Cholesterol, High Cholesterol

Summary: Hyperlipidemia, Dyslipidemia, High Cholesterol and Triglycerides

• Hyperlipidemia leads to atherosclerosis, which is the primary disease process of the coronary arteries leading to coronary heart disease. Atherosclerosis was described by a world renowned Cardiologist, William C. Roberts, MD as the leading cause of heart attacks, stroke, and peripheral vascular disease. This author described that cholesterol intake causes atherosclerosis. (1)

• Individuals age 20 -79 are recommended by the American Heart Association to have cholesterol levels checked every four to six years as part of a cardiovascular risk assessment. The lipid profile should be monitored by the primary care physician who should work with the patient to achieve ideal lipid profile goals:

• Achieve LDL, HDL, triglyceride and total cholesterol goals. The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol has established that the following lipid profile is optimal (as cited in Lichtenstein, 2006)(3):
  • LDL optimal under 100 mg/dl, near optimal 100-129 mg/dL, borderline high 130-159 mg/dL, high 160-189 mg/dL, and very high over 190 mg/dL.
  • Total cholesterol is recommended to be under 200 mg/dL.
  • An HDL goal of over 40 mg/dL for men and over 50 mg/dL for women is generally supported, but no specific official goals for HDL cholesterol and triglycerides exist. The  goal for triglycerides is generally supported to be under 150 mg/dL. An HDL under 40 mg/dL for men and under 50 mg/dL for women as well as a triglyceride level of over 150 mg/dL are all associated with metabolic syndrome.

• Roberts views of the lipid profile goals are more strict than the AHA and recommends the following (1):
  • LDL cholesterol goal <100 mg/dL and ideally <70 mg/dL.
  • Total cholesterol goal <150 mg/dL, and the high-density lipoprotein (HDL) cholesterol >20 mg/dL.
  • The low HDL goal is rationalized by the author that levels below 20 are not dangerous if LDL and total cholesterol is also low.

• In addition to improvement of the lipid profile, modifying other risk factors reduces the risk for cardiovascular disease. For further information on weight loss, hypertension, diabetes mellitus, aerobic exercise, resistance training, or smoking cessation, please see these individual sections in Preventive Health Advisor.

• According to the American Heart Association (AHA) Scientific Statement, Diet and Lifestyle Recommendations: Revision 2006 by Lichtenstein, AH et al, the key to the prevention of coronary heart disease (CHD) or improvement of the CHD course is the emphasis of the following goals for cardiovascular disease risk reduction (3):
  • Diet recommendations by the AHA:
    • Eat a healthful diet the majority of the time including vegetables, fruits, whole grains, fat-free or low fat dairy, beans, lean meat, poultry, and oily fish at least twice weekly. Limit total cholesterol to 300 mg per day for healthy adults and for patients with LDL cholesterol under 100 mg/dl. Limit cholesterol to 200 mg per day for patients with coronary artery disease.
    • Total fat intake limited to under 25–35 percent of total calories per day.
    • Saturated fat intake limited to under 7 percent of total calories per day.
    • Trans fat intake should be under 1 percent of total calories per day.
    • Other fat in the diet should come from monounsaturated or polyunsaturated oils from unsalted nuts, seeds, oily fish, and vegetable oil such as canola or olive oil.
  • Maintain a healthy bodyweight: Patients should strive for a body mass index (BMI) between 18.5-24.9 kg/m²: Preventive Health Advisor recommends a diet focused on weight loss for body mass index over 25 kg/m² for control of lipid levels, and then continued weight loss to reach ideal body weight. Overweight and obese individuals run a much higher risk of developing type 2 diabetes, elevated cholesterol, and high blood pressure. Patients have the ability to reverse this risk by losing 8%-10% of initial body weight, an even a 5% weight loss maintained long term can have beneficial effects on cholesterol and glucose control (4).
    • The AHA defines overweight as 25-29.9 kg/m², and obesity as greater than or equal to 30 kg/m². BMI can be calculated from the basic formula: [Weight (lb) / (Inches of height)²] x 703. BMI may also be calculated using a commonly available BMI calculator such as that available here: http://www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm from the NIH National Heart, Lung and Blood Institute.
    • Weight loss leads to an improved lipid profile. Please see weight loss in Preventive Health Advisor. To reach ideal body weight, Preventive Health Advisor recommends a low calorie diet with fat intake about 30% of calories with mostly monounsaturated fat and at least 1 gram of protein per kilogram of bodyweight plus an exercise program to maintain a higher metabolic rate.
  • Blood pressure:
    • Focus on achieving normal blood pressure.
    • According to the AHA, the lifetime risk of hypertension is about 90% and any elevation above a normal blood pressure of 120 systolic over 80 diastolic increases risk of coronary heart disease even if elevated into pre-hypertensive levels.
  • Blood glucose levels:
    • Keep blood glucose in normal range:
    • According to the AHA, normal fasting blood glucose is less than or equal to 100 mg/dL and a fasting blood glucose of of greater than or equal to 126 is diagnostic of diabetes.
    • Weight loss, exercise, and avoidance of concentrated sweets can greatly improve control of glucose and insulin resistance.
  • Exercise goals: Maintain a physically active lifestyle as regular activity promotes cardiovascular fitness and helps control cholesterol levels.
  • Smoking: Patients should be counseled to stay away from tobacco.

• The American Heart Association metrics were applied by Artero, EG et al in The Aerobics Center Longitudinal Study. The authors described that in order to reduce the risk of cardiovascular mortality over the course of 11 years by 50-60% goals must meet at least 3 out of 4 of the following (2):
  • 1) Total cholesterol lower than 200 mg/dL
  • 2) Blood pressure lower than 120/80 mm Hg
  • 3) Not having diabetes
  • 4) Free of heart disease
  • AND meet at least 2 out of 4 of the following:
  • 1) No smoking
  • 2) Normal body mass index (BMI)
  • 3) Engaging in physical activity
  • 4) Eating healthfully

• Preventive Health Advisor views both dietary changes and an exercise program of vital importance for control of hyperlipidemia. We believe that striving for an ideal diet alone will have a greater health benefit than exercise alone, but if both aspects are combined, then these health benefits will be greatly potentiated.

• Preventive Health Advisor recommends a diet focused on weight loss for body mass index over 25 kg per meter squared for control of lipid levels, then continued weight loss to achieve ideal body weight. For adult patients with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease, the U.S. Preventive Services Task Force (USPSTF) recommends intensive behavioral dietary counseling, and primary care clinicians or other specialists such as nutritionists or dietitians are qualified to provide this counseling (5). Lowering serum cholesterol involves much more than simply lowering cholesterol in the diet. The most effective diet intervention for lowering cholesterol is to replace saturated and trans-fat with monounsaturated and polyunsaturated fats. Additional goals include increasing soluble fiber intake, include soy protein in the diet, and including a fruit and vegetable with every meal.

• The Therapeutic Lifestyle Changes Diet for coronary heart disease (6,7):
  • Saturated fat below 7% of the total calories.
  • Total fat intake 25-35% of daily total calories.
  • Cholesterol intake below 200 milligrams each day.
  • Sodium intake under 2400 mg per day.
  • Calorie intake should be kept to a level needed for maintaining healthy weight but reduce blood cholesterol level.

• Schaefer, S et al found that after dietary fat intake was decreased by 58% and intensive risk factor reduction was implemented, the following benefits were observed after 24 months (8):
  • LDL levels dropped from 120 mg/dL to 104 mg/dL (p = 0.05).
  • Net increase in arterial diameter of 0.05 mm to 2.81 mm (p = 0.01) was seen.
  • 1 out of 8 mild coronary disease lesions < or = 20% regressed, and 4 progressed.
  • Severe lesions with over 50% initial stenosis regressed, but mild lesions under 20% continued to progress, showing that modifying risk factors improves severe lesions.

• Weickert reviewed the following dietary changes and described the expected results from some of these changes (9):
  • Fat intake: Reduction in total fat intake (<30%) has a modest benefit on weight loss but is less effective than low-carbohydrate, high-protein diets and probably reduces insulin resistance, diabetes risk, lowers LDL cholesterol and reduces the risk of cardiovascular disease (CVD).
  • Dietary monounsaturated fatty acids: An increase in monounsaturated fatty acids (>10%) lowers LDL cholesterol, triglycerides, and blood pressure.
  • Low carbohydrate diets, a.k.a. ketogenic diet: Low-carbohydrate diets with a minimum of 130 grams of carbohydrates daily have a modest benefit on weight loss, improves HDL cholesterol and lowers triglycerides.
  • High protein diets: A high protein intake was reported to increase satiety, result in short term weight loss, plus results in beneficial effects on HDL, LDL cholesterol, and blood pressure.
  • Low glycemic index diets: Low glycemic index diets, such as the American Diabetic Association Diet commonly includes foods without concentrated sweets to avoid causing spikes in blood glucose. This diet has a modest benefit on weight loss, improve LDL cholesterol, and probably reduce cardiovascular risk.
  • Soluble fiber: Soluble fiber from fruit and vegetables has a modest benefit on weight loss, lowers glycemic index, LDL cholesterol, and triglycerides.
  • Insoluble fiber: Insoluble cereal fiber including cereals, wheat bran and whole grain products has a modest benefit on weight loss and a strong benefit on insulin resistance.
  • Mediterranean style diets: Mediterranean style diets have a modest benefit on weight loss and have beneficial effects on insulin resistance and diabetes risk. Mediterranean style diets are associated with reduced risk for cardiovascular disease, lower inflammatory cytokines, improved lipid profiles and increased survival.

• Dietary changes for diabetes patients with hyperlipidemia:
  • Low glycemic index diets with a 500 kcal restriction have been known to improved glycemic control, lower hemoglobin A1C by 0.5%, help reduce diabetes medication, and result in a weight loss of 6.9 kg (10).
  • A low carbohydrate diet without restriction other than 20 grams of carbohydrates per day for 24 weeks was known to improve glycemic control, reduce/eliminate medication, reduce hemoglobin A1C in diabetics by as much as -1.5%, reduce body weight by -11.1 kg, and increase HDL by 5.6 mg/dL (10).
  • American Diabetes Association diet vs. vegan diet: Type 2 diabetes. Participants consumed a low-fat vegan diet or a standard American Diabetes Association diet for 74 weeks showed the following outcomes (11):
    • Weight significantly decreased by 4.4 kg and 3.9 kg in the vegan and conventional groups, respectively.
    • The vegan diet resulted in a total and LDL cholesterol decrease by 20.4 mg/dL and 13.5 mg/dL, respectively. Corresponding values for those on the conventional diet was a decrease of 6.8 mg/dL and 3.4 mg/dL. In conclusion changes in overall lifestyle that include a vegan or nearly-vegan diet may be effective in improving the health of people with diabetes.

• Avoid high cholesterol containing foods:
  • Preventive Health Advisor recommends consuming as low an amount of cholesterol as possible.
  • See common foods with high cholesterol content at: Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at (12): https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w601.pdf

• Aerobic Exercise: Preventive Health Advisor recommends a combined aerobic and resistance exercise program for all ages, but patients should seek approval by the primary physician prior to starting an exercise program.
  • Individuals of all ages capable of aerobic exercise should do so most days of the week for the following benefits: heart and lung conditioning, improved pumping efficiency of the heart, improved circulatory system (14), weight control and less obesity (15), cholesterol reduction (15,16), triglyceride lowering (15), lowering of blood pressure (17), lower rate of smoking (20), control of diabetes (18,19), lower cardiac mortality (20), and reduced all-cause mortality (20).
  • Benefits of aerobic exercise, 1 hour per day, 5 days per week, over 10 years (15):
    • With exercise alone: Decrease body mass index about 11.5 kg/m^2, reduce total cholesterol by about 11 points, and reduce their triglycerides by about 105 mg/dl.
    • With exercise plus low fat, high fiber, complex carbohydrate diet: Decrease in body mass index about 16.5 kg/m^2, lower total cholesterol about 33 points, reduction of LDL about 20 points, and reduction of triglycerides about 109 mg/dl.
  • Aerobic exercise done along with or without a cardiac rehab program reduces cardiac and all-cause mortality in coronary artery disease.
  • Starting exercise in apparently healthy adults: According to the American College of Sports Medicine (ACSM) and the American Heart Association (AHA), older adults need moderate-intensity (between 5-6 on a 10-point scale) aerobic endurance activity for a minimum of 30 min which can be achieved in short 10 minute sessions on five days each week or vigorous-intensity aerobic, (rated a 7-8 on a 10-point scale) activity for a minimum of 20 min on 3 days each week.
  • Exercise cardiac stress testing referral is required in patients with (31):
    • Patients with suspected or known coronary artery disease, typical and atypical angina or prior heart attack.
    • Healthy patients without symptoms with multiple heart risk factors (high cholesterol, high blood pressure, family history, obese, diabetes mellitus) or concurrent chronic diseases or those in a high-risk stressful occupations
    • Men over age 40 and women over age 50 who have been inactive but plan to start vigorous exercise.
    • Evaluation of exercise capacity in patients with heart disease involving one or more of the valves of the heart, those with heart rhythm disorders, and those with pacemakers.
  • Cardiac Rehab Programs:
    • Silberman and colleagues reported that 2974 patients participating in an intensive cardiac rehabilitation program reported significant improvements in body mass index (BMI), triglycerides, low density lipoprotein cholesterol, total cholesterol, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, depression, hostility, exercise, and functional capacity at 12 weeks and 1 year. (22)
    • A systematic review and meta-analysis of randomized controlled trials by Taylor et al found that exercise based cardiac rehabilitation for a duration of 0.25–30 months reduces risk of all cause and cardiac mortality by 20% amd 26% respectively, and improves a number of cardiac risk factors in patients with coronary heart disease (20).
  • For further information about exercise in apparently healthy adults or in chronically ill patients, please see aerobic exercise and resistance training sections.

• Resistance training, protein supplements, and hyperlipidemia: Preventive Health Advisor recommends a combined aerobic and resistance exercise program with or without a protein supplement for patients of all ages if approved by the primary care physician. Denysschen, CA et al studied overweight men with a cholesterol level over 200 mg/dl and given 26 grams of whey protein, soy protein, or placebo (23). The subjects were supervised during resistance training for 12 weeks, and total cholesterol reduction of 10.4 mg/dL for placebo, 11.2 mg/dL for soy, and 15.9 mg/dL for whey was noted (23). See resistance training section for further information.

• Evidence-based diet and exercise combination programs for hyperlipidemia and coronary artery disease:
  • The Pritikin Program evidence-based benefits after 12-15 days (25,26,27):
    • Body mass index, 3% reduction
    • Blood pressure, glucose and LDL, all with 10%-15% reduction
    • Triglycerides, 36% reduction
    • Slowed or reversed progression of coronary heart disease and reduce the need for coronary artery bypass grafts (CABG), rates of angioplasty procedures and percutaneous interventions.
    • Usually program is done for 3-4 weeks allowing additional benefit.
  • Pritikin Program includes (24,25,26):
    • Very low fat, less than 10% of calories.
    • Low sodium and avoid salty foods.
    • High fiber with at least five ½-cup servings of whole grains daily (wheat, oats, and brown rice or starch vegetables such as potatoes, and dried beans and peas.
    • Refined grain products (white flour, regular pasta, white rice) are limited to two servings daily.
    • At least four 1-cup servings of raw vegetables daily or ½-cup servings of cooked vegetables. Dark green, leafy, and orange or yellow vegetables are preferred
    • At least three servings of fruit, one of which can be fruit juice.
    • Two servings daily of calcium-rich foods such as nonfat milk, nonfat yogurt or fortified and enriched soymilk.
    • No more than one caffeinated drinks daily. Instead drink water, low-sodium vegetable juices, grain-based coffee substitutes or caffeine-free teas.
    • No more than four alcoholic drinks per week for women and no more than seven for men, with red wine preferred over beer or distilled spirits.
    • No more than seven egg whites per week.
    • No more than 2 ounces (about 1/4 cup of nuts) daily.
    • Moderate amounts of fish, nonfat dairy, and lean meat with no more than one 3.5 cooked serving of animal protein per day with fish and shellfish are preferred. Lean poultry should optimally be limited to once a week and lean beef to once a month.
    • Adapted to vegetarians by replacing animal protein with protein from soy products, beans, or lentils.
    • Avoid fried foods, dressing with fat, and fatty sauces, animal fats, processed meat, dairy products not made with non-rat milk, egg yolks, salty snacks, cakes, cookies, and similar high-calorie choices.
    • Eat frequently with three meals a day plus two snacks.
    • Artificial sweeteners such as Splenda are okay.
    • 45 minutes of moderate exercise daily such as walking.
    • Medicare may approve coverage for qualifying individuals with a history or risk of cardiovascular events. The program has been approved for coverage under Part B of Medicare. Medicare will reimburse eligible beneficiaries for up to 72 one-hour ICR sessions, up to 6 sessions per day, at the Pritikin Longevity Center & Spa.
  • The Dean Ornish Program for Reversing Heart Disease (27):
    • The Ornish program evidence-based benefits:
    • Weight loss of 13.3 pounds in the first 12 weeks and 15.9 pounds after 1 year.
    • Significant reductions in systolic blood pressure (BP), diastolic BP, total cholesterol, triglycerides, and LDL-cholesterol after 12 weeks were still significant after 1 year.
    • Exercise capacity increased by 18% after 12 weeks and 24% after one year.
    • Reductions in depression were still significant after 1 year.
    • Hemoglobin A1C in diabetics continued to decrease after one year.
    • Improvement in severity of angina after 1 year.
  • Ornish Program includes (27):
    • Plant-based, meatless diet, meditation, and regular exercise with adherence to the program between 85 to 90% after one year in hospitals and clinics that have offered it.
    • Medicare Part B covers The Dean Ornish Program for Reversing Heart Disease, under Intensive Cardiac Rehabilitation (ICR). Eligibility includes acute myocardial infarction within the preceding 12 months, a coronary artery bypass surgery, current stable angina pectoris, heart valve repair or replacement, percutaneous transluminal coronary angioplasty or coronary stenting, a heart or heart-lung transplant, or other cardiac conditions as specified through a national coverage determination. (27)

• Effect of adding 30 minutes of daily exercise at 50-75% of age-predicted maximum heart rate, to a Therapeutic Lifestyle Changes Diet (TLC) in 6 months (6):
  • Assisted 89% of participants to reach an LDL cholesterol goal of under 130 mg/dL without lowering HDL levels or needing to add or increase lipid lowering therapy.
  • Mean total cholesterol, LDL cholesterol and triglycerides decreased by 9.2% (p=0.08), 9.3% (p<0.018), and 18.8% (p<0.05), on average respectively.
  • HDL cholesterol increased 2.6% on average (p=0.41).
  • Women: 12.3% reduction in LDL cholesterol and an 11.4% increase in HDL cholesterol
  • Men: 7.9% reduction in LDL cholesterol and no change in HDL
  • Systolic and diastolic blood pressure (BP) decreased 9% (p<0.001) and 13%, respectively (p <0.0001).
  • BP reductions were two-fold greater than in the Diet and Systolic Hypertension study (DASH).
  • 50% reduction in angina.

• Nut consumption, high cholesterol, and risk of coronary events according to Fraser (28):
  • Consumption of almonds and walnuts may result in an 8% to 12% reduction in LDL.
  • Frequent consumption of nuts has been linked with a 30% to 50% decreased risk of coronary heart disease.

• Tree nuts, peanut consumption, and the lipid profile according to Kris-Etherton PM et al (29):
  • Four most recent U.S. studies reviewed by this author estimates that Americans who eat five or more servings of nuts per week have a 35% reduced risk of developing coronary heart disease.
  • Improve CHD related oxidation, inflammation, vascular reactivity.
  • Lower total and LDL cholesterol based on their fatty acid profile plus contain other bioactive compounds with cholesterol-lowering properties.

• Oats for treatment of high cholesterol:
  • Consumption of 100 grams of instant oat cereal for 6 weeks resulted in a lower total cholesterol by 6.2% and reduction of LDL cholesterol by 8.4% (30).
  • A review of studies on oat β-glucan, soluble fiber found in oats, found that 3g oat β-glucan daily lowers LDL cholesterol by about 5%-10% in individuals with normal or high cholesterol, and the effect of this agent is supported by the US Food and Drug Administration  and the UK Joint Health Claims Initiative (31).
  • A randomized controlled trial tested a diet low in saturated fat with 1.8 grams of oil-based phytosterols and 2.8 g beta-glucan daily lowered total and LDL cholesterol by 3.7% and 2.3 % respectively without a significant change in controls after 6 weeks (32).
  • A 6-week randomized controlled trial on hypertensive and hyperinsulinemic subjects by Keenan et al, tested an oat cereal group on 5.52 grams daily of β-glucan or a low-fiber cereal daily and found these results (33):
    • Systolic blood pressure decrease of 7.5 points and a diastolic pressure reduction of 5.5 points
    • Decrease in both total cholesterol of 9% and LDL cholesterol of 14%
    • Trend toward improved insulin sensitivity.
  • Another study showed that 10 grams daily of β-glucan rich oat bran or wheat bran only improved total cholesterol temporarily (34).

• Soy isoflavones, flavonoids, and cholesterol:
  • In total 115 women participating in a cross-sectional study on flavonoid consumption from vegetables (72.3%), fruits (15.6%), green tea (5.4%), potatoes (3.8%) and tofu (2.9%) found that the intake of flavonoids was inversely related with LDL cholesterol, intake of other phytochemicals was not correlated with lipid levels, and  there was no correlation between green tea consumption and plasma lipids seen (35).
  • Crouse et al found that subjects with high LDL cholesterol levels on a diet of 25 grams of isolated soy protein with 62 mg of isoflavones showed significant decreases in LDL cholesterol by 6% vs 4% with a diet including 25 grams of casein (36).
  • Soy protein and hyperlipidemia: The FDA supports that soy protein may reduce the risk of coronary artery disease by lowering cholesterol levels when included in a diet low in saturated fat and cholesterol (37).

• Fiber supplements for treatment of hyperlipidemia: Fiber supplements add volume to the stomach to curb hunger, bind fats and cholesterol to reduce absorption, and promote weight loss by overall reduction of calorie density in the gastrointestinal tract. Guar gum, glucomannan, or psyllium husk fibers are recommended as a fiber supplement to reduce HbA1C, fasting blood glucose, improve the lipid profile, lowered blood pressure and assisted in weight loss by providing fullness to reduce hunger.
  • Guar gum has been taken at a dose of 10 grams per day for 8 weeks (39), 20 grams per day for 4 weeks (40), 15 grams per day for 42 weeks (42), or 30 grams per day for 6 weeks (43). Benefits of guar gum include:
    • Reduction in fasting blood glucose of 16.9 mg/dL (38)
    • Improvement of HbA1C by 0.5-1% (38,39,42)
    • Total cholesterol reduction in one study of 21% (40), another study showed cholesterol reduction of 13% (42), and a third study showed total cholesterol was lowered by 0.6 mmol/L (43).
    • Lowered post-prandial blood glucose (40,49)
    • Reduced insulin requirement (40,49)
    • Weight loss (41)
    • LDL reduction of 8% (42)
    • Decreased systolic and diastolic blood pressure by 6 mmHg and 3 mmHg, respectively (43)
    • Increase in insulin sensitivity (43).
    • One study showed no improvement of total cholesterol, triglycerides, HDL, or LDL (38).
    • One study showed no improvement of insulin sensitivity or HbA1C (40).
    • Guar gum adverse reactions and interactions: 62.5% of patients receiving guar gum experienced side effects including abdominal cramps, diarrhea (most common), and skin itching (38). Another study noted flatulence, loose stools, and a feeling of stomach discomfort (42).
  • Psyllium fiber and hyperlipidemia: Psyllium fiber at a dose of 10.2-21 grams daily for at least 3 weeks lowers total cholesterol by 4-6 % or 30mg/dL, lowers LDL cholesterol by about 7% or 15 mg/dL, may slightly increase or decrease HDL cholesterol, and has also shown significant reductions in fasting blood glucose, and lowering of HbA1c.
    • Psyllium fiber at a dose of 5.1 grams twice daily for 8 weeks improved total cholesterol 5.8%, LDL cholesterol 7.2% on a high fat diet and 4.2% and 6.4%, respectively for those on a low-fat diet (44).
    • A meta-analysis with 8 studies and 656 subjects on a low fat diet plus 10.2 grams of psyllium daily for at least 8 weeks was well tolerated, reduced total cholesterol by 4%, lowered LDL cholesterol by 7%, and decreased the ratio of apolipoprotein B to apolipoprotein A-I by 6%, but change in HDL or triglycerides was not seen. (45)
    • 26 weeks of treatment with 5.1 g psyllium twice daily lowered total and LDL-cholesterol levels by 4.7% and 6.7% respectively compared to placebo. (46)
    • A study followed 7 men on 21 g/day of psyllium fiber for 3 weeks reduced total cholesterol, by 30mg/dL, LDL cholesterol by 15 mg/dL and HDL by 4 mg/dL (47).
    • Psyllium enriched cereal lowered total, and LDL cholesterol more than cereal or pectin enriched cereal (48).
    • Patients taking metformin and experiencing side effects of flushing, may obtain relief of these symptoms from psyllium fiber (50).
  • Konjac glucomannan and hyperlipidemia: Glucomannan is a water-soluble dietary fiber that is derived from the konjac root.
    • Glucomannan taken at a dose range of 1.2 to 15.1 grams per day for 3-16 weeks yielded the following average benefit across 14 studies (51):
      • Decreases in total cholesterol by -19.28 mg/dL
      • Lowered LDL cholesterol by -15.99 mg/dL
      • Triglycerides reduced by -11.08 mg/dL
      • Reduction in body weight by – 0.79 kg (-1.74 lbs)
      • Lowered fasting blood glucose by -7.44 mg/dL.
      • No effect on HDL or blood pressure was seen.
    • Glucomannan at a dose of 10 grams per day plus plant sterols at a dose of 1.8 grams per day was more effective than glucomannan alone (52):
      • LDL was 2.95 mmol/L after glucomannan plus plant sterols vs. 3.60 mmol/L after placebo.
      • Total cholesterol was also lower after glucomannan plus sterols at 4.72 mmol/L vs. placebo of 5.47 mmol/L.
    • Glucomannan at a dose of 3.6 grams per day for 28 days reduced LDL by 20.7% and fasting glucose levels by 23.3% (53).
    • Glucomannan-enriched biscuits with 0.7 grams glucomannan daily or placebo of wheat bran fiber biscuits taken by subjects on medication and a low cholesterol diet every day for three weeks lowered systolic blood pressure by 6.9% but body weight, HDL, LDL, and total cholesterol, triglycerides, glucose, insulin, and diastolic blood pressure were unchanged (54).
    • Glucomannan at a dose of 1240 mg to 4320 mg per day plus a low-calorie diet (1200 kcal) was more effective than placebo and a low calorie diet for improvement in body weight, total cholesterol, and hunger/satiety (55). Weight loss contributes to improvement of hyperlipidemia. Weight loss over 5 weeks was 3.8–4.4 kg with the doses of glucomannan mentioned above (55)
    • Glucomannan and a low-calorie diet (1200 kcal) was more effective than placebo and a low calorie diet for improvement in body weight, total cholesterol, and hunger/satiety in a 60-day study that included 30 participants (56).
  • Fiber adverse reactions and interactions.
    • Dry powdered fibers are generally safe when mixed with adequate water or another liquid, but are not without health risks.
    • At least 8 ounces of fluid is recommended when taking dry fibers such as glucomannan, Konjac root, guar gum, Citrucel, and psyllium (Metamucil).
    • Health Canada issued a warning that glucomannan fiber has resulted in choking, obstruction of the throat, esophagus or bowels according to reports when not consumed with an adequate amount of fluid (57).
    • The warning also stated that the fiber should not be taken before bed (57).
    • Less flatulence occurred in a psyllium treatment group compared to a placebo group, and also experienced similar diarrhea and constipation in both groups (50).
    • Fibers may also bind medications and interfere with absorption resulting in a reduction in the desired effect of the medication. Therefore, medications should be taken at least 2 hours before or after the fiber.

• Increasing HDL- A regimen which may assist to raise HDL could include the following. Recheck lipid panel in 3-6 months. If not at goal, then can increase policosanol to 10 mg.
  • Sustained release Niacin, 500 mg daily.
  • Policosanol 5mg daily
  • 2 kiwifruits daily.
  • 250 ml of red wine nightly.
  • Cardiovascular exercise 30 min daily and resistance training three times per week.

• Increasing HDL cholesterol with niacin:
  • Niacin may be used with or without statin medications. Niacin is not a benign supplement, but is used more like a standard medication as one of the strongest acting agents known to increase high-density lipoprotein (HDL). Niacin is the recommended treatment to lower lipoprotein (a) which helps reduce the risk of heart disease (58,59), and result in less cardiac events (62). Niacin also lowers LDL cholesterol a small amount (60).
  • We recommend immediate release niacin over sustained release niacin due to a lower risk of hepatotoxicity, especially since niacin is often considered for use with statins which further increases this risk.
  • Niacin dose:
    • Immediate release niacin is generally started at a dose of 250 mg -1000 mg twice daily, may be increased to up to 1000 mg three times daily as tolerated, and is safe if monitored appropriately (65).
    • Sustained release niacin dose should be limited to 1000 mg daily because it is tolerated well and has less hepatotoxicity than higher doses (64).
  • A study compared both immediate release and sustained release niacin therapy starting at 500 mg daily with a dose escalation every 6 weeks up to 3000 mg daily yielded the following results (61):
    • Immediate release niacin increased HDL cholesterol more than the sustained release form.
    • Sustained release niacin lowered LDL better than immediate release niacin at a dose of 1500 mg per day.
    • Triglycerides were decreased to similar levels with both forms of niacin.
    • According to the author, sustained release niacin was unsafe since hepatotoxicity occurred in over 50% of this group, but did not occur in any subjects taking the immediate release form.
  • The ADMIT study (Arterial Disease Multiple Intervention Trial), evaluated immediate release niacin at a dose escalation up to 3000 mg daily in a large study group for 48 weeks and found the following results (65):
    • Significant lowering of total cholesterol, LDL, and triglycerides.
    • Significant increase in HDL.
  • Sustained release niacin at 500 mg daily for 4 weeks followed by 1000 mg daily for 4 weeks resulted in compliance of over 90%, increased HDL by 17%, LDL decreased by 11%, and did not result in any significant transaminase elevations (64).
  • Use of niacin was associated with a 31% increase in high-density lipoprotein (HDL), at a dose of 1g low-dose long-acting niacin daily but did not change total cholesterol or triglyceride levels (58).
  • Extended-release niacin 1000 mg/day added to statin therapy in a double-blind randomized placebo-controlled trial over 1 year had the following results (62):
    • Slowed the progression of atherosclerosis among patients with known coronary heart disease plus low HDL cholesterol.
    • Carotid intima-media thickness increased significantly in the placebo group and was unchanged in the statin plus niacin group.
    • 21% increase in HDL cholesterol in the niacin group.
    • Cardiovascular events were reported in 3.8% and 9.6% of patients in the niacin group and placebo group, respectively.
  • In a 3-year double-blinded, placebo-controlled trial by Brown et al, treatment with sustained release niacin added to simvastatin dramatically reduced cardiac events, improved stenosis of coronary arteries, and reduced LDL cholesterol (LDL-C) levels in coronary heart disease (67).
  • Extended-release niacin (500-3000 mg/day) reduced LDL cholesterol 5.7-11% in women and had a greater effect than in men at all doses, and triglycerides were also decreased greater for women than for men but was only significant at the 1500 mg/day dose (60).
  • Niacin adverse reactions and interactions:
    • The most common adverse effects of niacin include flushing, hyperglycemia, and hyperuricemia (67,59), which results in about 40% of subjects to discontinue the drug (58).
    • Niacin may cause hepatotoxicity in sustained release and immediate release forms, but at a much higher rate when taken in the form of sustained release niacin (67,61). Both forms require monitoring of transaminases.
    • Higher creatine kinase levels, uric acid, and insulin (67).
    • If switching from immediate to sustained release niacin, begin at a much lower dose. A case report showed that when switching from 3 g/daily of immediate-release niacin to same dose slow-release niacin an individual developed hepatitis (63).
    • Niacin has been known to induce overt diabetes (58), increase plasma glucose (130), but has left hemoglobin A1C unchanged (65).
    • Niacin may cause fatigue, elevation in liver function tests, hepatotoxicity, gastrointestinal complaints, and acanthosis nigricans (61).
    • Niacin administration long term is associated with increased plasma homocysteine levels of 17-55% (66).
    • Blood pressure is decreased by use of nicotinic acid (Niacin).

• Red wine and hyperlipidemia:
  • Red wine both increases HDL cholesterol and decreases LDL cholesterol significantly at doses of 150-400 ml daily.
  • Drinking red wine has significantly better cardiovascular disease risk reduction compared to beer, vodka, whiskey, gin, tequila, or rum (71).
  • Red wine appears to provide cardiovascular disease benefit by both increasing HDL cholesterol from the alcohol content, and by inhibiting platelet aggregation (68).
  • Moderate red wine consumption has been associated with an improved cholesterol profile including an increase in HDL cholesterol and reduction of both mortality risk and risk of cardiovascular disease (69).
  • At the end of a 4-week study period, results showed that drinking red wine in moderation increased HDL cholesterol by 11–16%, decreased fibrinogen by 8–15% and according to the authors was associated with beneficial changes in blood lipids and fibrinogen that may help to reduce the risk of CVD (70).
  • De Gaetano and Cerletti reported that after red wine consumption (30 g alcohol daily for 4 weeks) as compared to the same amount of alcohol given as spirit such as vodka, whiskey, gin, tequila, or rum resulted in a significant increase in HDL cholesterol levels and a decreased oxidation of LDL cholesterol. The authors reviewed a meta-analysis which indicated a significant negative relationship between moderate wine drinking of 150-300 ml daily and the risk of cardiovascular events. In conclusion, moderate wine consumption is linked with prevention of cardiovascular disease. (71)
  • 400 mL/day of red wine for 6 weeks significantly decreased LDL cholesterol concentrations by 8% and increased HDL cholesterol concentrations by 17% and reduced cardiovascular disease risk compared to no effect for placebo (72).
  • Andrade, AC et al found that subjects with baseline triglycerides under 139 mg/dL taking 250 ml of red wine nightly for 15 doses had the following results (73) :
    • Subjects with hypercholesterolemia
      • Total cholesterol reduction by 17 mg/dL
      • HDL decreased by 4 mg/dL
      • LDL decreased by 17 mg/dL
      • Triglycerides increased 13 mg/dL
    • Subjects with hypertension
      • Total cholesterol reduction by 7 mg/dL
      • HDL increased by 1 mg/dL
      • LDL decreased by 14 mg/dL
      • Triglycerides increased 31 mg/dL
    • Healthy control subjects
      • Total cholesterol increased by 22 mg/dL
      • HDL increased 7 mg/dL
      • LDL increased 13 mg/dL
      • Triglycerides increased 11 mg/dL

• Lowering elevated triglycerides with Omega-3 fatty acids:
  • Please see the section on omega-3 fatty acids for more information.
  • American Heart Association (AHA) fish, fish oil, and oil intake recommendation (75):
    • All adults are recommended to eat fish (particularly fatty fish) at least two times per week.
    • AHA also recommends eating plant-derived omega-3 fatty acids, tofu and other forms of soybeans, walnuts and flaxseeds and their oils.
    • For patients with coronary heart disease, it is recommended they consume about 1 gram of the two kinds of omega-3 fatty acids shown to be cardio-protective, EPA and DHA
    • Omega-3 fish oil is beneficial for treatment of elevated triglycerides. Patients needing triglyceride-lowering, should have fish oil prescribed by a qualified healthcare provider. The AHA recommends a daily intake of 2-4 grams of EPA+DHA for elevated triglycerides.
    • Expected triglyceride lowering effect by omega-3 fish oil (dose range 0.045 to 5.9 grams of EPA and DHA per day) in a meta-analysis that included 21 (76):
    • Total average decrease in triglycerides of 27 mg/dL.
    • Increase in HDL cholesterol of 1.6 mg/dL.
    • Increase in LDL cholesterol of 6 mg/dL.
    • Total cholesterol was not affected by fish oil intake.
    • The more fish oil consumed, the greater the reduction in triglycerides by a dose-dependent effect.
    • Patients with higher triglyceride level prior to starting fish oil experienced a greater response.
    • For every 1 gram of fish oil intake, triglycerides were reduced about 8 mg/dl.
    • Benefit of plant-based omega-3 fatty acids (ALA) were inconclusive.
  • 3g daily fish oil for 5 weeks had lowered blood pressure and plasma triglyceride levels with omega-3 compared to placebo (77).
  • In a randomized controlled trial called the GISSI-Prevenzione trial done in Italy, 11,324 patients with pre-existing coronary heart disease (CHD) were randomly allocated to either 300 mg vitamin E, 850 mg omega-3 fatty acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), both, or no treatment and followed for 3.5 years noted the following results (78):
    • 15% reduction in mortality, nonfatal myocardial infarction, and nonfatal stroke was seen in participants taking 850 mg omega-3 fatty acid alone.
    • Participants taking omega-3 fatty acid after 6-months experienced a 2.5% increase in HDL cholesterol and a 4% reduction in triglycerides.
    • 20% reduction in all-cause mortality and a 45% reduction in sudden death.
  • A review of 14 randomized clinical trials reported that fish oil is associated with a reduction in total mortality and sudden death, but not nonfatal heart attacks (79).
  • A 3.5-year study including 11,324 myocardial infarction (MI) survivors with an MI occurring within 3 months) showed that fish oil supplementation at a dose of 1 gram daily, but not vitamin E at a dose of 300 mg daily, significantly reduced the total rate of all-cause death, nonfatal MI, and nonfatal stroke (80).
  • Omega-3 fish oil adverse reactions and interactions:
    • A total of 10 studies were reviewed by Villani AM et al to determine potential serious adverse effects of fish oil at a dose of under 1.86 grams per day (98). It was found that there were no serious adverse effects reported in 994 adults over 59 years of age and other non-serious adverse effects were not significantly different from placebo (81).
    • Fish oil has been reported to affect platelet aggregation, reduce vitamin K dependent factors which may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding (82).
    • A case of a 67-year old woman taking warfarin (1.5 mg/day), an increase in her fish oil intake from 1 g/day to 2 g/day was associated with an increase in time for blood to clot as measured by the international normalized ratio (INR) which went from 2.8 to 4.3 within 1month, and decreased to 1.6 after the fish oil dose was reduced (83).
    • An intake of 6 grams per day of docosahexaenoic acid (DHA) found no significant difference found in blood coagulation, platelet function, or thrombotic parameters including prothrombin time, activated partial thromboplastin time, antithrombin-III levels, and platelet aggregation (84).
    • Fish oil may contain harmful contaminants such as heavy metals including mercury, dioxins, and polychlorinated biphenyls (PCBs). This risk can be reduced by purchasing fish oil that has undergone a purification process specified on the label (approved by the FDA, EPA, or US Pharmacopeia) (85)

• Kiwi fruit, HDL, and trigycerides:
  • Consuming 2-3 kiwi fruit per day may lower blood triglycerides levels by about 15% and may reduce platelet aggregation as a benefit in cardiovascular disease (86).
  • A small study on men with high cholesterol who ate 2 kiwi fruit per day for 8 weeks experienced the following (87):
    • No change was seen in total or LDL cholesterol.
    • HDL cholesterol increased significantly.
    • Ratio of LDL cholesterol to HDL cholesterol and the ratio of total cholesterol to HDL cholesterol decreased significantly.
    • Levels of vitamin C and vitamin E increased significantly.

• Areca-nut associated with higher triglyceride levels: Areca-nut chewing has been associated with hyperglycemia, type 2 diabetes, metabolic syndrome, obesity, increased body mass, and higher triglyceride levels (88).

• Coenzyme Q10 and hyperlipidemia: For further information about co-enzyme Q10, please see coenzyme Q10 sections of Preventive Health Advisor. Although there is no standard for co-enzyme Q10 replacement, and monitoring, we recommend a co-enzyme Q10 supplement with statin medications to keep the level over 0.70 micromol/L, closer to healthy controls. As a guidance for dosing, a trial used co-enzyme Q10 to control blood pressure gradually over months by using doses of 75–360 mg daily to attain a therapeutic level of CoQ10 over 2.0 mcg/ml (89).

• This recommendation is due to depletion of co-enzyme Q10 by statins, its association with improvement in endothelial function, it’s inverse association with coronary artery disease, and it’s favorable effect on blood pressure:
  • For further information about co-enzyme Q10, please see the coenzyme Q10 section of Preventive Health Advisor.
  • Both hyperlipidemia and hypertension are risk factors for coronary artery disease which have been treated with some success using coenzyme Q10 supplementation.
  • Patients beginning treatment with 80 mg oral atorvastatin were noted to have an average drop of coenzyme Q10 level by 50% after 30 days of treatment, and lower CoQ10 levels appeared to contribute to muscle pain, exercise intolerance and myoglobinuria (90).
  • On standard doses of atorvastatin 10 mg and 20 mg, simvastatin 10 mg and 20 mg, or pravastatin 20 mg and 40 mg not only lowered cholesterol, but also decreased production of coenzyme Q10. (91).
  • Yalcin et al. indicated that a relation between low plasma coenzyme Q10 (CoQ10) concentration and coronary artery disease (CAD) exists, and CoQ10 concentrations in patients with CAD was different from healthy individuals (0.41 vs. 0.77 micromol/L, respectively) (93). Additionally, compared to healthy individuals, patients with CAD had a significantly lower ratio of CoQ10 to low density lipoprotein (LDL) (p < 0.01). (93)
  • Coenzyme Q10 and vascular endothelial function: Supplemental coenzyme Q10 resulted in a clinically significant, 1.7% increase in flow-dependent endothelial-mediated dilation (94).
  • Coenzyme Q10 at 50 mg twice daily for 10 weeks decreased systolic blood pressure from an average of 164.5 mmHg to 146.7 mmHg, and diastolic blood pressure decreased from an average of 98.1 mmHg to 86.1 mmHg (92).
  • Coenzyme Q10 levels should be monitored to achieve desired therapeutic level while monitoring for response. Rosenfeldt FL et al expressed that co-enzyme Q10 levels are patient dependent based on variable absorption, use of other medications, and patient response. As cited by Rosenfeldt, FL et al, a large trial used co-enzyme Q10 to control blood pressure gradually over months by using doses of 75–360 mg daily to attain a therapeutic level of CoQ10 over >2.0 g/ml. (89)

• Garlic and hyperlipidemia:
  • 12 weeks of garlic supplementation in a double-blind randomized, placebo-controlled trial, (with 9.6 mg allicin-releasing potential) reduced total cholesterol by 4.2%, decreased LDL cholesterol by 6.6%, and reduced HDL cholesterol by 0.9% (95).
  • In a review of 29 randomized controlled trials, Garlic in comparison with placebo was associated with a significant reduction in levels of total cholesterol by 0.19 mmol/L and trigycerides by 0.11 mmol/L, but garlic had no effect upon LDL cholesterol or HDL cholesterol (96).
  • A separate review of 13 randomized controlled trials with 1,056 subjects taking garlic for 12-24 weeks showed no significant change compared to placebo in levels of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides or apolipoprotein B (97).
  • Allicor, hyperlipidemia, and risk of ischemic heart disease (98):
    • After 1 year of Allicor treatment, a long-acting garlic drug, the 10-year absolute risk of IHD was reduced by10.7%, and the 10 year risk of both acute myocardial infarction, and sudden death were reduced 22.7%.
    • A reduction in total cholesterol and LDL cholesterol for men (by 27.9 and 22.5 mg/dl, respectively) and women (by 11.4 and 10.8 mg/dl, respectively) was reported.
    • Allicor used by women was also reported to prevent age-related cardiovascular risk.

• Plant sterol-esters and hyperlipidemia: Plant sterol-esters, chemical name β-sitosterol, are additives to butter, margarine or other spreads with a chemical structure similar to cholesterol, which take the place of cholesterol in the intestines and result in reducing cholesterol absorption (99). When purchasing a spread product for lowering cholesterol, Preventive Health Advisor recommends a product which specifies that it contains at least 8 grams of plant stanol esters, plant sterol esters, or phytosterols per 100 grams of product. Most studies showed a benefit in lowering total cholesterol, LDL cholesterol, and triglycerides. The recommended dose is 2-9 grams of the phytosterols per day which has been taken in studies for 3 weeks to 1 year.
  • Phytosterols were found to be safe, tolerated well, and was not associated with any adverse effects at a dose of 3.4 grams per day (105), and up to a dose of 9 grams per day for 8 weeks (103,100).
  • In general, stanol ester in margarine at a dose of 2-3 grams daily of stanols is associated with a reduction in total and LDL cholesterol of about 15% and 20% respectively (102).
  • Davidson, MH et al found that 3 grams daily reduced triglycerides about 13%, and 9 grams daily reduced the ratio of total cholesterol to HDL by about 10% , but in this trial, there was no significant changes in LDL cholesterol (103).
  • Ayesh et al found a reduction in total and LDL cholesterol of 18% and 23%, respectively, after 21–28 d consumption of 8.6 g plant sterols, provided through margarines in a study of 24 healthy individuals (50% male) (100).
  • 20 grams of spread taken daily with 1.6 grams of plant sterols in a 1-year double-blind, placebo-controlled trial reduced total cholesterol by 4% and LDL cholesterol by 6% on average (101).

• Policosanol and high cholesterol: Policosanol is a natural therapy derived from sugar cane which is effective for hyperlipidemia, is superior to plant sterols, and has an excellent safety profile .
  • Castano, G. et al found that 1 gram omega-3 fatty acid plus policosanol, at a dose of 5 mg or 10 mg  improved lipids significantly in 8 weeks compared to 1 gram omega-3 fatty acid plus placebo (104):
    • Reduction of total cholesterol 12.7% and 15.3% respectively.
    • Reductions in LDL cholesterol, 21.1% and 24.4% respectively.
    • Increase in HDL cholesterol 14.4% and 15.5%, respectively.
    • Lowered triglycerides by 13.6% and 14.7%, respectively.
    • Placebo reduced triglycerides 14.2%, but did not improve total, LDL, or HDL.
  • A meta-analysis by Chen, JT et al evaluated 23 plant sterol/stanol and 29 policosanol RCTs which found that this supplement is not only more effective than plant sterol supplements, but also nearly as effective as common cholesterol lowering medications.
  • In a double blind placebo controlled trial on 29 type 2 diabetics, policosaol at a dose of 10 mg daily resulted in lowering of total cholesterol by 17.5%, LDL was lowered by 21.8%, and HDL was raised by 11.3% and triglycerides were lowered by 6.6% over placebo. These findings were statistically significant other than the positive effects seen on HDL and triglycerides which was not statistically significant (142).
• Policosanol adverse reactions and interactions
  • This agent is generally well tolerated by most individuals. Adverse effects reported include lethargy, headaches, insomnia, anxiety, dizziness, nausea, painful urination, weight loss, rash, redness of the skin, gum bleeding, and nose bleeding (142).
  • Policosanol has been reported to affect platelet aggregation which may be associated with an anticoagulation or reduced blood clotting effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, ticlopidine, heparin, fish oil, nonsteroidal anti-inflammatory drugs (NSAIDs), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, and many others because of the potential increased risk of bleeding (143).