Feb
11
2017

Genetic Switches To Treat Obesity And Diabetes

Dr. Michael Nova gave a talk about the role of genetic switches to treat obesity and diabetes. He gave this talk as part of the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas that I attended. The full title of the talk was “Nutritional Genetics and Epigenetics in Diabetes and Obesity Management”. Dr. Michael Nova is the Chief Innovation Officer at Pathway Genomics, San Diego, CA 92121.

Twin studies are a powerful tool to show that longevity is both genetically caused as well as environmentally.

In the light of these studies the results showed that 80% of a long life (longevity) is due to a healthy lifestyle and 20% comes from genetics. In addition, there are powerful epigenetic factors that can slow down aging and that can interfere with the inflammatory process that causes heart disease, obesity and diabetes. Also, there are specific inflammatory markers, which blood tests can determine. As a matter of fact, one of the first inflammatory markers detected was the C-reactive protein.

What diseases are caused from inflammation?

Dr. Nova showed a slide depicting MS and Alzheimer’s disease. In the heart area atherosclerosis was shown to cause heart attacks and strokes. Next diabetes, lupus, obesity and irritable bowel disease were depicted. Finally there is arthritis that interferes with joint movements. In other words, all of these conditions have inflammation at the core, which leads to worsening of the conditions, if the inflammation is not stopped through nutritional or medical means.

Age-related diseases also due to inflammation

Furthermore, inflammation is not only confined to these conditions. Research has shown that the following age-related diseases belong into the inflammatory category. These are: osteoporosis, depression, diabetes, cancer, neurodegenerative diseases (Parkinson’s disease, Alzheimer’s), asthma, central obesity, metabolic syndrome and cardiovascular disease. In these diseases the C-reactive protein is often up, so is the fasting insulin level. The rest of the talk concentrated on how various changes in food intake and supplements could lead to epigenetic changes that improve the patients’ conditions.

Human genetics are complicated

The speaker mentioned how complex the human genetics are, and he showed a number of slides that are too complicated to discuss here. There are unstable genes, which can become important in the development of illnesses, particularly when you don’t exercise and you eat a Standard North American diet. There are genes involved that cause diabetes, but they need environmental triggering to get expressed. Dr. Nova showed one slide that listed two genetic variants, which when activated by inflammation rendered the person positive for diabetes or heart disease. On the other hand, if inflammation is vigorously treated with a Mediterranean diet and Metformin, the hemoglobin A1C will decrease to less than 6.0% and diabetes will disappear.

Obesity and genetic factors

Obesity has a 40% to 60% hereditary rate. The fat mass and obesity-associated gene, FTO gene for short is the reason some people gain weight. When this gene is not present, the person has no problem maintaining a normal weight. The FTO gene is located on chromosome 16. Moreover, there are other genes with complicated names that can also increase weight.

It is important that there are many factors that work together in developing obesity. Dr. Nova called this the “epigenetic modulation”. He explained further that there are at least 12 factors working together that can reduce obesity. These are:

  1. Diet
  2. Diurnal/seasonal correlations
  3. Smoking and other toxic chemicals
  4. Street drug use
  5. Disease exposure
  6. Financial status
  7. Exercise status
  8. Microbiome healthy?
  9. Therapeutic drugs
  10. Alternative medicine
  11. Social interactions
  12. Psychological state

First, low carbohydrate diets and the ketogenic diet are helping to reduce weight. Second, financial stress leads to more cortisol production, which leads to weight gain. Third, an unhealthy bacteria composition in your gut causes you to gain weight, while a good composition of bacteria helps you lose weight. Furthermore, overcoming depression with cognitive therapy can help reduce your weight. Those are just a few examples in more detail from the list of 12 factors.

Extensive research has shown that genetic factors and environmental factors interact to lead to epigenetic marks or imprinting. It is important to realize that epigenetic factors have an influence on gene expression, but they don’t change the underlying DNA sequencing.

As can be seen, there are still gaps of knowledge how obesity develops, what percentage is due to genetic factors and how much is due to other factors including diets.

Diabetes and genetic factors

Nutrition can influence major metabolic processes in our body cells like phosphorylation, acetylation and methylation. This allows epigenetic mechanism of actions to interfere with the expression of inherited health problems like diabetes and other diseases. This has the potential to improve quality of life.

Useful supplements

Dr. Nora showed a slide with a number of useful supplements.

  • EGCG is the effective component of green tea. It supports the viability of the beta-islets of the pancreas that produce insulin. It leads to more secretion of insulin.
  • Naringin and Hesperidin decrease high blood sugar levels.
  • Anthocyanin decreases high blood sugar levels.
  • Quercetin increases cell proliferation in the liver and the pancreas.
  • Vitamin D3 reduces diabetes incidence and inflammation of the insulin-producing cells.
  • Biotin in combination with chromium increases insulin secretion and lowers blood sugars.
  • Vitamin B2, also known as riboflavin has anti-inflammatory effects.
  • Alpha-lipoic acid protects against diabetes by reducing blood sugar levels.

There are several genes responsible for the development of type 2 diabetes, one of them is the FTO gene that is also important in the development of obesity. But Dr. Nora projected a slide that showed 14 other genes that may lead to the development of diabetes. I have elected to not get into all of those details.

What Dr. Nora concluded is that healthy nutrition plays a vital role in preventing FTO gene expression. He talked about silencing genes, which good nutrition and supplements can do.

Silencing diabetes genes

A Mediterranean diet can stabilize the metabolism and fight inflammation. In like manner zinc and magnesium are important cofactors in enzymes necessary to prevent diabetes. In the same fashion Vitamin D3 and omega-3 intake are helping to control inflammation and preserve beta cells in the pancreas in diabetes patients.

Nutritional genetic modifiers

Foods that methylate DNA and silence genes are: citrus (hesperidin), apples (phloretin) and tomatoes (lycopene). The following foods do both DNA methylation and histone modifications: turmeric (curcumin), cinnamon (coumaric acid), green tea (EGCG), soybean (genistein), coffee (caffeic acid) and broccoli (isothiocyanates). These three foods only do histone modifications: garlic (allyl mercaptan), grapes, (resveratrol) and cashew nuts (anacardic acid).

Functional foods with regard to obesity and diabetes

Here are a few food items and their effects on your health.

  • The lignans of flaxseed lower LDL cholesterol and total cholesterol.
  • The catechins of green tea prevent obesity, but also obesity-induced type 2 diabetes.
  • Saponins of fenugreek lower lipid peroxidation and increase the antioxidant level.
  • Soy proteins contain phytoestrogen, genistein and daidzein; this lowers cholesterol levels in the blood, prevents lipid peroxidation and also has antioxidant activity.
  • Banaba leaves extract contains corosolic acid and ellagitannins. These substances are able to lower glucose levels in the blood. It also has an anti-obesity effect.
  • Grapes and related products contain anthocyanin, flavan-3-ols and flavonols. They have blood pressure lowering qualities, lower blood fat levels and prevent hardening of the arteries.
  • Dark chocolate contains flavanols that are the main type of flavonoid found in it. Flavanols decrease blood pressure and make platelets in the blood less sticky. This prevents heart attacks and strokes. In addition these flavanols also decrease LDL cholesterol, which prevents hardening of the arteries.

Here are more items that help your health

  • Red wine, berries, pears, and apples: proanthocyanidins are the active polyphenols that make all of these fruit valuable. Proanthocyanidins prevent LDL cholesterol from oxidizing through their antioxidant effects, which in turn slows down hardening of the arteries. It reduces the inflammation associated with narrowing of blood vessels and normalizes the lining of arteries.
  • Onions contain two active ingredients, allyl propyl disulfide (which makes you cry when you cut onions) and S-methyl-cysteine sulfoxide. These substances have anti-diabetic effects and lower blood fatty substances.
  • Turmeric contains curcumin, which possesses antidiabetic properties.
  • Fruit and vegetables contain fiber, which lowers blood sugars and hemoglobin A1C.
  • Stevia from the stevia plant reduces blood sugars following a meal in patients with type 2 diabetes.

In summary, all these substances are examples of triggering epigenetic mechanisms to interfere with the expression of negative health problems where inheritance may also play a role.

Genetic Switches To Treat Obesity And Diabetes

Genetic Switches To Treat Obesity And Diabetes

Conclusion

This was a whirlwind review of how a healthy diet, supplements, fruit and vegetables, exercise and other healthy lifestyles can overcome genetic and epigenetic traits. After reading about this huge line-up of substances that can contribute to your health, you may feel slightly overwhelmed. Are you going to get all these wonderful items from the health food store and live on a bunch of supplements? Of course this is not the fact! Some herbals can be extremely helpful to combat inflammation, such as curcumin.

The essential facts of treatment of obesity and diabetes

But the most essential fact remains very simple: to cut down sugar and too many starchy foods, as they will trigger repressed genes to cause diabetes, obesity, heart attacks and strokes. We need to inform ourselves and stay vigilant to the fact how toxic foods may be, and we have to cut them out in order to stay healthy. We can become much more resilient to health challenges than we may have thought possible.

Aug
10
2013

Bioidentical Hormone Replacement

In many previous blogs I have mentioned that bioidentical hormone replacement prolongs life. Here is a more detailed look at what such hormone replacement looks like for both women and men. Before I get into details I want to stress that I am talking about replacing what is missing and replacing only with natural hormones, not some artificial hormone derivative produced by a drug company. The reason this is immensely important is that hormone receptors in the body are distributed all over our vital organs including bones, blood vessels and the nervous system. If there is no lock and key fit (bio-identical hormone fitting the hormone receptor), there is trouble as the Women’s Health Initiative in 2002 has shown. Unfortunately they had used synthetic hormones for HRT that were not fitting the hormone receptors, and this caused many problems (heart attacks, strokes, osteoporosis, cancer).

Physiology of aging

As we age, we gradually produce fewer hormones in our hormone glands, but the various hormone glands deteriorate in their functions at different rates. Beyond the age of 30 we produce less melatonin and less growth hormone. As a result our sleep pattern may change, as melatonin is necessary for a deep sleep. The decreasing growth hormone production means that we are losing some of our muscle mass and accumulate more fat in the subcutaneous tissues. Our adrenal glands produce less DHEA at the age of 35 to 40, a hormone that is a precursor to our sex hormones in males and females. The gonads (testicles and ovaries) also produce fewer hormones, a process which already starts 5 years before menopause and about 5 years before andropause (the male menopause equivalent).

Typically a woman will get into menopause at the age of 45 to 55 at which time the periods stop and postmenopausal symptoms are interfering with her well-being.  Men get into andropause (the male equivalent of menopause) at the age of 55 to 65 at which time erectile dysfunction occurs and often the individual will become the “grumpy old man”.

Other hormones such as thyroid hormones are also affected by the slow down. Hypothyroidism is common in people above the age of 50.

Bioidentical Hormone Replacement

Bioidentical Hormone Replacement

Baseline laboratory tests

In order to know what is going on, the physician or naturopath needs to order a number of tests to assess whether there is inflammation, how your key hormone levels are; the cardiovascular system markers should also be checked, the liver enzymes and vitamin D3 level. Inflammatory markers are fasting insulin levels and C-reactive protein (CRP). Fasting cholesterol and subfractions (HDL, LDL, VDLP, small LDL) and fasting triglycerides are also measured. Thyroid hormones (T3 and T4, TSH) are measured to rule out over or under function. Typically hypothyroidism is found, which would have to be rectified by taking Armour (a mix of T3 and T4 thyroid hormones).

At this point I need to explain that long time ago the research by Dr. Lee has shown that progesterone hormone levels are notoriously unreliable when blood tests are done. All of the other sex hormones, and cortisol are also not that reliable with blood tests. For this reason the saliva hormone tests have been invented that conveniently report a panel of 5 hormones from one saliva sample: DHEAS (which is the storage form of DHEA), estradiol (the major estrogen in a woman), progesterone, testosterone and cortisol. The saliva hormone tests correlate very well with the actual tissue hormone levels. You can order the saliva tests through Dr. Lee’s website. Another longstanding lab in the US is Dr. David Zava’s lab. In Canada the Rocky Mountain Analytical Lab can process your saliva tests.

Women’s hormone replacement

Let us assume that a woman is getting postmenopausal symptoms and bioidentical hormone replacement is being discussed. The physician will want to first rule out that insulin resistance is not present by ordering a fasting insulin level. If this is normal and the other baseline tests are normal as well except for missing estrogen and progesterone, the physician will usually start to replace progesterone first using a bioidentical hormone cream to be applied once or twice per day. If estrogen levels were also low, the next step in 4 weeks or so is to add Bi-Est, a bioidentical estrogen replacement cream. After 8 weeks of hormone replacement the saliva hormone test is repeated to see whether the estrogen and progesterone levels have come up and also, whether the ratio of progesterone to estrogen is at least 200 or more. Dr. Lee has extensively researched this and found that women with a ratio of less than 200 to 1 (progesterone/estrogen ratio) were more prone to breast cancer. He also stated in this link that there are 3 basic rules with regard to bioidentical hormone replacement:

1. only replace hormones, when they were measured to be low.

2. use only bioidentical hormones (never synthetic hormones) and

3. only replace with low doses of bioidentical hormones to bring hormone levels to physiological levels (body levels that were experienced to be normal before).

Many women who are not replaced in menopause have estrogen dominance meaning that the progesterone/estrogen ratio is less than 200:1, which puts these women at risk of developing breast cancer. Women who are overweight or obese also are estrogen dominant (from estrogen produced in excess through aromatase in the fatty tissue, explained further below), which makes them more prone to breast cancer, uterine cancer and colon cancer. Without bioidentical hormone replacement inflammatory processes take place in the joints (causing arthritis), in the nervous system (causing Alzheimer’s and dementia) and in the blood vessels (causing heart attacks and strokes). Rebalancing your hormones to a youthful state by paying attention to the hormone levels and the hormone ratios mentioned will remove the inflammatory reactions and reduce the risk for cancer.

Men’s hormone replacement

Males enter andropause 10 to 15 years later than women are entering menopause. Typically testosterone production slows down leading to hair loss, erectile dysfunction, loss of muscle mass, osteoporosis and Alzheimer’s/dementia. Blood tests (bioavailable testosterone) or saliva tests are both reliable in determining a deficiency. Replacement with bioidentical hormone creams once per day is the preferred method of treatment. Overweight and obese men produce significant amounts of estrogen through an enzyme localized in fatty tissue, called aromatase.

Aromatase converts testosterone and other male type hormones, called androgens, into estrogen. Estrogen causes breast growth, weakens muscles, and leads to abdominal fat accumulation, heart disease and strokes.

Similar to women, where the progesterone/estrogen ratio is important, there is another ratio for men, called testosterone/estrogen ratio. This should be in the 20 to 40 range for a man to feel good and energetic. Unfortunately many men above the age of 55 have testosterone/estrogen ratios much smaller than 20. This makes them more prone to heart disease and prostate cancer (Ref.1).

However, a male also does need a small amount of estrogen and normal thyroid hormones as well as all of the other hormones for his “hormonal symphony” (mentioned in Ref. 2) to function at his best.

Safety of hormone replacement

There are still otherwise reputable websites that state that bioidentical hormones are not safer than standard synthetic hormones. This confuses the consumer and does not serve the public well. I much prefer the text of the Wikipedia, which is a more thorough review regarding safety of hormone replacement and explains what the issues are.

In the US there is a collective experience of about 25 years on thousands of patients, but there have not been any randomized studies, as Big Pharma that would have the money to finance such studies is not interested in proving that bioidentical drugs would be safer than their distorted synthetic hormone copies that will not fit the body’s hormone receptors. There are some noble exceptions as Big Pharma is producing bioidentical insulin and human growth hormone that had toxicity studies done and showed safety. In Europe bioidentical hormones have been used since the 1960’s, on a larger scale since the 1970’s. So the European experience of safety of bioidentical hormones is presently about 40 to 50 years.

The FDA is contributing to the confusion of the public as can be seen from this publication. One example where the FDA is confusing the consumer, is the progesterone product Prometrium, a bioidentical micronized progesterone capsule that can be taken by mouth. By law the manufacturer had to put a warning label on the package identical to progestin, which is the synthetic, non-bioidentical hormone having been shown to have severe side effects. As is explained in this last publication Prometrium should not have been required to have a warning label in it ; the paper explains what I have already stated above, namely that bioidentical hormones are the safest form of hormone replacement and administered in the right ratios will actually prevent cancer and prevent premature cardiovascular and joint deterioration. In other words, bioidentical hormone replacement can add many years of useful life when started early enough before permanent organ damage sets in from the aging process (which would be due to missing hormones).

Why bother about hormone replacement?

Nature has a plan of “knocking us off” to make room for the next generation. The only way that you can change nature’s plan of killing us prematurely through cardiovascular disease, arthritis, dementia and loss of your sexual life is by bioidentical hormone replacement. Of course you also need the other ingredients of known life prolongers such as healthy (preferably organic) foods, exercise and detoxification. Many women are scared to treat the hormone deficiencies that cause their menopausal symptoms because of the Women’s health Initiative results with synthetic hormones. Men who would benefit from testosterone are often anxious that they may get prostate cancer, when in reality it is the exact opposite: testosterone prevents prostate cancer (Ref.3).

Conclusion

I wrote this blog about bioidentical hormone replacement in order to clarify this often-misunderstood topic. Don’t get confused by the FDA, by highbrow medical websites (such as the likes I mentioned). Big Pharma has a powerful lobby that attempts to keep the medical profession in the belief that their products are better than those that nature has provided (I call it “defend your patent rights”). We are still in a flux state where anybody who tells the truth about hormones gets much criticism. In another few decades it will be an accepted fact and people will wonder why the Women’s Health Initiative was done without a control with bioidentical hormones. With bioidentical hormone replacement you can add about 20 years of youthful life without disabilities to the normal life expectancy. Exercise, detoxification and organic food with avoidance of wheat, starch and sugar can add another 5 to 10 years to your life. The baby boomers are lucky that they have this new tool to prolong life. I wonder whether they will put it to good use.

More information about bioidentical hormone replacement: http://nethealthbook.com/hormones/anti-aging-medicine-women-men/

References:

1. John R. Lee: “Hormone Balance for Men – What your Doctor May Not Tell You About Prostate Health and Natural Hormone Supplementation”, © 2003 by Hormones Etc.

2. Suzanne Somers: “Breakthrough” Eight Steps to Wellness– Life-altering Secrets from Today’s Cutting-edge Doctors”, Crown Publishers, 2008

3. Abraham Morgentaler, MD “Testosterone for Life – Recharge your vitality, sex drive, muscle mass and overall health”, McGraw-Hill, 2008

Last edited Nov. 7, 2014

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Sep
01
2003

Poor Lungs And Heart Attacks Related To Leptin Levels

It is known from the medical literature that poor lung function can often lead to heart attacks making it one of the important causes of premature death for patients with poor lungs (due to emphysema, chronic bronchitis, COPD etc.).

A research team led by Dr. Don Sin from the University of Alberta, Edmonton, Canada, asked the question recently whether there may be a circulating factor that would be responsible for this association of poor lung function and increased cardiovascular disease.

They studied serum leptin and a variety of other inflammatory markers such as C reactive protein, leukocytes, and fibrinogen in 2808 participants in the Third National Health, Nutrition, and Examination Survey. Apart from blood tests they also measured lung function by spirometry (forced expiratory volume in 1 second, called FEV1). The leptin levels found in these patients were then divided into 5 groups from low to high levels. They also carefully adjusted the data for body mass index, sex, age and other factors. They compared the group with the lowest leptin concentration (lowest quintile) with the highest group of leptin concentration (highest quintile) and looked for any significant differences in any of the markers.

Results: The highest quintile group (high leptin in blood samples) had also the highest other inflammatory markers in their blood (C-reactive protein, leukocytes and fibrinogen). This group was the one that was associated with advanced lung diseases as well as heart disease. The authors of this study, which was recently published in a medical journal (Thorax 2003;58:695-698), concluded that leptin plays an important role, if not the major role, in the development of both chronic lung disease and cardiovascular complications.

Poor Lungs And Heart Attacks Related To Leptin Levels

Poor Lungs And Heart Attacks Related To Leptin Levels

Links to lung disease: http://www.nethealthbook.com/articles/chronicobstructivepulmonarydisease.php
Links to heart attacks:

http://www.nethealthbook.com/articles/cardiovasculardisease_heartdisease.php

Last edited December 9, 2012