Homogenized milk and atherosclerosis

Homogenized milk and atherosclerosis are connected by the theory that the enzyme xanthine oxidase or XO, which is abundant in cow’s milk, transforms inflammation following physical, chemical or emotional stress into a degenerative disease process resulting in atherosclerosis. XO is implicated in the formation of free radicals and in cyclical episodes of tissue damage or oxidative stress with degenerative disease symptoms largely characterized by the locale of the initial, inflammatory event. As a central generator of reactive oxygen species (ROS) during inflammation, XO is linked to as many as 50 illnesses from and arthritis to diabetes and cancer.
Cardiologist Kurt A. Oster, Donald J. Ross, and Nicholas Sampsidis first suggested that a food thought to be as wholesome as milk might have a sinister side more than 40 years ago. In peer-review, scientific journals, books and the mass media the research team elucidated a common pathogenesis for degenerative disease triggered by XO as well as how diverse symptoms are amenable to a common treatment employing xanthine oxidase inhibitors (a.k.a. ORS Method). Therapy inhibits XO activity long enough for healing processes to outpace oxidative stress. Whether XO in degenerative disease stems from the liver or from cow’s milk remains the subject of investigation.
Pathogenesis of degenerative disease
The source of XO
Xanthine oxidase (XO) is an important digestive enzyme in mammals. With respect to degenerative disease or lifestyle diseases such as , arthritis and heart disease, problems start when XO starts to digest human tissues instead of food. It is not known whether XO causing the damage during inflammatory phases of degenerative disease development comes from the human liver, whether it is introduced through cow’s milk or whether it might stem from both sources.
Humans consume XO in organ meats like liver and kidney but cooking inactivates the enzyme. The primary source of active XO in the diet is cow’s milk and dairy products made from it. One liter of cow’s milk contains between 120 to 180 mg. of XO. According to the XO theory, homogenization processing of milk increases XO’s bioavailability or its incorporation into the body in an active form.
Milk homogenization concerns
Homogenization is a process first patented in 1899. It disperses milk fat evenly in milk preventing cream from rising to the top by forcing milk through a fine mesh grid at high speed, 600-800 feet per second, and pressures, 2,000-4,500 pounds per square inch (psi), up to 14,500 psi in contemporary, super homogenizers. The higher the pressure the smaller the fat globules, which is significant with respect to the absorption of cow’s milk XO into the human system.
In the U.S., homogenization was introduced, commercially, in the year 1919 to extend milk’s shelf life (refrigerators weren’t mass produced until after WW II) and to prevent cream from getting in the way of drinking it. It was marketed to a skeptical public as being easier on the stomach. Medical pioneers studying XO and heart disease noted a correlation, early on, between the cardiovascular disease epidemic in the U.S. and the advent of milk homogenization. Prior to the technology, heart attacks were a rarity.
In unprocessed, “raw” milk, XO is found mostly free-floating and situated outside of the milk fat globule membrane, where it’s vulnerable, like all proteins, to digestion by gastric acids and proteolytic enzymes. In comparison, after milk is homogenized, most XO is blended into the fat reducing its exposure to digestion. Fats are processed further along in the digestive tract, not in the stomach. By churning up milk fat, homogenization reduces the size of fat globules 3-50 fold. The medical pioneers, who made the early discoveries about XO, referred to the artificially created, micronized, fat globules as liposomes.
How XO is transported
Standard liposomes, such as those employed by the pharmaceutical industry to transport medications beyond the hostile environment of the stomach, have one outer, fatty membrane. In contrast, the homogenized, milk fat “liposome” is onion-like in that it contains numerous, concentrically layered, fat membranes. By trapping XO between layers, the homogenized milk fat globule, according to the XO theory, becomes an even more effective liposome from the perspective of shielding the XO passenger from digestion and immune surveillance.
After fat-encapsulated XO is endocytoically absorbed through the intestinal wall, it enters the lymph circulation. Researchers describe the smaller liposomes as being virtually indistinguishable from chylomicrons - the smallest fat particles in the blood stream. About 50 percent of milk fat globules after homogenization are in the range of 200-500 nanometers, which falls within the range of very large chylomicrons, 75-1,200 nanometers. Chylomicrons are lipoproteins, containing 1-2% protein with XO one of the proteins suspected of being contained within. Upon activation by signals from sites of inflammation, white blood cells are apparently able to release XO in target tissues nearly anywhere in the human system, including arterial endothelium and cardiac muscle.
The buffering effect of milk
The Trojan Horse delivery of active XO beyond the stomach and the pyloric sphincter gate into the small intestine is also facilitated by the buffering effect of milk, which largely neutralizes stomach acid. One glass of homogenized milk (240 ml or about 8 fluid ounces) neutralizes an average volume of hydrochloric acid in the stomach to a nearly neutral pH leaving 75% to 90% of ingested XO intact and active upon entering the small intestine.
Inflammation
Inflammation is the response of the body to an irritant, a normal part of the wound healing process, however, in chronic inflammation the irritant doesn’t leave. XO is suspected of being a long-term irritant whose catalytic action during inflammatory flare-ups breaks down a fatty component in the bilayer of cell membranes.
Reactive oxygen species or free radical byproducts are formed as a result, namely, superoxide and hydrogen peroxide, producing attendant, biochemical cascade reactions, which can lead to peroxynitrite formation. Peroxynitrite is highly toxic and results in cell death or necrosis. Repeat episodes of oxidative stress produce lesions. They may be internal or external ulcers, such as chronic wounds in peripheral vascular disease and in peripheral neuropathy, complications of diabetes.

Each cyclical episode of oxidative stress damage to tissues is interspersed by healing, characterized by smooth muscle cell proliferation, plaque and scar formation, which interfere with the proper functioning of tissues and organs resulting in a decline in general health. Degenerative disease accounts for over 60 percent of all deaths in the U.S.
Plasmalogen - point of attack by XO
The substrate for enzymatic attack by XO is the fatty component, plasmalogen, an integral structural and functional constituent of cell membranes. Plasmalogen comprises up to 40% of the protein-lipid bilayer enveloping cells outside of the digestive tract. Heart muscle, white matter of the brain, myelin sheath of nerves, skeletal muscle, skin and connective tissue, eye lens, and seminal fluid are characteristically rich in plasmalogen.
Plasmalogen is a structural cousin of the phospholipid phosphatidylcholine, commonly called lecithin, but unlike lecithin, plasmalogen is highly vulnerable to the action of XO.
Plasmalogen is largely absent from the liver, the gall bladder, the bile duct, and the inner lining of the small intestine or mucosa, where its absence is attributed to the enzymatic activity of human or endogenous XO. Plasmalogen and XO are mutually exclusive and plasmalogen-rich tissues do not normally contain XO.
Stress in disease origins
According to the XO theory, a chronic degenerative disease like gout or an acute condition like a heart attack is traceable to a stressful event. Physical, chemical or emotional irritants or stresses let loose a reaction cascade that ends with inflammation. Stress unleashes the adrenal glands to produce catecholamines, including the fight-or-flight response hormones, adrenaline and noradrenaline. Together with calcium, they can activate the enzyme, phospholipase A2 (PLA2), resident inside human cells. PLA2 and XO break down plasmalogen, sequentially.
The structure of the plasmalogen molecule resembles a scarecrow in having a head section, one leg and two fatty acid arms. Before XO can act on plasmalogen in cell membranes to deplete it, PLA2 first “softens” up plasmalogen by cleaving one of its two, fatty acid arms. In so doing, it makes room for bulky XO and it creates the precise, stereochemical configuration required for XO to cleave plasmalogen’s remaining fatty acid arm.
The 1-2 cleavage of plasmalogen by PLA2 and XO degrades plasmalogen into a molecule with just a head and leg component, lysoplasmalogen, whose strong chemical polarity has a detergent effect on the cell membrane and contributes to its dissolution. Liberated fatty acids, such as arachidonic acid, can be inflammatory in their own right. Fish without scales, such as mackerel and tuna, are the main source of arachidonic acid in the human diet.
Link between diseases
The breakup of plasmalogen in cell membranes by PLA2 and XO does the same to the cohesiveness of tissues as does the erosion of mortar to the integrity of a brick wall, only tissues don’t just break apart. XO’s cleavage of plasmalogen produces superoxide and hydrogen peroxide. After antioxidant defenses are overcome, free radicals and a chain reaction of instability cause tissues to smolder and plasmalogen is depleted.
Plasmalogen depletion in the pathogenesis or development of degenerative disease is a basic tenet of the XO theory. Such depletion apparently occurs not only in cardiovascular tissues but also wherever plasmalogen is abundant. In the myelin sheath of nerves, plasmalogen depletion has been linked to the development of multiple sclerosis. It’s depletion in the white matter of the brain is associated with the start of and with cognitive decline. Plasmalogen depletion under the skin can result in psoriasis or Lupus, affecting kidneys. Within joints, plasmalogen depletion occurs at the start of gout and arthritis.
Researchers have also found that plasmalogen levels in the blood plasma of cardiovascular disease patients are a sensitive surrogate marker of oxidative stress. Measuring plasmalogen depletion in bodily fluids also offers promise in detecting degenerative diseases, including cancer.
XO basics
XO theory overview
In the late 1960s, when most heart disease research was focused on supposed “risk factors,” including smoking, saturated fat and cholesterol, the XO theory introduced the contrarian hypothesis that cholesterol’s role in atherosclerosis and degenerative disease is limited to stop-gap healing of cyclical, inflammation damage - plugging the holes in tissues - caused by the action of XO from homogenized milk. Emanating from the ranks of mainstream medicine, the “heretical” XO theory reduced cholesterol to a marker of healing episodes following oxidative stress rather than an agent instigating disease processes.

The XO theory encountered theoretical objections, from the start. Skeptics, including two American Heart Association Committee of Nutrition chairpersons, expressed interest but questioned XO’s ability to escape digestion and reach internal tissues, intact and functional. Diary sponsored researchers have not been able to create atherosclerotic plaque in lab animals injecting them with XO. The same researchers concede, however, that very small amounts of active XO can enter the human blood circulation. Nevertheless, the industry remains in denial, holding firm to the view that no unequivocal evidence exists proving that cow’s milk XO contributes to the development of atherosclerotic disease. Theoretical objections to the XO theory have been largely addressed.
Interest in XO became widespread in 1985 following the discovery of XO’s role in reperfusion injury or tissue damage after blood flow is restored to oxygen-deprived tissues such as the brain following stroke or heart muscle following a heart attack.
XO’s presence in diseased coronary arteries and its apparent contribution to the atherosclerotic process, as determined by early research, was upheld in 2003 by electron spin resonance spectroscopy.
In the following year, inflammation’s apparent link to many degenerative diseases became the subject of a ‘’Time’’ magazine cover story. With XO aggravating inflammatory processes, the nature of each condition and resulting symptoms appear to be largely determined by where inflammation starts in the human system.

A growing awareness of XO’s significance in relation to a wide range of degenerative diseases is behind its notoriety. In September, 2009, XO was featured as the “Molecule of the Month” in an article published by the Research Collaboratory for Structural Bioinformatics (RCSB), an entity backed by groups such as the National Science Foundation, the National Institute of General Medical Sciences, The National Library of Medicine, The National Cancer Institute, etc.
XO’s presence in mammals
Xanthine oxidase or xanthine oxidoreductase - considering that it is essentially two enzymes in one, xanthine dehydrogenase (XDH) and xanthine oxidase (XO), is a broad substrate, digestive enzyme in mammals whose structural characteristics are well documented.
In the year 1902, approximately 11 years after XO was discovered by I.Y. Gorbachevsky, Franz Schardinger noted XO’s presence in cow’s milk.
The milk of all mammals contains XO but amounts, potency and enzyme kinetics vary widely between species. Cow’s milk contains 103.9 ImU/ml of XO while human milk has about 15 times less or 7.3 ImU/ml and its activity is up to 20 times lower, a determination attributed to the relatively, low amounts of molybdenum in human milk. The quantity of XO in goat’s milk and ewe’s milk is also minimal, (10.7 ImU/ml and 9.9 ImU/ml, respectively).
Besides its presence in mammalian milk, XO is found in the blood sera of some mammals. Representative species include: mice, guinea pigs, cows, rats and rabbits. In contrast, XO is normally absent from the blood sera of sheep, pigs and humans, a consideration that largely negates extrapolations from experimental observations in animals such as rats and rabbits to the human condition. XO’s role in oncology remains an area of active research, with XO activity having been found significantly elevated in certain brain tumors.
Plasmalogen depletion in cardiovascular disease
Plasmalogen, (ethanolamine plasmalogen), in the cell membrane is especially vulnerable to two-step degradation by phospholipase A2 and XO.
In 1959, the depletion of plasmalogen in atherosclerotic plaque was first noted by a German research team. Subsequently, the German findings were confirmed, with researchers in the U.S. noting definite and significant reduction of plasmalogen in atherosclerotic aortic tissue.
Along the lines of such work, plasmalogen was found to be missing from heart muscle in a case of fatal myocardial infarction. Significant depletion of plasmalogen from the aorta of a 22-year-old drowning victim, who was otherwise healthy, has also been documented. The term, “plasmalogen disease,” has been introduced considering that plasmalogen depletion seems to characterize the appearance of symptoms in diverse degenerative diseases.
The determination that adrenal hormones released during stress can activate phospholipase A2 led to a key understanding in the XO theory, namely, that phospholipase A2 and XO apparently work together to deplete plasmalogen in the myelin coating or insulation of nerves, including those of the heart, resulting in the short-circuiting of impulses. In support of such, it has been pointed out that the heart almost always stops beating during a heart attack because of electrical malfunction and not because of a diminished oxygen supply due to "clogged" arteries.
Consistent with the XO theory and XO’s ability to deplete plasmalogen in nerves, recent studies have shown that in early stage a dramatic decrease in ethanolamine plasmalogen content (up to 40 mol%) in white matter, of the brain is evident.
In another study, plasmalogen in the white matter of the brain in Alzheimer's disease decreased 73% compared to controls. Phospholipid, cholesterol, and triglyceride concentrations remained unchanged. Earlier studies also report plasmalogen depletion in Alzheimer's disease.
Assays that measure plasmalogen depletion are currently used as biomarkers of cognitive decline in Alzheimer's.
Investigators noting the depletion of plamalogen in the Alzheimer's studies did not measure phospholipase A2 or XO activity. On the basis of the XO theory, plasmalogen depletion occurs according to nearly the same biochemical pathway in each degenerative disease.
Diseases linked to XO
XO’s involvement has been implicated in over 50 inflammatory diseases. A partial list includes:
• Atherosclerosis
• Angina Pectoris (chronic chest pain)
• Diabetes mellitus
• Peripheral vascular disease
• Diabetic foot ulcer (Non-healing peripheral wounds)
• Myocardial Infarction (Heart attack)
• Chronic kidney disease
• Stroke
• Gout (Podagra)
• Arthritis
• Rheumatism
• Psoriasis
• Lupus
• Keratoconus
• Cataract
• Autoimmune disease
• Multiple sclerosis (MS)
• Alzheimer's disease (AD)
• Parkinson's disease
• Huntington's disease
• Progressive supranuclear palsy
• Dementia
• Amyotrophic lateral sclerosis (ALS-Lou Gehrig’s disease)
• Chronic traumatic encephalopathy
• Sudden infant death syndrome (SIDS)
• Allergy
• Aphthous ulcers (canker sores)
• Inflammatory bowel disease
• Behçet's disease
• Coeliac disease
• Crohn's disease
• Chronic fatigue syndrome
• Prostatitis and Prostate cancer
• Brain tumor
• Breast cancer
• Ovarian cancer
Factors affecting XO activity
XO and gender
The XO theory accounts for why the incidence of atherosclerosis and certain degenerative diseases is affected by gender and age. Women experience degenerative diseases, such as gout and cardiovascular disease, about five times less than men prior to the age of 50. Only 1 in 17 pre-menopausal women experience a coronary compared to 1 in 5 men. Subsequently, the gender gap narrows and after a lag time of about ten years, beginning at the age of 60, 1 in 4 deaths in both sexes result from cardiovascular events. Supposed risk factors - cholesterol, high blood pressure, smoking, etc. - do not adequately account for the statistics.
It has been demonstrated that bovine milk XO activity is stimulated by androsterone and testosterone and inhibited by the estrogens (beta-esradiol, 17 alpha-estradiol, estrone and estriol) and progesterone. Female hormones apparently provide protection from certain degenerative diseases by reducing the activity of XO prior to menopause. In contrast, male hormones heighten XO activity.
XO activators
Numerous factors stimulate XO activity. They include conditions under which XO activity is measured - whether studied in vitro or in vivo - as well as temperature and pH. The optimal temperature and pH of XO is reported to be 10°C and 7.5, respectively, (Egwim, Vunchi, Egwim). Others describe a higher optimal pH range, 8.2-8.4, (Zikakis and Silver). XO in each species has unique, enzyme kinetic activity.

The minerals molybdenum, iron, and aluminium apparently increase XO activity in humans and lab animals.
Sterols also increase XO activity, including vitamin D in both of its forms. Vitamin D2, ergocalciferol, is added to milk and used in supplements. D3, cholecalciferol, is produced naturally by the skin from sunlight (UV rays). Cholesterol, another sterol, seems to stimulate XO under certain conditions. However, cholesterol in the human diet seems to have no effect in increasing XO activity at sites of inflammation.
XO inhibitors and therapy
Therapy or the reversal of degenerative disease symptoms based on inhibiting XO is an important tenet of the XO theory. If XO is the common cause of many illnesses, they should amenable to a common therapy based on inhibiting XO.
The pioneering research team that first linked cow’s milk XO to cardiovascular disease, treated atherosclerosis, chest pain, (angina pectoris), heart attacks (myocardial infarction), diabetes, and non-healing, chronic wounds (diabetic foot ulcers) in peripheral vascular disease using a natural XO inhibitor.
Folic acid, (tetrahydrofolic acid or the reduced form) in mega dosages of 80 mg/day is a competitive inhibitor that blocks the activity of XO (through XO’s flavin active sites). The methodology reduces the vulnerability of tissues to oxidative stress through dietary guidelines and over-the-counter xanthine oxidase inhibitors. Research continues in the development of therapeutic modalities that inhibit XO without the deleterious side-effects of drugs like Allopurinol.
XO, cholesterol and fats
XO in relation to cholesterol
Understandings tied to the XO theory help make sense of cholesterol study results that contradict 60-plus years of mainstream dogma advocating the need to reduce serum cholesterol by minimizing consumption of cholesterol-containing foods and ingesting cholesterol-lowering drugs.
Results from several, large-scale studies (Framingham, MRFIT, LRC, etc.) are mostly inconclusive linking cause and effect between cholesterol and heart disease, with some follow-up investigations even showing higher overall mortality associated with lower cholesterol readings.
Framingham Heart Study researchers conducted a follow-up study 30 years after the original trial. Contrary to expectations, they found an association between lower cholesterol levels and increased mortality. In another important study, low-serum cholesterol was also associated with increased mortality in elderly persons examined over a 20 year period.
Attempts to lower serum cholesterol by way of diet and drugs make little sense and can be counterproductive according to the XO theory considering that cholesterol participates in wound healing and tissue regeneration following cyclical episodes of inflammation. Researchers who first linked XO to atherosclerosis saw no need for healthy persons or even those with chronic illnesses to restrict consumption of foods containing cholesterol.
XO in relation to dietary fat
Researchers investigating XO and heart disease in the 1970s noted that little in the docile nature of saturated fat justifies the lesions and the almost knife-like cuts evident in post-mortem examinations of diseased sections of aorta. Another observation apparently clearing saturated fat of wrongdoing is the early appearance of the fatty streak, the first phase of atherosclerosis, which becomes evident in the arteries of infants and children well before saturated fat in eggs, bacon and beef steaks can have a possible effect (or before supposed risk factors such as alcohol, smoking and a lack of exercise can even be considered).
The once, much touted polyunsaturated fatty acids (omega-6 fatty acids) dominant in cooking oils such as corn oil or safflower oil are being reevaluated regarding their supposed benefits. They oxidize or become rancid faster than saturated fatty acids, such as those abundant in coconut oil, palm kernel oil or butter.
In cell membranes, the same, basic chemistry applies, i.e., saturated fats are not as vulnerable as polyunsaturated fats to oxidants such as XO and to reactive oxygen species formed by way of XO’s metabolism of plasmalogen.
Some 70-odd fatty acids have been identified in the cell membrane. They’re in constant flux and either free-floating or packaged in pairs attached to plasmalogen molecules. The relative abundance of saturated fats versus polyunsaturated fats attached to plasmalogen mirrors the relative abundance of each introduced through diet - “You are what you eat.” When polyunsaturated vegetable oils are consumed in abundance, polyunsaturated fatty acids tend to dominate in cell membrane plasmalogens, apparently making tissues dry kindling for ignition or oxidation by PLA2 and XO.
The heightened volatility of polyunsaturated fatty acids has been suggested as one possible reason why the incidence of inflammatory, degenerative diseases is highest in countries in which polyunsaturated vegetable oils are consumed most. Saturated fat has been associated, paradoxically, with slowing the progression of cardiovascular disease. The reduced vulnerability of saturated fat to the action of XO in cell membranes, compared to polyunsaturated fat, has been advanced as a possible explanation.
Unlike plasmalogen, its structural cousin, lecithin, has been compared to a wet rag that prevents smoldering, XO fires from igniting in tissues. As a target or substrate for PLA2, lecithin is broken down 16 times slower than plasmalogen in test animals. Subsequent action by XO on lecithin is effectively thwarted. The finding reinforces lecithin’s long-standing association with heart health.
According to the XO theory, not only the advent of milk homogenization but also the switch from butter and pork fat to polyunsaturated vegetable oils in the 20th Century shares the blame for the exponential rise in the incidence of fatal heart attacks in the U.S. A rarity before 1910, the heart attack incidence increased, dramatically, with roughly 3,000 fatalities in 1930, skyrocketing to over 500,000 in 1960.
XO, Fats and food safety
Consistent with the XO theory, egg yolks contain quality, saturated fat as well as lecithin, both of which reduce the vulnerability of the cell membrane to the action of PLA2 and XO. Because of the way butter is made, it contains virtually no active XO making it a safe source of quality, saturated fat. In contrast, trans-fats and partially hydrogenated fats in margarine are incompatible with the integrity and with the health of the cell membrane. Homogenized milk simmered on low heat for 20 minutes inactivates most XO. Powdered milks, whey milk and ultra-pasteurized milk are generally XO-free. Hard cheeses tend to contain less XO than soft cheeses. Goat’s milk, ewe’s (sheep) milk and certified, raw cow’s milk are not homogenized and the relatively, small quantities of low-potency XO present in the milk and cheese of goats and ewes is free-floating facilitating its digestion.
Government interest in the XO theory
In 1971, the U.S. Food and Drug Administration (FDA or U.S. Department of Health and Human Services) granted researchers studying XO inhibitors an “Investigator’s New Drug Application” and folic acid in its reduced form was administered to patients in “pharmacologic doses.” 80 mg/day achieved tissue saturation and inhibition of XO activity was reported in most cases with the average treatment lasting four years.
By the year 1975, the XO theory raised sufficient interest for the FDA to commission the Life Sciences Research Office of the Federation of American Societies for Experimental Biology (FASEB) to investigate and critique available evidence. Subsequently, a comprehensive, 65 page, technical review on behalf of the FASEB was published expressing the opinion that existing evidence is inconclusive, for or against the XO theory. The treatise is reported as being balanced and fair considering what was known at the time.
XO and the American Heart Association (AHA)
In the year 2003, interest in XO and related topics, including free radicals, superoxide, and oxidative stress grew with the publication of an important study confirming by way of electron spin resonance spectroscopy that XO activity in the arteries of subjects with coronary artery disease (CAD) is elevated. In one group it was elevated more than 200 percent over age-matched controls. The authors conclude that elevated XO activity apparently promotes the atherosclerotic process and that therapy directed at inhibiting XO may prove beneficial in treating vascular disease.
Research - for and against the XO theory
Human trials - antibody testing
No double-blind trials with human subjects have been pursued that prove or disprove the XO theory.
Considering that specific antibodies, (IgM), to cow’s milk xanthine oxidase are measureable in human blood serum, five independent studies show that antibodies to cow’s milk proteins and cow’s milk XO are highest in patients with ischaemic heart disease or related cardiovascular disease. Such results support the contention that bovine milk XO penetrating the gut barrier and entering lymph is biologically active.
After finding elevated bovine milk xanthine oxidase antibody levels in persons with cardiovascular disease, Harrison et al. examined healthy human subjects and found that antibodies to human XO (XOR) comprise 3% of total IgM antibodies in blood, significantly more than IgM antibodies to cow’s milk XO. The finding is the first to confirm that IgM antibodies to human XOR exist in healthy humans, opening the possibility that both human XOR and cow’s milk XO are involved in inflammation and disease.
Cow’s milk XO antibody testing is employed in diagnosis, measuring a patient’s exposure to cow’s milk XO and the need for appropriate therapy based on inhibiting XO. Assays have been patented to measure XO antibody titers in prognostic, clinical use. Higher XO antibody levels (IgM) correlate to an increased frequency of myocardial infarction.
Human trials - therapy
A study involving 200 patients, diagnosed with diverse cardiovascular disease symptoms, investigated the effects of high dose, folic acid therapy, (80 mg/day). 100 patients were placed in a control group and received placebo. Saturation, folic acid blood levels in the test group were maintained at 200 ng/dl. The average duration of treatment was four years, ranging from 4 months to 8 years, when the study was terminated over ethical concerns tied to experimenting on patients with life-threatening conditions.
The significant reduction of recurrent myocardial infarction, the relief of angina pectoris and the healing of leg lesions in peripheral vascular disease, which commonly deteriorates to gangrene and requires amputation, were noted. In the U.S., such wounds account for roughly 50% of all lower extremity amputations, at a cost of over 3 billion dollars per year.
Folic acid in the study was prepared as tetrahydrofolic acid or the reduced form in 20 mg tablets, formulated with an equal amount of ascorbic acid for antioxidant purposes and for better absorption through the gut. The study also involved the curtailment of homogenized dairy products.
Independent studies investigating folic acid’s effect on cardiovascular disease, in doses of 15 mg. or less per day, failed to demonstrate significant benefits. The studies didn’t aim to employ folic acid as a xanthine oxidase inhibitor, nor was homogenized milk intake restricted in study subjects.
XO and animal experiments
Little has been learned about XO’s role in degenerative disease through animal studies.
Among fatal flaws in experimental design has been the failure to consider the participation of PLA2 in the depletion of plasmalogen during inflammation - a two-step process, involving two enzymes, not just XO. Another shortcoming has been the construction of animal experiments using animals, such as rats, rabbits and chicks, which, unlike humans, normally harbor XO in the bloodstream with no untoward effect.
When acceptable species have been used with respect to mirroring the human condition, results have done little beyond reinforce existing understandings. After pigs were fed milk in two studies, XO wasn’t found in blood serum fractions, an expected result considering that neither humans or pigs have XO in sera. XO has only been isolated in the white blood cell fraction of human blood. In milk loading experiments, human volunteers drank milk and their blood was subsequently tested for bovine milk XO. It wasn’t present in blood serum but it was detected in the leukocyte fraction of blood 2 hours after 1 liter of homogenized, pasteurized milk was consumed.
Molecules with a molar mass greater than 90,000 Daltons are not supposed to pass through the gut barrier. The molar mass of XO is 280,000 Daltons.
Despite the theoretical size restriction, protein molecules significantly larger than XO pass through the intestine intact and active, such as the iron transporting protein, ferritin, which is 50% larger than XO. Another large protein molecule, one that passes through the gut with remarkable efficiency, is botulinum toxin. It’s roughly three times larger than XO. After a person consumes spoiled food, the toxin traverses the intestine, entering spinal fluid intact and active. It results in death some 70 percent of the time.
It has been hypothesized that the absorption of large molecules takes place by way of an endocytoic process in which the intestinal endothelial cells engulf the large molecule, a process indistinguishable from pinocytosis described in human macrophages.
Epidemiology
A correlation exists between the advent of milk homogenization, its increased consumption country-by-country, and the rise in atherosclerosis-related deaths.
Data from 32 countries established a correlation between the national average consumption of milk protein and national mortality rates from ischaemic heart disease (IHD). Based on extensive observations in 20 countries, it has been determined that food intake to disease death ratios with a coefficient of 0.7, or more, require closer attention for a possible causal explanation. It was found that only milk consistently gives a correlation coefficient higher than 0.7.
Examination of the relationship between the consumption of milk and the mortality rate, nation by nation, led to the conclusion in yet another study that the outstanding result emerging from investigations is that the single item in the diet having a critical effect on atherosclerosis is milk.
On the basis of an extensive, multination study, it was determined that death rates from coronary heart disease (CHD) positively correlate to milk, country-by-country.
Apparently contradicting such determinations are three reports from a research group in England. They show no significant correlation between milk consumption and cardiovascular disease. One of the three studies even reports a drop in cardiovascular events among certain milk consumers. None of the studies indicate whether milk consumed by participants was homogenized or not. From the perspective of the XO theory such information is determinative.
The Maasai in Africa consume large amounts of milk with little evidence of cardiovascular disease but the milk is not homogenized. Traditional consumption is in curdled or sour form.
Epidemiologists struggle with limiting investigation into the etiology of disease by limiting study variables to the extent possible. Conflicting findings and interpretations over food statistics are commonplace considering that food introduces many variables. Epidemiological evidence is a needed cog in the XO theory yet it doesn’t drive the XO theory mechanism.
The observation that a secondary source of XO arrives via leukocytes is consistent with the XO theory according to which activated leukocytes transport bovine milk XO sequestered in “liposomes” or chylomicrons from lymph to sites of inflammation.
To determine if the origin of XO in infiltrating leukocytes is from cow’s milk, it has been suggested that bovine milk XO be tracked through the human system employing tracers, such as stable isotopes of XO’s cofactor molybdenum incorporated into cow’s milk XO. If molybdenum-labeled, bovine milk XO is found at the site of inflammation as determined in the Danish study, bovine milk XO’s heightened enzyme kinetics would explain how it becomes the tipping point factor that transforms inflammation from a normal wound healing process to a generator of ROS and degenerative disease.

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