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Biomedical subjects

M F McCarty

Publications and source records attributed to M F McCarty.

At least 127 records · Page 7Linked to original sources
PubMed1995

Optimizing exercise for fat loss.

From the standpoint of promoting fat loss, the chief benefits of aerobic exercise are attributable to fat oxidation during exercise and a post-exercise reduction of respiratory quotient. The ability of exercise to selectively promote fat oxidation should be optimized if exercise is done post-absorptively (preferably during morning fasting metabolism), if caffeine and possibly hydroxycitrate/carnitine are administered prior to exercise, if the exercise regimen is of moderate intensity and prolonged duration, and if no calories are ingested for several hours following exercise. A simple mathematical model is presented which delineates the factors that determine daily fat balance during exercise training. This model clarifies the crucial importance of low-fat eating if exercise is to have an optimal impact on fat stores. As a complement to aerobics, resistance exercise can benefit dieters by helping to preserve lean mass and metabolic rate in the face of a persistently negative caloric balance.

Adipose Tissue↗
PubMed1994

The neglect of glucosamine as a treatment for osteoarthritis--a personal perspective.

Osteoarthritis results from progressive catabolic loss of cartilage proteoglycans, owing to an imbalance between synthesis and degradation. Standard drug therapy is only of palliative benefit and may exacerbate loss of cartilage. Glucosamine is an intermediate in mucopolysaccharide synthesis, and its availability in cartilage tissue culture can be rate-limiting for proteoglycan production. A number of double-blind studies dating from the early 1980s demonstrate that oral glucosamine decreases pain and improves mobility in osteoarthritis, without side effects. Nevertheless, medical researchers and physicians in the US have totally ignored this rational and safe therapeutic strategy. By mechanisms that are still unclear, the natural methyl donor S-adenosylmethionine also promotes production of cartilage proteoglycans, and is therapeutically beneficial in osteoarthritis in well-tolerated oral doses. These and other safe nutritional measures supporting proteoglycan synthesis, may offer a practical means of preventing or postponing the onset of osteoarthritis in older people or athletes.

Animals↗
PubMed1994

Enhancing central and peripheral insulin activity as a strategy for the treatment of endogenous depression--an adjuvant role for chromium picolinate?

Depression is often associated with insulin resistance, owing to cortisol overproduction; conversely, many studies suggest that diabetics are at increased risk for depression. Recent evidence indicates that insulin is transported through the blood-brain barrier and influences brain function via widely distributed insulin receptors on neurons. These receptors are particularly dense on catecholaminergic synaptic terminals, and, while effects are variable dependent on brain region, several studies indicate that insulin promotes central catecholaminergic activity, perhaps by inhibiting synaptic re-uptake of norepinephrine. Additionally, it is well known that insulin enhances serotonergic activity in increasing blood-brain barrier transport of tryptophan. Since impaired monoaminergic activity in key brain pathways is believed to play an etiological role in depression, techniques which promote effective insulin activity, both centrally and peripherally, may be therapeutically beneficial in this disorder. This may rationalize anecdotal reports of improved mood in clinical depressives and diabetics receiving the insulin-sensitizing nutrient chromium picolinate. This nutrient, perhaps in conjunction with other insulin-sensitizing measures such as low-fat diet and aerobic exercise training (already shown to be beneficial in depression), should be tested as an adjuvant for the treatment and secondary prevention of depression.

Brain↗
PubMed1994

Longevity effect of chromium picolinate--'rejuvenation' of hypothalamic function?

The first rodent longevity study with the insulin-sensitizing nutrient chromium picolinate has reported a dramatic increase in both median and maximal lifespan. Although the observed moderate reductions in serum glucose imply a decreased rate of tissue glycation reactions, it is unlikely that this alone can account for the substantial impact on lifespan; an effect on central neurohormonal regulation can reasonably be suspected. Recent studies highlight the physiological role of insulin as a modulator of brain function. I postulate that aging is associated with a reduction of effective insulin activity in the brain, and this contributes to age-related alterations of hypothalamic functions that result in an 'older' neurohormonal milieu; consistent with this possibility, diabetes leads to changes of hypothalamic regulation analogous to those seen in normal aging. Conversely, promoting brain insulin activity with chromium picolinate may help to maintain the hypothalamus in a more functionally youthful state; increased hypothalamic catecholamine activity, sensitization of insulin-responsive central mechanisms regulating appetite and thermogenesis, and perhaps trophic effects on brain neurons may play a role in this regard. Since both the pineal gland and thymus are dependent on insulin activity, chromium may aid their function as well. Thus, the longevity effect of chromium picolinate may depend primarily on delay or reversal of various age-related changes in the body's hormonal and neural milieu. A more general strategy of hypothalamic 'rejuvenation' is proposed for extending healthful lifespan.

Aging↗
PubMed1994

Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control.

There is considerable evidence that hepatic vagal afferents monitor the availability of liver glycogen and glucose metabolites, and that this mechanism participates in appetite regulation. Thus, promotion of gluconeogenesis and liver glycogen storage may enhance satiety. Hepatic lipid oxidation drives gluconeogenesis by positive allosteric modulation of pyruvate carboxylase and fructodiphosphatase. The rate-limiting enzyme for hepatic lipid oxidation, carnitine acyltransferase I, is activated by exogenous carnitine, and inhibited by malonyl coA. The lipogenesis inhibitor (-)-hydroxycitrate--a natural fruit acid found in the Brindall berry--can decrease production of malonyl coA in hepatocytes by potent inhibition of citrate lyase; many studies demonstrate that (-)-hydroxycitrate can reduce body fat accumulation in growing rats, owing in large part to a reduction in appetite. Joint administration of (-)-hydroxycitrate and carnitine should therefore promote hepatic lipid oxidation, gluconeogenesis, and satiety. Thermogenic effects as well as a reduction of the respiratory quotient can also be predicted. If this technique proves clinically useful in weight management, it could be used in conjunction with chromium picolinate and soluble fiber supplements, which appear to aid hunger control at the level of the hypothalamus and terminal ileum, respectively.

Animals↗
PubMed1994

Insulin resistance--not hyperinsulinemia--is pathogenic in essential hypertension.

A correlation between essential hypertension and insulin resistance/hyperinsulinemia is well documented, and there is adequate reason to believe that this association is causal. The common presumption that hyperinsulinemia mediates this connection is based on studies demonstrating various pressor effects of insulin, such as sodium retention, activation of the sympathetic nervous system, and stimulation of renin output. However, a consideration of physiological parameters in essential hypertensives indicates that these insulin-mediated pressor effects are unlikely to play a crucial pathogenic role in most cases of essential hypertension. Moreover, physiological elevation of insulin following a meal is typically associated with a reduction of blood pressure in hypertensives and the elderly. Euglycemic insulin clamps tend to reduce blood pressure in elderly subjects, and prolonged maintenance of hyperinsulinemia in animals does not raise blood pressure. In fact, insulin has long been known to have direct vasodilatory or antipressor effects on resistance vessels, and there is recent evidence that insulin reduces vascular resistance in skeletal muscles to facilitate glycogen storage after a meal. I propose that essential hypertensives experience a net deficit of insulin activity in vascular muscle, and that, in conjunction with other genetic or acquired defects of electrolyte transport, this leads to an increase in basal vascular tone and a hypersensitivity to pressor agents. Correction of insulin resistance usually aids blood pressure control, and in addition may mitigate the excess cardiovascular risk associated with hypertension.

Animals↗
PubMed1993

Insulin resistance in Mexican Americans--a precursor to obesity and diabetes?

Mexican Americans appear to have a strong genetic predisposition to insulin resistance, android obesity, and type II diabetes, apparently as a function of Native American genetic heritage. Theoretical considerations suggest that insulin resistance may be a primary factor that plays a causative role in the induction of both obesity and diabetes. Measures which promote optimal insulin sensitivity--chromium picolinate, brewer's yeast, soluble fiber supplements, metformin, very-low-fat diet, exercise training--may have value for preventing, treating, or retarding the onset of obesity and diabetes, and merit clinical evaluation in this regard. Correction of insulin resistance may also lessen cardiovascular risk, in part by reducing LDL cholesterol and improving risk factors associated with Syndrome X. These comments are likely to be valid for other Native American groups at high risk for diabetes.

Animals↗
PubMed1993

Homologous physiological effects of phenformin and chromium picolinate.

The insulin-sensitizing drug phenformin, in addition to its clinical utility in type II diabetes, has been reported to lower blood lipids, reduce body fat, enhance cellular immunity, and--in rodents--to increase mean lifespan and retard the development of growth of cancer. Initial studies with the insulin-sensitizing nutrient chromium picolinate indicate that it aids glucose tolerance in type II diabetes, lowers elevated LDL cholesterol, reduces body fat while increasing lean mass, and--in rats--increases median lifespan. These effects are thus analogous to those reported for phenformin; chromium picolinate should be tested to determine whether it likewise has a favorable impact on cellular immunity and cancer risk. The ability of both phenformin and chromium picolinate to increase lifespan suggests that age-related insulin resistance may play a profound role in the aging process. It may not be coincidental that caloric restriction--the best documented technique for increasing lifespan--markedly increases insulin sensitivity. Safe, appropriate measures for promoting lifelong insulin sensitivity include a low-fat diet, exercise training, and supplemental chromium picolinate.

Adipose Tissue↗
PubMed1987

Homologous physiological effects of nutritional antioxidants and eicosapentaenoic acid.

Dietary fish oils rich in eicosapentaenoic acid (EPA) possess immunostimulant, anti-inflammatory, cancer-retardant, antithrombotic and ischemia-protective properties that are remarkably parallel to the effects of high-dose nutritional antioxidants. EPA and nutritional antioxidants may show complementary activities in a wide range of preventive and therapeutic applications.

Adjuvants, Immunologic↗
PubMed1986

An antithrombotic role for nutritional antioxidants: implications for tumor metastasis and other pathologies.

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.

Adjuvants, Immunologic↗
PubMed1986

The unique merits of a low-fat diet for weight control.

The virtual freedom from obesity enjoyed by many primitive societies may be traceable to the low fat content of their traditional diets. Recent studies indicate that humans have a very limited capacity for de novo lipogenesis from dietary carbohydrate; this implies that it should be easy to achieve negative fat balance if dietary fat intake is kept low and fat oxidation is promoted by regular exercise. Overfeeding with carbohydrate--but not with fat--provokes an insulin-mediated thermogenesis which acts to retard weight gain. Low-fat starchy foods have a relatively low caloric density, resulting in lower caloric consumption with meals. Once absorbed, carbohydrate has greater satiety value than fat. These considerations suggest that avoidance of dietary fat may be a more successful approach to weight control than "calorie counting". The efficacy of low-fat diets may be promoted by supplementary carnitine, which stimulates fat oxidation, and by chromium, which aids insulin-mediated thermogenesis. An unrefined low-fat diet, eaten to satiety and accompanied by regular exercise, may be the ideal means of maintaining a trim figure throughout life while minimizing one's risk for "Western" degenerative diseases.

Basal Metabolism↗
PubMed1985

A general strategy for the use of allogeneic lymphocyte infusions in the treatment of disorders characterized by impaired helper or suppressor T cell function: autoimmune diseases and the acquired immunodeficiency syndrome (AIDS).

Allogeneic lymphocytes can exert very potent non-specific immunomodulatory effects both in vitro and in vivo. Repeated infusions of allogeneic suppressor or helper populations may find use in the treatment of diseases characterized by impaired suppressor function (such as many autoimmune diseases) or impaired helper function (such as AIDS), respectively. Nutritional adjuvants for use with allogeneic suppressor therapy may include essential fatty acids, zinc, selenium, and vitamin E; the latter two nutrients as well as vitamin C and beta carotene may have value as adjuvants for allogeneic helper therapy. In a small preliminary trial, long-lasting normalization of rheumatoid factor titers and clinical symptoms has been achieved in 5 of 7 cases of chronic rheumatoid arthritis treated with allogeneic lymphocyte infusions, selenium, and vitamin E. These results indicate that allogeneic lymphocyte infusions accompanied by antioxidant support can promote the induction of new appropriate suppressor activity in the host. This phenomenon of allogeneic suppressor induction may be more clinically important than direct allosuppression of host B cells under the conditions of this study, and may find application in the treatment of a number of autoimmune disorders.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Integration of allogeneic lymphocyte immunotherapy with short-course chemotherapy and hypoenergic hyperthermia: a "triple-threat" treatment for disseminated cancer.

A strategy for treatment of disseminated cancer is proposed which unites short-course chemotherapy, local hyperthermia, and allogeneic lymphocyte immunotherapy, designed and timed so as to optimize their synergistic interactions. Short-course chemotherapy potentiates allogeneic lymphocyte immunotherapy, and in turn is potentiated by subsequent courses of local hyperthermia. Response to hyperthermia can be enhanced by measures which selectively inhibit tumor blood flow, impair tumor energy metabolism, and produce tumor acidification; these include induction of prolonged hyperglycemia, and administration of selectively activated "hypoenergic" agents which inhibit or uncouple tumor respiration. It is anticipated that these methods will enable a significant advance in the control of metastasized solid tumors.

Antineoplastic Agents↗
PubMed1984

Rationale for a novel immunotherapy of cancer with allogeneic lymphocyte infusion.

A simple method of cancer immunotherapy has been developed which achieves marked objective response in 20-30% of patients with disseminated disease. Each course consists of a low dose of chemotherapy followed two days later by intravenous infusion of allogeneic lymphocytes. Courses are repeated on a monthly basis as needed. The function of the chemotherapy--too mild to significantly influence tumor growth directly--appears to be depletion of suppressor T cells, which sensitizes the patient to the immunostimulant action ("allogeneic effect") of the subsequently infused lymphocytes. The rationale for this method is discussed in the context of a review of past attempts at lymphocyte immunotherapy. We are now attempting to improve response rates by combatting anergy with nutritional immunopotentiators, and by preventing prostaglandin-mediated or -dependent immunosuppression with prostaglandin synthetase inhibition. By understanding and counteracting the various specific and general means by which a growing tumor induces host tolerance, it should prove possible to achieve immune-mediated tumor regression in a high proportion of patients. Best results may be seen when allogeneic lymphocyte therapy is initiated at an earlier stage of the disease, and is used in conjunction with surgery, radiotherapy, short-course intensive chemotherapy, or hyperthermia-based methods.

Combined Modality Therapy↗
PubMed1984

Rationales for micronutrient supplementation in diabetes.

Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes.

Animals↗
PubMed1984

Hormonal and nutritional enhancement of Na+-K+-ATPase activity may aid the prevention and treatment of essential hypertension.

Subnormal activity of the Na+-K+-ATPase appears to be a common feature of essential hypertension, and may in fact play a pathogenic role in this disorder. If so, methods which relieve inhibition or enhance the activity of the sodium pump should have therapeutic or preventive value. Diuretics enhance the activity of the sodium pump in hypertensives, apparently by suppressing secretion of an inhibitory natriuretic factor, and it is likely that low-sodium diets have a similar effect. Activity of the Na+-K+-ATPase is also stimulated by thyroid hormone and insulin, and there are indications that thyroid therapy, as well as various measures which increase tissue insulin sensitivity, may have therapeutic value in essential hypertension. Nutritional measures which may enhance sodium pump activity include potassium supplementation, insurance of adequate magnesium intake, and consumption of rich sources of gamma-linolenic acid.

Blood Pressure↗
PubMed1984

Potential clinical applications for high-dose nutritional antioxidants.

High but well-tolerated doses of the nutritional antioxidants selenium and vitamins E and C have significant immunostimulant, anti-inflammatory, and anti-carcinogenic effects which are well documented in the existing biomedical literature. In addition, these antioxidants help to protect the structural integrity of ischemic or hypoxic tissues, and may have useful anti-thrombotic actions as well. Supplementation with high-dose nutritional antioxidants may eventually gain a broad role in the prevention, treatment, or palliation of cancer, cardiovascular disease, infection, inflammatory disorders, and certain diabetic complications.

Adjuvants, Immunologic↗