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LDL cholesterol

  • Garlic, a popular culinary herb, has been used as a medical remedy in traditional medicine, for centuries and confirmed for its protective health benefits in current medical science. The intake of fresh garlic, in amounts needed for its health efficacy is accompanied by side effects of unpleasant odor that lingers on the breath and skin and potential gastrointestinal adverse effects of diarrhea and flatulence. Thus, many shun this important herb and are deprived of its benefits.

    An important and effective alternative was developed by the Wakunaga Company, originally in Japan and now also as Wakunaga of America, in California. The company manufactures Kyolic® Aged Garlic Extract (AGE™), an odorless supplement that has been shown in over 700 peer reviewed scientific and medical publications to have the health benefits of fresh garlic and often even a higher efficacy, without any of the side effects of the fresh bulb.

    While the health benefits of AGE are many, helping protect against cardiovascular disease, neurodegenerative disease, some forms of cancer, and has anti-aging and anti-inflammatory effects, this article will focus on the cardiovascular benefits as proven in research and in the clinic.

    Aged Garlic Extract
    Aged garlic extract is manufactured from organic fresh garlic, by extraction and aging for 20 months at room temperature. The result is a highly bioavailable odor-free supplement, rich in organosulfur compounds, largely water soluble, such as S-allyl Cysteine and S-allyl meractocysteine (unique to AGE), as well as other substances with antioxidant activity, including oil soluble organosulfur compounds, allixin, selenium, saponins and flavonoids. AGE is a supplement with high quality control, standardized by S-ally cysteine, its key compound.

    Risk Factors for Cardiovascular Disease
    Risk factors for cardiovascular disease include oxidative stress, elevated LDL cholesterol and triglycerides, low HDL (the good cholesterol), hypertension and high homocysteine; being overweight also increases risk.

    High LDL cholesterol promotes inflammation in the arteries, causing further accumulation of cholesterol in the arterial walls; this in turn produces more inflammation. Eventually the deposited cholesterol hardens into a plaque, which can rupture and lead to blood clots that cause heart attacks and strokes.

    Oxidant Stress
    Reactive oxygen species and oxidant stress are implicated in cardiovascular diseases. Oxidative damage to DNA, proteins, lipids, and other molecules rank highly as a major cause in the onset and development of these diseases. Reactive oxygen species, including free radicals, that are the cause of oxidant stress, in the absence of enough antioxidants, are byproducts of normal metabolism and increase during infection and inflammation, elevated homocysteine and exposure to exogenous sources, including environmental pollutants, smoking, certain drugs (e.g., acetaminophen), and radiation.

    AGE and Cardiovascular Disease
    AGE, with its antioxidant activities, has been shown to modulate cardiovascular risk factors in both clinical and preclinical settings. AGE has been found to reduce blood pressure, inhibit platelet aggregation and adhesion, lower LDL and elevate HDL cholesterol, reduce smoking-related oxidative damage, inhibit the production of prostaglandins involved in inflammation, and lower homocysteine. S-allyl cysteine has been found to lower cholesterol by deactivating the enzyme involved in cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA) by as much as 41 percent. AGE efficacy in reducing cholesterol synthesis is additive with statins. Other possible contributors to protection against cardiovascular disease are the effects of AGE in increasing microcirculation and protecting the lining of arteries, (endothelial cells) from oxidative damage, a factor notably important in diabetes, where microvasculature is damaged and the risk of heart disease is high. AGE can also temporarily increase, by 30–40 percent, the synthesis of cellular nitric oxide that helps regulate blood pressure. Major findings have shown that AGE inhibits the progression of coronary-artery calcification, thus reducing the risk of a myocardial infarct.

    Calcification and Heart Disease
    Calcium deposition in the walls of coronary arteries is an active process. Calcification is an early feature of atherosclerotic plaque formation, beginning with fatty-streak formation and continuing throughout the development of the plaque, resulting in a narrowing of the arteries.

    Studies by Dr. Matthew Budoff and colleagues at the University of California (UCLA) have shown repeatedly in a number of placebo-controlled randomized clinical studies, that AGE significantly reduces the progression of plaque formation compared to placebo, as determined by serial coronary artery calcium measurements, as described below. Other findings in patients taking AGE showed improved endothelial function, reduced LDL cholesterol, a lowering of an inflammation marker C reactive protein, and homocysteine and improving HDL cholesterol. The investigators concluded that the study, “helps establish garlic therapy as an anti-atherosclerosis therapy in patients with, and without coronary artery disease.”

    The early one year study by the Budoff group on the role of AGE in plaque progression, was a placebo-controlled, double-blind, randomized pilot study to determine if atherosclerotic plaques, detected by electron beam tomography, will progress at a different rate with the intake of AGE, as compared with a placebo. 19 patients (14 men, five women, mean age of 59.9 ± 10.5 y) completed the study. Subjects received either 1200 mg AGE a day or the equivalent amount of placebo. The patients were on statin therapy and aspirin during the study. The blood marker used for compliance was S-allyl cysteine, the major active compounds in AGE, considered the only reliable human compliance marker in studies on garlic consumption.

    The results of this yearlong study showed that patients taking AGE had an absolute change in the calcium score, (indicating plaque progression) of 45.2 +/-57.2, while the placebo group was 129.0 ± 102.1, significantly greater than the AGE group. All patients in this study were on statin therapy, meaning that the improvement seen by the intake of AGE was additive to the benefit of statin therapy. Plaque progression was at a rate of 22.2 percent per year in the placebo group, while the intake of AGE reduced progression to 7.5 percent. In the most recent study, presented by Dr. Budoff's group at the American College of Cardiology's 64th annual scientific meeting, in May 2015, the investigators pooled four placebo-controlled, double-blind, randomized studies to examine AGE's effect on blood pressure as well as progression of calcification. The studies involved 161 people, randomized to take, daily, either 1000 mg AGE or placebo, for one year. Blood pressure was checked at the beginning and end of the study. Testing was done to examine coronary artery calcification.

    One year later, the UCLA researchers found a reduction in blood pressure in the subjects taking AGE; AGE also inhibited the progression of coronary artery calcification by 1.78 fold, compared with placebo, over the course of the study. The principal investigator, Dr. Matthew Budoff, stated, "these new findings provide cardiologists and internists with an additional tool for patients who are at a high risk of cardiovascular disease. It also gives patients with mild to moderate cardiovascular disease a proactive way to reduce those risk factors."

    Elevated homocysteine damages endothelial cells that line blood vessels and induces thrombosis that can lead to heart attacks and stroke. Homocysteine produces breaks in DNA and induces apoptosis, a programmed cell death. Consumption of AGE has been shown to reduce homocysteine levels. In a preclinical study, levels of homocysteine in a 4-week folatedeficient diet containing AGE were compared with a folatefortified diet containing AGE. Plasma homocysteine was 30 percent lower in the folate-deficient models that received AGE, but not in those with adequate folate. The results suggest that AGE may serve as an added treatment in hyperhomocyteinemia. A clinical study, showing that AGE inhibits the progression of coronary artery calcification, also showed a trend in lowering homocysteine levels.

    Age And Inflammation
    Prostaglandins, play a key role in Inflammation, a risk factor in heart disease as well as other pathological conditions, including neurodegenerative disease and cancer. In a study by Rahman and colleagues the role of AGE in modifying prostaglandins was tested in smokers and non smokers. At the start of the trial, the plasma concentration of prostaglandin 8 iso PGF2ƒ¿ was about 58 percent greater in smokers than in nonsmokers. A 14 days supplementation with AGE resulted in a 35 percent reduction in the plasma prostaglandin in smokers, and a 29 percent reduction in non smokers.

    The prostaglandin studied plays a role in cardiovascular disease by increasing the stickiness and adhesion of platelets, thus increasing the risk of plaque formation, constriction of arteries and atherosclerosis; the prostaglandin has been shown to be present in increased amounts in human atherosclerotic vascular tissue compared with healthy tissue. The decrease in 8 iso PGF2ƒ¿ following AGE intake supports earlier findings of AGE decreasing platelet aggregation. This study further confirmed that dietary supplementation with AGE with its powerful antioxidant capabilities, can protect against heart atherosclerosis and heart disease, which are associated with increased oxidative stress and inflammation.

    Bottom line
    Kyolico Aged Garlic Extract (AGE), a natural odorless supplement produced from organically grown fresh garlic, by Wakunaga of America has a wide range of health effects including the ability to lower the risk of heart disease. AGE has been shown in clinical studies to reduce atherosclerotic plaque formation, lower LDL cholesterol and triglycerides, decrease hypertension, prevent platelet aggregation, lower levels of homocysteine, and other inflammatory factors, including a critical prostaglandin. AGE taken daily can help reduce the risk of heart disease that is a major cause of death in our society.

    1. Varshney R, Budoff MJ. Garlic and Heart Disease. J Nutr. 2016 Jan 13. pii: jn202333. [Epub ahead of print] Review.
    2. Budoff M. Aged garlic extract retards progression of coronary artery calcification. J Nutr. 2006 Mar;136:741S.4S.
    3. Allison GL, Lowe GM, Rahman K. Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sci. 2012 Dec 17;91(25.26):1275.80. doi:10.1016/j.lfs.2012.09.019. Epub 2012 Oct 13.
    4. Dllon SA, Lowe GM, Billington D, Rahman K. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. J Nutr. 2002 Feb;132:168.71.
    5. Ide N, Keller C, Weiss N. Aged garlic extract inhibits homocysteine-induced CD36 expression and foam cell formation in human macrophages. J Nutr. 2006 Mar;136:755S.8S
    6. Borek C. Garlic reduces dementia and heart-disease risk. J Nutr. 2006 Mar;136: 810S.812S.
  • They are used to construct the cells and tissues that form our bodies, provide sources of energy to power metabolism (as well as provide a mechanism for storing energy between meals), and are used to form the countless enzymes that drive our metabolism. Unlike the micronutrients (vitamins and minerals) which are needed in small amounts and are generally reused, macronutrients undergo a constant flux in our body, necessitating a consistent intake to provide enough energy for our survival and enough building blocks for the growth, maintenance, and repair of our bodies.

    Each of the macronutrients is actually a complex of smaller building blocks with important nutritional roles. Proteins are constructed of amino acids, carbohydrates of sugars or monosaccharides, and fats of fatty acids. As macronutrients are absorbed from a meal, they are broken down into their individual constituents, which are used for the various purposes in metabolism. The great adaptability of our body chemistry gives us the ability to take these individual building blocks (amino acids, sugars, and fatty acids) and reassemble them or even interconvert them to satisfy our metabolic needs. This explains how an Innuit can consume a diet predominantly of fish protein and fat, yet still have enough carbohydrate (glucose) in their blood to fuel the demand of their brains. Or how someone can adopt a completely fat-free diet, yet still become obese through the conversion of excessive dietary carbohydrates into body fat. Because of their interconversion in the body, macronutrients themselves are not nutritionally essential, although some of their building blocks may be (nine of the amino acids and two of the fatty acids are considered essential). Evidence also suggests that although macronutrients can be readily interconverted in the body, each may have additional benefits when present in the diet as a particular percentage of total dietary intake.

    To gain an appreciation of the function of each of the macronutrients and ultimately understand how much we may need, it is really necessary to discuss each individually. In this first part of the series, we will examine the roles and requirements for dietary protein.

    Out of all the macronutrients, protein has the most diverse set of roles in metabolism. It forms the connective tissues that hold our organs together; it is a significant portion of our bones, and the predominant component of muscle fibers. Moreover, protein forms the thousands of enzymes which carry out critical chemical reactions, the various transporters that move nutrients in and out of cells and throughout the body, the antibodies of our immune system, and many of the hormones that direct our growth, energy utilization, and homeostasis. Due to its ubiquitous nature in the function of all living things, dietary protein occurs in most whole food sources. Muscle meats are the most concentrated sources (muscle fibers are constructed of protein filaments); milk and eggs are also good sources. Legumes, exotic grains, and many vegetables are good protein sources, such that a balanced vegetarian or vegan diet can provide adequate protein for the body’s needs. Once consumed, dietary protein is broken down by the action of stomach acid and several digestive enzymes secreted from the stomach and pancreas (called proteases). From here, the resulting individual amino acids or small protein fragments (called peptides) are absorbed from the small intestine, and distributed throughout the body to satisfy various roles. We generally don’t absorb enzymes or other proteins intact.

    Dietary protein has several fates in human metabolism:

    New Protein Synthesis. The amino acids liberated from dietary protein can be used to make other proteins in the body. While organisms can make amino acids from other sources (such as fats or carbohydrates), making new proteins from dietary amino acids is the quickest and most energetically economical way. This is especially important for sustaining periods of rapid growth, such as during childhood development or intense weight training. Perhaps more importantly, dietary protein is the only source of essential amino acids for metabolism. Of the twenty different amino acids used to make proteins, humans have lost the ability to produce nine of them on their own (methionine, lysine, valine, tryptophan, phenylalanine, isoleucine, leucine, threonine, and histidine). Therefore, a minimal amount of dietary protein is required to supply enough of these essentials to maintain protein synthesis in the body.

    Precursors to other biomolecules. Several of the essential amino acids from dietary protein are used to construct important “non-protein” chemicals for the body. For example, the hormones seratonin and melatonin, and vitamin B3 (niacin) are derived from the essential amino acid tryptophan; thyroxine (thyroid hormone), adrenaline, and the endorphins (natural analgesics) depend on intake of the essential amino acid phenylalanine. Thus, our ability to produce these hormones and neurotransmitters is heavily dependent on the presence of essential amino acids in the diet.

    Dietary protein is also the predominant sources of the elements nitrogen and sulfur, both essential to metabolism. Nitrogen from dietary amino acids is redistributed in the body to make other amino acids, nucleotides (the building blocks of DNA, as well as the energy molecule ATP), and glycosaminoglycans (components of connective tissues, such as chondroitin, keratan, and hyaluronic acid). Sulfur is also used in the construction of glycosaminoglycans, as well as several important antioxidants (such as glutathione and alpha lipoic acid).

    Fuel Source. Dietary protein can serve as an energy source. Following a meal, about 50 percent of the amino acids that have been released from dietary protein are metabolized by the liver into energy (ATP). Unlike carbohydrates or fats, excess amino acids from the diet are not stored in the body; if they are not immediately used to make new protein or energy, they are converted to carbohydrates or fats for storage. The liver can also metabolize most amino acids into glucose, to provide energy to the brain and other tissues. Proteins are less efficient at raising blood glucose than are carbohydrates; while they provide the same number of calories on a gram-for-gram basis (4 calories/gram), they only raise blood glucose 50–80 percent as much as an equivalent amount of carbohydrates.

    Skeletal muscles depend heavily on amino acids for energy. The essential amino acids leucine, isoleucine, and valine (called the branched chain amino acids or BCAAs) are preferentially taken up by muscle cells after a meal to be burned as fuel. Healthy individuals will metabolize upwards of 10 grams/ day of BCAAs in their muscles if they are available in the diet.

    In addition to their standard roles in metabolism, dietary protein has been associated with specific health effects, including:

    Weight Loss and Satiety. High protein diets have been associated with better glycemic control, and have been shown to promote greater fat reduction than high carbohydrate or high fat diets that provide the same number of calories. Dietary proteins are more difficult to convert into energy than the carbohydrates or fat; diets high in protein have been reported to have a greater thermogenic effect and expend more energy than lower protein diets. Randomized, controlled trials comparing low and high-protein diets studies have shown that diets higher in protein are more effective at preserving lean muscle, reducing body fat, and maintaining lower insulin levels after a meal.

    There is convincing evidence that proteins are more satiating than the other macronutrients, and that the satiating ability of proteins may be related to their amino acid composition and how quickly they are digested. Much of this effect has been attributed to the rapid appearance of the essential branched chain amino acids in the blood; leucine, one of the BCAAs, has been shown to influence the metabolic pathways in the brain that regulate food intake, at least in animal models. Evidence also suggests that higher protein intake at one meal may significantly decrease appetite at the next meal, although the studies in this area are not consistent.

    Promoting Healthy Levels of Blood Lipids. Dietary protein, particularly dietary soy protein, has been studied for its ability to lower cholesterol levels by either increasing the removal of low-density lipoprotein cholesterol (LDL or “bad” cholesterol) from the blood, or as a replacement for other high fat/ high cholesterol protein sources. Over 60 controlled trials of soy protein consumption in humans have been performed, many in hypercholesterolemic patients. Taken together, these studies revealed that an average intake of 47 g/day of soy protein resulted in significant improvements in blood lipid/lipoprotein parameters, with average reductions in total cholesterol of 9 percent and LDL cholesterol of 12.9 percent. These data were the foundation for the FDA approved health claim for soy protein in the prevention of cardiovascular disease.

    Promoting Healthy Blood Pressure. Several human trials and epidemiological studies have indicated an inverse associate between dietary protein intake and blood pressure. Forty-six human studies of protein intake and blood pressure (20 clinical trials, 15 observational studies and 13 biomarker studies) have demonstrated a clear, beneficial effect for plant protein on reductions in blood pressure. The reductions averaged up to a 1.4 mm Hg reduction in systolic blood pressure and a 1 mm Hg reduction in diastolic blood pressure for every 11 g of plant protein consumed per day, based on observational studies. The mechanism by which protein may reduce blood pressure is unclear; it may be helping to rid the body of sodium, it may increase insulin sensitivity, or it may increase the blood concentration of the amino acid arginine, the precursor to the blood-pressure lowering hormone nitric oxide.

    As with most macronutrients, the required amount of dietary protein depends on individual needs. Discussion of the research regarding the merits of diets differing in the relative ratios of protein, carbohydrate, and fats will be the subject of a future article, but some general considerations on dietary protein content bear mentioning here.

    The Food and Nutrition Board of the National Institute of Medicine has established a dietary reference intake of 56 g/day for adult men, 46 g/day for adult women, based on metabolic studies. These figures are based on a reference (“average”) body weight; a more individualized assessment of daily protein requirements for a healthy individual would be 0.8 g/kg (about 0.36 g/lb) body weight. Under circumstances of increased metabolic demand, higher protein intakes may be warranted. In pregnant and lactating women, for example, daily protein requirements increase to approximately 1.1 g/kg of body weight, or 71 g/day for the “average” woman. The dietary protein requirements of athletic individuals who wish to increase their lean body mass has been the subject of considerable debate, but is generally believed to exceed the reference values. Studies have suggested protein requirements of 1.1 g/ kg per day for endurance athletes and 1.3 g/kg per day in strength-trained athletes.

    There are some circumstances where reduced protein intake may be warranted. Since excess dietary protein is not stored in the body, it must be immediately used up (to make new proteins), converted into energy, or converted to carbohydrates or fat for storage. In the latter two cases, amino acids are broken down, and the nitrogen they carry is eliminated from the body (as urea). The breakdown of amino acids and excretion of nitrogen are fundamental functions of the liver and kidneys, but for individuals with kidney or liver disease, excessive protein consumption can be problematic. Low-protein diets (below 0.8 g/kg per day) may be beneficial in these cases. Dietary protein requirements should also be carefully considered in individuals with hyperuricemia, a condition of excessive uric acid in the blood. Hyperuricemia affects an estimated 21 percent of Americans, and is a primary risk factor for gout, a type of arthritis typified by a rapid onset of inflammation, usually in the joints of the extremities. Elevated blood uric acid is also a risk for kidney and cardiovascular diseases, and diabetes. While dietary protein itself does not elevate blood uric acid, compounds found in some sources of animal protein (called purines) do increase hyperuricemia risk. Therefore, individuals with elevated blood uric acid should limit their intake of protein from meats (other animal proteins, such from milk or eggs, as well as vegetable protein, do not appear to be associated with hyperuricemia risk and may actually reduce it).

    To read the series on Macronutrients: