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Cancer and Insulin Resistance

January 7, 2015
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Cancer and Insulin resistance ,recent research is showing a strong correlation between the two.

The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following:
  
  • Central obesity: waist circumference ≥ 94 cm (male), ≥ 80 cm (female) 
  • Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia 
  • Hypertension: blood pressure ≥ 140/90 mmHg or antihypertensive medication 
  • Fasting plasma glucose ≥ 6.1 mmol/L 
  • The US National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following: 
  • Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 36 inches(female) 
  • Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl) 
  • Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) 
  • Blood pressure ≥ 130/85 mmHg 
  • Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl)

Body Mass Index (BMI)


There is confusion as to whether, in 2004, the AHA/NHLBI intended to create another set of guidelines or simply update the NCEP ATP III definition. According to Scott Grundy, University of Texas Southwestern Medical School, Dallas, Texas, the intent was just to update the NCEP ATP III definition and not create a new definition.

Elevated waist circumference:
  
  • Men — greater than 40 inches (102 cm)
  • Women — greater than 35 inches (88 cm)
  • Elevated triglycerides: Equal to or greater than 150 mg/dL (1.7 mmol/L)
  • Reduced HDL ("good") cholesterol:
  • Men — Less than 40 mg/dL (1.03 mmol/L)
  • Women — Less than 50 mg/dL (1.29 mmol/L)
  • Elevated blood pressure: Equal to or greater than 130/85 mm Hg or use of medication for hypertension
  • Elevated fasting glucose: Equal to or greater than 100 mg/dL (5.6 mmol/L) or use of medication for hyperglycemia

C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease in correlation with serum markers that indicated lipid and glucose metabolism.[9]

Background of Metabolic Syndrome


The term "metabolic syndrome" dates back to over 60 years and came into common usage in the late 1970s to describe various associations of risk factors with diabetes that had been noted as early as the 1920s.

The Causes of Metabolic Problems are as Complex as Cancer


The exact mechanisms of the complex pathways of metabolic syndrome are not yet completely known. The metabolic pathways are extremely complex and have been only partially elucidated. Most patients are older, obese, sedentary, and have a degree of insulin resistance. Stress can also be a contributing factor. Cortisol comes from stress as do the other stress hormones which affect glucose levels and metabolism. Toxic cellular stress, endocrine disruptive substances, chemical imbalances also play a roll along with other important factors such as  weight, genetics, endocrine disorders (such as polycystic ovary syndrome in women of reproductive age), aging, and sedentary lifestyle, (i.e., low physical activity and excess caloric intake).

There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome. I believe there are more far-reaching metabolic problems that are not being recognized or yet to be tested for in clinical practice. A number of markers of systemic inflammation, including C-reactive protein, are often increased, as are fibrinogen, interleukin 6, tumor necrosis factor-alpha (TNFα), and others. Some have pointed to a variety of causes, including increased uric acid levels caused by dietary fructose.

Biomarkers Tell the Story of Metabolic Problems


It is common for there to be a development of fat, especially around the abdomen and after the fat cells increase plasma levels of a biomarker called TNFα, then there is altered levels of a number of other biomarkers of metabolic problems called adiponectin, resistin, and PAI-1.

Tnfα is Related to Insulin Resistance


TNFα has been shown not only to cause the production of inflammatory cytokines, but also possibly to trigger cell signaling by interaction with a TNFα receptor that may lead to insulin resistance. 

An experiment with rats fed a diet with 33% sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance.[28] The progression from visceral fat to increased TNFα to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells present within, which play a role in inflammation.

I believe inflammation contributes to an increased risk of cancer, hypertension, artherosclerosis and diabetes.

Risk Factors Promote a Negative Domino effect that can lead to cancer predisposition


Recent research indicates prolonged stress can be an underlying cause of metabolic syndrome by upsetting the hormonal balance of the hypothalamic-pituitary-adrenal axis that causes high cortisol levels to circulate, which results in a domino effect with an increase in glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing diseases and even osteoporosis. This is a cycle that works like a perpetual motion machine. I have been working on ways to test, treat, and prevent this cycle. Psychosocial stress is also linked to heart disease and may contribute to others via an adverse metabolic pathway towards cancer.

Central or Abdominal Obesity


Central obesity is a key feature of the syndrome, reflecting the fact that the syndrome's prevalence is driven by the strong relationship between waist circumference and increasing adiposity. However, despite the importance of obesity, patients who are of normal weight may also be insulin-resistant and have the syndrome.

Lifestyle


Physical inactivity is a predictor of CVD events and related mortality. Many components of metabolic syndrome are associated with a sedentary lifestyle, including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome.

Cancer and Aging due to Metabolic Problems


Metabolic syndrome affects 44% of the U.S. population older than age 50.  The percentage of women having the syndrome is higher than that of men. The age dependency of the syndrome's prevalence is seen in most populations around the world and some populations may be more sensitive (such as in Mexico or India).


The approximate prevalence of the metabolic syndrome in patients with coronary heart disease (CHD) is 50%, with a prevalence of 37% in patients with premature coronary artery disease (age 45), particularly in women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced.[34]

Fat disorders in general are associated with metabolic syndrome. Both genetic (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan familial partial lipodystrophy) and acquired (e.g., HIV-related lipodystrophy in patients treated with highly active antiretroviral therapy) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndrome's components.

Prevention of the Underlying Conditions that Cause Cancer


Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day),[41] and a healthy, reduced calorie diet.[42] Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily due to a lack of compliance with lifestyle and diet changes.[23] The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.[43]

A 2007 study of 2,375 male subjects over 20 years suggested the daily intake of a pint (~568 ml) of milk or equivalent dairy products more than halved the risk of metabolic syndrome.[44] Some subsequent studies support the authors' findings, while others dispute them.[45]

Therapy

The first line treatment is change of lifestyle (e.g., Dietary Guidelines for Americans and physical activity). However, if in three to six months of efforts at remedying risk factors prove insufficient, then drug treatment is frequently required. Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Cholesterol drugs may be used to lower LDL cholesterol and triglyceride levels, if they are elevated, and to raise HDL levels if they are low. Use of drugs that decrease insulin resistance, e.g., metformin and thiazolidinediones, is controversial; this treatment is not approved by the U.S. Food and Drug Administration.

A 2003 study indicated cardiovascular exercise was therapeutic in approximately 31% of cases. The most probable benefit was to triglyceride levels, with 43% showing improvement; but fasting plasma glucose and insulin resistance of 91% of test subjects did not improve.[23] Many other studies have supported the value of increased physical activity and restricted caloric intake (exercise and diet) to treat metabolic syndrome.

Restricting the overall dietary carbohydrate intake is more effective in reducing the most common symptoms of metabolic syndrome than the more commonly prescribed reduction in dietary fat intake. [46]

Terms and Classification


The clinical value of using "metabolic syndrome" as a diagnosis has come under fire as far as its use of a medical classification. It is asserted that different sets of conflicting and incomplete diagnostic criteria are in existence, and there are factors such as obesity that are important, and that is why I suggest the use of the term “Metabolic Impairment” instead, plus test for it, treat it, study it further. 

Hormonal Imbalance also is involved with Metabolic Syndrome and Cancer in Women


Hormones may play a role in metabolism. For instance, in polycystic ovary syndrome (PCOS) that affects fertility there is a relationship to hormonal imbalance with metabolic syndrome and increased risk of endometrial cancer, ovarian cancer and breast cancer in women.

Proper Ratio of Omegas Help Metabolic Syndrome and Reduce Inflammation that may be Linked to Cancer


Omegas fight against metabolic syndrome according to a study published in Nutrition 2012, titled “Association between interaction and ratio of ω-3 and ω-6 polyunsaturated fatty acid and the metabolic syndrome in adults” by Mirmiran P, et al, to investigate the association of the intakes of ω-3 (including α-linolenic acid [ALA], eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) and ω-6 polyunsaturated fatty acids (PUFAs), the interaction, and the ratio of these PUFAs with the metabolic syndrome (MetS) in adults.

Among the PUFAs, the ALA and ω-6 PUFA intakes were inversely associated with the MetS. Subjects in the highest quartile of ALA and ω-6 fatty acid intakes had a 38% (odds ratio 0.62, 95% confidence interval 0.41-0.95) and a 0.47% (odds ratio 0.53, 95% confidence interval 0.31-0.89) lower prevalence of MetS, respectively, compared with those in the lowest quartile. The dietary ratio of ω-6 to ω-3 fatty acids was not associated with the MetS. When the interaction between ALA and ω-6 fatty acid was assessed, the ALA intake was associated with a lower prevalence of the MetS, without modification by the ω-6 PUFA intake. Subjects with at least the median ALA intake (1084 mg/d) had a lower prevalence of the MetS, irrespective of an ω-6 PUFA intake lower or higher than the median compared with subjects with intakes below the median for both.

The ALA intake was inversely associated with the MetS, irrespective of the background intake of ω-6 PUFAs, in adults.

Chemicals Causing Cell Damage


Comparison of Endocrine Disruptive Chemicals can cause cellular damage and may relate to mitochondrial dysfunction and cancer. This is also related to pathogenesis of type 2 diabetes. Intake of more calories than people need with the availability of cheap fast foods and less exercise with genetic factors adds to the problem.

New evidences suggest exposure to endocrine disrupting chemicals (EDCs) makes body insulin resistant, adding or contributing to obesity with increased risk of cancer, particularly by stimulating fat deposition in abdomen. Phenotypes of MS, high levels of blood glucose, insulin, and lipids along with high blood pressure are regarded as response of body to exposure to EDCs.

Mitochondrial dysfunction can lead to insulin resistance since cells with mitochondria damage become insulin resistant. Environmental toxins, particularly organic pollutants affect mitochondrial function and induce insulin resistance. Effects on fetus and intergeneration are linked to mitochondrial dysfunction which in turn increases risk of cancer or aggravation of cancer pathogenesis.

Diet for Diabetes and Prediabetes


The diet for Diabetes and Prediabetes should also be an anti-disease diet.  This may consist of choosing health organic based foods that are more medicinal, less toxic, more alkaline, and more therapeutic.  In the near future there will be new ways to evaluate the effects of diet and lifestyles that can be based on individualized testing. 

I have been doing research on this a part of a anti-diabetes, anti-cancer, and an anti-disease diet and protocol.  This may include a diet high in balanced and stabilized essentially fatty acids, certain nutraceuticals, low glycemic foods, low protein diet based on individual abilities to metabolize and disease state, foods high in vegetables, low in protein from anything with a face (animal) on it, high in proteins from vegetables, and organic foods. These foods have higher levels of antioxidants. I suggest the avoidance of dairy and beef that have growth hormone, brief with prions, chemicals, or antibiotics attached. A healthy diet includes drinking 6 to 8 glasses of isotonic or alkaline fluids or water.  It is a good idea to include Vitamin D, calcium, magnesium, potassium, and other foods based on body mass index, Wellness Index, Cancer Risk Index, body habitus, history, lifestyle, chemical and metabolic states. I am working on tests with an individualized computer analysis to assist with a diet and exercise program.

There are many different diets and many books on diets. There are also many studies done on nutrition.   Here are some things that I have learned from research and experience.

Dietary Suggestions to Improve Metabolic Balance
  
  1. Reduce the total number of calories each day. Overuse or excess of any food group does not allow for chemical balance.
  
  1. Reduce or eliminate protein from animals. Protein from plants is 400 percent more alkaline and if organic, there are much less toxic chemicals. If animal meat is used, limit the amount, beef and diary should be grass fed, and fish should be free of heavy metals and dioxin (wild trout, salmon). Avoid bottom feeders (crab, tuna, shrimp, etc.).
  
  1. For those people with disease, consider reduction of protein to 5 to 10 percent of the total daily calorie count. I have found this to be true in those with cancer, arthritis, and some other diseases.  Protein is very acidic. 
  
  1. Vitamin D, calcium, and magnesium help with healthy metabolic pathways with many studies demonstrating medical benefits.
  
  1. Organic foods are preferred.  There are many studies on this subject and I predict that the importance of organic diets will continue to be demonstrated.
  
  1. Avoid transfats, GMO foods, and corn syrup.  Studies show that since the introduction of corn syrup and transfats that diabetes, heart disease, and obesity has incident has risen dramatically. This is not just for control of blood sugars, this is important for avoid metabolic problems.
  
  1. Salads, beans, lintels, hemp products, sprouts, various vegetables, seaweeds, and algae are excellent sources of antioxidants, minerals, vitamins and other nutrients.
  
  1. Diet plus exercise are key to a healthy lifestyle.

Nutritional Support against Metabolic Problems to Prevent Cancer


Nutrition is vital because the foods we eat create the cellular chemistry of the body. Our internal environment can support the growth of or fight against disease. The pH of our body is regulated in part by diet. The pH is an important measurement referring to the level of acidity or alkalinity of a substance. Metabolic impairment has a more acidic environment, which is conducive to an environment favoring bacteria, fungi, and viruses around tumors releasing cancer promoting growth factors.

The predominant American diet of processed foods, meat, white flour and sugar, refined carbohydrates, transfats, non-organic foods with too many chemicals, and too few vegetables increases acidity and inflammation in the body. Instead, I recommend an alkaline diet with a high amount of vegetables, fruits, seeds, and lentils.

A healthy metabolic diet should also include tomatoes or tomato sauce, garlic, shitake and Maitake mushrooms, fiber, fish, pumpkin seeds, and green tea. Also, eating organic foods is better in the long run. Non-organic foods contain many different pesticides that have a cumulative effect in the body causing cell damage and other harmful conditions.

Environmental factors and use of antioxidants

There are huge amounts of toxins contaminating our water, soil, and air. Some examples are organophosphates, hydrocarbons like benzene and other chemicals like phthalates, a widely used industrial compound in plastics, perfumes, hairsprays, lubricants, wood finishers, and other materials. Phthalates have been associated with cancer, adult infertility, male reproductive development, and other devastating conditions. Unfortunately, today’s water supply contains an elevated level of phthalates that impacts our drinking water, not to mention fish and other animals in our lakes and streams. As a result, only mineral or filtered water should be consumed, and in glass, not plastic. Water with fluoride should not be used since fluoride competes with selenium, an important mineral associated with the prevention of prostate and other types of cancer. Again, cancer prevention involves many factors. Taking antioxidants in the food we eat and in supplements may help with the oxidative stress to our cells. 

There are many potential foods and food extracts that have potential for use in human health.  If you have suggestions and information on these and wish to get updates on this subject, please go to www.cancer.im.

Here is some information I have found about nutrients, food processing, and food extracts to help with inflammation and topics that need further research:
  1. Diet: Ingest less food overall, fewer calories or exercise more so that you maintain a healthy weight.
  2. Go organic: studies have shown better survival in those who avoid toxic chemicals found in non-organic foods.
  3. Fat: Limit the amount and kind of fat you get from red meat and dairy products.
  4. Fish and foods with omega 3: evidence from several studies suggest that fish can help protect against prostate cancer because they have "good fat" particularly omega-3 fatty acids. Avoid trans fatty acids (found in many foods that are processed and in margarine).
  5. Try to incorporate cooking with olive oil, and cruciferous vegetables (like broccoli and cauliflower) into many of your weekly meals.  Green tea is also potential food that may be helpful.
  6. Avoid smoking due to carcinogens. Avoid alcohol if at all.
  7. Avoid Stress: seek medical treatment for stress, high blood pressure, high cholesterol, and depression. Treating these conditions may save your life and will improve your survivorship with prostate cancer
  8. Supplements: Research this important topic, avoid over-supplementation with megavitamins. Follow a healthy diet with lots of fruits, vegetables, whole grains, fish, and healthy oils.
  9. Avoid stress:  reducing stress in the workplace and home will improve your survivorship and lead to a longer, happier life.

Fried Foods

The researchers found that men who ate French fries, fried chicken, fried fish and/or doughnuts at least weekly had an increased risk of prostate cancer that ranged from 30 to 37 percent.
Weekly consumption of these foods was associated also with a slightly greater risk of more aggressive prostate cancer. The researchers controlled for factors such as age, race, family history of prostate cancer, body-mass index and cancer screening history when calculating the association between eating deep-fried foods and prostate cancer risk.

Stress and metabolic impairment


Stress increases cortisone levels and stress hormones that are linked to a higher risk of disease.  A healthy game plan should aim to reduce the amount of stress. Meditation, rest, yoga, and other methods of stress reduction can improve the body’s chemical balance.



Good fats and bad fats


Transfats, broken fats, partially hydrogenated fats are all very unhealthy and toxic fats.   Transfats for example, block the conversion of omega-9 fats to the much needed omega 3 fatty acids which is lacking in the American diet.  There is an excess of omega 6.  More omega 3 fatty acids are needed for their antioxidant and anti-inflammatory benefits.

Lipids

                
Lipids are fats and made up of different substances such as triglycerides, phospholipids, sterols, and lipoproteins.

Triglycerides


                Making up more than 95% of our body fat.
Triglycerides are made of 3 fatty acids and glycerol. When the end of a fatty acid chain of car=bon atoms join a triglyceride, they are called “fats.” Triglycerides may contain saturated or unsaturated trans-fatty acids.

Fatty acids


Arrangement of Fatty Acids

The pattern of the fatty acids effect the characteristics of the fat, such as melting point.

Three Categories of Fatty Acids

                Saturated
                Monounsaturated
                Polyunsaturated

Fatty acids can contain as many as 35 carbon atoms. There are over 500 kinds of fatty acids.

The number of carbon atoms, and the arrangement of hydrogen atoms is what make different kinds of fatty acids. Fatty acids become saturated when bonding with hydrogen atoms.

Examples of fatty acids are; acetic acid, capric acid, caproic acid, arachnic acid, lignoceric acid, behenic acid, palmitic acid, lauric acid, and stearic acid. The link of the carbon atom chain determines the absorbability and characteristics. Too much ingestion of long chain fatty acids, can lead to blood clotting disorders, heart disease and diabetes.

Monounsaturated Fats


These fats are missing their hydrogen partners, unlike the saturated fats that bond with hydrogen atoms. These are more healthy than saturated fats because the do not increase LDL “bad” lipid profiles. The do not reduce the HDL “good” cholesterol.

Polyunsaturated Fats


The examples include the omega 3 (Alpha-linolenic acid), omega 6 (linoleic acid and Arachidonic acid), EPA, and DHA.

Diabetics and Triglycerides


                The regimen for control of elevated triglyceride levels is to reduce saturated fats, alcohol, and refined sugars. After dietary ingestion of triglycerides, the normal individual will process and clear triglycerides after several hours. With diabetes, elevated triglycerides can still be circulating all night after fasting.
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