Juvenon Health Journal – June 2013, No. 6
This month we circle back to an important Harvard study –identifying the top preventable risk factors for premature mortality – as a healthy lifestyle discussion conversation starter. We’ve examined the latest research on high blood pressure, physical inactivity and blood glucose and how to translate these findings into important lifestyle and diet tweaks.
The sixth highest cause of premature death in the study was high low-density lipoproteins, LDL, which was linked to 113,000 deaths annually. Research indicates that more than 70 million Americans either have high cholesterol or are being treated for it. And another third of Americans have high LDL (“bad”) cholesterol, but less than half of them are being treated for it.
The University of California, Berkeley provides additional statistics. More than 16 million Americans suffer from coronary artery disease. And a startling 785,000 Americans suffer a first heart attack each year. In this oft-discussed medical topic, myths abound. For instance, it’s true that more men have heart attacks, and they have them at a younger age. However, after menopause the rates of heart disease in women increase two to three times and their risk of a heart attack rises dramatically.
What is cholesterol?
High cholesterol is a well-known risk factor for heart disease. The liver primarily makes this waxy, fat-like substance, although some comes from the diet. Cholesterol is often portrayed as the evil dietary villain. Truth is, there are two different types of cholesterol and one of them is actually “good” for your body.
Cholesterol is carried through the bloodstream attached to two different compounds called lipoproteins: low-density lipoproteins (LDL) and high-density lipoproteins (HDL). LDL is commonly known as the “bad” cholesterol because it transports cholesterol from the liver throughout the body, and potentially allows it to be deposited in artery walls. HDL, known as the “good cholesterol,” picks up cholesterol from the blood and delivers it to cells that use it, or takes it back to the liver to be recycled or eliminated from the body.
LDL Cholesterol and The Role of Inflammation
Evidence points to elevated blood levels of LDL cholesterol as a cause of atherosclerosis, which is a hardening of an artery specifically due to an atheromatous plaque related to LDL. However, the connection between high cholesterol and disease is complex. Most of our cholesterol is synthesized in the liver and subsequently combines with additional cellular constituents, such as lipids and proteins, before being released into the bloodstream.
There is a question regarding whether high LDL cholesterol is in itself a cause of vascular disease (the lipid hypothesis), or a response to an inflammatory condition that is the true cause of vascular disease (the inflammation hypothesis).
Indeed, recent research suggests LDL cholesterol’s clever accomplice is actually inflammation – the rush of white blood cells and chemicals that our immune system releases to combat damage or infection. Scientists now believe that cholesterol wouldn’t be nearly as dangerous without this process that is thought to be a key player in atherosclerosis.
According to the latter theory, chronically high levels of inflammation create small lesions on arterial walls. The body sends LDL to heal those lesions, but it ultimately accumulates and oxidizes, causing an accumulation of plaque that can form blood clots and blockages that may result in strokes and heart attacks. In fact, some studies show that a substance known as C-reactive protein (CRP), one of the so-called markers released by cells during the inflammation process, may be more effective than cholesterol in assessing the risk of cardiovascular disease and heart attacks. Some experts take the inflammation theory even further, positing that inflammation is the link between the many diseases and conditions that affect the heart and brain. The two theories – cholesterol itself as the enemy and cholesterol in response to inflammation – are not mutually exclusive; they may both be true to some extent.
Role of Mitochondria in Vascular Disease
Mitochondria are the powerhouses of our cells and their health is critical for normal metabolic function. Growing evidence supports the notion that oxidative damage to mitochondrial proteins leads to progressive dysfunction and that dysregulated mitochondrial function is the major unifying mechanism of several risk factors associated with atherosclerosis. Mitochondria play a critical role in the formation of abnormal fatty or lipid masses in arterial walls (called atherogenesis) by affecting the function of the cells lining the blood vessels (endothelial function), and the proliferation of vascular smooth muscle cells (VSMC).
Mitochondrial dysfunction can result in increased reactive oxygen species ROS (also known as free radicals) and calcium dysregulation. These effects promote the death of vascular cells, through apoptosis (programmed cell death) and senescence (aging), which are key processes in the development of vulnerable atherosclerotic plaques.
An elevated level of low-density lipoprotein (LDL) is associated with increased risk of coronary artery disease. Oxidative modification of LDL, and its transport deeper (subendothelial space) into the arterial wall at the sites of blood vessel lining cell (endothelial) damage, is considered an initiating event for atherosclerosis. Oxidative modification of LDL results from the interaction of ROS and reactive nitrogen species. The resulting increased oxidative stress induces endothelial dysfunction by impairing the bioactivity of endothelial nitric oxide and promotes adhesions, inflammation, thrombosis (platelet buildup), and smooth muscle cell proliferation–all processes that exacerbate atherosclerosis. Of the many potential cellular sources of chronic ROS production, mitochondria are a major source, and increased mitochondrial ROS generation and dysfunction are associated with cardiovascular and many other diseases. Thus, mitochondrial dysfunction plays an important role in the initiation and development of atherosclerosis.
Simply put, this process is a downward spiral. LDL combined with artery wall inflammation (which can be partially caused by poor mitochondrial function) creates a build up of oxidized LDL, which in turn creates more stress, inflammation, mitochondrial dysregulation/dysfunction, and cell death, and more ROS. This triggers more oxidized LDL and ultimately attracts more build up to the inflamed area.
Dysfunction of the mitochondrial respiratory chain and overproduction of reactive oxygen species (ROS) are associated with atherosclerosis and cardiovascular disease. A previous study demonstrated that oxidized LDL increased activity of mitochondrial complex I in human umbilical vein EC (endothelial cells). Scientists conducted a study on cultured pig aorta cells to work out the detail of how the build up of oxidized LDL might affect the mitochondria in the lining of blood vessels (endothelial cells), including oxygen consumption and the activities of key enzymes in the mitochondrial respiratory chain.¹ Mitochondria- associated intracellular ROS and release of ROS from EC (endothelial cells) were significantly increased after eoLDL (extensively oxidized LDL) treatment. These findings suggest that eoLDL impairs enzyme activity in mitochondrial respiratory chain complexes and increases ROS.
There is increasing evidence that mitochondrial damage/dysfunction occurs both in normal aging and in atherosclerosis. Mitochondrial dysfunction also has key metabolic effects, whose systemic manifestations may also promote atherosclerosis. Mitochondrial damage/dysfunction is thus a target for therapeutic intervention by targeted medicines or lifestyle changes.
However, the question of whether abnormalities in mitochondrial function are the cause or response to atherosclerosis and other cardiovascular dysfunctions is far from resolved.
Prescription cholesterol-lowering drugs are effective in decreasing total cholesterol but many are not as effective with regard to increasing the levels of healthy cholesterol or improving the HDL to LDL ratio. The B vitamin niacin, prescribed in combination with the common cholesterol-lowering drugs, does have a significant effect on lowering LDL and raising HDL. Dietary supplements that recharge the mitochondria also may offer some hope.
However, lifestyle, exercise and diet are important factors, too, in improving heart health. Consider adopting a Mediterranean diet featuring lots of fruits and vegetables, lean protein, nuts, tea and fish oil, as well as low to moderate alcohol intake.
In the coming months, the Juvenon Health Journal will continue to feature research that will help you stay informed and healthy. By offering effective, all-natural supplements and health news you can use, Juvenon provides an essential toolkit to battle aging enemies.
¹Effects of extensively oxidized low- density lipoprotein on mitochondrial function and reactive oxygen species in porcine aortic endothelial cells. Am J Physiol Endocrinol Metab 298: E89-E98, 2010. First published October 20, 2009; doi:10.1152/ajpendo.00433.2009].