US20150024062A1 - Medical Food for the Dietary Management of Major Depression - Google Patents
Medical Food for the Dietary Management of Major Depression Download PDFInfo
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- US20150024062A1 US20150024062A1 US14/282,322 US201414282322A US2015024062A1 US 20150024062 A1 US20150024062 A1 US 20150024062A1 US 201414282322 A US201414282322 A US 201414282322A US 2015024062 A1 US2015024062 A1 US 2015024062A1
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- 235000013305 food Nutrition 0.000 title claims abstract description 29
- 208000024714 major depressive disease Diseases 0.000 title claims abstract description 20
- 235000005911 diet Nutrition 0.000 title claims abstract description 15
- 230000000378 dietary effect Effects 0.000 title claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 48
- 239000003651 drinking water Substances 0.000 description 15
- 235000020188 drinking water Nutrition 0.000 description 15
- 241000699670 Mus sp. Species 0.000 description 13
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 12
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 12
- 229930006000 Sucrose Natural products 0.000 description 12
- 229910052805 deuterium Inorganic materials 0.000 description 12
- 239000005720 sucrose Substances 0.000 description 12
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 238000011161 development Methods 0.000 description 9
- 230000018109 developmental process Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000008239 natural water Substances 0.000 description 8
- 208000007415 Anhedonia Diseases 0.000 description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 6
- 239000001110 calcium chloride Substances 0.000 description 6
- 229910001628 calcium chloride Inorganic materials 0.000 description 6
- 235000011148 calcium chloride Nutrition 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000012048 forced swim test Methods 0.000 description 5
- 229910001629 magnesium chloride Inorganic materials 0.000 description 5
- 235000015097 nutrients Nutrition 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 4
- 230000007267 depressive like behavior Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 235000021590 normal diet Nutrition 0.000 description 4
- 235000021048 nutrient requirements Nutrition 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229960004801 imipramine Drugs 0.000 description 3
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 3
- 238000001307 laser spectroscopy Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 238000005292 vacuum distillation Methods 0.000 description 3
- WSEQXVZVJXJVFP-HXUWFJFHSA-N (R)-citalopram Chemical compound C1([C@@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 WSEQXVZVJXJVFP-HXUWFJFHSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010011971 Decreased interest Diseases 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960001653 citalopram Drugs 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000000155 isotopic effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000037326 chronic stress Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000019007 dietary guidelines Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 235000021056 liquid food Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000004630 mental health Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000010346 psychosocial stress Effects 0.000 description 1
- 238000001671 psychotherapy Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
Classifications
-
- A23L1/30—
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/30—Dietetic or nutritional methods, e.g. for losing weight
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention is in the field of food industry and healthcare. More specifically, the present invention relates to medical foods for the dietary management of major depression.
- Major depression is a disorder characterized by a combination of symptoms such as lowered mood, loss of energy, loss of interest, feeling of physical illness, poor concentration, altered appetite, altered sleep and a slowing down of physical and mental functions resulting in a relentless feeling of hopelessness, helplessness, and guilt.
- MDD major depressive disorder
- National Institute of Mental Health estimates prevalence of major depressive disorder (MDD) as 6.7% of U.S. adult population, 56.8% of those with disorders are receiving treatment.
- MDD is a major cause of disability and premature death. Average-age-of onset of MDD is estimated as of 32 years old. The exact cause of MDD is not known.
- Present treatment of depression consists of psychotherapy, antidepressant drugs, or a combination of both. However, there are no special nutritional requirements related to the dietary management of patients with MDD.
- Water is an essential nutrient. Total water intake includes drinking water, water in beverages, and water contained in food. The adequate intake for total water was set based on the median total water intake from U.S. survey data as 3.7 and 2.7 liters per day for men and women, respectively. Dietary Guidelines for Americans, 2005, U.S. Department of Health & Human Services.
- the natural water is a composition of nine water isotopologues (H 2 16 O, H 2 17 O, H 2 18 O, H 16 OD, H 17 OD, H 18 OD, D 2 16 O, D 2 17 O, D 18 O) formed by stable isotopes of hydrogen (H and D) and oxygen ( 16 O, 17 O, 18 O), wherein content of major water isotopologue H 2 O (H 2 16 O) is 99.7317 molecular % (mol. %) and major deuterium-containing isotopologue HOD (H 16 OD) is 0.0311 mol. % (Vienna Standard Mean Ocean Water, VSMOW). Rothman et al., J. Quant. Spectrosc. Radiat.
- HOD levels in natural water slightly vary on Earth district. Only exclusion is natural water of Antarctica, which water contains HOD at levels of about 0.0178 mol. % (Standard Light Antarctic Precipitation, SLAP). A majority of people reside at Earth districts, where they consume natural water with HOD levels from 0.0280 to 0.0311 mol. %. On a calculation basis, when consume 2.7 and 3.7 liters of natural water per day, women and men consume no less than 0.8 and 1.0 ml of HOD as the obligate nutrient per day, respectively.
- HOD is a highly undesirable nutrient for a subject suffering from depression and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone.
- mammals are highly sensitive to HOD levels in drinking water and even change of HOD content in drinking water within the range of its natural concentrations provides a significant effect on susceptibility to psychosocial stress and predisposition to the development of depression.
- the dietary management of major depression can be achieved by restriction of HOD daily consumption.
- It is an object of the present invention is to provide a medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 molecular % of isotopologue HOD.
- the present invention provides a medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 molecular % of isotopologue HOD.
- the medical food comprises water containing from 0.0178 to 0.0278 molecular % of isotopologue HOD.
- medical food refers to a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of depression and/or anxiety, for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.
- the medical food is specially formulated and processed as a drink product.
- drink products include, but are not limited by, drinking water, beverage, and liquid food.
- major depression also known as major depressive disorder
- major depressive disorder refers to a mental disorder typically characterized by a lasting sad mood and/or loss of interest or pleasure in most activities.
- isotopologue is in accordance with IUPAC Compendium of Chemical Terminology 2nd Edition (1997) and refers to a molecular entity that differs only in isotopic composition (number of isotopic substitutions).
- examples of such isotopologues include H 2 16 O, H 2 17 O, H 2 18 O, H 16 OD, H 17 OD, 1 H 18 OD, D 2 16 O, D 2 17 O, and D 2 18 O.
- the isotopologue H 16 OD is indicated in the present invention as HOD.
- HOD content in the water can be determined by methods well-known from the art.
- HOD levels can be directly measured by laser spectrometry.
- HOD levels can be determined by conventional isotope mass-spectrometry as D/H ratio and re-calculated to HOD contents given that content of other deuterium-containing isotopologues in water is negligible as compared to HOD.
- VSMOW water contains 0.00006 mol. % H 18 OD; 0.00001 mol.
- the range 0.0002 to 0.0278 mol. % of isotopologue HOD in the water of the invention corresponds to the range of D/H ratio 1 to 139 ppm.
- the range 0.0178 to 0.0278 mol. % of isotopologue HOD in the water of the invention corresponds to the range of deuterium content 89 to 139 ppm.
- the water containing 0.0002 to 0.0278 mol. % of isotopologue HOD can be prepared by a variety of industrial procedures well-known from the art, e.g. vacuum distillation of natural water.
- the water containing 0.0178 to 0.0278 mol. % of isotopologue HOD can be obtained from rare natural sources (e.g. Antarctic precipitations) or prepared by a variety of industrial procedures well-known from the art, e.g. vacuum distillation of natural water.
- the medical food of the invention may be prepared by well-known procedures using well-known optional ingredients.
- Such optional ingredients generally are used individually at levels from about 0.0005% to about 10.0%, preferably from about 0.005% to about 1.0% by weight of the composition.
- suitable optional ingredients include, but are not limited to, buffers, sweeteners, colorants, carriers, and etc.
- the medical food is a liquid medical food specially formulated and manufactured in form of drinking water or beverage.
- the liquid medical food may be prepared by saturation of water containing 0.0002 to 0.0278 mol. % of isotopologue HOD with carbon dioxide or/and inorganic salts typically abandoned in natural drinking water.
- the examples of such salts include, but are not limited to, sodium chloride, sodium bicarbonate, calcium chloride, magnesium sulfate, etc.
- the medical food can be administered orally for a period of one day or longer and in amounts as prescribed by a physician which manages the diet and/or provides medical supervision.
- the medical food may be formulated as the drinking water or beverage that can be administered in amounts from 0.1 to 4.0 liters per subject per day.
- the medical food may be consumed by mammals.
- mammals include, but are not limited to, animals such as a dog, a cat, a horse, and a human.
- the medical food is consumed by a human.
- This example demonstrates the preparation of water samples with different contents of isotopologue HOD.
- the samples were prepared by mixing in certain proportions the conventional distilled water containing 0.0300 mol. % HOD and water containing 0.0002 mol. % HOD, wherein the last water was prepared by high-effective vacuum distillation of the conventional distilled water at 60° C. and pressure 0.2 bars using the distillation column of 10 m of height.
- HOD levels were measured by isotope laser spectroscopy using Los Gatos Research (LGR) Liquid Water Isotope Analyzer.
- Table 1 shows water samples comprising 0.0002 to 0.0278 mol. % of isotopologue HOD and D/H ratios corresponding therewith.
- This example demonstrates the medical food for the dietary management of major depression.
- the medical foods were formulated as mineralized drinking waters with HOD content as indicated in Table 2.
- the medical foods No 1 through 4 were prepared by dissolution of Calcium Chloride, Magnesium Chloride, and Sodium Bicarbonate in Waters No 1 through 4, respectively, and subsequent bottling in bottles of 330 ml volume.
- Results of forced swim test are presented in Table 4 as mean ⁇ SEM latency to floating (Latency) and duration of floating (Duration). As shown in Table 4, the increase in HOD levels in drinking water results in significant decrease in the latency to floating and increase in the duration of floating, meaning that deuterium-containing isotopologue HOD predisposes to the development of depression.
- HOD is a very undesirable nutrient for elderly subjects with depressive disorders and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention relates to medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 mol. % of isotopologue HOD, preferably, from 0.0178 to 0.0278 mol. % of isotopologue HOD.
Description
- This is a divisional of application Ser. No. 13/686,372 filed Nov. 27, 2012, which is incorporated herein by reference, and which claims priority on Russian patent application 2011149370 filed Dec. 5, 2011, which priority claim is repeated here.
- The present invention is in the field of food industry and healthcare. More specifically, the present invention relates to medical foods for the dietary management of major depression.
- Major depression is a disorder characterized by a combination of symptoms such as lowered mood, loss of energy, loss of interest, feeling of physical illness, poor concentration, altered appetite, altered sleep and a slowing down of physical and mental functions resulting in a relentless feeling of hopelessness, helplessness, and guilt. National Institute of Mental Health estimates prevalence of major depressive disorder (MDD) as 6.7% of U.S. adult population, 56.8% of those with disorders are receiving treatment. Worldwide, MDD is a major cause of disability and premature death. Average-age-of onset of MDD is estimated as of 32 years old. The exact cause of MDD is not known. Present treatment of depression consists of psychotherapy, antidepressant drugs, or a combination of both. However, there are no special nutritional requirements related to the dietary management of patients with MDD.
- Water is an essential nutrient. Total water intake includes drinking water, water in beverages, and water contained in food. The adequate intake for total water was set based on the median total water intake from U.S. survey data as 3.7 and 2.7 liters per day for men and women, respectively. Dietary Guidelines for Americans, 2005, U.S. Department of Health & Human Services. The natural water is a composition of nine water isotopologues (H2 16O, H2 17O, H2 18O, H16OD, H17OD, H18OD, D2 16O, D2 17O, D18O) formed by stable isotopes of hydrogen (H and D) and oxygen (16O, 17O, 18O), wherein content of major water isotopologue H2O (H2 16O) is 99.7317 molecular % (mol. %) and major deuterium-containing isotopologue HOD (H16OD) is 0.0311 mol. % (Vienna Standard Mean Ocean Water, VSMOW). Rothman et al., J. Quant. Spectrosc. Radiat. Transfer, 1998, 60, 665. Rothman et al., J. Quant. Spectrosc. Radiat. Transfer, 2003, 82, p.9. Because of process of evaporation and condensation of ocean water, HOD levels in natural water slightly vary on Earth district. Only exclusion is natural water of Antarctica, which water contains HOD at levels of about 0.0178 mol. % (Standard Light Antarctic Precipitation, SLAP). A majority of people reside at Earth districts, where they consume natural water with HOD levels from 0.0280 to 0.0311 mol. %. On a calculation basis, when consume 2.7 and 3.7 liters of natural water per day, women and men consume no less than 0.8 and 1.0 ml of HOD as the obligate nutrient per day, respectively.
- We discovered that HOD is a highly undesirable nutrient for a subject suffering from depression and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone. Surprisingly, we found that mammals are highly sensitive to HOD levels in drinking water and even change of HOD content in drinking water within the range of its natural concentrations provides a significant effect on susceptibility to psychosocial stress and predisposition to the development of depression. Thus, the dietary management of major depression can be achieved by restriction of HOD daily consumption.
- It is an object of the present invention is to provide a medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 molecular % of isotopologue HOD.
- The present invention provides a medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 molecular % of isotopologue HOD.
- In a preferred embodiment of the invention, the medical food comprises water containing from 0.0178 to 0.0278 molecular % of isotopologue HOD.
- As used herein, the term “medical food” refers to a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of depression and/or anxiety, for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation.
- In a preferred embodiment of the invention, the medical food is specially formulated and processed as a drink product. Such drink products include, but are not limited by, drinking water, beverage, and liquid food.
- As used herein, the term “major depression” (also known as major depressive disorder) refers to a mental disorder typically characterized by a lasting sad mood and/or loss of interest or pleasure in most activities.
- As used herein, the term “isotopologue” is in accordance with IUPAC Compendium of Chemical Terminology 2nd Edition (1997) and refers to a molecular entity that differs only in isotopic composition (number of isotopic substitutions). Examples of such isotopologues include H2 16O, H2 17O, H2 18O, H16OD, H17OD, 1H18OD, D2 16O, D2 17O, and D2 18O. The isotopologue H16OD is indicated in the present invention as HOD.
- In preferred embodiments of the invention, HOD content in the water can be determined by methods well-known from the art. HOD levels can be directly measured by laser spectrometry. R. Van Trigt. R. van Trigt. Laser Spectrometry for Stable Isotope Analysis of Water Biomedical and Paleoclimatological Applications. 2002, Groningen: University Library Groningen. Also, HOD levels can be determined by conventional isotope mass-spectrometry as D/H ratio and re-calculated to HOD contents given that content of other deuterium-containing isotopologues in water is negligible as compared to HOD. For the reference, VSMOW water contains 0.00006 mol. % H18OD; 0.00001 mol. % H17OD; and less than 0.00001 mol. % for sum of isotopologues D2 16O, D2 17O, and D2 18O. The range 0.0002 to 0.0278 mol. % of isotopologue HOD in the water of the invention corresponds to the range of D/H ratio 1 to 139 ppm. The range 0.0178 to 0.0278 mol. % of isotopologue HOD in the water of the invention corresponds to the range of deuterium content 89 to 139 ppm.
- In preferred embodiments of the invention, the water containing 0.0002 to 0.0278 mol. % of isotopologue HOD can be prepared by a variety of industrial procedures well-known from the art, e.g. vacuum distillation of natural water. The water containing 0.0178 to 0.0278 mol. % of isotopologue HOD can be obtained from rare natural sources (e.g. Antarctic precipitations) or prepared by a variety of industrial procedures well-known from the art, e.g. vacuum distillation of natural water.
- In practicing the invention, the water containing 0.0002 to 0.0278 mol. % of isotopologue HOD may contain other water isotopologues at levels equal or other than in VSMOW standard of natural water, e.g. 0<H2 18O≦0.2000 mol. %; 0<H2 17O≦0.0370 mol. %; 0<H17OD≦0.0270 mol. %; 0<H18OD≦0.0270 mol. %; 0<D2 16O≦0.0270 mol. %; 0<D2 17O≦0.0270 mol. %; 0<D2 18O=0.0270 mol. %, and 0<H2 16≦99.9998 mol. %.
- The medical food of the invention may be prepared by well-known procedures using well-known optional ingredients. Such optional ingredients generally are used individually at levels from about 0.0005% to about 10.0%, preferably from about 0.005% to about 1.0% by weight of the composition. Examples of suitable optional ingredients include, but are not limited to, buffers, sweeteners, colorants, carriers, and etc.
- In the preferred embodiments of the invention, the medical food is a liquid medical food specially formulated and manufactured in form of drinking water or beverage. The liquid medical food may be prepared by saturation of water containing 0.0002 to 0.0278 mol. % of isotopologue HOD with carbon dioxide or/and inorganic salts typically abandoned in natural drinking water. The examples of such salts include, but are not limited to, sodium chloride, sodium bicarbonate, calcium chloride, magnesium sulfate, etc.
- In practicing the invention, the medical food can be administered orally for a period of one day or longer and in amounts as prescribed by a physician which manages the diet and/or provides medical supervision.
- In practicing the invention, the medical food may be formulated as the drinking water or beverage that can be administered in amounts from 0.1 to 4.0 liters per subject per day.
- In practicing the invention, the medical food may be consumed by mammals. Nonexclusive examples of such mammals include, but are not limited to, animals such as a dog, a cat, a horse, and a human. Preferably, the medical food is consumed by a human.
- The following examples are presented to demonstrate the invention. The examples are illustrative only and are not intended to limit the scope of the invention in any way.
- This example demonstrates the preparation of water samples with different contents of isotopologue HOD. The samples were prepared by mixing in certain proportions the conventional distilled water containing 0.0300 mol. % HOD and water containing 0.0002 mol. % HOD, wherein the last water was prepared by high-effective vacuum distillation of the conventional distilled water at 60° C. and pressure 0.2 bars using the distillation column of 10 m of height. HOD levels were measured by isotope laser spectroscopy using Los Gatos Research (LGR) Liquid Water Isotope Analyzer. Table 1 shows water samples comprising 0.0002 to 0.0278 mol. % of isotopologue HOD and D/H ratios corresponding therewith.
-
TABLE 1 Water samples Sample HOD content, mol. % D/H ratio, ppm Water No 1 0.0278 139 Water No 2 0.0240 120 Water No 3 0.0178 89 Water No 4 0.0002 1 - This example demonstrates the medical food for the dietary management of major depression. The medical foods were formulated as mineralized drinking waters with HOD content as indicated in Table 2.
-
TABLE 2 Medical foods Ingredient (HOD, mol. %) Content, wt. % Medical food 1 Water No 1 (0.0278) 99.953 Calcium Chloride 0.015 Magnesium Chloride 0.007 Sodium Bicarbonate 0.025 Medical food 2 Water No 2 (0.0240) 99.953 Calcium Chloride 0.015 Magnesium Chloride 0.007 Sodium Bicarbonate 0.025 Medical food 3 Water No 3 (0.0178) 99.953 Calcium Chloride 0.015 Magnesium Chloride 0.007 Sodium Bicarbonate 0.025 Medical food 4 Water No 4 (0.0002) 99.953 Calcium Chloride 0.015 Magnesium Chloride 0.007 Sodium Bicarbonate 0.025 - The medical foods No 1 through 4 were prepared by dissolution of Calcium Chloride, Magnesium Chloride, and Sodium Bicarbonate in Waters No 1 through 4, respectively, and subsequent bottling in bottles of 330 ml volume.
- This example shows that deuterium-containing isotopologue HOD dose-dependently predisposes to the development of depression. Water samples of Table 3 were prepared by mixing in certain proportions of two equally mineralized waters having HOD level of 0.0184 mol. % (D/H ratio=92 ppm) and HOD level 0.0282 mol. % (D/H ratio=141 ppm).
-
TABLE 3 Water samples Water sample HOD content, mol. % D/H ratio, ppm W1 0.0184 92 W2 0.0240 120 W3 0.0258 129 W4 0.0282 141
Three-months-old male C57BI/6 mice were randomly assigned by 15 animals per group and received W1, W2, W3, and W4 (Table 3) as drinking waters ad libitum for 14 days and then were tested for depressive-like behavior in a forced swim test and novel cage test, commonly accepted paradigms for pre-clinical testing of a depressive-like behavior. Antidepressant Imipramine (15 mg/kg per day) was administered to mice that were taken as positive control in the test. Results of forced swim test are presented in Table 4 as mean±SEM latency to floating (Latency) and duration of floating (Duration). As shown in Table 4, the increase in HOD levels in drinking water results in significant decrease in the latency to floating and increase in the duration of floating, meaning that deuterium-containing isotopologue HOD predisposes to the development of depression. -
TABLE 4 Forced swim test Sample (HOD, mol. %) Latency, s Duration, s W1 (0.0184) 46 ± 6# 89 ± 15# W2 (0.0240) 48 ± 9# 80 ± 14# W3 (0.0258) 47 ± 11# 86 ± 19# W4 (0.0282) 31 ± 6* 128 ± 12* Imipramine 58 ± 4*# 79 ± 8#* *Differs significantly of W1 (p < 0.05). #Differs significantly of W4 (p < 0.05).
Results of novel cage test are presented in Table 5 as mean±SEM number of exploratory rearings in the new cage. As found, the increase in HOD levels in drinking water results in significant decrease in the number of exploratory rearings in the new cage, meaning that deuterium-containing isotopologue HOD predisposes to the development of depression. -
TABLE 5 Novel cage test Sample (HOD, mol. %) Number, n W1 (0.0184) 35.0 ± 1.5# W2 (0.0240) 35.5 ± 1.5# W3 (0.0258) 33.0 ± 1.5 W4 (0.0282) 30.0 ± 1.0* Imipramine 34.0 ± 1.5# *Differs significantly of W1 (p < 0.05). #Differs significantly of W4 (p < 0.05).
Thus, these results suggest that deuterium-containing water isotopologue HOD in drinking water predisposes to depressive-like behavior. Therefore, HOD is a very undesirable nutrient for subjects with major depressive disorder and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone. - This example demonstrates that deuterium-containing isotopologue HOD predisposes to the development of anhedonia, the core symptom of depression. Young adult male C57BI/6J mice received ad libitum waters W1 or W4 (Table 3) for one week prior the onset of stress and during the ten days of a chronic stress. Citalopram 15 mg/kg per day per os was used as the reference antidepressant drug. There was no difference between groups at baseline. At 10th day of the stress procedure, animals were tested on the sucrose preference, common test for assessment of anhedonia. Results are presented in Table 6 as mean±SEM percent of sucrose preference.
-
TABLE 6 Sucrose preference test Group (HOD, mol. %) Sucrose preference, % W1 (0.0184) 73.5 ± 3.0# W4 (0.0282) 62.5 ± 2.0* Citalopram 70.0 ± 3.0# *Differs significantly of W1 (p < 0.05). #Differs significantly of W4 (p < 0.05).
As shown in Table 6, the increase in HOD levels in drinking water results in significant decrease in sucrose preference, meaning that deuterium-containing isotopologue HOD predisposes to the development of anhedonia, the core symptom of depression. Therefore, HOD is a very undesirable nutrient for subjects with major depressive disorder and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone. - This example demonstrates that deuterium-containing isotopologue HOD predisposes to the development of depression in elderly. Table 7 shows that sucrose preference in old C5BI/6J mice is significantly decreased in comparison with young adult C5BI/6J mice, meaning that normal aging induces spontaneous anhedonia in mice.
-
TABLE 7 Group Sucrose preference, % Young adult C57BI/6J mice (3 months old) 78.0 ± 2.5 Old C57BI/6J mice (18 months old) 60.6 ± 3.1* *Differs significantly of young adult mice (p < 0.05).
To estimate effect of HOD on anhedonia in elderly, 18 month old male C57BI/6J mice received ad libitum waters W1 or W4 (Table 3) for 14 days. There was no difference between groups at baseline. At the end of the experiment, mice were tested in sucrose preference test. Results are presented in Table 8 as mean±SEM percent of sucrose preference. As found, the increase in HOD levels in drinking water results in significant decrease in sucrose preference, meaning that deuterium-containing isotopologue HOD predisposes to the development of anhedonia, the core symptom of major depression, in elderly. -
TABLE 8 Sucrose preference test Group (HOD, mol. %) Sucrose preference, % W1 (0.0184) 81.3 ± 1.9 W4 (0.0282) 69.4 ± 4.4* *Differs significantly of W1 (p < 0.05).
To estimate effect of HOD on depressive-like behavior in elderly, 18 month old male C57BI/6J mice received ad libitum waters W1 or W4 (Table 3) for 14 days. There was no difference between groups at baseline. At the end of the experiment, mice were tested in forced swim test. Results are presented in Table 9 as mean±SEM of latency to floating (Latency) and duration of floating (Duration). As found, the increase in HOD levels in drinking water results in decrease in the latency to floating and significant increase in the duration of floating, meaning that deuterium-containing isotopologue HOD predisposes to the development of depression in elderly. -
TABLE 9 Forced swim test Group (HOD, mol. %) Latency, s Duration, s W1 (0.0184) 17.4 ± 4.2 126.7 ± 13.9 W4 (0.0282) 13.7 ± 3.1 186.7 ± 10.0* *Differs significantly of W1 (p < 0.05). - Therefore, HOD is a very undesirable nutrient for elderly subjects with depressive disorders and HOD restriction may represent a special medically determined nutrient requirement, the dietary management of which cannot be achieved by the modification of the normal diet alone.
Claims (2)
1. A medical food for the dietary management of major depression comprising a water containing from 0.0002 to 0.0278 molecular % of isotopologue HOD.
2. The medical food of claim 1 , wherein the water contains from 0.0178 to 0.0278 molecular % of isotopologue HOD.
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US13/686,372 US9220727B2 (en) | 2011-12-05 | 2012-11-27 | Method of dietary management of depression |
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US14/282,322 Abandoned US20150024062A1 (en) | 2011-12-05 | 2014-05-20 | Medical Food for the Dietary Management of Major Depression |
US14/534,290 Abandoned US20150064276A1 (en) | 2011-12-05 | 2014-11-06 | Method for the Dietary Management of Anxiety |
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WO2014088441A1 (en) * | 2012-12-03 | 2014-06-12 | Igor Anatolievich Pomytkin | Food for the dietary management of burnout |
RU2542491C1 (en) * | 2013-12-02 | 2015-02-20 | Антон Сергеевич Чернопятко | Using water low-deuterium water for increasing body resistance to aircraft flight |
WO2015142209A1 (en) * | 2014-03-20 | 2015-09-24 | Igor Anatolievich Pomytkin | Water with low deuterium content for the dietary management of psychological distress |
JP2017526638A (en) * | 2014-06-30 | 2017-09-14 | ミトコンドリアル サブストレート インベンション リミテッドMitochondrial Substrate Invention Limited | Nutrient solutions for improving cognitive function |
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US6376531B1 (en) * | 1998-11-13 | 2002-04-23 | Rupert Charles Bell | Method of treatment using deuterium compounds |
US6872408B2 (en) * | 2001-09-07 | 2005-03-29 | Rupert C. Bell | Method of treating bipolar disorders using deuterium-substituted carbonate |
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