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Biomedical subjects

M F McCarty

Publications and source records attributed to M F McCarty.

152 records · Page 9Linked to original sources
PubMed1981

An expanded concept of "insurance" supplementation--broad-spectrum protection from cardiovascular disease.

The preventive merits of "nutritional insurance" supplementation can be considerably broadened if meaningful doses of nutrients such as mitochondrial "metavitamins" (coenzyme Q, lipoic acid, carnitine), lipotropes, and key essential fatty acids, are included in insurance supplements. From the standpoint of cardiovascular protection, these nutrients, as well as magnesium, selenium, and GTF-chromium, appear to have particular value. Sophisticated insurance supplementation would likely have a favorable impact on many parameters which govern cardiovascular risk--serum lipid profiles, blood pressure, platelet stability, glucose tolerance, bioenergetics, action potential regulation--and as a life-long preventive health strategy might confer substantial benefit.

Antihypertensive Agents↗
PubMed1980

Synergistic denaturant therapy--a general strategy for treatment of solid malignancies.

"Synergistic denaturant therapy" is defined as the acute disruption of tumor cell structure by concurrent application of "denaturant" modalities such as hyperthermia, tumor-specific acidification, hypoenergia, ischemia, sulphydryl blockade, free-radical generation, detergents, and chemical denaturants (e.g. DMSO). Possible techniques for effective and tumor-specific clinical application of these modalities are discussed, and experimental investigations of their use in cancer therapy, alone or in synergistic combinations, are cited. Various of these modalities may also be used to potentiate the efficacy and specificity of traditional anti-mitotic therapies. Numerous therapeutic advantages are offered by a "synergistic denaturant" approach.

Adenosine Triphosphate↗
PubMed1980

The therapeutic potential of glucose tolerance factor.

Glucose Tolerance Factor (GTF) is synthesized in vivo from absorbed dietary chromium, and acts as a physiological enhancer of insulin activity, binding to insulin and potentiating its action about three-fold. Since GTF is well absorbed orally, the development of sufficiently concentrated and stable supplementary sources of this agent may enable convenient and physiologically appropriate pharmacological modulation of insulin activity. A review of the numerous physiological actions of insulin suggests a number of therapeutic applications for GTF, in such diverse ailments as diabetes mellitus, hyperlipidemia, reactive hypoglycemia, obesity, cancer, protein malnutrition or malabsorption, endogenous depression, Parkinsonism, hypertension and cardiac arrhythmias. GTF supplementation may also have value in preventive medicine.

Amino Acids↗
PubMedDate not supplied

PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight.

Increased free intracellular calcium ([Ca(2+)](i)) in adipocytes blunts the lipolytic response to catecholamines by activating phosphodiesterase 3B - the same enzyme that mediates the antilipolytic effect of insulin - while also compromising the efficiency of insulin-stimulated glucose uptake. Physiological increases in parathyroid hormone (PTH) have been shown to increase [Ca(2+)](i) in adipocytes. These considerations may rationalize recent evidence that high dietary intakes of calcium and/or dairy products may reduce risk for obesity, diabetes, and insulin-resistance syndrome, and they predict that other dietary measures which down-regulate PTH - such as good vitamin D status, and moderation in phosphate and salt intakes - may likewise be beneficial in these respects. Consistent with this position are reports that body weight is elevated in elderly subjects with both primary and secondary hyperparathyroidism; furthermore, insulin resistance is a well-known complication of both forms of hyperparathyroidism. The fact that regular alcohol consumption is associated with decreased PTH secretion may help to explain why moderate drinkers are less prone to insulin resistance, diabetes, and - in women - obesity. Down-regulation of PTH cannot be expected to promote dramatic weight loss, but in the long-term it may lessen risk for significant weight gain and diabetes, and conceivably may potentiate the fat loss achievable with caloric restriction and/or exercise.

Adipocytes↗
PubMedDate not supplied

A moderately low phosphate intake may provide health benefits analogous to those conferred by UV light - a further advantage of vegan diets.

Although exposure to ultraviolet light is often viewed as pathogenic owing to its role in the genesis of skin cancer and skin aging, there is growing epidemiological evidence that such exposure may decrease risk for a number of more serious cancers, may have a favorable impact on blood pressure and vascular health, and may help to prevent certain autoimmune disorders - in addition to its well-known influence on bone density. Most likely, these health benefits are reflective of improved vitamin D status. Increased synthesis or intake of vitamin D can be expected to down-regulate parathyroid hormone (PTH), and to increase autocrine synthesis of its active metabolite calcitriol in certain tissues; these effects, in turn, may impact cancer risk, vascular health, immune regulation, and bone density through a variety of mechanisms. Presumably, a truly adequate supplemental intake of vitamin D - manyfold higher than the grossly inadequate current RDA - could replicate the benefits of optimal UV exposure, without however damaging the skin. Diets moderately low in bioavailable phosphate - like many vegan diets - might be expected to have a complementary impact on disease risks, inasmuch as serum phosphate suppresses renal calcitriol synthesis while up-regulating that of PTH. A proviso is that the impact of dietary phosphorus on bone health is more equivocal than that of vitamin D. Increased intakes of calcium, on the other hand, down-regulate the production of both PTH and calcitriol - the latter effect may explain why the impact of dietary calcium on cancer risk (excepting colon cancer), hypertension, and autoimmunity is not clearly positive. An overview suggests that a vegan diet supplemented with high-dose vitamin D should increase both systemic and autocrine calcitriol production while suppressing PTH secretion, and thus should represent a highly effective way to achieve the wide-ranging health protection conferred by optimal UV exposure.

Autoimmunity↗
PubMedDate not supplied

Iatrogenic lipodystrophy in HIV patients - the need for very-low-fat diets.

In HIV patients, chronic treatment with protease inhibitors often precipitates a peripheral lipodystrophy associated with insulin resistance syndrome and premature coronary disease. In vitro studies demonstrate that these drugs can compromise the ability of adipocytes to store triglycerides; in vivo, peripheral subcutaneous adipocytes appear to be most affected, such that body fat often redistributes to visceral or truncal adipose stores. Dysfunction of peripheral subcutaneous adipocytes - ordinarily quite efficient for storing fat - can be expected to give rise to an excessive flux of free fatty acids (FFAs) following fatty meals; chronic overexposure of tissues to FFAs is a likely explanation for the insulin resistance syndrome associated with lipodystrophy. These considerations suggest that a very-low-fat diet - less than 15% fat calories - may ameliorate the cardiovascular risk associated with lipodystrophy; such diets are known to have a favorable effect on the insulin sensitivity of healthy subjects. Very-low-fat whole-food vegan diets are particularly recommendable in this context, as they may help to shrink visceral fat depots while markedly reducing LDL cholesterol. Appropriate adjunctive measures may include aerobic exercise training - beneficial both for insulin sensitivity and weight control - as well as administration of statins or policosanol, and of fibrates or fish oil, to decrease LDL and triglycerides, respectively. Despite perceptions to the contrary, very-low-fat diets can meet with good compliance in well-motivated subjects given appropriate instruction.

Adipocytes↗
PubMedDate not supplied

Hyperinsulinemia may boost both hematocrit and iron absorption by up-regulating activity of hypoxia-inducible factor-1alpha.

There is growing evidence that increases in both hematocrit and body iron stores are components of the insulin resistance syndrome. The ability of insulin and of IGF-I - whose effective activity is increased in the context of insulin resistance - to boost activity of the transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha), may be at least partially responsible for this association. HIF-1alpha, which functions physiologically as a detector of both hypoxia and iron-deficiency, promotes synthesis of erythropoietin, and may also mediate the up-regulatory impact of hypoxia on intestinal iron absorption. Insulin/IGF-I may also influence erythropoiesis more directly, as they are growth factors for developing reticulocytes. Conversely, the activation of HIF-1alpha associated with iron deficiency may be responsible for the increased glucose tolerance noted in iron-deficient animals; HIF-1alpha promotes efficient glucose uptake and glycolysis - a sensible adaptation to hypoxia - by inducing increased synthesis of glucose transporters and glycolytic enzymes. Recent reports that phlebotomy can increase the efficiency of muscle glucose uptake in lean healthy omnivores are intriguing and require further confirmation. Whether increased iron stores contribute to the elevated vascular risk associated with insulin resistance is doubtful, inasmuch as most prospective studies fail to correlate serum ferritin or transferrin saturation with subsequent vascular events. However, current data are reasonably consistent with the possibility that moderately elevated iron stores are associated with increased overall risk for cancer - and for colorectal cancer in particular; free iron may play a catalytic role in 'spontaneous' mutagenesis. Thus, iron excess may mediate at least some of the increased cancer risk associated with insulin resistance and heme-rich diets. People who are insulin resistant can minimize any health risk associated with iron overload by avoiding heme-rich flesh foods and donating blood regularly.

Erythropoiesis↗