Feb
11
2017

Genetic Switches To Treat Obesity And Diabetes

Dr. Michael Nova gave a talk recently about the role of genetic switches to treat obesity and diabetes. The talk was given 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.

These types of studies have shown that a long life (longevity) has been caused by about 20% from genetics. 80% was contributed by a healthy lifestyle. 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. There are specific inflammatory markers done with blood tests that detect inflammation. 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 head. 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. 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

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. 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. 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

Low carbohydrate diets and the ketogenic diet are helping to reduce weight. Financial stress leads to more cortisol production, which leads to weight gain. An unhealthy bacteria composition in your gut causes you to gain weight, while a good composition of bacteria helps you lose weight. 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. These epigenetic factors have an influence on gene expression, but they don’t change the underlying DNA sequencing.

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

Major metabolic processes in our body cells like phosphorylation, acetylation and methylation can be influenced by nutrition. 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 involved in the development of type 2 diabetes, one of them is the FTO gene that is also involved in the development of obesity. But Dr. Nora projected a slide that showed 14 other genes that can be involved in the development of diabetes. I have elected to not get into all of those details.

What Dr. Nora concluded is the fact that nutrition could play a vital role in preventing these genes from being expressed. 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. Zinc and magnesium are important cofactors in enzymes necessary to prevent diabetes. Vitamin D3 and omega-3 intake are helping to control inflammation and preserve beta cells in the pancreas in diabetes patients.

Nutritional genetic modifiers are

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 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 LDL cholesterol is decreased.
  • Red wine, berries, pears, and apples: proanthocyanidins are the active polyphenols that make all of these fruit valuable. The antioxidant effects of proanthocyanidins prevent LDL to get oxidized, 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 inherited health problems.

Genetic Switches To Treat Obesity And Diabetes

Genetic Switches To Treat Obesity And Diabetes

Conclusion

This was a whirlwind review of how genetic and epigenetic traits can be overcome by a healthy diet, by supplements, fruit and vegetables, exercise and other healthy lifestyles. 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. But the most essential fact remains very simple: to cut down sugar and too many starchy foods, as they will trigger suppressed genes to cause diabetes, obesity, heart attacks and strokes. We need to inform ourselves and stay vigilant to the fact how toxic processed foods are, 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.

Feb
04
2017

Benefits Of The Ketogenic Diet

Dr. Jeff Volek, PhD, RD gave a talk that clarified the benefits of the ketogenic diet. He is a professor at the Department of Human Sciences at The Ohio State University, Columbus, OH, and teaches in the Kinesiology Program. His lecture was part of the 24th Annual World Conference on Anti-Aging Medicine in Las Vegas, Dec. 9 to 11, 2016.

There were 58 slides, some of them very detailed. I will summarize as best as I can what the presentation was all about.

History of diets

Dr. Volek stated that there were unintended consequences when the low fat/ high carb diet was introduced in the 1970’s and 1980’s. Ancel Keys, a physiologist had proposed in his diet heart hypothesis that saturated fat was the culprit that caused heart attacks.

As a result all major health agencies recommended the low fat/high carb diet. Obesity, diabetes, heart attacks, and strokes were the consequences. Another offshoot later from this was the statin craze where everybody was put on statins as high cholesterol was symptomatically treated. Nothing changed the diabetes and obesity wave and heart attacks and strokes continued to kill the affected persons. Among performance athletes the hypothesis was formed that carb loading would increase muscle performance. Researchers showed evidence that carb loading would improve performance. But athletes were dissatisfied with prediabetes and metabolic problems. Both the average consumer as well as the performance athlete noted that they felt better on a low carb/high fat diet. This is what the ketogenic diet is all about.

Diet heart hypothesis

With the diet heart hypothesis the saturated fat was removed from the diet and replaced by vegetable oils rich in linoleic acid. Dr. Volek explained that blood tests and other investigations were done on people who ingested the low saturated fat/high carb diet. The question was whether this would reduce heart attack rates and deaths by lowering serum cholesterol.

The Minnesota Coronary Experiment was a double blind study, which answered this question.

Cholesterol was reduced in the experimental group. But there was no reduction of heart attacks or strokes compared to a control group. Of concern was the large amount of refined carbohydrate content with the low fat diet. This essentially was responsible for the obesity and diabetes wave. The excess sugar turned into fat deposits and to insulin resistance, which caused diabetes. The low saturated fat/high carb diet of the 1960’s to 1990’s did not reduce heart attacks and strokes. To the contrary: the obesity/type 2 diabetes wave it had caused increased mortality from strokes and heart attacks further.

Laboratory tests on low fat/high carb diet versus the ketogenic diet

Forget hypotheses for a moment. Let us review what the different diets do in terms of lab tests. In a study where 40 overweight people with metabolic syndrome were put on a low fat diet or a low carb/ketogenic diet, the following blood test results were found. There were 20 patients in each group.

  1. Low fat/high carb diet

Triglycerides in the blood went down by 20%, saturated fatty acids by 22%. LDL (the bad cholesterol) rose by 4%. Insulin levels went down by 17% and leptin levels also down by 17%. Glucose levels were down by 1%.

  1. Low carb/ketogenic diet

Triglycerides went down by 52%, saturated fatty acids by 57%. LDL (the bad cholesterol) went down by 18%. Insulin levels went down by 49% and leptin levels by 42%. Glucose levels were down by 11%.

In this group of 20 subjects for each group the body mass index went down by 5% for the low fat diet and by 10% for the ketogenic diet after 3 months. The abdominal fat went down in that time by 12% for the low fat diet and by 20% for the ketogenic diet. The conclusion from these laboratory results and from the body measurements is that the low fat diet is showing some results of weight loss, but the ketogenic diet has superior results. The same is true for the blood tests. Only the ketogenic diet showed reduction of 7 key anti-inflammatory markers. In contrast, the low fat diet did not trigger the production of a single anti-inflammatory marker.

Anti-inflammatory benefits of the ketogenic diet

A 2008 study showed that several anti-inflammatory markers were greatly reduced from the ketogenic diet while a low fat diet did not show such a reduction.

As this 2009 study showed the LDL particles were getting bigger under the influence of a ketogenic diet, but they were getting smaller with a low fat diet.

Large LDL particles are also called pattern A particles, while small LDL particles are also called pattern B particles.

As this link shows there is good evidence that small LDL particles oxidize easier and are more atherogenic (causing hardening of the arteries). This means they lead to hardening of the arteries easier translating into heart attacks and strokes down the road. It is one thing that a ketogenic diet leads to larger LDL particles, which are more resistant to oxygenation. But it is another good thing that this diet is also anti-inflammatory. Overall this means that a ketogenic diet is counteracting the development of heart attacks and strokes.

Are saturated fatty acids in the diet causing heart attacks or strokes?

Dr. Volek discussed several large studies that have investigated this question. One of these studies discussed was a metaanalysis from 2010. Like all the other studies it showed that saturated fatty acids do not cause heart attacks and strokes. This is the secret behind the Inuit and the Eskimo diet. It is a high fat and meat diet. Lots of seafood is consumed as well, which provides omega-3 fatty acids.

Dr. Volek pointed out that if you replace a certain percentage, let’s say 5% of saturated fatty acids with carbohydrates, this would cause 7% more heart attacks. He showed literature evidence to back this up. What causes increased heart attacks and strokes is more refined carbs in your diet (sugar and starchy foods!).

Do saturated fatty acids in your blood increase the risk for disease?

Dr. Volek showed several slides with references to various publications. Elevated saturated fatty acids in the blood cause a higher risk of getting a heart attack, heart failure, metabolic syndrome and diabetes. But this does not happen with a ketogenic diet. The values of the saturated fatty acids in the blood are 4% lower when a ketogenic diet is started. With a low carb diet the calories derived from carbs are 12%. In comparison a low fat diet has 56% of carbs. Protein content in the low fat diet is 20%, in the ketogenic diet 28%. Saturated fat content in the low fat diet is 24%, in the ketogenic diet it is 59%. Let’s assume that both diets are kept at 1500 Cal. per day. Then the saturated fat content for the low fat diet is 12 grams and the carbohydrate content is 208 grams. For the ketogenic diet these values are as follows: 36 grams of saturated fat and 45 grams of carbohydrates. Despite a threefold higher saturated fatty acid intake the circulating level of saturated fatty acids in the blood were decreased by 4%.

You are what you eat, but go easy on carbs

Dr. Volek pointed out that what makes you healthy or sick is how many carbs you include in your diet. If you follow a ketogenic diet with only 12% carbs you are much better off than when you follow a diet like the low fat diet with 56% of carbs. The higher the carb percentage in your food, the higher the production of saturated fatty acids in your system and the higher the storage of saturated fatty acids in your body fat. Conversely, the lower the carb percentage in your food is the higher the oxidation of saturated fatty acids will be. In other words the saturated fatty acids disappear from your blood. Also, with a ketogenic diet the storage of saturated fatty acids is lower in your body fat. With a low fat diet your insulin resistance increases, while with a ketogenic diet insulin resistance decreases. The difference in calories in these two diets (56% derived from carbs in a low fat diet versus 12% derived from carbs in a ketogenic diet) explains why the obesity/type 2 diabetes wave has developed and why heart attacks and strokes still top the mortality figures today.

Endurance athletes win medals on a ketogenic diet

Dr. Volek shared a few cases of world-class athletes that are on a ketogenic diet. They did well for themselves winning medals. Tim Olsen won the Western States 100-mile endurance run from Squaw Valley to Auburn, CA in 2012. Zach Bitter was the 100-mile track record holder in 2015. Mike Morton won the American 24-hour distance running record for 172 miles. Two Tour De France bicyclists made first and second place, Chris Froome (first place) and Romain Bardet (second place).

Sports teams also have been successful on a ketogenic diet: the Columbus Crew soccer team; New Zealand national rugby union team, commonly called the All Blacks; the Los Angeles Lakers basketball team are all on ketogenic diets.

Dr. Volek also pointed out that the ketogenic diet has even been tested for the military. A ketogenic diet restores metabolic health, gives the soldiers more endurance, more stress resistance and decreased fatigue.

Benefits Of The Ketogenic Diet

Benefits Of The Ketogenic Diet

Conclusion

A ketogenic diet is on the one end of the carb spectrum with only 10 to 12% of calories derived from carbs. At the other end is the low fat/high carb diet that caused the obesity/diabetes wave. The Mediterranean diet is in the center. The more you are able to cut down the carb percentage in your diet by cutting out sugar and starchy foods, the more your metabolism gets stabilized and this can be measured with blood tests. The ketogenic diet makes you lose weight down to your ideal weight and makes you gain more muscle strength and physical endurance. Sophisticated blood tests have shown that inflammatory markers go down on a ketogenic diet and factors that lead to hardening of arteries also go down. The end result on the ketogenic diet is that the rate of heart attacks and strokes goes down, something which was the original goal of Ancel Keys. It did not work, but it promoted a wave of diabetes and heart disease! Ironically adding saturated fat and other healthy fats while cutting down carbs will achieve disease prevention. This is the opposite of what Ancel Keys had recommended to do and what the processed food industry has mimicked. The ketogenic diet lowers mortality by cutting down heart attacks and strokes. With this knowledge it will finally be possible to get people on a path to better health.

More information about ketogenic diet: https://www.dietdoctor.com/low-carb/keto

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Jan
14
2017

How To Avoid Being Hungry

Dr. Ludwig gave a lecture about how to avoid being hungry at a conference in Las Vegas. The actual topic was “Always Hungry?” I attended the 24th Annual World Congress on Anti-Aging Medicine (Dec. 9-11, 2016) in Las Vegas where this lecture was given. Dr. Ludwig is a Harvard-based endocrinologist who has been researching weight loss methods and obesity for over 20 years. Here is a list of his major publications.

Dr. Ludwig stated that the low fat/high carb diet popular in the1980’s until the early 2000’s was misguided and probably even harmful. The theory at that time was that obesity was caused by too much saturated fat. This has since been proven to be wrong. Instead it has been proven that increased sugar intake is responsible for the obesity wave.

General information about weight gain

The carbohydrate-insulin model states that without insulin you cannot gain weight, because in order to store fat in fatty tissue you need insulin to transport fatty acids across the cell membrane of fat cells.

In this context it is important to note that high glycemic index food increases the blood sugar. This leads to stimulated insulin production, and the liver converts the extra sugar into fatty acids that get deposited as fat in fatty tissue.

The glycemic load from a person’s diet is the single best predictor for a rising blood sugar level. After food intake the blood sugar goes up, glucagon goes up, epinephrine goes up within 4 hours. It is the epinephrine, which after 4 hours makes you hungry again.

The nucleus accumbens is the addiction center. At 4 hours after a high glycemic index milk shake the nucleus accumbens was stimulated in 12 subjects of a double blind trial.

The nucleus accumbens does not work in isolation. It is not only involved in food satisfaction, but also in sexual satisfaction and even plays a role in satisfaction that some people get from playing video games.

Low-carbohydrate, Mediterranean or low-fat diet

In an Israeli study from the New England Journal of Medicine in 2008 investigators were interested to find out which diet was helping people to lose most weight. h

322 moderately obese subjects that were aged 52 years on average were randomized to one of the following diet groups.

They compared

  1. a low fat diet (Atkins type, restricted calorie) with a
  2. Mediterranean diet (low carb, restricted-calorie) and a
  3. Low fat/high carb diet (low fat, non-restricted-calorie)

What was the result? The mean weight losses were: 2.9 kg (low fat group), 4.4 kg (Mediterranean diet group), and 4.7 kg (low fat/high carb group). Of the 272 participants who had completed the intervention after two years of the study the weight loss was 3.3 kg, 4.6 kg, and 5.5 kg in the same sequence as above.

The ratio of total cholesterol to high-density lipoprotein cholesterol, which is a measure for the heart attack risk, was examined next. It was 20% lower from the baseline in group 2 (Mediterranean diet group). The low fat groups (group 1 and 3) were 12% lower from the baseline.

36 subjects had diabetes. There was a clear winner with respect to lower fasting blood sugar and insulin levels, namely the Mediterranean diet (group 2).

The authors concluded that the Mediterranean diet is preferable to low fat diets as they have shown an improvement in lipid profiles and in control of diabetes.

The “POUNDS LOST” study

This was a 2-year study that investigated 4 different lower calorie diets to help people lose weight. Despite the significant difference in diet composition, these 811 free-living overweight or obese adults ages 30-70 from Boston, MA and Baton Rouge, LA lost 16 pounds at 6 months and 9 pounds at the end of two years. The diets were 1) low fat (20%) or 2) high fat (40%) 3) average protein (15%) or 4) high protein (25% of total calories).

The authors concluded that any reduced, calorie-controlled diet would help obese or overweight people to achieve weight loss that lasts. It is interesting that it did not matter whether the diet was low or high in fat, or had low or high protein content. What did matter was that all diets were low in sugar.

Sugar is the driving force

Dr. Ludwig pointed out that without insulin you couldn’t gain weight. High glycemic index food increases blood sugar. The glycemic load is the single best predictor to indicate whether a person will gain weight or lose weight when this food is consumed. It is an irony that in the 1980’s and 1990’s the obesity wave was created by the wrong assumption that a low fat/high carb diet would be heart healthy. We have abundant data available that show otherwise: high sugar content of food brings the calorie count up as everybody can read on the food labels.This will lead to weight increase, which has been abundantly proven. Sugar also stimulates your nucleus accumbens, the food addiction center. As you probably know it is extremely difficult to get out of this food addiction cycle unless you cut out sugar. You even need to go one step further and include many starchy foods that will within 30 minutes of digesting them turn into sugar. Your system makes no difference whether you eat a few teaspoons of sugar or two slices of white bread. The response of your pancreas is insulin, which gladly stores the fatty substances your liver made as fat.

How to get out of the vicious food cycle

As the quoted publications and many other ones have shown, it only matters that you limit your refined carb intake. You can vary the fat content and you can vary the protein content and still lose weight provided you watch the low carb intake. You also need portion control, which is a given! Study glycemic index and glycemic load sites on the Internet. The links I provided are just some examples. The more you educate yourself about carbs, the better for you. Note that many fruit and vegetables belong to the low-glycemic load/index foods. Avoid the high glycemic index foods like dates and cornflakes. Stick to low-glycemic index foods, which are less than 55. With regard to low-glycemic load food the values should be below 10.

The Mediterranean diet is a very desirable diet, which has been proven to be anti-inflammatory.

The zone diet of Barry Sears is also an anti-inflammatory diet and he summarizes this in this link.

How To Avoid Being Hungry

How To Avoid Being Hungry

Conclusion

I have summarized the content of a talk given by Dr. Ludwig. We learnt from this that sugar and refined carbs are the driving force that leads to “feeling hungry”. This stimulates your nucleus accumbens, the food addiction center. Let’s assume that a person is obese or overweight and wants to lose some weight. You need to start by being strict with yourself. Cut out sugar and high-glycemic foods. This will remove the food addiction factor that keeps you going back to the wrong, high calorie foods. You will also consume more low calorie vegetables and fruit, which have more fiber that fills you up. Once you are used to the new way of eating, there is no need to count calories. I recommend that you weigh yourself daily on body composition scales and record the results. This allows you to monitor your body mass index (BMI), your weight, your fat percentage, and your muscle percentage. Typically you will lose 2 to 3 pounds per week on such a low-calorie diet. Later the weight loss will slow down to 1 to 2 weeks per week until you reach your goal. Don’t go lower than a BMI of 21.0 to 22.0 and discuss your goal with your doctor.

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