The Nutrition Consultation in Age Management Medicine

The leading causes of death in America are heart disease, cancer, stroke, lung disease, injuries, diabetes, flu and pneumonia. Of these, heart disease, cancer, stroke and diabetes are all modifiable with dietary and lifestyle intervention. Slide 1

The goals in age management medicine to enhance vitality, vigor and health through proper diet, nutritional supplementation, exercise and hormone optimization. The following slide is a curve of the average American: age is on the X-axis; quality of life and health are on the Y-axis. Around ages 40 to 45, quality of life and health peak out. From that point on, they slowly decline until we die. Age management medicine is all about rectangularizing that curve, so quality of life and health remain optimal until just before we die. Slide 2

There are obvious advantages to this, but a hidden advantage also exists: There will continue to be medical breakthroughs, which can increase longevity. If we are on the declining slope of this curve prior to entering a nursing home, we really aren’t physically able to take advantage of these breakthroughs—and probably wouldn’t want to. But if we can maintain health and a high quality of life, then we would be physically able to take advantage of these medical breakthroughs, welcoming an opportunity to add another 10 or 15 years to our life.

Cardiovascular Disease

Cardiovascular disease claims more lives each year than the next 5 leading causes of death combined, costing Americans $351.8 billion in 2003 alone. Approximately 105 million American adults have a blood cholesterol level equal or greater than 200 mg/dl. (1) Consider that 61.8 million Americans have cardiovascular disease; of these, 13 million have coronary artery disease, resulting in 2,000 deaths in the United States daily. Also, 1 in 2.4 women die from cardiovascular disease, compared to 1 in 29 from breast cancer. If we could eliminate all major forms of cardiovascular disease, we could add 7 years to our life expectancy. Slide 3

Clearly, as Galen said, “Prevention is better than cure.”

Healthy Endothelium: The primary role of the endothelium is to maintain vascular tone, accomplished by different dilators and constrictors. The major vasodilators that are endothelium-derived include nitric oxide and Prostacylin (PC). Prostacylin works synergistically with nitric oxide to inhibit platelet aggravation. Bradykinin stimulates nitric oxide and Prostacylin and endothelium-derived hyperpolarizing factor. It also stimulates tissue plasminogen activator (fibrinolysis).

The most potent endothelium-derived vasoconstrictor is endothelin. Angiotensin II stimulates the production of endothelin, and it is a pro-oxidant. Both angiotensin II and endothelin promote smooth muscle cell proliferation and contribute to plaque formation.

Functions of nitric oxide: Nitric oxide mediates endothelium-dependent vasodilation. It inhibits platelet adherence and aggregation as well as inhibits proliferation of smooth muscle cells. It prevents oxidative modification of LDL cholesterol. When nitric oxide production is impaired, it promotes atherosclerosis. Vasoconstriction, platelet aggregation, smooth muscle cell proliferation and migration, leukocyte adhesion and oxidative stress are all accelerated as nitric oxide levels are diminished. Slide 4 Therefore, the mechanisms for reducing endothelial and nitric oxide availability and increasing endothelial dysfunction are all promoted by hypercholesterolemia, hypertension, diabetes and smoking. These all produce reactive oxygen species, which in turn inhibit the production of the enzyme DDAH, resulting in increased levels of nitric oxide synthase inhibitor—resulting in decreased endothelial nitric oxide availability. (2)(3)

Reactive oxygen species also reacts with nitric oxide, causing a loss of nitric acid bioactivity. Reactive oxygen species also cause oxidative degradation of H4B, which is a critical nitric oxide synthase cofactor. That results in decreased endothelial nitric oxide availability, which increases endothelial dysfunction.

The oxidation of LDL in the vessel wall hastens the atherogenic process by recruiting macrophages, stimulating auto antibodies, increasing LDL uptake and increasing vascular tone and coagulability. Supplementation with antioxidants may act to inhibit this oxidation, retarding, or even preventing, the formation of atherosclerotic plaque. (4)

Lipids & Cardiovascular Disease

LDL cholesterol is a major cholesterol carrier in the blood. LDL cholesterol promotes atherosclerosis and is influenced by genetics, high-saturated fatty acid diets and inactivity. Secondary causes include diabetes, hypothyroidism, obstructive liver disease, chronic renal failure and certain drugs.

HDL cholesterol carries cholesterol away from the arteries. HDL cholesterol removes excess cholesterol from atherosclerotic plaque and has antioxidant and anti-inflammatory properties. It is influenced by genetics, insulin resistance, high triglyceride levels, overweight and obesity, inactivity, cigarette smoking, high-carbohydrate diets and certain drugs like beta-blockers, anabolic steroids and progestational agents.

Triglycerides are obtained from the blood and also made by the liver. They are transported through the blood on either chylomicrons or VLDL. Triglycerides are influenced by genetics, obesity, insulin resistance, inactivity, smoking, high-carbohydrate diets and diseases, such as Type 2 diabetes, chronic renal failure and nephrotic syndrome, excess alcohol and certain drugs, including corticosteroids, oral estrogen and retinoids.

LDL cholesterol is the primary atherogenic factor. Trial after trial has shown that lowering LDL drives down cardiac events. Low HDL remains an important independent risk factor for cardiac events. The Air Force/Texas Coronary Atherosclerosis Prevention Study (5) (6)showed that aggressive statin therapy is an appropriate treatment for low HDL syndrome. Triglycerides are a secondary risk factor in coronary artery disease.

The “Big Four” low-LDL trials are . . .

Heart Protection Trial from Great Britain, published in Lancet in 2002 (7)
Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in MI 22 (PROVE –IT) Trial. The PROVE-IT trial was published in the New England Journal of Medicine in 2004. (8)
“A to Z” Trial. The “A to Z” Trial was published in JAMA in 2004. (9)
Treating to New Targets, published in the New England Journal of Medicine 2005. (10) Slide 5

The bottom line to all these trials is that LDL should be lowered to less than 70 in all patients with recent or remote coronary artery disease. Ultra-low LDL should also be a goal for all diabetic patients and patients with metabolic syndrome.

Can a low cholesterol/saturated fat diet help reduce LDL? The truth is that diet has minimal effect on reducing LDL. Statins must be used as the primary therapy for LDL management with diet as a supplementary factor.

Non-Pharmacologic Ways To Decrease Cholesterol

Reduce saturated fat and completely avoid trans-fat in the diet.
Increase fiber: 25-35 grams of fiber are recommended per day. Good sources of soluble fiber include beans, lentils, apples, citrus fruits, oats, oat bran, apple pectin, barley, peas, carrots and freshly ground flaxseeds. Eating 5 grams of soluble fiber daily has been shown to decrease LDL by 5%.
Increase Omega 3s. A handful of almonds (70 grams) daily can decrease LDL by 8%. You can also get molecularly distilled fish oil.
Substitute and increase soy protein in place of animal protein. One study showed 13% drop in LDL when eating 50% soy, compared to 8% on meat protein only.
Green tea (240 mg to 320 mg of polyphenols) has been associated with lower LDL-cholesterol and lower risk of death from coronary artery disease. Daily recommendation: 4 to5 cups.

Supplements Shown To Decrease Cholesterol

Gugulipid: A resin, used in Ayurvedic medicine. In studies, guggul has lowered total cholesterol by more than 20% while increasing HDL by 36% without dietary adjustments. The active constituent is guggalsterone—which acts to halt bile acid production—leading to a reduction of cholesterol and triglycerides. Dose of 1500 mg, 3 times a day is recommended; the max dose is 6 grams a day.
Red yeast rice (Cholestin in other countries): Contains seven different statins, derived from strains of red yeast, cultivated on rice used for centuries in China. Be sure to check the label to verify the product contains a red rice yeast extract. The brand “Cholestin” by Pharminex was the only one verified in studies to significantly decrease cholesterol, but this was banned from the United States for containing the same compound as Lovastatin.
Arjuna Bark: Used in Ayurvedic medicine and a strong antioxidant. Capsule form. Dose is 1-3 grams per day.
Prickly Pear Extract: A small Italian study in 2003, published in the Nuclear Medicine Review of Central and Eastern Europe, indicated prickly pear extract can lower LDL cholesterol. (11) The supplements used in the study had no affect on levels of HDL or triglycerides.
Ultrameal: A combination product with soy, fiber and plant sterols, shown to reduce LDL by 33% along with a Mediterranean diet.

Anyone taking statins definitely needs to supplement with coenzyme Q10. Statin drugs deplete the body of coenzyme Q10, an essential supplement for providing energy to the body’s cells, especially heart and muscle cells needing more energy. Coenzyme Q10 depletion can result in muscle damage also associated with aches and pains. Since the heart is basically a muscle, it may be damaged as well, which would obviously impair its ability to pump blood and increase the risk of congestive heart failure. Over time statins can weaken the heart and impair its function. Coenzyme Q10 is a powerful antioxidant, shown to be beneficial for heart health by preventing the oxidation of LDL cholesterol and supporting energy metabolism at the cellular level.

Plant sterols, stanols and LDL. The value of sterols and stanols really center around the structural similarities between cholesterol and phytosterols. Phytosterols can displace cholesterol from micells in the process of cholesterol absorption from the gut. This displacement of cholesterol from the micelle decreases cholesterol absorption from the gut by 30% to 50 %. (12)(13) This can significantly decrease serum cholesterol levels in those who regularly consume phytosterols. The addition of 2 grams of sterol ester to a standard Western diet results in a 10% decrease in LDL cholesterol levels without a significant effect on HDL or triglyceride levels. (14) The U.S. National Cholesterol Education Program (NCEP) recommends a dietary phytosterol intake of 2 gm/day. (15) This results in a 10% reduction in LDL cholesterol, inferring a 25% decrease in cardiovascular disease (16). Finally, there seems to be an additive effect with the combination of phytosterols and statins in the LDL-cholesterol-lowering objectives. (17)

Hyperhomocysteinemia and cardiovascular disease. Homocysteine is a substance produced when the body breaks down the amino acid methionine. High levels of homocysteine are inflammatory and injure arterial endothelial cells, which promotes proliferation of arterial smooth muscle cells, vascular inflammation, atherogenesis and destabilization of established plaque. (18) Deficiencies of folic acid, vitamin B6 and B12 are associated with hyperhomocysteinemia. Whether correction of elevated homocysteine levels with vitamins reduces vascular events is currently under investigation. (19) In 1999, the American Heart Association recommended all patients with a family history of cardiovascular disease should exceed the recommended dietary allowance values for folic acid, vitamin B6 and vitamin B12. (20)

Treating hyperhomocysteinemia: At this time, there is no consensus on homocysteine management, regarding B vitamin supplementation. Baseline serum levels of B12 should be checked prior to supplementation to avoid masking a B12 deficiency. Dosages of B6 greater than 500mg/day are not recommended and may cause irreversible nerve damage. (21)

A Side Note About Homocysteine Levels & Sample Handling

Homocystine is released from cells in whole blood left at room temperature. Rapid separation of plasma homocysteine is required for test reliability. The plasma should be cooled on ice immediately, then frozen below -20 °C until time of analysis. (22)

Nutrition & Inflammation Slide 6

Nutrition, it turns out, is a key player in preventing or causing low-grade cellular inflammation. This manifests in the form of weight gain, high glycemic diets, trans-fats, obesity, saturated fats, low monounsaturated fatty acids, low-fiber diet, metabolic syndrome, low omega-3 diets, hyperglycemia and glycation, and high polyunsaturated fatty acid diets.

Inflammation & Dental Health

Periodontal disease may increase the risk of cardiovascular disease by approximately 20%, so the dentist plays a key role in helping control and prevent cardiovascular disease. Other contributors to inflammation in the dental world would be aggressive teeth brushing, aggressive flossing and plaque. The recently marketed counter-rotational and oscillating-rotating electric brushes have shown to reduce levels of gingival bleeding and inflammation.

Visceral Adiposity

The most critical factor in reducing inflammation is loss of adiposity, especially visceral adiposity. We used to think adipose tissue was just dormant—now we know it’s anything but dormant. It is quite metabolically active, producing Interleukin-6, which causes increased C-reactive protein levels. IL-6 is a powerful pro-inflammatory cytokine and is the most important factor in controlling hepatic acute-phase response (hs-CRP). Total body adiposity is the single most important determinant of serum IL-6 concentrations. (23)(24) Adipose tissue also produces Tumor Necrosis Factor Alpha and causes insulin resistance. Slide 7

The obesity problem in America. Today two-thirds of Americans are overweight or obese. Almost one-third of all Americans are obese. The prevalence of overweight people has increased 50% in all populations since 1960. One in four children are overweight. Americans have decreased fat intake from 42% to 34% of total calories since 1960. In spite of that, American children may have a shorter like expectancy than their parents because of obesity-related illnesses. The number one cause of liver disease in America is fatty liver.

How do we assess overweight and obesity? Slide 8 The body mass index is the weight in pounds, divided by height (in inches) and squared x 703. However, the body mass index does not accurately reflect how much body fat an individual has. Estimates of total body fat include skin-fold measurements, bioelectrical impedance, total body conductivity methods, hydrostatic weighing and DEXA scan. Body fat distribution is another way to assess overweight and obesity, which can be done by waist measurement, an inch above the umbilicus. The waist-to-hip ratio also is used, though it isn’t as accurate as waist circumference. The greatest risk for men is a waist-to-hip ratio greater than 1; for women, it is greater than 0.8. (26)(27). Slide 9

This brings us to the metabolic syndrome, which is a huge cause of inflammation.

Metabolic Syndrome

Metabolic syndrome—also known as Syndrome X or Insulin Resistance Syndrome—is a cluster of metabolic risk factors for coronary heart disease and cognitive decline. Features of this syndrome include abdominal obesity, insulin resistance, dyslipidemia, hypertension and elevated levels of cytokines and adhesion molecules . . . in other words, increased inflammation. Slide 10

The risk factors for metabolic syndrome include men whose waist is greater than 40 inches (measured an inch above the umbilicus) and women with waists greater than 35 inches; triglycerides of 150 or greater; HDL-cholesterol (men less than 40, women less than 50); blood pressure equal to or greater than 130/85; and a fasting blood sugar of 100 or greater. Having any three of these meets the criteria for metabolic syndrome. (28)(29) Slide 11

Visceral fat – central fat or abdominal fat are all associated with the greatest metabolic risk. Metabolic syndrome is present in 23.7% of U.S. adults. And 43.5% of individuals 60 years and older have metabolic syndrome; 30% of obese children have metabolic syndrome. The end result is we now have almost 50 million Americans with metabolic syndrome.

The consequences of metabolic syndrome are horrendous. Individuals with metabolic syndrome experience a six-fold higher rate of cardiovascular events and mortality than the general population.

Published in 1998: Soon metabolic syndrome will overtake cigarette smoking as the number one risk factor for heart disease among the U.S. population. Now, metabolic syndrome has overtaken cigarette smoking as the number one risk factor for heart disease in the United States. (30)

Mechanisms involved in the production of obesity-related low-grade inflammation. Fat tissue is an important source of pro-inflammatory Tumor Necrosis Factor Alpha and Interleukin-6, and anti-inflammation (adiponectin) cytokines. Elevated pro-inflammatory cytokines can lead to insulin resistance by interfering with the anti-inflammatory effects of insulin. Obesity is characterized by oxidative stress; excessive oxidative stress leads to increased production of Reactive oxygen species. Dietary restriction leads to reduction in oxidative stress and inflammation.

Insulin resistance is the key factor in metabolic syndrome, making it so deadly. Insulin resistance is central to the metabolic syndrome and to Type 2 diabetes. Insulin resistance perpetuates the diabetic state and is directly related to adiposity. Omental fat in the intramyocellular compartment plays the key role. An increased ratio of trunk to leg fat is more highly correlated with insulin resistance than is BMI.

Type 2 Diabetes

In the U.S., 17 million people have Type 2 diabetes. Sadly, 5.2 million of them remain undiagnosed—equating to almost a third of all diabetics in this country. If we look at age-adjusted prevalence in people age 20 years or older by race and ethnicity, we find 17.6% of the American Indians and Alaska Natives population are Type 2 diabetic. Additional stats: non-Hispanic blacks, 12.5%; Hispanic and Latino Americans, 11.4%; non-Hispanic whites, 7.7%.

By 2025 (less than 20 years from now), the prevalence is estimated to increase to nearly 22 million or roughly 9% of our population. This is not only a problem in our country, but also worldwide. In 2000, there were 171 million Type 2 diabetics in the world; by 2030, there will be 366 million worldwide.

What are the risk factors for Type 2 diabetes? The first one is age (45 years old or older), being overweight (BMI of 25 or greater), having metabolic syndrome, a family history of diabetes, habitual physical inactivity, race and ethnicity, previously identified abnormal fasting blood sugar of 100 or greater or an abnormal glucose tolerance test, a history of gestational diabetes or delivering a baby weighing 9 pounds or more, hypertension 140/90 or higher, an HDL of less than 35 and/or a triglycerides of 250 or greater, polycystic ovary syndrome and a history of vascular disease.

We used to call Type 2 diabetes adult-onset, but we can no longer do that because we now have an epidemic of Type 2 diabetes in children and adolescents in this country. The youngest Type 2 diabetic in the U.S. is 4 years old. Type 2 diabetes severely impacts the health of our society. Type 2 diabetics have a 5 to 10 year reduction in their life expectancy—and CVA and MI are increased by 5. Approximately 75% of type 2 diabetics will die of coronary artery disease.

The natural history of Type 2 diabetes starts with adiposity. Slide 12 Adiposity results in insulin resistance, which is the primary defect, then after that the beta cells of the pancreas compensate by increasing insulin production. This ultimately results in beta cell exhaustion, which is the secondary defect. Next is pre-diabetes, followed by full-blown Type 2 diabetes and then, insulin-requiring Type 2 diabetes since the beta cells become completely burned out. This is the absolute insulin deficiency state.

Targeting Inflammation & Insulin Resistance

The Thiazolidinediones (TZD) act directly to reduce insulin resistance. They also appear to improve beta cell function and have anti-inflammatory properties. TZDs have become quite popular in the treatment of Type 2 diabetes and reduce C-reactive protein and MMP-9 (stabilize plaque from rupture). TZDs also suppress two key acute-phase proteins-CRP and serum amyloid A. Finally, TZDs suppress production of pro-inflammatory cytokines.

Metformin is used frequently in this country to treat Type 2 diabetes. The home study entitled “Hyperinsulinemia: The outcome of its metabolic effect” reviews all this. Treatment with metformin for 16 weeks showed a significant improvement in endothelial function, but not in chronic, low-grade inflammation. Metformin decreases plasma levels of VCAM-1, E-selectin, t-PA, PAI-1. C-reactive protein levels were not affected. (31)

As little as a 5% weight loss can significantly reduce fasting blood sugars and insulin levels as well as reduce inflammatory markers. When lifestyle intervention produces a weight loss of 5% to 7%, there is a 58% reduction in the number of cases of Type 2 diabetes over a 4-year period.

Orlistat: Treatment For Obesity

Used for long-term management of obesity, orlistat is a lipase inhibitor with a recommended dose of 120mg t.i.d., 20 minutes prior to each meal. It has pharmacological lipid-lowering effects, improves insulin resistance and decreases body fat and serum leptin levels. Orlistat combined with diet and exercise significantly reduces BMI, waist circumference, HOMA IR, hs-CRP, leptin and increased adiponectin. It significantly reduces risk for diabetes. It also reduces markers of chronic inflammation, so it is anti-atherogenic.

In summary, decreasing body fat results in a decreased LDL, decreased triglycerides, improved insulin sensitivity, reduced total cholesterol, improved HDL and decreased inflammation. Slide 13

How do we get rid of body fat? Firstly, by keeping insulin and glucose levels as low as possible. That is absolutely essential. With elevated insulin levels, people cannot burn body fat for energy. It is physiologically impossible. Exercise (both aerobically and anaerobically) increases metabolic rate and actually can turn people into an energized “fat-burning machine!” Resistance training preserves muscle mass while losing body fat. The more muscle mass people have the more calories they burn at rest. The more aerobically fit people are the more efficient they are at burning body fat for energy.

Dietary Fiber & Inflammation

The NHANES study with 4,900 adults, whose median CRP level was 2.0, showed subjects who ate the most fiber had the lowest CRP levels. CRP was inversely related to the amount of fiber people ate. Also, the more fiber people ate, the more weight they lost. Weight loss equal to or greater than 10% has been associated with the greatest reduction of inflammatory markers of inflammation. (32)

A closer look at fiber content in foods: Many fruits are quite high in fiber, as are vegetables and grains. Legumes (such as green peas, kidney beans, pinto beans and lentils) all have high fiber content, as do nuts and seeds. High-fiber cereals are another easy way to increase fiber intake—although they are a processed food and should be used in moderation to other natural foods. Slide 14 Slide 15 Slide 16

Fats & Inflammation

Classification of fatty acids. Slide17

Saturated fats have no double bonds and are solid at room temperature. The major source of saturated fats comes from animals, including meat and dairy products. Other sources include palm oil and coconut oil. Saturated fats should not exceed 10% of our total caloric intake. Red meat should be limited to once or twice a month. Saturated fats contribute significantly to the inflammatory state.

Unsaturated fats have one or more double bonds and are liquid at room temperature. The unsaturated fats include monounsaturated fatty acids, such as olive oil, canola oil, avocados and nuts.

The polyunsaturated fatty acids fall into three categories:

Omega-3 fatty acids, such as fish oil, flaxseed, walnuts and soybeans. They are anti-thrombotic and anti-inflammatory. Slide18
Omega-6 fatty acids, present in most seeds, vegetable oils (such as corn oil, safflower oil and sunflower oil) and meats. They are pro-thrombotic and pro-inflammatory .
Trans-fats are man-made as well as highly inflammatory and atherogenic. They are formed by the industrial hydrogenation of vegetable oils (i.e. man-made fat). Average consumption in the U.S. is 4% to 7% of total fat calories. Data supports an association between TFA intake and systemic inflammation. Some experts consider TFAs to be the major cause of CAD. The impact of TFAs on human lifespan and degenerative disease is unknown at this time; we will find out in 20 to 30 years. Mensink and Katan in 1990 looked at the effect of trans and saturated fat (10% calories) on blood lipids versus monounsaturated fat. (36) The results are shown in Slide19

Hu, et al in 1997 compared the various fatty acids and their effect on CHD. See Slide20 for the astounding results of this study. (37)

Levels of trans-fats must be on food labels. Dietary sources rich in trans-fats include store-bought cookies, crackers, baked goods, margarine and commercial deep-frying oils as well as the foods cooked in them. Labels may claim to contain “0 grams trans fat,” if they have less than
0.5g per serving. Read labels for partially hydrogenated oil. If they’re present, avoid them! Slide21

Monounsaturated fats are the omega-9 fatty acid group. Monounsaturated fatty acids reduce inflammation. Most of our dietary fat should come from monounsaturated fatty acids or the omega-9s. Olive oil should be the predominant oil consumed to assure a diet high in monounsaturated fatty acids and low in saturated fat. Olive oil (extra virgin) is the preferred most healthy form of olive oil. Canola oil contains healthy omega-9 fats as well as pro-inflammatory omega-6 fats and should be used sparingly. Peanut oil, like canola oil, also contains pro-inflammatory omeg-6 fats and a fair amount of saturated fats—and should be used sparingly. Avocados and almonds, cashews, macadamia nuts, pecans and pistachios are all great sources of omega-9 monounsaturated fatty acids.

Omega-6/Omega-3 ratios: Americans consume large amounts of vegetable oils, which are quite high in omega-6s, such as corn oil, safflower oil, sunflower oil and cottonseed oil. Americans also eat large quantities of meats, obtained from domesticated animals that have been fed grains high in omega-6 fatty acids. Americans also take in very little omega-3 fatty acids. The end result is an omega-6 to omega-3 fatty acids ratio of about 14:1 to 20:1. In the early human diet, it was 1:1. Should this ratio be greater than 10:1, we are put at high risk for inflammation and thrombosis.(33)(34) Slide22