Articles

Hyperlipidemia

Introduction

Hyperlipidemia is an elevation of one or more of the following: cholesterol, cholesterol esters, phospholipids, or triglycerides. Although cholesterol has received much negative press, in normal quantities, it is essential for life. Cholesterol and triglycerides, as the major plasma lipids, are essential substrates for cell membrane formation, steroidal hormone synthesis, and production of bile acids. Effective management of hypercholesterolemia requires understanding the biochemistry of cholesterol and the importance of cholesterol in normal physiology. In recent years, studies have consistently shown that abnormalities of plasma lipoproteins can result in a predisposition to coronary artery disease, pancreatitis, xanthomas, or neurologic disease. Accumulating evidence has linked elevated total and low-density lipoprotein cholesterol (LDL-C) and reduced high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease.

Lipids, being water immiscible, are not present in the free form in plasma, but are transported as lipoproteins. Hyperlipoproteinemia describes the increased concentration of the lipoprotein macromolecules that transport lipids in the plasma. (1) Lipoproteins have a lipid core made up of cholesterol esters and triglyceride with an outer hydrophilic shell of phospholipids and unesterified cholesterol. The outer shell has at least one protein that provides a very important ligand for attaching to receptors on cell surfaces. This protein, in very simple perspective, is the delivery address for that specific lipoprotein. (2) Density, composition, and electrophoretic mobility have been used to divide the lipoproteins into four classes: chylomicrons, VLDL, LDL, and HDL.

Chylomicrons are large triglyceride-rich particles containing apolipoprotein B-48, B-100, and E, that transport cholesterol to the liver from cholesterol in the diet and/or from cholesterol synthesized in the intestines. Chylomicrons are normally not present in the plasma after a 12-14 hour fast and are catabolized by the enzyme lipoprotein lipase (LPL). If lipoprotein lipase levels are low, triglyceride levels can be very high.

VLDL or very low-density lipoproteins are formed primarily in the liver, and to a lesser extent, the intestines. VLDL has been subdivided into three classes, and it carries about 10-15 percent of serum cholesterol and most of the triglyceride in the fasting state. VLDL is a precursor of LDL, and VLDL "remnants" may also be atherogenic. VLDL serves to distribute cholesterol and triglycerides to the cells. As VLDL complexes circulate, they become progressively smaller. Metabolism occurs through the action of two enzymes, lipoprotein lipase and hepatic lipase. Drugs that enhance these enzymes hasten the process and are effective in lowering triglyceride levels. Current therapies directed at preventing atherosclerosis do not focus on VLDL, but instead affect elements that are produced by VLDL. (3)

LDL, or low-density lipoprotein, has been further divided into LDL1 and LDL2. LDL2 carries 60-70 percent of the total serum cholesterol. This is considered the "bad" lipoprotein, since the likelihood of atherosclerosis is directly related to the concentration of LDL in the blood. Lowering LDL is the primary target for therapy of hypercholesterolemia.

HDL, or high-density lipoprotein, functions in transporting cholesterol from peripheral cells to the liver. It is often known as the "good" cholesterol, since high levels mean that much of the peripheral cholesterol is being transferred to the liver for disposal.

The most common classification for hypercholesterolemia is the Fredrickson-Levy-Lee Classification of Hyperlipoproteinemia illustrated below:

Type Lipoprotein Elevation Cholesterol (mg/dl)approx. mean Triglycerides (mg/dl)approx. mean
I Chylomicrons 324 3316
IIa LDL 368 148
IIb LDL +VLDL 354 135
III IDL (LDL1) 441 694
IV VLDL 251 438
V VLDL+ chylomicrons 373 2071

While commonly used, this classification system does not explain the many variants seen due to genetic and metabolic defects in cholesterol metabolism. It has become apparent recently that specific genetic defects with disrupted protein, cell, and organ function give rise to several disorders within each family of lipoproteins. The first of these abnormalities involve defective clearance.

Familial hypercholesterolemia (FH) is probably the best understood of the primary hyperlipoproteinemia disorders and is characterized by an elevation of LDL cholesterol, deposition of LDL-derived cholesterol in tendons (xanthomas) and arteries (atheromas), and inheritance as an autosomal dominant trait with homozygotes more severely affected than heterozygotes. The incidence in the United States is about 1 in 500. It is inherited from one generation to another and results in defects in the LDL receptors. Another type of clearance defect is familial defective apolipoprotein B-100. The result of this defect is decreased binding to LDL receptors. Diagnostic features are indistinguishable from FH.

Familial dysbetalipoproteinemia (type III) is a result of defective cholesterol clearance. The defect is in apolipoprotein E and results in elevations of cholesterol and triglycerides, because apolipoprotein E is necessary for the clearance of VLDL and chylomicrons from systemic circulation. The E class of apolipoproteins are ligands for multiple cellular receptors, and often patients also suffer from diabetes, hypertension, obesity, and hyperuricemia. Family history is usually positive for premature atherosclerotic disease and xanthomas of the palms. Tuberoeruptive xanthomas are also commonly present.

Polygenic hypercholesterolemia is the most common form of dyslipidemia in the U.S. population. The cause is unknown, but is thought to be due to dietary and genetic factors. LDL levels are usually moderately elevated. History of premature coronary heart disease is present in only about 20 percent of cases, and there are no distinguishing diagnostic features. Dietary control of this condition is often possible, as dietary saturated fatty acids act to reduce LDL receptor activity.

The second general category of dyslipidemia is disorders with increased lipoprotein production. Familial combined hyperlipidemia (FCHL) is a classic example of increased production of lipoproteins. Many patients have both elevated triglycerides and/or lipoproteins. These patients appear to overproduce apolipoprotein B-100. Clinical features include obesity, hypertension, diabetes, or hyperuricemia. FCHL is presumed in patients with elevated cholesterol and or triglycerides, a strong family history of coronary disease, and a family history of dyslipidemias. (4)

Hyperbetalipoproteinemia patients have increased hepatic apolipoprotein production with acceptable LDL and triglyceride levels, but still have a positive family history of premature CHD. Hypoalphaproteinemia is a condition involving the so-called "isolated low HDL" patients. Little is known about the cause, but it is associated with increased CHD, obesity, smoking and lack of exercise. Evidence of drug effectiveness is lacking for these patients; therefore, lifestyle changes that increase HDL and lower LDL are most often advocated. (5)

Before determining a treatment plan for patients, potential causes of secondary hypercholesterolemia must be identified and evaluated. Chronic diseases such as hypothyroidism, diabetes mellitus, and elevated cortisol must be considered and controlled as a part of the therapy plan of controlling hypercholesterolemia. Drugs such as alcohol, progestins, beta-blockers, thiazide diuretics, and glucocorticoids may cause secondary hypercholesterolemia, and their use should be evaluated in patients with elevated cholesterol levels. In addition, xenotoxin exposure such as heavy metals or pesticides as well as the excessive intake of partially hydrogenated oils may contribute to elevated lipids.

Type Lipoprotein Elevation Cholesterol (mg/dl)approx. mean Triglycerides (mg/dl)approx. mean
I Chylomicrons 324 3316
IIa LDL 368 148
IIb LDL +VLDL 354 135
III IDL (LDL1) 441 694
IV VLDL 251 438
V VLDL+ chylomicrons 373 2071

Adapted from Schafer EJ, Levy RI. Pathogenesis and management of lipoprotein disorders. N Engl J Med. 1985;312:1302.

Statistic

World Health Organization, 2002.

  • Almost one fifth (18%) of global stroke events (mostly nonfatal events) and about 56% of global heart disease are attributable to total cholesterol levels above 3.2 mmol/l.
  • This amounts to about 4.4 million deaths (7.9% of the total) and 2.8% of the global disease burden.

U. S. Department of Health and Human Services Public Health Service, National Institutes of Health.

    Blood cholesterol levels in men and women begin to rise at about age 20. Women have lower blood cholesterol levels prior to menopause (45-60 yrs.) than men. Women’s levels rise after menopause becoming higher than men’s levels. Levels stabilize for men at around age 50. More than 1/2 of all adult Americans have blood cholesterol levels of 200 mg/dl or higher. 25% of adults 20 yrs. or older have "high" levels 240 mg/dl or above. People with 240 mg/dl or above are twice as likely to develop atherosclerosis.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

While some forms of hyperlipidemia have diagnostic features, others do not. Many patients may not be tested for lipid abnormalities until other health complications appear. Hypercholesterolemia is strongly associated with coronary heart disease (CHD). There is little doubt that hypercholesterolemia is the most significant contributory cause to the development of atherosclerosis. Atherosclerotic lesions in blood vessels begin with the deposition of cholesterol, followed by the development of fatty streaks. As the process continues, atherosclerotic lesions form, increasing the possibility of myocardial infarction.

Total cholesterol and HDL measurements should be done every five years in adults aged 20 and over. Once hyperlipidemia is suspected, major components of the evaluation are the history (including age, gender, and if female, menstrual and estrogen replacement status), physical exam, and laboratory investigations. The history and physical should assess: presence or absence of cardiovascular risk; factors or definite cardiovascular disease; family history of premature cardiovascular disease of lipid disorder; presence or absence of secondary causes of hyperlipidemia, including concurrent medications; and presence or absence of xanthomas or abdominal pain, or history of pancreatitis, renal or liver disease, peripheral vascular disease (carotid bruits, stroke or transient ischemic attack). (6) Measurement of plasma cholesterol, triglyceride, and HDL-C levels after a 12-hour fast is important.

Other positive risk factors for the development of CHD include:
  • Age: men, 45 years of age or older and women over 55, or premature menopause without estrogen replacement therapy.
  • Family history of premature CDH (definite MI or sudden death before age 55 in father or other male first degree relative, or before 65 years of age in mother or other first degree female relative).
  • Current cigarette smoking.
  • Hypertension (>140/90 mm Hg on antihypertensive medications).
  • Low HDL cholesterol (<35mg/dl).
  • Diabetes mellitus.
  • Negative risk factor: High LDL cholesterol.

Treatment Options

Conventional

The adult treatment panel II of the National Cholesterol Education Program (NCEP) has recommended that total serum cholesterol determination and risk factor assessment be used in the initial classification of adults. (7) If a patient has a total cholesterol of 160 2 risk factors >130 100 190 2 risk factors >160 130

Nutritional Supplementation


Chromium

Chromium produces a beneficial effect on blood cholesterol levels. In a double-blind crossover study, 28 individuals were administered either 200mcg of chromium or a placebo daily for 42 days. The ones taking the chromium experienced a significant decrease in total cholesterol and LDL-cholesterol levels, and a slight elevation of HDL-cholesterol. (8) Chromium has also been reported to improve blood sugar and Hmg A1C levels in diabetics. (9) This will have a positive impact on the process of glycosylation and thus reduce cardiovascular risk. In general, American diets are chromium-poor and therefore, place the population at added risk. Those with diets high in refined sugar, athletes, pregnant women, and the elderly are all at additional risk for chromium deficiency.

Chromium is biologically active only in the trivalent state in which it forms complexes with organic compounds. The most important of these complexes is glucose tolerance factor (GTF) which is comprised of trivalent chromium, niacin, glycine, glutamic acid, and cysteine.


Vitamin C

Vitamin C is another nutrient that reportedly produces favorable changes in blood cholesterol levels. Vitamin C was given to 10 women in a double-blind study at a dose of 1,000mg daily for four weeks. A 16 percent reduction in LDL-cholesterol along with a slight improvement in HDL-cholesterol levels resulted. Similar results were obtained in a much larger study with 256 men and 221 women. In men and women, those taking large doses of vitamin C, greater than 1000mg per day, experienced larger reductions in total cholesterol, LDL-cholesterol and triglycerides, elevations of HDL-cholesterol, and an improvement in the total cholesterol to HDL ratio. (10) , (11) Because vitamin C is an antioxidant, it may also help to prevent the oxidation of LDL, which could possibly lower the risks for developing atherosclerosis. (12)


Vitamin B5

Pantethine is the active form of vitamin B5, which is also known as pantothenic acid. Pantethine has been reported to lower elevated triglycerides and LDL cholesterol while raising levels of the beneficial HDL cholesterol. (13) Pantethine apparently helps lower the amount of cholesterol that is made in the liver. In one study, 24 women with cholesterol levels above 240ng/dl were given 900mg of pantethine daily. After 16 weeks, eighty percent of the women experienced significant lowering of total cholesterol and LDL-cholesterol levels without side effects. (14)


Omega-6 Fatty Acids, Gamma Linolenic Acid (GLA)

Omega-6 fatty acid, also known as linoleic acid, is a dietary fat that helps lower LDL-cholesterol levels. Under normal conditions, the body converts omega-6 into a longer chain fatty acid known as gamma-linolenic acid (GLA). It has been determined that GLA plays a role in the metabolism of LDL-cholesterol, converting it to bile acids, which can be eliminated via the colon. Researchers have reported that GLA is 170 times more effective at lowering LDL-cholesterol levels than omega-6. (15) It is important to note that trans fats from partial hydrogenation can decrease this benefit by inhibiting the conversion of omega-6 to GLA. It is important to carefully read labels and avoid consuming processed foods where partially hydrogenated fats and oils are contained in the list of ingredients.

Borage oil, black currant oil, and evening primrose oil all contain relatively high amounts of GLA, 26%, 18% and 9% respectively. Therefore, consuming supplemental amounts of one of these oils on a daily basis is one of the most effective ways to lower LDL-cholesterol levels. These oils must be kept refrigerated.


Sterols (Sitosterol) and Sterolins (Sitosterolin)

There are many chemical constituents (termed phytochemicals) found in plant medicines that have beneficial pharmacological effects in humans. Some bioactive phytochemicals include tannins, resins, polysaccharides, saponins, glycosides and volatile oils among others. Recent literature has reported that two of these phytochemicals, sterols and sterolins (plant "fats"), occur naturally in fruits, vegetables, seeds and nuts are, have clinically beneficial effects in human subjects in many conditions.

Sterol is found in all plant-based foods, and sterolin is a glucoside moiety joined to the sterol chemical structure. Both sterols and sterolins were identified as early as 1922. In the natural state, these plant "fats" are bound to the fibers of the plant, making the sterols and sterolins difficult to be absorbed during the normal transit of digested food through our gut. Seeds are the richest source of the sterols and sterolins, but are usually removed during processing by the food industry.

Plant sterols and sterolins have been reported to be effective adjunctive agents in the management and treatment of disease states such as high cholesterol levels, benign prostatic hyperplasia, pulmonary tuberculosis and stress-induced immune suppression and HIV among others. (16) , (17) , (18) , (19) , (20) Some of the most promising uses of these plant "fats" is in the management of autoimmune disorders such as lupus, multiple sclerosis, rheumatoid arthritis and myasthenia gravis. Of note is that the sterols should be combined with sterolin in order to be an effective agent for the immune system. (21)

Sterols and sterolins have been reported to modulate the function of T-cells, significantly enhancing the proliferation of the CD-4 TH-1 cells and increasing the production of the interleukin 2 (IL2) and gamma-interferon (FN-g and IFN-y). (22) These results indicate that sterols and sterolins are adaptogenic in that they modulate the immune and stress response.

Care should be taken if an individual is taking immunosuppressive agents. Based on pharmacology, if an individual is taking hypocholesterolemic agents concurrently with plant sterols and sterolins, a dosage adjustment in the pharmaceutical medication may be necessary.


Vitamin E

Studies suggest that vitamin E is one of the most effective nutrients in preventing the oxidation of LDL-cholesterol. It reduces platelet adhesion and, more importantly, reduces lipid peroxidation of LDL cholesterol. (23) In the Cambridge Heart Antioxidant Study (CHAOS), vitamin E supplementation of 400 to 800 IU daily resulted in a 47 percent reduction in "cardiovascular endpoints." (24) Some experts feel that using a combination of antioxidants including carotenoids, vitamin C, and selenium along with vitamin E is the best way to supplement.

Vitamin E includes eight compounds, which includes four tocopherols, alpha, beta, gamma, and delta. The natural form of vitamin E, d-alpha tocopherol, has been reported to have greater bioavailability than synthetic iso-forms of the vitamin. (25)


Coenzyme Q10 (CO-Q10)

CoQ10 is an antioxidant that can reportedly help to prevent the oxidation of LDL cholesterol as well as reduce risks associated with several other aspects of cardiovascular disease. CoQ10 is carried throughout the body on LDL-cholesterol molecules. Adequate coenzyme Q10 is an important nutrient to protect LDL-cholesterol from damage, which substantially reduces an individual’s risk for developing atherosclerosis. (26)

Many individuals with high cholesterol will be using a cholesterol-lowering drug, likely a member of the class of drugs known as the “statins." These effective agents inhibit the body’s ability to manufacture coenzyme Q10. The drug known as gemfibrozil may also deplete coenzyme Q10. As was mentioned above, coenzyme Q10 helps protect LDL-cholesterol from being damaged. CoQ10 also plays a role in the generation of energy at the cellular level. The heart is the most energy-demanding muscle in the body; a deficiency of coenzyme Q10 could affect the heart.


Soy Isoflavones

Soy protein has been reported to be hypocholesterolemic in individuals with elevated cholesterol. (27) This fact that soy protein diets rather than animal protein diets can lower serum cholesterol levels tends to be well documented among animal studies, but has historically been inconclusive in humans. One meta-analysis of 38 controlled human clinical trials evaluated the relationship between serum cholesterol and soy protein intake. This evaluation concluded that an average soy protein intake of 47g per day led to significant decreases in lipid levels. The soy based diets led to a 9.3% decrease in total cholesterol, a 12.9% decrease in low-density lipoprotein (LDL) cholesterol, a 10.5% decrease in triglycerides and a nonsignificant 2.4% increase in high-density lipoprotein (HDL) cholesterol. (28)


Beta-1,3 Glucan

Beta-glucans appear to be the major cholesterol lowering agents in oat bran fiber. Studies reveal that soluble beta-1,3 glucans in oat bran can lower total cholesterol and LDL cholesterol levels in patients with hyperlipidemia. (29) , (30) Similar cholesterol lowering effects are reported in studies where barley is used as the source of beta-1,3 glucans. (31)

A randomized crossover study fed a high-fiber (beta-glucan or psyllium) and a control low-fat, low-cholesterol diet for 1 month each to 68 hyperlipidemic adults. Reductions in numerous cholesterol measures and ratios were observed. Based on these reductions a risk reduction of 4.2 +/- 1.4% (P = 0.003), as calculated by the Framingham cardiovascular disease risk equation, was noted for cardiovascular disease. (32)


Policosanol

Policosanol is a natural mixture of higher aliphatic primary alcohols isolated from sugar cane wax with cholesterol-lowering effects demonstrated in experimental models and in patients with type II hyperlipoproteinemia. (33) , (34) , (35) , (36) A new proprietary product has been developed that is made from beeswax, and is reported to be a more stable form than other products.

There have been several reports of policosanol lowering cholesterol levels in human subjects. One study has compared policosanol to HMG-CoA reductase inhibitors in patients with Type II hypercholestrolemia. (37) Patients with a LDL cholesterol over 160 mg/dl were included in the studied. A 24% LDL cholesterol reduction was obtained with policosanol, compared with a 22% reduction with lovastatin and a 15% reduction with simvastatin. HDL cholesterol significantly increased in patients on policosanol and did not change in the other treatment groups. Adverse effects of policosanol were mild and unspecific, with no changes in hepatic enzymes observed. The authors concluded that policosanol is a safe and effective cholesterol-lowering agent.

A large double-blind, randomized, placebo controlled study of 437 patients was conducted to study the effects of policosanol in reducing serum cholesterol levels. (38) Policosanol (5 and 10 mg/day) significantly reduced serum low-density lipoprotein cholesterol (18.2% and 25.6%, respectively), and cholesterol (13.0% and 17.4%), and it significantly raised HDL cholesterol (15.5% and 28.4%). Triglycerides remained unchanged after the first 12 weeks and lowered significantly at study completion. Policosanol was reported safe and well tolerated, and no drug-related interactions and adverse effects were observed.

Policosanol has been reported to lower elevated levels of cholesterol and LDL cholesterol in non-insulin-dependent diabetes mellitus (NIDDM) patients, potentially decreasing the development of coronary artery disease through the direct action of hyperglycemia on the arteries as well as the dyslipidemia induced by NIDDM. (39) Policosanol (10 mg/day) significantly reduced total cholesterol by 17.5% and LDL cholesterol by 21.8% compared with baseline and placebo.

In a laboratory animal study, oral administration of policosanol in rats provided a partial inhibition of lipid peroxidation, protecting against membrane lipid peroxidation and to some extent against free radical-associated diseases. (40) Policosanol has also been reported to protect against the development of atherosclerotic lesions in laboratory animal studies. (41)

Herbal Supplementation


Guggul

Guggul oleoresin has been used in the Indian (Ayurvedic) medical system for centuries as an anti-arthritic, carminative, antispasmodic, diaphoretic, and aphrodisiac. (42) In the early 1960's, researchers began to explore the ancient Sanskrit description of guggul being used by Ayurvedic physicians in the management of lipid disorders. After years of research and scientific studies, guggul was approved for marketing in India in 1986 as a lipid-lowering drug. (43) Guggul has also been reported to inhibit platelet aggregation and have fibrinolytic activity, as well as being an antioxidant, preventing the heart from being damaged by free radicals. (44)

The lipid lowering effects of guggul may be explained by four proposed mechanisms of action. (45) , (46) First, guggul reportedly inhibits the biosynthesis of cholesterol in the liver, interfering with the formation of lipoproteins (LDL, VLDL). Secondly, it may increase the fecal excretion of bile acids and cholesterol, resulting in a low rate of absorption of fat and cholesterol in the intestines. Thirdly, it is claimed to stimulate the LDL receptor binding activity in the liver cellular membranes, reducing serum LDL levels. Lastly, guggul reportedly stimulates thyroid function, which may lead to blood lipid lowering and weight loss. (47) In addition to its lipid lowering effects, guggul has been reported to prevent the formation of atherosclerosis and aid in the regression of pre-existing atherosclerotic plaques in animals. (48)


Garlic

Garlic has been reported to lower total cholesterol, LDL cholesterol and triglycerides, and increase HDL cholesterol. (49) , (50) , (51) Garlic may be of benefit in the prevention of heart disease and atherosclerosis. (52) , (53) Garlic may inhibit platelet aggregation and influence blood viscosity through its fibrinolytic activity. (54) , (55) , (56) This leads to the use of garlic in the prevention of strokes, heart attacks, and various thrombus events. (57) , (58) , (59) Also, the antioxidant effect in aged garlic has been reported to be beneficial in preventing stroke and arteriosclerosis. (60)

One study reported no effect of garlic oil on serum lipids. (61) However, the product used was garlic oil, which is processed and heated garlic. The impact of processing is an important fact to keep in mind when recommending garlic supplements. Changes can occur in the active constituents when exposed to cooking or other processing that can render the garlic product virtually ineffective. Cooking is known to denature proteins, and therefore, may inactivate the enzyme (allinase) that is necessary in converting alliin into allicin, the major bioactive constituent in garlic.

Also, research has reported that allinase may be irreversibly inhibited by stomach acid and may fail to form adequate amounts of allicin or other thiosulfinates below a pH of 3.6. (62) , (63) Recommending a quality garlic supplement is essential, and enteric coating may be advantageous. Of further note, as reported in a few laboratory studies, is the potential for large amounts of allicin to damage liver tissue if absorbed due to its oxidation potential. (64) , (65) However, there are positive studies using garlic preparations standardized to allicin potential without adverse effects.


Red Yeast Rice

In 1976, Japanese researchers reported the discovery of mevastatin, a fungal metabolite isolated from the cultures of Penicillium citrinum and P. brevicompactin. (66) Mevastatin was found to be a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), the enzyme that is the rate-limiting step in the synthesis of cholesterol. These agents play a prominent role in the management of hypercholesterolemia, a significant risk factor for coronary artery disease. (67)

In recent years, at least 34 separate clinical studies (17 controlled and 17 open-label) in China and the United States have assessed the efficacy of M. purpureus red yeast rice as a cholesterol-lowering agent. One major randomized, single-blind, multicenter clinical trial involved 446 hyperlipidemic subjects. (68) After eight weeks, blood levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in the red yeast rice treatment group were reduced by 22.7, 30.9, and 34.1 percent, respectively. In addition, HDL-c levels increased by 19.9 percent in the red yeast rice treatment group. This increase was significantly greater than the 8.4 percent increase observed in the control group.

In a major prospective double-blind, randomized clinical trial involving 152 subjects, total cholesterol was reduced by 19 percent compared to 1.5 percent in the placebo group. (69) Triglycerides were reduced by 36 percent compared to 10 percent in the placebo group.

In another double-blind, placebo-controlled randomized clinical study, researchers evaluated the efficacy and safety of a proprietary red yeast rice product. After eight weeks, total cholesterol levels of the treatment group decreased by 18 percent while those in the placebo group remained unchanged. (70) No serious adverse effects were observed in the study group. (71)

Released findings of a U.S. multi-center, open-label trial confirmed the consistent cholesterol-lowering effects of red yeast rice. (72) In a two-month study involving 187 subjects, a twice-daily regimen of a proprietary red yeast rice product was found to reduce total cholesterol and LDL-c levels by 16 and 22 percent, respectively. Moreover, when the treatment was discontinued, these levels returned to pretreatment values within two weeks.

Red yeast rice was compared with pravastatin in a randomized, single-blind, controlled study. (73) Forty-four subjects diagnosed with essential hyperlipidemia were randomly divided into two equal groups. After four weeks, both treatments caused significant and comparable reductions in total serum cholesterol and LDL-c. The clinical evidence strongly suggests that red yeast rice is an effective, natural dietary supplement for controlling serum cholesterol, and that the product is well tolerated in humans.


Psyllium Seed

Psyllium has the potential to aid in the management of cholesterol levels. (74) , (75) There have been several clinical trials reporting the effectiveness of psyllium in hyperlipidemia. (76) , (77) , (78) , (79) Fiber in the diet, especially soluble fiber, can reportedly reduce absorption of blood cholesterol and fecal bile acids that can lower cholesterol levels, decreasing the risk for heart disease and stroke.

A meta-analysis of eight studies, including 384 people taking 10.2 gm of psyllium per day, found it lowered serum total cholesterol by 4 percent, LDL cholesterol by 7 percent, and the ratio of apo B to apo A-1 by 6 percent compared to placebo. (80) Also of interest, is that adding psyllium to half the usual dose of bile acid sequestrant resins maintained the efficacy and improved the tolerability of these resins. (81)

A randomized crossover study fed a high-fiber (beta-glucan or psyllium) and a control low-fat, low-cholesterol diet for 1 month each to 68 hyperlipidemic adults. Reducation in numerous cholesterol measures and ratios were noted. Based on these reductions a risk reduction of 4.2 +/- 1.4% (P = 0.003), as calculated by the Framingham cardiovascular disease risk equation, was noted for cardiovascular disease. This supports the FDA's approval of a cardiovascular disease health claim for four servings a day of psyllium, 1.78 grams per serving. (82)

Acupuncture & Acupressure

A group of studies showed positive results with acupuncture treatment. Two groups of acupuncture points are alternated daily. The first group is San Yin Jiao (SP 6), Zu San Li (S 36), and Nei Guan (PC 6). The second group is Tai Bai (P 6), Yang Liang Quan (SP 3), and Feng Long (S40). Ten treatments comprise one course of treatment. Rest three days between treatments. Continue for 2-4 units. After 2 units, check cholesterol level. If the level is found to be normal after 2 units, discontinue treatment. Results showed 73 of 82 cases of lowered cholesterol levels, an 82% success rate. 2 cases increased cholesterol levels prior to decreasing. 2 cases showed no response. 5 cases increased cholesterol levels through treatment. In 11 cases, triglycerides decreased. In 6 cases, there was no change. (83)

Yan Jie chose 4 acupuncture points bilaterally: Tai Chong (LV 3), Nei Guan (PC 6), Zu San Li (S 36), San Yin Jiao (SP 6) once/day for 10 days. After two treatment units, of the 26 patients with high triglycerides had an average reduction of 100 +/- 32.16mg%. Compared to non-treatment, there was enormous improvement (p < 0.01). 45 patients with high cholesterol showed an average decrease in blood cholesterol levels of 23.31 +/- 5.32mg% (p < 0.001). (84)

Traditional Chinese Medicine

Hyperlipidemia

Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.

Diet & Lifestyle

Diet: The first and most important factor for reducing cholesterol is diet. Most low fat, low protein diets that are designed to improve cardiovascular risk are also a high-carbohydrate (no matter what the source) diet. This type of diet has proven to actually increase LDL cholesterol and triglycerides. Many foods labeled "cholesterol free" actually contain hydrogenated oils or trans-fatty acids, which have been associated with an increased risk of cardiovascular disease. (85) Partially hydrogenated oils may increase LDL, triglycerides, and lipoprotein (a) levels, while decreasing HDL levels. (86) In addition, these foods are generally rich in refined sugars, which can aggravate insulin response and contribute to the whole process of hyperinsulinemia and related glycosylation. It is essential for long-term control of cardiovascular disease that efforts are focused on education regarding food selection. Currently only 9 percent of the American population eats five fruits and vegetables a day. People also do not include legumes or enough whole grains in their diet. These foods are essential for providing dietary fiber, which not only is known to reduce cholesterol levels, but also the water soluble fiber found in legumes helps to regulate blood sugar.

The second important dietary factor affecting cardiovascular disease is the reduced dietary intake of essential fatty acids and, in particular, the omega-3 fatty acids. Low levels of omega-3 (alpha-linolenic acid), coupled with the excess intake of omega-6 (linoleic) fatty acids from refined polyunsaturated vegetable oils can contribute to increased triglycerides and elevated blood pressure, as well as increasing platelet adhesiveness.

Foods that may help to lower elevated cholesterol levels include soy products, oat bran, yogurt, carrots, walnuts, and onions. High fiber foods such as whole grains, vegetables, fruits, and legumes can also help to lower cholesterol levels. Although egg yolks contain high levels of cholesterol, studies report that eating eggs regularly does not elevate serum cholesterol levels in most people. (87) Although switching to a vegetarian (low-cholesterol) diet may help some individuals lower elevated cholesterol levels, many health professionals now believe that the ingestion of dietary cholesterol is not a major contributor to cholesterol levels.

In the late 1940's and early 1950's, food processors began dramatically increasing their use of inexpensive, polyunsaturated vegetable oils in the production of a wide variety of processed foods. During this time, food processors created a new industrial process called partial hydrogenation. This process involved bubbling hydrogen gas into the vegetable oils under extremely high temperatures and pressures with metal catalysts. This process changes the consistency of the vegetable oils from a liquid to the semi-solid hydrogenated fats and oils in processed foods. The process of partial hydrogenation gave food processors another benefit. It increased the shelf life of processed food products by making the fats and oils in processed foods less likely to become rancid.

There are health-related problems associated with partially hydrogenated fats and oils. The high temperatures and pressures that are required during the process of partial hydrogenation causes many of the fats to change their shape, resulting in trans fatty acids. One of the problems associated with trans fats is they block 6-delta desaturase, an enzyme that is required for the metabolism of cholesterol. By blocking this enzyme, trans fats inhibit the ability to excrete cholesterol. Foods containing partially hydrogenated oils, also known as trans fatty acids, actually act to raise LDL-cholesterol levels and increase the risk of cardiovascular disease. (88)

Exercise: Regular exercise is another way to have a positive effect on cholesterol levels. Regular endurance exercise training has been associated with decreased levels of total cholesterol and increased HDL-cholesterol. (89) Various forms of aerobic exercise that can help improve HDL levels include regular walking, aerobics, dancing, jogging, swimming, and cycling.

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Fatty Acids

Dietary polyunsaturated fatty acids (PUFA) are primarily composed of omega-3 and omega-6 fatty acids. PUFA are vital in the production of eicosanoids – components involved in regulating inflammatory response, blood vessel leakage, lipid accumulation, immune cell response, and optimal control of virtually every body tissue. (90)

Glucose

Blood glucose levels vary in response to food intake, stress, physical exertion, and various disorders. Elevations of serum glucose should lead to confirmatory testing such as fasting insulin, serum phosphorus, magnesium, hemoglobin A1c, and/or fructosamine.

Hormone Assessment

Insulin: Elevated insulin levels may indicate increased insulin resistance. Insulin resistance is a contributing factor to hyperlipidemia and monitoring levels may be useful. (91)

Lipid Profile

Cholesterol, Total Triglycerides HDL LDL

Oxidative Stress

Increased oxidation is a documented dynamic accompanying hyperlipidemia. (92) Oxidant levels increase in relationship to the inflammatory process. Antioxidants exhibit a protective effect on LDL. (93) Most medications used for the treatment of hyperlipidemia deplete a variety of nutrients, most notably the B vitamins and CoQ10. (94) , (95) CoQ10 has been studied as a marker for liver dysfunction contributing to hyperlipidemia. (96) Monitoring of oxidant stress may be useful.

Clinical Notes

One of the more hidden causes of elevated lipids includes subclinical hypothyroidism, excessive carbohydrate consumption, and prolonged stress leading to elevated cortisol with subsequent hyperlipidemia.

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