High Cholesterol: Natural and Pharmaceutical Management

High Cholesterol: Natural and Pharmaceutical Management
Event Type
Live Online
ACPE Expiration Date
5/23/2016
Credits
1 Contact Hour
Target Audience
Nurses, Pharmacists, Pharmacy Technicians
Program Overview
Dietary cholesterol is essential for health, but too much is likely harmful. High blood
cholesterol is considered a major risk factor associated with heart disease, although it is
causality is not clear. About 17% of adult Americans aged 20 years and older have high total
cholesterol, which is defined as 240 mg/dL or above. Various medications are effective at
lowering blood cholesterol, but side effects are common and sometimes debilitating. A number
of natural approaches may be just as effective for lowering blood cholesterol without the
negative symptoms.
Nurse Educational Objectives
 Describe the physiology, incidence and prevalence of high blood cholesterol and its
relationship to increased risk of cardiovascular disease
 Outline the non-pharmacological methods used to treat high blood cholesterol
 Compare and contrast the most common pharmaceuticals used to reduce blood cholesterol,
including mechanisms of action and potential side effects
Pharmacist Educational Objectives
 Describe the physiology, incidence and prevalence of high blood cholesterol and its
relationship to increased risk of cardiovascular disease
 Outline the non-pharmacological methods used to treat high blood cholesterol
 Compare and contrast the most common pharmaceuticals used to reduce blood cholesterol,
including mechanisms of action and potential side effects
Pharmacy Technician Educational Objectives
 List medications used to treat high blood cholesterol
 List lifestyle changes that can treat high blood cholesterol
Activity Type
Knowledge
Accreditation
Nurse
Pharmacist
Pharmacy Technician
N-833
0798-0000-13-172-L01-P
0798-0000-13-172-L01-T
PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a
provider of continuing pharmacy education.
PharmCon, Inc. has been approved as a provider of continuing education for nurses by the
Maryland Nurses Association which is accredited as an approver of continuing education in
nursing by the American Nurses Credentialing Center’s Commission on Accreditation.
Faculty
J Dufton , MD
Medical Writer, Wellness Partners
Financial Support Received From
Pharmaceutical Education Consultants, Inc.
Disclaimer
PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the
value of the material is decreased. The content of the activity was planned to be balanced and
objective. Occasionally, authors may express opinions that represent their own viewpoint.
Participants have an implied responsibility to use the newly acquired information to enhance
patient outcomes and their own professional development. The information presented in this
activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions
drawn by participants should be derived from objective analysis of scientific data presented
from this activity and other unrelated sources.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
High Cholesterol: Natural and Pharmaceutical
Management
Accreditation
Faculty
Pharmacists: 0798-0000-13-172-L01-P
Pharmacy Technicians: 0798-0000-13-172-L01-T
Nurses: N-809
Johnathon Dufton
MD
Wellness Partners
CE Credit(s)
Faculty Disclosure
1.0 contact hour(s)
Dr. Dufton has no actual or potential conflicts of interest in
relation to this program.
Learning Objectives
•
•
•
Describe the physiology, incidence and prevalence of high blood cholesterol and its relationship to increased risk of
cardiovascular disease
Outline the non-pharmacological methods used to treat high blood cholesterol
Compare and contrast the most common pharmaceuticals used to reduce blood cholesterol, including mechanisms of
action and potential side effects
Legal Disclaimer
The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that
support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed.
Participants should verify all information and data before treating patients or employing any therapies described in this educational activity.
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High Cholesterol: Natural &
Pharmaceutical Management
Introduction
OBJECTIVES:
• Describe the physiology, incidence and prevalence of high
blood cholesterol and its relationship to increased risk of
cardiovascular disease.
• Outline the non-pharmacological methods used to reduce
high blood cholesterol.
• Compare and contrast the most common medications
used to reduce blood cholesterol, including mechanisms of
action and potential side effects.
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3
•
A type of fat called a sterol
that’s primarily made in the liver.
•
One of 3 main classes of lipids that
animal cells use to make membranes.
•
A precursor for steroid hormones, bile acids and vitamin D.
•
Essential, but high levels in the bloodstream can increase the risk of
cardiovascular disease and heart attack.
•
The propensity for high blood cholesterol (hypercholesterolemia) can be
inherited, but it's usually caused by unhealthy diet / lifestyle.
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High Cholesterol: Natural and Pharmaceutical Management
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Reproduction in whole or in part without permission is prohibited.
High Density Lipoprotein (HDL)
“Good”
Blood Cholesterol
• Hydrophobic, does not dissolve in water, carried by special
proteins within blood (lipoprotein)
• Smallest lipoprotein - least cholesterol.
• HDL transports cholesterol away from arteries and back to the
liver for excretion or recycling.
• In healthy people, about 30% of cholesterol is carried by HDL.
• Higher levels of HDL …less risk of cardiovascular disease, lower
HDL levels ….increased risk of heart attack.
• Blood cholesterol tests measure the types and proportions of
lipoproteins.
• “good” vs “bad” cholesterol
• The 3 main types of lipoproteins:
⁻ high density (HDL)
⁻ HDL of 60 mg/dL or more is desirable.
⁻ Levels less than 40 mg/dL is considered a
major risk factor for heart disease.
⁻ low density (LDL)
⁻ very low density (VLDL)
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Low Density Lipoprotein (LDL)
“Bad”
Very Low Density Lipoprotein
(VLDL)
• largest carriers of cholesterol - aside from chylomicrons.
• Main carriers of triglycerides
• Excess calories converted into triglycerides and stored in fat
cells throughout the body.
• Larger than HDL –carries more cholesterol & triglycerides.
• Transports cholesterol away from liver and towards cells.
• Also transports cholesterol into arterial walls, which attract
macrophages and trigger the formation of plaques.
• Arterial plaques are associated with atherosclerosis.
• Studies show that LDL type-B (as opposed to type-A) most
strongly associated with cardiovascular disease.
⁻ Triglycerides below 130 mg/dL are considered healthy, although the
American Heart Association claims100 mg/dL or less is optimal and
70 mg/dL best for heart disease patients.
⁻ Levels greater than 200 mg/dL are considered too high.
⁻ Once in the bloodstream, VLDL can be converted to LDL.
⁻ LDL less than 100 mg/dL is considered optimal.
⁻ Levels greater than 160 mg/dL are considered much too high.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Total Cholesterol Levels
Diagnosing High Cholesterol
• A blood test to check cholesterol levels (typically called a lipid panel or
profile) measures HDL, LDL, triglycerides and total cholesterol.
•
Everyone over the age of 20 - measured at least once every five years;
then routine screening for men >35 years and women >45 years.
• Cholesterol levels are measured in
mg/dL in the U.S. but most
European countries measure blood
cholesterol in mmol/L.
•
Diagnosis based entirely on the lipoprotein profile
•
In addition to blood testing, a physical
exam and medical history normal.
• Cholesterol recommendations vary
slightly between countries and
organizations.
•
High cholesterol and other
risk factors for heart disease lead to
treatment recommendations.
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Factors Affecting Cholesterol
Levels
10
Prevalence of High Cholesterol
•
Diet: saturated, trans fat and cholesterol in food raise total and LDL
cholesterol levels, the liver plays an important regulating role.
•
Weight: increases the amount of LDL / triglycerides in blood.
•
Exercise: can lower LDL and raise HDL.
•
Age: men aged 45 years & women aged 55 years or older at increased risk
of high total cholesterol and heart disease.
•
Gender: before menopause, women tend to have lower total cholesterol
levels than men of the same age, after menopause, LDL levels tend to rise.
•
Diabetes: poorly controlled diabetes increases LDL levels.
•
Heredity: genes partly determine how much cholesterol the body makes.
•
Diseases: some diseases increase cholesterol.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Those with High Cholesterol
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Cholesterol Levels Over Time
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Cholesterol Screening
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Global Prevalence
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Those at Greatest Risk
Diseases Linked to High Cholesterol
⁻ eat lots of trans & saturated fats
•
Atherosclerosis: a build-up of fatty material and cholesterol (plaques) on
the inside of arterial walls - harden the arteries and reduce blood flow
⁻ smoke cigarettes
⁻ abuse alcohol
– Coronary heart disease: atherosclerosis of the coronary arteries significantly increase
the risk of clots and myocardial infarction; reduced blood flow to heart – angina
⁻ don’t control their diabetes
– Stroke: atherosclerosis of arteries in the brain significantly increases the risk of ischemic
stroke.
⁻ hypertension (140/90 mmHg or higher)
⁻ family or personal history of heart disease
– Peripheral vascular disease: atherosclerosis of peripheral arteries (typically in the legs
and feet) significantly increases the risk of vascular claudication.
⁻ male 45 years or older (especially Hispanic);
women 55 years or older (especially Caucasian).
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Hypertension: plaque accumulation narrows lumens and increases BP.
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Spotlight on Atherosclerosis
Atherosclerosis
•
• Atherosclerosis more than clogging of arteries with cholesterol or
fat
•
•
• Interrelated processes:
⁻ lipid oxidation
⁻ blood platelet cell activation
•
⁻ thrombus (blood clot) formation
•
•
⁻ endothelial cell dysfunction
⁻ inflammation
⁻ oxidative stress
⁻ vascular smooth cell activation
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Initiated by damage to the inside of the artery, not high levels of blood
cholesterol.
Artery damage triggers a cascade of events that starts with cellular repair.
Cholesterol rushed to the damaged area
by LDL to repair and make new cells, acts as
a bandage along with platelet cells / fibrin.
Inflammation develops as soon as LDL within
the arterial wall is oxidized by free radicals.
Oxidized LDL induces harmful processes.
Ongoing inflammation provides continuous signals
for more LDL uptake and leukocyte infiltration,
which increases size of the atheroma.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Natural Approaches – Lowering
Cholesterol
Correlation with CHD
•
Many studies don’t show a good correlation between reduced prevalence
of high cholesterol and reduced prevalence of coronary heart disease
(CHD).
⁻ lifestyle changes
⁻ herbal remedies
⁻ dietary supplements
•
The above numbers come from a large U.K. study and show that CHD
prevalence stayed the same over 12 years despite lower cholesterol levels.
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Diet
22
High Cholesterol Foods
• Dietary cholesterol effects blood cholesterol, but it varies substantially.
• About 50% of dietary cholesterol absorbed, but the liver regulates.
• Reducing dietary fat also impacts cholesterol levels.
• In controlled settings, dietary change can reduce blood cholesterol
levels by 15%, but in practice, the decreases are more modest.
• Dietary recommendations:
⁻ eliminate trans fat – found in heavily processed food
⁻ limit saturated fat – no more than 10% of daily calories
⁻ limit dietary cholesterol - no more than 300 mg a day (200 mg w/ heart problem)
⁻ eat more soluble fiber
• The most concentrated sources of cholesterol include organ
meats, egg yolks and whole milk products.
• Consuming lean cuts of meat,
egg substitutes and skim
milk significantly reduces
cholesterol intake.
• Saturated fat should not be
eliminated from the diet
because some cholesterol is
essential for health.
⁻ eat more fish - omega-3 fatty acids have anti-inflammatory properties
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Cholesterol Lowering Foods
Lifestyle Change - Smoking
• Soluble fiber attaches to
bile in the intestines and
drags it out of the body,
modest impact on blood
cholesterol.
• Quitting smoking can improve HDL cholesterol levels, less toxins
in the blood, less damage to the insides of arteries and reduced
risk of atherosclerosis and related sequelae.
• Other benefits include:
⁻
⁻
⁻
⁻
• Sterols and/or stanols in
plants prevent cholesterol
from being absorbed into
the bloodstream, a slightly
bigger impact.
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about 20 minutes after quitting, blood pressure starts to decrease
within 24 hours of quitting, risk of a heart attack decreases
within 1 year of quitting, risk of heart disease is 50% of a smoker's
within 15 years of quitting, risk of
heart disease is similar to that of
someone who never smoked
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Herbal Remedies
Other Herbs
⁻ red yeast rice: the product of yeast grown on rice, which is eaten in Asia. It
contains monacolins, which inhibit cholesterol synthesis like statins do. One such
monacolins is also called lovastatin - a potent inhibitor of HMG-CoA reductase
also found in Mevacor. There’s legal dispute as to whether red yeast rice extract is
a drug or dietary supplement. Regardless, it’s been found to significantly lower
total and LDL cholesterol in studies.
⁻ garlic: according to some studies, garlic decreases total blood
cholesterol by up to 5%. It also acts as a potent antimicrobial
(deterring blood infections) and effective blood “thinner” – which
deters clot formations.
⁻ soybeans: have been shown to help prevent CHD by lowering LDL
cholesterol and triglycerides by a few percentage points.
⁻ fenugreek seeds / leaves
⁻ artichoke leaf extract
⁻ ginger
⁻ turmeric
⁻ rosemary
⁻ gugulipids: a gum resin from the mukul myrrh tree. In studies performed in India,
guggulsterone reduced total cholesterol by up to 27% and triglycerides by up to
30% within12 weeks in patients with hypercholesterolemia.
⁻ grapefruit: contains lots of compounds helpful for cardiovascular health (pectin,
vitamin C, flavonoids). Blond and red grapefruits can significantly reduce
cholesterol in just 30 days. Specifically, red grapefruit lowers total cholesterol by
15%, LDL by 20% and triglycerides by 17%. Blond grapefruit lowers total
cholesterol by 7.5%, LDL by 10.5% and triglycerides by 5.5%.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Dietary Supplements
Supplements
• Niacin: is vitamin B-3, also called nicotinic acid.
⁻ common in food, but not in amounts that affect cholesterol levels
⁻ megadoses of 500 mg and higher can raise HDL levels by 15-35% according to
some studies.
⁻ niacin only modestly reduces LDL and triglyceride levels
⁻ nicotinic acid is in some medications such as Niaspan
⁻ niacin has vasodilating properties, which is helpful for reducing high BP
• Policosanol: produced from sugar cane, policosanol was found to
be effective in lowering LDL cholesterol in several studies.
⁻ some OTC products contain policosanol
derived from beeswax (such as Cholestin),
but there is no evidence that this type can
lower cholesterol
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• Phytosterols: sterols and stanol esters are a lot like cholesterol
(molecularly), so when they travel through the digestive tract, they get
in the way of cholesterol absorption.
⁻ intentionally added to some margarines (Benecol, Promise, Smart Balance),
salad dressings, juices and granola bars
⁻ also available as dietary supplements
⁻ research shows that three servings / day can reduce cholesterol by 20 points
• Omega-3 fatty acids: decrease liver production of LDL & triglycerides.
⁻ anti-inflammatory properties limit the growth of plaque in arteries and aid in
thinning blood
⁻ found in fatty fish like salmon, mackerel, herring, tuna and sardines
⁻ other good sources include flaxseed and walnuts
⁻ widely available as dietary supplements (500 or 1,000 mg capsules)
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Drug Therapy
Statins
• The first line of treatment for high cholesterol is dietary
change combined w/ increased exercise (which can drop
total blood cholesterol by 15-20%), but people with very
high levels typically need meds.
• The most commonly prescribed cholesterol-lowering
meds include:
⁻ statins
• Statins (HMG-CoA reductase inhibitors) inhibit HMG-CoA reductase needed for making cholesterol in liver.
• Statins lower LDL & triglycerides, but only mildly raise HDL.
• Also help reabsorb cholesterol from deposits on artery walls.
• First-line of treatment for most people with high cholesterol.
• Research mixed for reducing prevalence of heart attacks.
⁻
⁻
⁻
⁻
⁻
⁻
⁻ bile-acid resins
⁻ cholesterol absorption inhibitors
⁻ fibric acid derivatives
⁻ niacin-based drugs
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atorvastatin (Lipitor, Torvast): best-selling statin (and pharmaceutical)
fluvastatin (Lescol): also exhibits antiviral activity
lovastatin (Mevacor, Altocor): found naturally in red yeast rice
pravastatin (Pravachol, Lipostat): evidence for use weaker than others
simvastatin (Zocor): derived from yeast, like lovastatin
rosuvastatin (Crestor): unusual in that it contains sulfur
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Statin Doses
Statin Side Effects
•
Rosuvastatin (Crestor): most potent agent, as 20 mg reduces LDL by 5055%. Max dose is 40 mg daily due to side effects.
•
Effective at reducing LDL (up to 50% in most people), but side effects are
relatively common and some are serious.
•
Atorvastatin (Lipitor, Torvast): second-most potent agent, as 20 mg daily
reduces LDL by 40-45%. Max dose is 80 mg daily (anytime).
•
•
Simvastatin (Zocor): relatively potent, as 20 mg reduces LDL by 30-40%.
Best to take at night.
•
•
• Lovastatin (Mevacor, Altocor): mildly potent, as 20 mg reduces LDL by 2030%. Best to take with meals.
Most common side effects include GI problems, muscle pain / cramps and
liver damage.
In severe cases, skeletal muscle destroyed (rhabdomyolysis).
Deplete the body of CoQ10, which is needed for heart health and muscle
function.
•
Trigger memory loss, confusion, high blood glucose.
•
Interact with many other meds.
•
Consumption of grapefruit and bitter oranges inhibits the metabolism of
some statins (especially lovastatin and simvastatin), which increases risk
of dose-related adverse effects.
•
Pravastatin (Pravachol): mildly potent, as 20 mg reduces LDL by 20-30%.
Can take anytime.
•
Fluvastatin (Lescol): least potent agent, as 20 mg reduces LDL by 10-20%.
Best to take at night.
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Bile-Acid Resins
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Cholesterol Absorption Inhibitors
• The liver uses cholesterol to make bile acids, which are needed for
fat digestion in the small intestine.
• Bile-acid resins work in the intestines, where they bind to bile salts
and prevent them from being reabsorbed into the blood.
• This triggers the liver to use excess cholesterol to make more bile,
which reduces blood cholesterol levels.
• Absorption inhibitors limit intestinal absorption by blocking
uptake of cholesterol by chylomicrons.
• Most common bile-acid resins are:
• Ezetimibe combined with simvastatin in a drug marketed as
Vytorin.
• Phytosterols are natural cholesterol absorption inhibitors.
• Main cholesterol absorption inhibitor is ezetimibe (Zetia,
Ezetrol), which can safely be used w/ statins.
⁻ colestipol (Colestid): 2 to 16 g / day given once or in divided doses
⁻ colesevelam (WelChol, Lodalis): 4 g daily reduces LDL by up to 18%
⁻ cholestyramine (Questran, Questran Light, Prevalite): 4-8 g once or twice
daily, max dose 24 g daily
• When used alone, relatively mild side effects such as GI
problems, steatorrhea and headaches.
• Mild side effects because not absorbed by body - constipation, gas
and allergic reactions.
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• Ezetimibe available as 10 mg tablets in most markets.
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High Cholesterol: Natural and Pharmaceutical Management
© 2013 Pharmaceutical Education Consultants, Inc. unless otherwise noted. All rights reserved.
Reproduction in whole or in part without permission is prohibited.
Fibric Acid Derivatives
•
•
•
Niacin-Based Drugs
Fibric acid derivatives, or fibrates, primarily reduce the liver's production
of VLDL, which lowers blood triglycerides, but they also decrease LDL
levels.
Fibrates also speed up the removal of triglycerides from the blood and can
marginally increase HDL levels.
The most common fibrates include:
⁻ fenofibrate (Tricor, Lipofen): reformulated in 2005 and now available in 48 mg
or 145 mg tablets
⁻ gemfibrozil (Lopid, Jezil): more toxic than fenofibrate and not as effective at
lowering triglycerides and LDL
•
•
Can be used in conjunction with statins.
When used alone, relatively mild side effects such as GI problems, allergic
skin reactions, muscle tenderness.
• High-dose niacin primarily increases HDL levels, but it also lowers
LDL, VLDL and triglycerides.
• The main niacin-based meds:
⁻ Niaspan: in multiple clinical studies, increased HDL levels by 14-32% at doses
of 1,000-2,000 mg daily, although a large recent (2013) study questions
efficacy
⁻ Niacor: comes in 500 mg tablets like Niaspan does
⁻ Laropiprant: contains 1,000 mg of niacin with 20 mg of a prostaglandin D2
antagonist to suppress flushing, although recently withdrawn worldwide
• Most common side effect of niacin-based meds is flushing, which is
characterized by redness, tingling, or itching that occurs on the
face, neck and chest.
• Taking an aspirin prior to mega-dosing niacin can suppress flushing.
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Prescription Omega-3
38
How Low is Too Low?
• Omega-3 fatty acids available as supplements and as a
prescription med.
• Every single cell needs cholesterol to thrive – especially neurons.
• Lovaza - a brand-name drug that contains esterified and
purified (no mercury contamination) fish oils.
• Most clinical studies outside the U.S. conclude that cholesterol
levels below 150 mg/dL are too low and greatly increase the risk
of depression, suicide & violent behavior.
⁻
⁻
⁻
⁻
FDA approved to lower very high triglyceride levels (>500 mg/dL)
main problem - can raise LDL levels
considered a pharmaceutical, rather than a supplement
each 1-gram capsule is 38% DHA,
47% EPA and 17% other fish oils
•
•
•
•
⁻ can be combined with statins
⁻ very minimal side effects
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Cholesterol affects the metabolism of
serotonin, a substance involved in mood
regulation. Very low cholesterol levels
lead to less serotonin activity in the brain.
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`