Annie Sawyer, Ph. D.
Cholesterol is a lipid produced in the liver, and also obtained from animal products in the diet: red meats, eggs and dairy products (Freeman & Junge, 2005). As a fat-like substance, cholesterol does not dissolve in blood, but instead it connects with proteins to form small particles known as lipoproteins. There are known four types of lipoproteins: chylomicrons, very-low-density lipoprotein (VLDL), low-density (LDL) lipoprotein and high-density lipoprotein (HDL). The overproduction of very low-density lipoproteins (VLDL) is described as the hallmark of dyslipidemia and the metabolic syndrome appearance in a study by Adiels et al. (2008). The emergence of cholesterol reduction as a marker is a major event for the pharmaceutical industry and metabolic syndrome promises to be as “big or bigger" (Breistein, 2004).
According to Reaven, unbalanced levels of cholesterol can lead to a cluster of metabolic cardiovascular diseases known as “metabolic syndrome” (Reaven, 1988). He taught that there are known two types of fat—subcutaneous and visceral. The first type of body fat, which is a noticeable layer of fat that lies just below the skin, is called “subcutaneous fat”. The second type, “visceral fat”, can go largely unnoticed because it is not visible to the naked eye. The only effective way researchers can locate visceral fat is by magnetic resonance imaging (MRI). Where adipose tissue is stored is critical to diagnose metabolic syndrome and determining of its health consequences. As proven in several experiments, individuals who consume large amounts of saturated fat and those who perform little or no physical activity are likely to have high stores of visceral fat (Fauci, 2008; Ford et al., 2002).
Atherosclerosis can occur in arteries throughout the body, including the coronary arteries (those feeding the heart). In time, narrowing or clogging of the coronary arteries by atherosclerosis can produce the signs and symptoms of heart disease, including angina (chest pain) and heart attacks. Metabolic syndrome and the risk of heart incidents and mortality are studied in mega-analytical, longitudinal studies (Gami et al., 2007). As known in the literature, hypercholesterolemia (dyslipidemia) may significantly increase the risk of heart disease as it can lead to atherosclerosis—a condition in which fat and cholesterol are deposited on the walls of the arteries. Recent study published in Lancet is showing the effect of statins and 3-omega fatty acids in heart failure cases (Fonarow, 2008).
Many factors appear to contribute to the development of high cholesterol:
(a). Heredity—genes partly influence how the body makes and handles cholesterol.
(b). Diet—a high intake of saturated fat, dietary cholesterol, and excess calories can cause cholesterol levels increase.
(c). Age and gender—Cholesterol levels begin to increase in both men and women beginning around 20 years of age. Premenopausal women usually have lower levels of cholesterol when compared with men of the same age. After menopause, a woman's LDL cholesterol levels typically go up, as so does her risk for heart disease.
(d). Other medical conditions—Conditions such as diabetes, obesity, liver steatosis, or kidney disease can cause elevated cholesterol.
(e). Lack of physical activity—Increased physical activity lowers LDL and raises HDL levels.
Treatment of dyslipidemia is generally aimed at lowering the low-density lipoproteins (LDL) or "bad cholesterol," lowering triglyceride levels, and increasing the high-density lipoproteins (HDL) or "good cholesterol” (Freeman & Junge, 2005). The Cholesterol and Recurrent Events Study (CARE) performed in 1996 showed benefits of cholesterol lowering especially in heart attack patients. This study reported that even in patients with normal cholesterol the use of statin drug decreases the risk of having another repetitive heart attack by 24%. Women benefited more than men by reducing their risk of having another heart attack by 45%. The final conclusions done after the CARE study calculated on the basis of 1000 patient’s treatment showed 153 fewer heart attacks and deaths from heart attack and in patients over 60- they would be 214 fewer deaths for men and 248 fewer for women (CARE, 1996).
Another study published in 1998, also known as the “long-term intervention with Pravastatin in ischemic disease” (LIPID) study, was based on the examination of the effects of cholesterol lowering in people with CHD who already experienced a heart attack or had been hospitalized for angina. They all presented normal cholesterol levels. The patients were placed on a cholesterol-lowering diet, and on a statin drug. The final results showed a drop of 18% in the total cholesterol and 25% in the LDL cholesterol leading to 24% decreased in death rate among the treatment group comparatively with the placebo group. In the group of patients who needed bypass surgery or angioplasty the results showed a decline by 22 of death rates, a decline by 20% in the need for bypass surgery or angioplasty, a decline by 29% from heart attack, and 19% from stroke (LIPID, 1998).
Link between Metabolic Syndrome and the Adipokines
The metabolic syndrome is associated with the adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness is a statement published by Perls et al. (1999). A protein hormone produced and secreted exclusively by the adipocytes (fat cells), adiponectin can regulate the metabolism of lipids and glucose. Adiponectin influences the body's response to insulin. It also has anti-inflammatory effects on the cells lining the walls of blood vessels. High blood levels of adiponectin are associated with a reduced risk of heart attack while low levels of adiponectin are found in people who are obese and therefore at increased risk of a heart attack (Matsuzawa et al., 2004).
Dyslipidemia (abnormal cholesterol levels) is a marker of the metabolic syndrome cluster, characterized with elevated triglycerides, decreased HDL, and increased VLDL. Atherogenic dyslipidemia consists in an aggregation of lipoproteins abnormalities (elevated serum triglycerides and apo (a), increased small LDL (VLDL), and reduced HDL levels). All of the above factors plus glucose intolerance, a prothrombotic and a proinflammatory state are atherogenic factors. Increased LDL is not exactly part of the metabolic syndrome, but it makes a lot of sense to be considered in the treatment panel. Abnormal cholesterol levels and more specifically high LDL (low density lipoprotein) levels are strong predictors for cardiovascular disease, especially in men (Armstrong, 2006). Highly elevated LDL cholesterol in the blood causes plaque formation and can signal the beginning of atherosclerosis (Ridker et al., 2002).
The connection between HDL-cholesterol, triglyceride, and body weight in women aged 40-65 years is shown in the Prospective Cardiovascular Münster Study (PROCAM, 1997). Determinants of mortality are showing that with increasing BMI, there is an increase in fasting triglyceride levels and a decrease in HDL-cholesterol levels. An important question of the study is if age-related changes in lipid risk factors in women are due to increasing age alone or due to effects of menopause. Thus, all the women have been divided into two groups—a premenopausal group and menopausal group. The difference in many risk factors between both groups was greater than can be explained on the basis of age alone, including LDL cholesterol, triglycerides and BMI (Cullen, Schulte, & Assmann, 1997). The HDL cholesterol levels did not differ between premenopausal and postmenopausal women. Fasting insulin and apolipoproteins B levels and low density lipoprotein particle size are seen as risk factors for ischemic heart disease (Cullen et al., 1997; Lamarche et al., 1998).
Anticholesterol Drugs (PDR, 2008)
Statins
HMG-CoA reductase inhibitors (statins) are used as first and initial allopathic choice of treatment in case of hypercholesterolemia. Their prescription is a reason of the millions of profit by the Big Pharmaceutical companies. Currently, there are six statin drugs available, which prescription choice depends on doctor’s preference, insurance benefits and how much cholesterol reduction is requested. There are several studies that show that certain high risk patients, such as those with metabolic syndrome and diabetes, benefit from cholesterol lowering therapy with statins. The anti-inflammatory effect of statin therapy on C-reactive protein levels are proved in a randomized trial and a cohort study (Albert, Danielson & Rifai, 2001).
Due to the well-known connection between high cholesterol and heart disease, a complete cholesterol profile should be issued for adults with family history of metabolic syndrome, obesity and coronary heart disease. The lipid panel includes measuring total cholesterol, triglycerides, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL). According to the opinion of Sinatra (2008), despite the increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with the metabolic syndrome. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) levels of cholesterol has received less attention. According to the author’s statement people should be aware that statins may cause multiple side effects.
The family of statins is also proved to lower body's ability to produce CoQ10 due to both substances- CoQ10 and cholesterol are derived from the same substance, mevalonate. As the main purpose of statins is to inhibit the creation of cholesterol, and by extension, it suppresses the creation of CoQ10. Sinatra believed that it is extremely important to consider adding a high quality CoQ10 supplement to the daily regimen, in order to help maintain optimal health. He states that fortunately, we are living in time of huge importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease (Sinatra, 2008).
A low fat or low cholesterol diet and exercise are essential in helping to lower cholesterol and to maintain low cholesterol levels. While drug therapy is often needed to lower cholesterol, diet and exercise are additionally recommended helping the drug therapy to lower and control cholesterol levels (Chapman et al., 2005). The authors claim that to patients with established cardiovascular disease (CVD) are offered more intense lifestyle changes. They believe that a correct decision is to start a patient with dietary therapy while drug therapy is usually based on a patient's LDL cholesterol levels, presence of heart disease, and risk factors, especially the so called “Framingham Risk”.
Fibrates
Fibric acid derivatives (fibrates) are another class of medications directed to lower blood triglyceride levels. The available US registered fibrates are gemfibrozil (Lopid) and fenofibrate (Tricor). Their main mechanism of action is to lower blood triglyceride levels by reducing VLDL liver’s production and by increasing their elimination.
Fibrates are moderately effective in increasing blood HDL cholesterol levels and not effective in lowering LDL cholesterol levels. In high risk patients, a combination between fenofibrate with statin may be prescribed to a metabolic syndrome patient with dyslipidemia. According to a new study there is strong evidence indicating that fibrates may reduce significantly cardiovascular risk (Tenenbaum & Fisman, 2004).
The side effects of fibrates include gallstones formation, nausea, stomach upset, and diarrhea. Along with statins fibrates can cause liver toxicity or liver inflammation. Nature can also help you support LDL and HDL cholesterol levels. There are formulas and ingredients in them that have shown ability to inhibit platelet aggregation, reduce triglyceride levels, enhance circulation and reduce clotting potential.
Omega-3 Fatty Acids
There are many clinical studies that prove regular consumption of fish oils can lower risk of sudden cardiac death and to protect against heart disease. Working as anti-inflammatory substances, they can reduce inflammation and oxidation as a byproduct of degenerative diseases including metabolic syndrome, obesity, Alzheimer’s disease, gout, kidney disease, diabetes (Mori et al., 2000).
Omega- 3 fatty acids may be used for their anti-clotting properties. UCLA scientists have confirmed that fish oil is a missing link to Alzheimer’s disease, recently also known also as ‘diabetes of the brain’. There was a report that recapitulated that omega-3-fatty acid DHA could increase production of LR11, a protein found in Alzheimer’s patients (Azzi, Gysin & Kempna, 2004).
Omega-3 EFA’s have been found intimately related with increased insulin secretion and improved insulin sensitivity (Kris-Etherton & Hill, 2008). Omega-3 EFA effects in patients with chronic heart failure were studied in a randomized, double-blind, placebo-controlled trial (GISSI-HF investigators). Omega-3 EFA can improve amino acid transport to muscle tissue, metabolic rate, cholesterol and energy levels (Mori et al., 2000). Omega-3 EFA could also play role in alleviating inflammation by decreasing cyclooxygenase (COX-2) enzymes associated with cytokines related with inflammation (Sears & Lawren, 1995). Mori et al (2000) concluded that by simply incorporating high omega-3 sources into the metabolic syndrome diet in a form of fish or fish oil would be very beneficial for alleviating the syndrome and its consequences. Authors also added that other natural sources of 3-omega fats are: salmon, flaxseeds, whitefish, tuna, algae, and spirulina for daily supply (Mori et al., 2000). Giampapa et al. (2004) calculated that fat should constitute 20% of the food supply. The authors claimed that omega-3 EFA could have beneficial effects on lipid metabolism by reducing bad cholesterol and triglycerides, positive anti-inflammatory effects, reducing insulin response to glucose, and diminishing risk of cardiovascular disease and cancer.
Supplementation with omega-3 seems was linked to an increase of vigor and a decrease of depression, anger, and anxiety. 3 EFAs were found beneficial in adult’s dementia, depression and mood disorders, as they may act as mood stabilizers. The above correlation was shown in subjects the Zone diet and the results confirm the influence of omega-3 on the central nervous system (Sears & Lawren, 1995).
The beneficial role of omega-3 EFAs in term of influencing obesity was studied by (Kris-Etherton & Hill, 2008). A mega-analytical study executed by a team (Balk, Chung & Lichtenstein, 2004) combined the results of 31 placebo-controlled studies of fish oil (3-omega) and 1,356 hypertensive individuals. The authors’ concluded that there was a dose-response hypotensive effect of fish oil in hypertensive patients. Final conclusion from this study was that omega -3 EFAs did reduce blood pressure in people with mild hypertension. The use of omega 3 fatty acids for cardioprotection was also studied by (Lee, O'Keefe, Lavie, Marcholi & Harris., 2008). Based on results of a 20-year nutritional study two authors scientifically illustrated that a “plant-based- oil-free diet” can not only prevent and stop the progression of heart disease as a consequence of metabolic syndrome, but it can also reverse its effects (Caldwell & Esselstyne Jr, 2008).
Olive Oil
Recent study results showed that olive oil also has a powerful protective effect upon experimental inflammation models in cases of a polyphenol-supplemented virgin olive oil diet (Martinez-Dominguez, de la PR., & Ruiz-Gutierrez, 2001). The polyphenols of olive oil and red wine antioxidant polyphenols inhibit the endothelial activation and have strong antiatherogenic properties, as seen in the “Mediterranean Diet” (Carluccio et al., 2003).
One of the largest and most comprehensive studies of lifestyle risk factors titled The Nurses’ Health Study (NHS) lead by a team of (Hu et al., 2001) followed 85,000 women for a period of 16 years. This study was dedicated to the diet, lifestyle, and risk of Type 2 diabetes mellitus in women and made an effort to convince Western civilization that most cases of Type 2 diabetes may be prevented by losing weight. It was found that eliminating trans-fatty acids and reducing polyunsaturated fatty acids may reduce the risk of metabolic syndrome. Although no direct causal link between trans-fat acids effect and diabetes was identified, in the presence of an underlying insulin resistance, researchers found trans-fats and other hydrogenated fats to increase the probability of developing the syndrome and its consequences (Hu et al., 2001). All the above studies and observations open a new path to the development of nutraceuticals and nutraceutical combinations tailored to specifically affect the function of the human genomic control, being named genome-directed nutraceuticals (Azzi et al., 2004)
Fiber
These important micronutrients are needed to keep the body in a good balance. Vegetables, especially non-starchy vegetables, contain fiber and important micronutrients such as vitamins and minerals. Daily fiber may help metabolic syndrome patients to regulate blood sugar levels. The ability of oat beta-glucan to reduce blood cholesterol in hypercholesterolemic subjects it is shown in a study by Braaten, Wood and Scott (1994). Oats, spelt, corn, barley, peas, beans, fruits and vegetables are rich in fiber and complex carbohydrates. The connection between soluble fiber and serum lipids is shown in a literature review published by the team of researchers (Glore, Van Treeck & Knehana, 1994).
Glucomannan. Glucomannan is another natural plant-based fiber that benefits digestive health. It is a calorie-free nutrient, what may promote healthy blood sugar levels and a significant decrease of elevated cholesterol. Derived from the konjac root, it is a water-soluble dietary fiber that acts as a bulk-forming laxative (Anderson, Algood & Turner, 1999). Another team of researchers (Anderson, Kendall & Jenkins, 2004) offered carbohydrate and fiber recommendations for individuals with diabetes. The lipid-and glucose-lowering efficacy of Plantago psyllium in Type 2 diabetes are studied by another team (Rodrigers-Moran, Guerrero-Romero & Lazcano-Burciaga, 1998).
Choline Bitartrate. Choline Bitartrate prevents fats from accumulating in the liver, and is essential for the health of nerves, kidneys and liver. It aids in emulsifying cholesterol so it doesn't settle on the arterial walls. Most people with metabolic syndrome, hypertonia, heart abnormalities (heart palpitation), liver steatosis, and even liver cirrhosis are discovered to show choline deficiency. It is an important lipotropic (fat emulsifier) involved in the biosynthesis of lecithin and the formation of the amino acid methionine (Mindell, 1999).
Inositol. Inositol is not considered a vitamin per se because it can be synthesized by the body. It is beneficial in case of diabetic neuropathy, metabolic syndrome, panic disorder, high cholesterol, insomnia, cancer, depression, schizophrenia, Alzheimer's disease, attention deficit-hyperactivity disorder (ADHD), polycystic ovarian syndrome, hypertension, high triglycerides, high LDL cholesterol, peripheral vascular disease and Raynaud's disease (Goodman, Rall, Nies & Taylor, 1996).
Vitamin B-3 (Niacin) is important for maintaining cell energy. It assists in transforming carbohydrates into fats, and also processes alcohol. Experts in cardiology research explain in their study the benefits of niacin by influencing the glycemic status in patients with healed myocardial infarction. According to this study vitamin B3 (niacin) was found to improve cholesterol regulation in terms of decreasing LDL cholesterol and increasing HDL cholesterol (Canner, Furberg, Terrin & McGovern, 2005). The study is a randomized, placebo-controlled coronary study known also as the Coronary Drug Project (CDP, 2009) compared five lipid-modifying agents in men with previous myocardial infarction (MI). The study identified strong benefits of niacin in metabolic syndrome; it improved glycemic status in patients with myocardial infarction. Results of this study supported the use of B3 in post-myocardial infarcts (MI) and proved that there is a decreased 6-year (MI) mortality and 15-year total mortality (CDP, 2009) in people with metabolic syndrome. What took the attention of the authors was that benefits of niacin were found greater in patients with metabolic syndrome, versus patients without the syndrome. Niacin was confirmed as a low-cost, highly effective agent capable of reducing total cholesterol, raising HDL and lowering VLDL and triglycerides (Canner et al., 2005).
Guggulipid (Myrrh). This plant extract is used to lower high cholesterol, and to treat atherosclerosis, arthritis, and assist in weight loss. Guggul is the extract of the gum resin of the Commiphora mukul tree, which is native to India. Guggulsterones can inhibit the synthesis of cholesterol in the liver, may have an antioxidant effect on lipids and may have thyroid-stimulating activity. Preliminary evidence suggests that it has protective effects against drug-induced myocardial necrosis. A study suggests guggul extracts might have anti-inflammatory, antiplatelet and anticoagulant activity and may also lower lipoprotein and C-reactive protein (Vaidya, 1997).
Phosphatidyl Choline. Phosphatidyl choline is a phospholipid and a main constituent of lecithin. As such, it is essential to form acetylcholine, one of the main neurotransmitters in the central nervous system. It demonstrates an inhibitory effect on cholesterol absorption and is used in metabolic syndrome with dyslipidemia. It may be beneficial in cases of high C-reactive protein and homocysteine blood levels (associated with inflammation), heart disease, metabolic syndrome, obesity, Type 2 diabetes with peripheral vascular disorders, liver steatosis and cirrhosis, elevated triglycerides, memory loss, and in advanced aging in case of Alzheimer's disease (Murray, 1994)
Red yeast rice (Monascus purpureus). Red yeast rice is a byproduct of the yeast (Monascus purpureus). It contains fiber, starch and fatty acids, as well as monacolin and mevinolin that are proven to provide natural benefits for cholesterol health. Red yeast is proven to effectively inhibit cholesterol production in the liver similarly to statins. At the same time red yeast may lower Coenzyme Q 10 levels thus, recommendation on daily supplementation with Co Q 10 must be advised. Lately they were contraindications mentioned in the literature for its side effects, reminding to those of the statins family (Bartram, 2002).
Green tea. Green tea may improve cognitive performance as well as treat stomach disorders, vomiting, diarrhea and headaches. It is used as a diuretic and in combination products for weight loss (Luo, Kannar, Wahlqvist & O'Brien, 1997). It may be beneficial to in prevention of heart disease, glucose abnormalities and kidney stones. Preliminary studies show that flavonoids found in green tea might reduce lipoprotein oxidation. In vitro tests indicate that catechins in green tea reduce proliferation of vascular smooth muscle that occurs with high concentrations of low-density lipoproteins (LDL). There is some evidence that an unidentified compound in green tea and caffeine suppresses thromboxane formation during blood clotting by inhibiting the release of arachidonic acid from platelets. A study indicated that a green tea extract rich in EGCG can increase calorie and fat metabolism (Luo et al., 1997). Polyphenols such as gallic acid and catechins such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC) are abundant in green tea and were found to be responsible for many of its proposed benefits.
Policosanol. A natural derivative of sugarcane (Saccharum officinarum), policosanol was found to control elevated cholesterol levels in multiple studies in Cuba and in 25 other countries in Central and South America. As a natural mix of higher aliphatic alcohols, policosanol is considered one of the most useful nutritional supplement in case of metabolic syndrome with dyslipidemia, diabetes, hypertonia, high risk of CVD with insulin resistance (Castano, Mas, Gomez, Fernandez & Illnait, 2004; Castano, Mas, Fernandez, Gomez & Amor, 2002).
Another long-term follow-up study by the same authors established the beneficial role of policosanol in patients with intermittent claudication (Castano, Mas, & Fernandez 2001; Castano et al., 1999) with no observable side effects (Castano et al., 2001) Type 2 diabetes development (Castano et al., 1999; Crespo et al., 1999) and high coronary risk and type II hypercholesterolemia (Castano et al., 2001). The teams concluded that doses of policosanol at 40 mg/day are able to lower triglyceride levels in hypercholesterolemic subjects. They proved policosanol works like lovastatin in dyslipidemia cases without the side effects of the synthetic drug (Castano et al., 2002).
Policosanol is described in the literature as decreasing the total cholesterol, bad (LDL) cholesterol, and triglycerides as well as increasing good (HDL) cholesterol levels. Thus, it is considered useful for heart attack prevention. In another direct comparative trial with statins, policosanol performed better than both lovastatin and simvаstаtin. Policosanol at 10 mg/day resulted in a 24% reduction in LDL, whereas lovastatin at 20 mg/day reduced LDL 22%, and simvastatin at 10 mg/day reduced LDL 15%. The same study showed that policosanol may significantly increase HDL, while HDL levels did not change in patients taking statins (Pratt & Matthews, 2003). Comparative effects of policosanol and two HMG-CoA- reductase inhibitors on type II hypercholesterolemia are studied by Prat (1999).
Cholesterol is a lipid produced in the liver, and also obtained from animal products in the diet: red meats, eggs and dairy products (Freeman & Junge, 2005). As a fat-like substance, cholesterol does not dissolve in blood, but instead it connects with proteins to form small particles known as lipoproteins. There are known four types of lipoproteins: chylomicrons, very-low-density lipoprotein (VLDL), low-density (LDL) lipoprotein and high-density lipoprotein (HDL). The overproduction of very low-density lipoproteins (VLDL) is described as the hallmark of dyslipidemia and the metabolic syndrome appearance in a study by Adiels et al. (2008). The emergence of cholesterol reduction as a marker is a major event for the pharmaceutical industry and metabolic syndrome promises to be as “big or bigger" (Breistein, 2004).
According to Reaven, unbalanced levels of cholesterol can lead to a cluster of metabolic cardiovascular diseases known as “metabolic syndrome” (Reaven, 1988). He taught that there are known two types of fat—subcutaneous and visceral. The first type of body fat, which is a noticeable layer of fat that lies just below the skin, is called “subcutaneous fat”. The second type, “visceral fat”, can go largely unnoticed because it is not visible to the naked eye. The only effective way researchers can locate visceral fat is by magnetic resonance imaging (MRI). Where adipose tissue is stored is critical to diagnose metabolic syndrome and determining of its health consequences. As proven in several experiments, individuals who consume large amounts of saturated fat and those who perform little or no physical activity are likely to have high stores of visceral fat (Fauci, 2008; Ford et al., 2002).
Atherosclerosis can occur in arteries throughout the body, including the coronary arteries (those feeding the heart). In time, narrowing or clogging of the coronary arteries by atherosclerosis can produce the signs and symptoms of heart disease, including angina (chest pain) and heart attacks. Metabolic syndrome and the risk of heart incidents and mortality are studied in mega-analytical, longitudinal studies (Gami et al., 2007). As known in the literature, hypercholesterolemia (dyslipidemia) may significantly increase the risk of heart disease as it can lead to atherosclerosis—a condition in which fat and cholesterol are deposited on the walls of the arteries. Recent study published in Lancet is showing the effect of statins and 3-omega fatty acids in heart failure cases (Fonarow, 2008).
Many factors appear to contribute to the development of high cholesterol:
(a). Heredity—genes partly influence how the body makes and handles cholesterol.
(b). Diet—a high intake of saturated fat, dietary cholesterol, and excess calories can cause cholesterol levels increase.
(c). Age and gender—Cholesterol levels begin to increase in both men and women beginning around 20 years of age. Premenopausal women usually have lower levels of cholesterol when compared with men of the same age. After menopause, a woman's LDL cholesterol levels typically go up, as so does her risk for heart disease.
(d). Other medical conditions—Conditions such as diabetes, obesity, liver steatosis, or kidney disease can cause elevated cholesterol.
(e). Lack of physical activity—Increased physical activity lowers LDL and raises HDL levels.
Treatment of dyslipidemia is generally aimed at lowering the low-density lipoproteins (LDL) or "bad cholesterol," lowering triglyceride levels, and increasing the high-density lipoproteins (HDL) or "good cholesterol” (Freeman & Junge, 2005). The Cholesterol and Recurrent Events Study (CARE) performed in 1996 showed benefits of cholesterol lowering especially in heart attack patients. This study reported that even in patients with normal cholesterol the use of statin drug decreases the risk of having another repetitive heart attack by 24%. Women benefited more than men by reducing their risk of having another heart attack by 45%. The final conclusions done after the CARE study calculated on the basis of 1000 patient’s treatment showed 153 fewer heart attacks and deaths from heart attack and in patients over 60- they would be 214 fewer deaths for men and 248 fewer for women (CARE, 1996).
Another study published in 1998, also known as the “long-term intervention with Pravastatin in ischemic disease” (LIPID) study, was based on the examination of the effects of cholesterol lowering in people with CHD who already experienced a heart attack or had been hospitalized for angina. They all presented normal cholesterol levels. The patients were placed on a cholesterol-lowering diet, and on a statin drug. The final results showed a drop of 18% in the total cholesterol and 25% in the LDL cholesterol leading to 24% decreased in death rate among the treatment group comparatively with the placebo group. In the group of patients who needed bypass surgery or angioplasty the results showed a decline by 22 of death rates, a decline by 20% in the need for bypass surgery or angioplasty, a decline by 29% from heart attack, and 19% from stroke (LIPID, 1998).
Link between Metabolic Syndrome and the Adipokines
The metabolic syndrome is associated with the adipokines in older adults across a wide range of adiposity, including in those with low or normal overall fatness is a statement published by Perls et al. (1999). A protein hormone produced and secreted exclusively by the adipocytes (fat cells), adiponectin can regulate the metabolism of lipids and glucose. Adiponectin influences the body's response to insulin. It also has anti-inflammatory effects on the cells lining the walls of blood vessels. High blood levels of adiponectin are associated with a reduced risk of heart attack while low levels of adiponectin are found in people who are obese and therefore at increased risk of a heart attack (Matsuzawa et al., 2004).
Dyslipidemia (abnormal cholesterol levels) is a marker of the metabolic syndrome cluster, characterized with elevated triglycerides, decreased HDL, and increased VLDL. Atherogenic dyslipidemia consists in an aggregation of lipoproteins abnormalities (elevated serum triglycerides and apo (a), increased small LDL (VLDL), and reduced HDL levels). All of the above factors plus glucose intolerance, a prothrombotic and a proinflammatory state are atherogenic factors. Increased LDL is not exactly part of the metabolic syndrome, but it makes a lot of sense to be considered in the treatment panel. Abnormal cholesterol levels and more specifically high LDL (low density lipoprotein) levels are strong predictors for cardiovascular disease, especially in men (Armstrong, 2006). Highly elevated LDL cholesterol in the blood causes plaque formation and can signal the beginning of atherosclerosis (Ridker et al., 2002).
The connection between HDL-cholesterol, triglyceride, and body weight in women aged 40-65 years is shown in the Prospective Cardiovascular Münster Study (PROCAM, 1997). Determinants of mortality are showing that with increasing BMI, there is an increase in fasting triglyceride levels and a decrease in HDL-cholesterol levels. An important question of the study is if age-related changes in lipid risk factors in women are due to increasing age alone or due to effects of menopause. Thus, all the women have been divided into two groups—a premenopausal group and menopausal group. The difference in many risk factors between both groups was greater than can be explained on the basis of age alone, including LDL cholesterol, triglycerides and BMI (Cullen, Schulte, & Assmann, 1997). The HDL cholesterol levels did not differ between premenopausal and postmenopausal women. Fasting insulin and apolipoproteins B levels and low density lipoprotein particle size are seen as risk factors for ischemic heart disease (Cullen et al., 1997; Lamarche et al., 1998).
Anticholesterol Drugs (PDR, 2008)
Statins
HMG-CoA reductase inhibitors (statins) are used as first and initial allopathic choice of treatment in case of hypercholesterolemia. Their prescription is a reason of the millions of profit by the Big Pharmaceutical companies. Currently, there are six statin drugs available, which prescription choice depends on doctor’s preference, insurance benefits and how much cholesterol reduction is requested. There are several studies that show that certain high risk patients, such as those with metabolic syndrome and diabetes, benefit from cholesterol lowering therapy with statins. The anti-inflammatory effect of statin therapy on C-reactive protein levels are proved in a randomized trial and a cohort study (Albert, Danielson & Rifai, 2001).
Due to the well-known connection between high cholesterol and heart disease, a complete cholesterol profile should be issued for adults with family history of metabolic syndrome, obesity and coronary heart disease. The lipid panel includes measuring total cholesterol, triglycerides, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), and high-density lipoprotein (HDL). According to the opinion of Sinatra (2008), despite the increasing use of statins, a significant number of coronary events still occur and many of such events take place in patients presenting with the metabolic syndrome. Since the introduction of statins, dietary therapy for control of elevated low-density lipoprotein (LDL) levels of cholesterol has received less attention. According to the author’s statement people should be aware that statins may cause multiple side effects.
The family of statins is also proved to lower body's ability to produce CoQ10 due to both substances- CoQ10 and cholesterol are derived from the same substance, mevalonate. As the main purpose of statins is to inhibit the creation of cholesterol, and by extension, it suppresses the creation of CoQ10. Sinatra believed that it is extremely important to consider adding a high quality CoQ10 supplement to the daily regimen, in order to help maintain optimal health. He states that fortunately, we are living in time of huge importance of maximal dietary therapy as a cost-effective means for treatment of elevated LDL concentrations and for lifetime prevention of coronary heart disease (Sinatra, 2008).
A low fat or low cholesterol diet and exercise are essential in helping to lower cholesterol and to maintain low cholesterol levels. While drug therapy is often needed to lower cholesterol, diet and exercise are additionally recommended helping the drug therapy to lower and control cholesterol levels (Chapman et al., 2005). The authors claim that to patients with established cardiovascular disease (CVD) are offered more intense lifestyle changes. They believe that a correct decision is to start a patient with dietary therapy while drug therapy is usually based on a patient's LDL cholesterol levels, presence of heart disease, and risk factors, especially the so called “Framingham Risk”.
Fibrates
Fibric acid derivatives (fibrates) are another class of medications directed to lower blood triglyceride levels. The available US registered fibrates are gemfibrozil (Lopid) and fenofibrate (Tricor). Their main mechanism of action is to lower blood triglyceride levels by reducing VLDL liver’s production and by increasing their elimination.
Fibrates are moderately effective in increasing blood HDL cholesterol levels and not effective in lowering LDL cholesterol levels. In high risk patients, a combination between fenofibrate with statin may be prescribed to a metabolic syndrome patient with dyslipidemia. According to a new study there is strong evidence indicating that fibrates may reduce significantly cardiovascular risk (Tenenbaum & Fisman, 2004).
The side effects of fibrates include gallstones formation, nausea, stomach upset, and diarrhea. Along with statins fibrates can cause liver toxicity or liver inflammation. Nature can also help you support LDL and HDL cholesterol levels. There are formulas and ingredients in them that have shown ability to inhibit platelet aggregation, reduce triglyceride levels, enhance circulation and reduce clotting potential.
Omega-3 Fatty Acids
There are many clinical studies that prove regular consumption of fish oils can lower risk of sudden cardiac death and to protect against heart disease. Working as anti-inflammatory substances, they can reduce inflammation and oxidation as a byproduct of degenerative diseases including metabolic syndrome, obesity, Alzheimer’s disease, gout, kidney disease, diabetes (Mori et al., 2000).
Omega- 3 fatty acids may be used for their anti-clotting properties. UCLA scientists have confirmed that fish oil is a missing link to Alzheimer’s disease, recently also known also as ‘diabetes of the brain’. There was a report that recapitulated that omega-3-fatty acid DHA could increase production of LR11, a protein found in Alzheimer’s patients (Azzi, Gysin & Kempna, 2004).
Omega-3 EFA’s have been found intimately related with increased insulin secretion and improved insulin sensitivity (Kris-Etherton & Hill, 2008). Omega-3 EFA effects in patients with chronic heart failure were studied in a randomized, double-blind, placebo-controlled trial (GISSI-HF investigators). Omega-3 EFA can improve amino acid transport to muscle tissue, metabolic rate, cholesterol and energy levels (Mori et al., 2000). Omega-3 EFA could also play role in alleviating inflammation by decreasing cyclooxygenase (COX-2) enzymes associated with cytokines related with inflammation (Sears & Lawren, 1995). Mori et al (2000) concluded that by simply incorporating high omega-3 sources into the metabolic syndrome diet in a form of fish or fish oil would be very beneficial for alleviating the syndrome and its consequences. Authors also added that other natural sources of 3-omega fats are: salmon, flaxseeds, whitefish, tuna, algae, and spirulina for daily supply (Mori et al., 2000). Giampapa et al. (2004) calculated that fat should constitute 20% of the food supply. The authors claimed that omega-3 EFA could have beneficial effects on lipid metabolism by reducing bad cholesterol and triglycerides, positive anti-inflammatory effects, reducing insulin response to glucose, and diminishing risk of cardiovascular disease and cancer.
Supplementation with omega-3 seems was linked to an increase of vigor and a decrease of depression, anger, and anxiety. 3 EFAs were found beneficial in adult’s dementia, depression and mood disorders, as they may act as mood stabilizers. The above correlation was shown in subjects the Zone diet and the results confirm the influence of omega-3 on the central nervous system (Sears & Lawren, 1995).
The beneficial role of omega-3 EFAs in term of influencing obesity was studied by (Kris-Etherton & Hill, 2008). A mega-analytical study executed by a team (Balk, Chung & Lichtenstein, 2004) combined the results of 31 placebo-controlled studies of fish oil (3-omega) and 1,356 hypertensive individuals. The authors’ concluded that there was a dose-response hypotensive effect of fish oil in hypertensive patients. Final conclusion from this study was that omega -3 EFAs did reduce blood pressure in people with mild hypertension. The use of omega 3 fatty acids for cardioprotection was also studied by (Lee, O'Keefe, Lavie, Marcholi & Harris., 2008). Based on results of a 20-year nutritional study two authors scientifically illustrated that a “plant-based- oil-free diet” can not only prevent and stop the progression of heart disease as a consequence of metabolic syndrome, but it can also reverse its effects (Caldwell & Esselstyne Jr, 2008).
Olive Oil
Recent study results showed that olive oil also has a powerful protective effect upon experimental inflammation models in cases of a polyphenol-supplemented virgin olive oil diet (Martinez-Dominguez, de la PR., & Ruiz-Gutierrez, 2001). The polyphenols of olive oil and red wine antioxidant polyphenols inhibit the endothelial activation and have strong antiatherogenic properties, as seen in the “Mediterranean Diet” (Carluccio et al., 2003).
One of the largest and most comprehensive studies of lifestyle risk factors titled The Nurses’ Health Study (NHS) lead by a team of (Hu et al., 2001) followed 85,000 women for a period of 16 years. This study was dedicated to the diet, lifestyle, and risk of Type 2 diabetes mellitus in women and made an effort to convince Western civilization that most cases of Type 2 diabetes may be prevented by losing weight. It was found that eliminating trans-fatty acids and reducing polyunsaturated fatty acids may reduce the risk of metabolic syndrome. Although no direct causal link between trans-fat acids effect and diabetes was identified, in the presence of an underlying insulin resistance, researchers found trans-fats and other hydrogenated fats to increase the probability of developing the syndrome and its consequences (Hu et al., 2001). All the above studies and observations open a new path to the development of nutraceuticals and nutraceutical combinations tailored to specifically affect the function of the human genomic control, being named genome-directed nutraceuticals (Azzi et al., 2004)
Fiber
These important micronutrients are needed to keep the body in a good balance. Vegetables, especially non-starchy vegetables, contain fiber and important micronutrients such as vitamins and minerals. Daily fiber may help metabolic syndrome patients to regulate blood sugar levels. The ability of oat beta-glucan to reduce blood cholesterol in hypercholesterolemic subjects it is shown in a study by Braaten, Wood and Scott (1994). Oats, spelt, corn, barley, peas, beans, fruits and vegetables are rich in fiber and complex carbohydrates. The connection between soluble fiber and serum lipids is shown in a literature review published by the team of researchers (Glore, Van Treeck & Knehana, 1994).
Glucomannan. Glucomannan is another natural plant-based fiber that benefits digestive health. It is a calorie-free nutrient, what may promote healthy blood sugar levels and a significant decrease of elevated cholesterol. Derived from the konjac root, it is a water-soluble dietary fiber that acts as a bulk-forming laxative (Anderson, Algood & Turner, 1999). Another team of researchers (Anderson, Kendall & Jenkins, 2004) offered carbohydrate and fiber recommendations for individuals with diabetes. The lipid-and glucose-lowering efficacy of Plantago psyllium in Type 2 diabetes are studied by another team (Rodrigers-Moran, Guerrero-Romero & Lazcano-Burciaga, 1998).
Choline Bitartrate. Choline Bitartrate prevents fats from accumulating in the liver, and is essential for the health of nerves, kidneys and liver. It aids in emulsifying cholesterol so it doesn't settle on the arterial walls. Most people with metabolic syndrome, hypertonia, heart abnormalities (heart palpitation), liver steatosis, and even liver cirrhosis are discovered to show choline deficiency. It is an important lipotropic (fat emulsifier) involved in the biosynthesis of lecithin and the formation of the amino acid methionine (Mindell, 1999).
Inositol. Inositol is not considered a vitamin per se because it can be synthesized by the body. It is beneficial in case of diabetic neuropathy, metabolic syndrome, panic disorder, high cholesterol, insomnia, cancer, depression, schizophrenia, Alzheimer's disease, attention deficit-hyperactivity disorder (ADHD), polycystic ovarian syndrome, hypertension, high triglycerides, high LDL cholesterol, peripheral vascular disease and Raynaud's disease (Goodman, Rall, Nies & Taylor, 1996).
Vitamin B-3 (Niacin) is important for maintaining cell energy. It assists in transforming carbohydrates into fats, and also processes alcohol. Experts in cardiology research explain in their study the benefits of niacin by influencing the glycemic status in patients with healed myocardial infarction. According to this study vitamin B3 (niacin) was found to improve cholesterol regulation in terms of decreasing LDL cholesterol and increasing HDL cholesterol (Canner, Furberg, Terrin & McGovern, 2005). The study is a randomized, placebo-controlled coronary study known also as the Coronary Drug Project (CDP, 2009) compared five lipid-modifying agents in men with previous myocardial infarction (MI). The study identified strong benefits of niacin in metabolic syndrome; it improved glycemic status in patients with myocardial infarction. Results of this study supported the use of B3 in post-myocardial infarcts (MI) and proved that there is a decreased 6-year (MI) mortality and 15-year total mortality (CDP, 2009) in people with metabolic syndrome. What took the attention of the authors was that benefits of niacin were found greater in patients with metabolic syndrome, versus patients without the syndrome. Niacin was confirmed as a low-cost, highly effective agent capable of reducing total cholesterol, raising HDL and lowering VLDL and triglycerides (Canner et al., 2005).
Guggulipid (Myrrh). This plant extract is used to lower high cholesterol, and to treat atherosclerosis, arthritis, and assist in weight loss. Guggul is the extract of the gum resin of the Commiphora mukul tree, which is native to India. Guggulsterones can inhibit the synthesis of cholesterol in the liver, may have an antioxidant effect on lipids and may have thyroid-stimulating activity. Preliminary evidence suggests that it has protective effects against drug-induced myocardial necrosis. A study suggests guggul extracts might have anti-inflammatory, antiplatelet and anticoagulant activity and may also lower lipoprotein and C-reactive protein (Vaidya, 1997).
Phosphatidyl Choline. Phosphatidyl choline is a phospholipid and a main constituent of lecithin. As such, it is essential to form acetylcholine, one of the main neurotransmitters in the central nervous system. It demonstrates an inhibitory effect on cholesterol absorption and is used in metabolic syndrome with dyslipidemia. It may be beneficial in cases of high C-reactive protein and homocysteine blood levels (associated with inflammation), heart disease, metabolic syndrome, obesity, Type 2 diabetes with peripheral vascular disorders, liver steatosis and cirrhosis, elevated triglycerides, memory loss, and in advanced aging in case of Alzheimer's disease (Murray, 1994)
Red yeast rice (Monascus purpureus). Red yeast rice is a byproduct of the yeast (Monascus purpureus). It contains fiber, starch and fatty acids, as well as monacolin and mevinolin that are proven to provide natural benefits for cholesterol health. Red yeast is proven to effectively inhibit cholesterol production in the liver similarly to statins. At the same time red yeast may lower Coenzyme Q 10 levels thus, recommendation on daily supplementation with Co Q 10 must be advised. Lately they were contraindications mentioned in the literature for its side effects, reminding to those of the statins family (Bartram, 2002).
Green tea. Green tea may improve cognitive performance as well as treat stomach disorders, vomiting, diarrhea and headaches. It is used as a diuretic and in combination products for weight loss (Luo, Kannar, Wahlqvist & O'Brien, 1997). It may be beneficial to in prevention of heart disease, glucose abnormalities and kidney stones. Preliminary studies show that flavonoids found in green tea might reduce lipoprotein oxidation. In vitro tests indicate that catechins in green tea reduce proliferation of vascular smooth muscle that occurs with high concentrations of low-density lipoproteins (LDL). There is some evidence that an unidentified compound in green tea and caffeine suppresses thromboxane formation during blood clotting by inhibiting the release of arachidonic acid from platelets. A study indicated that a green tea extract rich in EGCG can increase calorie and fat metabolism (Luo et al., 1997). Polyphenols such as gallic acid and catechins such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG) and epicatechin (EC) are abundant in green tea and were found to be responsible for many of its proposed benefits.
Policosanol. A natural derivative of sugarcane (Saccharum officinarum), policosanol was found to control elevated cholesterol levels in multiple studies in Cuba and in 25 other countries in Central and South America. As a natural mix of higher aliphatic alcohols, policosanol is considered one of the most useful nutritional supplement in case of metabolic syndrome with dyslipidemia, diabetes, hypertonia, high risk of CVD with insulin resistance (Castano, Mas, Gomez, Fernandez & Illnait, 2004; Castano, Mas, Fernandez, Gomez & Amor, 2002).
Another long-term follow-up study by the same authors established the beneficial role of policosanol in patients with intermittent claudication (Castano, Mas, & Fernandez 2001; Castano et al., 1999) with no observable side effects (Castano et al., 2001) Type 2 diabetes development (Castano et al., 1999; Crespo et al., 1999) and high coronary risk and type II hypercholesterolemia (Castano et al., 2001). The teams concluded that doses of policosanol at 40 mg/day are able to lower triglyceride levels in hypercholesterolemic subjects. They proved policosanol works like lovastatin in dyslipidemia cases without the side effects of the synthetic drug (Castano et al., 2002).
Policosanol is described in the literature as decreasing the total cholesterol, bad (LDL) cholesterol, and triglycerides as well as increasing good (HDL) cholesterol levels. Thus, it is considered useful for heart attack prevention. In another direct comparative trial with statins, policosanol performed better than both lovastatin and simvаstаtin. Policosanol at 10 mg/day resulted in a 24% reduction in LDL, whereas lovastatin at 20 mg/day reduced LDL 22%, and simvastatin at 10 mg/day reduced LDL 15%. The same study showed that policosanol may significantly increase HDL, while HDL levels did not change in patients taking statins (Pratt & Matthews, 2003). Comparative effects of policosanol and two HMG-CoA- reductase inhibitors on type II hypercholesterolemia are studied by Prat (1999).
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These statements have not been evaluated by the Food and Drug Administration. The material in this newsletter is provided for informational purposes only. Thus our intentions are not to diagnose, cure, mitigate, treat or prevent any disease. If you use the information in this newsletter without the approval of your health professional, the authors of this letter do not assume any responsibility. Copyright @ 2009, Natural Health-Wellness LLC. All rights reserved.
These statements have not been evaluated by the Food and Drug Administration. The material in this newsletter is provided for informational purposes only. Thus our intentions are not to diagnose, cure, mitigate, treat or prevent any disease. If you use the information in this newsletter without the approval of your health professional, the authors of this letter do not assume any responsibility. Copyright @ 2009, Natural Health-Wellness LLC. All rights reserved.
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