Life Extension Magazine®

Issue: Nov 2000

What's Missing from Multi-Vitamin Supplements?

Dietary supplements provide concentrated doses of nutrients that are found in fruits and vegetables. But not all multi-vitamin formulas are created equal. Find out what’s missing from the typical supplement on the market.

Multi-Vitamin Supplements  

The primary reason that people take dietary supplements is to obtain concentrated doses of beneficial nutrients that are found in fruits and vegetables.

Consuming lots of fruits and vegetables dramatically lowers the risk of degenerative disease. This fact has been documented in epidemiological studies showing that people are healthier if they incorporate more of the right kinds of plants into their diet.

In addition to the epidemiological data, researchers have evaluated the molecular effects that fruits and vegetables possess in protecting against cellular damage. These findings provide biologic mechanisms to explain why those who eat a plant-rich diet have such low incidences of chronic disease.

The problem is that few people consistently eat enough fruits and vegetables to protect against aging-related diseases such as stroke, cancer, macular degeneration and heart attack.1 This is one reason why vitamin supplements are becoming so popular in the United States. The concern about multi-vitamin formulas, however, is that they do not provide all the vital plant components needed to maintain good health.

In 1985, The Life Extension Foundation introduced the first multi-nutrient formula that included disease-preventing extracts from plants. Over the last 15 years, an enormous amount research data has confirmed the health benefits of these types of plant extracts.

Scientists have identified new fruit and vegetable extracts that protect cells against the deleterious effects of aging. In response to these findings, the Life Extension Mix multi-nutrient formula has been upgraded to provide these new disease-preventing agents from plants.

Moving beyond vitamins

Vitamin C, carotenoids and folic acid are examples of plant-based nutrients that can be efficiently consumed in the form of dietary supplements. Researchers are now moving beyond traditional nutrients in their quest to discover additional ways of protecting against disease. One botanical extract that offers tremendous potential is called D-glucarate. This extract appears to protect against cancer and other diseases via different mechanisms than antioxidants.

D-glucarate is found in grapefruit, apples, oranges, broccoli and brussels sprouts.2-3 Consumption of these types of fruits and vegetables confers a protective effect against cancer, and D-glucarate is a component of these foods that has scientists very excited.

The body is bombarded with carcinogens on a daily basis. These cancer-causing agents include pesticides, over-cooked food, alcohol, food additives, tobacco, fungal mutagens and industrial pollutants. While avoiding carcinogens is difficult, it may be possible to mitigate their lethal effects by providing the body with phyto-nutrients (plant extracts) that facilitate the detoxification and removal of these dangerous substances from the body.

D-glucarate is one of these phyto-nutrients that protects against cancer-causing agents in a way that is separate and apart from the beneficial effects of antioxidants (vitamins C, E, cysteine, etc,) and methylation-enhancing agents (folic acid, vitamin B12 and TMG). D-glucarate works by supporting detoxification and removal of dangerous chemicals, and also by protecting against the mutating effects that these carcinogens induce on cellular DNA.3

There are several mechanisms by which the body detoxifies itself. One way of protecting against toxic overload involves the use of antioxidants to inhibit the damaging effects of free radicals. Uncontrolled free radical reactions have been identified as causative or contributing factors in most human disease states. The consumption of antioxidants (vitamin E, n-acetyl-cysteine, selenium, carotenoids, etc.) are essential to protect against toxic free radical reactions. Neutralizing free radicals, however, is only one part of the detoxification process. There are additional pathways the body must use if it is to sufficiently rid itself of DNA-damaging toxins that can cause cancer and other diseases.

Another pathway of detoxification occurs when toxins or carcinogens are combined with water soluble substances, thus making them more easily removed from the body. This process is called glucuronidation. The phyto-extract D-glucarate has been shown to support this important detoxification mechanism. The following known carcinogens are removed from the body by the glucuronidation process:

  • Polycyclic aromatic hydrocarbons
  • Mutated sex steroid hormones
  • Nitrosamines
  • Heterocyclic amines
  • Fungal toxins
  • Aromatic amines

Note: To give you some idea about how dangerous heterocylic amines are, refer to the article in this issue entitled “Barbequer Beware!”

How does D-Glucarate work?

D-Glucarate  

As just discussed, glucuronidation is a process by which the body naturally detoxifies itself. As people grow older and become overly exposed to toxins, a dangerous enzyme forms in the body called beta-glucuronidase. When levels of beta-glucuronidase become too high, it reverses the glucuronidation process and releases the toxins or carcinogens back into the bloodstream. This means that harmful compounds that would normally bind to inert molecules to be removed from the body are permitted to go free and damage cells.

D-glucurate functions by inhibiting the dangerous beta-glucuronidase enzyme, thus protecting the critical “glucuronidation” detoxification mechanism. One example of the importance of glucuronidation can be seen in the risk factors for breast cancer. Excess levels of free estrogens and the beta-glucuronidase enzyme are associated with increased incidence of breast cancer.4,5 The beta-glucuronidase enzyme is associated with an increase in the number of estrogen receptors. D-glucarate has been shown to lower estrogen receptors while reducing tumor growth.6 When breast cells hyper-proliferate in response to excess estrogen stimulation, the risk of breast cancer increases. In men, excess estrogen stimulation in the prostate gland can result in benign enlargement. D-glucurate suppresses the “bad” enzyme beta-glucuronidase, thus helping to protect against the carcinogenic effects of estrogen. This discovery helps explain why those who eat certain types of vegetables and fruits have relatively low rates of cancer.

At the University of Texas M.D. Anderson Cancer Center, repeated in vitro and animal studies have demonstrated the effectiveness of D-glucarate. Oral ingestion of D-glucarate has been positively shown to inhibit the dangerous beta-glucuronidase enzyme. This means the body is better able to get rid of carcinogens and toxic waste products. In one animal study, a single dose of D-glucarate was able to suppress beta-glucuronidase activity by 57% in the blood, 44% in the liver, 39% in the intestines and 37% in the lungs.3

In a rat study, the administration of D-glucarate for five months inhibited the initiation stage of liver cancer after the rats had been intentionally exposed to a known carcinogen. Researchers concluded that D-glucarate has a direct effect in preventing liver cancer that was attempted to be induced by the carcinogen, diethylnitrosamine.4

Research studies have shown that D-glucarate inhibits mammary tumor incidence.7-10 One study in rats who already had breast cancer showed that oral D-glucurate administration resulted in a 50% inhibition of beta-glucuronidase resulting in a 30% reduction in mammary tumor growth during the promotion stage and a four-fold reduction in the absolute number of tumors.11

In a study conducted in Europe, rats fed D-glucarate and a vitamin A analog drug demonstrated a 20% reduction in mammary tumor volume.12 Another study showed a more than 70% decrease in mammary tumor development in rats exposed to carcinogens who were also administered D-glucarate.13 Still another study looked at the effects of D-glucarate on the initiation and promotional stages of mammary cancer. The results showed a reduction of 28% during the initiation stage, while cell replication was reduced by 42% during the promotion stage.14 Inhibition at the initiation stage is a very important part of D-glucarate’s actions since it lessens the risk that cancer will even start.

D-glucarate is being used in a Phase I human trial at Memorial Sloan-Kettering Cancer Center in women at high risk for developing breast cancer. This study is in collaboration with the National Cancer Institute and National Institutes of Health.

When mice were exposed to known carcinogens found in tobacco smoke, D-glucarate was shown to inhibit lung cancer development.6,15 On a molecular basis, D-glucarate was shown to cause a 70% decrease in the binding of the carcinogen benzopyrene to DNA in both mouse livers and lungs.6 Since benzopyrene is a potent carcinogen found in cigarette smoke, D-glucarate could be of particular benefit to smokers and those exposed to environmental airborne carcinogens.6,16

When a carcinogen known to induce intestinal cancer was given to rats, D-glucarate was shown to inhibit adenocarcinoma formation when given at the initiation stage. When administered after tumor development, D-glucarate significantly inhibited the size and metastatic potential of intestinal and colon cancers.17 The researchers made comments suggesting that D-glucurate may be effective in the prevention and treatment of cancer by inhibiting the beta-glucuronidase enzyme and by inhibiting cancer cell proliferation induced by chemical carcinogens.

One study indicates a potential for D-glucurate to prevent bladder cancer, while two studies indicate D-glucarate may have a protective effect against skin cancer.18-21,145,146 A preliminary study showed that orally administered D-glucarate inhibited the growth of transplanted rat prostate tumors and reduced the levels of a tumor marker for prostate cancer.21,147

The results of various animal studies on D-glucarate indicates that this plant extract may be effective in inhibiting cancer during the initiation, promotion and progression phases. Human studies are just now beginning to determine if the results seen in animals will also be found in people. Since D-glucarate has no known side effects when ingested in moderate doses, and is a component of fruits and vegetables that have demonstrated a powerful cancer preventative benefits, it would appear appropriate to add this plant-constituent as part of an overall program designed to lower the risk of the following cancers:

  • Breast cancer
  • Bladder cancer
  • Lung cancer
  • Skin cancer
  • Colon cancer
  • Prostate cancer
  • Liver cancer

The new Life Extension Mix provides 200 mg of standardized D-glucarate (in the form of calcium-D-glucarate) per daily dose, in addition to the naturally occurring D-glucarate found in the new broccoli concentrate that is included in the formula.

The DNA protecting effects of ellagic acid

Ellagic acid is a cancer preventing compound found in red raspberries, strawberries and other fruits.22-29 Ellagic acid acts as a detoxifying agent by binding to carcinogens and making them inactive.30-33 Molecular studies show that ellagic acid prevents binding of carcinogens to DNA,23,34 reduces the incidence of cancer in cultured human cells exposed to carcinogens, may circumvent carbon tetrachloride toxicity and subsequent fibrosis,35 and has anti-mutagenic properties.25,36-39 Epidemiological studies show that people who consume fruits high in ellagic acid have lower rates of cancer and heart disease. It has also been shown to provide protection against chromosome damage and DNA strand breaks in lymphocytes produced by radiation, in animals.40

European medical research also demonstrates that ellagic acid promotes wound healing, and may reduce or reverse chemically induced liver fibrosis.35,144

Clinical tests conducted at the Medical University of South Carolina (MUSC) show that ellagic acid may help to prevent cancer, inhibit the growth of cancer cells, and arrest the growth of cancer in persons with a genetic predisposition for the disease. These studies show that ellagic acid induces cervical cancer cells to undergo apoptosis (normal cell death).24 Tests reveal similar results for breast, pancreas, esophageal, skin, colon and prostate cancer cells.31,33,37,41-46 Researchers showed that ellagic acid leads to G1 arrest of cancer cells, thus inhibiting and stopping cancer cell division. Ellagic acid was also shown to prevent destruction of the P53 gene in cancer cells.24 P53 is a regulating gene that enables cells to divide normally. Additional studies suggests that ellagic acid inhibits mutagenesis and carcinogenesis by forming adducts with DNA, thus blocking binding sites on cells that would be occupied by a mutagen or carcinogen.22,36,43,47-50 In another study ellagic acid was protective in experimental liver injuries.51 Ellagic acid has also been shown to provide protection against chromosome damage produced by radiation, as well as protect against radiation induced lipid peroxidation.40,52 In animal studies it was shown to be embryoprotective.53

The daily dose of the new Life Extension Mix contains 130 mg of a raspberry extract that provides 38.5% ellagic acid. When ellagic acid is extracted from other fruits, the concentration is much lower.

Published studies on ellagic acid

“Ellagic acid protects rat embryos in culture from the embryotoxic effects of N-methyl-N-nitrosourea.” Teratology 1992, Aug (2): 109-15.

“Expression and its possible role in G1 arrest and apoptosis in ellagic acid treated cancer cells.” Cancer Letters 1999 Mar 1; 136(2):215-21.

“Protective effect of curcumin, ellagic acid and bixin on radiation induced genotoxocity.” Journal of Experimental Cancer Research; 1998 Dec; 17(4);431-4.

“Inhibitory effects of ellagic acid on the direct-acting mutagenicity of aflatoxin B1 in the Salmonella microsuspension assay.” Mutation Research; 1998 Feb 26;398(1-2); 183-7.

“Isothiocyanates and plant polyphenols as inhibitors of lung and esophageal cancer.” Cancer Letters; 1997 Mar 19;114(1-2):113-9.

“Structure-function relationships of the dietary anticarcinogen ellagic acid.” Carcinogenesis; 1996 Feb;17(2):265-9.

“The dietary anticancer agent ellagic acid is a potent inhibitor of DNA topoisomerases in vitro.” Nutrition and Cancer; 1995;23(2):121-30.

“Inhibition of liver fibrosis by ellagic acid.” Indian Journal of Physiology and Pharmacology;1996 Oct;40(4): 363-6.

“Ellagic acid binding to DNA as possible mechanism for its antimutagenic and anticarcinogenic action.” Cancer Letters; 1986 Mar;30:339-36.

“Ellagic acid induces NAD(P)H:quinone reductase through activation of the antioxidant responsive element of the rat NAD(p)H:quinone reducase gene.” Carcinogensis;1994 Sept; 15(9):2065-8.

“Polyphenols as cancer chemoprevention agents.” Journal of Cell Biochemistry Supplemental; 1995;22:169-80.

“Pulmonary carcinogenesis and its prevention by dietary polyphenolic compounds.” Annals of the New York Academy of Sciences; 1993 May 28; 686:177-85.

“Lung tumors in strain A mice: application for studies in cancer chemoprevention.” Journal of Cell Biochemistry Supplemental; 1993; 7F:95-103.

Broccoli: a wealth of phytochemicals

Broccoli  

Broccoli may contain more cancer-preventing nutrients than any other plant. In 1992, scientists identified a broccoli compound called sulforaphane that helps mobilize the body’s natural cancer-fighting resources and reduces the risk of developing cancer.54-60

Sulforaphane has been shown to block the formation of tumors initiated by chemical carcinogens. Moreover, sulforaphane has been demonstrated to induce cancer cell death via the apoptosis (natural cell death) process.61,62 A large amount of data shows that sulforaphane and other broccoli compounds act as cancer chemopreventive agents by favorably modifying carcinogen metabolism via modulation of both Phase 1 and Phase 2 detoxification enzyme systems.62-66 These results suggest that broccoli compounds prevent cancer by activating detoxifying enzyme systems and inducing cancer cell apoptosis.

Phase II detoxifying enzymes, such as glutathione S-transferase, play an important role in the detoxification of chemical carcinogens. Recent studies have demonstrated that sulforaphane not only induces beneficial glutathione S-transferases but also inhibits of some major P450 enzymes that block the detoxification of organic poisons.64,67,68

Studies show that high human gastrointestinal tissue levels of glutathione S-transferase protect against a wide range of cancers. One study showed that a sulforaphane analog increased glutathione-S-transferase activity in all organs studied including the small intestine, liver and stomach. This study showed sulforaphane to be more potent than indole-3-carbinol in boosting beneficial glutathione S-transferase.68

Cancer Institute  

Inhibiting DNA-adduct formation is known to reduce incidence of mammary tumor incidence. Sulforaphane was shown in one study to inhibit chemical-induced DNA adduct formation by 68% to 80%, suggesting that this extract from broccoli may function as a breast cancer preventive.64 On the basis of mechanisms of carcinogenic effects cigarette smoke, sulforaphane appears to be a component in the prevention of lung cancer.

Broccoli contains a high percentage of D-glucarate compared to most plants studied. As mentioned earlier in this article, D-glucarate is critical in maintaining the important glucuronidation detoxification process.

Broccoli provides a cornucopia of carotenoids and other nutrients that provide a wide range of health benefits. The new Life Extension Mix contains a super-concentrated broccoli extract that is standardized to deliver precise amounts of sulforaphane and D-glucarate in each dose.

A potent flavonoid

Apigenin is a flavonoid found in parsley, artichoke, basil, celery and other plants. Over the last three years, a large number of published studies have demonstrated the anti-cancer properties of apigenin.

To study the effects of various plant constituents, an examination was made of 21 different flavonoids on the growth of human breast cancer cells. Apigenin was shown to the most effective anti-proliferative flavonoid tested.69 A related study showed that flavonoids such as apigenin bind to estrogen receptor sites on cell membranes in order to prevent over-proliferation of these cells in response to estrogen.70

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, only apigenin, rutin and quercetin were more effective than vitamin C in reducing DNA oxidative damage.71

Apigenin was tested to ascertain its effect on human leukemia cells. Apigenin was shown to induce apoptosis more effectively than quercetin and other flavonoids tested. The researchers attributed a unique mechanism of inducing apoptosis to the cancer preventive activity of apigenin.72 Another study showed that apigenin and another flavonoid called luteolin strongly inhibited the growth of human leukemia cells and induced these cells to differentiate.73 Topoisomerases are involved in many aspects of leukemic cell DNA metabolism such as replication and transcription reactions. In one study, quercetin or apigenin were shown to inhibit topoisomerase-catalyzed DNA irregularities.74 In a study of various agents used to induce differentiation of human promyelocytic leukemia cells, apigenin and luteolin were among the flavonoids shown to cause these leukemia cells to mature into healthy moncytes and macrophages.75

In studies against thyroid cancer cell lines, apigenin and luteolin were the most effective inhibitors found. Apigenin was shown to inhibit cancer cell signal transduction and induce apoptosis. The scientists concluded that apigenin may provide a new approach for the treatment of human anaplastic thyroid carcinoma for which no effective therapy is presently available.76 Another study compared the effects genistein, apigenin, luteolin, chrysin and other flavonoids on human thyroid carcinoma cell lines. Among the flavonoids tested, apigenin and luteolin were shown to be the most potent inhibitors of these cancer cell lines. The scientists noted that because these thyroid cancer cells lacked an anti-estrogen receptor binding site and an estrogen receptor, that apigenin and luteolin are inhibiting these cancer cells via previously unknown mechanisms. The scientists concluded that apigenin and luteolin may represent a new class of therapeutic agents in the management of thyroid cancer.77

apigenin and luteolin  

In a study on colorectal cancer cell lines, apigenin or quercitin were shown to interfere with epidermal growth factor cell stimulation. The researchers speculated that these flavonoids could be primary components in fruits and vegetables that reduce the risk colorectal cancer by inferring with the cancer cell growth signaling pathway.78

The epidermal growth factor signal transduction pathway is an essential component of both cancer cell growth and differentiation. Certain gelatinases are expressed in human cancers and are thought to play a critical role in tumor cell invasion and metastasis. Apigenin was shown to inhibit these gelatinases and interfere with the growth factor signaling pathways. The scientists concluded that compounds like apigenin may provide a novel means of controlling growth and invasive potential of certain tumors via these dual mechanisms.79 In a related study, apigenin was shown to prevent the degradation of tissue components by cultured human carcinoma cells, a mechanism by which cancer spreads to other parts of the body.80

The soy isoflavone genistein has been shown to be a potent inhibitor of cancer cell proliferation and in vitro angiogenesis. Moreover, the concentration of genistein in the urine of subjects consuming a plant-based diet is 30-fold higher than that in subjects consuming a traditional Western diet. Scientists have found in one study that apigenin and luteolin are more potent cancer inhibitors than genistein, and suggest that these plant components may contribute to the preventive effect of a plant-based diet on chronic diseases, including certain cancers. The scientists noted that the consumption of a plant-based diet can prevent the development and progression and growth of solid malignant tumors.81

Protein kinase C is over-expressed in many human tumors. One group of scientists has shown that apigenin blocks several points in the process of tumor promotion, including inhibiting kinases, reducing transcription factors and regulating cell cycle.82 Another group of scientists showed that apigenin and other flavonoids inhibit prostate cancer cell growth by blocking tyrosine kinase activity.83 Moreover, another study demonstrated that apigenin blocks mammary cell proliferation induced by several kinase-related pathways.84

The mutation and oxidation of estrogens is related to the development of certain cancers. The favorable influence of apigenin, genistein and other flavonoids on estrogen metabolism led researchers in one study to speculate that these plant extracts could be used in the prevention or treatment of estrogen-related diseases.85

Another mechanism by which cells mutate into malignancies involves a process known as sulfation. One study showed that apigenin and ellagic acid were potent inhibitors of sulfation compared to quercetin.86

In a study on human promyelocytic leukemia cells, genistein, followed by apigenin and daidzein, were the most potent inhibitors of toxic free radical byproducts generated by these leukemia cells. Other flavonoids showed no effect. The scientists stated that the antioxidant effects of these flavonoids may contribute to their chemopreventive potentials against human cancers.87

Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley, containing high levels of apigenin, on biomarkers for oxidative stress. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin in one of the intervention weeks. The scientists observed increased activity of the natural antioxidants glutathione reductase and superoxide dismutase in red blood cells during intervention with parsley as compared to people taking the basic diet without added parsley.88

A group of scientists studied the potential preventive effects of skin tumor promotion by apigenin. When topically applied, apigenin was shown to inhibit UV-induced skin tumorigenesis in mice. The scientists observed that apigenin facilitated several tumor suppressor factors including the important p53 binding activity.89

Grape skin and red wine contain resveratrol, which has been shown to inhibit platelet aggregation both in vivo and in vitro. One study showed that genistein, daidzein or apigenin produced inhibitory effects against an underlying cause of abnormal platelet aggregation similar to those seen with resveratrol.90

grape  

In order to better understand the mechanisms by which apigenin may prevent cancer, scientists looked at the effects this flavonoid would have on new blood vessel growth. Apigenin was shown to inhibit some factors involved in the process of tumor angiogenesis (new blood vessel growth that feeds rapidly dividing cells).91

Many types of cancer cells use cyclooxygenase-2 (COX-2) to propagate. COX-2 inhibiting drugs are being prescribed to cancer patients to slow the growth of existing tumors. One study showed that apigenin or genistein also suppresses formation of COX-2. The scientists conducting this study suggest that apigenin and related flavonoids may be important in the prevention of cancer and inflammation, partly via their COX-2 inhibiting properties.92

These studies as a whole provide a basis for cancer patients to consume a diet rich in certain fruits and vegetables as an adjunctive treatment for their disease. Apigenin is an antioxidant flavonoid with chemopreventive properties. It has been shown to arrest the growth of cancer cells, with concomitant inhibition of intracellular signaling cascades and decreased oncogene expression.

The Life Extension Foundation first introduced apigenin in 1985, but was unable to find a standardized plant extract that could consistently provide a specific number of milligrams per dose. The new Life Extension Mix contains a plant concentrate that provides 10 to 18 mg of apigenin and apigenin 7-glucoside per daily dose. Apigenin 7-glucoside is broken down into apigenin in the small intestine where it is absorbed.

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).

Keep the blood flowing

As people grow older, their blood platelets become “sticky” and develop the propensity to clot inside blood vessels. While conventional doctors accept this as a normal consequence of aging, the scientific facts are that the risks of stroke and heart attack could be reduced dramatically by adhering to a program that inhibits abnormal platelet aggregation. Life Extension Mix contains a variety of nutrients that inhibit platelet aggregation.

Enhanced imaging techniques have confirmed that aging people suffer a significant circulatory deficits to the brain and other parts of the body. These deficits often manifest in the microcapillaries in the eyes and skin in addition to the brain. The maintenance of a youthful vascular system is mandatory for healthy neurological and cardiovascular function. Many factors affect the body’s vascular system, and the scientific community has made it clear that a lot more than cholesterol control is required to maintain youthful arterial elasticity and blood flow to all the cells of the body. Life Extension Mix contains an abundance of nutrients that have been shown to help maintain vascular perfusion throughout the body.

The leading cause of disability and death in the Western world is thrombosis (the formation of an abnormal blood clot inside a blood vessel, blocking the flow of blood). Most heart attacks and strokes are caused by thrombotic events. Many of the nutrients in Life Extension Mix have proven anti-thrombotic properties. Ginger is consumed worldwide as a spice and flavoring agent. Ginger extract possesses antioxidative and anti-inflammatory properties.133,138 It may also be one of the most effective nutrients in preventing thrombosis. In two studies, powdered ginger produced a significant reduction in platelet aggregation.134,135 Other findings suggest that ginger could be an effective and inexpensive anti-emetic (preventing nausea and vomiting) for patients on cancer chemotherapy.136 There is evidence that ginger protects against skin tumor-promotion. In a mouse study, the topical application of ginger extract protected against the genesis and spread of skin tumors.137,138 A pharmaceutical ginger extract is included in the Life Extension Mix to provide additional protection against thrombosis, inflammation and other pathological conditions. Life Extension Mix also provides flavonoids found in bilberry, grape seed and grape skin. One of the most potent natural free radical scavenger may be the proanthocyanidins found in grape seed and skin. Proanthocyanidins and other extracts from the grape have been shown to inhibit abnormal blood clotting, promote the formation of collagen in the skin, and protect against cancer.139-141 Grape and pine bark supplements have become popular because of the many health benefits the natural flavonoids in these plants provide.

Dr. Linus Pauling’s last great work was to show that specific components in the blood called apolipoproteins are involved in atherosclerosis and aortic valve stenosis. Dr. Pauling showed that vitamin C and lysine can protect against apolipoprotein-induced vascular disease. Life Extension Mix contains the amount of lysine (500 mg) found in most lysine supplements. Those with valvular stenosis or atherosclerosis may want to take additional lysine.

Magnesium deficiency is a prime culprit in the epidemic of arterial disease that plagues the Western world. Foundation members have obtained high doses of magnesium ever since Life Extension Mix was introduced. Studies show that different forms of magnesium provide beneficial effects at the cellular level in addition to vascular protection. Life Extension Mix contains an advanced magnesium complex consisting of magnesium arginate, magnesium taurinate and magnesium glycinate to provide magnesium to different parts of the cell.

Modulating immune function

The immune system has been extensively studied over the last 20 years, and scientists have shown how specific nutrients can enhance components of immune function decimated by normal aging. Life Extension Mix contains a wide variety of nutrients that have been shown to improve immune function compromised by HIV, chemotherapy and aging.

Age-related autoimmunity can create a state of chronic inflammation throughout the body. New studies relate subclinical chronic inflammatory disease to the development of senility, atherosclerosis, aortic valve stenosis, some cancers and a host of other known inflammatory diseases such as arthritis and colitis. Despite their known toxicities, non-steroidal anti-inflammatory drugs (NSAIDS) have been shown to reduce the risks of Alzheimer’s disease and several types of cancer. Life Extension Mix contains nutrients that can be taken to safely alleviate chronic inflammatory disease at the cellular level.

Nutrient deficiencies have been implicated as a causative factor in almost every disease that occurs as a consequence of aging. Zinc and selenium supplements, for instance, when given to elderly populations, significantly reduce the incidences of infectious disease.142 One of the most important disease-preventing nutrients is selenium. While too much selenium can be toxic, it appears that most people take too little supplemental selenium out of concern over toxicity. Optimal supplemental selenium intake for healthy people ranges from 200 mcg to 600 mcg a day. Life Extension Mix contains 200 elemental micrograms of two different types of selenium and 35 elemental milligrams of zinc from two different forms of zinc to insure maximum absorption.

Choosing a multi-nutrient formula

There are a number of factors to consider when deciding on a multi-nutrient formula that you may be taking for the rest of your life. A significant concern among vitamin consumers is the quality of the individual ingredients that are contained in commercial formulas. Life Extension Mix contains only pharmaceutical-grade nutrient and herbal extracts. Many commercial companies use food-grade components that may not provide the same therapeutic benefits.

Another factor to consider is whether the potencies contained in a multi-nutrient formula are adequate to provide the desired health benefit. The Life Extension Foundation reviews thousands of published studies in order to determine the ideal potencies of each vitamin, mineral, amino acid and plant extract that is blended into the Life Extension Mix formula. Most commercially available multi-vitamin preparations do not provide enough lutein, lycopene and other expensive nutrients to produce a statistically significant disease risk reduction effect.

In some cases, minor modifications can mean a big difference in the benefit one obtains from a multi-nutrient formula. For instance, most people readily convert vitamin B6 to an enzymatically-active form the body needs called pyridoxal-5-phosphate. Some people, however, do not convert vitamin B6, so Life Extension Mix contains enough biologically available pyridoxal-5-phosphate to insure that no one taking this formula will suffer from a vitamin B6 deficiency. The same is true with pantothenic acid. While Life Extension Mix provides a huge dose of Roche-brand pantothenic acid, it also provides a small amount of the more biologically active pantothene.

The most important reason one should choose a particular multi-nutrient formula is the state-of-the-art ingredients it provides. Thousands of published studies show that the risk of contracting cancer, stroke, ocular disorders and heart disease can be reduced by the proper intake of vitamins, minerals, amino acids and plant extracts. The difficulty for most people is that they don’t know what nutrients are most important, or how much of each nutrient to take. Commercial supplement companies have fallen way behind in keeping up with the breakthroughs in preventive medicine appearing in the medical literature. The Life Extension Mix has been updated 14 times since its introduction in 1983 to provide the best disease-prevention nutrients known to science. Consideration is also given to the interaction between individual nutrients and the synergistic benefits that may be derived by incorporating a wide range of plant-based nutrients that work via a variety of mechanisms to protect against disease.

Despite the fact that costly pharmaceutical-grade nutrients are used in Life Extension Mix, Foundation members find that they save a considerable amount of money compared to the cost of other multi-nutrient formulas, or of taking the ingredients separately. Life Extension Mix provides more potency for less money than commercial formulas, while providing unique health-protecting extracts from plants.

A comprehensive multi-nutrient formula
multi-nutrient formula

The new Life Extension Mix formula contains more free radical-suppressing antioxidants than ever before. It also contains nutrients that:

  • Aid in detoxification via Phase I and Phase II (glucuronidation) enzymatic pathways (23,32,37,48, 63,64,153)
  • Reduce the binding of carcinogens to cellular DNA (6,23,30,34,36,40,42,45,57,64)
  • Inhibit excess calcium infiltration into cells (90)
  • Protect against excess binding of estrogen to cell receptor sites (70,100,103)
  • Regulate normal cell division to protect against certain cancers (140)
  • Enhance DNA methylation. . . an essential process that declines during aging (36,154-156)
  • Suppress apolipoprotein serum levels—a factor in atherosclerosis (150,155,160)
  • Suppress homocysteine. . . a cause of heart disease and stroke (149-151,154,155)
  • Suppress mitochondrial oxidative stress—a major cause of cellular aging (88,123)
  • Protect against thrombosis. . . the leading cause of death in the Western world (134,135,139)
  • Maintain microcapillary circulation— to keep your eyes and brain nourished (157-160)
  • Protect against DNA mutation. . . to protect against certain cancers (22, 25, 32, 89, 94)
  • Enhance insulin-sensitivity. . . to protect against diabetes and atherosclerosis (111-122,152)
  • Enhance immune cell surveillance— to defend against cancer and infectious disease (123,124,142)
  • Inhibit autoimmune attack. . . to protect against chronicinflammatory disease (93,133,138)

What is Life Extension Mix?

For the enlightenment of new members, Life Extension Mix is a multi-ingredient composition of extracts from vegetables, fruits, herbs and other food concentrates that have been documented in published scientific studies to prevent disease and slow premature aging. In addition, Life Extension Mix provides pharmaceutical potencies of the vitamins, minerals and amino acids that have demonstrated significant health benefits. Most Foundation members use Life Extension Mix as the cornerstone of their overall program to attempt to live longer in optimal health.

Life Extension Mix has been designed, tested and used by life extensionists who insist on the strictest standards of pharmaceutical purity for every nutrient included in the formula. Some people erroneously refer to Life Extension Mix as a multivitamin supplement, but a careful review of its ingredients shows that the formula is light years ahead of any other nutrient formula on the market. Every ingredient in Life Extension Mix is based on scientific findings about the role that specific nutrients play in defending the body against degenerative disease.

New members are pleasantly surprised when they discover that Life Extension Mix can replace many of the individual supplements they were previously taking. The convenience of obtaining potent doses of pharmaceutical-grade nutrients is the prime motivation for taking Life Extension Mix. Another reason that Life Extension Mix is so popular is that it saves the serious supplement user hundreds of dollars a year compared to the cost of buying the ingredients in the formula on an individual basis.

The Life Extension Mix makes it practical to follow a scientifically-designed disease prevention program. The latest improvements in Life Extension Mix are the most extensive in the product’s 17-year history. The Foundation regularly receives input from physicians, scientists and knowledgeable members about ways to improve Life Extension Mix. The Life Extension Mix formula has been improved to provide protection against newly identified mechanisms that have been implicated in the development of degenerative disease. The result is a formula that is constantly evolving to provide the user with the best that medical science has to offer.

There are two charts that clearly compare Life Extension Mix with eight other multi-nutrient supplements:

Multivitamin Supplements: A Comparison - jpg (Image - 90K). This document will load into a separate window.

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