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FRANCESCHI CCAMPISI J: "Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases", J GERONTOL SER A, vol. 69, 2014, pages S4 - S9, XP055285093, DOI: 10.1093/gerona/glu057
VASTO SCANDORE GBALISTRERI MCOLONNA-ROMANO GGRIMALDI MPLISTI F ET AL.: "Inflammatory networks in ageing, age-related diseases, and longevity", MECH AGEING AND DEV, vol. 128, 2007, pages 83 - 91, XP005827801
ZHAI YYIN ZXXU JWLIU YZSHI XM: "Anemia status and its relevant factors among elderly people aged above 80 years old in longevity areas in China", CHINESE J OF PREV MED, vol. 44, 2010, pages 115 - 118
LYU YYIN ZLUO JSHI XZENG Y, ZHONGHUA LIUXINGBINGXUE ZAZHI, vol. 36, 2015, pages 682 - 686
KRIESBERG RAKASIM S: "Cholesterol metabolism and aging", AM J MED, vol. 82, 1987, pages 54 - 60
ANDERSON KMCASTELLI WPLEVY D: "Cholesterol and mortality: 30 years of follow-up from the Framingham Study", JAMA, vol. 257, 1987, pages 2176 - 2180
VAARHORST AAMBEEKMAN MSUCHIMAN EHDVAN HEEMST DVHOUWING-DUISTERMAAT JJWESTERNDORP RG ET AL.: "Lipid metabolism in long-lived families: the Leiden Longevity Study", AGE, vol. 33, 2010, pages 219 - 227, XP019909866, DOI: 10.1007/s11357-010-9172-6
GREGG EWZHUO XCHENG YJALBRIGHT ALNARAYAN KMVTHOMPSON TJ: "Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: A modelling study", LANCET DIAB ENDOCRINOL, vol. 2, 2014, pages 867 - 874
PAOLISSO GBARBIERI MRIZZO MRCARELLA CROTONDI MBONAFE M ET AL.: "Low insulin resistance and preserved p-cell function contribute to human longevity but are not associated with TH-INS genes", EXP GERONTOL, vol. 37, 2001, pages 147 - 156
NOVELLE MGALL ADIEGUEZ CBERNIER MDE CABO R: "Metformin: A hopeful promise in aging research", CSH PERSPECTIVES, vol. 6, 2016, pages a025932
LIM YSKIM WR: "The global impact of hepatic fibrosis and end-stage liver disease", CLINICS IN LIVER DIS, vol. 12, 2008, pages 733 - 746
HIROSE WIKEMATSU KTSUDA R: "Age-associated increases in heme oxygenase-1 and ferritin immunoreactivity in the autopsied brain", LEGAL MED, vol. 5, 2003, pages 360 - 366
BARTZOKIS GTISHLER TALU PHVILLABLANCA PALTSHULER LLCARTER M ET AL.: "Brain ferritin iron may influence age- and gender-related risks of neurodegeneration", NEUROBIOL AGING, vol. 28, 2007, pages 414 - 423, XP005868191, DOI: 10.1016/j.neurobiolaging.2006.02.005
FARAGE MAMILLER KWEISNER PMAIBACH HI: "Characteristics of the aging skin", ADV WOUND CARE, vol. 2, 2013
PATEL KV ET AL.: "Prevalence and impact of pain among older adults in the United States: Findings from the 2011 National Health and Aging Trends Study", PAIN, vol. 154, 2013, pages 2649 - 2657, XP028786428, DOI: 10.1016/j.pain.2013.07.029
LEE AS ET AL.: "A current review of molecular mechanisms regarding osteoarthritis and pain", GENE, vol. 527, 2013, pages 440 - 447
IWAKURA Y ET AL.: "The roles of IL-17A inflammatory immune responses and host defense against pathogens", IMMUNOL REV, vol. 226, 2008, XP055088151, DOI: 10.1111/j.1600-065X.2008.00699.x
MARTINIS MD ET AL.: "Allergy and aging: an old/new emerging health issue", AGING AND DIS, vol. 8, 2017, pages 162 - 175
VITIELLO TV1V: "Sleep disorders and aging: understanding the causes", J GERONTOL, vol. 52A, 1997, pages M189 - M191
MONJAN AFOLEY D: "Incidence of chronic insomnia associated with medical and psychosocial factors: an epidemiologic study among older persons", SLEEP RES, vol. 25, 1996, pages 108
BAUM C ET AL.: "Seventh annual review", 1986, FOOD AND DRUG ADMINISTRATION, CENTER FOR DRUGS AND BIOLOGIES, article "Drug utilization in the U.S- 1985"
HAYAISHI 0: "Molecular mechanisms of sleep-wake regulation: roles of prostaglandins D2 and E2", FASEB J, vol. 5, 1991, pages 2575 - 2581
SHAMBUREK RDFARRAR JT: "Disorders of the digestive system in the elderly", NEW ENGL ] MED, vol. 322, 1990, pages 438 - 443
ANANTHAKRISHNAN AN ET AL.: "Inflammatory bowel disease in the elderly is associated with worse outcomes: a national study of hospitalizations", INFLAMM BOWEL DIS, vol. 15, 2009, pages 182 - 289
COCCIA M ET AL.: "IL-1P mediates chronic intestinal inflammation by promoting the accumulation of IL-17A secreting innate lymphoid cells and CD4+ Th17 cells", J EXP MED, vol. 209, 2012, pages 1595
SGNOC RGRUBER J: "Age-related aspects of cutaneous wound healing: a mini review", GERONTOL, vol. 59, 2013, pages 159 - 164
BEANES SR ET AL.: "Down-regulation of deconn, a transforming growth factor-beta modulator, is associated with scarless fetal wound healing. .1", PEDIATR SURG, vol. 36, 2001, pages 1666 - 71
LIECHTY KW: "Diminished interleukin-8 (IL-8) production in the fetal wound healing response", J SURG RES, vol. 77, 1997, pages 80 - 84
KENDLER BS: "Carnitine: an overview of its role in preventive medicine", PREY MED, vol. 15, 1986, pages 373 - 390, XP023040133, DOI: 10.1016/0091-7435(86)90005-8
REBOUCHE CJ: "Kinetics, pharmacokinetics, and regulation of L-carmtine and acetyl-L-carnitine metabolism", ANN NY ACAD SCI, vol. 1033, 2004, pages 30 - 41
FLANAGAN, J.L.SIMMONS, P.A.VEHIGE, J.WILCOX, M.D.P.GARRETT, Q.: "Role of carnitine in disease", NUTR METABOL, vol. 7, 2010, pages 30, XP021080299, DOI: 10.1186/1743-7075-7-30
INDIVERI, CLACOBAZZI, V.TONAZZI, A.GIANGREGORIO, N.INFANTINO, V.CONVERTING P. ET AL.: "The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology", MOL ASP MED, vol. 32, 2011, pages 223 - 233, XP028119044, DOI: 10.1016/j.mam.2011.10.008
JARRELL, Z.R.SMITH, M.R.HU, X.ORR, M.LIU, K.H.QUYYUMI, A.A. ET AL.: "Plasma acylcarnitine levels increase with healthy aging", AGING, vol. 12, 2020, pages 13555 - 13570
KALIM, S.CLISH, C.B.WENGER, JELMARIAH, S.YEH, R.W. ET AL.: "A plasma long-chain acylcarnitine predicts cardiovascular morality in incident dialysis patients", J AM HEART ASSOC, vol. 2, 2013, pages e000542
KOH, A.S.GAO, F.LIU, J.FRIDIANTO, K.T.CHING, J.TAN, R.S ET AL.: "Metabolomic profile of arterial stiffness in aged adults", DIAB VASE DIS RES, vol. 15, 2018, pages 74 - 80
KENDLER BS: "Carnitine: an overview of its role in preventive medicine", PREV MED, vol. 15, 1986, pages 373 - 390, XP023040133, DOI: 10.1016/0091-7435(86)90005-8
BOUCHOUIRAB ET AL.: "Plasma Palmitoyl-Carnitme (AC16:0) Is a Marker of Increased Postprandial Nonestenfied Incomplete Fatty Acid Oxidation Rate in Adults With Type 2 Diabetes", CAN J DIABETES, vol. 42, no. 4, 9 November 2017 (2017-11-09), pages 382 - 388
TOOTSI, KKALS, J.ZILMER, M.PAAPSTEL, K.OTTAS, A.MARTSON, A.: "Medium- and long-chain acylcarnitines are associated with osteoarthritis severity and arterial stiffness in end-stage osteoarthritis patients: a case-control study", INT J RHEUM DIS, vol. 21, 2018, pages 1211 - 1218
JARRELL ET AL.: "Plasma acylcarnitine levels increase with healthy aging", AGING (ALBANY NY, vol. 12, no. 13, 15 July 2020 (2020-07-15), pages 13555 - 13570
JENKINS, B. ET AL.: "A review of odd-chain fatty acid metabolism and the role of pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) in health and disease", MOLECULES, vol. 20, 2015, pages 2425 - 2444, XP055258173, DOI: 10.3390/molecules20022425
FOROUHI, N.G. ET AL.: "Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study", LANCET DIAB ENDOCRINOL, vol. 14, 2014, pages 70146 - 9
TRIEU, K. ET AL.: "Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis", PLOS MED, vol. 18, 2021, pages e1003763
DJOUSSE, L. ET AL.: "Serum individual nonesterified fatty acids and risk of heart failure in older adults", CARDIOLOGY, vol. 146, 2021, pages 351 - 358
ZHUANG, P.CHENG, L.WANG, J.ZHANG Y.: "Saturated fatty acid intake is associated with total mortality in a nationwide cohort study", J NUTRITION, vol. 149, 2019, pages 68 - 77
TRIEU ET AL.: "Biomarkers of dairy fat intake, incident cardiovascular disease, and all-cause mortality: A cohort study, systematic review, and meta-analysis", PLOS MEDICINE, 21 September 2021 (2021-09-21)
MANCA, C.CARTA, GMURRU, E.ABOLGHASEMI A ET AL.: "Circulating fatty acids and endocannabiniodome-related mediator profiles associated to human longevity", GEROSCI, 2021
VENN-WATSON, S.LUMPKIN, RDENNIS, E. A.: "Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential", SCI REP, vol. 10, 2020, pages 8161
FU, W.C. ET AL.: "Pentadecanoic acid promotes basal and insulin-stimulated glucose uptake in C2C12 myotubes", FOOD NUTR RES, 2021
TO, N.B.NGUYEN, Y.T.MOON, J.Y.EDMWEERA, M.K.CHO, S.K.: "Pentadecanoic acid, an odd-chain fatty acid, suppresses the sternness of MCF-7/SC human breast cancer stem-like cells through JAK2/STAT3 signaling", NUTRIENTS, vol. 12, 2020, pages 1663, XP055930553, DOI: 10.3390/nu12061663
GUNN-MOORE, D.KAIDANOVICH-BEILM, 0.IRADI, M.C.G.GUNN-MOORE, F.LOVESTONE, S.: "Alzheimer's disease in humans and other animals: A consequence of post reproductive life span and longevity rather than aging", ALZ DEMENTIA, vol. 14, 2018, pages 195 - 204
VENN-WATSON, S.SMITH, C.R.GOMEZ, F.JENSEN, E.D.: "Physiology of aging among healthy, older bottlenose dolphins (Tursiops truncatus): comparisons with aging humans", J COMP PHYSIOL, vol. 181, 2011, pages 667 - 680
VENN-WATSON, S.BENHAM, C.CARLIN, K.DERIENZO, D.ST. LEGER, J.: "Hemochromatosis and fatty liver disease: building evidence for insulin resistance in bottlenose dolphins (Tursiops truncatus", J ZOO WILDLF MED, vol. 43, no. 10, 2012, pages 1638
VENN-WATSON, S.SMITH, C.R.STEVENSON, S.PARRY, C.DANIELS, R.JENSEN, E. ET AL.: "Blood-based indicators of insulin resistance and metabolic syndrome in bottlenose dolphins (Tursiops truncatus", FRONT ENDOCRINOL, vol. 10, 2013, pages 3389
VENN-WATSON, S.BAIRD, M.NOVICK, B.PARRY, C.JENSEN, E.D.: "Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids", PLOS ONE, 2020
"Remington: The Science and Practice of Pharmacy", 1 June 2003, LIPPINCOTT WILLIAMS & WILKINS
"Remington's Pharmaceutical Sciences", December 1985, MACK PUB. CO.
"Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers", July 2005, U.S. FOOD AND DRUG ADMINISTRATION
VENN-WATSON, S.BAIRD, M.NOVICK, B.PARRY, C.JENSEN, ED: "Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottleiiose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids", PLOS ONE, 2020
PERTWEE, R.G.: "Emerging strategies for exploiting cannabinoid receptor agonists as medicines", BR J PHARMACOL, vol. 156, 2009, pages 397 - 411, XP055567676, DOI: 10.1111/j.1476-5381.2008.00048.x
BRYK, M.STAROWICZ, K.: "Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review", PHARMACOL REP, vol. 73, 2021, pages 681 - 699
BOUCHOURIAB, F.Z.FORTIN, M.NOLL, C.DUBE, J.CARPENTIER, A.C.: "Plasma palmitoyl-carnitine (AC16:0) is a marker of increased postprandial nonesterified incomplete fatty acid oxidation rate in adults with type 2 diabetes", CAN J DIABETES, vol. 42, no. el, 2018, pages 382 - 388
LIGRESTI, A.PETROSMO, S.DI MARZO, V.: "From endocannabinoid profiling to 'endocannabinoid therapeutics", CURR OPIN CHEM BIOL, vol. 13, 2009, pages 21 - 31
GREENBERG JABELL SJAUSDAL WV: "Omega-3 Fatty Acid supplementation during pregnancy", REVIEWS IN OBSTETRICS & GYNECOLOGY, vol. 1, 2008, pages 162 - 169
MIHALIK, S.J.GOODPASTER, B.H.KELLEY, D.E.CHACE, D.H.VOCKLEY, J.TOLEDO, F.G.S. ET AL.: "Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicit", OBESITY, vol. 18, 2010, pages 1695 - 1700
VENN-WATSON, S.PARRY, C.BAIRD, M.STEVENSON, S.CARLIN, K.DANIELS, R: "Increased dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated with decreasing ferritin and alleviated metabolic syndrome in dolphins", PLOS ONE, 2015
WHAT IS CLAIMED IS: 1. A composition for treatment, management, amelioration, or prophylaxis of a condition selected from the group consisting of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug-seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive- compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, behavioral problems with Tourette’s syndrome, the composition comprising: pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 2. A composition for supporting appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, and weight loss, the composition comprising: pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 3. The composition of Claim 1 or 2, comprising pentadecanoylcarnitine. 4. The composition of Claim 1 or 2, comprising pentadecanoic acid. 5. The composition of Claim 1 or 2, comprising pentadecanoylcarnitine and pentadecanoic acid. 6. The composition of any one of Claims 1-5, configured for administration of from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. 7. The composition of any one of Claims 1-6, configured for administration once per day. 8. The composition of any one of Claims 1-7, in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, stereoisomers, or esters thereof. 9. The composition of any one of Claims 1-7, wherein the composition is in a form selected from the group consisting of a foodstuff, a dietary supplement, a unit dosage form, a prescription drug, or a pharmaceutical drug. 10. The composition of any one of Claims 1-7, wherein the composition is in a form selected from the group consisting of a dietary supplement, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. 11. Use of a composition of any one of Claims 1-10, in the manufacture of a medicament for achieving a body concentration of pentadecanoylcarnitine of from1 μM to 20 μM. 12. A method of treatment, management, amelioration, or prophylaxis of a condition selected from the group consisting of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug-seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive-compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, behavioral problems with Tourette’s syndrome, the method comprising: administering to a subject in need thereof, an effective amount of pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 13. A method of supporting appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, and weight loss, the composition comprising: administering to a subject in need thereof, an effective amount of pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 14. The method of Claim 12 or 13, wherein a body concentration of pentadecanoylcarnitine of from 1 μM to 20 μM is achieved in the subject. 15. The method of any one of Claims 12-14, wherein pentadecanoylcarnitine is administered. 16. The method of any one of Claims 12-14, wherein pentadecanoic acid is administered. 17. The method of any one of Claims 12-14, wherein pentadecanoylcarnitine and pentadecanoic acid are administered. 18. The method of any one of Claims 12-17, wherein from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered. 19. The method of any one of Claims 12-18, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered once per day. 20. The method of any one of Claims 12-19, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, stereoisomers, or esters thereof. 21. The method of any one of Claims 12-20, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered in a form selected from the group consisting of a foodstuff, a dietary supplement, a unit dosage form, a prescription drug, or a pharmaceutical drug. 22. The method of any one of Claims 12-20, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered in a form selected from the group consisting of a dietary supplement, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. 23. A dietary supplement comprising pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 24. The dietary supplement of Claim 23, configured for administration of a minimum of 0.1 mg per 1 kg of body weight, optionally of a minimum of 0.3 mg per 1 kg of body weight, optionally of a minimum of 1 mg per 1 kg of body weight, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. 25. The dietary supplement of any one of Claims 23-24, configured for administration of from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. 26. The dietary supplement of any one of Claims 23-25, configured for administration once per day. 27. The dietary supplement of any one of Claims 23-26, in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 1 mg to 1000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. 28. The dietary supplement of any one of Claims 23-27, in a form of a pharmaceutical drug or prescription drug. 29. The dietary supplement of any one of Claims 23-27, in a form selected from the group consisting of a foodstuff, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. 30. The dietary supplement of any one of Claims 23-27, in a form of a foodstuff. 31. The dietary supplement of any one of Claims 23-27, in a form of a medical food. 32. The dietary supplement of any one of Claims 23-27, in a form of a food additive. 33. The dietary supplement of any one of Claims 23-27, in a form of a food fortifier. 34. The dietary supplement of any one of Claims 23-27, in a form of a beverage additive. 35. The dietary supplement of any one of Claims 23-27, in a form of a beverage fortifier. 36. The dietary supplement of any one of Claims 23-27, in a form of a fortified food. 37. The dietary supplement of any one of Claims 23-27, in a form of a fortified beverage. 38. The dietary supplement of any one of Claims 23-27, in a form of an additized food. 39. The dietary supplement of any one of Claims 23-27, in a form of an additized beverage. 40. The dietary supplement of any one of Claims 23-39, for veterinary use. 41. The dietary supplement of any one of Claims 23-39, for human use. 42. A composition substantially as described herein. 43. A method substantially as described herein. 44. A use substantially as described herein. |
Foodstuffs
[0145] Foodstuffs and other comestibles including pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, are provided, wherein an amount of the pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof in the foodstuff has been fortified (e.g., enriched or concentrated). Pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof may be added to foodstuffs for consumption by a subject. The pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof may be integrated into one or more ingredients of a foodstuff. The pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof may be prepared as an ingredient, or may be unprepared. The pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, or preparation including the pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, may be added prior to preparation, during preparation, or following preparation. Preparation may without limitation include cooking, mixing, flavoring, seasoning, blending, boiling, frying, baking, or other processes known in the art. Fortification is preferably at a level so as to provide a therapeutic daily dosage of pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof as described elsewhere herein, or to achieve a body concentration of pentadecanoylcarnitine as described herein; however, beneficial effects may also be obtained at amounts below' such dosages. Pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof can be administered as a dietary supplement in a unit dosage form (a tablet, a capsule, an encapsulated pill, or gelcap pill), or in a dispensable form of an oral or injectable liquid suspension or solution, a spray, an aerosol, powder, or granules), or as a dietary supplement, additive, ingredient, or fortifier added to a comestible substance (food or beverage). In certain embodiments, pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof as a dietary supplement or food/beverage ingredient or additive can be utilized to promote or support health, e.g., to promote or support metabolic health, to promote or support heart health, to promote or support liver health, to promote or support red blood cell, to promote or support immune health; and/or slow an aging rate. Accordingly, pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof is suitable for administration in those forms and by those methods known in the pharmaceutical and nutraceutical arts, including but not limited to a dietary supplement, a medical food, a food additive, a food ingredient, a food fortifier, a beverage additive, a beverage ingredient, a beverage fortifier, a fortified food, a fortified beverage, an additized food, an additized beverage, as well as pharmaceutical drug in any form, including as a tablet, encapsulated pill, gelcap pill, liquid suspension, liquid solution, spray, or powder. [0146] Pentadecanoylcarnitine or pentadecanoic acid or salt thereof as provided herein may be present as a constituency in foodstuffs by operation of processes known in nature, for example, by altering the metabolic processes of a plant, animal, bacteria, or fungus. Genetic alteration of a plant, animal, bacteria, or fungus to increase the concentration of pentadecanoylcarnitine or pentadecanoic acid or salt thereof, is contemplated. By way of example, the pentadecanoylcarnitine or pentadecanoic acid or salt thereof can be present in the foodstuff in a concentration of at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, or higher, for example, 1% to 2% or 3% or 4% or 5% or 6% or 7% or 8% or 9% or 10% or 20% or 30% or 40%, 50%, or ranges including and/or spanning the aforementioned values. The pentadecanoylcarnitine or pentadecanoic acid or salt thereof, if naturally present in a foodstuff, can be present in an enriched amount above that which is naturally occurring for the foodstuff, e.g., a concentration of 10% or more above the average or highest naturally occurring observed concentration, e.g., 20% or 30% or 40% or 50% or 100% or 200% or 300% or 400% or 1000% or 2000% or 5000% or more above the average or highest naturally occurring observed concentration. Indications [0147] Provided are compositions and methods for treatment, management, amelioration, or prophylaxis of a condition selected from the group consisting of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug- seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive- compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, behavioral problems with Tourette’s syndrome. [0148] Provided are compositions and methods for supporting appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, and weight loss. [0149] Provided are compositions and methods for achieving a body concentration of pentadecanoylcarnitineof from1μM to 20 μMis achieved in a ubject. [0150] In some embodiments, levels of serum, plasma, or erythrocyte membrane pentadecanoylcarnitine may increase following administration pentadecanoylcarnitine or pentadecanoic acid or salt thereof. [0151] In some embodiments, the compositions and methods provided herein modulate a marker of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug-seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive- compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, or behavioral problems with Tourette’s syndrome, or a marker associated with appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, or weight loss. In certain embodiments, the marker is serum, plasma, or red blood cell membrane pentadecanoylcarnitine percentage; serum, plasma, or red blood cell membrane concentration of pentadecanoylcarnitine contained herein; or serum plasma, or red blood cell membrane total pentadecanoylcarnitine. In some embodiments, the pentadecanoylcarnitine is measured as a constituent of glycolipids. In further embodiments, the pentadecanoylcarnitine is measured as a constituent of phospholipids. In still further embodiments, the marker is serum or red blood cell membrane pentadecanoylcarnitine percentage, serum concentration of pentadecanoylcarnitine , or serum total pentadecanoylcarnitine. [0152] In some embodiments, the methods provided herein include the step of measuring the concentration of a marker. One of skill in the art will be able to perform suitable methods for such measurements, including but not limited to those described herein. [0153] Provided herein are methods for treating including the step of administering a dose of pentadecanoylcarnitine or pentadecanoic acid or salt thereof, at a predetermined interval, or at an interval left to the discretion of the subject. [0154] In some embodiments, the compounds and methods provided herein may provide a threshold serum, plasma, or red blood cell membrane percentage of pentadecanoylcarnitine relative to all serum, plasma, or red blood cell membrane small molecule metabolites. For example, the threshold value may be a value of about 0.05% or lower to 90% or higher, e.g., a value of at least about 0.05%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1.0%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2.1%, at least about 2.2%, at least about 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3.0%, at least about 3.5%, at least about 4.0%, at least about 4.5%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, more than 90%, or ranges including and/or spanning the aforementioned values. [0155] In some embodiments, the compositions and methods provided herein may provide an increase above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) in a serum or plasma concentration of pentadecanoylcarnitine , or red blood cell membrane concentration of pentadecanoylcarnitine . For example, a serum or plasma pentadecanoylcarnitine or red blood cell membrane concentration of pentadecanoylcarnitine may be increased by at least about 1 μg/ml, at least about 2 μg/ml, at least about 3 μg/ml, at least about 4 μg/ml, at least about 5 μg/ml, at least about 6 μg/ml, at least about 7 μg/ml, at least about 8 μg/ml, at least about 9 μg/ml, at least about 10 μg/ml, at least about 15 μg/ml, at least about 20 μg/ml, at least about 25 μg/ml, at least about 30 μg/ml, at least about 35 μg/ml, at least about 40 μg/ml, at least about 45 μg/ml, at least about 50 μg/ml, more than 50 μg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the serum concentration of pentadecanoylcarnitine, or red blood cell membrane concentration of pentadecanoylcarnitine may increase above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) by at least about 0.01x10 -4 M, at least about 0.05x10 -4 M, at least about 0.1x10 -4 M, at least about 0.2x10 -4 M, at least about 0.3x10 -4 M, at least about 0.4x10 -4 M, at least about 0.5x10 -4 M, at least about 0.6x10- 4 M, at least about 0.7x10 -4 M, at least about 0.8x10 -4 M, at least about 0.9x10 -4 M, at least about 1x10 -4 M, at least about 2x10 -4 M, at least about 3x10 -4 M, or ranges including and/or spanning the aforementioned values. [0156] In some embodiments, the compounds and methods provided herein may provide an increase in serum or plasma total pentadecanoylcarnitine and pentadecanoic acid, or red blood cell membrane total pentadecanoylcarnitine and pentadecanoic acid. For example, serum total pentadecanoylcarnitine and pentadecanoic acid, or red blood cell membrane total pentadecanoylcarnitine and pentadecanoic acid, may be increased above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) by at least about 5 μg/ml, at least about 6 μg/ml, at least about 7 μg/ml, at least about 8 μg/ml, at least about 9 μg/ml, at least about 10 μg/ml, at least about 15 μg/ml, at least about 20 μg/ml, at least about 25 μg/ml, at least about 30 μg/ml, at least about 35 μg/ml, at least about 40 μg/ml, at least about 45 μg/ml, at least about 50 μg/ml, at least about 60 μg/ml, at least about 70 μg/ml, at least about 80 μg/ml, at least about 90 μg/ml, at least about 100 μg/ml, at least about 150 μg/ml, at least about 200 μg/ml, at least about 250 μg/ml, at least about 300 μg/ml, at least about 350 μg/ml, at least about 400 μg/ml, at least about 450 μg/ml, at least about 500 μg/ml, or more than 500 μg/ml. [0157] In some embodiments, the compounds and methods provided herein may provide an increase above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) in a serum, plasma, or red blood cell membrane pentadecanoylcarnitine relative to all serum or red blood cell membrane small molecule metabolites, respectively. For example, a serum, plasma, or red blood cell membrane pentadecanoylcarnitine may be increased above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) by at least about 0.01%, at least about 0.05%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2%, at least about 2.1%, at least about 2.2%, at least about 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3%, at least about 3.5%, at least about 4%, at least about 4.5%, at least about 5%, more than 5%, or ranges including and/or spanning the aforementioned values. [0158] In some embodiments, pentadecanoylcarnitine or pentadecanoic acid or salt thereof is administered to maintain serum or plasma total percent of pentadecanoylcarnitine above a predetermined threshold value. In further variations, the pentadecanoylcarnitine or pentadecanoic acid or salt thereof is administered to maintain serum phospholipid percent of the pentadecanoylcarnitine above about 0.1%, about 0.2%, about 0.3%, about 0.4%, about 0.5%, about 0.6%, about 0.7%, about 0.8%, about 0.9%, about 1%, about 1.2%, about 1.4%, about 1.6%, about 1.8%, about 2%, about 2.2%, about 2.4%, about 2.6%, or ranges including and/or spanning the aforementioned values. [0159] In some embodiments, the compounds and methods provided herein may provide a threshold serum, plasma, or red blood cell membrane percentage of pentadecanoylcarnitine relative to all serum or red blood cell membrane small molecule metabolites, respectively. For example, the threshold value may be a value of about 0.05% or lower to 90% or higher, e.g., a value of at least about 0.05%, at least about 0.1%, at least about 0.2%, at least about 0.3%, at least about 0.4%, at least about 0.5%, at least about 0.6%, at least about 0.7%, at least about 0.8%, at least about 0.9%, at least about 1.0%, at least about 1.1%, at least about 1.2%, at least about 1.3%, at least about 1.4%, at least about 1.5%, at least about 1.6%, at least about 1.7%, at least about 1.8%, at least about 1.9%, at least about 2.1%, at least about 2.2%, at least about 2.3%, at least about 2.4%, at least about 2.5%, at least about 2.6%, at least about 2.7%, at least about 2.8%, at least about 2.9%, at least about 3.0%, at least about 3.5%, at least about 4.0%, at least about 4.5%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, more than 90%, or ranges including and/or spanning the aforementioned values. [0160] In some embodiments, the compounds and methods provided herein may provide an increase above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) in a serum or plasma concentration of pentadecanoylcarnitine, or red blood cell membrane concentration of a pentadecanoylcarnitine. For example, a serum pentadecanoylcarnitine or red blood cell membrane concentration of pentadecanoylcarnitine may be increased by at least about 0.01 μg/ml, at least about 0.05 μg/ml, at least about 0.1 μg/ml, at least about 0.4 μg/ml, 1 μg/ml, at least about 2 μg/ml, at least about 3 μg/ml, at least about 4 μg/ml, at least about 5 μg/ml, at least about 6 μg/ml, at least about 7 μg/ml, at least about 8 μg/ml, at least about 9 μg/ml, at least about 10 μg/ml, at least about 15 μg/ml, at least about 20 μg/ml, at least about 25 μg/ml, at least about 30 μg/ml, at least about 35 μg/ml, at least about 40 μg/ml, at least about 45 μg/ml, at least about 50 μg/ml, more than 50 μg/ml, or ranges including and/or spanning the aforementioned values. In some embodiments, the serum concentration of pentadecanoylcarnitine, or red blood cell membrane concentration of pentadecanoylcarnitine may increase above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) by at least about 0.001x10 -4 M, at least about 0.005x10 -4 M, at least about 0.05x10 -4 M, at least about 0.01x10 -4 M, at least about 0.05x10 -4 M, at least about 0.1x10 -4 M, at least about 0.2x10 -4 M, at least about 0.3x10 -4 M, at least about 0.4x10 -4 M, at least about 0.5x10 -4 M, at least about 0.6x10 -4 M, at least about 0.7x10 -4 M, at least about 0.8x10 -4 M, at least about 0.9x10 -4 M, at least about 1x10 -4 M, at least about 2x10 -4 M, at least about 3x10 -4 M, or ranges including and/or spanning the aforementioned values. [0161] In some embodiments, the compounds and methods provided herein may provide an increase in serum or plasma total pentadecanoylcarnitine and pentadecanoic acid or salt thereof, or red blood cell membrane total pentadecanoylcarnitine and pentadecanoic acid or salt thereof. For example, serum total pentadecanoylcarnitine and pentadecanoic acid or salt thereof, or red blood cell membrane total pentadecanoylcarnitine and pentadecanoic acid or salt thereof, may be increased above a baseline value (e.g., pretreatment value in a patient being treated, or general value observed in a particular patient population) by at least about 0.05 μg/ml, at least about 0.1 μg/ml, at least about 0.5 μg/ml, at least about 1 μg/ml, at least about 5 μg/ml, at least about 6 μg/ml, at least about 7 μg/ml, at least about 8 μg/ml, at least about 9 μg/ml, at least about 10 μg/ml, at least about 15 μg/ml, at least about 20 μg/ml, at least about 25 μg/ml, at least about 30 μg/ml, at least about 35 μg/ml, at least about 40 μg/ml, at least about 45 μg/ml, at least about 50 μg/ml, at least about 60 μg/ml, at least about 70 μg/ml, at least about 80 μg/ml, at least about 90 μg/ml, at least about 100 μg/ml, at least about 150 μg/ml, at least about 200 μg/ml, at least about 250 μg/ml, at least about 300 μg/ml, at least about 350 μg/ml, at least about 400 μg/ml, at least about 450 μg/ml, at least about 500 μg/ml, more than 500 μg/ml, or ranges including and/or spanning the aforementioned values. Combination Therapies [0162] In some embodiments, the pentadecanoylcarnitine or pentadecanoic acid or salt thereof may be used in combination with one or more additional active agents. Examples of additional active agents that can be used in combination include a small molecule metabolite, or a salt or derivative thereof, or a composition that includes a compound of a small molecule metabolite, or a salt or derivative thereof, include, but are not limited to, agents currently used for treating conditions provided herein, and as otherwise known to medical science. [0163] In some embodiments, pentadecanoylcarnitine or pentadecanoic acid or salt thereof, can be used with one, two, three or more additional active agents described herein. Such agents include, but are not limited to, a small molecule metabolite, or a salt or derivative thereof. [0164] In some embodiments, pentadecanoylcarnitine or pentadecanoic acid or salt thereof can be used (for example, administered or ingested) in combination with another agent or agents for treatment, prevention, maintenance, or prophylaxis of a condition provided herein. [0165] Additionally, pentadecanoylcarnitine or pentadecanoic acid or salt thereof can be used in combination with one or more agents selected from Altoprev (lovastatin), Crestor (rosuvastatin), Lescol (fluvastatin), Lipitor (atorvastatin), Livalo (pitavastatin), Pravachol (pravastatin), Zocor (simvastatin), an anti-platelet medication, a beta blocker, an ACE inhibitor, a calcium channel blocker, a diuretic, anticoagulants, aspirin, bile acid sequestrants, Ezetimibe, Fibrates, Glycoprotein IIb/IIIa Receptor Inhibitors, Niacin (Nicotinic Acid), Nitrates, Platelet Inhibitors, Thrombolytics, lisinopril oral, atenolol oral, Bystolic oral, Diovan oral, hydrochlorothiazide oral, metoprolol succinate oral, amlodipine oral, Norvasc oral, Toprol XL oral, Benicar oral, metoprolol tartrate oral, losartan oral, lisinopril-hydrochlorothiazide oral, clonidine HCl oral, Diovan HCT oral, Cozaar oral, propranolol oral, spironolactone oral, Azor oral, carvedilol oral, Coreg oral, Benicar HCT oral, Exforge oral, Avapro oral, Lotrel oral, verapamil oral, furosemide oral, Lasix oral, Hyzaar oral, Tekturna oral, enalapril maleate oral, Micardis oral, losartan-hydrochlorothiazide oral, ramipril oral, Lopressor oral, Altace oral, Micardis HCT oral, Avalide oral, diltiazem oral, triamterene-hydrochlorothiazide oral, labetalol oral, terazosin oral, amlodipine-benazepril oral, hydralazine oral, Atacand oral, benazepril oral, Tribenzor oral, triamterene oral, doxazosin oral, nifedipine oral, Ziac oral, Aldactone oral, Maxzide oral, Cartia XT oral, prazosin oral, Cardizem CD oral, Zestril oral, Dyazide oral, bisoprolol fumarate oral, Tenex oral, Tenormin oral, Coreg CR oral, Prinivil oral, valsartan oral, atenolol-chlorthalidone oral, Edarbyclor oral, benazepril-hydrochlorothiazide oral, ferrous sulfate oral, Ferrlecit intravenous, Feraheme intravenous, Feosol oral, Infed injection, Integra oral, Ferrex 150 Forte oral, Tandem Dual Action oral, Ferrex 150 oral, ferrous gluconate oral, Corvite 150 oral, Integra F oral, NovaFerrum oral, Iron (ferrous sulfate) oral, Vitron-C oral, Folic acid, corticosteroids, rituximab, IVIG, prednisone, methylprednisolone oral, Kenalog injection, Medrol (Pak) oral, Medrol oral, dexamethasone oral, Depo-Medrol injection, prednisolone oral, DexPak 13 Day oral, Solu-Medrol intravenous, hydrocortisone oral, Cortef oral, Deltasone oral, triamcinolone acetonide injection, cortisone oral, cholinesterase inhibitors such as Donepezil (Aricept), Rivastigmine (Exelon), and Galantamine (Razadyne), Memantine, Aricept, Namenda, Namenda XR, Razadyne ER, Alpha E, vitamin E, Hydergine, Namzaric, Dopamine Agonists such as pramipexole (Mirapex), ropinirole (Requip), rotigotine (Neupro patch) and apomorphine (Apokyn), Anticholinergics such as benztropine (Cogentin) and trihexyphenidyl, MAO-B Inhibitors such as (Eldepryl, Zelapar) and rasagiline (Azilect), COMT Inhibitors such as Entacapone (Comtan), Carbidopa/Levodopa (Sinemet®), amantadine, Tetrabenazine (Xenazine), haloperidol (Haldol), chlorpromazine, risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), indomethacin, sulindac, etodolac, mefenamic acid, meclofenamic acid, meclofenamate sodium, flufenamic acid, tolmetin, ketorolac, diclofenac, diclofenac sodium, ibuprofen, naproxen, naproxen sodium, fenoprofen, ketoprofen, flurbiprofen, oxaprozin piroxicam, meloxicam, ampiroxicam, droxicam, lornoxicam, cinnoxicam, sudoxicam, and tenoxicam. [0166] Additionally, pentadecanoylcarnitine or pentadecanoic acid or salt thereof can be used in combination with one or more agents selected from iron dextran, iron sumalate, polysaccharide iron, ferrus fumarate, carbonyl iron, ferrous asparto glycinate, heme iron polypeptide can be sometimes indicated, ferrus bisglycinate as can be the administration of other medicaments such as androgen hormones, such as erythropoietin, folic acid, vitamin B12, vitamin C, succinic acid, niacin, pyridoxine, riboflavin, biotin, thiamine, calcium formate, Aminoxin, Anadrol-50, Chromagen Forte, Epoetin alfa, Epogen, Fe C Tab Plus, FeRiva, FeRivaFA, Ferocon, Ferotrin, Ferralet 90, Ferrex 28, Ferrogels Forte, FoliTab 500, Fumatinic, Hematogen Forte, Hemetab, Integra Plus, Irospan 42/6, Lenalidomide, Maxaron Forte, Myferon 150 Forte, MyKidz Iron, NovaFerrum, Oxymetholone, Procrit, Proferrin-Forte, Pyridoxine, Repliva 21/7, Revlimid, and Tricon. Dosing [0167] As will be readily apparent to one skilled in the art, the useful in vivo dosage to be administered and the particular mode of administration will vary depending upon the age, weight, the severity of the condition, and mammalian species treated, the particular forms of the compounds employed, and the specific use for which these compounds are employed. The determination of effective dosage levels (the dosage levels necessary to achieve the desired result) can be accomplished by one skilled in the art using routine methods, for example, in vivo studies. Reference may be made to, for example, “Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers,” U.S. Food and Drug Administration, July 2005. [0168] In some embodiments, a method provided herein may comprise administering a therapeutically effective amount of a composition provided herein. In some embodiments, a therapeutically effective amount may be determined by reference to the modulation of a marker of a condition provided herein. In some embodiments, a therapeutically effective amount may be determined by reference to the modulation of a symptom of a condition provided herein. In still other embodiments, reference may be made to established guidelines for the conditions described herein, including, but not limited to, guidelines for the treatment of a condition provided herein including inflammation. [0169] The dosage may vary broadly, depending upon the desired effects and the therapeutic indication, such as marker values. Alternatively, dosages may be based and calculated upon the surface area or weight of the patient, as understood by those of skill in the art. The exact dosage will be determined on a case-by-case basis, or, in some cases, will be left to the informed discretion of the subject. The daily dosage regimen for an adult human patient may be, for example, an oral dose of pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, or a mixture of pentadecanoylcarnitine and pentadecanoic acid, or salts thereof, from about 0.01 mg to about 10000 mg, from about 1 mg to about 5000 mg, from about 5 mg to about 2000 mg, from about 10 mg to about 1000 mg, from about 50 mg to about 500 mg, or from about 100 mg to about 200 mg. A single dose, e.g., a minimum dose, may include pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, in about 0.01 mg, about 0.1 mg, about 1 mg, about 5 mg, about 10 mg, about 20 mg, about 50 mg, about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, about 600 mg, about 800 mg, about 900 mg, about 1000 mg, about 2000 mg, about 5000 mg, or more, or ranges including and/or spanning the aforementioned values. The dosage may be adjusted according to the body mass of the subject, for example, the dosage, e.g., a minimum dosage, may be about 0.001 mg/kg, about 0.01 mg/kg, about 0.1 mg/kg, 0.3 mg/kg , about 0.5 mg/kg, about 1 mg/kg, about 2 mg/kg, about 3 mg/kg, about 4 mg/kg, about 5 mg/kg, about 6 mg/kg, about 7 mg/kg, about 8 mg/kg, about 9 mg/kg, about 10 mg/kg, about 15 mg/kg, about 20 mg/kg, about 25 mg/kg, about 30 mg/kg, or higher or ranges including and/or spanning the aforementioned values. For example, the dosage may be f rom about 0.001 mg/kg to about 30 mg/kg, f rom about 0.01 mg/kg to about 10 mg/kg, f rom about 0.1 mg/kg to about 5 mg/kg, f rom about 0.3 mg/kg to about 3 mg/kg, or f rom about 1 mg/kg to about 3 mg/kg. The dosage may be a single one or a series of two or more given in the course of one or more days, as is appropriate for the individual subject. In some embodiments, the pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof will be administered for a period of continuous therapy, for example for about a week or more (e.g., one week, two weeks, three weeks, four weeks, five weeks, six weeks, seven weeks, eight weeks, or more), for several weeks, for about a month or more (e.g., one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, or more), for about a year or more, or for a plurality of years. In some embodiments, pentadecanoylcarnitine or pentadecanoic acid, or a salt thereof, can be administered or ingested one time per day, two times per day, three times per day, or more. [0170] As will be understood by those of skill in the art, in certain situations it may be necessary to administer the compounds disclosed herein in amounts that exceed the above-stated, preferred dosage range in order to effectively treat a subject. [0171] Unit dosage forms can also be provided, e.g., individual packages with a premeasured amount of the composition, configured for administration on a predetermined schedule. Unit dosage forms configured for administration one to three times a day are preferred; however, in certain embodiments it may be desirable to configure the unit dosage form for administration more than three times a day, or less than one time per day. [0172] Dosage amount and interval may be adjusted to the individual subject to provide plasma levels of the active moiety which are sufficient to maintain predetermined parameters, indicators, or marker values, or minimal effective concentration (MEC). Dosages necessary to achieve the desired result will depend on individual characteristics and route of administration. However, assays, for example, HPLC assays or bioassays, may be used to determine serum concentrations. [0173] In some embodiments, the compounds and methods provided herein may be used in conjunction with devices and methods of using devices, for example, as provided in U.S. Pat. No. 7,651,845; U.S. Pat. No. 8,251,904; U.S. Pat. No. 8,251,904; U.S. Pat. No. 4,985,015; U.S. Pat. No. 8,827,957; U.S. Pat. No. 4,252,159; U.S. Pat. No. 5,318,521; U.S. Pat. No. 4,718,430; U.S. Pat. No. 9,713,600, U.S. Pat. No. 9,707,199, U.S. Pat. No. 9,687,461, U.S. Pat. No. 9,662,306, U.S. Pat. No. 9,561,206, U.S. Publ. No. 2011/0190702; U.S. Publ. No. 2017/0266144, U.S. Publ. No. 2016/0324814, U.S. Publ. No. 2016/0195559, U.S. Publ. No. 2016/0195558, U.S. Publ. No. 2016/0193172, 2 U.S. Publ. No. 016/0193171, U.S. Publ. No. 2016/0193170, WO 2016/111843, DE 2615061; and in conjunction with diagnostic devices, for example, as provided in U.S. Publ. No.2012/0072236. The contents of each of the foregoing patent documents is incorporated herein by reference in its entirety. Diagnosis and monitoring [0174] Provided herein are methods for the diagnosis and monitoring of conditions provided herein. [0175] In some embodiments, the method of diagnosis or monitoring may comprise the step of measuring a percentage of pentadecanoylcarnitine as described herein, in a bodily fluid. In some embodiments, the method of diagnosis or monitoring may comprise the step of measuring a marker of a condition provided herein in a subject. In some embodiments, a correlation between one marker and another may prove instructive. In some embodiments, a condition provided herein may be diagnosed by reference to a threshold level of a marker of the condition, for example, serum pentadecanoylcarnitine percentage, serum concentration of pentadecanoylcarnitine , serum total pentadecanoylcarnitine and pentadecanoic acid, or a ratio between pentadecanoylcarnitine and pentadecanoic acid. For example, the threshold may be determined by reference to a symptom or marker of a condition provided herein. [0176] The percentage of pentadecanoylcarnitine , or a marker of a condition provided herein in a subject may be monitored by any means. Samples for analysis may be derived any fluid or tissue of the subject. For example, from serum, plasma, erythrocyte membranes, urine, and feces. EXAMPLE 1 [0177] A series of studies were conducted to identify additional serum-based compounds in dolphins, beyond pentadecanoic acid, which were associated with a lower risk of chronic disease indices. Promising compounds were then tested at a variety of concentrations for direct, clinically relevant activities that are known to prevent, manage, treat or cure chronic conditions. [0178] Among bottlenose dolphins fed a modified fish diet containing higher concentrations of C15:0, it was hypothesized that downstream C15:0 metabolites may be contributing to the observed health benefits in this case-control study (Venn-Watson, S., Baird, M., Novick, B., Parry, C., Jensen, E.D. Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids. PLoS ONE doi10.1371/journal.pone.0230769 (2020)). To test this hypothesis, changes in the dolphin serum metabolome during Months 0, 1, 3 and 6 were evaluated and compared between dolphins on the baseline and modified fish diet. Methods [0179] Methods for this modified diet study, including metabolomics, were those previously described (Venn-Watson, S., Baird, M., Novick, B., Parry, C., Jensen, E.D. Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids. PLoS ONE doi10.1371/journal.pone.0230769 (2020)), including bioinformatics, principal component analysis, hierarchical clustering, and random forest regression to identify metabolites that best predicted dolphins on the modified versus baseline diet. Bioinformatics [0180] The informatics system consisted of four major components, the Laboratory Information Management System (LIMS), the data extraction and peak-identification software, data processing tools for QC and compound identification, and a collection of information interpretation and visualization tools for use by data analysts. The hardware and software foundations for these informatics components were the LAN backbone, and a database server running Oracle 10.2.0.1 Enterprise Edition. Peaks were quantified using area-under-the-curve. For studies spanning multiple days, a data normalization step was performed to correct variation resulting from instrument inter-day tuning differences. Essentially, each compound was corrected in run-day blocks by registering the medians to equal one (1.00) and normalizing each data point proportionately (termed the “block correction”). For studies that did not require more than one day of analysis, no normalization is necessary, other than for purposes of data visualization. In certain instances, biochemical data may have been normalized to an additional factor (e.g., cell counts, total protein as determined by Bradford assay, osmolality, etc.) to account for differences in metabolite levels due to differences in the amount of material present in each sample. Two-way ANOVA main effects models, including study group, month, and sex, were used to determine primary drivers of differences in the metabolome. Principal components analysis and hierarchical clustering [0181] Each principal component was a linear combination of every metabolite and the principal components were uncorrelated. The number of principal components was equal to the number of observations. The first principal component was computed by determining the coefficients of the metabolites that maximized the variance of the linear combination. The second component found the coefficients that maximize the variance with the condition that the second component was orthogonal to the first. The third component was orthogonal to the first two components and so on. The total variance was defined as the sum of the variances of the predicted values of each component (the variance is the square of the standard deviation), and for each component, the proportion of the total variance was computed. Hierarchical clustering was used as an unsupervised method for clustering the data to show any large-scale differences. Complete clustering using the Euclidean distance was applied, where each sample was a vector with all metabolite values. Random forest regression [0182] Random forest, a supervised classification technique based on an ensemble of decision trees, was used to provide “importance” rank ordering of serum biochemicals that changed due to the modified diet. A random subset of the data with identifying true class information was selected to build the tree (“bootstrap sample” or “training set”), and then the remaining data, the “out-of-bag” (OOB) variables, were passed down the tree to obtain a class prediction for each sample. This process was repeated thousands of times to produce the forest. The final classification of each sample was determined by computing the class prediction frequency (“votes”) for the OOB variables over the whole forest. This method was unbiased since the prediction for each sample was based on trees built from a subset of samples that did not include that sample. When the full forest was grown, the class predictions were compared to the true classes, generating the “OOB error rate” as a measure of prediction accuracy. Thus, the prediction accuracy was an unbiased estimate of how well one can predict sample class in a new data set. To determine which biochemicals made the largest contribution to the classification, a “variable importance” measure was computed. The “Mean Decrease Accuracy” (MDA) was used as this metric. The MDA was determined by randomly permuting a variable, running the observed values through the trees, and then reassessing the prediction accuracy. Results [0183] FIG.1A shows increased serum pentadecanoic acid (C15:0) and FIG.1B shows increased pentadecanoylcarnitine concentrations within 1 month on the modified fish diet that was sustained through 6 months. While there were no significant differences in serum C15:0 or pentadecanoylcarnitine concentrations between case and control groups at baseline (Month 0) (p = 0.81 for C15:0 and p = 0.86 for pentadecanoylcarnitine) using an ANOVA contrast model, both serum C15:0 and pentadecanoylcarnitine concentrations were higher among case versus control groups at Month 1 (p < 0.0001 for C15:0 and p < 0.0001 for pentadecanoylcarnitine), Month 3 (p < 0.0001 for C15:0 and p < 0.0001 for pentadecanoylcarnitine), and Month 6 (p < 0.0001 for C15:0 and p < 0.0001 for pentadecanoylcarnitine). As outlined in Table 1, both C15:0 (pentadecanoic acid) and pentadecanoylcarnitine were ranked within the top 30 important biochemical predictors of dolphins on the modified fish diet by the first month. Further, as the study moved from Month 1 to Month 6, pentadecanoylcarnitine’ s ranking increased to become the most important biochemical among dolphins on the modified diet. TABLE 1. EXAMPLE 2 [0184] Given the observed increase in circulating concentrations of pentadecanoylcarnitine among dolphins on the modified fish diet, it was hypothesized that higher serum pentadecanoylcarnitine concentrations would correlate with changes in clinically relevant indices. Methods [0185] Methods for this correlation study have been previously described (Venn- Watson, S., Baird, M., Novick, B., Parry, C., Jensen, E.D. Modified fish diet shifted serum metabolome and alleviated chronic anemia in bottlenose dolphins (Tursiops truncatus): Potential role of odd-chain saturated fatty acids. PLoS ONE doi10.1371/journal.pone.0230769 (2020)), including Pearson’s correlations to evaluate correlations between relative changes in serum pentadecanoylcarnitine concentrations and log-transformed cholesterol, glucose, hemoglobin, red blood cell count, and platelets; and Spearman correlations for glomerular filtration rate and insulin. Results [0186] Table 2 shows that rising serum pentadecanoylcarnitine concentrations observed in the modified diet study were correlated with lower cholesterol and lower insulin. Rising serum pentadecanoylcarnitine concentrations were correlated with higher hemoglobin, red blood cell count, platelets, and glomerular filtration rate. These data support that increasing serum pentadecanoylcarnitine concentrations may play a role in improving chronic conditions, including hypercholesterolemia, hyperinsulinemia, anemia, thrombocytopenia, and renal disease. TABLE 2. EXAMPLE 3 [0187] Given our prior demonstration of C15:0’s biologically relevant activities in human cell systems mimicking various chronic disease states, including lowering inflammation and fibrosis (Venn-Watson, S., Lumpkin, R., Dennis, E.A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? Sci Rep 10:8161 (2020)), it was hypothesized that pentadecanoylcarnitine would have similar biologically relevant activities. Methods [0188] Methods for this human primary cell phenotypic profiling study were those previously described (Venn-Watson, S., Lumpkin, R., Dennis, E.A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? Sci Rep 10:8161 (2020)). Significant activities of pentadecanoylcarnitine were those that were equal to or greater than 0.1 |log10| at 6.7 μM. Biomarkers with significant changes caused by pentadecanoylcarnitine were compared with results from the same study using pentadecanoic acid (C15:0). Results [0189] Table 3 demonstrates clear differences in primary cell-based activities between pentadecanoylcarnitine and pentadecanoic acid. Of 24 identified biological activities caused by pentadecanoylcarnitine, no specific biomarkers changed significantly in the same direction with pentadecanoic acid. [0190] This study supports that pentadecanoylcarnitine has biologically activities relevant to preventing, managing or treating autoimmune diseases, allergies, asthma, chronic inflammation, cardiovascular disease, oncology, chronic obstructive pulmonary disease, lung inflammation, restenosis, fibrosis, dermatitis, psoriasis, and wound healing that are surprisingly distinct from pentadecanoic acid.
TABLE 3. EXAMPLE 4 [0191] Given demonstration of pentadecanoylcarnitine as a biologically active compound in human cell systems mimicking various disease states, it was hypothesized that pentadecanoylcarnitine would have receptor-based pharmacological activities. Methods [0192] Methods for this study have been previously described (Venn-Watson, S., Lumpkin, R., Dennis, E.A. Efficacy of dietary odd-chain saturated fatty acid pentadecanoic acid parallels broad associated health benefits in humans: could it be essential? Sci Rep 10:8161 (2020)). Significant activities of pentadecanoylcarnitine were those tagged as having maximum pharmacological activities that were greater than or equal to 70% that of the internal control between the concentrations of 1 to 20 μM. Significant pharmacological activities caused by pentadecanoylcarnitine were compared with results from the same assays using pentadecanoic acid (C15:0). Results [0193] Table 4 shows multiple pharmacological activities, at RC50 concentrations between approximately 3 and 10 μM, of pentadecanoylcarnitine, approximately matching maximum activities of positive controls. [0194] Pentadecanoylcarnitine is a cannabinoid receptor 1 and receptor 2 agonist at approximately 1 to 20 μM, further supporting its role in preventing, managing and treating cardiovascular disease, cancer, inflammation, arthritis and cholestatic pruritis (as shown at 6.7 μM in Example 3). Compounds with these activities have also been used or proposed to be used to prevent, manage, or treat nausea, obesity, neuropathic pain with multiple sclerosis, pain, gastrointestinal disorders, atherosclerosis, symptoms of multiple sclerosis, spinal cord injury, Alzheimer’s disease, and amyotrophic lateral sclerosis, tics and behavioral problems with Tourette’s syndrome, anxiety disorders, attention-deficit hyperactivity disorder, depression, brain damage, tardive dyskinesia, glaucoma, and cough (Pertwee, R.G. Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol 156:397-411 (2009), Bryk, M. and Starowicz, K. Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review. Pharmacol Rep 73:681-699 (2021)). [0195] The two most potent endogenous cannabinoids (also called endocannabinoids) are anadamide and 2-arachidonoylglyerol (Battista, N., Tommaso, M.D., Bari, M., Maccarrone, M. The endocannabinoid system: an overview. Front Behav Neurosci doi 10.3389/fnbeh.2012.00009 (2012). [0196] Bouchouriab, F.Z., Fortin, M., Noll, C., Dube, J., Carpentier, A.C. Plasma palmitoyl-carnitine (AC16:0) is a marker of increased postprandial nonesterified incomplete fatty acid oxidation rate in adults with type 2 diabetes. Can J Diabetes 42:382-388.e1 (2018)). These compounds bind to an activate both cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors found throughout the body, as well as peroxisome proliferator-activated receptors (PPARs). Through these mechanisms, naturally occurring endocannabinoids in the body have demonstrated a wide array of health benefits, including those related to modulating memory, cancer, appetite, fertility, pain, obesity, nausea, osteoarthritis, cardiovascular disease, metabolic disorders, hepatic diseases, inflammation, and neurological and neuropsychiatric disorders (Ligresti, A., Petrosino, S. Di Marzo, V. From endocannabinoid profiling to ‘endocannabinoid therapeutics’. Curr Opin Chem Biol 13:21-31 (2009)). [0197] Pentadecanoylcarnitine is a histamine H1 and H2 receptor antagonist at approximately 1 to 20 μM, further supporting its role in preventing, managing and treating allergies, asthma and dermatitis (as shown at 6.7 μM in Example 3). Compounds with these activities have also been used to manage or treat other hypersensitivity disorders and peptic ulcers. [0198] Pentadecanoylcarnitine is a dopamine receptor D1 antagonist at approximately 1 to 20 μM. Compounds with these activities have been used or proposed to be used to prevent, manage, or treat neurological diseases, including Parkinson disease, as well as mental disorders, schizophrenia, cocaine abuse, obesity, pathological gambling, and Tourette’s syndrome. [0199] Pentadecanoylcarnitine is an α-2A adrenergic receptor agonist at approximately 1 to 20 μM, further supporting its role in preventing, managing and treating allergic reactions, asthma, nasal and sinus congestion, allergic rhinitis and facial erythema associated with rosacea (as shown at 6.7 μM in Example 3). Compounds with these activities have been used or proposed to be used to support weight loss. [0200] Pentadecanoylcarnitine is a cholinergic receptor muscarinic 1 antagonist at approximately 1 to 20 μM, further supporting its role in preventing, managing and treating allergies, chronic obstructive pulmonary disease (COPD), and asthma (as shown at 6.7 μM in Example 3). Compounds with these activities have been used or proposed to be used to prevent, manage, or treat movement disorders including Parkinson disease, sleep disorders, nausea, inflammatory bowel syndrome spasms, mental disorders, peptic ulcers, hyperactive bladder, and depression. [0201] Pentadecanoylcarnitine is a SERT blocker at approximately 1 to 20 μM. Compounds with these activities have been used or proposed to be used to prevent, manage, or treat depression and obsessive-compulsive disorders. [0202] Pentadecanoylcarnitine is a 5-HT1A receptor agonist at approximately 1 to 20 μM. Compounds with these activities have been used or proposed to be used to regulate mood, sleep, nausea, sexuality and appetite, including increased sociability, decreased impulsivity, facilitation of sex drive and arousal, diminished food intake, and prolonged REM sleep. Compounds that activate this receptor have also been used as a means to prevent, manage, and treat depression, migraines, bipoloar disorder, anxiety, hypertension, pain, schizophrenia, Parkinson’s disease, aggression, drug-seeking behavior, and opioid-induced respiratory depression. [0203] Pentadecanoylcarnitine is a 5-HT1B receptor agonist at approximately 1 to 20 μM. Compounds with these activities have been used or proposed to be used to manage depression and anxiety, and to reduce of aggression and impulsivity. [0204] In summary, this study has identified pentadecenoyl carnitine as a newly discovered endocannabinoid that fully activates both cannabinoid 1 and 2 receptors at concentrations between 1 and 20 μM.
TABLE 4.
TABLE 4, CONT.
TABLE 4, CONT.
[0205] Various literature references include teachings related to fatty acid supplementation, including but not limited to Greenberg JA, Bell SJ, Ausdal WV. Omega-3 Fatty Acid supplementation during pregnancy. Reviews in obstetrics & gynecology 2008, 1:162-169; Mihalik, S.J., Goodpaster, B.H., Kelley, D.E., Chace, D.H., Vockley, J., Toledo, F.G.S. et al. Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity 18:1695-1700 (2010); Venn-Watson, S., Parry, C., Baird, M., Stevenson, S., Carlin, K., Daniels, R, et al. Increased dietary intake of saturated fatty acid heptadecanoic acid (C17:0) associated with decreasing ferritin and alleviated metabolic syndrome in dolphins. PLoS ONE doi10.1371 (2015); Venn-Watson, S., Smith, C.R., Stevenson, S., Parry, C., Daniels, R. Jensen, E., et al. Blood-based indicators of insulin resistance and metabolic syndrome in bottlenose dolphins (Tursiops truncatus). Front Endocrinol:10.3389 (2013); Venn-Watson, S., Benham, C., Carlin, K., DeRienzo, D., St. Leger, J. Hemochromatosis and fatty liver disease: building evidence for insulin resistance in bottlenose dolphins (Tursiops truncatus).J Zoo Wildlf Med 43:10.1638 (2012); Venn-Watson, S., Smith, C.R., Gomez, F., Jensen, E.D. Physiology of aging among healthy, older bottlenose dolphins (Tursiops truncatus): comparisons with aging humans. J Comp Physiol 181:667-680 (2011). Exemplary Compositions, Uses, and Methods [0206] Composition 1: A composition for treatment, management, amelioration, or prophylaxis of a condition selected from the group consisting of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug- seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive-compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, behavioral problems with Tourette’s syndrome, the composition comprising: pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0207] Composition 2: A composition for supporting appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, and weight loss, the composition comprising: pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0208] Composition 3: Composition 1 or 2, comprising pentadecanoylcarnitine. [0209] Composition 4: Composition 1 or 2, comprising pentadecanoic acid. [0210] Composition 5: Composition 1 or 2, comprising pentadecanoylcarnitine and pentadecanoic acid. [0211] Composition 6: Any one of Compositions 1-5, configured for administration of from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. [0212] Composition 7: Any one of Compositions 1-6, configured for administration once per day. [0213] Composition 8: Any one of Compositions 1-7, in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, stereoisomers, or esters thereof. [0214] Composition 9: Any one of Compositions 1-7, wherein the composition is in a form selected from the group consisting of a foodstuff, a dietary supplement, a unit dosage form, a prescription drug, or a pharmaceutical drug. [0215] Composition 10: Any one of Compositions 1-7, wherein the composition is in a form selected from the group consisting of a dietary supplement, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. [0216] Use 11: Use of any one of Compositions 1-10, in the manufacture of a medicament for achieving a body concentration of pentadecanoylcarnitineof from 1 μM to 20 μM. [0217] Method 12: A method of treatment, management, amelioration, or prophylaxis of a condition selected from the group consisting of aggression, allergies, allergic rhinitis, Alzheimer’s disease, anxiety, anxiety disorders, amyotrophic lateral sclerosis, arthritis, asthma, atherosclerosis, attention-deficit hyperactivity disorder, bipoloar disorder, brain damage, cancer, cardiovascular disease, cholestatic pruritis, depression, chronic obstructive pulmonary disease (COPD), cocaine abuse, cough, dermatitis, depression, drug- seeking behavior, gastrointestinal disorders, facial erythema associated with rosacea, glaucoma, hepatic diseases, hyperactive bladder, hypersensitivity disorders, hypertension, impulsivity, inflammation, mental disorders, mental conditions, metabolic disorders, migraines, nasal congestion, sinus congestion, nausea, neuropathic pain with multiple sclerosis, symptoms of multiple sclerosis, neurological disorders, neuropsychiatric disorders, obesity, obsessive-compulsive disorders, opioid-induced respiratory depression, osteoarthritis, pain, Parkinson disease, pathological gambling, peptic ulcers, schizophrenia, sleep disorders, spinal cord injury, tardive dyskinesia, tics with Tourette’s syndrome, behavioral problems with Tourette’s syndrome, the method comprising: administering to a subject in need thereof, an effective amount of pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0218] Method 13: A method of supporting appetite, cardiovascular health, hematologic health, memory, metabolic health, mood, prolonged REM sleep, renal health, sexuality, sociability, metabolic health, hematological health, renal health, and weight loss, the composition comprising: administering to a subject in need thereof, an effective amount of pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0219] Method 14: Method 12 or 13, wherein a body concentration of pentadecanoylcarnitineof from1μM to 20μM is achieved in the subject. [0220] Method 15: Method 12-14, wherein pentadecanoylcarnitine is administered. [0221] Method 16: Method 12-14, wherein pentadecanoic acid is administered. [0222] Method 17: Method 12-14, wherein pentadecanoylcarnitine and pentadecanoic acid are administered. [0223] Method 18: Method 12-17, wherein from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered. [0224] Method 19: Method 12-18, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered once per day. [0225] Method 20: Method 12-19, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, stereoisomers, or esters thereof. [0226] Method 21: Method 12-20, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered in a form selected from the group consisting of a foodstuff, a dietary supplement, a unit dosage form, a prescription drug, or a pharmaceutical drug. [0227] Method 22: Method 12-20, wherein pentadecanoylcarnitine or pentadecanoic acid, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof is administered in a form selected from the group consisting of a dietary supplement, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. [0228] Dietary Supplement 23: A dietary supplement comprising pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0229] Dietary Supplement 24: Dietary Supplement 23, configured for administration of a minimum of 0.1 mg per 1 kg of body weight, optionally of a minimum of 0.3 mg per 1 kg of body weight, optionally of a minimum of 1 mg per 1 kg of body weight, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. [0230] Dietary Supplement 25: Any one of Dietary Supplements 23-24, configured for administration of from 0.1 mg to 50 mg, per 1 kg of body weight, optionally from 0.3 mg to 5 mg, per 1 kg of body weight, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof to a subject in need thereof. [0231] Dietary Supplement 26: Any one of Dietary Supplements 23-25, configured for administration once per day. [0232] Dietary Supplement 27: Any one of Dietary Supplements 23-26, in a unit dosage form comprising from 0.01 mg to 10000 mg, optionally from 1 mg to 1000 mg, optionally from 10 mg to 200 mg, of the pentadecanoylcarnitine, or pharmaceutically acceptable salts, solvates, or stereoisomers thereof. [0233] Dietary Supplement 28: Any one of Dietary Supplements 23-27, in a form of a pharmaceutical drug or prescription drug. [0234] Dietary Supplement 29: Any one of Dietary Supplements 23-27, in a form selected from the group consisting of a foodstuff, a medical food, a food additive, a food fortifier, a beverage additive, a beverage fortifier, a fortified food, a fortified beverage, an additized food, and an additized beverage. [0235] Dietary Supplement 30: Any one of Dietary Supplements 23-27, in a form of a foodstuff. [0236] Dietary Supplement 31: Any one of Dietary Supplements 23-27, in a form of a medical food. [0237] Dietary Supplement 32: Any one of Dietary Supplements 23-27, in a form of a food additive. [0238] Dietary Supplement 33: Any one of Dietary Supplements 23-27, in a form of a food fortifier. [0239] Dietary Supplement 34: Any one of Dietary Supplements 23-27, in a form of a beverage additive. [0240] Dietary Supplement 35: Any one of Dietary Supplements 23-27, in a form of a beverage fortifier. [0241] Dietary Supplement 36: Any one of Dietary Supplements 23-27, in a form of a fortified food. [0242] Dietary Supplement 37: Any one of Dietary Supplements 23-27, in a form of a fortified beverage. [0243] Dietary Supplement 38: Any one of Dietary Supplements 23-27, in a form of an additized food. [0244] Dietary Supplement 39: Any one of Dietary Supplements 23-27, in a form of an additized beverage. [0245] Dietary Supplement 40: Any one of Dietary Supplements 23-39, for veterinary use. [0246] Dietary Supplement 41: Any one of Dietary Supplements 23-39, for human use. [0247] Composition 42: A composition substantially as described herein. [0248] Method 43: A method substantially as described herein. [0249] Use 44: A use substantially as described herein. [0250] While the disclosure has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive. The disclosure is not limited to the disclosed embodiments. Variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed disclosure, from a study of the drawings, the disclosure and the appended claims. [0251] All references cited herein are incorporated herein by reference in their entirety. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification, the specification is intended to supersede and/or take precedence over any such contradictory material. [0252] Unless otherwise defined, all terms (including technical and scientific terms) are to be given their ordinary and customary meaning to a person of ordinary skill in the art, and are not to be limited to a special or customized meaning unless expressly so defined herein. It should be noted that the use of particular terminology when describing certain features or aspects of the disclosure should not be taken to imply that the terminology is being re-defined herein to be restricted to include any specific characteristics of the features or aspects of the disclosure with which that terminology is associated. Terms and phrases used in this application, and variations thereof, especially in the appended claims, unless otherwise expressly stated, should be construed as open ended as opposed to limiting. As examples of the foregoing, the term ‘including’ should be read to mean ‘including, without limitation,’ ‘including but not limited to,’ or the like; the term ‘comprising’ as used herein is synonymous with ‘including,’ ‘containing,’ or ‘characterized by,’ and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps; the term ‘having’ should be interpreted as ‘having at least;’ the term ‘includes’ should be interpreted as ‘includes but is not limited to;’ the term ‘example’ is used to provide exemplary instances of the item in discussion, not an exhaustive or limiting list thereof; adjectives such as ‘known’, ‘normal’, ‘standard’, and terms of similar meaning should not be construed as limiting the item described to a given time period or to an item available as of a given time, but instead should be read to encompass known, normal, or standard technologies that may be available or known now or at any time in the future; and use of terms like ‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words of similar meaning should not be understood as implying that certain features are critical, essential, or even important to the structure or function of the invention, but instead as merely intended to highlight alternative or additional features that may or may not be utilized in a particular embodiment of the invention. Likewise, a group of items linked with the conjunction ‘and’ should not be read as requiring that each and every one of those items be present in the grouping, but rather should be read as ‘and/or’ unless expressly stated otherwise. Similarly, a group of items linked with the conjunction ‘or’ should not be read as requiring mutual exclusivity among that group, but rather should be read as ‘and/or’ unless expressly stated otherwise. [0253] As used in the claims below and throughout this disclosure, by the phrase “consisting essentially of” is meant including any elements listed after the phrase, and limited to other elements that do not interfere with or contribute to the activity or action specified in the disclosure for the listed elements. Thus, the phrase “consisting essentially of” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present depending upon whether or not they affect the activity or action of the listed elements. [0254] Where a range of values is provided, it is understood that the upper and lower limit, and each intervening value between the upper and lower limit of the range is encompassed within the embodiments. [0255] With respect to the use of substantially any plural and/or singular terms herein, those having skill in the art can translate from the plural to the singular and/or from the singular to the plural as is appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for sake of clarity. The indefinite article “a” or “an” does not exclude a plurality. A single processor or other unit may fulfill the functions of several items recited in the claims. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measures cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope. [0256] It will be further understood by those within the art that if a specific number of an introduced claim recitation is intended, such an intent will be explicitly recited in the claim, and in the absence of such recitation no such intent is present. For example, as an aid to understanding, the following appended claims may contain usage of the introductory phrases “at least one” and “one or more” to introduce claim recitations. However, the use of such phrases should not be construed to imply that the introduction of a claim recitation by the indefinite articles “a” or “an” limits any particular claim containing such introduced claim recitation to embodiments containing only one such recitation, even when the same claim includes the introductory phrases “one or more” or “at least one” and indefinite articles such as “a” or “an” (e.g., “a” and/or “an” should typically be interpreted to mean “at least one” or “one or more”); the same holds true for the use of definite articles used to introduce claim recitations. In addition, even if a specific number of an introduced claim recitation is explicitly recited, those skilled in the art will recognize that such recitation should typically be interpreted to mean at least the recited number (e.g., the bare recitation of “two recitations,” without other modifiers, typically means at least two recitations, or two or more recitations). Furthermore, in those instances where a convention analogous to “at least one of A, B, and C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, and C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). In those instances where a convention analogous to “at least one of A, B, or C, etc.” is used, in general such a construction is intended in the sense one having skill in the art would understand the convention (e.g., “a system having at least one of A, B, or C” would include but not be limited to systems that have A alone, B alone, C alone, A and B together, A and C together, B and C together, and/or A, B, and C together, etc.). It will be further understood by those within the art that virtually any disjunctive word and/or phrase presenting two or more alternative terms, whether in the description, claims, or drawings, should be understood to contemplate the possibilities of including one of the terms, either of the terms, or both terms. For example, the phrase “A or B” will be understood to include the possibilities of “A” or “B” or “A and B.” [0257] All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term ‘about.’ Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims in any application claiming priority to the present application, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches. [0258] Furthermore, although the foregoing has been described in some detail by way of illustrations and examples for purposes of clarity and understanding, it is apparent to those skilled in the art that certain changes and modifications may be practiced. Therefore, the description and examples should not be construed as limiting the scope of the invention to the specific embodiments and examples described herein, but rather to also cover all modification and alternatives coming with the true scope and spirit of the invention.