~ What's Missing from Multi-Vitamin Supplements?

By Elizabeth Wagner, ND

Promoting a long, healthy life requires preventing diseases associated with poor lifestyle choices and normal aging. Collectively, cardiovascular disease, cancer, and diabetes account for approximately two thirds of all deaths in the US and about $700 billion in direct and indirect economic costs.1 

Scientists are discovering that vitamins, minerals, amino acids, and plant phytochemicals have powerful impacts on many of the biochemical pathways that go awry in disease processes such as diabetes, cancer, and heart disease. Nutrients and phytochemicals work by many mechanisms to reduce inflammation, inhibit free radicals, prevent glycation reactions, help remove toxins from the body, increase natural antioxidant status, interfere with the proliferation of undesirable cell lines, optimize glucose metabolism, support healthy methylation reactions, and boost the circulatory system.

By arresting disease processes at the molecular and cellular levels, these therapeutic nutrients help arm us against the scourges of disease and aging, and thus build the foundation for a future of optimal health. In this article, we discuss some of the agents that have been identified by leading researchers as among the most promising in fighting illness and promoting health.

Chinese researchers investigated the effects of dietary intake of lycopene and other carotenoids on the prevention of prostate cancer in men.67 Information on food consumption, including fruits and vegetables, was gathered using an interview and questionnaire. The researchers found that prostate cancer risk declined with increasing consumption of lycopene, alpha carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin. Consumption of tomatoes, pumpkin, spinach, watermelon, and citrus fruits was also associated with a reduced risk of prostate cancer. The dose-response relationships were also significant in this study, suggesting that increasing one's intake of lycopene and other carotenoid-rich vegetables and fruits may offer protection from prostate cancer.
Scientists at Harvard Medical School have advised all adults to take a multi-vitamin supplement to help prevent suboptimal levels of nutrients that may contribute to the onset of diseases such as cancer, heart disease, and osteoporosis.2 For example, suboptimal levels of folic acid and vitamins B6 and B12 are a risk factor for cardiovascular disease and cancer of the colon and breast.2 Deficient levels of calcium and vitamin D can contribute to osteoporosis and the loss of bone mass.3 While multi-vitamins can help to prevent certain illnesses, research indicates that abundant intake of fruits and vegetables can prevent some of the major diseases of aging.4 Studies at the UCLA Center for Human Nutrition in Los Angeles, CA, have reported that higher intake of fruits and vegetables is associated with a reduced incidence of many common forms of cancer.4

The World Cancer Research Fund published an extensive review of the effects of vegetable and fruit consumption on cancer risk.5 After reviewing hundreds of studies, this not-for-profit group determined conclusively that vegetables and fruits protect against cancer. The panel noted that consumption of at least five servings a day of vegetables and fruits was associated with an approximately 50% reduced risk for cancer compared to the risk associated with consuming only one or two servings.5 The panel also noted that the cancer-preventive effects of fruits and vegetables were dose dependent, with in-creased intake conferring greater protection.5

Compelling evidence likewise suggests that a diet rich in fruits and vegetables can lower the risk of heart disease, the leading cause of mortality and morbidity in the US and worldwide. People who consume more fruits and vegetables often have a lower prevalence of important risk factors for cardiovascular disease, including hypertension, obesity, and type II diabetes.6 Regular and frequent consumption of fruits and vegetables has also been shown to lower the risk of coronary heart disease, stroke, atherosclerosis, and hypertension.5,7

A large study conducted in Finland examined the effects of dietary fruit, berry, and vegetable intake on cardiovascular mortality and all-cause mortality in men.8 More than 2,000 Finnish men participated in the study, with a mean follow-up time of 12.8 years. Men with the highest consumption of fruits, berries, and vegetables had a 41% lower risk of death from cardiovascular disease and a 44% lower risk of all-cause death than men who consumed the least amount of fruits, berries, and vegetables.8 The study authors concluded, "…diets that are rich in plant-derived foods can promote longevity."8

While intake of fruits and vegetables has been correlated with a decreased risk of numerous cancers, how such intake influences breast cancer risk is less clear.

Researchers at the University of North Carolina investigated how fruit and vegetable intake relates to breast cancer, using a large, population-based, case-controlled study.69 Intake of fruits, vegetables, and vitamin supplements was assessed in nearly 3,000 participants. Postmenopausal women who consumed the most vegetables experienced a 37% decreased risk of breast cancer compared to women with the lowest vegetable intake. Intake of carotenoids such as alpha carotene, beta-carotene, lutein, and (especially) lycopene was also associated with a decreased risk of breast cancer in postmenopausal women. By contrast, premenopausal women did not show a reduced breast cancer risk related to fruit and vegetable intake. The study authors concluded that fruit and vegetable consumption is associated with a decreased risk of breast cancer in postmenopausal women.
Fruits and vegetables not only contain beneficial vitamins, minerals, and enzymes, but also provide a wealth of phytonutrients. These plant-based compounds likely are responsible for some of the protective effects of fruits and vegetables. Phytonutrients are versatile and powerful agents that help to modulate disease risk through a variety of mechanisms. For example, the glucosinolates in broccoli have been associated with a reduced risk of cancer, particularly of the lung and gastrointestinal tract.9 These compounds appear to offer protection by stimulating the liver's Phase II enzymes, which are powerful detoxifiers of chemical carcinogens.10 By contrast, the polyphenols present in olive extract promote health through a different mechanism. In humans, olive polyphenols have been shown to increase the resistance of low-density lipoprotein (LDL) to oxidation.11 Oxidized LDL is a significant risk factor for the development of heart disease and atherosclerosis.

Pomegranate Promotes Heart Health

The pomegranate is a widely cultivated tropical fruit that is native to Asia. Valued throughout history as a symbol of health and fertility, pomegranates contain many seeds enclosed in juicy red pulp and covered in a tough red rind. Pomegranate appears to be one of the most powerful sources of antioxidants among dietary plants, demonstrating a number of actions that can help prevent disease and aging.12 Ellagic acid, a polyphenol compound found in pomegranate, has been associated with antioxidant, anti-cancer, and anti-atherogenic biological properties.13 Pomegranate polyphenols have been found to protect LDL against cell-mediated oxidation.14 In mice, polyphenol-rich pomegranate juice significantly inhibited the development of atherosclerotic lesions.14

In a study of pomegranate juice supplementation, atherosclerotic patients with carotid artery stenosis who consumed pomegranate juice for one year saw a significant reduction in their carotid intima-media thickness, a marker for coronary artery disease.15 They also experienced a significant reduction in their serum LDL basal oxidative state, an increase in their serum total antioxidant status, and a reduction in their systolic blood pressure.15 The study investigators suggested that pomegranate poly-phenols may have been responsible for these effects.

Diabetics often experience elevated lipid levels and a correspondingly higher risk of heart disease. Pomegranate juice supplementation has been reported to improve lipid profiles in diabetics.16 Diabetic men and women with hyperlipidemia consumed 40 grams of concentrated pomegranate juice daily for eight weeks. At the study's end, the participants demonstrated significant reductions in total cholesterol and LDL.16 This important finding suggests that pome-granate juice may help to lessen the increased risk of heart disease associated with diabetes.

High blood pressure often is a silent yet dangerous condition that increases the risk of heart disease and stroke. Diet has been reported to influence arterial blood pressure.

Researchers in Athens, Greece, investigated the effects of the Mediterranean diet—rich in fruits, vegetables, and olive oil—on blood pressure in adults.68 Over 20,000 subjects who had never been diagnosed with hypertension participated in the study. Adherence to the Mediterranean diet was significantly associated with lower levels of systolic and diastolic blood pressure. By contrast, intake of cereals, meat and meat products, and ethanol was associated with higher levels of arterial blood pressure. A diet rich in fruits, vegetables, and olive oil has been demonstrated to promote healthy blood pressure levels.
Sesame Reduces Inflammation, Boosts Antioxidants

Sesamin, one of the lignans found in sesame seeds, has been reported to possess antioxidant effects and to scavenge reactive oxygen species.17 It apparently acts as an anti-inflammatory as well, reducing inflammation by increasing levels of dihomo-gamma linolenic acid, a precursor of anti-inflammatory prostaglandin E1. Sesame also decreases production of pro-inflammatory prostaglandin E2 and leukotriene B4 by inhibiting delta-5 desaturase enzyme activity.18 Studies in rats demonstrate that sesamin can lower serum lipids,19 while other animal studies suggest that sesamin may prevent hypertension.20

The tocopherols, the family of nutrients that includes vitamin E, are believed to play an important role in preventing some major diseases associated with aging, including heart disease and cancer. In humans, consumption of a moderate amount of sesame seeds has been found to significantly increase blood levels of gamma tocopherol,21 which appears to be an especially beneficial member of the vitamin E family. Animal studies likewise have demonstrated that intake of sesame seeds and sesame lignans, particularly sesamin, increases blood levels of gamma tocopherol.22 Sesame and its lignans appear to offer numerous benefits, including promoting healthy vitamin E levels, reducing inflammation, and promoting healthy blood lipids and blood pressure.

Health Benefits of Olive Extract

Health-conscious adults have long prized olive oil. As the principal source of fat in the Mediter-ranean diet, olive oil has been associated with a lower incidence of coronary heart disease and certain cancers. Extra-virgin olive oil contains abundant phenolic compounds such as hydroxytyrosol that are responsible for its strong flavor and high stability.23 Accu-mulating evidence indicates that the phenolic compounds in olives are powerful antioxidants (both in vitro and in vivo) and exert other potent biological actions that may be partly responsible for the health-promoting effects of the Mediterranean diet.23

Although epidemiological studies have indicated that fruits and vegetables offer protection from numerous degenerative disorders such as cardiovascular disease, the exact mechanisms of their actions remain to be elucidated.

French researchers investigated the effects of lettuce ingestion on lipid metabolism and antioxidant status in rats.70 Rats that were fed a diet of 20% lettuce for three weeks demonstrated a decreased ratio of low-density lipoprotein to high-density lipoprotein and a 41% decrease in liver cholesterol levels. Additionally, absorption of dietary cholesterol decreased by 37%, and excretion of total steroids, including cholesterol, increased by 44%. Lettuce intake significantly increased plasma levels of vitamin C and vitamin E, both of which contribute to plasma antioxidant capacity. The researchers concluded that lettuce consumption has a beneficial effect on cholesterol metabolism, improves antioxidant status, and should help protect against cardiovascular disease.
One byproduct of the processing of olive oil is a water extract of olive that contains phenolic compounds that are strong scavengers of free radicals.24 The most potent of these appears to be hydroxytyrosol, which has also demonstrated antibacterial activity.24

In-vitro studies have demonstrated that olive polyphenols increase LDL's resistance to oxidation.25 In a recent study examining whether this effect occurs in humans, subjects consumed virgin olive oil containing differing concentrations of phenolic compounds over the course of three weeks.10 Consumption of olive oil resulted in a decrease of in-vivo oxidized LDL, an increase in ex-vivo resistance of LDL to oxidation, and an increase in high-density lipoprotein (HDL).10 These effects were more pronounced in those who consumed olive oil with higher concentrations of polyphenols, suggesting that the polyphenols were responsible for the beneficial effects of preventing LDL oxidation and boosting HDL.10

A high intake of antioxidants is protective against the oxidative stress that is involved in the onset of several degenerative diseases. Animal studies suggest that olive polyphenols may protect against oxidative stress by sparing the consumption of vitamin E, a critical antioxidant, during normal physiological processes.26 Another study in animals found that hydroxytyrosol offered protection from the oxidative stress associated with inhaling sidestream smoke.27

Because dietary sources of olive oil may not provide enough of the potent polyphenols needed to obtain maximal antioxidant benefits,28 a potent supplemental dose rich in hydroxytyrosol is recommended.

Green Tea: Cancer Preventive and Cardioprotective

Tea consumption has been associated with reduced risk for numerous diseases, including cancer, coronary heart disease, stroke, and osteoporosis.29 Green tea is known for its antioxidant effects. Its main constituent is a polyphenol called epigallocatechin-3 gallate, or EGCG. Polyphenols may be responsible for green tea's cancer-preventive effects. In-vitro studies show that green tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells, but not in their normal cell counterparts.30 Various animal studies have shown that green tea inhibits tumor incidence and multiplicity in different organ sites such as the skin, lungs, liver, stomach, mammary glands, and colon.30 EGCG has been demonstrated to inhibit cyclooxy-genase-2 (COX-2) in human prostate carcinoma cells.31 Over-expression of COX-2 has been implicated in many pathological conditions, including cancer.31

Colorectal cancer is the second leading cause of cancer death in men and women combined. Investigators in the United Kingdom examined the effects of vegetable, fruit, and meat intake in relation to colorectal cancer and genes that modify cancer risk.71 Fruit and vegetable consumption was found to be protective against colorectal cancer, while overall meat and red meat consumption were found to increase cancer risk.

Many genes have been identified that encode for the enzymes involved in the metabolism of dietary carcinogens or anticarcinogens. The UK researchers found that one of these genes, GSTT1, appears to be related to the protective effect of vegetables. People with deficient or intermediate GSTT1 phenotypes experienced a protective effect of vegetable consumption against colorectal cancer, while other participants did not. The study demonstrated that both dietary and genetic factors are involved in modulating colorectal cancer risk.
Green tea extract helps protect the cardiovascular system. EGCG has been found to reduce LDL oxidation,32 which has been implicated in the formation of atherosclerotic plaques in the cardiovascular system. Green tea consumption has been associated with a lower incidence of coronary artery disease.33 A recent study demonstrated that regular consumption of green tea reduces the risk of developing hypertension,34 which accelerates atherogenesis and is associated with an increased risk of stroke.

Epidemiological studies suggest that green tea may play a role in preventing type II diabetes, while human studies have shown that green tea promotes healthy glucose metabolism.35 In diabetic mice, green tea lowered blood glucose levels,35 suggesting its promise in promoting healthy blood sugar levels.

Oxidative stress is known to play a pivotal role in the development of neurodegenerative diseases. Researchers are examining wheth-er green tea, with its potent poly-phenols, may protect the nervous system and alter brain aging. Ongoing epidemiological studies are investigating whether green tea may help to prevent progressive neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease.36

Broccoli: Broad-Spectrum Cancer Protection

Broccoli is a rich source of disease-preventive compounds. D-glucarate from broccoli has been shown to be an effective phytonutrient against cancer, offering cancer protection by supporting healthy mechanisms of detoxification. Specifically, D-glucarate inhibits beta-glucuronidase, an enzyme found in certain gut bacteria.

Age-related macular degeneration is the leading cause of vision loss in the elderly. Researchers at Harvard Medical School examined the effects of dietary fruits and vegetables on age-related maculopathy in a study involving over 100,000 participants.73 People who consumed three or more daily servings of fruit experienced a 44% lower risk of developing neovascular age-related maculopathy, though vegetable intake was not correlated with a decreased risk of maculopathy in this study.
One important mechanism by which the body eliminates toxic chemicals and hormones is by attaching glucuronic acid to them in the liver. Through the process of glucuronidation, the body removes carcinogenic substances such as nitrosamines, polycylic aromatic hydrocarbons, sex steroid hormones, and heterocylic amines. Beta-glucuronidase breaks the bond between these harmful metabolites and glucuronic acid, allowing toxins to be reabsorbed by the body. Elevated beta-glucuronidase activity has been correlated with increased risk for cancers, particularly hormone-dependent cancers such as breast, prostate, and colon cancers.37 By inhibiting beta-glucuronidase, D-glucarate supports the body's excretion of toxins and hormones.

High intake of cruciferous vegetables has been associated with a reduced risk of cancer, particularly of the lung and gastrointestinal tract.8 This protective effect has been linked to the presence of glucosinolates,8 which are metabolized to compounds that have been shown to be powerful inducers of the liver's Phase II detoxification enzymes.9 These liver enzymes are known to protect against chemical carcinogenes.9 Induction of Phase II enzymes also promotes the scavenging of free radicals and may relieve oxidative stress, thereby ameliorating hypertension and atherosclerotic changes.38

Numerous studies show that broccoli may contain more cancer-preventive nutrients than any other plant. In addition to containing D-glucarate, broccoli is rich in sulforaphane, a compound that has been found to block the formation of tumors initiated by chemical carcinogens and to induce cancer cell death.39 Sulforaphane and other broccoli compounds have been shown to prevent cancer by supporting the liver's Phase II detoxifying enzyme systems.40 Broccoli sprouts contain 30-50 times more of these protective chemicals than are found in mature broccoli plants.41

Excess weight and obesity are increasingly prevalent health problems, contributing to 280,000 premature deaths each year in the US. Overweight and obese individuals experience an increased risk of developing diabetes and heart disease.

In a recent study, Northwestern University researchers examined the effects of fruit and vegetable consumption on obesity and weight gain in women.74 More than 74,000 women who were free of cardiovascular disease, cancer, and diabetes at the study's onset were followed for 12 years. Dietary information was collected using a food frequency questionnaire. After 12 years, the women who consumed the largest amounts of fruits and vegetables were found to have a 24% lower risk of becoming obese compared to those who had the lowest fruit and vegetable intake. The study authors concluded that increasing intake of fruits and vegetables may reduce the long-term risk of obesity and weight gain in middle-aged women.
The Role of Flavonoids and Carotenoids

Luteolin, a flavonoid found in parsley, artichoke, basil, celery, and other foods, has been found to actively scavenge free radicals.42 Perilla leaf, one of the richest sources of luteolin, is known to inhibit inflammation, allergic response, and the production of tumor necrosis factor-alpha.43 In studies involving human cancer cell lines, luteolin greatly sensitized apoptotic cell death induced by tumor necrosis factor-alpha, suggesting a role for luteolin as an anti-cancer agent.44 Luteolin has also been demonstrated to be a potent inhibitor of thyroid cancer cell lines in vitro.45

Carotenoids are brightly colored pigments found in fruits and vegetables. Lutein, an antioxidant in the carotenoid family, is found in the macula, the central area of the eye's retina. It may act as a filter to protect the macula from damaging forms of light. Lutein is associated with protection from age-related macular degeneration, the leading cause of blindness in older adults.46

Lycopene, another carotenoid, is a potent antioxidant found in its highest concentrations in tomato products. Lycopene has been found to offer protection from prostate cancer, the second leading cause of cancer death in men,47 as well as from other cancers such as breast cancer.48 High intake of lycopene has been associated with a reduced risk for heart disease,49 and also helps prevent LDL oxidation.50

The various colors of fruits and vegetables help to promote optimal health, according to the federal Centers for Disease Control and Prevention (CDC).72

By choosing a variety of colors, people are more likely to consume the recommended five to nine daily servings of fruits and vegetables. Red foods such as tomato, pink grapefruit, and watermelon contain the powerful antioxidant lycopene, which has demonstrated benefits for fighting heart disease and cancer. Green foods such as spinach, kale, and collards contain the carotenoids lutein and zeaxanthin, which help protect eye health. The cruciferous vegetables contain several phytochemicals that help prevent cancer. Orange and yellow foods provide vitamin C, beta-carotene, and folate, helping to protect immune and heart health. Blue and purple foods offer proanthocyanadins, powerful antioxidants that protect eye health and help defend the body from carcinogens. White vegetables such as onions, garlic, and leeks contain compounds such as allicin, known to help lower cholesterol and blood pressure. The CDC recommends that when it comes to fruits and vegetables, people should seek not only abundant quantity but also the full spectrum of colors.
Fruits Rich in Antioxidants

Rich in vitamins, fiber, and phytochemicals, fruits are an excellent source of antioxidants12 and may provide protection from cancer by inhibiting angiogenesis.51 Current research suggests that some of the most beneficial health-promoting fruits are blueberries, bilberries, blackberries, cranberries, elderberries, cherries, plums, persimmons, and grapes.

Blueberries have been found to possess powerful antioxidant effects, as measured by their capacity to absorb oxygen radicals.51 In one animal study, supplementation with blueberry extract prevented memory loss associated with brain aging.52 Bilberry is a close relative of the American blueberry. Its ripe berries are a rich source of flavonoids that improve microcapillary circulation, decrease capillary permeability and fragility, and inhibit platelet aggregation.53 Bilberry consumption has been associated with a lower risk of cardiovascular disease and with improved visual function.54 Bilberry has also been reported to lower blood glucose levels and to prevent diabetic retinopathy.53

Blackberry extract has been used as a traditional herbal treatment for diabetes.55 In animal models, blackberry extract has demonstrated protective effects against inflammation56 and endotoxins.57 Cranberry has long been known for its efficacy in preventing urinary tract infections.58 Recent research indicates that cranberry may also inhibit the proliferation of certain human tumor cell lines.59 Elderberry extract has been used for centuries to treat colds, flu, sinusitis, and viral infections. Contemporary research confirms its efficacy in supporting a healthy immune system, and suggests possible applications for its use in supporting immune health in people who have cancer or the human immunodeficiency virus (HIV).60

Plants such as fruits, vegetables, and green tea are rich sources of powerful antioxidants called flavonoids. Because oxidative stress is thought to play a role in dementia, French scientists investigated whether dietary intake of flavonoids could offer a protective effect.75

A group of 1,367 subjects over the age of 65 was followed for five years. A questionnaire was used to evaluate their intake of flavonoids. Those who consumed the most flavonoids experienced a 51% lower relative risk of developing dementia than those who consumed the least amount. Since fruits, vegetables, and green tea are rich in flavonoids, these foods may be helpful in preventing dementia.
Cherry fruit has been used as a folk remedy for gout for many years. Human research indicates that cherries lower plasma levels of urate, a metabolic marker that is elevated in gout.61 Cherry consumption has also been found to lower plasma levels of C-reactive protein, a marker of inflammation.61 Plums are a potent source of antioxidant activity, with one serving providing antioxidant protection equivalent to 144-889 mg of vitamin C.62 Persimmon fruit has demonstrated antioxidant and cholesterol-lowering effects in animal studies,63 and components of its extract have shown cytotoxic activity against human carcinoma cells.64 A rich source of dietary fiber, phenolic compounds, minerals, and trace elements, persimmon has been proposed as a valuable component of an anti-atherosclerotic diet.65

Grape seed extract possesses powerful antioxidant effects that protect the body from premature aging and disease.66 Grape seed contains proanthocyanidins, beneficial polyphenol substances whose effects include promoting youthful skin, supporting joint flexibility, and improving vision.66 The proanthocyanidins in grape seed extract may improve blood circulation by strengthening capillaries, arteries, and veins.66

Choosing a Multi-Nutrient Formula

While the market is flooded with multi-nutrient formulas, few stand up to a careful analysis of purity and potency. Many formulas contain only the US government's recommended dietary allowance (RDA) of vitamins. While the RDA may be sufficient to prevent diseases such as scurvy, extensive studies have demonstrated that promoting optimal health requires nutrients in amounts that far exceed the RDA. Additionally, many of today's multi-vitamin supplements use components that are inferior in quality compared to the pharmaceutical-grade nutrients used in premium products.

Research also shows that the body more readily uses certain forms of vitamins and minerals than others. Many vitamin combinations on the market today use the cheapest available forms of vitamins and minerals. These are difficult for the body to absorb and use, and thus provide only marginal nutritional support. When choosing a multi-vitamin product, it is advisable to seek not only high potencies of nutrients, but also formulations designed for optimal absorption and use by the body.

Vitamins and minerals play crucial roles in optimizing health and preventing disease, through mechanisms as diverse as maintaining normal homocysteine levels and reducing the occurrence of damaging glycation reactions.

To determine the relationship between vegetable and fruit intake and cancer risk, scientists at the World Cancer Research Fund in London, England, reviewed over 200 human epidemiological studies and 22 animal studies.76 They found evidence for a protective effect of greater fruit and vegetable consumption against cancers of the stomach, esophagus, lung, oral cavity and pharynx, endometrium, pancreas, and colon.

The types of foods that most often appeared to be protective against cancer were raw vegetables, including those in the allium family (onions, garlic, chives, leeks, and shallots), carrots, green vegetables, cruciferous vegetables, and tomatoes. The scientists noted that numerous substances in fruits and vegetables may confer cancer protection, including dithiolethiones, isothiocyanates, indole-3-carbinol, allium compounds, isoflavones, protease inhibitors, saponins, phytosterols, vitamin C, D-limonene, lutein, folic acid, beta-carotene, lycopene, selenium, vitamin E, flavonoids, and dietary fiber. The researchers also noted other possible health effects of increased fruit and vegetable consumption, including benefits against cardiovascular disease, diabetes, stroke, obesity, diverticulosis, and cataracts.

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