Eleven current test criteria for LifePak®

1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11
references

Criterion 1: Uses exclusively natural vitamin E because of its documented higher bioavailability.

Documentation.
Recent well-designed human pharmacokinetic studies demonstrate clearly that natural vitamin E has significantly higher bioavailability than synthetic vitamin E, even on an IU-for-IU basis (1;2). In fact a recent study by Kiose et al. (3) indicated that 100 mg of the natural RRR-a-tocopherol results in the same serum and lipoprotein uptake as 300 mg of the synthetic all-rac-a-tocopherol.

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Criterion 2: Provides at least 50% of the most recently established nutrient intake recommendations of the National Research Council (NRC) for adult men and women of all essential vitamins and minerals, except electrolytes, phosphorus, fluoride, and iron.

Documentation.
Meaningful long-term dietary multivitamin/mineral supplementation should provide at least 50 % of the most recently published recommended intakes for all vitamins and minerals, except those for which there is no general need for supplementation and a potential for harm (electrolytes, fluoride, phosphorus, iron). As a basis for recommended vitamin and mineral intakes, the most recent, scientific sets of nutrient recommendations should be selected, such as the Recommended Dietary Allowances (RDAs) or Estimated Safe and Adequate Daily Dietary Intakes (ESADDIs) established by the National Research Council (NRC), Food and Nutrition Board (FNB) in 1989(4), and the recently released preliminary RDAs or Adequate Intakes (AIs) established by the NRC FNB for calcium, phosphorus, magnesium, vitamin D, fluoride, and the B vitamins (Dietary Reference Intakes, prepublication copies, 1998). The RDAs, ESADDIs, or AIs are taken from the age range of 19–50 years for men and women, whichever is highest. The table below (next page) shows the minimum nutrient levels.

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Criterion 3: Uses optimum amounts of antioxidant nutrients: 100–400 IU vitamin E, 200–500 mg vitamin C, 5,000–15,000 IU beta-carotene, and 70–200 mcg selenium.

Documentation
Vitamin E. Stampfer and Rimm concluded from the existing epidemiological data, such as the Nurses' Health Study and the Health Professionals Follow-Up Study, that beneficial cardiovascular effects were observed with supplemental intakes of at least 100 IU/d vitamin E (11). Most long-term human supplementation studies show benefits at daily vitamin E intakes between 100 and 400 IU (11-14). Kappus et al. concluded from the large number of studies in humans that a daily dosage of up to 300 mg (400 IU) vitamin E can be considered harmless from a toxicological point of view (15). Based on these data it can be concluded that the optimum range for long-term vitamin E supplementation is from 100 to 400 IU/d.

Vitamin C. In 1995, Levine et al. recommended 200–500 mg/d vitamin C (16). Based on further pharmacokinetic studies, the same authors determined recently that at single vitamin C doses of 500 mg and higher, bioavailability declined and the absorbed amount was excreted. Oxalate and urate excretion were elevated at 1,000 mg of vitamin C daily compared to lower doses (17). Levine et al. recommended that oral intakes over 400 mg/d have no evident additional benefits, and that amounts up to 1,000 mg/d can be considered safe (17). Based on these findings, it can be concluded that optimum vitamin C intakes for healthy individuals should be at least 200 mg/d, but no greater than 500 mg/d.

Beta-Carotene. Blumberg suggested that dietary intakes of at least 3 mg (5,000 IU) of beta-carotene are required to attain plasma beta-carotene concentrations that have been associated with beneficial health effects (18). In the light of the recently observed negative effects of high-dose beta-carotene supplementation (20-30 mg/d) in smokers and asbestos workers (19;20), it appears prudent to recommend supplemental intakes of beta-carotene that can be obtained from diets high in fruits and vegetables. Lachance estimated that fruit and vegetable rich diets recommended by the USDA and National Cancer Institute would deliver 5–6 mg carotenes daily (21), which is equivalent to up to 10,000 IU of beta-carotene. Likewise, diets designed to have high carotenoid content provided 6 mg beta-carotene (22). Therefore, long-term supplementation with more than 10,000 IU (6 mg) beta-carotene daily can be considered unnecessary or excessive, especially given the lack of additional health benefits and potential adverse effects at higher supplemental intakes (19;20). Based on these data, the optimum range for long-term beta-carotene supplementation appears to be from 5,000–15,000 IU/d (3-6 mg/d).

Selenium. The 1989 NRC RDA for selenium is 55 mg for women and 70 mg for men (4). Clinical studies have used daily selenium supplements of 100–200 mcg (23-26), and the Council for Responsible Nutrition has established a NOAEL (no observed adverse effect level) for selenium of 200 mcg/d (27). As a result, the optimum range for selenium supplementation appears to be within 70–200 mcg/d.

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Criterion 4: Uses optimum amounts of B vitamins involved in homocysteine metabolism: at least 200 mcg folic acid, 1.5 mg vitamin B6, and 2.4 mcg vitamin B12.

Documentation.
The B-vitamins B6, B12 and folic acid are necessary to maintain normal, low blood levels of homocysteine. Homocysteine is an amino acid derived from methionine metabolism that can adversely affect lipid deposition and inflammation of the vascular wall (28;29). Supplementation studies showed that primarily folic acid, but also vitamins B6 and B12 promote normal, low homocysteine levels (30;31). Initially, pharmacological doses of folic acid, e.g., 1–5 mg/day, were used to lower homocysteine serum levels (31–33). However, recent studies showed that as little as 200 mcg/day folic acid is effective (30;34–37). Recently, Ward et al. determined in a dose-response study that 200 mcg/day of folic acid was as effective as 400 mcg/day, and that 100 mcg/day of folic acid was clearly less effective (34). As a result, the currently available data supports that the minimum effective supplemental folic acid dose is 200 mcg/d.

Less information is available about effective doses of vitamins B6 and B12, although both vitamins are clearly essential for normal homocysteine metabolism. Most homocysteine studies have used amounts of 1-20 times RDA of these B-vitamins in conjunction with folic acid (37-39). Based on these data, it appears prudent to recommend to supplement with at least 100% of the 1998 RDA for both vitamins B6 and B12 as long-term supplementation levels to maintain normal homocysteine levels, i.e., 1.5 mg vitamin B6 and 2.4 mg vitamin B12.

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Criterion 5: Uses optimum amounts of bone nutrients: 500–1,500 mg calcium, 210–700 mg magnesium, 200–800 IU vitamin D, at least 40 mcg vitamin K, and at least 1 mg boron.

Documentation.
Calcium. Most clinical calcium supplementation trials showing positive effects on bone mineralization have used at least 500 mg—and more commonly—1,000 mg of calcium (40–45). Supplementation with 500 mg is also equivalent to 50% of the RDA (4). Data from the USDA 1987-88 Nationwide Food Consumption Survey showed that mean per capita daily consumption of calcium for the total U.S. population was 737 mg (46). A supplement providing an additional 500 mg of calcium would ensure that most individuals meet the new 1998 AI (Adequate Intake) values for calcium (1,000 to 1,300 mg/d). From these data it can be concluded that 500 mg is a significant minimum amount for long-term supplementation of calcium to promote bone health. Based on the No-Observed Adverse Effect Level (NOAEL) established by the Council for Responsible Nutrition (CRN), 1,500 mg/d is a safe upper level for calcium supplementation (27). Thus, a reasonable optimum range for calcium supplementation is 500–1,500 mg per day.

Magnesium. The importance of magnesium in calcium and bone metabolism is well-established (47;48). Stendig-Lindberg et al. reported increases in bone mineral density in 71 percent of osteoporotic post-menopausal women taking 250 mg/d magnesium for two years (49). Daily supplementation with 210 mg of magnesium is equivalent to 50% of the 1998 RDA for adult men. According to the CRN NOAEL, 700 mg/d is a safe upper level for magnesium supplementation (27). Based on these data, a reasonable optimum range for daily magnesium supplementation is 210–700 mg.

Vitamin D. Most human vitamin D intervention trials support supplements of 400 IU daily (50;51). There is also clinical evidence that supplementation of 200 IU/d is sufficient to limit bone loss from the spine and whole body but inadequate to minimize bone loss from the femoral neck in healthy calcium-supplemented, postmenopausal women (52). Vitamin D insufficiency and deficiency are common, especially in women and elderly people (53;54). To prevent insufficiency and deficiency, experts encourage responsible exposure to sunlight and/or consumption of a multivitamin that contains 400 IU vitamin D (55). The new 1998 AI (Adequate Intake) is 200 IU until age 50, 400 IU from age 51–70, and 600 IU above age 70. The CRN's NOAEL for vitamin D is 800 IU/d (27). Based on these data, a reasonable optimum range for daily vitamin D supplementation for the general adult population is 200–800 IU, and for supplements targeted at the elderly, an optimum range is 400–800 IU/d.

Vitamin K. Recent research established vitamin K as an important nutrient for bone metabolism (56;57). A prospective analysis within the Nurses' Health Study showed that women in the lowest quintile of vitamin K intake (<109 mcg/d) had an increased risk of hip fractures (58). Low circulating levels of vitamin K have been associated with low bone mineral density (59). Vitamin K intakes in U.S. adults were found to be less than 90 mcg/d (60). In the absence of reliable data to establish an optimum vitamin K intake to promote bone health, a reasonable minimum would be 40 mcg/d, which is equivalent to 50% of the 1989 RDA for vitamin K (4).

Boron. Boron appears to have essential functions in vitamin D, estrogen, testosterone and bone metabolism (61–65). Although dietary boron intake is variable, average dietary intakes range from 1–3 mg/d (63;66). Boron supplements of 3 mg/d have been shown to normalize steroid hormone levels and urinary calcium and magnesium excretion in postmenopausal women consuming low-boron diets (64). Nielsen recommends desirable dietary boron intakes of 1–13 mg/d (67). Based on these data, a reasonable minimum for boron supplementation is 1 mg/d.

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Criterion 6: Provides significant amounts of carotenoids from multiple sources. Must provide at least 6 mg carotenoids which must include at least three out of the five most important dietary carotenoids: beta-carotene, alpha-carotene, lutein, lycopene and cryptoxanthin. Amounts must be specified.

Documentation.
Carotenoids are a major class of phytonutrients with many well-documented health benefits (68;69). After disappointing results from high-dose beta-carotene supplementation trials, many experts now emphasize the importance of multiple carotenoids (70-72). Average dietary total carotenoid intakes of 547 elderly subjects of the Framingham Heart Study were 14.8 and 15.5 mg from diets providing 4.4 and 5.1 servings of fruits and vegetables for men and women, respectively (73). Others found that controlled diets high in fruits and vegetables provided 16 mg carotenoids daily (22). On average, these data suggest that one serving of fruits and vegetables provides about 3 mg total carotenoids. The major dietary as well as blood serum carotenoids are beta-carotene, lycopene, lutein, alpha-carotene, and cryptoxanthin (22;69;73-75). Based on these data, a reasonable recommendation for minimum carotenoid supplementation would be at least 6 mg/d, which can also be obtained from two additional servings of fruits and vegetables. Since all five major carotenoids are present in diets and serum, and all have demonstrated health benefits, supplementation with at least three of the major carotenoids can be advised.

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Criterion 7: Provides significant amounts of flavonoids from multiple sources. Must provide at least 20 mg of dietary flavonoids from at least three different, well-characterized sources. Amounts must be specified.

Documentation
Flavonoids are recognized as an important group of phytonutrients with many health benefits. It is estimated that there are over 600 different flavonoids present in foods and beverages. Large epidemiological studies suggest that dietary flavonoid intake from fruits, vegetables, tea, grape juice and red wine is positively associated with cardiovascular health (76–79). Individual flavonoids and flavonoid extracts can reduce LDL oxidation (80–82), promote normal platelet aggregation (83;84), and positively affect many other aspects of cardiovascular health (85). Estimates of average daily flavonoid consumption in industrialized nations vary from 20 to 100 mg per day (86–88). Because of the large variety of dietary flavonoids, supplementation with multiple flavonoids or flavonoid extracts that have demonstrated health benefits can be recommended. Meaningful supplementation should supply at least 20 mg of total flavonoids from at least three different sources. Only those flavonoids should be present in multivitamins that are normal constituents of human diets.

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Criterion 8: Uses well-absorbable, bioavailable sources of the trace minerals zinc, copper, and chromium, such as organic acid salts and amino acid chelates.

Documentation
Bioavailability and intestinal absorption efficiency for the divalent trace minerals iron, zinc, and copper, as well as for trivalent chromium is variable and depends to a great extent on solubility and the type of chemical ligand of these trace minerals. Typically, minerals present as soluble organic acid salts, e.g., citrates, malates, gluconates, etc., or amino acid chelates are better absorbed or utilized than their often insoluble inorganic salt forms (89–93). For example, ferrous glycinate (iron amino acid chelate) has greater bioavailability than ferrous sulfate (94). The inorganic zinc salts, zinc oxide and zinc carbonate are insoluble and poorly absorbed (95). These differences in bioavailability tend to be greatest for the divalent trace minerals iron, zinc, and copper (89;96), and to some extent for chromium (93). These differences are less obvious with the other minerals and trace minerals, which is why they are not considered in this criterion.

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Criterion 9: Free of potentially unsafe amounts of vitamins and minerals.

Documentation
The recently published No-Observed Adverse Effect Levels (NOAEL) by the Council for Responsible Nutrition (CRN) serve as a credible guideline for all essential vitamins and minerals (27). The NOAEL are the highest daily amounts used as supplements in clinical studies without any significant adverse effects.

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Criterion 10: Free of artificial fillers, binders, colors, flavors and preservatives.

Documentation
This is largely a philosophical issue. The artificial ingredients typically used as excipients in capsules, tablets, softgels etc. are Generally Recognized as Safe (GRAS) by the Food and Drug Administration (FDA). However, in a few cases, safety concerns did surface even though the compounds were listed as GRAS. For example, among others, the artificial colors FD&C Reds #1 and #2, Yellows #3 and #4 were banned by the FDA for use in foods, drugs and cosmetics, and the safety of FD&C Red #3 (erythrosine) is currently an issue due to its high iodine content. Even though the FDA-required toxicity data may indicate no concerns at the time of approval, subsequent research may identify safety problems. Typically, many natural excipients do not have these safety concerns, since they are and have always been present in natural foods with a long safety record. As a result, it may be wise to avoid the use of artificial fillers, binders, colors, flavors, preservatives and other artificial excipients whenever possible.

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Criterion 11: Manufacturer certifies that the product has been tested and is guaranteed to meet USP XXIV disintegration guidelines. (30 minutes for capsules and uncoated tablets, 45 minutes for coated tablets.)

Documentation
The United States Pharmacopeia (USP) XXIV disintegration test methods and guidelines for vitamin capsules and tablets are widely recognized standards in the industry to ensure that the nutrients in capsules and tablets are made available for digestion and intestinal absorption in a timely manner.

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