Lactic Acid and Insulin

As mentioned, under hypoxic conditions lactic acid may stimulate production of angiogenic factors by macrophages. Unfortunately, few natural compounds have been tested for their effects on lactic acid generation in cancer cells. In one study, apigenin and luteolin inhibited both proliferation and lactic acid release from a human adenocarcinoma cell line in vitro.127 In other studies, the flavonoid quercetin reduced the production of lactic acid in healthy rat cells, probably by blocking the transport of lactic acid out of the cell.128,129 Anti-oxidants may also inhibit lactic acid production. For example, vitamin C has been reported to increase oxy-

a Mast cells derive from basophils and reside in a variety of tissues.

gen consumption and reduce lactic acid production in tumor and normal cell cultures.130'131

Insulin may stimulate cell proliferation and angiogenesis. Among its effects, insulin stimulates hypoxic cells to produce greater amounts of lactic acid. One way to regulate insulin production is through dietary modifications. When food is digested, its carbohydrate content is converted to glucose, and elevated plasma concentrations of glucose stimulate the secretion of insulin. Foods that are slowly converted to glucose raise insulin levels less dramatically than foods that contain glucose or are easily converted to glucose. The ability of foods to increase insulin concentrations is referred to as their glycemic index. Thus, insulin secretion can be kept to a minimum by eating foods that have a low glycemic index, such as vegetables and protein and, to a lesser extent, whole grains and beans. The glycemic index has been used extensively by diabetic patients to control their insulin requirements.

Some natural compounds have also been reported to inhibit the cancer-promoting effects of insulin. For example, genistein inhibited insulin-induced proliferation of human breast cancer cells in vitro.132 This likely occurred via inhibition of PTK activity. In addition, some natural compounds may be able to reduce insulin production by reducing insulin resistance. Insulin resistance occurs when cells are no longer sensitive to insulin and thus more is produced in an effort to reduce blood glucose levels. Insulin resistance has been implicated as a risk factor for breast cancer.133,134 135 Diets high in omega-6 fatty acids promote insulin resistance, possibly via chronic activation of PKC.136,137138 Natural compounds that can reduce insulin resistance include omega-3 fatty acids and other PKC inhibitors.139142

Omega-3 fatty acids have been reported to effectively reduce both lactic acid and insulin production in vivo. For example, in a randomized, double-blind, placebo-controlled study, a diet containing about 6 percent fish oil (containing omega-3 fatty acids) and 3 percent argin-ine (an amino acid) enhanced the antitumor effect of doxorubicin in dogs with spontaneous lymphoma. The treatment reduced plasma concentrations of insulin and lactic acid, and low lactic acid concentrations were associated with greater survival.143

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