WO2019165222A1

WO2019165222A1 - Dietary macro/micronutritional supplement and applications thereof

Info

Publication number: WO2019165222A1
Application number: PCT/US2019/019171
Authority: WO
Inventors: Atif DABDOUB
Original assignee: Dabdoub Atif
Priority date: 2018-02-23
Filing date: 2019-02-22
Publication date: 2019-08-29

Abstract

Provided herein is a nutritional supplement designed to support kidney and cardiac function as well as mitochondrial energy function needs in patients undergoing hemodialysis. This supplement replenishes essential vitamins and minerals that are lost during dialysis, does not contain compounds that may specifically cause harm to dialysis patients, and provides support for tissues undergoing oxidative stress. The supplement is also useful for addressing chronic health conditions and illnesses.

Description

DIETARY MACRO/MICRONUTRITIONAL SUPPLEMENT AND APPLICATIONS

THEREOF

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority upon U.S. provisional application Serial No. 62/634,252, filed February 23, 2018. This application is hereby incorporated by reference in its entirety for all of its teachings.

BACKGROUND

The kidneys of an adult human filter approximately 190 liters of blood daily; due to their role, these organs are susceptible to damage and dysfunction that may progress, over time, to disease. Chronic Kidney Disease: http://www.lifeextension.com/protocols/kidnev-urinarv/kidnev-disease/paqe-04 High blood pressure, elevated blood sugar (including the presence of diabetes), high-protein diets, smoking, obesity, family history of kidney disease or failure, and a patient’s history of heart problems all threaten the health of the kidneys, inflicting damage that has the potential to be lethal. In many cases, when the kidneys fail to perform adequately, kidney dialysis is required.

Essential amino acids such as L-carnitine can be essentially lost (70-80%) during dialysis; L-carnitine deficiency is associated with muscle aches and fatigue, confusion, hypoglycemia, cardiomyopathy, fatty liver, muscle necrosis, abnormal lipid storage, and other conditions.

Oxidative stress, which is caused by an excess of free radicals and harmful molecules that can damage basic cellular constituents such as lipids, proteins, and DNA, can result from L-carnitine deficiency and is an especially dangerous condition for patients undergoing dialysis. Inadequate energy management in cardiac tissues brought on by L-carnitine deficiency can lead to cardiovascular complications including heart attack and heart failure. Further stressors include an excessive filtration burden on the kidneys resulting from the need to handle advanced glycation and lipoxidation end products and inflammation, especially when kidney function decreased to the point that dialysis is required. Many essential nutrients, including water-soluble vitamins such as B complex vitamins and vitamin C and minerals such as zinc and selenium are depleted from the body during dialysis treatment. Further, other nutrients such as vitamin D, which is primarily produced by the healthy kidney and, in case of kidney failure, vitamin D synthesis ceases, or, is significantly affected. Other nutrients, however, such as fat-soluble vitamins, can accumulate in the tissues to dangerous levels in dialysis patients and should not be supplemented.

What is needed is a nutritional supplement that can replenish the supply of basic nutrients to the body that are lost by dialysis, without providing the excess of fat soluble vitamins that could be damaging in high quantities. Ideally, this supplement would also provide nutrients, including but not limited to L-carnitine, that support overall kidney health and combat the effects of oxidative stress. In addition to replenishing these essential nutrients, the supplement would ideally provide coenzyme Q₁₀, which is a key component of the mitochondrial electron transport chain that is known to be important to mitochondrial energy generation (i.e. , ATP synthesis). Finally, polyunsaturated fatty acids such as, for example, marine omega 3 fatty acids, are also removed from the body with chronic kidney dialysis. These compounds are lipid soluble macronutrients that are important to metabolism (i.e., energy production captured in the form of ATP).

Ideally, the nutritional supplement could also address illnesses and medical conditions, including those associated with lifestyle factors or chronic health issues including, but not limited to, diet, such as type II diabetes, dementia including Alzheimer’s disease, cholesterol, heart disease, stroke, stress, hypertension, anemia, overweight, oral health, athletic performance, and sleep.

SUMMARY

Provided herein is a nutritional supplement designed to support kidney and cardiac function as well as mitochondrial energy function needs in patients. The supplement is also useful for addressing chronic health conditions and illnesses.

The advantages of the materials, methods, and devices described herein will be set forth in part in the description that follows, or may be learned by practice of the aspects described below. The advantages described below will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several aspects described below.

Figure 1 demonstrates how the supplements described herein can improve the ability of subjects to do physically strenuous activities.

Figure 2 demonstrates how the supplements described herein can improve the ability of subjects to do moderate strenuous activities.

Figure 3 demonstrates how the supplements described herein can improve the mood in subjects.

Figure 4 demonstrates how the supplements described herein can reduce fatigue in subjects.

DETAILED DESCRIPTION

Before the present materials, articles, and/or methods are disclosed and described, it is to be understood that the aspects described below are not limited to specific compounds, synthetic methods, or uses, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting.

In the specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings:

It must be noted that, as used in the specification and the appended claims, the singular forms“a,”“an,” and“the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to“a citrus bioflavonoid” includes mixtures of two or more citrus bioflavonoids, and the like.

“Optional” or“optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. For example, the nutritional supplements described herein may optionally contain turmeric, where the turmeric may or may not be present.

As used herein, the term“about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be“a little above” or“a little below” the endpoint without affecting the desired result.

“Unit dose” refers to a discrete amount of formulation to be administered to a subject. The compositions and formulations disclosed herein are packaged into discrete dosages each containing predetermined quantities of active compounds calculated based on the needs and medical history of the subject.

A“pharmaceutically-acceptable compound” is used to refer to a neutral complex. In some aspects, a pharmaceutically-acceptable compound may be more economical to produce, may have increased chemical stability, may allow manipulation of the compound’s pharmacokinetics and bioavailability, may make the compound easier to administer, or a combination thereof. In a further aspect, a pharmaceutically-acceptable compound can alter a compound’s dissolution or solubility. In one aspect, the pharmaceutically-acceptable compound can be an ionic compound. For example, the pharmaceutically-acceptable compound can be the reaction product between an organic acid (e.g., citric acid) and base (e.g., calcium hydroxide) to produce the ionic compound calcium citrate.

The term“reduce” as used herein is defined as decreasing the likelihood of the occurrence of one or more symptoms using the supplements described herein when compared to the same symptom in the absence of using the supplements described herein.

The term“prevent” as used herein is defined as eliminating or reducing the likelihood of the occurrence of one or more symptoms using the supplements described herein when compared to the same symptom in the absence of using the supplements described herein.

The term“promote” as used herein is defined as increasing the likelihood of improving one or more symptoms using the supplements described herein when compared to the same symptom in the absence of using the supplements described herein.

Throughout this specification, unless the context dictates otherwise, the word “comprise,” or variations such as “comprises” or “comprising,” will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the inclusion of any other integer or step or group of integers or steps.

References in the specification and concluding claims to parts by weight, of a particular element or component in a composition or article, denote the weight relationship between the element or component and any other elements or components in the composition or article for which a part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight of component Y, X and Y are present at a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are contained in the compound.

As used herein, a plurality of items, structural elements, compositional elements, and/or materials may be presented in a common list for convenience. However, these lists should be construed as though each member of the list is individually identified as a separate and unique member. Thus, no individual member of any such list should be construed as a de facto equivalent of any other member of the same list based solely on its presentation in a common group, without indications to the contrary.

Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and thus should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range was explicitly recited. As an illustration, a numerical range of “about 1 to about 5” should be interpreted to include not only the explicitly recited values of about 1 to about 5, but also to include individual values and sub-ranges within the indicated range. Thus, included in this numerical range are individual values such as 2, 3, and 4, the sub ranges such as from 1-3, from 2-4, from 3-5, etc., as well as 1 , 2, 3, 4, and 5 individually. The same principle applies to ranges reciting only one numerical value as a minimum or maximum. Furthermore, such an interpretation should apply regardless of the breadth of the range or the characteristics being described.

Disclosed are materials and components that can be used for, can be used in conjunction with, can be used in preparation for, or are products of the disclosed compositions and methods. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc., of these materials are disclosed, that while specific reference to each individual and collective combination and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, if a water soluble vitamin is disclosed and discussed and a number of different minerals are discussed, each and every combination of water soluble vitamin and mineral that is possible is specifically contemplated unless specifically indicated to the contrary. For example, if a class of water soluble vitamins A, B, and C are disclosed, as well as a class of minerals D, E, and F, and an example combination of A + D is disclosed, then even if each is not individually recited, each is individually and collectively contemplated. Thus, in this example, each of the combinations A + E, A + F, B + D, B + E, B + F, C + D, C + E, and C + F is specifically contemplated and should be considered from disclosure of A, B, and C; D, E, and F; and the example combination of A + D. Likewise, any subset or combination of these is also specifically contemplated and disclosed. Thus, for example, the sub-group of A + E, B + F, and C + E is specifically contemplated and should be considered from disclosure of A, B, and C; D, E, and F; and the example combination of A + D. This concept applies to all aspects of the disclosure including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed with any specific embodiment or combination of embodiments of the disclosed methods, each such combination is specifically contemplated and should be considered disclosed. As used herein, a vitamin is an organic compound that is required in small quantities to support essential body functions including growth and cellular maintenance. In some aspects, vitamins cannot be produced by the body (e.g., vitamin C) or are not produced in sufficient quantities to meet a patient’s needs and must be supplied via external sources. Handbook of Nonprescription Drugs, 11^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 361. In one aspect, many diets are insufficient in one or more key vitamins and supplements are often indicated, especially in the cases of chronically ill individuals such as patients undergoing kidney dialysis. In one aspect, a vitamin can act as a cofactor to assist an enzyme in carrying out an essential biochemical reaction.

In one aspect, the formulations disclosed herein include one or more water soluble vitamins. In one aspect, water-soluble vitamins are depleted during kidney dialysis and should be replenished to maintain overall health and well- being. In a further aspect, the supplement disclosed herein provides water- soluble vitamins including the B complex vitamins and vitamin C.

B Complex Vitamins

In one aspect, the formulations disclosed herein include one or more B vitamins. In this aspect, B vitamins generally act as cofactors or coenzymes or precursors needed to make cofactors or coenzymes. In a further aspect, B vitamins are not stored in the body and must be regularly supplied by dietary or other means to avoid deficiency. In one aspect, co-supplementation of vitamins B₆, Bg_, and B_I2 along with iron is especially effective against osteoporosis and anemia while also improving immune function. In a further aspect, all B complex vitamins can be used instead of just one or two.

In another aspect, low levels of B vitamins can affect the manufacture of neurotransmitters and contribute to stress and anxiety. In this aspect, supplementation of B vitamins can reduce stress related to their deficiency. In one aspect, low levels of B vitamins are caused by chronic kidney dialysis, the use of diuretics, and overconsumption of refined carbohydrates, since digestion of many carbohydrates requires the use of B vitamins. In one aspect, inadequate B vitamin intake is linked to blood sugar surges in patients who consume too many refined carbohydrates.

In one aspect, thiamin, or vitamin B^ is included in the formulations disclosed herein. In this aspect, thiamin may be important to nerve and muscle health, production of hydrochloric acid in the stomach, and treatment of constipation and fatigue, as well as assisting digestion of some carbohydrates and proteins. In one aspect, the thiamine source is thiamine mononitrate. In one aspect, the amount of vitamin B-\ present per unit dose is from 0.1 mg to 50 mg, 0.1 mg to 25 mg, 0.1 mg to 10 mg, 0.1 mg to 5 mg, 0.1 mg to 2 mg, or 0.1 mg to 1 mg. In another aspect, 0.5 mg to 2 mg of thiamine is present per unit dose of the supplement.

In another aspect, riboflavin, or vitamin B₂, is included in the formulations disclosed herein. In this aspect, riboflavin may be important for growth, red blood cell production, and eye health, as well as assisting in the digestion of some carbohydrates, fats, ketone bodies, and proteins. In one aspect, the riboflavin source is molecular riboflavin. In one aspect, the amount of vitamin B₂ present per unit dose is from 0.1 mg to 2 mg, 0.5 mg to 2 mg, or 0.5 mg to 1 mg. In another aspect, 0.5 to 2 mg of riboflavin is present per unit dose of the supplement.

In still another aspect, nicotinic acid or nicotinamide, also known as niacinamide or vitamin B₃, is included in the formulations disclosed herein. Further in this aspect, vitamin B₃ is important to digestive system health and may assist in the digestion of some carbohydrates, as well as in the production of various sex and stress-related hormones. Still further in this aspect, niacin may be useful in reducing cholesterol levels in the blood. In one aspect, the niacinamide source is molecular niacinamide. In one aspect, the amount of vitamin B₃ present per unit dose is from 1 mg to 40 mg, 5 mg to 30 mg, or 5 mg to 25 mg. In another aspect, 5 to 25 mg of niacinamide is present per unit dose of the supplement. In one aspect, the formulations disclosed herein include pantothenic acid, or vitamin B₅. In this aspect, pantothenic acid may be important for red blood cells production, digestive system health, adrenal gland health, and the digestion of some carbohydrates. In one aspect, the pantothenate source is D-calcium pantothenate. In one aspect, the amount of vitamin B₅ present per unit dose is from 1 mg to 20 mg, 1 mg to 15 mg, or 5 mg to 10 mg. In another aspect, 5 to 10 mg of L- or D-calcium pantothenate is present per unit dose of the supplement.

In another aspect, the formulations disclosed herein include pyridoxal phosphate (also occurring as pyridoxine), or vitamin B₆. Further in this aspect, pyridoxal phosphate may be important for brain health and the production of red blood cells and immune system cells. In a further aspect, deficiencies in vitamin B₆ have been linked to diabetes, nervous system disorders, and heart disease. In one aspect, the pyridoxine source is pyridoxine hydrochloride. In one aspect, the amount of vitamin B₆ present per unit dose is from 1 mg to 100 mg, 1 mg to 50 mg, or 1 mg to 10 mg. In another aspect, 1 to 10 mg of pyridoxine hydrochloride is present per unit dose of the supplement.

In still another aspect, the formulations disclosed herein include biotin, or vitamin B₇. In a further aspect, biotin is important to various aspects of metabolism and may be important in strengthening the hair and nails as well as in the metabolism of fats and amino acids. In one aspect, the biotin source is molecular biotin. In one aspect, the amount of vitamin B₇ present per unit dose is from 10 pg to 500 pg, 10 pg to 300 pg, or 10 pg to 100 pg. In another aspect, 10 to 100 pg of biotin is present per unit dose of the supplement.

In one aspect, the formulations disclosed herein include folate, also known as folic acid or vitamin B₉. Further in this aspect, folic acid may be important for brain function, mental health, red blood cells production, and production of nucleic acids. In one aspect, the folate source is folic acid. In one aspect, the amount of vitamin B₉ present per unit dose is from 0.05 mg to 1 mg, 0.1 mg to 1 mg, or 0.1 mg to 0.5 mg. In another aspect, 0.2 to 0.4 mg of folic acid is present per unit dose of the supplement. In another aspect, cobalamin, or vitamin B₁₂, is included in the formulations disclosed herein. Further in this aspect, the cobalamin may be present as the cyanocobalamin, hydroxycobalamin, adenosylcobalamin, or methylcobalamin form. In another aspect, cobalamin is important to nervous system health, the production of red blood cells, and synthesis of nucleic acids. In a further aspect, cobalamin works synergistically with folate with respect to red blood cell production. In one aspect, the cobalamin source is cyanocobalamin. In one aspect, the amount of vitamin B₁₂ present per unit dose is from 1 pg to 150 pg, 1 pg to 100 pg, 1 pg to 50 pg, 1 pg to 25 pg, or 1 pg to 10 pg. In another aspect, 3 to 6 pg of cyanocobalamin is present per unit dose of the supplement.

Vitamin C

In one aspect, the formulations disclosed herein include ascorbic acid or vitamin C. In a further aspect, vitamin C is important to the immune system, collagen production, and wound healing. Further in this aspect, vitamin C is needed for the biosynthesis of hydroxyproline, which is important in the synthesis of collagen, osteoid, and dentin.

In a further aspect, vitamin C is a potent antioxidant that can fight free radical damage. In a still further aspect, vitamin C may assist with the uptake of non-heme iron. In yet another aspect, vitamin C helps to protect folate from oxidative damage.

In one aspect, the amount of vitamin C present per unit dose is from 10 mg to 2,000 mg, 10 mg to 1 ,500 mg, 10 mg to 1 ,000 mg, 100 mg to 500 mg, or 100 mg to 300 mg. In another aspect, 100 to 300 mg of vitamin C (as ascorbic acid) is provided per unit dose of the supplement.

Fat-soluble vitamins are absorbed in the small intestine and are stored in and can accumulate in body tissues. In some aspects, when excessive quantities of fat-soluble items are ingested, this can be toxic to the body.

Vitamins A, E, and K

In one aspect, vitamins A, E, and K can accumulate to toxic levels in body tissue of patients undergoing dialysis. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 366. Further in this aspect, supplementation of these vitamins for kidney dialysis patients is contraindicated. In another aspect, the supplements disclosed herein do not include vitamins A, E, and K.

Vitamin D

In another aspect, vitamin D is a fat-soluble vitamin that is usually activated by healthy or well-functioning kidneys. In one aspect, in the case of kidney failure, the body cannot produce enough vitamin D and it should be supplemented in patients with kidney failure. However, in another aspect, a patient’s medical providers may decide vitamin D supplementation is not required and/or would cause further harm. In any of the above aspects, the supplement may or may not include a source of vitamin D, to be given at the discretion of healthcare providers on a case-by-case basis.

In one aspect, when vitamin D is included in the formulations disclosed herein, it may improve bone health and immune system function and may protect against certain cancers. In a further aspect, vitamin D can increase calcium and phosphate absorption from the small intestine, is important in bone mineralization, and maintains proper calcium and phosphorus levels in the serum. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 368.

In one aspect, the amount of vitamin D present per unit dose is from 1 pg to 100 pg, 1 pg to 50 pg, or 1 pg to 20 pg. In another aspect, 5 to 10 pg of vitamin D (as cholecalciferol) are provided per unit dose of the supplements disclosed herein.

As used herein, a mineral is an inorganic element that is obtained from food or supplementation and is required for the functioning of the human body. Minerals include, but are not limited to, calcium, chromium, copper, iron, magnesium, manganese, molybdenum, nickel, potassium, selenium, sodium, vanadium, cobalt, and zinc. In one aspect, a mineral can act as a cofactor. In other aspects, minerals can be used for cell signaling, or can be an essential structural component of the body (e.g., calcium in bone), or can associate with proteins, nucleic acids, lipids, and carbohydrates to maintain particular secondary, tertiary, and quaternary structures.

In another aspect, the mineral can be part of a chelate complex. Chelates have a cyclic structure in which a central metallic ion is held tight via covalent- coordinate bonds to form a coordinate compound, or, a chelate complex. Furthermore, chelates occur abundantly in nature; for example, chlorophyll complexed with magnesium, hemoglobin with iron, Vitamin B12 with cobalt hemocyanin with copper as well as enzymes that contain vanadium or molybdenum.

Chronic kidney dialysis can deplete the body of essential minerals. In this aspect, the supplements disclosed herein include a number of important minerals.

Calcium

In one aspect, the formulations disclosed herein include a pharmaceutically-acceptable compound of calcium. In a further aspect, calcium supplementation can be useful in preventing osteoporosis since calcium is a major component of bones and teeth. In a still further aspect, calcium’s absorption and effects are enhanced or aided by vitamin D and parathyroid hormone. In still another aspect, calcium may be important to B complex vitamin absorption and is important to the functional integrity of many cells. In yet another aspect, calcium requirements may increase with increased protein consumption.

In one aspect, the calcium is provided as an ionic compound of calcium. Examples of such compounds include, but are not limited to, calcium citrate, calcium citrate tetrahydrate, calcium lactate pentahydrate, and calcium ascorbate. In one aspect, the formulations described herein include an ionic compound of calcium in an amount such that there is 100 mg to 2,500 mg, 100 mg to 2,000 mg, 100 mg to 1 ,500 mg, 100 mg to 1 ,000 mg, or 100 mg to 750 mg of calcium per unit dose. For example, calcium citrate tetrahydrate has a molecular weight of 570.49, of which calcium is 21.08%. Thus, in order for the formulation to have 500 mg of calcium per unit dose, there will be approximately 2,372.3 mg of calcium citrate tetrahydrate per unit dose. In another aspect, 250 to 500 mg of calcium is provided per unit dose of the supplements disclosed herein.

Magnesium

In one aspect, the formulations disclosed herein include a pharmaceutically-acceptable compound of magnesium. In a further aspect, magnesium is necessary for the proper functioning of calcium in the body such as, for example, assisting in entry of calcium ions into cells, thus preventing calcification of tissues. In some aspects, magnesium supplementation may support healthy heart function.

In one aspect, magnesium is required for normal bone structure formation and the functioning of several hundred enzymes, especially those with ATP- dependent phosphorylation, protein synthesis, and carbohydrate metabolism. In a further aspect, magnesium in the extracellular matrix is important to electrical potentials in nerve and muscle cells and the transmission of impulses across neuromuscular junctions.

In one aspect, the magnesium is provided as an ionic compound of magnesium. Examples of such compounds include, but are not limited to, magnesium citrate, magnesium sulfate monohydrate or heptahydrate, magnesium acetate tetrahydrate, magnesium D-gluconate hydrate, or magnesium nitrate hexahydrate. In one aspect, the formulations described herein include an ionic compound of magnesium in an amount such that there is 100 mg to 500 mg, 150 mg to 500 mg, 200 mg to 500 mg, 250 mg to 500 mg, or 300 mg to 500 mg of magnesium per unit dose.

Zinc

In one aspect, the formulations disclosed herein include a pharmaceutically-acceptable compound of zinc. In a further aspect, zinc is especially depleted (from 40% to 78%) during dialysis. In some aspects, zinc is anti-inflammatory, anti-depressant, and functions to support the immune system. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 388. In another aspect, zinc is integral to the function of many metalloenzymes and is a cofactor in the synthesis of nucleic acids. In a further aspect, zinc is important in the mobilization of vitamin A from the liver and in several reproductive system hormones and functions in both men and women.

In one aspect, the zinc is provided as an ionic compound of zinc. Examples of such compounds include, but are not limited to, zinc citrate, zinc citrate dihydrate, zinc acetate dihydrate, or zinc nitrate hexahydrate. In one aspect, the formulations described herein include an ionic compound of zinc in an amount such that there is 1 mg to 40 mg, 1 mg to 30 mg, 1 mg to 20 mg, or 5 mg to 20 mg of zinc per unit dose.

Selenium

In one aspect, the formulations disclosed herein include a pharmaceutically-acceptable compound of selenium. In a further aspect, selenium is highly concentrated in the liver and kidneys and is thus especially depleted during dialysis. In a still further aspect, selenium is a powerful antioxidant and is especially useful when employed against the damaging effects of free radicals. In another aspect, selenium supplementation may protect against hardening of the arteries and harmful molecules. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 387.

In one aspect, the selenium is provided as an ionic compound of selenium such as, for example, sodium selenate, sodium selenite, or a combination thereof. In one aspect, the formulations described herein include an ionic compound of selenium in an amount such that there is 10 pg to 400 pg, 10 pg to 300 pg, 10 pg to 200 pg, 10 pg to 100 pg, or 25 pg to 80 pg of selenium per unit dose.

Iron

In one aspect, the formulations disclosed herein include a pharmaceutically-acceptable compound of iron. In a further aspect, iron is vital in preventing anemia. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 380. In still another aspect, biochemically, iron is important to oxygen and electron transport as well as prevent anemia and improve the quality and quantity of red blood cells. In a further aspect, heme iron is found in meats and is well-absorbed, while non- heme iron is poorly absorbed. In a still further aspect, supplementation of iron may be particularly important for patients consuming diets that include little or no meat.

In one aspect, the iron is provided as an ionic compound of iron such as, for example, iron gluconate, iron gluconate dihydrate, or iron sulfate heptahydrate. In one aspect, the formulations described herein include an ionic compound of iron in an amount such that there is 1 mg to 45 mg, 1 mg to 30 mg, 1 mg to 20 mg, or 5 mg to 20 mg of iron per unit dose.

In one aspect, the formulations disclosed herein incorporate one or more amino acids. In a further aspect, these amino acids can be proteinogenic or non- proteinogenic.

L-Carnitine

L-carnitine is a vitamin-like molecule that is used by the body to transport fatty acids into the mitochondria for breakdown. It is a non-proteinogenic amino acid that is synthesized in the liver and kidneys from lysine and methionine. This essential amino acid is completely or almost completely depleted from the blood with chronic kidney dialysis. L-carnitine deficiency has been linked to adverse cardiac conditions including, but not limited to, arrhythmias and angina; thus, in one aspect, supplementing with L-carnitine can reduce the incidence of cardiac damage and cardiac events associated with kidney dialysis. In a further aspect, L- carnitine deficiency has been shown to limit mitochondrial fat metabolism in the heart and other organs; in this aspect, supplementation with L-carnitine may help restore normal mitochondrial fat metabolism. In still another aspect, L-carnitine supplementation can provide support in cases of muscle weakness and may protect against circulatory disorders. In a still further aspect, L-carnitine has been shown to be important in oxidation of fatty acids and cellular energy management. In one aspect, the formulations disclosed herein include pharmaceutically- acceptable compound of L-carnitine. Examples of pharmaceutically-acceptable compounds of L-carnitine include, but are not limited to, acetyl-L-carnitine or L- carnitine-L-tartrate, which can be metabolized in the blood by plasma esterases to produce L-carnitine. In other aspects, L-carnitine can be used directly. In one aspect, the amount of the pharmaceutically-acceptable compound of L-carnitine present per unit dose is from 100 mg to 3,500 mg, 500 mg to 2,500 mg, 500 mg to 1 ,000 mg, 1 ,000 mg to 2,000 mg of L-carnitine per unit dose. For example, 2,239 mg of L-carnitine-L-tartrate will provide 1 ,500 mg of L-carnitine per unit dose. In a further aspect, 500 mg to 2,500 mg of acetyl-L-carnitine or L-carnitine-L-tartrate is included in the supplements disclosed herein.

In one aspect, depending on the patient needs as assessed by the healthcare provider, additional ingredients can be included in the supplements disclosed herein.

Citrus Bioflavonoids

In one aspect, the formulations disclosed herein include citrus bioflavonoids. In a further aspect, citrus fruits are excellent sources of vitamin C and citrus bioflavonoid preparations sourced from whole citrus fruits or citrus rinds/peels or pith may be rich in vitamin C. In a further aspect, the citrus bioflavonoids can be from lemons, limes, grapefruits, oranges, tangerines, or a combination thereof. In a further aspect, the citrus bioflavonoids can include rutin, quercetin, tangeritin, diosmetin, diosmin, naringin, nairrutin, neohesperidin, nobiletin, hesperidin, and combinations thereof.

In a still further aspect, citrus bioflavonoids may be anti-inflammatory, antioxidant, or anti-microbial. In still another aspect, citrus bioflavonoids may improve capillary permeability and circulation, hypertension, swelling or edema, and insulin response, or a combination thereof. In still another aspect, sources of citrus bioflavonoids may contain flavor compounds that render the compositions disclosed herein more palatable.

Powdered Extract of Cranberry and Cherry In one aspect, the formulations disclosed herein include powdered extracts of cranberry and cherry. In another aspect, cranberry and cherry extracts may contain flavor compounds that render the compositions disclosed herein more palatable. In a further aspect, cranberry and cherry extracts are high in antioxidants, vitamins, and minerals.

In a still further aspect, cranberry extract contains D-mannose, a sugar that has anti-biofilm (bacterial biofilm that is) properties, binds to and agglomerates bacteria in the urinary tract, thus helping to prevent urinary tract infections, which can be especially important for dialysis patients.

In one aspect, the cherry extract is from tart cherry. Further in this aspect, consumption of tart cherry extract may reduce side effects of statins, may improve blood cholesterol levels, may reduce inflammation related to arthritis and/or obesity, and may support a healthy metabolism.

In one aspect, some minerals are not to be included in the supplements disclosed herein.

Potassium

In one aspect, potassium is excluded from the formulations described herein. In some aspects, high potassium levels can cause muscle and heart problems. In a further aspect, potassium levels can rise between dialysis sessions and may affect the heartbeat.

Sodium

In another aspect, the formulations disclosed herein exclude sodium. In one aspect, increased sodium consumption causes thirst and may lead to water retention. In a further aspect, excess sodium consumption and/or high sodium levels can raise the blood pressure.

Phosphorus

In one aspect, the formulations disclosed herein exclude phosphorus. In a further aspect, too much phosphorus in the blood can cause calcium resorption from the bones. In still another aspect, too much phosphorus can cause the skin to itch. Handbook of Nonprescription Drugs, 1 1^th edition, 1996, American Pharmaceutical Association. 2215 Constitution Avenue, NW, Washington, DC 20037. Chapter 19, Nutritional Products, page 383-384. In one aspect, a phosphate binder is provided to the patient alongside the formulations disclosed herein.

The supplements described herein can be formulated using techniques known in the art. In one aspect, the minerals, vitamins, and amino acids supplied in dry form are admixed with one another to produce a dry powder. In addition to the minerals, vitamins, and amino acids, other pharmaceutically-acceptable fillers can be added to formulate the supplement in powder form. For example, polysaccharides such as, for example, maltodextrin, can be used to formulate the supplement.

In one aspect, the supplement is a unit dose composition composed of

(a) vitamin B-_\

(b) vitamin B₂

(c) vitamin B₃

(d) vitamin B₅

(e) vitamin B₆

(f) vitamin B₇

(g) vitamin B₉

(h) vitamin B₁₂

(i) vitamin C

G) vitamin D₃

(k) a pharmaceutically-acceptable compound of calcium

(L) a pharmaceutically-acceptable compound of magnesium

(m) a pharmaceutically-acceptable compound of zinc

(n) a pharmaceutically-acceptable compound of selenium

(o) a pharmaceutically-acceptable compound of iron

(p) a pharmaceutically-acceptable compound of L-carnitine.

In another aspect, the supplement includes the following components in a dry powder:

(a) vitamin B-_\ in the amount of 0.1 mg to 50 mg per unit dose; (b) vitamin B₂ in the amount of 0.1 mg to 2 mg per unit dose;

(c) vitamin B₃ in the amount of 1 mg to 40 mg per unit dose;

(d) vitamin B₅ in the amount of 1 mg to 20 mg per unit dose;

(e) vitamin B₆ in the amount of 1 mg to 100 mg per unit dose;

(f) vitamin B₇ in the amount of 10 pg to 500 pg per unit dose;

(g) vitamin B₉ in the amount of 0.05 mg to 1.0 mg per unit dose;

(h) vitamin B₁₂ in the amount of 1 pg to 150 pg per unit dose;

(i) vitamin C in the amount of 10 mg to 2,000 mg per unit dose;

G) vitamin D₃ in the amount of 1 pg to 100 pg per unit dose;

(k) a pharmaceutically-acceptable compound of calcium in the amount of 100 mg to 2,500 mg per unit dose;

(L) a pharmaceutically-acceptable compound of magnesium in the amount of 100 mg to 500 mg per unit dose;

(m) a pharmaceutically-acceptable compound of zinc in the amount of 1 mg to 40 mg per unit dose;

(n) a pharmaceutically-acceptable compound of selenium in the amount of 10 pg to 400 pg per unit dose;

(o) a pharmaceutically-acceptable compound of iron in the amount of 1 mg to 45 mg per unit dose; and

(p) a pharmaceutically-acceptable compound of L-carnitine in the amount of 100 mg to 3,500 mg per unit dose.

(a) vitamin B-\ n the amount of 0.5 mg to 2 mg per unit dose;

(b) vitamin B₂ n the amount of 0.5 mg to 2 mg per unit dose;

(c) vitamin B₃ n the amount of 1 mg to 20 mg per unit dose;

(d) vitamin B₅ n the amount of 1 mg to 15 mg per unit dose;

(e) vitamin B₆ n the amount of 1 mg to 10 mg per unit dose;

(f) vitamin B₇ n the amount of 10 g to 100 pg per unit dose;

(g) vitamin B₉ n the amount of 0.1 mg to 1 .0 mg per unit dose;

(h) vitamin B₁₂ in the amount of 1 pg to 10 pg per unit dose;

(i) vitamin C in the amount of 100 mg to 300 mg per unit dose; (j) vitamin D₃ in the amount of 1 pg to 20 pg per unit dose;

(k) a pharmaceutically-acceptable compound of calcium in the amount of 100 mg to 1 ,000 mg per unit dose;

(m) a pharmaceutically-acceptable compound of zinc in the amount of 5 mg to 20 mg per unit dose;

(n) a pharmaceutically-acceptable compound of selenium in the amount of 10 pg to 100 pg per unit dose;

(o) a pharmaceutically-acceptable compound of iron in the amount of 5 mg to 30 mg per unit dose; and

(p) L-carnitine-L-tartrate in the amount of 1 ,000 mg to 3,000 mg per unit dose.

In another aspect, the supplement has the following components as provided in Table 1.

The supplements described herein are intended to be taken orally. In one aspect, the supplements can be formulated as tablets or capsules. In other aspects, the supplements can be formulated as a powder that can be mixed with water or another beverage. Alternatively, the powder form of the supplement can be admixed with food such as yogurt, peanut butter, or other foods that readily mix with the supplement.

The formulations described herein are to be administered to patients with kidney disease and/or undergoing kidney dialysis, or individuals at risk of kidney diseases (lifestyle, family history, etc.). The amount of formulation administered to the patient should not exceed the recommended daily dose for each component. The formulations can be administered to the patient prior to dialysis, during dialysis, after dialysis, and any combination thereof. The nutritional supplement described herein is designed to support kidney and cardiac function as well as mitochondrial energy function needs in patients undergoing hemodialysis. This supplement replenishes essential vitamins and minerals that are lost during dialysis, does not contain compounds that may specifically cause harm to dialysis patients, and provides support for tissues undergoing oxidative stress. By replenishing the minerals and vitamins lost during dialysis, the subject will have increased energy levels that will permit the subject to lead a more productive life.

One or more additional supplements can be taken with the supplements described herein. In one aspect, an omega 3 fatty acid can be taken with the supplements described herein. Omega 3 fatty acids are lipid soluble macronutrients that are important to metabolism (i.e., energy production captured in the form of ATP). Omega 3 fatty acids are partially removed from the body with chronic kidney dialysis. Omega 3 fatty acids have been shown to reduce inflammation and thus to lower the risk of chronic diseases (including heart disease). They are believed to be important for cognitive function and also have been shown to reduce triglycerides while increasing high-density lipoproteins (HDL) cholesterol. Omega 3 fatty acids have been linked to improvement in a number of other conditions including from skin, joint, eye, and gastrointestinal conditions. In one aspect, supplementation with omega 3 fatty acids can be especially important for improving blood pressure, blood circulation, and blood vessel elasticity while preventing cardiovascular and coronary events in persons with high cardiovascular risk. Marine Omega 3 Fatty Acids: https://en.wikipedia.org/wiki/Fattv acid metabolism

Omega 3 fatty acids are found in fish, some plants, nut oils, and algae, and are not always consumed in high enough amounts through the standard diet. In one aspect, it is important to replenish the body’s supply of omega 3 fatty acids, since these important macronutrients cannot be synthesized by the body. In another aspect, marine omega 3 fatty acids (i.e., from fish or algae) have preferable amounts of DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) as compared to omega 3 fatty acids from plant sources, which primarily contain ALA (alpha linolenic acid), a compound that is not efficiently utilized by the body.

In still another aspect, the formulations disclosed herein include marine omega 3 fatty acids. In a further aspect, the marine omega 3 fatty acids can be sourced from salmon, mackerel, sardines, tuna, or herring. Many Western diets incorporate higher dietary omega 6 fatty acids, which can promote inflammation. In another aspect, it is important to supplement omega 3 fatty acids, especially in hemodialysis patients, to reduce inflammation and the risk of death. In another aspect, the amount of Omega 3 is significantly higher than the amount Omega 6.

In yet another aspect, hemodialysis is believed to upregulate oxidative mechanisms, which could lead to peroxidation of omega 3 fatty acids; this, in turn, can lead to breakdown of the fatty acid structure and loss of function. In this aspect, supplementation with omega 3 fatty acids can be used to replenish the supply of nutrients destroyed by peroxidation.

In one aspect, the marine omega 3 fatty acids are provided as wild Alaskan salmon oil or marine algal oil. In a further aspect, the EPA:DHA ratio of the marine omega 3 fatty acids is from 1 :1 to 4:1. In one aspect, the amount of marine omega 3 fatty acids present per unit dose is from 500 mg to 4,000 mg, 500 mg to 3,000 mg, 500 mg to 2,000 mg, or 500 mg to 1 ,500 mg. In another aspect, 1000 mg of marine omega 3 fatty acids are provided per unit dose of the supplements disclosed herein.

In another aspect, coenzyme Q₁₀ (CoQ₁₀) can be taken with the supplements described herein. CoQ₁₀ acts as an antioxidant and protects the cell membrane against oxidative stress. In another aspect, CoQ₁₀ is an important coenzyme in the mitochondria (and other parts of the cell) and participates in cellular respiration, which ultimately generates energy in the form of adenosine triphosphate. In still another aspect, C0Q10 protects against low-density lipoproteins (LDL) oxidation, which is vital for heart health. In a further aspect, reduced form of CoQ₁₀ (CoQ₁₀H₂) can regenerate vitamin E from the alpha- tocopheroxyl radical, thus leading to a reduction of oxidative stress.

In one aspect, certain patients require intake of C0Q10 that is higher than provided by the average diet. These include, but are not limited to, athletes, patients with hyperthyroidism, patients who are taking statins, and the elderly. Thus, in one aspect, elderly dialysis patients may especially benefit from CoQ₁₀ supplementation. In a related aspect, CoQ₁₀ can decrease insulin requirements in patients with diabetes; thus, diabetic dialysis patients may also benefit from CoQ₁₀ supplementation.

In another aspect, however, CoQ₁₀ supplementation should be avoided in patients taking warfarin or other blood thinners, as it can reduce the activity of these medications. In this aspect, the supplements disclosed herein do not include CoQ₁₀.

In one aspect, CoQ₁₀ in the supplements disclosed herein is provided as ubiquinol, a reduced form of CoQ₁₀ that has a particularly high uptake percentage and subsequently leads to an increase of CoQ₁₀ levels in the blood. Ubiquinol effectively regenerates vitamin E from alpha-tocopherol radical. In one aspect, the amount of CoQ₁₀H₂ (e.g., ubiquinol) present per unit dose is from 70 mg to 400 mg, 70 mg to 300 mg, or 150 mg to 250 mg. In another aspect, 200 mg of ubiquinol are included in the supplements disclosed herein. In one aspect, turmeric can be taken with the supplements described herein. Turmeric has anti-inflammatory and antioxidant properties that are in some aspects useful to the kidneys. In another aspect, the formulations disclosed herein do not include turmeric. In some aspects, turmeric should not be given to patients who are sensitive or allergic, pregnant or nursing, diabetic and taking blood thinners, patients with gall bladder conditions, and/or patients with digestive system disorders such as GERD (gastroesophageal reflux disease). In one aspect, turmeric is prepared in a separate distribution form (e.g., a separate capsule) and given to patients at their healthcare providers’ discretion. In still another aspect, turmeric is provided with the supplement unless the patient is going to undergo surgery and/or has a bleeding disorder, since turmeric is known to be a powerful blood thinner.

In one aspect, piperine can be taken with the supplements described herein. In some aspects, turmeric is not easily absorbed by the body and piperine enhances absorption by 10 to 20 fold. In one aspect, the formulations disclosed herein include 100 mg of piperine for every 500 mg of turmeric. In one aspect, the amount of turmeric present per unit dose is from 1 g to 3g, 1.5 g to 2.5 g, or 2 g.

In one aspect, the supplement is formulated as a kit, where one compartment or vial has a mixture of the supplement described herein composed of the minerals, vitamins, and amino acids supplied in dry form (e.g., tablet, powder), and a second compartment containing other supplements (e.g., marine omega 3 fatty acids in capsule form, ubiquinol in gel form, turmeric is in a capsule, or any combination thereof)ln one aspect, provided herein is a method for improving the health of a subject by administering to the subject omega 3 fatty acids, coenzyme Q10, and a unit dose composition described herein.

The supplements and methods described herein address one or more illnesses or medical conditions. In one aspect, the supplement replenishes essential vitamins and minerals that are lost during kidney dialysis, such as, for example, hemodialysis or peritoneal dialysis. In another aspect, the patient has a kidney disease or a kidney transplant. In one aspect, the method reduces the severity of or prevents the onset of type I or II diabetes. In another aspect, the methods described herein reduce the amount of insulin required by the subject having type II diabetes. In another aspect, the subject is undergoing kidney dialysis (e.g., hemodialysis or peritoneal dialysis) and has type I or II diabetes.

In another aspect, the method reduces one or more symptoms of dementia or Alzheimer’s disease (e.g., memory loss). In still another aspect, the method improves patient cholesterol levels by, for example, reducing the amount of LDL in the patient and/or increasing the amount of HDL in the patient. In one aspect, the method can reduce the severity of or prevent the onset of heart disease. In another aspect, the method can reduce the risk of a stroke. In some aspects, the method can reduce stress levels in a subject. In still another aspect, the method can reduce high blood pressure and/or maintain healthy blood pressure.

In a further aspect, the method can reduce the severity of or prevent the onset of anemia. In a still further aspect, the method can promote weight loss. For example, the combination of the omega 3 fatty acids, coenzyme Q10, and a unit dose composition described herein is effective in promoting weight loss compared to just the unit dose composition. In yet another aspect, the method can improve the well-being of a patient being treated for cancer. In an alternative aspect, the method can promote improved athletic performance. In a still further aspect, the method can reduce the severity of or prevent the onset of periodontal disease and/or can generally promote or improve oral hygiene. In another aspect, the method can promote better sleep. In another aspect, the method can reduce or alleviate one or more symptoms of ADHD, anorexia, or HIV infection. In another aspect, the method can prevent the onset of osteoporosis or reduce or alleviate one or more symptoms of osteoporosis.

In one aspect, the method can reduce one or more symptoms of chronic fatigue syndrome. In one aspect, the method can reduce one or more symptoms of muscle atrophy. In one aspect, the method can reduce general fatigue and improve endurance. In one aspect, the method can improve cognitive abilities. In one aspect, the method can reduce or prevent mental confusion. In one aspect, the method can reduce or prevent headaches. In one aspect, the method can aid in the healing process caused by a stroke. In one aspect, the method can reduce or prevent skin disorders. In one aspect, the method can reduce one or more symptoms of joint disease;

In any of the above aspects, the method for improving the health of a subject involves administering to the subject the nutritional supplements and compositions disclosed herein.

EXAMPLES

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the materials, articles, and methods described and claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of reaction conditions, e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process. Only reasonable and routine experimentation will be required to optimize such process conditions.

The components in Table 2 were admixed with one another in dry form to produce a supplement. Maltodextrin was added in an amount so that 8.5 g of supplement was produced.

Example 1

A supplement described herein was evaluated with a subject undergoing dialysis. The subject has been treated for dialysis for the last 20 years and for the last 13 years at his home. Dialysis is conducted at home every other night for 7 hours.

The subject initially started taking a full dose of the supplements (8.5 g of the powder provided in Table 2, 200 mg CoQ10, and 2,000 mg omega 3 fatty acids). However, the doze of the powder was adjusted to a half dose. The subject took a quarter of the powder together with fast carbohydrates for breakfast and the same dose for lunch with fast carbohydrates.

After three weeks, the subject’s mental condition improved. The subject did not need to sleep so much as before. The subject has more energy and is able to do more activities.

After taking the supplement for about six weeks, the subject has more energy and able to perform more outdoor activities. The subject perspires much more compared to when he was not taking the supplement, which is positive for dialysis patients that have problems getting rid of excess liquid in their body. The subject is also sleeping very well and is more focused. The subject’s blood pressure is good. Renal blood samples are also good except for the level of sodium, which has been adjusted due to dialysis treatment.

After taking the supplement (4.5 grams of powder, 200 mg CoQ10, and 2,000 mg omega 3 fatty acids) for 3 months, he was able to walk one kilometer each day with ease and, after a total of 4 months, he was able to play 18 holes of golf.

Example 2

The patient started taking the supplement (4.5 grams of powder in Table 2, 200 mg CoQ10, and 2,000 mg omega 3 fatty acids) each day for 4 months during which time he cut back on his insulin intake by 4 units. Furthermore, this patient started taking 6.5 grams with the CoQ10 and omega-3 fatty acids in the 5th month and is continuing this regimen. Additionally, the patient lost 5 kilograms after 4 months.

Example 3

The group that took the whole supplement (4.5 gm powder of Table 2, 1 ,000 mg omega 3 fatty acids, 100 mg CoQ10) vs. the group that took only the powder. The first group felt better, slept better, felt less stressed out and lost more weight compared to the second group.

Example 4

Provided below are testimonials from additional patients that took the supplement above in Examples 1-3.

Patient 1 (50 year old male administered supplement for 18 months):“First of all, the dialysis fog disappeared. It became easier to think and I was not so tired in my head anymore. Even the energy has become better and there is suddenly a little extra re-server to come up when needed. I have started running out after 6 weeks of training and I could run 6 km without interruption. It's the first time in 30 years that I could do this. In August, I ran a distance in the Vasaloppsstafet. During July I have gone about 9 to 18th rounds and probably as many 9-hole rounds. Although the energy was limited in heat, I had not hurried this without the addition.”

Patient 2 (53 year old female administered supplement for 9 months): “Since I started with the supplement, I have become both sparkling and happier. I've also got more energy, which means I'm able to do something about what I think is fun. Among other things, to throw darts and work in the garden." Patient 3 (51 year old male administered supplement for 16 months):“My goal n/as to be able to exercise more, gain more energy after dialysis, and to lower the insulin. Have today achieved my previously set goals and are now working on new ones to make even better"

Patient 4 (39 year old male administered supplement for 8 months): “Before I started with my supplement, I M/as stiff, had pain in my joints, and I had difficulty walking off the bed in the morning without the help of my children 6 and 9 years old. Have not had energy, pleasure in training and feeling good in the last 1.5 years. Now I've regained my energy, and have started training again. My children are glad that I regained my initiative again, which means we can play soccer, hockey, go to the movies and socialize much more than before

Patient 5 (61 year old female administered supplement for 7 months):“The goal for me was to take longer walks, not be tired of dialysis, more active at home, driving more cars, and being able to spend more time with y children and friends. Has now reached ail my goals and is now working on new set goals. My previous aches in my joints, shoulders and hands have disappeared."

Patient 6 (32 year old male administered supplement for 7 months):“Been kidney sick throughout my life. Has now got more energy after dialysis, my pain has decreased, and I have now begun looking for an employment. May now finally start thinking positively about my future. My dad sees a clear positive change on my energy "

Example 5

The following evaluation of the supplement is based on thirteen patients who have taken the supplement; some for three months, while others for twenty- eight months. This evaluation was followed by interviews and questionnaires to see if the supplement, when taken by patients undergoing kidney dialysis, can affect the energy and thereby increase the patient’s well-being. Our overall goal is to see if it is possible to improve the lifestyle, well-being, and mental health, i.e. , better quality of life for patients undergoing kidney dialysis.

The RAND 36-Item Health Survey Method was chosen for this survey (Orwelius et al. Journal of Patient-Reported Outcomes (2018); Nilsson, E.et al (2016) Patient-reported outcomes in the Swedish National Quality Registers. Journal of internal medicine, 279(2), 141-153).

Implementation

Thirteen kidney dialysis patients have participated in this evaluation. These patients come from Northern and Southern Gotaland, four women and nine men, 33 to 68 years old. The patients have received information about the supplement via various sources such as the Swedish Kidney Association, Kidney Pie, friends of patients, as well as by mail. When a patient decides to participate in the evaluation, the patient receives documents with information about the product and forms that must be filled in with personal data and a confidentiality agreement. The patients are required to discuss their situation with their healthcare doctor in order to obtain approval and get confirmation that the supplement will not interfere with other drugs that the patient is taking. When this is completed, a meeting with the patient is booked, (can be face-to-face, or by phone) where an interview about their medical history, the social situation regarding family, housing, work, leisure time, energy, sleep, and appetite is made. It also deals with expectations and per- sonal goals. The patient is asked to set specific long and short-term goals in order to facilitate measurement of potential changes. The patient starts taking the product and is then followed up after a few days with face-to-face interviews, mail, or phone calls. Each evaluation is done after one, two, and three months, via visit, telephone, or mail. The evaluation / interview includes specific questions related to dose, energy, sleep, appetite and progression towards given goals. If the short- term goals are achieved, new ones are defined.

Results

Since this nutritional supplement has the main goal of improving the well- being and quality of life of dialysis patients, issues from RAND-36 such as energy, mental health, and dialysis related fatigue were selected. Figures 1-4 show that most patients have improved their well-being and quality-of-life over a period of three months. The patients pointed out that the result could have been even better if they had avoided infections or other diseases during the study period. Several patients indicated that their situation would be much worse without the supplement.

Interviews

Below are the interviews for each patient.

Patient 1. A patient who has had hemodialysis for twenty years, including home hemodialysis for thirteen years. His wish was to feel better physically and mentally. After taking the supplement for about six weeks, the patient described that his head felt clearer and that he, had come out of “the dialysis fog”. The patient sleeps better during the night and his appetite has improved. Additionally, after several months, this patient started physical training and is much more active than before.

Today, the patient has been taking the supplement for nineteen months and, can play 18-hole golf rounds, has run a part of the“Vasaloppsstafetten”, and has plans on“The mile run” as well as the“Goteborgsvarvet, Half Marathon”.

Patient 2. A patient who has had hemodialysis for about four years and has developed diabetes 1 . This patient’s goal was to be able to exercise and lose weight. After two months of taking the supplement, the patient felt better during dialysis sessions because no oxygen was needed anymore. Before entering the study, the patient talked in terms like:“I am so ill, have a hard time doing it”, and now, after seventeen months on the supplement, he is saying:“it feels good, and I can do things even if I have a kidney disease”. The patient started to walk more and lost some weight.

During the study period, the patient has reduced his need for long-acting insulin by more than 50%. Before the evaluation period, the patient worked four days a week, but now, after a few months, he can work and be active most days of the week.

Patient 3. A patient who has had kidney disease for nine years and undergoes home hemodialysis four to five times a week, and sometimes, self- dialysis at the hospital. This patient sleeps very badly during the night and, often needs to rest for short periods in bed or on a couch during the day. This is partly due to restless legs, but also due to pain from an operation on her foot. After taking the supplement for one month, the patient felt more alert and was happier. Earlier, this patient waited for friends to call her, but now she calls them herself, indicative of a more positive attitude. After two months, the patient felt more alert and had more energy. This patient, however, was bitten by a cat, takes antibiotics and the foot had to be re-operated. After three months, the situation was worse. The foot continued to be infected and the patient is still on antibiotics treatment. Her mood is good, but she feels tired and affected by all procedures related to the infections. Sleep and appetite are worse due to the pain in the foot. The patient does not feel“the restless legs” as much as before. She says that the situation would have been even worse if she had not taken the supplement.

The patient has today taken the supplement for ten months, she still has problems with her foot, but her appetite is better, and the patient has begun to walk longer distances and aims to get started with muscle training at the beginning of 2019.

Patient 4. A patient who has undergone hemodialysis for three years, three times a week. This patient had no energy, was very tired, and had a lot of pain in the body. The patient spent most days on the couch and“can’t watch TV or talk on the phone”. The patient said: “it is very difficult to recover from a dialysis session until it is time again.”. She then started with the supplement and aimed to go to the mailbox (about 10m) and later to go out with her dogs. This patient had plans to go to Spain with one of her daughters but worried that she did not have enough energy to travel. After taking the supplement for one month, the patient met us at the door when we came for the interview; she spoke and was happy and said,“it was now possible to stay awake in front of the TV and to talk on the phone”, She also walked to her mailbox to get her mail and had been out on short rounds with her little dog. She can shower herself alone and does not need oxygen during dialysis anymore. She has also reduced the amount of sleeping pills, and still sleeps better during the night. On the next visit, after two months, the patient had been to Spain and felt good while she was there, but it became difficult to go home to ’’the usual routines” again. At the next meeting, three months after starting with the supplement, the patient had fallen and was admitted to the hospital. According to relatives, her mood is good, and she has come out of her depression. Unfortunately, the patient again broke her hip joint, she was operated on and she does not currently take the supplement.

Patient 5. A patient who has had kidney disease for almost fifteen years and now is on hemodialysis four to five times a week. This patient had previously been very active in sports but in recent years has had no strength. This patient sleeps four to five hours each night and has pain in his joints which made it difficult to get out of bed. After taking the supplement for one month, the joint pain had been reduced and the patient could rise instead of crawl out of bed. He has more energy and slept about eight hours during the night. Unfortunately, the patient felt so good that he thought the supplement was not needed any longer and he stopped taking the supplement for five days. However, the pain came back, and the patient had to crawl out of bed again, lost strength and lost his desire to be active. The patient began to take the supplement again and, after one week, the pain disappeared, and his strength returned. After three months, his friends pointed out that he looked alert and well.

Today after about nine months on the supplement, the patient can do things, which were unthinkable before, such as playing football with his children. The patient has started training ice hockey again and says that he is satisfied with the supplement and he will never stop taking it.

Patient 6. This patient was born with kidney disease and transplanted once. The organ was rejected and now he undergoes hemodialysis three times a week while waiting for a new transplant. The patient reports that after he started dialysis, he used to fall out of bed at night, causing injuries that required operations, which led to pain and infections. He has never been active in working life but now after starting with the supplement, he has set the goal of getting employment. Furthermore, this patient used to stay at home and rarely go outside his home. After taking the supplement for one month, this patient said,“it was easier to go out, especially to the store”. After two months, he was more alert, involved in conversations, smiled and sometimes laughed. The patient went to Copenhagen, where he “walked until his feet hurt”. Today, he has taken the supplement for eight months and, with the help of the municipality, he has started to look at potential jobs and plan for daily activities, etc.

Patient 7. A patient who has been on hemodialysis for ten years. This patient undergoes hemodialysis four times a week. She has osteoarthritis and pain in the joints, especially in the neck, shoulders and hands. She sleeps reasonably well but wake up a few times during the night. The patient had a gallstone operation in 2017, after which she lost her appetite and had difficulty in keeping her food. This patient wanted to be more active, go for longer walks and take better care of the home. After taking the supplement for one month, this patient had less pain in the joints and was more physically active. During follow-up after two months, the patient reported that the situation was the same as after one month, partly due to the summer heat, as well as due to a vascular accident.

The patient has now been on the supplement for nine months, she had a heart attack after three months, and developed backpain. However, the patient says she feels good and can now manage the home and takes several short walks and sleeps throughout the night. In interviews she says:“time is too short for everything I want to do.”.

Patient 8. A patient who has been on hemodialysis three times a week for thirteen years, felt tired and had poor appetite. During dialysis sessions, this patient was given nutritional solution intravenously. After one month on the supplement, the patient had more energy, could do small jobs around the house and garden and started to improve his appetite. However, due to the extreme summer heat in 2018, he had not been able to get much physical exercise, but he defined increased exercise as a goal for the next follow-up. After two months, the patient had stomach problems and, after three months on the supplement, the patient was diagnosed with aortic stenosis and stopped exercising.

The patient had successful surgery and he has now taken the supplement for seven months, his energy has increased, and his exercise program is progressing well.

Patient 9. A patient with kidney problems due to chemical poisoning. He had been on hemodialysis for five years, three times a week. Before his kidney problems, the patient had been very active with regular physical training, but when we met him, he had no strength. After taking the supplement for one month, the patient felt more alert despite a very low hematocrit (Hb of 90). After two months, still with low Hb, the patient started gym training. After three months, the patient was back on almost full exercise - programs at the gym.

Today, after five months, the patient feels much better and is significantly more active than before starting with the supplement.

Patient 10. A patient with polycystic kidney disease had been on hemodialysis three times a week for four years. Before the patient started with the supplement, she suffered from aches and pains all over her body and could not cope with daily routines in the home. The patient slept only three to four hours a night and had problems with falling asleep, and she has a long history of repeated infections. After taking the supplement for one month, the patient slept about six hours during the night and had improved ability to perform daily routines in her home. After two months, she still had problems with low hematocrit but said she was generally feeling quite good and that her sleeping was significantly improved. After three months, the patient had less pain and was able to walk six to seven km, with her dog.

Today, the patient has taken the supplement for four months and has bought a cross-trainer to train and maintain her muscle mass.

Patient 1 1 . A patient who at the age of ten suffered from an autoimmune disease that destroyed the kidneys. He was transplanted three times, unfortunately resulting in rejection of the trans-plant, and now he is on peritoneal dialysis three to four times a week with about eight hours each night. After taking the supplement for one month, the patient thought he felt better after each dialysis session and felt it was easier to focus because his “dialysis fog had been reduced”. After two months, the patient got an infection (common cold), but said he slept better and had less trouble with restless legs. After three months, the patient still suffered from an infection and was tired but“not as foggy”.

This patient who missed part of his basic education and never had a regular job, has now taken new secondary school exams and is currently studying a course at a university. Today, the patient has taken the supplement for five months and his mother describes his condition as:“The clearest is his healthier appearance. He has a better face color and luster in the skin and eyes. The hair quality which previously was poor has become significantly improved, same thing with the nails. He is somewhat more energetic than before, still very worn, but as said, a much-improved general condition.”

Patient 12. A patient who has had kidney disease for twentyfive years, transplanted twice, he has developed diabetes and has major problems with Neuropathy. This patient is currently on hemodialysis four times a week, after which he becomes very tired. The patient also has“restless legs” and pain in the hands and joints but he sleeps reasonably well when his feet don’t hurt. After one month on the supplement, the patient did not feel major changes, but after two months he was able to walk around with the neighbor without sitting down. The patient had a smaller fracture in the foot resulting in increased pain which made it difficult to walk for two months.

Today, after five months on the supplement, the patient has recovered from his leg problems and is walking without his orthosis. The patient has been to a gym and talked to them about starting physical training. Furthermore, his relatives say that he is’’clearer in the head,”, the patient himself describes it as“thinking more clearly”.

Patient 13. A patient with Diabetes type two which resulted in kidney failure, is currently undergoing hemodialysis four times a week. This patient has neuropathic pain problems. On dialysis days, the patient feels very tired and falls asleep after one hour. He must be awakened to eat and then he falls asleep again. On some days, he can walk slowly for about ten to fifteen minutes. The patient generally sleeps a lot but wakes up several times during the night due to the pain. After taking the supplement for one month, the patient felt much better. Some aches have disappeared, and the fatigue is less. The patient has been more active in his daily homework, washing dishes, cooking food, and general maintenance of his house. The patient reported improved sleeping and that he generally felt more rested. After two months, the patient said he was“clearer in the brain” and felt more active at home. After three months, the patient began to exercise twice a week and his feet were no longer hurting. Furthermore, after taking the supplement for three months, he felt more energetic and had more time left for other things due to reduced need to sleep.

Throughout this publication, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the methods, compositions, and compounds herein.

Various modifications and variations can be made to the materials, methods, and articles described herein. Other aspects of the materials, methods, and articles described herein will be apparent from consideration of the specification and practice of the materials, methods, and articles disclosed herein. It is intended that the specification and examples be considered as exemplary.

Claims

CLAIMS What is claimed:

1. A method for addressing one of the following conditions in a subject:

(a) reduce the amount of insulin required by the subject having type II diabetes;

(b) reduce or prevent the onset of type II diabetes;

(c) reduce one or more symptoms of type II diabetes;

(d) reduce one or more symptoms of dementia or Alzheimer’s disease;

(e) reduce the amount of LDL cholesterol in the subject and raise the amount of HDL cholesterol in the subject;

(f) reduce or prevent the onset of heart disease;

(g) reduce the risk of a stroke;

(h) reduce the level of stress;

(i) reduce and maintain blood pressure;

G) reduce or prevent the onset of anemia;

(k) promote weight loss;

(L) promote the well-being of the subject with cancer;

(m) promote the athletic performance of the subject;

(n) reduce or prevent the onset of periodontal disease and promote oral hygiene;

(o) promote better sleep;

(p) reduce one or more symptoms of ADHD, anorexia, or HIV infection;

(q) prevent the onset of osteoporosis or reduce or alleviate one or more symptoms of osteoporosis;

(r) reduce one or more symptoms of chronic fatigue syndrome;

(s) reduce one or more symptoms of muscle atrophy; (t) reduce general fatigue and improve endurance;

(u) improve cognitive abilities;

(v) reduce or prevent mental confusion;

(w) reduce or prevent headaches;

(x) aid in the healing process caused by a stroke;

(y) reduce or prevent skin disorders; and

(z) reduce one or more symptoms of joint disease;

the method comprising administering to the subject omega 3 fatty acids, coenzyme Q10, and a unit dose composition comprising

(a) vitamin B1

(b) vitamin B2

(c) vitamin B3

(d) vitamin B5

(e) vitamin B6

(f) vitamin B7

(g) vitamin B9

(h) vitamin B12

(i) vitamin C

G) vitamin D₃

(k) a pharmaceutically-acceptable compound of calcium

(L) a pharmaceutically-acceptable compound of magnesium

(m) a pharmaceutically-acceptable compound of zinc

(n) a pharmaceutically-acceptable compound of selenium

(o) a pharmaceutically-acceptable compound of iron

(p) a pharmaceutically-acceptable compound of L-carnitine.

2. The method of claim 1 , wherein the unit dose composition comprises

(a) vitamin B1 in the amount of 0.1 mg to 50 mg per unit dose;

(b) vitamin B2 in the amount of 0.1 mg to 2 mg per unit dose;

(c) vitamin B3 in the amount of 1 mg to 40 mg per unit dose; (d) vitamin B5 in the amount of 1 mg to 20 mg per unit dose;

(e) vitamin B6 in the amount of 1 mg to 100 mg per unit dose;

(f) vitamin B7 in the amount of 10 pg to 500 pg per unit dose;

(g) vitamin B9 in the amount of 0.05 mg to 1.0 mg per unit dose;

(h) vitamin B12 in the amount of 1 pg to 150 pg per unit dose;

(i) vitamin C in the amount of 10 mg to 2,000 mg per unit dose;

(j) vitamin D₃ in the amount of 1 pg to 100 pg per unit dose;

(L) a pharmaceutically-acceptable compound of magnesium in the

amount of 100 mg to 500 mg per unit dose;

(p) a pharmaceutically-acceptable compound of L-carnitine in the

amount of 100 mg to 3,500 mg per unit dose.

3. The method of claim 1 , wherein the pharmaceutically-acceptable compound of L-carnitine is L-carnitine-L-tartrate or acetyl-L-carnitine.

4. The method of claim 1 , wherein the calcium is calcium citrate, the magnesium is magnesium citrate, the zinc is zinc citrate; the selenium is sodium selenite; and the iron is iron gluconate.

5. The method of claim 1 , wherein the unit dose composition further comprises a citrus bioflavonoid, a powdered extract of cranberry and/or cherry, or a combination thereof.

6. The method of claim 1 , wherein the unit dose composition comprises a dry powder.

7. The method of claim 1 , wherein the unit dose composition comprises

(a) vitamin B1 in the amount of 0.5 mg to 2 mg per unit dose; (b) vitamin B2 in the amount of 0.5 mg to 2 mg per unit dose;

(c) vitamin B3 in the amount of 1 mg to 20 mg per unit dose;

(d) vitamin B5 in the amount of 1 mg to 15 mg per unit dose;

(e) vitamin B6 in the amount of 1 mg to 10 mg per unit dose;

(f) vitamin B7 in the amount of 10 g to 100 pg per unit dose;

(g) vitamin B9 in the amount of 0.1 mg to 1 .0 mg per unit dose;

(h) vitamin B12 in the amount of 1 pg to 10 pg per unit dose;

(i) vitamin C in the amount of 100 mg to 300 mg per unit dose;

G) vitamin D₃ in the amount of 1 pg to 20 pg per unit dose;

8. The method of claim 1 , wherein the unit dose composition further comprises a polysaccharide filler.

9. The method of claim 1 , wherein the polysaccharide filler comprises maltodextrin.

10. The method of claim 1 , wherein the marine omega 3 fatty acids are in a capsule.

1 1. The method of claim 10, wherein the marine omega 3 fatty acids comprise DHA and EPA in the weight ratio (EPA:DHA) of 1 :1 to 4:1 .

12. The method of claim 10, wherein the marine omega 3 fatty acids are in the amount of 500 mg to 4,000 mg per unit dose.

13. The method of claim 1 , wherein the coenzyme Q10 comprises a gel.

14. The method of claim 13, wherein coenzyme Q10 is ubiquinol.

15. The method of claim 13, wherein the coenzyme Q10 is in the amount of 70 mg to 400 mg per unit dose.

16. The method of claim 1 , wherein the subject is further administered turmeric, wherein the turmeric is in the amount of 1 g to 3 g per unit dose.

17. The method in any one of claims 1 to 16, wherein the unit dose

composition does not include a pharmaceutically-acceptable compound of potassium, sodium, or phosphorous.

18. The method in any one of claims 1 to 16, wherein the subject is undergoing kidney dialysis.

19. The method of claim 18, wherein the dialysis is hemodialysis or peritoneal dialysis.

20. The method in any one of claims 1 to 16, wherein the subject has a kidney disease or a transplanted kidney.

21. The method in any one of claims 1 to 16, wherein the subject has type I or II diabetes.

22. The method in any one of claims 1 to 16, wherein the subject is undergoing kidney dialysis and has type I or II diabetes.