Risk Factors / Causes
Nutrients & Rationale
Emerging research has revealed that levels of cholesterol account for only a portion of the cardiovascular risk profile, while the properties of the molecules responsible for transporting cholesterol through the blood, called lipoproteins, offer important insights into the development of atherosclerosis.
In fact, the size and density of lipoproteins are important factors for cardiovascular risk – for example, large, buoyant LDL (“bad cholesterol”) particles are much less dangerous than small, dense LDL particles. Likewise large, buoyant HDL (“good cholesterol”) particles offer greater vascular protection than smaller, denser HDL. Furthermore, metabolic processes, such as oxidation and glycation, modify the functionality of lipoproteins, transforming them from cholesterol transport vehicles into highly reactive molecules capable of damaging the delicate endothelial cells that line our arterial walls. Scientifically supported natural interventions can target the formation of these modified lipoproteins and help avert deadly cardiovascular diseases such as heart attack and stroke.
The pharmaceutical industry has been very successful in promoting cholesterol reduction with statin drugs as the most important strategy for reducing cardiovascular risk. However, although the use of pharmaceutical treatment has saved lives, optimal cardiovascular protection involves a multifactorial strategy that also targets risk factors responsible for vascular disease.
The Blood Lipids: Cholesterol and Triglycerides
CHOLESTEROL is a wax-like steroid molecule that plays a critical role in metabolism. It is a major component of cellular membranes, where its concentration varies depending on the function of the particular cell. For example, the membrane of liver cells contains fairly large fractions of cholesterol (~30%).1
The cholesterol in cell membranes serves two primary functions. First, it modulates the fluidity of membranes, allowing them to maintain their function over a wide range of temperatures. Second, it prevents leakage of ions (molecules used by the cell to interact with its environment) by acting as a cellular insulator.2 This effect is critical for the proper function of neuronal cells, because the cholesterol-rich myelin sheath insulates neurons (brain cells) and allows them to transmit electrical impulses rapidly over distances.
Cholesterol has other important roles in human metabolism. Cholesterol serves as a precursor to the steroid hormones, which include the sex hormones (androgens and estrogens), mineral-corticoids, which control the balance of water and minerals in the kidney, and glucocorticoids, which control protein and carbohydrate metabolism, immune suppression, and inflammation. Cholesterol is also the precursor to vitamin D. Finally, cholesterol provides the framework for the synthesis of bile acids, which emulsify dietary fats for absorption.
TRIGLYCERIDES are storage lipids that have a critical role in metabolism and energy production. They are molecular complexes of glycerol (glycerin) and three fatty acids. Fatty acids, on the other hand, when packaged as triglycerides, are denser sources of energy than carbohydrates, which make them superior for long-term energy storage.
Lipoproteins: Blood Lipid Transporters
Lipids (cholesterol and fatty acids) are unable to move independently through the blood stream, and so must be transported throughout the body as lipid particles. The lipid particles that transport cholesterol in circulation are called lipoproteins. Lipoproteins can also carry fat-soluble antioxidants, like CoQ10, vitamin E, and carotenoids, which protect the transported lipids from oxidative damage. This is why vitamin E and CoQ10 have performed so well in cardiovascular studies – because they prevent the oxidative modification of LDL particles, which in turn protects the blood vessel lining from damage.
4 main classes of lipoproteins exist, and each has a different, important function:
- Chylomicrons (CMs) are produced in the small intestines and deliver energy-rich dietary fats to muscles (for energy) or fat cells (for storage). They also deliver dietary cholesterol from the intestines to the liver.
- Very low density lipoproteins (VLDLs) take triglycerides, phospholipids, and cholesterol, from the liver and transport them to fat cells.
- Low density lipoproteins (LDLs) carry cholesterol from the liver to cells that require it. In aging people, LDL often transports cholesterol to the linings of their arteries where it may not be needed.
- High density lipoproteins (HDLs) transport excess cholesterol (from cells, or other lipoproteins like CMs or VLDLs) back to the liver, where it can be re-processed and/ or excreted from the body as bile salts. HDL removes excess cholesterol from the arterial wall.
Amongst its myriad of functions, the liver has a role in cholesterol metabolism. Following a meal, the liver converts excess glucose and fatty acids into triglycerides for storage, and packages them into VLDL particles for transit to fat cells. VLDLs travel from the liver to fat cells, where they transfer triglycerides/fatty acids to the cell for storage. VLDLs carry between 10 and 15% of the total cholesterol normally found in the blood.3
As VLDLs release their triglycerides to fat cells, VLDL transition to a low-density lipoprotein (LDL). The LDL particle, which averages about 45% cholesterol, is the primary particle for the transport of cholesterol from the liver to other cells of the body; about 60-70% of serum cholesterol is carried by LDL.4
Because of the correlation between elevated blood levels of cholesterol carried in LDL and the risk of heart disease, LDL is commonly referred to as the “bad cholesterol”. LDL is, however, more than just cholesterol, and its contribution to disease risk involves more than just the cholesterol it carries.
All LDL particles are not created equal. In fact, LDL subfractions are divided into several classes based on size (diameter) and density. Smaller, denser LDLs are significantly more atherogenic for two reasons; they are much more susceptible to oxidation,5,6,7 and they pass from the blood stream into the blood vessel wall much more efficiently than large buoyant LDL particles.8
HDLs are small, dense lipoprotein particles that are assembled in the liver, and carry about 20-30% of the total serum cholesterol.9 Cholesterol carried in the HDL particle is called “good cholesterol,” in reference to the protective effect HDL particles can have on cardiovascular disease risk. HDL particles can pick up cholesterol from other tissues and transport it back to the liver for re-processing and/or disposal as bile salts. HDL can also transport cholesterol to the testes, ovaries and adrenals to serve as precursors to steroid hormones.
The movement of cholesterol from tissues to the liver for clearance, mediated by HDLs, is called reverse cholesterol transport. If the reverse cholesterol transport process is not functioning efficiently, lipids can build up in tissues such as the arterial wall. Thus, reverse cholesterol transport is critical for avoiding atherosclerosis.
Association between Cholesterol and Cardiovascular Disease
When LDL particles are exposed to free radicals, they become oxidized and structural and functional changes occur to the entire LDL particle. The oxidized LDL (ox-LDL) particle can damage the delicate endothelial lining of the inside of blood vessels.17 Once the oxidized-LDL particle has disrupted the integrity of the endothelial barrier, additional LDL particles flood into the arterial wall (intima). Immune cells (macrophages) respond by engulfing it in an effort to remove it. But, the immune cells then become too enlarged and are unable to escape back through the endothelial layer. They become trapped within the intima, causing oxidative and inflammatory reactions to occur, resulting in the oxidation of additional native LDL particles and recruitment of more immune cells. This accumulative cycle results in the formation of atherosclerotic plaque deposits, which cause the arterial wall to protrude and disrupt blood flow.
Lowering serum cholesterol to an “optimal” range (total cholesterol 160 – 180; LDL-C 50-99) is one of the most frequently used strategies for reducing heart disease risk.18 This approach, however, only addresses a portion of the risk.
Optimal cholesterol management is important for reducing cardiovascular risk. Other risk factors of arterial disease are also associated with cholesterol issues.
Risk Factors of Arterial Disease:
- Low blood EPA/DHA
- Excess homocysteine
- Excess cholesterol
- Excess LDL
- Low HDL
- Oxidized LDL
- Excess triglycerides
- Excess insulin
- High glucose
- Hormone imbalance
- Excess fibrinogen
- Nitric oxide deficit
- Insufficient vitamin D
- Low vitamin k
High Blood Sugar Increases the Atherogenicity of LDL
Elevated levels of blood sugar create ideal conditions for glycation reactions to occur. Glycation is a process by which a protein or a lipid is joined together (non-enzymatically) with a sugar. The resultant product is a highly reactive molecule that is capable of damaging tissues it comes in contact with.
Glycation of LDL particles can greatly increase the atherogenicity of LDL. Glycated LDL has been shown to be significantly more susceptible to oxidation than native LDL,24 and to substantially impair endothelial function.25 Also, glycated LDL stimulates oxidative stress and inflammation in blood vessels and exacerbates plaque build-up within blood vessel walls. Glycated, oxidized LDL causes degradation of endothelial nitric oxide synthase (eNOS), a critical enzyme involved in maintaining proper vasodilatation and blood flow.27 Moreover, once LDL has become glycated, it is no longer recognized by the LDL receptor on cell surfaces, meaning that it will remain in circulation and is more likely to contribute to the atherosclerotic process.28
Individuals with diabetes are known to be at substantially greater risk for developing atherosclerosis . 29
Conventional medicine for cholesterol management may involve use of statins. Statins may induce serious side effects in some individuals, most common being muscle pain or weakness (myopathy). The prevalence of myopathy is fairly low in clinical trials (1.5-3.0%), but can be as high as 33% in community based studies and may rise dramatically in statin users who are active (up to 75% in statin-treated athletes.)35,36
Occasionally, statins may cause an elevation of the liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Additionally, by inhibiting HMG-CoA reductase (an enzyme not only required for the production of cholesterol, but other metabolites as well), statins may also reduce levels of the critically important antioxidant molecule CoQ10. Hence, supplementing with CoQ10 is essential.
NUTRITIONAL APPROACHES TO MANAGING CHOLESTEROL & LIPIDS
Nutritional approaches to cholesterol include:
- Dietary modifications that aim to reduce the intake and uptake of fats and cholesterol from the diet;
- Specific nutritional compounds with cholesterol-lowering (hypocholesterolemic) or cardioprotective properties.
Dietary and lifestyle changes are the first step in meeting cholesterol management goals.
General recommendations are:
- High vegetables and fruits intake
- Fiber (31 grams/day)
- Potassium (4.7 grams / day)
- Low in animal products
- Limit sodium (salt) to 1.5 grams/day45
Caloric restriction (CR)
Reduction of dietary calories slows down the body’s growth processes, causing it to instead focus on protective repair mechanisms; the overall effect is an improvement in several measures of wellbeing. Observational studies have tracked the effects of CR on lean, healthy individuals, and have demonstrated that moderate CR (22-30% decreases in caloric intake from normal levels) improves heart function, reduces markers of inflammation (C-reactive protein, tumor necrosis factor (TNF)), reduces risk factors for cardiovascular disease (LDL-C, triglycerides, blood pressure) and reduces diabetes risk factors (fasting blood glucose and insulin levels).47,48,49,50
Nutrients for Lipid Management
Several nutrients have been identified as potential agents for promoting a healthy lipid profile. They work by the same principles as conventional therapies (such as reducing cholesterol synthesis, or interfering with cholesterol absorption in the gut). Several also have additional activities (antihypertensive, inhibition of LDL-oxidation, anti-inflammatory) that complement their cholesterol-lowering activity.
(A) Inhibiting Cholesterol Synthesis
Pantethine is a derivative of pantothenic acid (vitamin B5), and can serve as a source of the vitamin. It appears to act on the body’s fat and cholesterol metabolism pathways. One notable function of vitamin B5 is its conversion into coenzyme A, a necessary factor in the metabolism of fatty acids into cellular energy. The pantethine derivative cysteamine may also function to reduce the activity of liver enzymes that produce cholesterol and triglycerides.56 Studies of pantethine consumption have demonstrated significant reductions in total- and LDL cholesterol (up to 13.5%), triglycerides, and elevation of HDL-C in hypercholesterolemic subjects (individuals with high cholesterol)57,58 and diabetic subjects59 when taken at 900-1,200mg/day, although significant effects on triglycerides have been observed at dosages as low as 600 mg / day.60
Red yeast rice
A traditional preparation of rice fermented by the yeast Monascus purpureus, the yeast produces metabolites (monacolins) that are naturally-occuring HMG-CoA Reductase inhibitors (one of these, monacolin K, is chemically identical to lovastatin61). A comprehensive review of 93 randomized trials including nearly 10,000 patients has demonstrated that commercial preparations of red yeast rice produced reduction in total cholesterol, LDL-C, triglycerides, and an increase in HDL-cholesterol.62
Garlic is substantiated by several human trials, particularly its ability to support favorable blood lipid profiles. While the average cholesterol reductions across all human studies are modest, greater reductions in total cholesterol were realized in patients who were initially hyperlipidemic or hypertriglycemic (>11 mg/dL reduction), took the extract for over 12 weeks (11 mg/dL reduction), or took a garlic powder (as opposed to an oil or aged extract; 12 mg/dL reduction).70
Garlic also reduces systolic- and diastolic- blood pressure (SBP and DBP) in hypertensive individuals, and systolic blood pressure in persons with normal blood pressure. A recent review and analysis of 11 controlled human trials of garlic showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo, while the mean decrease in the hypertensive subgroup was 8.4 mm Hg for SBP and 7.3 mm Hg for DBP.71
Indian Gooseberry (Amla; Emblica officinalis)
This has been used traditionally as a nutrient-dense food in Indian regions, and in Ayurvedic medicine for treating a variety of conditions. Analytical studies on extracts of Indian Gooseberry highlight its potent antioxidant properties. In human studies, extracts of amla have been shown to attenuate elevations in LDL, total cholesterol, and triglycerides, and boost levels of protective HDL.75 In a study examining the antioxidant activity of amla extract in subjects with metabolic abnormalities, four months of supplementation was shown to dramatically bolster plasma antioxidant power and suppress oxidative stress.76
Studies suggest that amla extract may also protect against LDL glycation by modulating blood glucose levels. In diabetic patients, amla not only significantly reduced post-prandial glucose levels, but also lowered lipid and triglyceride levels over a 21 day period77. In an animal model of metabolic syndrome induced by a high fructose diet, concomitant administration of amla extract reined in rising cholesterol and triglyceride levels, and also significantly repressed the expression of inflammation-related genes, which are typically elevated in metabolic syndrome models.78 Extracts of the antioxidant-rich fruit also reduce levels of advanced glycation end products (AGEs), which are formed by the same process as glycated LDL.79 By limiting the amount of LDL particles that become glycated, amla may help maintain proper cellular uptake of cholesterol and reduce the amount of LDL-C available to infiltrate the arterial wall.
Gynostemma pentaphyllum (G. pentaphyllum) is used in Asian medicine to treat several chronic conditions, including diabetes and inflammatory disorders. Its effects are due in part to its ability to activate a critical enzyme called adenosine monophosphate-activated protein kinase (AMPK).158,159 This enzyme, which affects glucose metabolism and fat storage, has been called a “metabolic master switch” because it controls numerous metabolic pathways.160,161
Activation of AMPK stimulates glucose uptake in muscles and beta oxidation, in which fatty acids are broken down, while reducing the production of fat and cholesterol in the liver.158 It can also prevent damage to blood vessel lining (endothelial) cells caused by oxidized LDL (“bad”) cholesterol.162 AMPK activation reduces cholesterol and triglyceride levels.163,164
G. pentaphyllum stimulates AMPK activation and affects cholesterol levels in the blood and liver. A study in obese mice showed eight weeks of supplementation with G. pentaphyllum led to weight loss and improvements in glucose metabolism and cholesterol levels. Mice treated with 150 mg/kg (about 900 mg for an adult human) or 300 mg/kg (about 1800 mg for an adult human) of the extract had total cholesterol reductions of 14.2% and 7.1%, respectively, compared with the control group.158
(B)Inhibiting Absorption of Dietary Cholesterol
Propolmannan is a polysaccharide fiber derived from a plant that grows only in the remote mountains of Northern Japan. Propolmannan is patented in 33 countries as a purified fiber that does not break down in the digestive tract. Published studies reveal propolmannan’s ability to not only increase the amount of bile acids in the feces, but also reduce the rate of carbohydrate absorption and the subsequent glucose/insulin spike in the blood. When propolmannan is taken before meals, consistent and significant reductions in blood triglyceride, LDL, and cholesterol are observed.80
These include non-digestable and fermentable carbohydrates, and their sufficient intake has been associated with lower prevalence of cardiovascular disease.81 When included as part of a low-saturated fat/low cholesterol diet, they can lower LDL-C by 5-10% in hypercholesterolemic and diabetic patients, and may reduce LDL-C in healthy individuals as well.82 The cholesterol-lowering properties of soluble oat fiber, psyllium, pectin, guar gum, ß-glucans from barley, and chitosan are substantiated by dozens of controlled human clinical trials. 83,84,85 Soluble fibers lower cholesterol by several potential mechanisms.86 They may directly bind bile acids or dietary cholesterol, preventing/disrupting their absorption. Their high viscosities (measure of a liquids thickness) and effects on intestinal motility may slow or limit macronutrient uptake. They can also increase satiety, which can limit overall energy intake.
Prebiotics, a subset of soluble fiber, have gained attention in recent years in their ability to be selectively fermented by gut flora for a diversity of potential health-promoting benefits. The fermentation of prebiotic fibers into short-chain fatty acids such as acetate, butyrate, or propionate may inhibit cholesterol synthesis in the liver.87 In human trials, the prebiotic fibers inulin and dextrin have induced reductions in serum levels of total cholesterol (-9% and -2% for inulin and dextrin, respectively), LDL-C (-1 % for dextrin), and triglycerides (-21% for inulin).88,89
Plant sterols (phytosterols)
These are steroid compounds found in plants that function similarly to cholesterol in animals (as components of plant cell membranes, and precursors to plant hormones). Esters of sterols have a higher activity and better fat solubility, which allows for lower effective dosages (2-3 g/day as opposed to 5-10 g/day for unesterified sterols).90 Sterols themselves are poorly absorbed from the diet, but because of their chemical similarity to cholesterol, they are thought to compete with cholesterol for absorption in the intestines, which has the effect of reducing LDL levels.91 Sterols may also reduce cholesterol production in the liver, reduce the synthesis of VLDLs, increase LDL particle size, and increase LDL uptake from the blood92,93 HDL and/or very low-density lipoproteins are generally not affected by sterol intake.94
This resin of the Commiphora mukul tree has a history of traditional usage in Ayurvedic medicine and is widely used in Asia as a cholesterol-lowering agent. Guggulipid is a lipid extract of the gum that contains plant sterols (guggulsterones E and Z), the proposed bioactive compounds.99 Recent studies have produced conflicting results.
This has value as an anti-hypercholesterolemic agent not only because of the potential lipid-lowering effects of its included isoflavones (which may increase the amount of LDL receptors and help to clear LDL particles from the blood), but also for its potential as an alternative to other high fat/high cholesterol protein sources. A 1995 meta-analysis of 38 controlled human clinical trials (30 conducted on hypercholesterolemic patients) revealed that compared to animal protein, an average intake of 47g/day of soy protein resulted in significant improvements in blood lipid/lipoprotein parameters. Across the studies there were observable average reductions in total cholesterol (9%), LDL-C (12.9%), triglycerides (10.5%), and VLDL-C (2.6%), as well as a non-significant increase in HDL-C (2.4%)104
More recently, a second meta-analysis of 41 soy protein studies (including 32 new studies performed after 1995) confirmed the anti-hypercholesterolemic properties of soy protein. The average reductions in blood lipids were smaller (5.3% for total cholesterol, 4.3% for LDL-C, 6.3% for triglycerides, and a 0.8% increase in HDL-C), but this analysis was limited to studies that used soy protein isolates (which contain no cholesterol-lowering fiber).106
(C)Inhibiting Oxidation and Glycation of LDL
Coenzyme Q10 (CoQ10)
Delicate endothelial cells that line the arterial walls depend on healthy mitochondrial function to control blood pressure and vascular tone. Oxidized or glycated LDL can sabotage endothelial mitochondrial function and damage the endothelial barrier, setting the stage for the atherosclerotic cascade to initiate.109,110 CoQ10 is an integral component of mitochondrial metabolism, serving as an intermediary transporter between two major check points along the road to ATP production. Interestingly, CoQ10 is also the only known endogenously synthesized lipid soluble antioxidant,111 and is thus incorporated into LDL particles, where it serves to protect against oxidation. Because of these dual roles, insufficient levels of CoQ10 expedite atherogenesis from two angles – by limiting mitochondrial efficiency in endothelial cells and leaving LDL particles vulnerable to oxidative damage.
As noted above, statin drugs, which are typically used to treat high cholesterol, ironically also suppress levels of CoQ10 in the blood.112 Individuals taking a statin drug should always supplement with CoQ10.
Carotenoids are common constituents of the LDL particle. ß-carotene is the second most abundant antioxidant in LDL; other common dietary carotenoids (lycopene, lutein) may be transported by LDL particles as well.113 Together, these three carotenoids have an indispensable role in the protection of LDL particles from oxidative damage; their serum levels have been demonstrated to be the most predictive of the degree of LDL oxidation in humans.114Carotenoids may also possess additional lipid-lowering activities independent of their antioxidant potential.
Natural tocopherols and tocotrienols together form vitamin E. These fat-soluble antioxidants have been studied for decades and are known to protect against some cardiovascular events. Vitamin E strongly inhibits the oxidation of LDL particles.118,119
Alpha tocopherol is the best known form of vitamin E and is found in the largest quantities in blood and tissue. It is critical, however, for anyone supplementing with vitamin E to make sure they are also getting adequate gamma tocopherol each day. The key benefit is gamma tocopherol’s ability to dramatically reduce inflammatory threats, a major cause of virtually all degenerative diseases. One of the most important benefits of gamma tocopherol is its ability to improve endothelial function by increasing nitric oxide synthase, the enzyme responsible for producing vessel-relaxing nitric oxide.120 One major way it produces this effect is by sponging up destructive reactive nitrogen species, such as peroxynitrite.121 In fact, gamma tocopherol is able to “trap” a variety of reactive nitrogen species and halt their negative effects on a host of cellular processes.122
Supplementation in humans with 100 mg per day of gamma tocopherol showed resulted in a reduction in several risk factors for vascular disease such as platelet aggregation and LDL cholesterol levels.123
Dozens of placebo controlled clinical trials have been carried out on pomegranate juice, or pomegranate extract. With respect to lipid management, the efficacy of pomegranate is rivaled by very few natural compounds. The high concentration of polyphenols (particularly punicalagins) in pomegranate make it an ideal ingredient for suppressing LDL oxidation.124,125
Consumption of pomegranate polyphenols significantly lowered total and LDL cholesterol concentrations while maintaining HDL levels in subjects with elevated cholesterol profiles.126 Pomegranate also suppresses immune-reactivity against oxidized LDL, a mechanisms which would be expected to limit plaque formation in the intimia.127 In fact, this is exactly what was shown in a long-term study of pomegranate consumption. Subjects received either pomegranate juice or placebo for three years; in the group receiving the placebo, carotid intima media thickness (cIMT; a measure of atherosclerosis) increased by 9% one year after study initiation, while in the group receiving pomegranate, cIMT was reduced by an astonishing 30%. Moreover, pomegranate significantly reduced oxidized LDL concentrations, and increased serum antioxidant activity, compared to placebo, while simultaneously lowering blood pressure. This study also showed that pomegranate nearly doubled the activity of paraoxonase-1 (PON-1), an anti-atherogenic enzyme that optimizes the function of HDL and protects lipids from oxidative damage.128
Polyphenols are a diverse set of phytonutrients that are ubiquitous in the diet. Polyphenol intake has been associate with lower risk of cardiovascular mortality, and may partially explain the health benefits of several common foods (tea, fruits, vegetables, wine, chocolate).129 Flavonoids, the largest and best studied class of polyphenols, include catechins from green tea and chocolate, theaflavins from black tea, soy isoflavones, flavan-3-ol polymers from red wine, and anthocyanidins from grapes and berries. A systematic analysis of over 130 human studies of flavonoids revealed significant improvements in endothelial function (cocoa and black tea polyphenols) and blood pressure (anthocyanidins, isoflavones, cocoa); however, only green tea catechins exhibited significant cholesterol (LDL-C) lowering in this analysis (averaging about 9 mg/dL over 4 studies).130 Subsequently, a study of black tea extract in 47 mildly hypercholesterolemic Japanese men and women demonstrated an 8% reduction in total cholesterol and 13% drop in LDL-C after 3 months.131
Other polyphenolic compounds with significant lipid modification potential based on human studies include methylated citrus flavonoids (polymethoxyflavones), which were shown to lower total-cholesterol, LDL-C, and triglycerides by 27%, 25%, and 31%, respectively when combined with tocotrienols in a small pilot trial.132Additionally, the red wine polyphenol resveratrol was shown to incorporate into the LDL particles of human volunteers following ingestion of a high-resveratrol wine, potentially acting as a resident antioxidant.133 This is consistent with resveratrol’s role in the prevention of LDL oxidation observed in humans.134
Curcumin has a variety of protective roles in CVD, potentially reducing oxidative stress, inflammation, and the proliferations of smooth muscle cells and monocytes. 95 Small human trials studies have revealed the effects of curcumin on reducing in lipid peroxidation135,136 and plasma fibrinogen,137 both factors in the progression of atherosclerosis.138 Curcumin may also reduce serum cholesterol by increasing the production of the LDL receptor,139,140 but despite successes in animal models, human data on the anti-hypercholesterolemic effects of curcumin is conflicting. A small study of 10 healthy volunteers revealed significant decreases in lipid oxidation products (-33%) and total cholesterol (-12%), with a concomitant increase in HDL-C (29%) when using 500 mg curcumin daily for 7 days.141 In two subsequent studies, low-dose curcumin showed a non-significant trend toward lowering total- and LDL-C in acute coronary patients,142 while high dose-curcumin (1-4 g/day) exhibited non-significant increases in total-, LDL-, and HDL cholesterol.143
(D)Enhancing Cholesterol Elimination
Artichoke has traditional usage as a liver protectant and choleretic (compound that stimulates bile flow). In stimulating bile flow, artichoke may aid the body in the disposal of excess cholesterol. In vitro studies suggest its anti-atherosclerotic effects may also be linked to an antioxidant capacity that reduces LDL oxidation, or the ability of one of its constituents, luteolin, to indirectly inhibit HMG-CoA reductase.144
In addition to several uncontrolled human studies and case reports145, two randomized, controlled trials support the ability of artichoke extracts to lower total- and/or LDL-cholesterol. In the first trial, artichoke extract (1800 mg/day) for 6 weeks reduced total cholesterol (-9.9%) and LDL-C (-16.6%) in 71 hypercholesterolemic patients, with no differences in HDL-C or triglycerides.146 In the second, also in hypercholesterolemic patients, 1280 mg artichoke extract/day for 12 weeks reduced total cholesterol by 6.1%, when compared to a control group. Changes in LDL-C, HDL-C, and triglycerides were insignificant.147 Artichoke extract also improved parameters of endothelial function in a small human trial.148
(E)Optimizing the Lipid Profile
Niacin/Nicotinic acid (vitamin B3)
Vitamin B3 is an essential nutrient with roles throughout human metabolism. At dosages substantially above the recommended daily intake (RDI), prescription niacin treatments can significantly raise HDL-C (by 30-35% in some cases, at dosages averaging 2.25 grams/day).149,150 Niacin can also change the distribution of LDL by increasing the amount of large buoyant LDL and reducing the amount of small dense LDL.151 Niacin can also reduce the susceptibility of LDL to oxidation.152
In 2010, the results of seven published studies on the effects of niacin therapy were combined to examine the overall effect. This meta-analysis is considered more powerful than an individual study because it increases the sample size. The results showed that patients taking niacin (compared with a placebo) had significant reductions in nonfatal myocardial infarction and transient ischemic attack.153
Fish oil is a source of omega-3 fatty acids (eicosapentaenoic acid -- EPA, and docosahexaenoic acid -- DHA), which cannot be synthesized by humans but are nonetheless essential for several metabolic processes. Aside from reductions in the risk of cardiovascular mortality and non-fatal cardiovascular events (supported by studies of tens of thousands of moderate and high risk patients)154, fish oil fatty acids significantly reduce serum triglycerides. Forty-seven studies, comprising over 15,000 patients, have confirmed an average triglyceride reduction of 30 mg/dL, at an average intake of 3.35g EPA+DHA over 24 weeks.155 Triglycerides were reduced in a dose-dependent manner, and were dependent on baseline levels (reductions of greater than 40% were observed in patients with the highest starting triglyceride levels). Slight increases in LDL-C and HDL-C were also observed in these studies, although other large analyses failed to detect any significant effects of fish oil on cholesterol.156 The mechanism by which EPA + DHA lowers triglycerides is thought to be by slowing the release of VLDL particles into the plasma, or increasing lipid degradation and clearance of triglyceride-rich lipoproteins from the blood.157 Lowering triglyceride levels is a known strategy for increasing the amount of large buoyant LDL and reducing the amount of small dense LDL.
Prescription fish oil uses a highly concentrated EPA+DHA fish oil ester that provides a dosage of 3.36 g of omega-3 in 4 capsules. Non-prescription fish oil supplements sell at a fraction of the price of prescription fish oil and usually require more capsules to be taken daily to obtain the same amount of EPA/DHA.
Those with vascular disorders often manifesting as coronary artery disease should consider using a wide range of supplements and medication to suppress the multiple risk factors involved in atherosclerosis progression. Healthy individuals should carefully follow blood test results to ascertain which nutrients are more important.
Inhibiting Cholesterol Synthesis
- Pantethine: 400 – 1200 mg daily
- Red Yeast Rice: 600 – 1200 mg daily
- Garlic; standardized extract: 1500 – 3000 mg daily
- Amla (Indian gooseberry); standardized extract: 500 – 1000 mg daily
- Gynostemma pentaphyllum (G. pentaphyllum) extract: 450 mg daily preferably in divided doses
Inhibiting Absorption of Dietary Cholesterol
- Dietary Fiber: 25 – 30 grams daily
- Propolmannan: 2000 – 6000 mg daily
- Prebiotics: 5000 – 10 000 mg daily
- Plant Sterols: 600 – 1200 mg daily
- Soy isoflavones: 54 – 108 mg daily
Enhancing Cholesterol Elimination
- Artichoke Leaf; standardized extract: 500 – 1000 mg daily
Inhibiting Oxidation and Glycation of LDL
- CoQ10 (as ubiquinol): 100 – 300 mg daily
- High Gamma Tocopherol Vitamin E: 350 – 700 mg daily
- Pomegranate; standardized extract: 500 – 1000 mg daily
- Beta Carotene: 25 000 IU daily
- Lycopene: 15 – 30 mg daily
- Trans-Resveratrol: 250 – 500 mg daily
- Green tea; standardized extract: 700 – 1400 mg daily
- Black Tea; standardized extract: 350 – 700 mg daily
- Curcumin: 400 – 800 mg daily
Optimizing the Lipid Profile
- Niacin: 1000 – 2500 mg daily
- Omega 3 fatty acids (EPA and DHA): 1400 mg of EPA 1000 mg DHA daily
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