WO2015161153A1 - Procédé d'augmentation de la biodisponibilité de rrr-alpha-tocophérol fourni par un complément nutritionnel prénatal et post-partum - Google Patents

Procédé d'augmentation de la biodisponibilité de rrr-alpha-tocophérol fourni par un complément nutritionnel prénatal et post-partum Download PDF

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WO2015161153A1
WO2015161153A1 PCT/US2015/026297 US2015026297W WO2015161153A1 WO 2015161153 A1 WO2015161153 A1 WO 2015161153A1 US 2015026297 W US2015026297 W US 2015026297W WO 2015161153 A1 WO2015161153 A1 WO 2015161153A1
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tocopherol
alpha
rrr
woman
nutritional supplement
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PCT/US2015/026297
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English (en)
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Christina Sherry
Chron-Si Lai
Barbara MARRIAGE
Matthew KUCHAN
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Abbott Laboratories
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E

Definitions

  • the present disclosure relates to methods of increasing the RRR-a ⁇ pha- tocopherol, also sometimes called "natural Vitamin E," in the body and tissues of a woman prior to, during, and after pregnancy, by providing nutritional supplements comprising a mixture of Ri?R-alpha-tocopherol and a//-rac-alpha-tocopherol ("synthetic Vitamin E") to the woman.
  • the method provides the woman's body with increased Ri?R-alpha-tocopherol, which is then preferentially available to her developing fetus.
  • the method also increases the amount of RftR-alpha-tocopherol that is present in the woman's breast milk, so that, postpartum, the infant continues to receive an increased amount of RftR-alpha-tocopherol from the breast milk.
  • Vitamin E An important nutrient for human health and development is Vitamin E, which is needed for the brain and central nervous system of a fetus and infant. Vitamin E is an important antioxidant, and Vitamin E helps to boost the immune system and maintain a healthy brain and central nervous system throughout life. Vitamin E is a nutrient naturally found in many foods such as seeds, nuts, and vegetable oils, including olive oil, sunflower oil, and safflower oil.
  • Vitamin E can encompass two classes of chemicals, tocopherols and tocotrienols.
  • the form of Vitamin E that is best absorbed by humans is alpha-tocopherol, and hence the terms “Vitamin E” and "alpha-tocopherol” are often used interchangeably in medical and non-technical communications.
  • Alpha-tocopherol is a chemical with three centers of asymmetry, which means that eight distinct stereoisomers of alpha-tocopherol exist.
  • the alpha-tocopherol that is found in vegetable oils is a single stereoisomer, Ri?R-alpha-tocopherol.
  • synthetic alpha-tocopherol is made up of essentially equal amounts of all eight stereoisomers. Hence, only about 12.5% of synthetic alpha-tocopherol is the "natural" stereoisomer, RRR -alpha-tocopherol.
  • RRR -alpha-tocopherol is more biologically active in the human body than the other seven stereoisomers of alpha-tocopherol, and that RRR -alpha- tocopherol is preferentially transferred from the liver into the bloodstream, and then preferentially absorbed by other organs such as the brain.
  • Ri?R-alpha-tocopherol it is not fully understood how the increased biological activity of Ri?R-alpha-tocopherol is conferred.
  • the present disclosure provides nutritional supplements containing an alpha-tocopherol combination comprising both Ri?R-alpha-tocopherol and non-RRR -alpha- tocopherol, wherein the weight ratio of RRR -alpha-tocopherol to non-RRR -alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • These nutritional supplements are used in methods to increase the RRR -alpha-tocopherol in the tissues, particularly the plasma, blood, and breast milk, of a woman who receives doses of the nutritional supplements.
  • Some embodiments are directed to methods of increasing RRR -alpha- tocopherol in the tissues of a woman.
  • One or more doses of nutritional supplements comprising both Ri?R-alpha-tocopherol and non-RftR-alpha-tocopherol, wherein the weight ratio of Ri?R-alpha-tocopherol to non-Ri?R-alpha-tocopherol is from about 0.5:1 to about 1000:1 , are administered to the woman.
  • the woman receiving the nutritional supplement may be pre-pregnant, pregnant, or lactating.
  • One embodiment is directed to a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol for use in increasing RRR-alpha- tocopherol in the tissues of a woman wherein the weight ratio of RRR-alpha-tocopherol to non-RRR-alpha-tocopherol is from 0.5:1 to about 1,000:1.
  • One embodiment provides use of a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol wherein the weight ratio of RRR- alpha-tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1 for the manufacture of a medicament for increasing RRR-alpha-tocopherol in the tissues of a woman.
  • Some embodiments are directed to methods of increasing RRR -alpha- tocopherol in the breast milk of a lactating woman.
  • One or more doses of nutritional supplements comprising both RRR -alpha-tocopherol and non-RRR -alpha-tocopherol, wherein the weight ratio of Ri?R-alpha-tocopherol to non-RRR -alpha-tocopherol is from about 0.5:1 to about 1000:1, are administered to the woman.
  • Breast milk from the woman containing increased RRR -alpha-tocopherol is fed to an infant, thereby increasing RRR -alpha-tocopherol in the plasma of the infant.
  • One embodiment is directed to a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol for use in increasing RRR-alpha- tocopherol in breast milk of a lactating woman, wherein the weight ratio of RRR-alpha- tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • One embodiment provides use of a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol wherein the weight ratio of RRR- alpha-tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1 for the manufacture of a medicament for increasing RRR-alpha-tocopherol in breast milk of a lactating woman.
  • Some embodiments are directed to methods of providing increased Ri?R-alpha-tocopherol to a fetus by increasing Ri?R-alpha-tocopherol in the tissues of a pre- pregnant or pregnant woman.
  • One or more doses of nutritional supplements comprising both Ri?R-alpha-tocopherol and non-RftR-alpha-tocopherol, wherein the weight ratio of RRR- alpha-tocopherol to non-RftR-alpha-tocopherol is from about 0.5:1 to about 1000:1, are administered to the woman.
  • One embodiment is directed to a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol for use in providing increased RRR- alpha-tocopherol to a fetus by increasing the RRR-alpha-tocopherol in the tissues of a pre- pregnant or pregnant woman wherein the weight ratio of RRR-alpha-tocopherol to non-RRR- alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • One embodiment provides use of a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol wherein the weight ratio of RRR- alpha-tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1 for the manufacture of a medicament for providing increased RRR-alpha-tocopherol in the tissues of a pre -pregnant or pregnant woman.
  • Some embodiments are directed to methods of increasing RRR-a ⁇ pha- tocopherol in the plasma of a breast milk-fed infant by increasing RftR-alpha-tocopherol in the breast milk of a lactating woman.
  • One or more doses of nutritional supplements comprising both Ri?R-alpha-tocopherol and non-RftR-alpha-tocopherol, wherein the weight ratio of Ri?R-alpha-tocopherol to non-Ri?R-alpha-tocopherol is from about 0.5:1 to about 1000 : 1 , are administered to the woman.
  • the breast milk from the lactating woman containing increased Ri?R-alpha-tocopherol is fed to the infant, thereby increasing Ri?R-alpha-tocopherol in the plasma of the infant.
  • One embodiment is directed to a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol for use in providing increased RRR- alpha-tocopherol to an infant being fed breast milk of a lactating woman when RRR-alpha- tocopherol is provided to the lactating woman with non-RRR-alpha-tocopherol, wherein the weight ratio of RRR-alpha-tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • One embodiment provides use of a nutritional supplement comprising RRR-alpha-tocopherol and non-RRR-alpha-tocopherol wherein the weight ratio of RRR- alpha-tocopherol to non-RRR-alpha-tocopherol is from about 0.5:1 to about 1000:1 for the manufacture of a medicament for providing increased RRR-alpha-tocopherol to an infant being fed breast milk of a lactating woman when RRR-alpha-tocopherol is provided to the lactating woman with non-RRR-alpha-tocopherol.
  • FIG. 1 shows the chemical structure of the tocopherol family.
  • FIG. 2 is a graph of the output of RftR -alpha-tocopherol in the breast milk of lactating women taking nutritional supplements containing only RRR-a ⁇ pha- tocopherol, a//-rac-alpha-tocopherol, or a mixture of both, normalized for the total intake of Ri?R-alpha-tocopherol in each woman's food plus nutritional supplements.
  • FIG. 3 is a graph of the output of RftR -alpha-tocopherol in the plasma of lactating women taking nutritional supplements containing only Ri?R -alpha-tocopherol, all- rac-alpha-tocopherol, or a mixture of both, normalized for the total intake of RftR-alpha- tocopherol in each woman's food plus nutritional supplements.
  • Alpha-tocopherol is a nutrient found in many vegetable oils such as sunflower oil, safflower oil, and olive oil. Alpha-tocopherol is also found in seeds, nuts, and some vegetables such as spinach. Alpha-tocopherol has three chiral carbons in its chemical structure, which create three centers of asymmetry. This means that eight stereoisomers exist, which are chemically the same but structurally and biologically somewhat different. Natural alpha-tocopherol, as found in foods, is a single stereoisomer, RftK-alpha-tocopherol. However, when alpha-tocopherol is synthetically produced, the manufacturing methods do not preferentially form any specific stereoisomer.
  • synthetic alpha-tocopherol contains substantially equal amounts of all eight stereoisomers, only one of which is RRR- alpha-tocopherol. In 100 g of synthetic alpha-tocopherol, each stereoisomer constitutes about 12.5 g of the total. Because it is made up of all eight stereoisomers, synthetic alpha- tocopherol is also known as "racemic-" or a//-rac-alpha-tocopherol.
  • RRR -alpha-tocopherol is preferentially transferred from the liver into very-low-density lipoproteins (VLDL), and then into plasma and red blood cells.
  • VLDL very-low-density lipoproteins
  • RRR -alpha-tocopherol is more bioavailable and biologically active than the other stereoisomers because certain metabolic systems of the human body preferentially absorb Ri?R-alpha-tocopherol over the non-RftR-alpha-tocopherol stereoisomers.
  • the human body prefers RRR -alpha-tocopherol over the non- Ri?R-alpha-tocopherol stereoisomers
  • the non-Ri?R-alpha-tocopherol stereoisomers in all-rac- alpha-tocopherol have typically been considered beneficial, providing antioxidant capacity and health benefits that, while less biologically active, are similar to the benefits provided by Ri?R-alpha-tocopherol.
  • ⁇ //-rac-alpha-tocopherol is also less expensive than RRR-a ⁇ pha- tocopherol.
  • a//-rac-alpha-tocopherol is commonly used as a dietary supplement, both alone and in multivitamins.
  • ⁇ //-rac-alpha-tocopherol is also used to fortify many processed foods, such as breakfast cereals. Therefore, many people regularly consume a//-rac-alpha-tocopherol, even if they do not take Vitamin E supplements.
  • Ri?R-alpha-tocopherol The absorption of Ri?R-alpha-tocopherol is of particular concern for pregnant women and infants.
  • the fetus requires alpha-tocopherol for the proper development of the brain and central nervous system.
  • alpha-tocopherol an antioxidant
  • alpha-tocopherol is thought to enhance the release of prostacyclin, which may then result in increased blood flow and nutrient supply to the fetus and reduced risk of preeclampsia in the mother.
  • alpha-tocopherol particularly Ri?R-alpha-tocopherol
  • methods are presented of increasing RRR-a ⁇ pha- tocopherol in the tissues of a woman, particularly a pre -pregnant or pregnant woman.
  • methods are presented of increasing RftR-alpha-tocopherol in the breast milk of a lactating woman.
  • methods are presented of providing increased amounts of RftR-alpha-tocopherol to a fetus by increasing RftR-alpha-tocopherol in the tissues of a pregnant woman.
  • methods are presented of increasing the amounts of RftR-alpha-tocopherol in the plasma of a breast milk-fed infant by increasing Ri?R-alpha-tocopherol in the breast milk of a lactating woman, and feeding this breast milk to the infant.
  • the methods of these embodiments all comprise administering doses of a nutritional supplement to the pre-pregnant, pregnant, or lactating woman, wherein the nutritional supplement comprises both Ri?R-alpha-tocopherol and non-Ri?R-alpha-tocopherol, and wherein the weight ratio of RftR-alpha-tocopherol to non-RftR-alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • the nutritional supplement may be in a medicine-like product form, such as a capsule, tablet, chewable soft gel, syrup, or elixir.
  • the nutritional supplement may also be in the form of a nutritional food or beverage product, such as a meal-replacement bar, protein bar, milk- or soy-based beverage, protein drink, energy drink, hydration beverage, enhanced fruit juice, enhanced water, or mix-in powder for a beverage.
  • a nutritional food or beverage product such as a meal-replacement bar, protein bar, milk- or soy-based beverage, protein drink, energy drink, hydration beverage, enhanced fruit juice, enhanced water, or mix-in powder for a beverage.
  • Nutritional supplement refers to nutritional products ingested by a person for generally maintaining or improving the health of that person.
  • Nutritional supplements may be in the form of a medicine-like product, such as a capsule, tablet, chewable soft gel, syrup, or elixir.
  • Nutritional supplements may also be in the form of a nutritional food or beverage product, such as a meal replacement bar, protein bar, milk- or soy-based beverage, protein drink, energy drink, hydration beverage, enhanced water, or mix-in powder for a beverage.
  • the term "nutritional supplement formulation” refers to the components or ingredients used in a nutritional supplement, including but not limited to the active ingredients (e.g., Ri?R-alpha-tocopherol), flavors, colorants, and excipients such as carrier oils or inert solids.
  • the nutritional supplement formulation may include macronutrients (e.g., protein, carbohydrate, or fat) or other optional ingredients (e.g., vitamins or minerals), as discussed below.
  • prenatal nutritional supplement as used herein is used to refer to nutritional products ingested by a pre -pregnant or pregnant woman for generally maintaining or improving the health of both the woman and her developing fetus.
  • postpartum nutritional supplement as used herein is used to refer to nutritional products ingested by a lactating woman after giving birth for generally maintaining or improving the health of both the lactating woman and her nursing infant.
  • Ri?R-alpha-tocopherol which is sometimes referred to as "natural Vitamin E,” is used to refer to the stereoisomer of alpha-tocopherol which is found naturally in foods.
  • Ri?R-alpha-tocopherol comprises about 12.5% of the alpha-tocopherol found in a//-rac-alpha-tocopherol.
  • RRR -alpha-tocopherol may come from natural or synthetic sources.
  • non-RRR -alpha-tocopherol refers to any or all of the seven stereoisomers of alpha-tocopherol that are not Ri?R-alpha-tocopherol.
  • non-Ri?R-alpha-tocopherol specifically includes any one of, any combination of, or all of the alpha-tocopherol stereoisomers RftS-alpha-tocopherol, RSR-alpha-tocopherol, RSS-alpha-tocopherol, SRi?-alpha-tocopherol, SRS-alpha-tocopherol, SSR-alpha-tocopherol, and SSS-alpha-tocopherol.
  • a//-rac-alpha-tocopherol which is sometimes referred to as “synthetic Vitamin E,” is used to refer to a blend of all eight stereoisomers of alpha- tocopherol in substantially equimolar amounts, i.e., each stereoisomer comprises about 12.5% of the total amount of alpha-tocopherol.
  • alpha-tocopherol combination refers to a blend of RRR -alpha-tocopherol and non-RftR-alpha-tocopherol, wherein the weight ratio of Ri?R-alpha-tocopherol to non-Ri?R-alpha-tocopherol is from about 0.5:1 to about 1,000:1.
  • the ATC may comprise alpha-tocopherols from natural or synthetic sources. For instance, the ATC would comprise all Ri?R-alpha-tocopherol that is naturally present in any oils or fats used in the nutritional supplement.
  • the Ri?R-alpha-tocopherol contained in the a//-rac-alpha-tocopherol is considered Ri?R-alpha-tocopherol for the purpose of calculating this weight ratio.
  • pre-pregnant woman is used herein to refer to a woman of reproductive age who is planning to become pregnant, and therefore chooses to perform actions such as taking nutritional supplements to prepare her body for the rigors of pregnancy.
  • tissue refers to the organs and fluids contained within or generated by the human body. Tissues include, but are not limited to: organs such as the brain, central nervous system, liver, gastrointestinal tract, uterus, placenta, and skin; and body fluids such as breast milk, blood, blood cells, plasma, lymph, and urine.
  • bioavailable refers to the amount of a nutrient made available to target tissues in the human body through the systemic circulation in the body.
  • bioavailable or “bioavailability” may specifically refer to the ability of a nutrient to transfer from the digestive tract into the lymphatic system or bloodstream of an individual and then into the organs and tissues of the body.
  • the degree of bioavailability of a nutrient increases, the nutrient becomes more likely to enter into and remain in the lymphatic system or bloodstream where it can be absorbed and used by the organs and tissues of the body.
  • the degree of bioavailability of a nutrient decreases, the nutrient becomes more likely to be excreted from the body before entering the lymphatic system or bloodstream.
  • baseline concentration refers to the amount of Ri?R-alpha-tocopherol measured in the tissue of an ingesting subject immediately before, preferably within 6 hours before, the nutritional supplement is ingested.
  • dosage element refers to a discrete item or measured amount of a nutritional supplement used to deliver a predetermined amount of the nutritional supplement to a subject.
  • One or more dosage elements may comprise a single dose of the nutritional supplement, e.g. , a dose may be two capsules or four teaspoons of syrup.
  • Non-limiting examples of dosage elements include capsules, tablets, syrups, protein bars, pre- portioned beverages, etc.
  • capsule refers to a dosage element used to deliver a predetermined amount of a nutritional supplement to a recipient, wherein the capsule comprises a shell surrounding and containing the nutritional supplement.
  • Capsules include, but are not limited to, hard gelatin capsules, starch capsules, cellulose-based capsules, and softgel capsules.
  • tablette refers to a dosage element used to deliver a predetermined amount of a nutritional supplement to a recipient, wherein the tablet is a compressed solid mixture comprising the nutritional supplement and, typically, a solid excipient such as starch or sugar.
  • the tablet is of an appropriate size and shape to be easily swallowed by the recipient.
  • the tablet may be swallowed whole or, where appropriate, may be swallowed after being chewed by the recipient.
  • the term "chewable soft gel” as used herein refers to a dosage element used to deliver a predetermined amount of a nutritional supplement to a recipient, wherein the chewable soft gel comprises the nutritional supplement contained within a gummy gelatin or gelatin-like matrix.
  • the chewable soft gel typically has a pleasant flavor and is designed to be chewed before being swallowed by the recipient.
  • syrup refers to a dosage element used to deliver a predetermined amount of a nutritional supplement to a recipient, wherein the syrup comprises the nutritional supplement in an aqueous liquid solution, suspension, or emulsion.
  • elixir refers to a dosage element used to deliver a predetermined amount of a nutritional supplement to a recipient, wherein the elixir comprises the nutritional supplement in an ethanol-based liquid solution, suspension, or emulsion.
  • the nutritional supplements and corresponding manufacturing methods of the present disclosure can comprise, consist of, or consist essentially of the essential elements of the disclosure as described herein, as well as any additional or optional element described herein or which is otherwise useful in nutritional supplement applications.
  • Tocopherols are a family of related chemicals comprising a chroman ring and a phytyl tail, conforming to the chemical structure shown in FIG. 1.
  • Tocopherols are available in four forms, alpha, beta, gamma, and delta, which differ in the number and position of the methyl (“Me”) groups on the chroman ring (see Table 1 below).
  • Alpha-tocopherol is the tocopherol most commonly referred to as "Vitamin E,” and is the best known and most studied of the tocopherol family.
  • the beta, gamma, and delta forms of tocopherol may also have Vitamin E-type properties in the body, and the American diet actually contains more gamma-tocopherol than alpha-tocopherol.
  • Tocopherols can exist in a number of stereoisomeric forms because of the three chiral carbons in the molecular structure, marked in FIG. 1 by asterisks ("*"). Each chiral carbon has two possible configurations, R or S, so the presence of three chiral carbons means that there are eight distinct stereoisomers (RRR, SSS, RSR, SRS, etc.) of the tocopherol molecule.
  • Natural Vitamin E is a single stereoisomer, Ri?R-alpha-tocopherol
  • synthetic vitamin E (a//-rac-alpha-tocopherol) is an equimolar mixture of all eight isomers, only one of which is RRR-alpha tocopherol.
  • RRR -alpha-tocopherol has the greatest biological activity of the stereoisomers, and is reported to be the dominant form of alpha-tocopherol in the brain.
  • Tocopherols are powerful antioxidants which scavenge reactive oxygen species and free radicals before these oxidants can cause damage in living cells. Tocopherols are particularly useful since they are lipophilic and therefore can protect the fatty structures of a cell, such as the cell wall, from oxidative damage. As discussed above, alpha-tocopherol is thought to prevent or lessen many medical and biological problems associated with oxidative stress. During pregnancy, oxidative stress and damage are associated with problems such as low birth weight and preterm delivery. In addition to its antioxidant properties, alpha- tocopherol is thought to reduce inflammation and enhance the release of prostacyclin in the mother.
  • Prostacyclin inhibits platelet aggregation and increases vasodilation, thereby regulating both the blood flow between the placenta and fetus and the blood flow within the fetus.
  • Increasing maternal blood flow also increases the nutrient supply to the fetus, leading to proper fetal growth.
  • Inadequate levels of prostacyclin can lead to vasoconstriction, which may contribute to preeclampsia in the mother and inadequate blood flow and nutrient supply to the fetus.
  • Tocopherols are prone to reaction and degradation over time, particularly when purified and stored long-term.
  • Tocopherol esters are more stable for long- term storage, and so tocopherols used in nutritional supplements and to fortify processed foods are often in the form of tocopherol acetate or tocopherol succinate. Once ingested, however, tocopherol esters are quickly converted back to free tocopherol in the digestive tract.
  • non-RftR-alpha-tocopherol stereoisomers in all-rac- alpha-tocopherol have typically been considered beneficial.
  • Non-RftR-alpha-tocopherol stereoisomers have typically been thought to provide antioxidant capacity and health benefits which, though less biologically active, are similar to the benefits provided by the RRR -alpha- tocopherol stereoisomer in all-rac-alpha-tocopherol.
  • All-rac-alpha-tocopherol is also less expensive than RRR-alpha-tocopherol.
  • all-rac-alpha-tocopherol is often used as a dietary supplement, both alone and in multivitamins. All-rac-alpha-tocopherol is also used to fortify many processed foods, such as breakfast cereals. Therefore, many people regularly consume all-rac-alpha-tocopherol, even if they do not specifically choose to take supplemental Vitamin E in capsules or multivitamins.
  • the dosage is typically increased to compensate for the lower activity of the non-Ri?R-alpha-tocopherol stereoisomers.
  • Ri?R-alpha-tocopherol The absorption of Ri?R-alpha-tocopherol is of particular concern for pregnant women and infants.
  • the fetus requires alpha-tocopherol for the proper development of the brain and central nervous system, and also for preventing various conditions related to oxidative stress, such as low birth weight and preterm delivery.
  • alpha-tocopherol is thought to enhance the release of prostacyclin, which may then result in increased blood flow and nutrient supply to the fetus and reduced risk of preeclampsia in the mother.
  • Newborns typically have low concentrations of plasma alpha-tocopherol, and premature or low-birth weight infants may be alpha-tocopherol deficient.
  • alpha tocopherol particularly RRR -alpha-tocopherol
  • women who are pre-pregnant, pregnant, or lactating so alpha-tocopherol is available for the developing fetus and infant. Therefore, it is desirable to find methods which increase the amount of Ri?R-alpha-tocopherol in the pre-pregnant, pregnant, or lactating woman's body tissues.
  • the nutritional supplements of the present disclosure comprise a combination of Ri?R-alpha-tocopherol and non-RftR-alpha-tocopherol, wherein the weight ratio of Ri?R-alpha-tocopherol to non-Ri?R-alpha-tocopherol is from about 0.5:1 to about 1000:1.
  • this combination is referred to herein as the "alpha-tocopherol combination" or "ATC.”
  • ATC alpha-tocopherol combination
  • the alpha-tocopherols in the ATC may be in the form of alpha-tocopherol acetates or other alpha-tocopherol esters, as discussed previously.
  • Non-limiting examples of nutritional supplements comprising the ATC include nutritional supplements contained in dosage elements intended for oral consumption.
  • Suitable dosage elements may include medicine-like forms, such as tablets, capsules, chewable soft gels, syrups, and elixirs.
  • Other suitable dosage elements may include nutritional food or beverage products, such as meal replacement bars, protein bars, milk- or soy-based beverages, protein drinks, energy drinks, hydration drinks, enhanced fruit juices, enhanced water, or mix-in powders for beverages.
  • a preferred dosage element for the present nutritional supplement is a capsule.
  • Capsules comprise a shell surrounding and containing the nutritional supplement formulation. The capsule shell dissolves or disintegrates in the digestive tract after the capsule is ingested, thereby releasing the nutritional supplement to be absorbed by the body of the individual ingesting the capsule.
  • Capsule shells are typically made of gelatin, starch, cellulose, or other components that readily dissolve or disintegrate after ingestion, and the composition, manufacture, and use of capsule shells are well known in the art.
  • a particularly preferred dosage element for the present nutritional supplement is a softgel capsule. Softgel capsules are particularly suitable for containing liquid-based ingredients, such as nutrients dissolved, dispersed, or suspended in carrier oil.
  • the shell of a softgel capsule is typically made of gelatin plasticized with glycerin and water, although vegetarian softgel capsules made from starch or carrageenan are also available.
  • Softgel capsule shells are typically made and filled with nutritional supplement formulations in continuous processes that are known in the art.
  • Softgel capsules are made by manufacturers such as Catalent Pharma Solutions, LLC (Somerset, NJ) and Captek Softgel International (Cerritos, CA).
  • Capsules come in a wide range of sizes, and the capsule size should be chosen to contain an appropriate volume or weight of the nutritional supplement formulation and, hence, an appropriate dosage of the ATC.
  • the capsule size can be chosen to contain at least about 0.1 g of nutritional supplement formulation, including from about 0.1 g to about 5 g, from about 0.2 g to about 2.5 g, from about 0.25 g to about 2 g, from about 0.3 g to about 1.5 g, from about 0.35 g to about 1 g, from about 0.4 to about 0.8 g, or from about 0.5 g to about 0.75 g of nutritional supplement formulation.
  • Preferred embodiments are capsules containing from about 0.1 g to about 1.5 g or from about 0.2 g to about 1.0 g of nutritional supplement formulation, as these capsule sizes are easy for most adults to swallow.
  • preferred capsule sizes should be chosen both to contain an effective amount of the ATC, and also be easily swallowed by the subject.
  • the dosage element may be in the form of a nutritional food or beverage product.
  • the dosage element may be in the form of a baked food product, such as a meal replacement bar or a protein bar.
  • the dosage element may be in the form of a mix-in powder which is reconstituted with a suitable liquid, typically water or milk, to form a beverage.
  • the mix-in powder can be in a pre-measured sachet, or can be scooped and measured with a spoon from a bulk container.
  • the dosage element may be in the form of a ready-to-drink beverage, such as a milkshake, protein drink, energy drink, enhanced juice, or enhanced water.
  • the dosage element may be a nutritional product that is formulated with sufficient kinds and amounts of nutrients so as to provide a sole, primary, or supplemental source of nutrition.
  • the nutritional supplements according to the present disclosure may include Ri?R-alpha-tocopherol in any amount that is sufficient for the intended purpose.
  • the nutritional supplements are in a capsule and include RRR-a ⁇ pha- tocopherol in any amount that is sufficient for the intended purpose.
  • RftR-alpha-tocopherol may be present in an amount of at least about 1 mg of RftR-alpha-tocopherol per dose of the nutritional supplement, including from about 1 mg to about 1 ,000 mg, including from about 2 mg to about 500 mg, including from about 5 mg to about 100 mg, including from about 10 mg to about 50 mg of RftR-alpha-tocopherol per dose of the nutritional supplement.
  • a preferred amount of Ri?R-alpha-tocopherol is from about 6 mg to about 200 mg of RRR- alpha-tocopherol per dose of the nutritional supplement.
  • the nutritional supplements according to the present disclosure should contain only a limited amount of non-RftR-alpha-tocopherol in the nutritional supplement formulation.
  • the amount of non-Ri?R-alpha-tocopherol in the nutritional supplement should be less than about 10 mg per dose of the nutritional supplement, preferably less than about 6 mg per dose, more preferably less than about 1 mg per dose, more preferably less than about 0.1 mg per dose, more preferably less than about 0.01 mg per dose, more preferably less than about 0.001 mg per dose of the nutritional supplement.
  • the ratio of the weight of RRR-a ⁇ pha- tocopherol to the weight of non-Ri?R-alpha-tocopherol in the nutritional supplement should be from about 0.5:1 to about 1,000:1, including from about 5:1 to about 500:1, including from about 10:1 to about 200:1, including from about 25:1 to about 100:1.
  • the bioavailability and absorption of Ri?R-alpha-tocopherol that has been added to the present nutritional supplements may be determined by extracting RRR- alpha-tocopherol from tissue samples (e.g., blood, plasma, breast milk, etc.) and analyzing the extract by high-performance liquid chromatography (HPLC).
  • tissue samples e.g., blood, plasma, breast milk, etc.
  • HPLC high-performance liquid chromatography
  • the extracts may be analyzed using an HPLC analysis method that is able to separate and quantify the individual stereoisomers of alpha-tocopherol.
  • Nutritional supplements according to the present disclosure may comprise one or more macronutrients selected from the group consisting of fat, protein, carbohydrate, and mixtures thereof. This is particularly true for nutritional supplements that are in the form of nutritional food or beverage products. Generally, any source of fat, carbohydrate, or protein that is suitable for use in nutritional food or beverage products is also suitable for use herein, provided that such macronutrients are also compatible with the essential elements of the nutritional supplements as defined herein.
  • Carbohydrate concentrations may typically range from about 5 wt% to about 70 wt%, including from about 7 wt% to about 60 wt%, including from about 10 wt% to about 55 wt%, by weight of the nutritional supplement.
  • Fat concentrations most typically range from about 0.5 wt% to about 35 wt%, including from about 0.75 wt% to about 30 wt%, including from about 1 wt% to about 28 wt%, and also including from about 2 wt% to about 5 wt%, by weight of the nutritional supplement.
  • Protein concentrations may range from about 1 wt% to about 85 wt%, from about 5 wt% to about 50 wt%, from about 7 wt% to about 32 wt%, or from about 8 wt% to about 30 wt%, by weight of the nutritional supplement. Additional ranges for carbohydrates, fats, and proteins, based on percent of calories of the nutritional supplement, are set forth in Table 2.
  • Non-limiting examples of suitable fats in the nutritional supplements described herein may be selected from the group of coconut oil, fractionated coconut oil, soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, medium chain triglyceride oil, sunflower oil, high oleic sunflower oil, palm and palm kernel oils, palm olein, canola oil, walnut oil, flaxseed oil, marine oils, cottonseed oil, borage oil, algal oils, fungal oils, and combinations thereof. It should be noted that fats and oil typically contain RRR-a ⁇ pha- tocopherol naturally.
  • the RftR-alpha-tocopherol contributed by any fats or oils in the nutritional supplements described herein should be considered as part of the RftR-alpha-tocopherol component of the ATC for the purpose of calculating the Ri?R-alpha-tocopherol to non-Ri?R-alpha-tocopherol weight ratio.
  • Non-limiting examples of suitable carbohydrates or sources thereof in the nutritional supplements may be selected from the group of maltodextrin, hydrolyzed or modified starch or cornstarch, glucose polymers, corn syrup, corn syrup solids, rice-derived carbohydrates, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols (e.g., maltitol, erythritol, or sorbitol), and combinations thereof.
  • Non-limiting examples of suitable protein or sources thereof in the nutritional supplements may be selected from the group of partially hydrolyzed or non- hydrolyzed proteins derived from any suitable source, such as milk (e.g., casein or whey), animal (e.g., meat or fish), cereal (e.g., rice or wheat), vegetable (e.g., pea, potato, or bean), or combinations thereof.
  • milk e.g., casein or whey
  • animal e.g., meat or fish
  • cereal e.g., rice or wheat
  • vegetable e.g., pea, potato, or bean
  • Non-limiting examples of such proteins include whole cow's milk, partially or completely defatted milk, milk protein isolates, milk protein concentrates, casemates, casein protein isolates, whey protein, whey protein concentrates, soy protein isolates, soy protein concentrates, pea protein isolates, pea protein concentrates, hydrolyzed yeast, potato, rice, wheat, canola, animal collagen, gelatin, bovine colostrum, human colostrum, glycomacropeptides, mycoproteins, amino acids, and combinations thereof.
  • the nutritional supplements include a protein component that consists of only intact or partially hydrolyzed protein; that is, the protein component is substantially free of any protein that has a degree of hydrolysis of 25% or more.
  • the term "partially hydrolyzed protein” refers to proteins having a degree of hydrolysis of less than 25%, including less than 20%>, including less than 15%o, including less than 10%, and including proteins having a degree of hydrolysis of less than 5%.
  • the degree of hydrolysis is the extent to which peptide bonds are broken by a hydrolysis chemical reaction.
  • the degree of protein hydrolysis is determined by quantifying the amino nitrogen to total nitrogen ratio (AN/TN) of the protein component of the selected supplement.
  • the amino nitrogen component is quantified by USP titration methods for determining amino nitrogen content, while the total nitrogen component is determined by the Tecator® Kjeldahl method. These analytical methods are well known.
  • the nutritional supplements described herein may further comprise other optional ingredients that may modify the physical, chemical, hedonic, or processing characteristics of the supplements or serve as additional nutritional components.
  • Many such optional ingredients are known or otherwise suitable for use in other nutritional products and may also be used in the supplements described herein, provided that such optional ingredients are safe and effective for oral administration and are compatible with the essential and other ingredients in the selected product form.
  • Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifying agents, buffers, additional nutrients as described herein, colorants, flavors, thickening agents, stabilizers, and so forth.
  • the supplements may further comprise minerals, non-limiting examples of which include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, selenium, chloride, and combinations thereof.
  • the supplements may further comprise vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B12, other carotenoids, niacin, folic acid, pantothenic acid, biotin, inositol, salts and derivatives thereof, and combinations thereof.
  • vitamins or related nutrients include vitamin A, vitamin C, vitamin D, vitamin K, thiamine, riboflavin, pyridoxine, vitamin B12, other carotenoids, niacin, folic acid, pantothenic acid, biotin, inositol, salts and derivatives thereof, and combinations thereof.
  • the supplements may comprise a compound selected from the group of beta-carotene, lycopene, lutein, zeaxanthin, astaxanthin, choline, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and combinations thereof.
  • the supplements may also include one or more masking agents to reduce or otherwise obscure bitter flavors and after taste.
  • Suitable masking agents include natural and artificial sweeteners, sodium sources such as sodium chloride, and hydrocolloids, such as guar gum, xanthan gum, carrageenan, gellan gum, and combinations thereof.
  • the amount of masking agent in the supplement may vary depending upon the particular masking agent selected, other ingredients in the nutritional supplement formulation, and other supplement or product target variables. Such amounts, however, most typically range from at least 0.1 wt%, including from about 0.15 wt% to about 3.0 wt%, and also including from about 0.18 wt% to about 2.5 wt%, by weight of the nutritional supplement formulation.
  • the nutritional supplements described herein increase the amount of Ri?R-alpha-tocopherol in body tissues of a pre-pregnant, pregnant, or lactating woman consuming the nutritional supplement.
  • the nutritional supplement comprises a combination of RftR -alpha-tocopherol and non-RftR -alpha-tocopherol, optionally in the form of alpha- tocopherol esters, wherein the weight ratio of Ri?R-alpha-tocopherol to non-RftR-alpha- tocopherol is from about 0.5:1 to about 1,000: 1.
  • this combination is referred to herein as the "alpha-tocopherol combination" or "ATC.”
  • Nutritional supplements including the ATC can be administered to pre- pregnant, pregnant, or lactating women to increase the RRR -alpha-tocopherol present in their tissues.
  • This increase in RRR -alpha-tocopherol in their bodies will provide antioxidants, promote cardiovascular health, and maintain overall health for the women, and will also provide an increased source of RRR -alpha-tocopherol for each woman's developing fetus or breastfeeding infant.
  • the methods of the present disclosure may be directed to pre-pregnant or pregnant women, who are administered prenatal nutritional supplements comprising the ATC to promote healthy development in their developing fetus.
  • the methods of the present disclosure may be directed to lactating women, who are administered post-partum nutritional supplements comprising the ATC to promote healthy development in their infant.
  • the methods of the present disclosure may be directed to developing fetuses, who receive RRR -alpha-tocopherol from pregnant women receiving prenatal nutritional supplements comprising the ATC.
  • the methods of the present disclosure may be directed to breast milk-fed infants, who receive RRR -alpha-tocopherol in breast milk from lactating women receiving post-partum nutritional supplements comprising the ATC.
  • the methods of the present disclosure preferably include continuous, daily administration of the nutritional supplements as described herein.
  • Such development and maintenance methods may be directed at subjects such as pre- pregnant, pregnant, and lactating women, developing fetuses, and breastfed infants.
  • RRR-a ⁇ pha- tocopherol is administered to the woman in a nutritional supplement comprising the ATC of the present invention.
  • the woman desirably consumes at least one dose of the nutritional supplement comprising the ATC daily, and in some embodiments, may consume two, three, or even more doses per day.
  • a dose of the nutritional supplement is typically one or two dosage elements, such as capsules, tablets, meal replacement bars, beverages, etc., although it is envisioned that doses containing more dosage elements may be used to deliver an effective amount of the ATC to the subject.
  • the methods of the present disclosure include continuous day after day administration, as well as periodic or limited administration, although continuous day after day administration is generally desirable.
  • the "RRR- alpha-tocopherol” (or “RRR”) supplement formulation comprised Ri?R-alpha-tocopherol acetate in safflower oil.
  • the "a//-rac-alpha-tocopherol” (or “all-rac”) supplement formulation comprised soybean oil and a//-rac-alpha-tocopherol acetate.
  • Soft gelatin capsule shells were filled with one of each supplement formulation.
  • the "RRR” capsules each contained about 20 mg of RftR-alpha-tocopherol acetate, and the "all-rac” capsules contained about 50 mg a//-rac-alpha-tocopherol acetate (i.e., about 6 mg Ri?R-alpha-tocopherol acetate and about 44 mg non-Ri?R-alpha-tocopherol acetate).
  • Healthy lactating women began the study 4-6 weeks post-partum. The women were divided into three groups, and each woman took two supplement capsules daily for six weeks. One group consumed two capsules of the "RRR” supplement daily; one group consumed one capsule of the "RRR” supplement and one capsule of the "all-rac” supplement daily; and the third group consumed two capsules of the "all-rac” supplement daily. The women also recorded their daily food consumption, so their total Ri?R-alpha-tocopherol intake could be determined. The women were asked not to take other daily vitamins or supplements containing any form of Vitamin E.
  • FIG. 2 illustrates the change, from baseline to 6 weeks post supplementation, of the output of RftR-alpha-tocopherol in the breast milk of the lactating women consuming the designated supplement capsules. The results are expressed as a change over time to correct for the baseline concentration of RftR-alpha-tocopherol in the breast milk of each woman.
  • FIG. 2 shows the average ratio of Ri?R-alpha-tocopherol measured in the breast milk to the total RftR-alpha-tocopherol intake from both the nutritional supplement and each woman's diet.
  • the women taking the "mixed" supplement had a 1.4-fold increase in the ratio of Ri?R-alpha-tocopherol in their breast milk as compared to the "all-rac” group.
  • the women taking two capsules daily of the "RRR” supplement had a 2.6-fold increase in the ratio of Ri?R-alpha-tocopherol in their breast milk as compared to the "all-rac” group.
  • FIG. 3 illustrates the change, from baseline to 6 weeks post supplementation, of the output of RftR-alpha-tocopherol in the plasma of the lactating women consuming the designated supplement capsules. The results are expressed as a change over time to correct for the baseline concentration of Ri?R-alpha-tocopherol in the plasma of each woman.
  • FIG. 3 shows the average ratio of plasma RftR-alpha-tocopherol to the total RRR- alpha-tocopherol intake from both the nutritional supplement and each woman's diet. Calculating this ratio corrected the results for any effect of merely taking a higher dose of Ri?R-alpha-tocopherol or eating more foods that are naturally high in Ri?R-alpha-tocopherol.
  • the data in the graph shows that the RftR-alpha-tocopherol ratio (plasma: total consumed) increases as the amount of non-RftR-alpha-tocopherol consumed decreases.
  • the women taking two capsules daily of the "all-rac” supplement showed a small decrease in the ratio of Ri?R-alpha-tocopherol in their plasma after six weeks.
  • the women taking the "mixed” supplement (one capsule each of the "all-rac” and “RRR” supplements daily) had a 6.8-fold increase in the ratio of RftR-alpha-tocopherol in their plasma as compared to the "all- rac” group.
  • the women taking two capsules daily of the "RRR” supplement had a 9.4-fold increase in the ratio of RftR-alpha-tocopherol in their plasma as compared to the "all-rac” group.

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Abstract

L'invention concerne des procédés d'augmentation de RRR-alpha-tocophérol dans les tissus d'une femme avant la grossesse, d'une femme enceinte ou d'une femme qui allaite. La femme reçoit un complément nutritionnel contenant un mélange d'alpha-tocophérols comportant du RRR-alpha-tocophérol et du non-RRR-alpha-tocophérol. Le mélange d'alpha tocophérols a un rapport en poids du RRR-alpha-tocophérol au non-RRR-alpha-tocophérol entre environ 0,5:1 à environ 1000:1. L'invention concerne aussi des procédés pour augmenter le RRR-alpha-tocophérol pour un fœtus, où le fœtus reçoit du RRR-alpha-tocophérol en quantité accrue d'une femme enceinte qui a reçu un complément nutritionnel prénatal contenant un mélange d'alpha-tocophérols avec un rapport en poids du RRR-alpha-tocophérol au non-RRR-alpha-tocophérol entre environ 0,5:1 à environ 1000:1. L'invention concerne aussi des procédés d'augmentation de RRR-alpha-tocophérol pour un nourrisson nourri au lait maternel, où le nourrisson reçoit du RRR-alpha-tocophérol en quantité accrue à partir du lait maternel d'une femme enceinte qui a reçu un complément nutritionnel post-partum contenant un mélange d'alpha-tocophérols avec un rapport en poids du RRR-alpha-tocophérol au non-RRR-alpha-tocophérol entre environ 0,5:1 à environ 1000:1. Ces procédés fournissent au corps de la femme du RRR-alpha-tocophérol en quantité accrue, qui est ensuite disponible de préférence pour son fœtus en développement ou le nourrisson.
PCT/US2015/026297 2014-04-18 2015-04-17 Procédé d'augmentation de la biodisponibilité de rrr-alpha-tocophérol fourni par un complément nutritionnel prénatal et post-partum WO2015161153A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210169114A1 (en) * 2017-12-01 2021-06-10 Societe Des Produits Nestle S.A Maternal supplement

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060171993A1 (en) * 2002-03-29 2006-08-03 Bridget Barrett-Reis Method of improving antioxidant status of an infant

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060171993A1 (en) * 2002-03-29 2006-08-03 Bridget Barrett-Reis Method of improving antioxidant status of an infant

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
CHARLOTTE LAURIDSEN ET AL: "Nutrient Requirements Lactating Sows and Suckling Piglets Preferentially Incorporate RRR-over All-rac-Tocopherol into Milk, Plasma and Tissues", 1 January 2002 (2002-01-01), pages 1258 - 1264, XP055197840, Retrieved from the Internet <URL:http://jn.nutrition.org/content/132/6/1258.full.pdf> [retrieved on 20150623] *
HIDIROGLOU N ET AL: "Serum total cholesterol, high-density lipoprotein-cholesterol and triglyceride concentrations in lambs following supplementation with various forms of tocopherol", REPRODUCTION NUTRITION DEVELOPMENT, vol. 33, no. 3, 1993, pages 263 - 268, XP055197586, ISSN: 0926-5287 *
JENSEN ET AL.: "Bioavailability of a-tocopherol stereoisomers in rats depends on dietary doses of all-rac- or RRR-a-tocopherol acetate", BR. J NUTR., vol. 95, 2006, pages 477 - 487
R V ACUFF ET AL: "Transport of deuterium-labeled tocopherols during pregnancy", THE AMERICAN JOURNAL OF CLINICAL NUTRITION, 1 March 1998 (1998-03-01), UNITED STATES, pages 459, XP055197764, Retrieved from the Internet <URL:http://www.ncbi.nlm.nih.gov/pubmed/9497190> [retrieved on 20150623] *
ROQUET ET AL: "Cattle blood plasma and red blood cell alpha-tocopherol levels in response to different chemical forms and routes of administration of vitamin E", J ANIM SCI., 1 January 1992 (1992-01-01), pages 2542 - 2550, XP055197829 *
SK JENSEN ET AL: "alpha-Tocopherol Stereoisomers", VITAMINS AND HORMONES, ACADEMIC PRESS, NEW YORK, NY, US, vol. 76, 1 January 2007 (2007-01-01), pages 281 - 308, XP008142974, ISSN: 0083-6729, Retrieved from the Internet <URL:http://www.sciencedirect.com/science/article/pii/S0083672907760107> DOI: 10.1016/S0083-6729(07)76010-7 *
SØREN K. JENSEN ET AL: "Bioavailability of [alpha]-tocopherol stereoisomers in rats depends on dietary doses of all-rac- or RRR-[alpha]-tocopheryl acetate", BRITISH JOURNAL OF NUTRITION, vol. 95, no. 03, 1 March 2006 (2006-03-01), pages 477, XP055120276, ISSN: 0007-1145, DOI: 10.1079/BJN20051667 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210169114A1 (en) * 2017-12-01 2021-06-10 Societe Des Produits Nestle S.A Maternal supplement
US11696595B2 (en) * 2017-12-01 2023-07-11 Societe Des Produits Nestle S.A. Maternal supplement

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