by Steve Hickey
The body constantly requires vitamin C to repair minor damage to its tissues. In the case of atherosclerosis, the repair mechanisms fail. This failure is a direct result of a lack of available antioxidants, particularly vitamin C. Risk factors for heart disease and stroke relate in some way to the arterial disease or its progress, but they are not the cause of the illness. The focus on supposed risk factors, such as cholesterol, reflects an ignorance of the underlying biological processes. This focus ignores the finding that animals that synthesize vitamin C internally are resistant to atherosclerosis.12 Humans may achieve a corresponding freedom from cardiovascular disease by supplementing with high, dynamic flow levels of vitamin C.
The Process of Atherosclerosis
Any chemical, mechanical, or immunological insult to an artery produces free radical damage. This damage triggers a cascade of inflammatory reactions aimed at local repair, the activation of the immune system, and a massive local increased need for antioxidants. The result is a local area of inflammation in which almost all of the traditional risk factors may play a minor part.
Blood Pressure: Risk or Explanation?
Risk factors such as cholesterol do not explain the location of plaques within the arterial system. Mechanical and other stresses on the artery produce inflammation and stimulate plaque formation. Plaques occur more frequently in places that are stressed—often near the heart, where blood vessels stretch and bend. High blood pressure and pulsating blood flow tend to flex the vessels in these areas. The flow of blood around an obstruction also causes mechanical stress as the blood shears along the inner lining of the artery. In the case of high blood pressure, there is a simple mechanical relationship between the “risk factor” and damage to the arterial wall. This mechanism explains at least part of the distribution of arterial damage and plaques in cardiovascular disease.
Blood pressure is controlled by several mechanisms, including nerves and hormones, but the detailed controls are not completely understood. Systolic pressure is the peak pressure in the arteries and corresponds to the contraction of the heart muscle. The diastolic pressure is the lowest pressure and corresponds to the relaxation of the heart muscle. Normal ranges of blood pressure in the adult are typically assumed to be:
• Systolic: 90–135 mm Hg • Diastolic: 70–90 mm Hg
Children tend to have lower pressures, while in the elderly the measurements are typically higher. The increase in the elderly may result from reduced flexibility of the arteries, but this is not necessarily a consequence of normal aging. Not everyone experiences increasing blood pressure with age, so the condition may be an indication of chronic shortage of vitamin C, magnesium, and other nutrients in the modern diet.
Typical values for a healthy young adult at rest are usually given as 120 mm Hg systolic and 80 mm Hg diastolic (“120 over 80”), but there are large individual variations. Values above 120/80 are potentially pre-hypertensive and dietary modification may be considered. Some people have higher values, some lower, and some have a variation in the difference between the measured pressures. Furthermore, the measured values vary rapidly throughout the day with time and conditions in a single individual. They also change in response to numerous factors, such as stress, nutrition, and disease. This stress response can lead to the “white coat” effect—higher values being found by doctors and other staff in clinical settings. Such increased pressures can lead to people being unnecessarily worried, or overmedicated, for a condition they do not have. A person concerned about possible hypertension should monitor their pressure with readings taken at the same time over a period of days or weeks. Blood pressure measurement is often unreliable.
When uncontrolled, high blood pressure can result in aneurysms, in which an artery balloons out like a weak spot on an inner tube. Alternatively, repeated stress can cause chronic local inflammation, generating an arterial plaque of scarlike tissue in an attempt to repair the damage.13 High blood pressure is often described as a “risk factor” for heart disease, but for once there is a clear causal relationship between the “risk factor” of blood pressure and localized arterial stress.
Atherosclerosis appears to start with a minor disruption or damage to the blood vessel wall when vitamin C is in short supply. The damage begins with endothelial cells that separate the blood from the arterial wall.14 These cells sense the current conditions and provide signals to control the healing response of the artery, maintain blood vessel tone, and maintain blood flow.15 Endothelial cells control the flow of nutrients to the artery wall and are intimately involved in the initiation of inflammation.
When injured, the endothelial cells release a number of molecules (fibronectin, selectins, interleukin-1, intracellular adhesion molecule, vascular cell adhesion molecule, and others) that signal monocyte white blood cells in the blood to penetrate the blood vessel wall. Specific signals to initiate an inflammatory response may also be released.16 Factors that affect blood clotting (thromboxane, von Willebrand factor, prostacyclin, and tissue plasminogen) may also be produced.17 One of the more important local hormones regulating vascular tone and blood flow is nitric oxide (NO), which is released by the endothelial cells. NO is a free radical used extensively by our cells as a chemical signal in the control of local blood flow and blood pressure.18 It typically acts to dilate and increase flow and is thus antagonistic to other better-known hormones, such as adrenaline.19 In order to function properly and maintain healthy vessels and blood flow, nitric oxide is dependent on adequate amounts of vitamin C.20
With an adequate supply of vitamin C, the epithelial cells can increase production of NO when the blood vessel wall is stressed or damaged.21 NO production is signaled by several chemical factors (acetylcholine, thromboxane, bradykinin, estrogen, substance P, histamine, insulin, bacterial endotoxins, and adenosine) and mechanical factors, such as the shear stress of the blood flow.22 Nitric oxide is a gas that can dissolve in and diffuse readily through water and fat. This molecule will dilate blood vessels. NO is an essential early part of the defense mechanism of the arterial wall. People who have a defective nitric oxide response, resulting from vitamin C deficiency, can suffer increased resistance to blood flow and thickening of the blood vessel wall.
In 2003, American pharmacologist Louis J. Ignarro, Ph.D., suggested that atherosclerotic plaques act like trash caught in a river bend, impeding the flow. The result is local stress on the epithelial wall of the artery. Dr. Ignarro proposed that treatment with vitamin C and other antioxidants (vitamin E and alpha-lipoic acid) together with the amino acid L-arginine could prevent blood vessel inflammation and subsequent damage. He received the 1998 Nobel Prize in Physiology or Medicine for his work on nitric oxide signaling in the cardiovascular system. His experiments suggested that dietary supplements of antioxidant vitamins and L-arginine could lower the risk of heart disease in mice.23 He believed this vitamin C–based approach would produce similar results in patients with heart disease.24
When smooth muscle cells within arteries contract, they reduce the diameter of the vessel and help maintain vascular tone and blood pressure. Unlike skeletal muscle, smooth muscle cells are not normally under conscious control. The autonomic nervous system and hormones such as adrenaline provide smooth muscle tone as well as the elasticity necessary for dissipating the energy of blood flow pulses arising from the beating of the heart. In people with high blood pressure or with atherosclerosis, the smooth muscle cells can secrete local hormones and other active chemicals, which attract white blood cells and act as growth promoters.25 This change is thought to add to the strength of the developing arterial plaque.26 As the smooth muscle cells proliferate, they secrete proteins that combine with collagen and elastic fibers to form a fibrous cap over the advancing plaque.27
As the plaque grows and develops, there is an increased cholesterol and lipid content. The smooth muscle cells in advanced plaques appear aged and have increased rates of cell death. These cells are more sensitive to damage by free radicals and may be killed by white
blood cells activated by the local inflammation. The death of these muscle cells can further stimulate the inflammatory process, weakening the arterial wall and causing it to balloon out as an aneurysm.28 If the fibrous cap ruptures, it releases fats and fragments of plaque into the bloodstream and is recognized by the blood as a wound (lesion). The blood responds by forming a clot to seal off the damaged blood vessel wall.29 With small plaque ruptures, the tissue may partially heal, including clot material into the plaque. Larger plaque ruptures can lead to clots that block the artery. Prevention of plaque rupture with orthomolecular levels of vitamin C could provide an effective prevention of heart attack and stroke.
White blood cells are a component of inflammation and their contribution to atherosclerosis is expected. Monocyte white blood cells migrate from the blood into the arterial wall, ultimately leading to further oxidative damage to the epithelial cells. When activated by injury, the endothelial cells cause monocytes to stick to the interior surface of the artery. The monocytes then squeeze through the gaps between the endothelial cells and enter the arterial wall. As the plaque develops further, more monocytes are recruited with the release of local hormones from cells in the inflamed tissue. Once in the plaque, monocytes can transform into another type of white blood cell called macrophages, which engulf microscopic foreign bodies as part of the immune response. Reactive oxygen species, typically present in inflammation, signal the change from monocyte to macrophage.30
In the absence of sufficient vitamin C, the inflammation continues and the activity of the macrophages may cease to be beneficial and cause the plaque to rupture. Once inside the plaque, macrophages help the repair process by taking up lipoproteins, such as LDL cholesterol, including those that have been oxidized or otherwise degraded. The oxidized cholesterol is, however, toxic and can damage the macrophage.31 Macrophages take lipids within their bodies, but if this accumulation becomes extreme, the interiors of the cells starts to look foamy and they are called “foam cells.” Foam cells often die within the plaque from apoptosis. They are considered harmful and a potential source of additional oxygen radicals.32 Macrophages accumulate in the core of the plaque as it ages, and this accumulation is associated with a softening of the plaque, increasing risk of plaque rupture and heart attack.33 Each stage of this pathological process depends on oxidation and free radical damage, suggesting a local deficit in antioxidants.
Is Heart Disease Infectious?
The role of infectious agents in common diseases in humans, such as heart disease and stomach ulcers, has been downplayed by conventional medicine. However, since the discovery that peptic ulcers are caused by Helicobacter pylori, we might expect the idea that other common long-term diseases are caused by infections to be given serious consideration.34 Vitamin C is a powerful antiviral, antibacterial, and immune-stimulating agent. It would therefore be predicted to prevent or eliminate heart disease under this model. The idea that heart disease might be an infection was suggested early in the twentieth century and is now being reconsidered because traditional risk factors do not explain the cause of the disease.35
There are a number of potential candidates for infectious agents that cause heart disease, including influenza A and B, adenovirus, enterovirus, coxsackie B4 virus, and various herpes viruses (especially cytomegalovirus). Viruses are known to infect the cells of blood vessels36 and atherosclerotic areas may be more available for viral attack.37 Bacterial infections with Chlamydia pneumoniae, H. pylori, Hemophilus influenzae, Mycoplasma pneumoniae, Mycobacterium tuberculosis, and gingivitis may also be involved.38 Multiple disease organisms can be found, such as those also found in gum disease (Porphyromonas gingivalis and Streptococcus sanguis), and the infection could provide a trigger for acute events resulting in clot formation.39 Multiple organisms can act together to give increased inflammation or a modified plaque.40 The available evidence suggests that the overall microbial burden is linked to opportunistic infection of the arteries and heart attack.41
Infection acts to speed up the process of inflammatory damage, as opportunistic viral and other organisms can give rise to increased oxidation and free radical damage.42 The idea that atherosclerosis is an infection is a scientifically reasonable hypothesis, and we can be fairly certain that if an infection produces or contributes to chronic local inflammation in an artery, a plaque will result. Both viral and bacterial infections aggravate lesion development in animal models of atherosclerosis.43 More importantly, perhaps, is the variability in host susceptibility to the pathogens, which appears to relate to the ability to generate a successful immune response and, particularly, control inflammation.
Herpes
In the 1970s, researchers found that a bird virus, called Marek’s disease herpes virus (MDV), caused atherosclerosis in chickens. The involvement of viruses in the progression of the disease in birds may be indirect by stimulation of the immune system generating a local inflammatory response.44 The resulting plaques had fibrous, thickening, and atherosclerotic changes similar to those found in human disease.45 Striking plaques were seen in large coronary arteries, aortas, and major aortic branches of chickens with both normal and high cholesterol levels. Uninfected chickens had no large plaques, whether or not they were fed high-cholesterol diets. Notably the development of atherosclerosis in these chickens could be prevented by immunization against herpes virus.46
By the 1980s, scientists were beginning to take the idea of atherosclerosis as an infectious disease seriously. The atherosclerotic plaques in Japanese quail were examined and herpes DNA was consistently found in the aortas of embryos selected for genetic susceptibility to atherosclerosis but in a far smaller fraction of unsusceptible quail embryos.47 These results suggest that genetic susceptibility to atherosclerosis in birds may be linked to an immune deficiency or viral genes being passed through the generations. Later research demonstrated that rats infected with herpes also developed blood vessel lesions48 and mice infected with herpes are more susceptible to atherosclerosis.49
When atherosclerotic plaques in humans were examined for herpes simplex DNA, it was present.50 DNA from other herpes viruses, such as cytomegalovirus, are also found within arteries in humans and is associated with atherosclerotic plaques.51 This virus also may be linked to aortic aneurysms in humans.52 Until 1995, active virus had not been isolated from atherosclerotic plaque, but a decade later it had been found associated with specific cell types.53 However, a latent virus can lie dormant for years until the immune system is unable to keep it in check. Latent herpes virus, waiting to infect people with weakened immune systems, is known to be common, especially in patients with atherosclerosis.54 Both the smooth muscle cells in arteries and white blood cells attracted to sites of arterial damage are candidates for harboring the virus.55 Immunosuppressed patients with herpes infection are prone to atherosclerosis; an infection with cytomegalovirus is also associated with reduced long-term survival in heart transplant patients.56 That heart transplants in children often fail through atherosclerotic changes appears quite inconsistent with the idea of lifestyle risk factors being the primary cause.57
Periodically activated virus may have a role in the pathogenesis of atherosclerosis. When the arteries of young trauma victims were examined, herpes virus was found both in normal sections of artery and in early atherosclerotic lesions.58 Since herpes viruses have been implicated in the initiation and development of atherosclerosis, it could be that immunization against these would prevent the disease.59 However, cytomegalovirus damages coronary arteries by a progressive inflammatory response that involves proliferation of smooth muscle cells. Inhibition of this cell proliferation can be obtained using antioxidants, suggesting that oxidative stress following viral exposure might be triggering the proliferation.60 If several infective agents are involved, vaccination against a specific organism would be futile. The available evidence suggests that high doses of vitamin C will prevent a wide range of infective agents and thus be more effective.
Chlamydia
Mo
st people know Chlamydia trachomatis as the cause of a common sexually transmitted disease. Most people with chlamydia have no symptoms and are unaware of the infection; it is also a frequent cause of preventable blindness in many parts of the world. However, with heart disease, we are mainly concerned with another form of chlamydia, Chlamydia pneumoniae. Chlamydia pneumoniae is a microorganism that infects the respiratory tract and is also claimed to be involved in atherosclerosis.61
It is transmitted person-to-person in the air with respiratory secretions. All ages are at risk of infection but it is most common in school-age children. About half of all adults in the United States have evidence of infection by age twenty. It has been estimated that it causes about 10 percent of all community-acquired pneumonia in adults and 5 percent of bronchitis and sinusitis. However, most infections with this organism do not produce symptoms but infections can flare up, causing common and important respiratory tract diseases. Re-infection remains common throughout life.
The association of heart disease with Chlamydia appears solidly based on the available evidence.62 In young adults, this organism is found in association with arterial plaques more frequently than in normal arterial wall, and there is some evidence that antibodies may be present in the blood early in atherosclerosis.63 Furthermore, Chlamydia has been found in arterial disease when no antibodies were apparent in the blood.64 Other researchers have found antibodies against both Chlamydia and cytomegalovirus to be linked with early and advanced carotid atherosclerosis.65