Vitamins and intelligence tests.
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Child↗
Biomedical subjects
L Pauling
Publications and source records attributed to L Pauling.
Effect of ascorbic acid on incidence of spontaneous mammary tumors and UV-light-induced skin tumors in mice.
Two large-scale studies of the effect of different amounts of L-ascorbic acid in the food on tumor-free survival have been conducted. One involved the incidence of spontaneous mammary tumors in RIII mice, with seven ascorbic acid and three control groups, 50 mice per group. With increasing ascorbic acid in the diet, there was a highly significant delay before appearance of the first tumor. Median age at first tumor was 82.5 wk in ad libitum controls, 124.9 wk in the highest-dose ascorbate group. The proportion of mice with tumors was also reduced. The other study involved dermal neoplasms in mice irradiated with ultraviolet light. A pronounced effect of vitamin C in decreasing the incidence and delaying the onset of malignant lesions was observed with high statistical significance. By 20 wk approximately five times as many mice had developed serious lesions in the zero-ascorbate as in the high-ascorbate group.
Animals↗
Hypothesis: lipoprotein(a) is a surrogate for ascorbate.
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.
Animals↗
Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells.
We have studied the action of ascorbate (vitamin C) on human immunodeficiency virus type 1 (HIV-1), the etiological agent clinically associated with AIDS. We report the suppression of virus production and cell fusion in HIV-infected T-lymphocytic cell lines grown in the presence of nontoxic concentrations of ascorbate. In chronically infected cells expressing HIV at peak levels, ascorbate reduced the levels of extracellular reverse transcriptase (RT) activity (by greater than 99%) and of p24 antigen (by 90%) in the culture supernatant. Under similar conditions, no detectable inhibitory effects on cell viability, host metabolic activity, and protein synthesis were observed. In freshly infected CD4+ cells, ascorbate inhibited the formation of giant-cell syncytia (by approximately 93%). Exposure of cell-free virus to ascorbate at 37 degrees C for 1 day had no effect on its RT activity or syncytium-forming ability. Prolonged exposure of virus (37 degrees C for 4 days) in the presence of ascorbate (100-150 micrograms/ml) resulted in the drop by a factor of 3-14 in RT activity as compared to a reduction by a factor of 25-172 in extracellular RT released from chronically infected cells. These results indicate that ascorbate mediates an anti-HIV effect by diminishing viral protein production in infected cells and RT stability in extracellular virions.
Antiviral Agents↗
Immunological evidence for the accumulation of lipoprotein(a) in the atherosclerotic lesion of the hypoascorbemic guinea pig.
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.
Animals↗
Biostatistical analysis of mortality data for cohorts of cancer patients.
The Hardin Jones principle states that for a homogeneous cohort of cancer patients the logarithm of the fraction surviving at time t has a constant slope. With use of this principle, the survival times of the members of a heterogeneous cohort can be analyzed to divide the cohort into subcohorts with different mortality rate constants. Probable values of the additional survival time can be estimated for members surviving at the closing date of a clinical trial, permitting them to be included in the biostatistical analysis of the results of the trial in a more significant way than through Kaplan-Meier renormalization.
Humans↗
Criteria for the validity of clinical trials of treatments of cohorts of cancer patients based on the Hardin Jones principle.
With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain.
Ascorbic Acid↗
One aspect of the physical sciences in relation to biology.
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Biophysics↗
Diamagnetic anisotropy of the peptide group.
A simple theory of the diamagnetic anisotropy of noncyclic planar groups of atoms with resonance structures (mobile electrons)leads to the value --5.36 x 10(-6) cm-g-sec electromagnetic units for the molar diamagnetic anisotropy of the peptide group.
Electromagnetic Phenomena↗
Dietary influences on the synthesis of neurotransmitters in the brain.
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Brain↗
Ascorbic acid and cancer: a review.
Host resistance to neoplastic growth and invasiveness is recognized to be an important factor in determining the occurrence, the progress, and the eventual outcome of every cancer illness. The factors involved in host resistance are briefly reviewed, and the relationship between these factors and ascorbic acid metabolism is presented in detail. It is shown that many factors involved in host resistance to neoplasia are significantly dependent upon the availability of ascorbate.
Animals↗
Experimental studies designed to evaluate the management of patients with incurable cancer.
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Ascorbic Acid↗
Supplemental ascorbate in the supportive treatment of cancer: reevaluation of prolongation of survival times in terminal human cancer.
A study has been made of the survival times of 100 terminal cancer patients who were given supplemental ascorbate, usually 10 g/day, as part of their routine management and 1000 matched controls, similar patients who had received the same treatment except for the ascorbate. The two sets of patients were in part the same as those used in our earlier study [Cameron, E. & Pauling, L. (1976) Proc. Natl. Acad. Sci. USA 73, 3685-3689]. Tests confirm that the ascorbate-treated patients and the matched controls are representative subpopulations of the same population of "untreatable" patients. Survival times were measured not only from the date of "untreatability" but also from the precisely known date of first hospital attendance for the cancer that eventually reached the terminal stage. The ascorbate-treated patients were found to have a mean survival time about 300 days greater than that of the controls. Survival times greater than 1 yr after the date of untreatability were observed for 22% of the ascorbate-treated patients and for 0.4% of the controls. The mean survival time of these 22 ascorbate-treated patients is 2.4 yr after reaching the apparently terminal stage; 8 of the ascorbate-treated patients are still alive, with a mean survival time after untreatability of 3.5 yr.
Adult↗
Vitamin homeostasis in the brain and megavitamin therapy.
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Animals↗
Magnetic properties and structure of oxyhemoglobin.
A review of the published evidence reinforces the conclusion reached by Pauling and Coryell in 1936 (Proc. Natl. Acad. Sci. USA 22, 210-216) that oxyhemoglobin in blood or in solution at 20 degrees has zero magnetic moment and fails to support a recent contradictory suggestion based on magnetic susceptibility of frozen samples at temperatures below 250 K. Predicted values of bond lengths and bound angles for carbonmonoxyhemoglobin and oxyhemoglobin are given.
Freezing↗