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Life Extension Magazine

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What's Missing from Multi-Vitamin Supplements?

November 2000

Another disease-preventing flavonoid

Luteolin is a flavonoid found in many of the same foods that contain apigenin. While luteolin produces effects similar to apigenin, it has its own unique beneficial properties as well.

When compared to other flavonoids, only luteolin and quercetin inhibited platelet activating factor and suppressed a type of inflammatory response induced by allergens. The scientists who conducted the study concluded that luteolin could be used to develop a novel type of anti-inflammatory, anti-allergic drugs.93

Another disease-preventing flavonoid  

Like apigenin, luteolin inhibits the effects of epidermal growth factor and tyrosine kinase, and therefore may have potential as an anti-cancer and anti-metastasis agent.94 When measured against 27 citrus flavonoids, luteolin had the most potent antiproliferative activities against several tumor and normal human cell lines.95

The soy flavonoid genistein is a specific inhibitor of tyrosine kinase and topoisomerase II. Genistein has been specifically shown to inhibit cancer during the phase G2 of the growth cycle. In contrast, luteolin and daidzein have been shown to arrest the cancer cell growth at the G1 phase of the cycle.96 When compared to other flavonoids, luteolin more effectively inhibited proliferation of human leukemia (CEM-C1 and CEM-C7) cells.97

The cancer chemotherapy drug adriamycin causes heart and bone-marrow toxicity by depleting cells of glutathione peroxidase activity. One study showed adriamycin reduced glutathione peroxidase activity levels by 73% in heart cells, but this effect was reversed by a combination of luteolin and rutin. These two flavonoids also prevented increased lipid peroxidation in bone marrow cells in response to adriamycin.98

A study assessed the antioxidant potencies of several dietary flavonoids compared with vitamin C. Pretreatment with all flavonoids and vitamin C produced dose-dependent reductions in oxidative DNA damage. When ranked in order of potency, luteolin was more effective than vitamin C and seven other flavonoids in reducing DNA oxidative damage.99

Luteolin may help prevent breast cancer. Several studies show that luteolin reduces excess estrogen formation100 by suppressing the aromatase enzyme101,102 and blocks the binding of estrogens to breast cell receptor sites. One study showed that administration of estrone for 11 days stimulated mammary cell proliferation and caused a nine-fold increase in the cells in G1 phase and a 48-fold increase in the cells in S phase. When luteolin was concurrently administered, estrone was blocked from binding to type II receptor sites on mammary cells. Luteolin significantly reversed the effects of estrone treatment on both proliferation and differentiation in these animals. Changes in proliferation and cell cycle kinetics have been shown to lead to genetic instability, ultimately resulting in cell transformation that can lead to cancer.103

Since estradiol stimulation in the rat uterus is highly correlated with cellular hypertrophy and hyperplasia, scientists assessed the effects of various flavonoids on estradiol stimulation of uterine growth in the immature rat. Luteolin or quercetin blocked estradiol stimulation in the immature rat uterus and this correlated with an inhibition of uterine growth. These studies suggest bioflavonoids may be involved in cell growth regulation.104

The incidences of fibrosarcoma is 100% in mice injected with a specific chemical carcinogen. When luteolin is supplemented in the diet of these mice, fibrosarcoma rates decline by 40%. The scientists stated that mode of action may be through their influence on the initiation and promotion phases of the carcinogenic process coupled with enhancement of the detoxification process.105 When a group of plant extracts were evaluated to ascertain if they could maintain normal cell regulation, luteolin demonstrated the highest anti-proliferative activity.106

vitamin c  

Flavonoids are known to protect against radiation-induced free radical damage. In a comparison study, luteolin was found to be the most effective extract in reducing radiation damage to cells. The scientists who conducted the study stated that these plant flavonoids show antioxidative potency in vitro, work as antioxidants in vivo, and their radioprotective effects may be attributed to their scavenging potency towards free radicals.107

How important are flavonoids in protecting against cancer? A human epidemiological study showed a 56% reduction in stomach cancer in those consuming the highest levels of flavonoids compared to the lowest. The results of this study show that the well-established protective effect of fruit and vegetables could, in part, be due to the presence of flavonoids.108

The new Life Extension Mix has the most concentrated flavonoid complex ever put into a dietary supplement and now includes a standardized ratio of luteolin.

Enhancing glucose metabolism

Cells require glucose for energy production. Glucose that is not absorbed by cells is eventually converted into body fat. Aging cells lose their ability to utilize insulin for the purpose of absorbing glucose. This insulin-resistance is a direct cause of type II diabetes, obesity, atherosclerosis and a host of aging-related diseases.

Some of the underlying mechanisms required by cell membranes for youthful glucose metabolism have been identified and the new Life Extension Mix has more nutrients to help reduce age-related insulin resistance than ever before.

An enzyme called glucokinase has a central regulatory role in glucose metabolism. Efficient glucokinase activity is required for normal glucose-stimulated insulin secretion, hepatic glucose uptake, and the appropriate suppression of hepatic glucose output and gluconeogenesis by elevated plasma glucose. Recent studies have shown that increased hepatic gluconeogenesis is the predominant contributor to high fasting blood sugar—the hallmark of type II diabetes.109,110

In high doses, biotin enhances beneficial glucokinase activity. Administration of high-dose biotin has improved glycemic control in several diabetic animals models, and a recent Japanese clinical study concludes that biotin can substantially lower fasting glucose in type II diabetics, without side-effects.111-122

Biotin is a B-complex vitamin that provides health benefits ranging from the control of blood sugar levels to the improved appearance of hair and nails. In order to improve glucose utilization in aging people, the new Life Extension Mix contains 3000 mcg of biotin in each daily dose. This is almost four times as much biotin as was contained in the previous version. (The recommended dose of biotin for type II diabetics is 8000 to 9000 mcg a day.)

Chromium supplementation by type II diabetes has been shown to improve peripheral insulin sensitivity—a parameter that is unlikely to be directly influenced by biotin. Thus, the joint administration of high doses of biotin and chromium is likely to combat insulin resistance, improve beta-cell function, enhance glucose uptake by both liver and skeletal muscle, and inhibit excessive hepatic glucose production. Conceivably, this safe, convenient, nutritional regimen will constitute a definitive therapy for many type II diabetics, and may likewise be useful in the prevention and management of gestational diabetes. Biotin should also aid glycemic control in type I patients.

In a recent study, chromium picolinate was given in 600 mcg daily doses to corticosteroid patients who had developed glucose intolerance. Chromium supplementation resulted in fasting glucose levels declining from greater than 250 mg/dl to less than 150 mg/dl. Supplementation with chromium also enabled doctors to reduce the dose of anti-diabetic drugs by 50%. This study demonstrated that steroid-induced diabetes can be reversed by chromium supplementation. This is one of several new studies showing that chromium has a favorable effect on glucose metabolism.152 Chromium improves insulin binding, insulin receptor number, insulin internalization, beta cell sensitivity and insulin receptor enzymes with overall increases in insulin sensitivity.109,112,115,120

There is now a total of 200 elemental micrograms of chromium in the daily dose of the new Life Extension Mix, double the amount than in the previous version. Both the picolinate and polynicotinate forms of chromium can be found in Life Extension Mix. For type II diabetics seeking to use chromium to lower sugar levels, an additional 400 mcg a day of chromium is suggested.

Protecting against mitochondrial aging

Massive free radical damage occurs in the cells’ energy power plants (the mitochondria), which can overwhelm the cells’ antioxidant defense systems. Mitochondrial damage due to aging is a serious health problem in elderly people, whose energy levels decline precipitously even when they remain disease-free. N-acetyl-cysteine (NAC) has been shown to stimulate glutathione production for the purpose of providing protection against free radicals that are continuously being generated in mitochondria.122 In addition to protecting against mitochondrial free radical damage, NAC has been shown to reduce the effect of intracellular hydrogen peroxide by 93%.123 Supplemental NAC can reduce the frequency and duration of infectious diseases.124 NAC is used as a mucous dissolving agent in chronic bronchitis,125-128 an antidote for liver damage induced by acetaminophen (the pain reliever),129-131 and an inhibitor of hemorrhagic inflammation of the urinary bladder caused by tumor suppressing drugs.

Free radical damage is both a causative and contributing factor in the development of degenerative disease. Scientists are now concentrating on specific free radicals, the different part of the cell that these free radicals attack, and the types of antioxidants that are needed to provide intra- and inter-cellular protection against oxidative stress. Life Extension Mix provides antioxidants, such as 600 mg of NAC and 500 mg of taurine per daily dose, to protect against differing types of free radicals both inside and outside of cells.132,148

Facilitating youthful methylation

Life Extension Mix  

Enzymatic and genetic activity throughout the body depends on the continuous re-methylation of DNA. The age-related breakdown of youthful methylation metabolism predisposes the body to a wide range of degenerative diseases. Maintaining healthy methylation patterns protects against DNA mutations that damage cells and can cause cancer.

Vitamin B12 works synergistically with folic acid and TMG to enhance DNA methylation and reduce toxic homocysteine in the blood. Scientific studies confirm that orally administered vitamin B-12 supplements are effectively absorbed by more than 99% of humans without gastric related diseases.149 Vitamin B12 plays a critical role in many enzymatic processes required to maintain good health. Elderly people can suffer from severe neurological impairment if they are deficient in vitamin B12.150-151

Life Extension Mix contains high doses of folic acid and three different types of vitamin B12 along with a small amount of trimethylglycine (TMG).