Life Extension Final Clerance Sale



91. Vitamin E and heart disease: basic science to clinical intervention trials.
Free Radic Biol Med 2000 Jan 1;28(1):141-64
Pryor WA
The Biodynamics Institute, Louisiana State University, Baton Rouge 70803, USA.

A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.

92. Early lesions of atherosclerosis in childhood and youth: natural history and risk factors.

J Am Coll Nutr 1992 Jun;11 Suppl:51S-54S
Strong JP, Malcom GT, Newman WP 3d, Oalmann MC
Department of Pathology, Louisiana State University Medical Center, New Orleans 70112.

This paper traces the development of knowledge concerning early lesions of atherosclerosis and the relationship to risk factors in children, youth, and young adults. Autopsy studies have shown that atherosclerosis begins in childhood with the appearance of aortic fatty streaks. Aortic fatty streaks of some degree are present in practically all individuals from every human population. Coronary fatty streaks begin to form in adolescence. Most persons 20-29 years of age have coronary fatty streaks of some degree, regardless of sex, race, or national origin. While fatty streaking is clinically harmless and potentially reversible, progression to fibrous plaques and more advanced lesions often leads to a critical stage of atherosclerosis in which clinical disease develops. Development of fibrous plaques begins in the 20s. The most recent studies of atherosclerosis in youth and young adults provide additional details to establish the relationship of these lesions to serum lipids and lipoproteins and other identified risk factors for atherosclerosis and coronary heart disease in adults. One report shows that microscopic counterparts of fatty streaks occur in the left anterior descending coronary artery in the majority of children 10-14 years of age. Over 5% have more advanced microscopic lesions at this age. Autopsy studies of youth have shown that serum total cholesterol and low-density lipoprotein cholesterol levels are strongly related to aortic fatty streaks and the very-low-density lipoprotein cholesterol levels are positively correlated to coronary artery fatty streaks. Finally, a definitive report indicates that serum lipoprotein cholesterol concentrations and smoking are important determinants of the early stages of atherosclerosis in adolescents and young adults.

93. Atherosclerosis of the aorta and coronary arteries and cardiovascular risk factors in persons aged 6 to 30 years and studied at necropsy (The Bogalusa Heart Study).

Am J Cardiol 1992 Oct 1;70(9):851-8
Berenson GS, Wattigney WA, Tracy RE, Newman WP 3d, Srinivasan SR, Webber LS, Dalferes ER Jr, Strong JP
Department of Applied Health Sciences, Tulane University Medical Center, School of Public Health & Tropical Medicine, New Orleans, Louisiana 70112-2824.

Race and sex differences in aorta and coronary atherosclerotic lesions were studied in 150 persons aged 6 to 30 years. The intimal surface involvement with aorta fatty streaks was extensive, 0 to 71%, and greater in blacks than in whites (32 vs 20%, p less than 0.001). Coronary artery fatty streaks were more extensive in male than in female subjects (range 0 to 22%). Fibrous plaque lesions were present but not extensive in either the aorta (0 to 12%) or the coronary artery (0 to 24%) specimens. Lesions were more prevalent in male than in female persons, particularly white male subjects. The relation of fatty streaks to fibrous plaques was greater in the coronary vessels than in the aorta. In male subjects, aorta fatty streaks were strongly related to antemortem levels of total cholesterol, low-density lipoprotein cholesterol and ponderal index in white male subjects. Coronary artery fatty streaks in white male persons were significantly associated with serum triglycerides, very low density lipoprotein cholesterol, systolic and diastolic blood pressure and ponderal index. These results link antemortem risk factors to the development of atherosclerotic lesions and emphasize the need for preventive cardiology in early life.

94. Hypothesis: lipoprotein(a) is a surrogate for ascorbate.

Proc Natl Acad Sci U S A 1990 Aug;87(16):6204-7
Rath M, Pauling L
Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.

The concept that lipoprotein(a) [Lp(a)] is a surrogate for ascorbate is suggested by the fact that this lipoprotein is found generally in the blood of primates and the guinea pig, which have lost the ability to synthesize ascorbate, but only rarely in the blood of other animals. Properties of Lp(a) that are shared with ascorbate, in accordance with this hypothesis, are the acceleration of wound healing and other cell-repair mechanisms, the strengthening of the extracellular matrix (e.g., in blood vessels), and the prevention of lipid peroxidation. High plasma Lp(a) is associated with coronary heart disease and other forms of atherosclerosis in humans, and the incidence of cardiovascular disease is decreased by elevated ascorbate. Similar observations have been made in cancer and diabetes. We have formulated the hypothesis that Lp(a) is a surrogate for ascorbate in humans and other species and have marshaled the evidence bearing on this hypothesis.

95. Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.

Proc Natl Acad Sci U S A 1990 Dec;87(23):9388-90
Rath M, Pauling L
Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306-2025.

Lipoprotein(a) [Lp(a)] is an extremely atherogenic lipoprotein. Lp(a) has been found in the plasma of humans and other primates, but until now only in a few other species. The mechanism by which it exerts its atherogenicity is still poorly understood. We observed that Lp(a) has been found in the plasma of several species unable to synthesize ascorbate and not in other species. We have now detected apoprotein(a) in the plasma of the guinea pig. We induced atherosclerosis in this animal by dietary ascorbate depletion and, using SDS/PAGE and subsequent immunoblotting, we identified Lp(a) as accumulating in the atherosclerotic plaque. Most importantly, adequate amounts of ascorbate (40 mg per kg of body weight per day) prevent the development of atherosclerotic lesions in this animal model and the accumulation of Lp(a) in the arterial wall. We suggest an analogous mechanism in humans because of the similarity between guinea pigs and humans with respect to both the lack of endogenous ascorbate production and the role of Lp(a) in human atherosclerosis

96. Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of this Disease as a Cause for Human Mortality

Journal of Orthomolecular Medicine (1992; 7: 5-15.)
Matthias Rath M.D. and Linus Pauling Ph.D.

Until now therapeutic concepts for human cardiovascular disease (CVD) were targeting individual pathomechanisms or specific risk factors. On the basis of genetic, metabolic, evolutionary, and clinical evidence we present here a unified pathogenetic and therapeutic approach. Ascorbate deficiency is the precondition and common denominator of human CVD. Ascorbate deficiency is the result of the inability of man to synthesize ascorbate endogenously in combination with insufficient dietary intake.

The invariable morphological consequences of chronic ascorbate deficiency in the vascular wall are the loosening of the connective tissue and the loss of the endothelial barrier function. Thus human CVD is a form of pre-scurvy. The multitude of pathomechanisms that lead to the clinical manifestation of CVD are primarily defense mechanisms aiming at the stabilization of the vascular wall.

After the loss of endogenous ascorbate production during the evolution of man these defense mechanisms became life-saving. They counteracted the fatal consequences of scurvy and particularly of blood loss through the scorbutic vascular wall. These countermeasures constitute a genetic and a metabolic level. The genetic level is characterized by the evolutionary advantage of inherited features that lead to a thickening of the vascular wall, including a multitude of inherited diseases. The metabolic level is characterized by the close connection of ascorbate with metabolic regulatory systems that determine the risk profile for CVD in clinical cardiology today.

The most frequent mechanism is the deposition of lipoproteins, particularly lipoprotein(a) [Lp(a)], in the vascular wall. With sustained ascorbate deficiency, the result of insufficient ascorbate uptake, these defense mechanisms overshoot and lead to the development of CVD.

Premature CVD is essentially unknown in all animal species that produce high amounts of ascorbate endogenously. In humans, unable to produce endogenous ascorbate, CVD became one of the most frequent diseases. The genetic mutation that rendered all human beings today dependent on dietary ascorbate is the universal underlying cause of CVD.
Optimum dietary ascorbate intake will correct this common genetic defect and prevent its deleterious consequences. Clinical confirmation of this theory should largely abolish CVD as a cause for mortality in this generation and future generations of mankind.

97. Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries

Virchows Archives of Pathological Anatomy, 1990, Number 417, Pages 105-111
Axel Niendorf, Matthias Rath, Katrin Wolf, Susanne Peters,
Hartmut Arps, Ulrike Beisiegel, and Manfred Dietel

Summary. Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distributions of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n =74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.

98. Nutritional Supplement Program Halts Progression of Early Coronary Atherosclerosis Documented by Ultrafast Computed Tomography

Journal of Applied Nutrition (1996; 48: 68-78)
Matthias Rath, M.D. and Aleksandra Niedzwiecki, Ph.D.

ABSTRACT: The aim of this study was to determine the effect of a defined nutritional supplement program on the natural progression of coronary artery disease. This nutritional supplement program was composed of vitamins, amino acids, minerals, and trace elements, including a combination of essential nutrients patented for use in the prevention and reversal of cardiovascular disease. The study was designed as a prospective intervention before-after trial over a 12 month period and included 55 outpatients age 44-67 with various stages of coronary heart disease. Changes in the progression of coronary artery calcification before and during the nutritional supplement intervention were determined by Ultrafast Computed Tomography (Ultrafast CT). The natural progression rate of coronary artery calcification before the intervention averaged 44% per year. The progression of coronary artery calcification decreased on average 15% over the course of one year of nutritional supplementation. In a subgroup of patients with early stages of coronary artery disease, a statistically significant decrease occurred, and no further progression of coronary calcification was observed. In individual cases, reversal and complete disappearance of previously existing coronary calcifications were documented. This is the first clinical study documenting the effectiveness of a defined nutritional supplement program in halting early forms of coronary artery disease within one year. The nutritional supplement program tested here should be considered an effective and safe approach to prevention and adjunct therapy of cardiovascular disease.

99. Reduction of resuscitation fluid volumes in severely burned patients using ascorbic acid administration: a randomized, prospective study.

Arch Surg 2000 Mar;135(3):326-31
Tanaka H, Matsuda T, Miyagantani Y, Yukioka T, Matsuda H, Shimazaki S
Department of Traumatology, Kyorin University, Tokyo, Japan.

HYPOTHESIS: High-dose ascorbic acid (vitamin C) therapy (66 mg/kg per hour) attenuates postburn lipid peroxidation, resuscitation fluid volume requirements, and edema generation in severely burned patients. STUDY DESIGN AND SETTING: A prospective, randomized study at a university trauma and critical care center in Japan. SUBJECTS AND METHODS: Thirty-seven patients with burns over more than 30% of their total body surface area (TBSA) hospitalized within 2 hours after injury were randomly divided into ascorbic acid and control groups. Fluid resuscitation was performed using Ringer lactate solution to maintain stable hemodynamic measurements and adequate urine output (0.5-1.0 ml/kg per hour). In the ascorbic acid group (n = 19; mean burn size, 63% +/- 26% TBSA; mean burn index, 57 +/- 26; inhalation injury, 15/ 19), ascorbic acid was infused during the initial 24-hour study period. In the control group (n = 18; mean burn size, 53% +/- 17% TBSA; mean burn index, 47 +/- 13; inhalation injury, 12/18), no ascorbic acid was infused. We compared hemodynamic and respiratory measurements, lipid peroxidation, and fluid balance for 96 hours after injury. Two-way analysis of variance and Tukey test were used to analyze the data. RESULTS: Heart rate, mean arterial pressure, central venous pressure, arterial pH, base deficit, and urine outputs were equivalent in both groups. The 24-hour total fluid infusion volumes in the control and ascorbic acid groups were 5.5 +/- 3.1 and 3.0 +/- 1.7 mL/kg per percentage of burn area, respectively (P<.01). In the first 24 hours, the ascorbic acid group gained 9.2% +/- 8.2% of pretreatment weight; controls, 17.8% +/- 6.9%. Burned tissue water content was 6.1 +/- 1.8 vs 2.6 +/- 1.7 mL/g of dry weight in the control and ascorbic acid groups, respectively (P<.01). Fluid retention in the second 24 hours was also significantly reduced in the ascorbic acid group. In the control group, the ratio of PaO2 to fraction of inspired oxygen at 18, 24, 36, 48, and 72 hours after injury was less than that of the ascorbic acid group (P<.01). The length of mechanical ventilation in the control and ascorbic acid groups was 21.3 +/- 15.6 and 12.1 +/- 8.8 days, respectively (P<.05). Serum malondialdehyde levels were lower in the ascorbic acid group at 18, 24, and 36 hours after injury (P<.05). CONCLUSIONS: Adjuvant administration of high-dose ascorbic acid during the first 24 hours after thermal injury significantly reduces resuscitation fluid volume requirements, body weight gain, and wound edema. A reduction in the severity of respiratory dysfunction was also apparent in these patients.

100. Cisternal irrigation therapy with urokinase and ascorbic acid for prevention of vasospasm after aneurysmal subarachnoid hemorrhage. Outcome in 217 patients.

Surg Neurol 2000 Feb;53(2):110-7; discussion 117-8
Kodama N, Sasaki T, Kawakami M, Sato M, Asari J
Department of Neurosurgery, Fukushima Medical School, Japan.

BACKGROUND: Cisternal irrigation therapy with urokinase and ascorbic acid was introduced to prevent symptomatic vasospasm after aneurysmal subarachnoid hemorrhage (SAH). To dissolve and wash out the subarachnoid clot, cisternal irrigation with urokinase is used. Ascorbic acid is added to degenerate oxy-hemoglobin, one of the strongest spasmogenic substances, into verdohemelike products, which are nonspasmogenic. The efficacy and safety of this therapy were evaluated. METHODS: This therapy was performed consecutively in 217 patients. The degree of SAH of the patients was classified as Fisher CT Group 3, and the highest CT number (Hounsfield number) exceeded 60 in the SAH, which suggested a significant risk for symptomatic vasospasm. All patients underwent surgery within 72 hours from the onset of SAH. After clipping the aneurysm, irrigation tubes were placed in the Sylvian fissure (inlet) unilaterally or bilaterally and in the prepontine or chiasmal cistern (outlet). Lactated Ringer's solution with urokinase (120 IU/mL) and ascorbic acid (4 mg/mL) was infused at a rate of 30 mL/hour/side for approximately 10 days. RESULTS: Of the 217 patients studied, symptomatic vasospasm was observed in 6 cases (2.8%), and two of these six cases (0.9%) demonstrated sequelae. The average total blood volume calculated from the drainage fluid was approximately 114 mL. Analysis of the absorption spectrum of the drainage fluid revealed disappearance of the oxy-hemoglobin-specific 576-nm peak. Complications occurred in eight patients during irrigation therapy; two patients experienced seizures, two patients developed meningitis, and four patients had an intracranial hemorrhage. However, all of these patients recovered without neurological deficits. CONCLUSIONS: These results suggest that cisternal irrigation therapy with urokinase and ascorbic acid is effective in preventing symptomatic vasospasm after aneurysmal SAH.