Nutrition in Age Management Medicine

The goal of Age Management medicine is to enhance vitality, vigor, and health through proper diet, nutritional supplements, 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  (QOL) and health peak out. From that point on, there is a slow decline until death. Age Management Medicine (AMM) is all about rectangularizing that curve, so QOL and health remain optimal until just before we die. Slide01

The leading causes of death in America are heart disease, cancer, stroke, lung disease, injuries, diabetes, influenza, and pneumonia. Obesity has a greater impact on morbidity than mortality, but increases the risk of death and disability due to obesity-related cardiovascular diseases. Heart disease, cancer, stroke, and diabetes are all modifiable to reduce obesity with dietary and lifestyle intervention.  Slide02

There are obvious advantages to long life, but a hidden advantage also exists: there will continue to be medical breakthroughs  which could 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 healthy with a high QOL, then one  would be physically able to take advantage of 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. 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, which results 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. Slide03

Healthy Heart

The primary role of endothelium is to maintain vascular tone. This is 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 edothelin.  Pro-oxidant angiotensin II stimulates the production of endothelin.  Both angiotensin II and endothelin promote smooth muscle cell proliferation and contribute to plaque formation.   

Nitric oxide (NO) 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.  As a vasodilator, NO helps move oxygen into muscles when they need it most, sparking muscle growth and strength gains. Nitric oxide supplementation may naturally enhance sexual performance, as increased oxygen flow occurs all over the body as a result of vasodilation. Finally, good levels of NO have been found to promote immune response and wound healing. In other words, even the low doses of NO that the body naturally produces have great impacts on overall health, from muscular growth to healthy blood flow.

When NO production is impaired, it promotes atherosclerosis.  Vasoconstriction, platelet aggregation, smooth muscle cell proliferation and migration, leukocyte adhesion and oxidative stress are all accelerated as NO levels are diminished Therefore, the mechanisms for reducing endothelial and NO availability and increasing endothelial dysfunction are all promoted by hypercholesterolemia, hypertension, diabetes, and smoking.  With the addition of obesity, these are the basic elements of MetS. All conditions further produce reactive oxygen species, which in turn inhibit the production of the enzyme DDAH. This results in increased levels of NO synthesis  inhibitor, which in turn results in decreased endothelial NO availability. ^2,3 And the cycle continues. . Slide04

Reactive oxygen species reacts with NO to cause  a loss of nitric acid bioactivity. Reactive oxygen species also cause oxidative degradation of H4B, which is a critical NO synthase cofactor.  Degraded H4B  results in decreased endothelial NO 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. 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.

In a series of landmark clinical trials, statin class drugs have been show to reduce initial and recurrent myocardial infarction (MI). Lower target LDL levels might prompt physicians to consider  combination therapy to control other lipid abnormalities. Goals of combination therapies address three areas: to lower LDL; to raise HDL; and to lower triglycerides. R M Guthrie, professor of internal medicine and pharmacology (Ohio State University), reviewed over 25  drug studies on the effects of  cholesterol management.⁴ He concluded that addition of a second drug to a statin to enhance lowering of LDL has the most scientific support, while treatment of low HDL remains unsettled. The addition of a fibrate, niacin, and omega-3 supplements has mixed findings.

Use of antioxidant supplements  may inhibit  oxidation, retarding, or even preventing, the formation of atherosclerotic plaque.⁵ Dietary studies related to hyperlipidema showed that the addition of a fibrate, niacin, and omega-3 fatty acid supplements had mixed findings. Although adverse events due to consumption of fish oil or ALA supplements appear to be minor,  claims that consumption of omega-3 fatty acids from fish or from supplements of fish oil reduce all causes of mortality and various CVD outcomes is unproven. The evidence for ALA supplements is sparse and inconclusive. The optimal quantity and type of omega-3 fatty acid, and the optimal ratio of omega-3 to omega-6 fatty acid (if such an optimal ratio exists), remain undefined. Not much data exists concerning the needs of different subpopulations. Different types of fish and the method of food preparation may have different effects.

Lipids

In 2004,  there were 6.5 million visits to doctors’ offices that included a cholesterol test being done or ordered.⁶   By 2006, the visits to office-based physicians with cholesterol measure ordered or provided was 7.1% , and the visits with co-morbid hyperlipidema identified was 13%.⁷    Among African Americans, about 16.6% of women and 12.5% of men had high total cholesterol.⁶   Mexican American women showed about 12.7%  and 17.6% of men had high total cholesterol.  Among whites, 17.4% of women and 17.0% of men measured a high cholesterol.⁶   All ethnic groups identified showed more women than men with elevated lipids.

The National Cholesterol Education Program recommends that all adults have their cholesterol checked once every 5 years. In 2005, 73% of adults reported that that they had their cholesterol checked within the previous 5 years, according to data from CDC’s Behavioral Risk Factor Surveillance System. According to data from that same study, 75.7% of whites, 73.7% of African Americans, and 52% of Hispanics reported having had their cholesterol checked within the previous 5 years.⁸ However, some 23% reported that they never had their cholesterol checked. 

Interestingly, the percentage of persons aged 20–74 years with high cholesterol dropped from 33% in 1960–1962 to 17% in 1999–2002, and to 16% in 2003-2006.. During that same time period, the average blood cholesterol levels in adults dropped from 222 mg/dL to 203 mg/dL⁶.  to a mean serum cholesterol level of  200 mg/dL  (2003-2006).⁷ The National Cholesterol Education Program recommendations and efforts after 2002 could have attributed to the drop. 

In the 7 year study of trends in T2DM control among black adults,  there were increases in the proportion of individuals who met the recommended HgA1c  (CRP) levels, and the number who met the HDL, LDL, and triglyceride, and total cholesterol levels.  Other risk factor s did not change or worsened. the prevalence of smoking remained at approximately 46%, and the population with a BMI  greater than or equal to 30 actually increased significantly (p 0.05).  Although there are many caveats to explain the findings, the message is that greater attention needs to be given to all risk factors, not only the presenting disease. ⁹

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 T2DM, 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 ^10,11  showed that aggressive statin therapy is an appropriate treatment for low HDL syndrome.  Triglycerides are a secondary risk factor in coronary artery disease. R M Guthrie, professor of internal medicine and pharmacology, reviewed over 25  drug studies on the effects of  cholesterol management to  conclude that addition of a second drug to a statin to enhance lowering of LDL has the most scientific support, while treatment of low HDL remains unsettled⁴.

Lipid problems lead to hypertension.  Goals of combination therapies address three areas: to lower LDL; to raise HDL; and to lower triglycerides. In a series of landmark clinical trials, statin class drugs were shown to reduce initial and recurrent myocardial infarction (MI). The lower target LDL levels might prompt physicians to consider combination therapy to control other lipid abnormalities of the heart.

The Classic “Big Four” low-LDL Trials that form the basis of current treatment guidelines are: Heart Protection Trial from Great Britain (2002)¹²; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in MI 22 (PROVE –IT) Trial (2004¹³;  “A to Z” Trial (2004)¹⁴ ; and Treating to New Targets (2005)¹⁵.  The bottom line to the Classic Big Four  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 MetS.Slide05

Hypertension and elevated cholesterol  Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) study found that reducing cholesterol and blood pressure in people with heart disease decreased their risk of dying of heart disease, and need for heart bypass surgery or angioplasty, and having a nonfatal heart attack. The study suggests that even people without heart disease can benefit from having cholesterol and blood pressure levels lower that those recommended by the national guidelines¹⁶.

Another study that looked at hypertension and lipid lowering treatment concluded that research findings failed to support calcium channel blockers, alpha-blockers, or angiotensin converting enzyme inhibitors compared with thiazide-type diuretics in patients with MetS, especially in black patients¹⁷.

Risk is not always recognized, despite the guidelines and research findings. A case study design tested physician (n=500) accuracy and determinants of CVD risk level assignment and application of guidelines among high-, intermediate-, or low-risk patients^(I)

Intermediate-risk women, as assessed by the Framingham risk score, were significantly more likely to be assigned to a lower-risk category by primary care physicians than men with identical risk profiles (P<0.0001), and trends were similar for obstetricians/gynecologists and cardiologists. Assignment of risk level significantly predicted recommendations for lifestyle and preventive pharmacotherapy. Fewer than 1 in 5 physicians knew that more women than men die each year from CVD. Perception of risk was the primary factor associated with CVD preventive recommendations. Gender disparities in recommendations for preventive therapy were explained largely by the lower perceived risk despite similar calculated risk for women versus men¹⁸

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.   However, Dietary Guides to decreasing cholesterol will also improve nutrition and decrease weight.

Dietary Ways To Decrease Cholesterol 

The position of the American Dietetic Association is that appropriately planned vegetarian diets, including total vegetarian or vegan diets, are healthful, nutritionally adequate, and may provide health benefits in the prevention and treatment of certain diseases. Well-planned vegetarian diets are appropriate for individuals during all stages of the life cycle. A vegetarian diet is defined as one that does not include meat (including fowl) or seafood, or products containing those foods. Vegetarians also appear to have lower low-density lipoprotein cholesterol levels, lower blood pressure, and lower rates of hypertension and T2DM  than non-vegetarians. Furthermore, vegetarians tend to have a lower BMI and lower overall cancer rates. Features of a vegetarian diet that may reduce risk of chronic disease include lower intakes of saturated fat and cholesterol and higher intakes of fruits, vegetables, whole grains, nuts, soy products, fiber, and phytochemicals¹⁹.

Diet is one of the modifiable risk factors of cardiovascular disease globally. The intake of food varies from region to region. It is not clear whether the association between diet (as assessed by dietary patterns and dietary scores) and acute myocardial infarction (AMI) is the same or different in various regions of the world. An analysis included participants from 52 countries (5,761 case subjects with AMI and 10,646 control subjects.). Using factor analysis, 3 major dietary patterns were identified: Asian (high intake of tofu and soy and other sauces), Western (high in fried foods, salty snacks, eggs, and meat), and prudent (high in fruit and vegetables). A higher intake of the prudent diet pattern was related to a 30% reduction in the risk of having an AMI

globally in every region of the world. A higher intake of the Western diet pattern was associated with a 35% increased risk of having an AMI globally and in every region of the world, whereas there was no association between the Oriental diet pattern and

AMI. We also created a dietary risk score (derived from meat, salty snacks, fried foods, fruits, green leafy vegetables, cooked vegetables, and raw vegetables) in which a higher score indicated a poorer diet. A higher score was associated with as much as

a 92% increased risk of AMI. The population-attributable risk of AMI for the top 3 quartiles compared with the bottom quartile is not clear whether the association An unhealthy dietary intake, assessed by a simple dietary risk score, increases the risk of AMI globally and accounts for about 30% of the population-attributable risk ²⁰.

High blood pressure (BP) is a major risk factor for heart disease, stroke, congestive heart failure, and kidney disease. Inverse associations between dairy product consumption and systolic blood pressure (SBP) and diastolic blood pressure (DBP) have been observed in cross-sectional studies; some studies, however, have reported an inverse association with only one BP parameter, predominantly SBP. Randomized clinical trials examining the effect of calcium and the combination of calcium, potassium and magnesium provide evidence for causality. In these studies, reductions in BP were generally modest (-1.27 to -4.6 mmHg for SBP, and -0.24 to -3.8 mmHg for DBP). Dairy nutrients, most notably calcium, potassium and magnesium, have been shown to have a blood pressure lowering effect. A low calcium intake increases intracellular calcium concentrations which increases 1,25-dihydroxyvitamin D(3) and parathyroid hormone (PTH), causing calcium influx into vascular smooth muscle cells, resulting in greater vascular resistance²¹. New research indicates that dairy peptides may act as angiotensin converting enzyme (ACE) inhibitors, thereby inhibiting the renin angiotensin system with consequent vasodilation. A growing evidence base shows that dairy product consumption is involved in the regulation of BP. Consequently, inclusion of dairy products in a heart healthy diet is an important focal point to attain BP benefits.

A simple list of Diet Dos to reduce cholesterol follows:

1. Reduce saturated fat and completely avoid trans-fat.

 2. Increase fiber to 25-35 gm 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 gm of soluble fiber daily has been shown to decrease LDL by 5%.

3. Increase Omega 3 fatty acids.  A handful of almonds (70 gm) daily can decrease LDL by 8%.  Molecularly distilled fish oil is also available.

4. 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. Anther study by AHRQ ²², a meta-analysis of research indicates that consumption of soy/omega-3 products appears to exert a small benefit on LDL and no significant effect on HDL. Across studies, there is the possible suggestion that higher doses of soy protein are associated with greater LDL reduction among those with elevated baseline LDL, but not with HDL or triglycerides. Dose of isoflavones was not associated with effect for any lipid.. Meta-analysis of blood pressure (BP) found no effect of soy consumption. No association was found between baseline BP, soy protein or isoflavone dose, and effect on BP. No significant effect of soy products was found for several markers of inflammation, vascular function, or lipid oxidation..However, soy products may reduce menopausal symptoms in post-menopausal women. The current literature does not support other effects of soy products. The evidence from human studies does not suggest any worrisome adverse events beyond mild gastrointestinal intolerance. Conclusions were often limited due to small numbers of studies or heterogeneity across studies.

5. Green tea (240 mg to 320 mg of polyphenols) Daily recommendation is 4 to 5 cups. Green tea has been associated with lower LDL-cholesterol and lower risk of death from coronary artery disease. 

Alternative Supplements 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 maximum dose is 6 gm a day.

• Red yeast rice (Cholestin in other countries):  Contains 7 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 by the FDA for containing the same compound as Lovastatin ²³. Arjuna Bark:  Capsule form used in Ayurvedic medicine and a strong antioxidant. Dose is 1to3 gm per day. 

• Prickly Pear Extract: A small Italian study in 2003, 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. 

• Ultra meal:  A combination product with soy, fiber, and plant sterols, shown to reduce LDL by 33% along with a Mediterranean diet. 

Anyone taking statins 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 associated with aches and pains.  Since the heart is 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.  However, research findings vary on the over-all effectiveness of coenzyme Q10. 

Plant sterols, stanols and LDL.  The value of sterols and stanols centers 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 %. ^24, This can significantly decrease serum cholesterol levels in those who regularly consume phytosterols.  The addition of 2 gm 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 ²⁵. The U.S. National Cholesterol Education Program (NCEP) recommends a dietary phytosterol intake of 2 gm/day²⁶.  Finally, there seems to be an additive effect with the combination of phytosterols and statins in the LDL-cholesterol-lowering objectives²⁷.  

Hyperhomocystein Homocysteine is 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 plaque²⁸. Deficiencies of folic acid, vitamin B₆ and B₁₂ are associated with hyperhomo-cysteinemia. Whether correction of elevated homocysteine levels with vitamins will reduce vascular events is currently under investigation²⁹.  In 1999, the American Heart Association³⁰ 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.  

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 as higher levels may cause irreversible nerve damage ³¹.   

Nutrition & Inflammation Slide06

Nutrition is a major factor 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, MetS, low omega-3 diets, hyperglycemia and glycation, and high polyunsaturated fatty acid diets.   

Visceral Adiposity

Approximately two thirds of U.S. adults and one fifth of U.S. children are obese or overweight. During 1980--2004, obesity prevalence among U.S. adults doubled, and recent data indicate an estimated 33% of U.S. adults are overweight (body mass index [BMI] 25.0-29.9), 34% are obese (BMI >or=30.0), including nearly 6% who are extremely obese (BMI >or=40.0). Being either obese or overweight increases the risk for chronic diseases including  CHD, T2DM, certain cancers, and stroke.

The most critical factor in reducing inflammation is loss of adiposity, especially visceral adiposity. Adipose tissue is not just dormant!  It is quite metabolically active, producing Interleukin-6, which causes increased C-reactive protein (CRP) 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 ^{32, 33}.  Adipose tissue also produces Tumor Necrosis Factor Alpha and causes insulin resistance.  produces Tumor Necrosis Factor Alpha and causes insulin resistance. Slide07

How do we assess overweight and obesity?  Slide08  The body mass index  (BMI) is the weight in pounds, divided by height (in inches) and squared x 703. However, the BMI does not accurately measure body fat. Estimates of total body fat include skin-fold measurements, bioelectrical impedance, total body conductivity methods, hydrostatic weight, and DEXA scan.  Visceral fat – central fat or abdominal fat are all associated with the greatest metabolic risk,  including men whose waist is greater than 40 inches (measured an inch above the umbilicus) and women with waists greater than 35 inches. 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 0.8³⁴. Slide09

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

Metabolic Syndrome

Although not every medical group agrees on the defining conditions that make up MetS, it is group of risk factors including:

• Abdominal obesity 

• Hyperlipidemia 

• Insulin resistance/ or glucose intolerance/ or diabetes 

• Prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor [-1] in the blood) 

• Hypertension (130/85 mm Hg or higher) 

• Proinflammatory state (e.g., elevated high-sensitivity C-reactive protein)

• Slide10

In addition to measurements of abdominal obesity, 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 are signals for risk. Having any three of these measurements meets the criteria for metabolic syndrome^{35, 36}.   Slide 11

The underlying causes of MetS are overweight/obesity, physical inactivity and genetic factors. MetS predisposes to increased risk of coronary heart disease (CHD), other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease {PVD}), and type 2 diabetes mellitus (T2DM)^37,38. Metabolic syndrome is present in 23.7% of U.S. adults. And 43.5% of individuals 60 years and older have MetS; 30% of obese children have MetS.  The end result is almost 50 million Americans with MetS.   The consequences of MetS are overwhelming.  Individuals with MetS experience a six-fold higher rate of cardiovascular events and mortality than the general population.   

Mechanisms involved in the production of obesity-related low-grade inflammation lead to development of the inflammatory aspect of MetS. 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 MetS, making it so deadly.  Insulin resistance is central to the metabolic syndrome and to T2DM. 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. 

Diabetes 

Diabetes now affects nearly 24 million people in the United States, an increase of more than 3 million in approximately two years, according to new 2007 prevalence data estimates³⁷. This means that nearly 8 percent of the U.S. population has diabetes. In addition to those with diabetes, another 57 million people are estimated to have pre-diabetes, a condition that puts people at increased risk for diabetes. Among people with diabetes, those who do not know they have the disease decreased from 30 percent to 25 percent; this is probably related to improved screening and diagnosis.

Among adults, diabetes increased in both men and women and in all age groups, but still disproportionately affects the elderly. Almost 25 percent of the population 60 years and older had diabetes in 2007. And, as in previous years, disparities exist among ethnic groups and minority populations including Native Americans, Blacks and Hispanics. After adjusting for population age differences between the groups, the rate of diagnosed diabetes was highest among Native Americans and Alaska Natives (16.5 percent). This was followed by Blacks (11.8 percent) and Hispanics (10.4 percent), which includes rates for Puerto Ricans (12.6 percent), Mexican Americans (11.9 percent), and Cubans (8.2 percent). By comparison, the rate for Asian Americans was 7.5 percent with whites at 6.6 percent³⁹.

By 2025, the prevalence is estimated to increase to nearly 22 million or roughly 9% of our population. This is not only a problem in the U S, but worldwide. In 2000, there were 171 million T2 DM in the world; by 2030, there will be 366 million worldwide.   

T2DM is no longer “adult-onset,”  but there is an epidemic of T2DM in children and adolescents in this country.  T2DM severely impacts the health of our society. Type 2 diabetics have a 5 to 10 year reduction in their life expectancy—and CVA and AMI are increased fivefold. Approximately 75% of T2DM will die of coronary artery disease.   

What are the risk factors for T2DM? The first one is age (45 years old or older), overweight (BMI of 25 or greater), MetS, a family history of diabetes, habitual physical inactivity, race, and ethnicity. Additional conditions to place a person at risk are: previously identified abnormal fasting blood sugar of 100 or greater; 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.   

The natural history of T2DM starts with adiposity.  Slide12  Adiposity results in insulin resistance, which is the primary defect. Then, the beta cells of the pancreas compensate by increasing insulin production. This ultimately results in the secondary defect, beta cell exhaustion. Next is pre-diabetes, followed by full-blown T2DM. Finally,  insulin-requiring T2DM since the beta cells become completely burned out.  This is the absolute insulin deficiency state.   

In a review of the current state of T2DM mellitus (T2DM) treatment and the management of CV risk factors associated with T2DM, unmet treatment needs are identified by Levy⁴⁰.  The treatment of T2DM requires a multifaceted approach of both lifestyle modification of diet, exercise, weight control, smoking cessation,  and pharmacological therapy. Patients often require pharmaceuticals to normalize hyperglycemia, and additional therapy to treat cardiovascular (CV) risk factors of hypertension and dyslipidemia.  Levy found that although the benefits of early, aggressive glycemic control are clearly established, medical treatment often remains remained suboptimal. This included poor adherence by patients to lifestyle and pharmacological treatment, lack of understanding by patients of the long-term benefits of treatment, patient concerns about adverse effects.

Stolar, et al, also discuss the need to aggressively manage T2DM to achieve treatment goals associated with glycemic control, fewer diabetes-related complications, cost and health care utilization⁴¹.  Reducing a patient's glycated hemoglobin (A1C) has been shown to decrease the risk of diabetes-related complications, as well as reduce medical costs and health care utilization. Despite this knowledge, achievement of the American Diabetes Association (ADA) goal A1C of < 7% is suboptimal, and < 1 in 10 patients also reach the ADA targets for cholesterol (low-density lipoprotein < 100 mg per dL) and blood pressure (< 130/80 mm Hg). To ensure that all ADA treatment goals are met, clinicians need to closely monitor patients and adjust therapy as needed, taking into consideration both a drug's glycemic and nonglycemic effects when selecting medication therapy⁴¹.  The  authors suggest that therapy is not managed to ensure that most patients sustain an adequate level of control using nondrug or single-drug therapeutic approaches. Choices among treatment options,do not always consider the nonglycemic as well as glycemic effects of various glucose-lowering agents.

In a study of medical knowledge in clinical settings, Polonsky, et al, concluded that PCPs can correctly identify glycemic abnormalities in structured, episodic self-monitoring blood glucose (SMBG) data. PCPs evaluated 23 case studies of patients who presented random SMBG, A1C data, and then combined data to assess T2DM management. Most (78%) participants (n=61) identified the same primary blood glucose feature identified by the diabetes specialists; 93.8% agreed with the diabetes care specialists regarding the need for therapy modification 18. The majority (77%) of participants changed the way they would manage the case after evaluating case studies with SMBG data made available to them. Eighty-six percent of participants considered the SMBG data to be of equal value or more valuable than an A1C test result; 71% of participants strongly agreed that they are now more likely to recommend structured, episodic SMBG to their non-insulin T2DM patients ⁴². Although a small sample size, the results are encouraging that about 75% of the PCP made treatment decisions consistent with the specialists about glycemic control.

Targeting Inflammation & Insulin Resistance   

Drug treatment with Thiazolidinedione (TZD) acts directly to reduce insulin resistance. They also appear to improve beta cell function and have anti-inflammatory properties.  TZDs are popular in the treatment of T2DM, and reduce CRP and MMP-9 (to 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 the U S  to treat T2DM.  Treatment with metformin for 16 weeks in a home study 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.  CRP levels were not affected.⁴³

Weight loss plays a major part in improving T2DM. 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 T2DM over a 4-year period.   

In summary, decreasing body fat results in a decreased LDL, decreased triglycerides, improved insulin sensitivity, reduced total cholesterol, improved HDL and decreased inflammation.  Slide13

How do we get rid of body fat?  First, by keeping insulin and glucose levels as low as possible.  This 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 can actually 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.   

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 inflammation⁴³.

Many fruits, vegetables, and grains are high in fiber. 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 can be used in moderation to other natural foods. Slide14 Slide15

Supplementation Slide17

Supplemental vitamins and minerals are important to maintaining nutrition, but not necessarily to prevent chronic diseases or cancer. Research findings from the Mayo Clinic support vitamin supplements for important nutrition, but not to avert serious illnesses. Findings include Vitamin B-3, or niacin, that can reduce LDL  and triglycerides and raise HDL levels in high doses. However, the doses need for therapeutic effects are usually greater than 1,000 mg per day and can cause liver damage. Recommendations are that higher doses of niacin be taken only under a physician/s supervision.

Studies do support that eating food high in Vitamin C can lower rates of cancer and heart disease; however, it unclear if Vitamin C supplements can provide the same protection. Studies have shown that vitamin C supplements taken with other antioxidants and zinc may slow the progress of age-related macular degeneration, but there is little evidence that vitamin C prevents colds or lessens cold symptoms.

Vitamin E is an antioxidant that protects red blood cells and support the body’s immune system. Diets rich in antioxidants, including vitamin E, are said to help lower the risk of some cancers and heart disease. Unfortunately, recent studies suggest that vitamin E supplements do not provide the same benefits, and may even be harmful to health^.45

Vitamin D and calcium can prevent or slow osteoporosis and reduce fractures; other  potential benefits of vitamin D are reducing risk of muscle pain and weakness, autoimmune disorders (such as RA and MS), CVD, and some cancers. New knowledge  recommends that the daily intake of vitamin D should be 800 to 1,000 IU daily (current U S government RDA for adults is from 200 to 600 IU daily).

The Mayo Clinic research supports an earlier Swiss study on falls and fractures in the elderly correlates higher 25-hydroxy vitamin D status with better bone and muscle health⁴⁶. Researchers found compelling dual benefit of vitamin D on bone and muscle health, a concept that is unique and important for optimal fracture prevention at older age. Calcium alone was insufficient for bone health and the conclusion was that vitamin D at a dose of at least 800 IU per day should be provided to all postmenopausal women and everybody starting at age 60 for optimal bone and muscle health. In combination with a vitamin D supplement, dairy products may be an optimal source of calcium at higher age as milk provides both calcium and protein.

Information is available from government sources on the availability, RDA and cost of nutritional components.⁴⁷

Calcium and Vitamin D

Calcium and vitamin D absorption decreases with aging, and older individuals with limited mobility tend to receive less sunlight, leading to rates of vitamin D deficiency (as measured by serologic testing) of up to 57% in this population. As a result, recommended daily allowance (RDA) of both calcium and vitamin D increase in this population. Total calcium intake should be 1,200 mg per day after age 50. Older individuals should be educated as to how to read labels for calcium content, since calcium is expressed as a percent of 1,000 mg on labels (RDA for younger adults). Since the calcium intake goal for older adults is greater than 1,000 mg per day, these individuals actually need to consume more than 120%  of the RDA on food labels. Since older persons may suffer constipation as a side-effect of calcium supplements, health care professionals should emphasize food sources of calcium and recommend increasing fluid and fiber intake. When inability to secrete acid in the stomach (achlorhydria) limits the absorption of calcium carbonate salts, citrated salts may be absorbed better in these patients.  However, carbonate salts will still be absorbed if taken with meals.

Individuals between the ages of 51 and 70 should consume 800 IU per day of vitamin D, while those over age 70 should get 1000 IU per day. Ten minutes of daily sun exposure on the arms is adequate for vitamin D absorption. Since it may be difficult for older individuals to achieve the levels of intake through food alone, many individuals will require multi-vitamins or specific vitamin D supplements. Individuals who have low vitamin D dietary intake and/or low sun exposure should have their vitamin D level measured. Persons found to have vitamin D deficiency should receive pharmacologic doses of vitamin D.

Recommendations for other nutrients for older adults are the same as those for younger adults. In addition, protein supplementation has been shown to speed healing and reduce mortality in older individuals suffering hip fractures. These patients should have a nutritional evaluation during post-fracture rehabilitation.

Fats & Inflammation  

Fatty acids are classified as saturated, unsaturated, and polyunsaturated. Slide18

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  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.  Slide19

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 (TFA) are man-made and highly inflammatory and atherogenic. They are formed by the industrial hydrogenation of vegetable oils. 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; the answer will be in 20 to 30 years. Hu, et al, ⁴⁸ in 1997 compared the various fatty acids and their effect on CHD.Slide20

Dietary sources rich in TFA include store-bought cookies, crackers, baked goods, margarine, and commercial deep-frying oils as well as the foods cooked in them. Levels of TFA must be on food labels.  Labels may claim to contain “0 gms 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 also 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 are 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.  If this ratio is greater than 10:1, there is high risk for inflammation and thrombosis.^49,50 Slide22

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