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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 syndrome35, 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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