabilize the heart rhythm as in the case of estradiol. But they can also strengthen the heart muscle directly through DHEA and estrogens in women and DHEA and testosterone in men. Thyroid hormones are another supportive force for the heart. Physicians can  use them therapeutically in chronic heart failure patients. When people age, their hormone glands will produce less hormones, but blood tests will show this. Replacing hormones that are missing can add years of active life. Taking care of the symphony of hormones means you are taking care of your most important organ, the heart!

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